Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

PubMed Central

Chen, Zhuo; Liu, Suixin; Cai, Ying; Xie, Kangling; Zhang, Wenliang; Dong, Lei; Liu, Yuan; Zheng, Fan; Dun, Yaoshan; Li, Ning

2016-01-01

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis. PMID:27588108

Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells.

PubMed

Chen, Zhuo; Liu, Suixin; Cai, Ying; Xie, Kangling; Zhang, Wenliang; Dong, Lei; Liu, Yuan; Zheng, Fan; Dun, Yaoshan; Li, Ning

2016-09-01

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus , has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis.

In vitro fibroblast migration by sustained release of PDGF-BB loaded in chitosan nanoparticles incorporated in electrospun nanofibers for wound dressing applications.

PubMed

Piran, Mehrdad; Vakilian, Saeid; Piran, Mehran; Mohammadi-Sangcheshmeh, Abdollah; Hosseinzadeh, Simzar; Ardeshirylajimi, Abdolreza

2018-01-23

Migration of fibroblasts into wound area is a critical phenomenon in wound healing process. We used an appropriate system to fabricate an electrospun bioactive scaffold with controlled release of PDGF-BB in order to induce migration of primary skin fibroblast cells. First of all, protein-loaded chitosan nanoparticles based on ionic gelation interaction between chitosan and sodium tripolyphosphate were prepared. Then polycaprolactone electrospun fibers containing chitosan nanoparticles or PDGF-BB-loaded chitosan nanoparticles were prepared. Cellular attachment and morphology of cells seeded on scaffolds with or without PDGF-BB were evaluated by using a fluorescence microscope and scanning electron microscopy. Cells were well-oriented 72 h after seeding on the scaffolds containing PDGF-BB. The mean aspect ratio of populations on scaffold containing PDGF-BB-loaded chitosan nanoparticles was significantly greater than those on the scaffold containing chitosan nanoparticles but no PDGF-BB. Furthermore, the Arp2 gene, which is involved in cell protrusion formation, showed about three times more expression at mRNA level, in cells seeding on PDGF-BB-containing scaffold compared to cells seeding on scaffold containing only chitosan nanoparticles, using Real Time PCR test. Finally, under agarose migration assay results demonstrated that cells' chemotaxic behavior was more toward scaffold containing PDGF-BB compared to the PDGF-BB alone or FBS group. In addition, in terms of distance, the cell mass could grow faster, in response to scaffold containing PDGF-BB compared to FBS or PDGF-BB alone; however, the number of migrating cells might be the same or significantly higher in the latter groups.

RP-1776, a novel cyclic peptide produced by Streptomyces sp., inhibits the binding of PDGF to the extracellular domain of its receptor.

PubMed

Toki, S; Agatsuma, T; Ochiai, K; Saitoh, Y; Ando, K; Nakanishi, S; Lokker, N A; Giese, N A; Matsuda, Y

2001-05-01

RP-1776, a novel cyclic peptide, was isolated from the culture broth of Streptomyces sp. KY11784. RP-1776 selectively inhibited the binding of PDGF BB to the extracellular domain of the PDGF beta-receptor with an IC50 value of 11 +/- 6 microM. Detailed binding experiments suggested that RP-1776 directly interacts with PDGF BB. RP-1776 inhibited the phosphorylation of the PDGF beta-receptor induced by PDGF BB. These results suggested that RP-1776 antagonizes the signaling of PDGF BB probably through the inhibition of PDGF BB binding to the PDGF beta-receptor.

PDGF-BB Does Not Accelerate Healing in Diabetic Mice with Splinted Skin Wounds

PubMed Central

Shah, Nihar M.; Teixeira, Leandro; Motta, Monica J.; Covert, Jill; Dubielzig, Richard; Schurr, Michael; Isseroff, Roslyn Rivkah; Abbott, Nicholas L.; McAnulty, Jonathan; Murphy, Christopher J.

2014-01-01

Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered to accelerate tissue repair of impaired chronic wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied PDGF-BB, we used a controlled full thickness splinted excisional wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined silicone-splinted wound model, with reduced wound contraction, controlled splint and bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice. Wounds were topically treated once daily with either 3 µg PDGF-BB in 30 µl of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound contraction, wound closure, reepithelialization, collagen content, and wound bed inflammation were evaluated clinically and histopathologically. The bioactivity of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted wound model. Considering that the predominant mechanism of wound healing in humans is by re-epeithelialization, the most appropriate model for evaluating therapeutics is one that uses splints to prevent excessive wound contraction. Here, we report that PDGF-BB does not promote wound closure by re-epithelialization in a murine splinted wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the wound model used. PMID:25121729

Platelet-Derived Growth Factor-BB Protects Mesenchymal Stem Cells (MSCs) Derived From Immune Thrombocytopenia Patients Against Apoptosis and Senescence and Maintains MSC-Mediated Immunosuppression

PubMed Central

Zhang, Jia-min; Feng, Fei-er; Wang, Qian-ming; Zhu, Xiao-lu; Fu, Hai-xia; Xu, Lan-ping; Liu, Kai-yan

2016-01-01

Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Mesenchymal stem cells (MSCs) from ITP patients (MSC-ITP) do not exhibit conventional proliferative abilities and thus exhibit defects in immunoregulation, suggesting that MSC impairment might be a mechanism involved in ITP. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types. Moreover, PDGF promotes MSC proliferation. The aim of the present study was to analyze the effects of PDGF-BB on MSC-ITP. We showed that MSC-ITP expanded more slowly and appeared flattened and larger. MSC-ITP exhibited increased apoptosis and senescence compared with controls. Both the intrinsic and extrinsic pathways account for the enhanced apoptosis. P53 and p21 expression were upregulated in MSC-ITP, but inhibition of p53 with pifithrin-α markedly inhibited apoptosis and senescence. Furthermore, MSCs from ITP patients showed a lower capacity for inhibiting the proliferation of activated T cells inducing regulatory T cells (Tregs) and suppressing the synthesis of anti-glycoprotein (GP)IIb-IIIa antibodies. PDGF-BB treatment significantly decreased the expression of p53 and p21 and increased survivin expression in MSC-ITP. In addition, the apoptotic rate and number of senescent cells in ITP MSCs were reduced. Their impaired ability for inhibiting activated T cells, inducing Tregs, and suppressing the synthesis of anti-GPIIb-IIIa antibodies was restored after PDGF-BB treatment. In conclusion, we have demonstrated that PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP. Significance Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types and promotes mesenchymal stem cell (MSC) proliferation. PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP. PMID:27471307

Regulation of human bone sialoprotein gene transcription by platelet-derived growth factor-BB.

PubMed

Mezawa, Masaru; Araki, Shouta; Takai, Hideki; Sasaki, Yoko; Wang, Shuang; Li, Xinyue; Kim, Dong-Soon; Nakayama, Youhei; Ogata, Yorimasa

2009-04-15

Platelet-derived growth factor (PDGF) is produced by mesenchymal cells and released by platelets following aggregation and is synthesized by osteoblasts. In bone, PDGF stimulates proliferation and differentiation of osteoblasts. PDGF also increases bone resorption, most likely by increasing the number of osteoclasts. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone, selectively expressed by differentiated osteoblast. To determine the molecular mechanisms PDGF regulation of human BSP gene transcription, we have analyzed the effects of PDGF-BB on osteoblast-like Saos2 and ROS17/2.8 cells. PDGF-BB (5 ng/ml) increased BSP mRNA and protein levels at 12 h in Saos2 cells, and induced BSP mRNA expression at 3 h, reached maximal at 12 h in ROS17/2.8 cells. Transient transfection analyses were performed using chimeric constructs of the human BSP gene promoter linked to a luciferase reporter gene. Treatment of Saos2 cells with PDGF-BB (5 ng/ml, 12 h) increased luciferase activities of all constructs between -184LUC to -2672LUC including the human BSP gene promoter. Effects of PDGF-BB abrogated in constructs included 2 bp mutations in the two cAMP response elements (CRE1 and CRE2), activator protein 1(3) (AP1(3)) and shear stress response element 1 (SSRE1). Luciferase activities induced by PDGF-BB were blocked by protein kinase A inhibitor H89 and tyrosine kinase inhibitor herbimycin A. Gel mobility shift analyses showed that PDGF-BB increased binding of CRE1, CRE2, AP1(3) and SSRE1 elements. CRE1- and CRE2-protein complexes were supershifted by CREB1 and phospho-CREB1 antibodies. Notably, AP1(3)-protein complexes were supershifted by c-Fos and JunD, and disrupted by CREB1, phospho-CREB1, c-Jun and Fra2 antibodies. These studies, therefore, demonstrate that PDGF-BB stimulates human BSP transcription by targeting the CRE1, CRE2, AP1(3) and SSRE1 elements in the human BSP gene promoter.

Effect of Photobiomodulation on Transforming Growth Factor-β1, Platelet-Derived Growth Factor-BB, and Interleukin-8 Release in Palatal Wounds After Free Gingival Graft Harvesting: A Randomized Clinical Study

PubMed Central

Lutfioğlu, Muge; Aydogdu, Ahmet; Saygun, N. Isil; Serdar, Muhittin A.

2016-01-01

Abstract Objective: This study evaluated the impact of photobiomodulation (PBM) on the healing of the donor palatal area following free gingival graft (FGG) harvesting by examining changes in transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-BB, and interleukin (IL)-8 levels in palatal wound fluid (PWF). Material and methods: Thirty patients were selected and randomly assigned to receive PBM (laser group) or PBM sham (sham group) in the palatine area after FGG harvesting. A neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (1064 nm) was applied to the test sites immediately after surgery and every 24 h thereafter for 4 days. PWF was collected on Days 7 and 12, and PWF TGF-β1, PDGF-BB, and IL-8 levels were analyzed by enzyme-linked immunosorbent assays (ELISA). Results: PWF TGF-β1, PDGF-BB, and IL-8 levels were significantly lower on Day 12 than on Day 7 for both groups. PWF TGF-β1, PDGF-BB, and IL-8 levels of the laser group were significantly higher than those of sham group on Day 7 (p < 0.05). PWF TGF-β1 levels were also significantly higher in laser group than in the sham group on Day 12; however, differences in PDGF-BB and IL-8 levels between groups on Day 12 were statistically nonsignificant. Conclusions: Observed increases in PWF TGF-β1, PDGF-BB, and IL-8 levels suggest that PBM may accelerate wound healing by stimulating production of selected mediators. PMID:27088277

Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson’s disease patients

PubMed Central

Paul, Gesine; Zachrisson, Olof; Varrone, Andrea; Almqvist, Per; Jerling, Markus; Lind, Göran; Rehncrona, Stig; Linderoth, Bengt; Bjartmarz, Hjalmar; Shafer, Lisa L.; Coffey, Robert; Svensson, Mikael; Mercer, Katarina Jansson; Forsberg, Anton; Halldin, Christer; Svenningsson, Per; Widner, Håkan; Frisén, Jonas; Pålhagen, Sven; Haegerstrand, Anders

2015-01-01

BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson’s disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 μg rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. TRIAL REGISTRATION. Clinical Trials.gov NCT00866502. FUNDING. Newron Sweden AB (former NeuroNova AB) and Swedish Governmental Agency for Innovation Systems (VINNOVA). PMID:25689258

Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson's disease patients.

PubMed

Paul, Gesine; Zachrisson, Olof; Varrone, Andrea; Almqvist, Per; Jerling, Markus; Lind, Göran; Rehncrona, Stig; Linderoth, Bengt; Bjartmarz, Hjalmar; Shafer, Lisa L; Coffey, Robert; Svensson, Mikael; Mercer, Katarina Jansson; Forsberg, Anton; Halldin, Christer; Svenningsson, Per; Widner, Håkan; Frisén, Jonas; Pålhagen, Sven; Haegerstrand, Anders

2015-03-02

BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 μg rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. TRIAL REGISTRATION. Clinical Trials.gov NCT00866502. FUNDING. Newron Sweden AB (former NeuroNova AB) and Swedish Governmental Agency for Innovation Systems (VINNOVA).

A biolayer interferometry-based enzyme-linked aptamer sorbent assay for real-time and highly sensitive detection of PDGF-BB.

PubMed

Gao, Shunxiang; Zheng, Xin; Wu, Jihong

2018-04-15

Accurate, fast and sensitive detection of disease-specific protein biomarkers, especially in blood, urine, or other bodily fluids, is an important approach to achieve early disease diagnosis. Platelet-derived growth factor-BB (PDGF-BB), a widely used biomarker, is involved in a substantial number of serious diseases, such as hepatic fibrosis, atherosclerosis, age-related macular degeneration and diabetic eye disease and is often over-expressed in human malignant tumors. Therefore, the development of sensitive and specific detection methods for PDGF-BB is of great importance for the early diagnosis of disease and assessments of patient recovery. In the current study, a biolayer interferometry-based enzyme-linked aptamer sorbent assay (BLI-ELASA) was successfully established for rapid (20-25min), high-throughput (8 or 16 samples) and real-time monitoring of PDGF-BB in clinical samples. The method exhibited a broad detection range from 0.5 to 1000ng/mL of PDGF-BB (good linear range from 0.5 to 10ng/mL), with a low detection limit of 0.08ng/mL. Moreover, BLI-ELASA was applied to the detection of PDGF-BB in spiked serum and urine samples and showed a high degree of selectivity for PDGF-BB, good reproducibility, and stability. We believe that the methodology in this work can be easily adapted to detect other biomolecules in clinical samples, including viruses, pathogens and toxins, in a rapid, sensitive, high-throughput and real-time manner. Copyright © 2017 Elsevier B.V. All rights reserved.

Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components

PubMed Central

Fekete, Natalie; Gadelorge, Mélanie; Fürst, Daniel; Maurer, Caroline; Dausend, Julia; Fleury-Cappellesso, Sandrine; Mailänder, Volker; Lotfi, Ramin; Ignatius, Anita; Sensebé, Luc; Bourin, Philippe; Schrezenmeier, Hubert; Rojewski, Markus Thomas

2012-01-01

Background aims The clinical use of human mesenchymal stromal cells (MSC) requires ex vivo expansion in media containing supplements such as fetal bovine serum or, alternatively, human platelet lysate (PL). Methods Platelet concentrates were frozen, quarantine stored, thawed and sterile filtered to obtain PL. PL content and its effect on fibroblast-colony-forming unit (CFU-F) formation, MSC proliferation and large-scale expansion were studied. Results PL contained high levels of basic fibroblast growth factor (bFGF), soluble CD40L (sCD40L), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-derived growth factor AA (PDGF-AA), platelet-derived growth factor AB/BB (PDGF-AB/BB), chemokine (C-C) ligand 5 (CCL5; RANTES) transforming growth factor-β1 (TGF-β1) and chemokine (C-X-C) ligand 1/2/3 (GRO), with low batch-to-batch variability, and most were stable for up to 14 days. Inhibition of PDGF-BB and bFGF decreased MSC proliferation by about 20% and 50%, respectively. The strongest inhibition (about 75%) was observed with a combination of anti-bFGF + anti-PDGF-BB and anti-bFGF + anti-TGF-β1 + anti-PDGF-BB. Interestingly, various combinations of recombinant PDGF-BB, bFGF and TGF-β1 were not sufficient to promote cell proliferation. PL from whole blood-derived pooled platelet concentrates and apheresis platelet concentrates did not differ significantly in their growth-promoting activity on MSC. Conclusions PL enhances MSC proliferation and can be regarded as a safe tool for MSC expansion for clinical purposes. \\in particular, PDGF-BB and bFGF are essential components for the growth-promoting effect of PL, but are not sufficient for MSC proliferation. PMID:22296115

Effects of ischemic preconditioning on PDGF-BB expression in the gerbil hippocampal CA1 region following transient cerebral ischemia

PubMed Central

Lee, Jae-Chul; Kim, Yang Hee; Lee, Tae-Kyeong; Kim, In Hye; Cho, Jeong Hwi; Cho, Geum-Sil; Shin, Bich-Na; Park, Joon Ha; Ahn, Ji Hyeon; Shin, Myoung Cheol; Cho, Jun Hwi; Kang, Il Jun; Won, Moo-Ho; Seo, Jeong Yeol

2017-01-01

Ischemic preconditioning (IPC) is induced by exposure to brief durations of transient ischemia, which results in ischemic tolerance to a subsequent longer or lethal period of ischemia. In the present study, the effects of IPC (2 min of transient cerebral ischemia) were examined on immunoreactivity of platelet-derived growth factor (PDGF)-BB and on neuroprotection in the gerbil hippocampal CA1 region following lethal transient cerebral ischemia (LTCI; 5 min of transient cerebral ischemia). IPC was subjected to a 2-min sublethal ischemia and a LTCI was given 5-min transient ischemia. The animals in all of the groups were given recovery times of 1, 2 and 5 days and change in PDGF-BB immunoreactivity was examined as was the neuronal damage/death in the hippocampus induced by LTCI. LTCI induced a significant loss of pyramidal neurons in the hippocampal CA1 region 5 days after LTCI, and significantly decreased PDGF-BB immunoreactivity in the CA1 pyramidal neurons from day 1 after LTCI. Conversely, IPC effectively protected the CA1 pyramidal neurons from LTCI and increased PDGF-BB immunoreactivity in the CA1 pyramidal neurons post-LTCI. In conclusion, the results demonstrated that LTCI significantly altered PDGF-BB immunoreactivity in pyramidal neurons in the hippocampal CA1 region, whereas IPC increased the immunoreactivity. These findings indicated that PDGF-BB may be associated with IPC-mediated neuroprotection. PMID:28627606

Synergistic effects of FGF-2 and PDGF-BB on angiogenesis and muscle regeneration in rabbit hindlimb ischemia model.

PubMed

Li, Jie; Wei, Yuquan; Liu, Kang; Yuan, Chuang; Tang, Yajuan; Quan, Qingli; Chen, Ping; Wang, Wei; Hu, Huozhen; Yang, Li

2010-07-01

Combinatorial strategy has been used in therapeutic angiogenesis in animal models of peripheral arterial disease (PAD) and coronary artery disease for decades. Previous studies have shown that basic fibroblast growth factor (FGF-2) and platelet-derived growth factor BB (PDGF-BB) proteins together establish functional and stable vascular networks on mouse corneal and also in animal model of hindlimb ischemia. However, the short half life of protein by single injection is not sufficient to achieve effective dosage, repeated and prolonged injection causes systemic toxicity. Here we study the synergistic effects of FGF-2 and PDGF-BB by intramuscular injection of naked plasmid DNA on therapeutic angiogenesis in rabbit model of hindlimb ischemia. We found that transient delivery of FGF-2 and PDGF-BB naked DNA together resulted in greater increases in capillary growth, collateral formation and popliteal blood flow compared with control and single gene delivery. Our data provided novel evidence of beneficial effects of DNA-based FGF-2 and PDFG-BB on muscle repair after ischemic injury. These findings reveal an alternative therapeutic approach in the treatment of ischemic diseases and even in muscular disorders. Copyright 2010. Published by Elsevier Inc.

Glutaredoxin modulates platelet-derived growth factor-dependent cell signaling by regulating the redox status of low molecular weight protein-tyrosine phosphatase.

PubMed

Kanda, Munetake; Ihara, Yoshito; Murata, Hiroaki; Urata, Yoshishige; Kono, Takaaki; Yodoi, Junji; Seto, Shinji; Yano, Katsusuke; Kondo, Takahito

2006-09-29

Glutaredoxin (GRX) is a glutathione-disulfide oxidoreductase involved in various cellular functions, including the redox-dependent regulation of certain integral proteins. Here we demonstrated that overexpression of GRX suppressed the proliferation of myocardiac H9c2 cells treated with platelet-derived growth factor (PDGF)-BB. After stimulation with PDGF-BB, the phosphorylation of PDGF receptor (PDGFR) beta was suppressed in GRX gene-transfected cells, compared with controls. Conversely, the phosphorylation was enhanced by depletion of GRX by RNA interference. In this study we focused on the role of low molecular weight protein-tyrosine phosphatase (LMW-PTP) in the dephosphorylation of PDGFRbeta via a redox-dependent mechanism. We found that depletion of LMW-PTP using RNA interference enhanced the PDGF-BB-induced phosphorylation of PDGFRbeta, indicating that LMW-PTP works for PDGFRbeta. The enhancement of the phosphorylation of PDGFRbeta was well correlated with inactivation of LMW-PTP by cellular peroxide generated in the cells stimulated with PDGF-BB. In vitro, with hydrogen peroxide treatment, LMW-PTP showed decreased activity with the concomitant formation of dithiothreitol-reducible oligomers. GRX protected LMW-PTP from hydrogen peroxide-induced oxidation and inactivation in concert with glutathione, NADPH, and glutathione disulfide reductase. This strongly suggests that retention of activity of LMW-PTP by enhanced GRX expression suppresses the proliferation of cells treated with PDGF-BB via enhanced dephosphorylation of PDGFRbeta. Thus, GRX plays an important role in PDGF-BB-dependent cell proliferation by regulating the redox state of LMW-PTP.

[Investigation of mechanisms of action of growth factors of autologous platelet-rich plasma used to treat erectile dysfunction].

PubMed

Epifanova, M V; Chalyi, M E; Krasnov, A O

2017-09-01

To determine the quantitative and qualitative composition of growth factors (PDGF-AA, PDGF-BB, VEGF, VEGF-D, FGF-acid, FGF-basic) and platelets in various modifications of APRP. Blood of 12 male volunteers (control group) and 12 patients with ED was used to prepare APRP and the subsequently determine the concentration of growth factors. The growth factor concentrations (FGF acid, FGF basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D) was determined using a flow cytometry-based xMAP Luminex (Gen-Probe) system. Concentration of platelets in APRP obtained by two stage centrifugation, reached 1480 (1120-1644) in the control group and 1232 (956-1502) in patients with ED. The concentration of growth factors in the samples prepared without preliminary freezing was: PDGF-AA 842 (22-3700), PDGF-BB 2837 (1460-4100), FGF-basic 7.9 (0.28-127), FGF-acid 3, 4 (0.14-11), VEGF 19 (4.6-46), VEGF-D 21 (14-38). After thawing, the concentration of all growth factors in the samples increased. The study findings suggest that the mechanism of erectile function recovery following the use of APRP is through the active substances detected in APRP, i.e. FGF-basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D and FGF-acid. Also, the study showed that the content of growth factors in APRP after of freezing/thawing is higher than in APRP that has not been frozen. This is due to the cell membrane destruction at extremely low temperatures during freezing.

Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated With rhPDGF-BB in Combination With a β-TCP-Collagen Matrix.

PubMed

Daniels, Timothy R; Younger, Alastair S E; Penner, Murray J; Wing, Kevin J; Le, Ian L D; Russell, Iain S; Lalonde, Karl-André; Evangelista, Peter T; Quiton, Jovelyn D; Glazebrook, Mark; DiGiovanni, Christopher W

2015-07-01

Ankle and hindfoot arthrodesis is often supplemented with autograft to promote bony union. Autograft harvest can lead to increased perioperative morbidity. Purified recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot fusion. This randomized controlled trial evaluated the efficacy and safety of rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate (β-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions. Seventy-five patients requiring ankle or hindfoot fusion were randomized 5:1 for rhPDGF-BB/β-TCP-collagen (treatment, n = 63) or autograft (control, n = 12). Prospective analysis included 142 autograft control subjects from another clinical trial with identical study protocols. Standardized operative and postoperative protocols were used. Patients underwent standard internal fixation augmented with autograft or 0.3 mg/mL rhPDGF-BB/β-TCP-collagen. Radiologic, clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary outcome was joint fusion (50% or more osseous bridging on computed tomography) at 24 weeks. Secondary outcomes included radiographs, clinical healing status, visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale score, Foot Function Index score, and Short Form-12 score. Noninferiority P values were calculated. Complete fusion of all involved joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63 (84%) rhPDGF-BB/β-TCP-collagen-treated patients and 100 of 154 (65%) autograft-treated patients (P < .001). Mean time to fusion was 14.3 ± 8.9 weeks for rhPDGF-BB/β-TCP-collagen patients versus 19.7 ± 11.5 weeks for autograft patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%) rhPDGF-BB/β-TCP-collagen patients and 120 of 154 (78%) autograft patients (P < .001). Safety-related outcomes were equivalent. Autograft controls had 2 bone graft harvest infections. Application of rhPDGF-BB/β-TCP-collagen was a safe, effective alternative to autograft for ankle and hindfoot fusions, eliminating the pain and morbidity associated with autograft harvesting. Level I, prospective randomized study. © The Author(s) 2015.

Cordyceps sinensis polysaccharide CPS-2 protects human mesangial cells from PDGF-BB-induced proliferation through the PDGF/ERK and TGF-β1/Smad pathways.

PubMed

Wang, Ying; Liu, Dan; Zhao, Huan; Jiang, Huixing; Luo, Chen; Wang, Min; Yin, Hongping

2014-02-15

CPS-2, a Cordyceps sinensis polysaccharide, has been demonstrated to have significant therapeutic activity against chronic renal failure. However, little is known about the underlying molecular mechanism. In this study, we found that CPS-2 could inhibit PDGF-BB-induced human mesangial cells (HMCs) proliferation in a dose-dependent manner. In addition, CPS-2 notably suppressed the expression of α-SMA, PDGF receptor-beta (PDGFRβ), TGF-β1, and Smad 3 in PDGF-BB-treated HMCs. Furthermore, PDGF-BB-stimulated ERK activation was significantly inhibited by CPS-2, and this inhibitory effect was synergistically potentiated by U0126. CPS-2 could prevent the PDGFRβ promoter activity induced by PDGF-BB, and return expression of PDGFRβ, TGF-β1, and TGFβRI to normal levels while cells were under PDGFRβ and ERK silencing conditions and transfected with DN-ERK. Taken together, these findings demonstrated that CPS-2 reduces PDGF-BB-induced cell proliferation through the PDGF/ERK and TGF-β1/Smad pathways, and it may have bi-directional regulatory effects on the PDGF/ERK cellular signaling pathway. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Atorvastatin calcium inhibits phenotypic modulation of PDGF-BB-induced VSMCs via down-regulation the Akt signaling pathway.

PubMed

Chen, Shuang; Liu, Baoqin; Kong, Dehui; Li, Si; Li, Chao; Wang, Huaqin; Sun, Yingxian

2015-01-01

Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the onset and progression of proliferative vascular diseases. In adult tissue, VSMCs exist in a physiological contractile-quiescent phenotype, which is defined by lack of the ability of proliferation and migration, while high expression of contractile marker proteins. After injury to the vessel, VSMC shifts from a contractile phenotype to a pathological synthetic phenotype, associated with increased proliferation, migration and matrix secretion. It has been demonstrated that PDGF-BB is a critical mediator of VSMCs phenotypic switch. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methyl-glutaryl l coenzyme A (HMG-CoA) reductase, exhibits various protective effects against VSMCs. In this study, we investigated the effects of atorvastatin calcium on phenotype modulation of PDGF-BB-induced VSMCs and the related intracellular signal transduction pathways. Treatment of VSMCs with atorvastatin calcium showed dose-dependent inhibition of PDGF-BB-induced proliferation. Atorvastatin calcium co-treatment inhibited the phenotype modulation and cytoskeleton rearrangements and improved the expression of contractile phenotype marker proteins such as α-SM actin, SM22α and calponin in comparison with PDGF-BB alone stimulated VSMCs. Although Akt phosphorylation was strongly elicited by PDGF-BB, Akt activation was attenuated when PDGF-BB was co-administrated with atorvastatin calcium. In conclusion, atorvastatin calcium inhibits phenotype modulation of PDGF-BB-induced VSMCs and activation of the Akt signaling pathway, indicating that Akt might play a vital role in the modulation of phenotype.

RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton.

PubMed

Tang, Lian; Dai, Fan; Liu, Yan; Yu, Xiaoqiang; Huang, Chao; Wang, Yuqin; Yao, Wenjuan

2018-05-20

The RhoA/ROCK signaling pathway regulates cell morphology, adhesion, proliferation, and migration. In this study, we investigated the regulatory role of RhoA/ROCK signaling on PDGF-BB-mediated smooth muscle phenotypic modulation and vascular remodeling and clarified the molecular mechanisms behind these effects. PDGF-BB treatment induced the activation of RhoA, ROCK, PDGF-Rβ, and the expression of PDGF-Rβ in HA-VSMCs (human aortic vascular smooth muscle cells). PDGF-Rβ inhibition and RhoA suppression blocked PDGF-BB-induced RhoA activation and ROCK induction. In addition, PDGF-BB-mediated cell proliferation and migration were suppressed by PDGF-Rβ inhibition, RhoA suppression, and ROCK inhibition, suggesting that PDGF-BB promotes phenotypic modulation of HA-VSMCs by activating the RhoA/ROCK pathway via the PDGF receptor. Moreover, suppressing both ROCK1 and ROCK2 blocked cell cycle progression from G0/G1 to S phase by decreasing the transcription and protein expression of cyclin D1, CDK2, and CDK4 via JNK/c-Jun pathway, thus reducing cell proliferation in PDGF-BB-treated HA-VSMCs. ROCK1 deletion, rather than ROCK2 suppression, significantly inhibited PDGF-BB-induced migration by reducing the expression of vimentin and preventing the remodeling of vimentin and phospho-vimentin. Furthermore, ROCK1 deletion suppressed vimentin by inhibiting the phosphorylation of Smad2/3 and the nuclear translocation of Smad4. These findings suggested that ROCK1 and ROCK2 might play different roles in PDGF-BB-mediated cell proliferation and migration in HA-VSMCs. In addition, PDGF-BB and its receptor participated in neointima formation and vascular remodeling by promoting cell cycle protein expression via the JNK pathway and enhancing vimentin expression in a rat balloon injury model; effects that were inhibited by treatment with fasudil. Together, the results of this study reveal a novel mechanism through which RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of Recombinant Human FGF-2 and PDGF-BB in Periodontal Regeneration: A Systematic Review and Meta-Analysis.

PubMed

Li, Feifei; Yu, Fanyuan; Xu, Xin; Li, Chunjie; Huang, Dingming; Zhou, Xuedong; Ye, Ling; Zheng, Liwei

2017-03-06

The prognosis for successful treatment of periodontal diseases is generally poor. Current therapeutic strategies often fail to regenerate infected periodontium. Recently an alternative strategy has been developed that combines conventional treatment with the application of recombinant human growth factors (rhGFs). But ambiguities in existed studies on the clinical efficacy of rhGFs do not permit either the identification of the specific growth factors effective for therapeutic interventions or the optimal concentration of them. Neither is it known whether the same rhGF can stimulate regeneration of both soft tissue and bone, or whether different patient populations call for differential use of the growth factors. In order to explore these issues, a meta-analysis was carried out. Particular attention was given to the therapeutic impact of fibroblast growth factor 2(FGF-2) and platelet derived growth factor BB (PDGF-BB). Our findings indicate that 0.3% rhFGF-2 and 0.3 mg/ml rhPDGF-BB show a greater capacity for periodontal regeneration than other concentrations and superiority to control groups with statistical significance. In the case of patients suffering only from gingival recession, however, the application of rhPDGF-BB produces no significant regenerative advantage. The findings of this study can potentially endow clinicians with guidelines for the appropriate application of these two rhGFs.

Atorvastatin Calcium Inhibits Phenotypic Modulation of PDGF-BB-Induced VSMCs via Down-Regulation the Akt Signaling Pathway

PubMed Central

Chen, Shuang; Liu, Baoqin; Kong, Dehui; Li, Si; Li, Chao; Wang, Huaqin; Sun, Yingxian

2015-01-01

Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the onset and progression of proliferative vascular diseases. In adult tissue, VSMCs exist in a physiological contractile-quiescent phenotype, which is defined by lack of the ability of proliferation and migration, while high expression of contractile marker proteins. After injury to the vessel, VSMC shifts from a contractile phenotype to a pathological synthetic phenotype, associated with increased proliferation, migration and matrix secretion. It has been demonstrated that PDGF-BB is a critical mediator of VSMCs phenotypic switch. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methyl-glutaryl l coenzyme A (HMG-CoA) reductase, exhibits various protective effects against VSMCs. In this study, we investigated the effects of atorvastatin calcium on phenotype modulation of PDGF-BB-induced VSMCs and the related intracellular signal transduction pathways. Treatment of VSMCs with atorvastatin calcium showed dose-dependent inhibition of PDGF-BB-induced proliferation. Atorvastatin calcium co-treatment inhibited the phenotype modulation and cytoskeleton rearrangements and improved the expression of contractile phenotype marker proteins such as α-SM actin, SM22α and calponin in comparison with PDGF-BB alone stimulated VSMCs. Although Akt phosphorylation was strongly elicited by PDGF-BB, Akt activation was attenuated when PDGF-BB was co-administrated with atorvastatin calcium. In conclusion, atorvastatin calcium inhibits phenotype modulation of PDGF-BB-induced VSMCs and activation of the Akt signaling pathway, indicating that Akt might play a vital role in the modulation of phenotype. PMID:25874930

Cordyceps sinensis polysaccharide inhibits PDGF-BB-induced inflammation and ROS production in human mesangial cells.

PubMed

Wang, Ying; Wang, Yan; Liu, Dan; Wang, Wang; Zhao, Huan; Wang, Min; Yin, Hongping

2015-07-10

CPS-F, a polysaccharide derived from Cordyceps sinensis, is a potential anti-inflammatory and anti-oxidative agent. We demonstrated that CPS-F not only inhibits platelet-derived growth factor BB (PDGF-BB)-induced intracellular reactive oxygen species (ROS) generation, and up-regulation of tumor necrosis factor-α (TNF-α), TNF-α receptor 1 (TNFR1), and monocyte chemotactic protein-1 (MCP-1), but also acts synergistically in combination with MAPK/ERK inhibitor U0126 and PI3K/Akt inhibitor LY294002. Additionally, up-regulation of pro-inflammatory factors was reversed by use of a combination of CPS-F and NADPH oxidase (NOX) inhibitor diphenyleneiodonium chloride (DPI) or silencing of NOX1. Furthermore, CPS-F prevents the PDGF receptor β (PDGFRβ) promoter activity induced by PDGF-BB in transfected cells and ameliorates increased levels of TNF-α, TNFR1, and MCP-1 when PDGFRβ is silenced, thereby suggesting that CPS-F possesses a bidirectional regulatory function. Our findings suggest CPS-F may exert its therapeutic effect for the treatment of glomerulonephritis related to human mesangial cells (HMCs) through the ERK1/2/Akt pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of calcium salts and bovine thrombin on growth factor release from equine platelet-rich gel supernatants.

PubMed

Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

2017-01-16

To compare five activation methods in equine platelet-rich plasma (PRP) by determination of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) concentrations in platelet-rich gel (PRG) supernatants. Platelet-rich plasma from 20 horses was activated by calcium chloride (CC), calcium gluconate (CG), bovine thrombin (BT), and their combinations, BTCC and BTCG. Both growth factor concentrations in PRG supernatants were measured by ELISA and compared with plasma and platelet lysates (PL) over time. Growth factor concentrations were significantly lower in plasma and higher for all PRG supernatants. Platelet lysates contained a significantly lower concentration of PDGF-BB than PRG supernatants and a significantly higher concentration of TGF-β1 than PRG supernatants. Clots from PRP activated with sodium salts were more stable over time and had significant growth factor release, whereas CC produced gross salt deposition. Significant correlations were noticed for platelet with leukocyte concentrations in PRP (r s : 0.76), platelet counts in PRP with TGF-β1 concentrations in PRG supernatants (r s : 0.86), platelet counts in PRP with PDGF-BB concentrations in PRG supernatants (r s : 0.78), leukocyte counts in PRP with TGF-β1 concentrations in PRG supernatants (r s : 0.76), and PDGF-BB concentrations with activating substances (r s : 0.72). Calcium gluconate was the better substance to induce PRP activation. It induced growth factor release free from calcium precipitates in the clots. Use of BT alone or combined with calcium salts was not advantageous for growth factor release.

Vertical ridge augmentation using an equine bone and collagen block infused with recombinant human platelet-derived growth factor-BB: a randomized single-masked histologic study in non-human primates.

PubMed

Nevins, Myron; Al Hezaimi, Khalid; Schupbach, Peter; Karimbux, Nadeem; Kim, David M

2012-07-01

This study tests the effectiveness of hydroxyapatite and collagen bone blocks of equine origin (eHAC), infused with recombinant human platelet-derived growth factor-BB (rhPDGF-BB), to augment localized posterior mandibular defects in non-human primates (Papio hamadryas). Bilateral critical-sized defects simulating severe atrophy were created at the time of the posterior teeth extraction. Test and control blocks (without growth factor) were randomly grafted into the respective sites in each non-human primate. All sites exhibited vertical ridge augmentation, with physiologic hard- and soft-tissue integration of the blocks when clinical and histologic examinations were done at 4 months after the vertical ridge augmentation procedure. There was a clear, although non-significant, tendency to increased regeneration in the test sites. As in the first two preclinical studies in this series using canines, experimental eHAC blocks infused with rhPDGF-BB proved to be a predictable and technically viable method to predictably regenerate bone and soft tissue in critical-sized defects. This investigation supplies additional evidence that eHAC blocks infused with rhPDGF-BB growth factor is a predictable and technically feasible option for vertical augmentation of severely resorbed ridges.

Portable aptamer biosensor of platelet-derived growth factor-BB using a personal glucose meter with triply amplified.

PubMed

Hong, Lu; Zhou, Fu; Shi, Dongmin; Zhang, Xiaojun; Wang, Guangfeng

2017-09-15

Sensitive and rapid detection of platelet-derived growth factor BB (PDGF-BB), a cancer-related protein, could help early diagnosis, treatment, and prognosis of cancers. Although some methods have been developed to detect PDGF-BB, few can provide quantitative results using an affordable and portable device that is suitable for home use or field application. In this work, we report the first use of a portable kind of personal glucose meter (PGM) combining a catalytic and molecular beacon (CAMB) system with a cation exchange reaction (CX reaction) for ultrasensitive PDGF-BB assay. It realized the amplification of the detection in three ways, including greater aptamer payload on nanoparticles, CX reaction releasing thousands of Zn 2+ and the cycle by the catalyzing cleavage of 8-17 DNAzyme. In the process, with the addition of PDGF-BB into the aptasensor, the specific recognition between aptamer and protein was initiated resulting in the combination of ZnS NNC for further CX reaction to release thousands of Zn 2+ , which could cleave the substrate DNA in the CAMB system realizing multiple cycle. The cleaved DNA fragment was designed with invertase-labeled could convert sucrose into glucose which could be detected and quantified by PGM accompanying with the change of color of the control window from yellow to green. The enhanced signal of the PGM has a relationship with the concentration of PDGF-BB in the range of 3.16×10 -16 M to 3.16×10 -12 M, and the detection limit is 0.11fM. Moreover, the catalytic and cleavage activities of 8-17 DNAzyme can be achieved in solution; thus, no enzyme immobilization is needed for detection. The triply amplified strategy showed high selectivity, stability, and applicability for detecting the desired protein. Copyright © 2017. Published by Elsevier B.V.

A monoclonal antibody against PDGF B-chain inhibits PDGF-induced DNA synthesis in C3H fibroblasts and prevents binding of PDGF to its receptor.

PubMed

Vassbotn, F S; Langeland, N; Hagen, I; Holmsen, H

1990-09-01

A monoclonal antibody (MAb 6D11) against platelet-derived growth factor (PDGF) was studied. We found that the MAb 6D11 in concentrations equimolar to PDGF blocked the [3H]thymidine incorporation in C3H/10T1/2 C18 fibroblasts stimulated by PDGF B-B and PDGF A-B. This inhibition was overcome by high doses of PDGF. The [3H]thymidine incorporation stimulated by other growth factors (aFGF, bFGF and bombesin) was not inhibited by the antibody. The MAb 6D11 blocked receptor binding of PDGF B-B, but not PDGF A-A. These findings suggest that the MAb 6D11 abolishes PDGF-induced DNA synthesis by blocking PDGF receptor binding. In this communication we demonstrate an isoform-specific monoclonal antibody against PDGF.

Role of magnolol in the proliferation of vascular smooth muscle cells.

PubMed

Wu, L; Zou, H; Xia, W; Dong, Q; Wang, L

2015-05-01

Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. Recently, magnolol has been reported to have a potential role in regulating tumor necrosis factor α-induced proliferation of VSMCs. However, the role of magnolol in platelet-derived growth factor (PDGF)-induced proliferation of VSMCs remains unknown. Our purpose was to elucidate the effect of magnolol on the proliferation of VSMCs induced by PDGF-BB and to investigate the underlying molecular mechanisms. Our data demonstrated that magnolol inhibited rat VSMC proliferation and DNA synthesis stimulated by 20 ng/ml PDGF-BB without causing cell cytotoxicity. Flow cytometric analysis showed that magnolol inhibited S-phase entry of VSMCs. We also demonstrated that magnolol caused this effect by inhibiting the mRNA and protein expression of cyclin D1, cyclin E, and cyclin-dependent kinases 2 and 4 in PDGF-BB-stimulated VSMCs. Further analysis showed that the inhibitory effect of magnolol on the proliferation of VSMCs was associated with the inhibition of the PDGF-BB-stimulated production of intracellular reactive oxygen species (ROS) and Ras, MEK, and ERK1/2 activation. These results demonstrate that magnolol can block the proliferation of VSMCs through inhibition of intracellular ROS production and Ras-MEK-ERK1/2 pathways. Magnolol, therefore, has a potential application in preventing atherosclerosis and restenosis.

Tangeretin, a citrus flavonoid, inhibits PGDF-BB-induced proliferation and migration of aortic smooth muscle cells by blocking AKT activation.

PubMed

Seo, Juhee; Lee, Hyun Sun; Ryoo, Sungwoo; Seo, Jee Hee; Min, Byung-Sun; Lee, Jeong-Hyung

2011-12-30

Tangeretin, a natural polymethoxylated flavone concentrated in the peel of citrus fruits, is known to have antiproliferative, antiinvasive, antimetastatic and antioxidant activities. However, the effect of tangeretin on vascular smooth muscle cells (VSMCs) is unknown. This study examined the effect of tangeretin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of rat aortic smooth muscle cells (RASMCs) as well as its underlying mechanisms. Tangeretin significantly inhibited proliferation, DNA synthesis and migration of PDGF-BB-stimulated RASMCs without inducing cell death. Treatment with tangeretin-induced cell-cycle arrest in the G₀/G₁ phase was associated with down-regulation of cyclin D1 and cyclin E in addition to up-regulation of p27(kip1). We also showed that tangeretin inhibited PDGF-BB-induced phosphorylation of AKT, while it had no effect on the phosphorylation of phospholipase Cγ (PLCγ), PDGF receptor β-chain (PDGF-Rβ) and extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs). An in vitro kinase assay revealed that tangeretin inhibited AKT activity in a dose-dependent manner. Moreover, treatment of LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, had similar effects than that of tangeretin on the expression of p27(kip1) and cyclin D1, as well as cell migration in PDFG-BB-stimulated RASMCs. Taken together, these findings suggest that tangeretin could suppress PDGF-BB-induced proliferation and migration of RASMCs through the suppression of PI3K/AKT signaling pathway, and may be a potential candidate for preventing or treating vascular diseases, such as atherosclerosis and restenosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Carbon-based nanocomposites with aptamer-templated silver nanoclusters for the highly sensitive and selective detection of platelet-derived growth factor.

PubMed

Zhang, Zhihong; Guo, Chuanpan; Zhang, Shuai; He, Linghao; Wang, Minghua; Peng, Donglai; Tian, Junfeng; Fang, Shaoming

2017-03-15

We synthesized two kinds of carbon-based nanocomposites of silver nanoclusters (AgNCs). An aptamer for targeted platelet-derived growth factor-BB (PDGF-BB) detection was used as the organic phase to produce AgNCs@Apt, three dimensional reduced graphene oxide@AgNCs@Aptamer (3D-rGO@AgNCs@Apt), and graphene quantum dots@AgNCs@Aptamer (GQD@AgNCs@Apt) nanocomposites. The formation mechanism of the developed nanocomposites was described by detailed characterizations of their chemical and crystal structures. Subsequently, the as-synthesized nanoclusters containing aptamer strands were applied as the sensitive layers to fabricate a novel electrochemical aptasensor for the detection of PDGF-BB, which may be directly used to determine the target protein. Electrochemical impedance spectra showed that the developed 3D-rGO@AgNCs@Apt-based biosensor exhibited the highest sensitivity for PDGF-BB detection among three kinds of fabricated aptasensors, with an extremely low detection limit of 0.82pgmL -1 . In addition, the 3D-rGO@AgNCs@Apt-based biosensor showed high selectivity, stability, and applicability for the detection of PDGF-BB. This finding indicated that the AgNC-based nanocomposites prepared by a one-step method could be used as an electrochemical biosensor for various detection procedures in the biomedical field. Copyright © 2016 Elsevier B.V. All rights reserved.

IGF-1 and PDGF-bb Suppress IL-1β-Induced Cartilage Degradation through Down-Regulation of NF-κB Signaling: Involvement of Src/PI-3K/AKT Pathway

PubMed Central

Mobasheri, Ali; Buhrmann, Constanze; Aldinger, Constance; Rad, Jafar Soleimani; Shakibaei, Mehdi

2011-01-01

Objective Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of osteoarthritis (OA). Growth factors (GFs) capable of antagonizing the catabolic actions of cytokines may have therapeutic potential in the treatment of OA. Herein, we investigated the potential synergistic effects of insulin-like growth factor (IGF-1) and platelet-derived growth factor (PDGF-bb) on different mechanisms participating in IL-1β-induced activation of nuclear transcription factor-κB (NF-κB) and apoptosis in chondrocytes. Methods Primary chondrocytes were treated with IL-1β to induce dedifferentiation and co-treated with either IGF-1 or/and PDGF-bb and evaluated by immunoblotting and electron microscopy. Results Pretreatment of chondrocytes with IGF-1 or/and PDGF-bb suppressed IL-1β-induced NF-κB activation via inhibition of IκB-α kinase. Inhibition of IκB-α kinase by GFs led to the suppression of IκB-α phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene products involved in inflammation and cartilage degradation (COX-2, MMPs) and apoptosis (caspase-3). GFs or BMS-345541 (specific inhibitor of the IKK) reversed the IL-1β-induced down-regulation of collagen type II, cartilage specific proteoglycans, β1-integrin, Shc, activated MAPKinase, Sox-9 and up-regulation of active caspase-3. Furthermore, the inhibitory effects of IGF-1 or/and PDGF-bb on IL-1β-induced NF-κB activation were sensitive to inhibitors of Src (PP1), PI-3K (wortmannin) and Akt (SH-5), suggesting that the pathway consisting of non-receptor tyrosine kinase (Src), phosphatidylinositol 3-kinase and protein kinase B must be involved in IL-1β signaling. Conclusion The results presented suggest that IGF-1 and PDGF-bb are potent inhibitors of IL-1β-mediated activation of NF-κB and apoptosis in chondrocytes, may be mediated in part through suppression of Src/PI-3K/AKT pathway, which may contribute to their anti-inflammatory effects. PMID:22194879

Localization and function of KLF4 in cytoplasm of vascular smooth muscle cell

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yan; The Third Hospital of Hebei Medical University, Shijazhuang; Zheng, Bin

2013-06-28

Highlights: •PDGF-BB prompts the translocation of KLF4 to the cytoplasm. •PDGF-BB promotes interaction between KLF4 and actin in the cytoplasm. •Phosphorylation and SUMOylation of KLF4 participates in regulation of cytoskeletal organization. •KLF4 regulates cytoskeleton by promoting the expression of contraction-associated genes. -- Abstract: The Krüppel-like factor 4 is a DNA-binding transcriptional regulator that regulates a diverse array of cellular processes, including development, differentiation, proliferation, and apoptosis. The previous studies about KLF4 functions mainly focused on its role as a transcription factor, its functions in the cytoplasm are still unknown. In this study, we found that PDGF-BB could prompt the translocationmore » of KLF4 to the cytoplasm through CRM1-mediated nuclear export pathway in vascular smooth muscle cells (VSMCs) and increased the interaction of KLF4 with actin in the cytoplasm. Further study showed that both KLF4 phosphorylation and SUMOylation induced by PDGF-BB participates in regulation of cytoskeletal organization by stabilizing the actin cytoskeleton in VSMCs. In conclusion, these results identify that KLF4 participates in the cytoskeletal organization by stabilizing cytoskeleton in the cytoplasm of VSMCs.« less

PDGF-beta receptor expression and ventilatory acclimatization to hypoxia in the rat.

PubMed

Alea, O A; Czapla, M A; Lasky, J A; Simakajornboon, N; Gozal, E; Gozal, D

2000-11-01

Activation of platelet-derived growth factor-beta (PDGF-beta) receptors in the nucleus of the solitary tract (nTS) modulates the late phase of the acute hypoxic ventilatory response (HVR) in the rat. We hypothesized that temporal changes in PDGF-beta receptor expression could underlie the ventilatory acclimatization to hypoxia (VAH). Normoxic ventilation was examined in adult Sprague-Dawley rats chronically exposed to 10% O(2), and at 0, 1, 2, 7, and 14 days, Northern and Western blots of the dorsocaudal brain stem were performed for assessment of PDGF-beta receptor expression. Although no significant changes in PDGF-beta receptor mRNA occurred over time, marked attenuation of PDGF-beta receptor protein became apparent after day 7 of hypoxic exposure. Such changes were significantly correlated with concomitant increases in normoxic ventilation, i.e., with VAH (r: -0.56, P < 0.005). In addition, long-term administration of PDGF-BB in the nTS via osmotic pumps loaded with either PDGF-BB (n = 8) or vehicle (Veh; n = 8) showed that although no significant changes in the magnitude of acute HVR occurred in Veh over time, the typical attenuation of HVR by PDGF-BB decreased over time. Furthermore, PDGF-BB microinjections did not attenuate HVR in acclimatized rats at 7 and 14 days of hypoxia (n = 10). We conclude that decreased expression of PDGF-beta receptors in the dorsocaudal brain stem correlates with the magnitude of VAH. We speculate that the decreased expression of PDGF-beta receptors is mediated via internalization and degradation of the receptor rather than by transcriptional regulation.

Control of Human Endometrial Stromal Cell Motility by PDGF-BB, HB-EGF and Trophoblast-Secreted Factors

PubMed Central

Schwenke, Maren; Knöfler, Martin; Velicky, Philipp; Weimar, Charlotte H. E.; Kruse, Michelle; Samalecos, Annemarie; Wolf, Anja; Macklon, Nick S.; Bamberger, Ana-Maria; Gellersen, Birgit

2013-01-01

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site. PMID:23349855

Chitosan-plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies.

PubMed

Jean, M; Smaoui, F; Lavertu, M; Méthot, S; Bouhdoud, L; Buschmann, M D; Merzouki, A

2009-09-01

Growth factor therapy is an emerging treatment modality that enhances tissue vascularization, promotes healing and regeneration and can treat a variety of inflammatory diseases. Both recombinant human growth factor proteins and their gene therapy are in human clinical trials to heal chronic wounds. As platelet-derived growth factor-bb (PDGF-BB) and fibroblast growth factor-2 (FGF-2) are known to induce chemotaxis, proliferation, differentiation, and matrix synthesis, we investigated a non-viral means for gene delivery of these factors using the cationic polysaccharide chitosan. Chitosan is a polymer of glucosamine and N-acetyl-glucosamine, in which the percentage of the residues that are glucosamine is called the degree of deacetylation (DDA). The purpose of this study was to express PDGF-BB and FGF-2 genes in mice using chitosan-plasmid DNA nanoparticles for the controlled delivery of genetic material in a specific, efficient, and safe manner. PDGF-BB and FGF-2 genes were amplified from human tissues by RT-PCR. To increase the secretion of FGF-2, a recombinant 4sFGF-2 was constructed bearing eight amino-acid residues of the signal peptide of FGF-4. PCR products were inserted into the expression vector pVax1 to produce recombinant plasmids pVax1-4sFGF2 and pVax1-PDGF-BB, which were then injected into BALB/C mice in the format of polyelectrolyte nanocomplexes with specific chitosans of controlled DDA and molecular weight, including 92-10, 80-10, and 80-80 (DDA-number average molecular weight or M(n) in kDa). ELISA assays on mice sera showed that recombinant FGF-2 and PDGF-BB proteins were efficiently expressed and specific antibodies to these proteins could be identified in sera of injected mice, but with levels that were clearly dependent on the specific chitosan used. We found high DDA low molecular weight chitosans to be efficient protein expressors with minimal or no generation of neutralizing antibodies, while lowering DDA resulted in greater antibody levels and correspondingly lower levels of detected recombinant protein. Histological analyses corroborated these results by revealing greater inflammatory infiltrates in lower DDA chitosans, which produced higher antibody titers. We found, in general, a more efficient delivery of the plasmids by subcutaneous than by intramuscular injection. Specific chitosan carriers were identified to be either efficient non-toxic therapeutic protein delivery systems or vectors for DNA vaccines.

Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells

PubMed Central

Han, Joo-Hui; Kim, Yohan; Jung, Sang-Hyuk; Lee, Jung-Jin; Park, Hyun-Soo; Song, Gyu-Yong; Cuong, Nguyen Manh; Kim, Young Ho

2015-01-01

The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G0/G1 to S phase of the cell cycle, as measured by [3H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G0/G1 phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis. PMID:26330754

Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation.

PubMed

Akar, Banu; Jiang, Bin; Somo, Sami I; Appel, Alyssa A; Larson, Jeffery C; Tichauer, Kenneth M; Brey, Eric M

2015-12-01

Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro, but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here, we report on a method for the generation of persistent in vivo gradients of growth factors in a three-dimensional (3D) biomaterial system. Fibrin loaded porous poly (ethylene glycol) (PEG) scaffolds were generated using a particulate leaching method. Platelet derived growth factor BB (PDGF-BB) was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres which were placed distal to the tissue-material interface. PLGA provides sustained release of PDGF-BB and its diffusion through the porous structure results in gradient formation. Gradients within the scaffold were confirmed in vivo using near-infrared fluorescence imaging and gradients were present for more than 3 weeks. The diffusion of PDGF-BB was modeled and verified with in vivo imaging findings. The depth of tissue invasion and density of blood vessels formed in response to the biomaterial increased with magnitude of the gradient. This biomaterial system allows for generation of sustained growth factor gradients for the study of tissue response to gradients in vivo. Published by Elsevier Ltd.

The Use of Recombinant Human Platelet-Derived Growth Factor for Maxillary Sinus Augmentation.

PubMed

Kubota, Atsushi; Sarmiento, Hector; Alqahtani, Mohammed Saad; Llobell, Arturo; Fiorellini, Joseph P

The maxillary sinus augmentation procedure has become a predictable treatment to regenerate bone for implant placement. The purpose of this study was to evaluate the effect of recombinant human platelet-derived growth factor BB (rhPDGF-BB) combined with a deproteinized cancellous bovine bone graft for sinus augmentation. The lateral window approach was used for maxillary sinuses with minimal residual bone. After a healing period of 4 months, dental implants were placed and then restored following a 2-month osseointegration period. The result demonstrated increased bone height and ISQ values and a 100% survival rate. This study indicates that the addition of rhPDGF-BB to deproteinized cancellous bovine bone accelerated the healing period in maxillary sinuses with minimal native bone.

Pretreatment with platelet derived growth factor-BB modulates the ability of costochondral resting zone chondrocytes incorporated into PLA/PGA scaffolds to form new cartilage in vivo.

PubMed

Lohmann, C H; Schwartz, Z; Niederauer, G G; Carnes, D L; Dean, D D; Boyan, B D

2000-01-01

Optimal repair of chondral defects is likely to require both a suitable population of chondrogenic cells and a biodegradable matrix to provide a space-filling structural support during the early stages of cartilage formation. This study examined the ability of chondrocytes to support cartilage formation when incorporated into biodegradable scaffolds constructed from copolymers (PLG) of polylactic acid (PLA) and polyglycolic acid (PGA) and implanted in the calf muscle of nude mice. Scaffolds were fabricated to be more hydrophilic (PLG-H) or were reinforced with 10% PGA fibers (PLG-FR), increasing the stiffness of the implant by 20-fold. Confluent primary cultures of rat costochondral resting zone chondrocytes (RC) were loaded into PLG-H foams and implanted intramuscularly. To determine if growth factor pretreatment could modulate the ability of the cells to form new cartilage, RC cells were pretreated with recombinant human platelet derived growth factor-BB IPDGF-BB) for 4 or 24 h prior to implantation. To assess whether scaffold material properties could affect the ability of chondrogenic cells to form cartilage, RC cells were also loaded into PLG-FR scaffolds. To determine if the scaffolds or treatment with PDGF-BB affected the rate of chondrogenesis, tissue at the implant site was harvested at four and eight weeks post-operatively, fixed, decalcified and embedded in paraffin. Sections were obtained along the transverse plane of the lower leg, stained with haematoxylin and eosin, and then assessed by morphometric analysis for area of cartilage, area of residual implant, and area of fibrous connective tissue formation (fibrosis). Whether or not the cartilage contained hypertrophic cells was also assessed. The amount of residual implant did not change with time in any of the implanted tissues. The area occupied by PLG-FR implants was greater than that occupied by PLG-H implants at both time points. All implants were surrounded by fibrous connective tissue, whether they were seeded with RC cells or not. The amount of fibrosis was reduced at eight weeks for both implant types. When RC cells were present, the amount of fibrosis was less than seen in cell-free scaffolds. Pretreatment with PDGF-BB caused a slightly greater degree of fibrosis at four weeks than was seen if untreated cells were used in the implants. However, at eight weeks, if the cells had been exposed to PDGF-BB for 24 h, fibrosis was comparable to that seen associated with cell-free scaffolds. The cells supported an equivalent area of cartilage formation in both scaffolds. PDGF-BB caused a time-dependent decrease in cartilage formation at four weeks, but at eight weeks, there was a marked increase in cartilage formation in PDGF-BB-treated cells that was greatest in cells exposed for 4 h compared to those exposed for 24 h. Moreover, PDGF-BB decreased the formation of hypertrophic cells. The results indicate that in this model, RC cells produce cartilage; pretreatment of the RC cells with PDGF-BB promotes retention of a hyaline-like chondrogenic phenotype; and the material properties of the implant do not negatively impact on the ability of the cells to support chondrogenesis.

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, Dong Ju; Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA; Kim, Soo Yeon

2012-10-19

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murinemore » model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.« less

Bone resorption analysis of platelet-derived growth factor type BB application on collagen for bone grafts secured by titanium mesh over a pig jaw defect model

PubMed Central

Herford, Alan Scott; Cicciù, Marco

2012-01-01

Purpose: The aim of this investigation was to evaluate whether the addition of the platelet derived growth factor type BB (PDGF-BB) to a collagen matrix applied on a titanium mesh would favor healing and resorption onto the grafted bone. A histologic and radiographic study of two different groups (test and control) was performed. Designs: A surgical procedure was performed on 8 pigs to obtain 16 bilateral mandibular alveolar defects. All the defects were then reconstructed with a mixture of autogenous bovine bone using titanium mesh positioning. Two groups, with a total of 16 defects were created: The first to study collagen sponge and PDGF-BB and the second to control collagen only. The collagen matrix was positioned directly over the mesh and soft tissue was closed without tensions onto both groups without attempting to obtain primary closure. Possible exposure of the titanium mesh as well as the height and volume of the new bone was recorded. Results: New bone formation averaged about 6.68 mm in the test group studied; the control group had less regenerated bone at 4.62 mm. Conclusion: PDGF-BB addition to the collagen matrix induced a strong increase in hard and soft tissue healing and favored bone formation, reducing bone resorption even if the mesh was exposed. PMID:23833493

Horizontal Guided Bone Regeneration in the Esthetic Area with rhPDGF-BB and Anorganic Bovine Bone Graft: A Case Report.

PubMed

Chiantella, Giovanni Carlo

2016-01-01

The present article describes the treatment given to a patient who underwent horizontal ridge augmentation surgery in the maxillary anterior area due to the premature loss of the maxillary central incisors. The complete dehiscence of the buccal plate was detected after elevation of mucoperiosteal flaps. The lesion was overfilled with deproteinized bovine xenograft particles combined with recombinant human platelet-derived growth factor BB (rhPDGF-BB) and covered with a porcine collagen barrier hydrated with the same growth factor. The soft tissues healed with no adverse complications. After 12 months, reentry surgery was carried out to place endosseous implants. Complete bone regeneration with the presence of bone-like tissue was observed. Cross-sectional computed tomography scan images confirmed integration of the bone graft and reconstruction of the lost hard tissue volume. The implants were inserted in an optimal three-dimensional position, thus facilitating esthetic restoration. Two years after insertion of final crowns, cone beam computed tomography scans displayed the stability of regenerated hard tissues around the implants. Controlled clinical studies are necessary to determine the benefit of hydrating bovine bone particles and collagen barriers with rhPDGF-BB for predictable bone regeneration of horizontal lesions.

A newly synthesized Ligustrazine stilbene derivative inhibits PDGF-BB induced vascular smooth muscle cell phenotypic switch and proliferation via delaying cell cycle progression.

PubMed

Peng, Chunlian; Zhang, Siming; Liu, Haixin; Jiao, Yanxiao; Su, Guifa; Zhu, Yan

2017-11-05

Vascular Smooth muscle cells (VSMCs) possess remarkable phenotype plasticity that allows it to rapidly adapt to fluctuating environmental cues, including the period of development and progression of vascular diseases such as atherosclerosis and restenosis subsequent to vein grafting or coronary intervention. Although VSMC phenotypic switch is an attractive target, there is no effective drug so far. Using rat aortic VSMCs, we investigate the effects of Ligustrazine and its synthetic derivatives on platelet-derived growth factor-BB (PDGF-BB) induced proliferation and phenotypic switch by a cell image-based screening of 60 Ligustrazine stilbene derivatives. We showed that one of the Ligustrazine stilbene derivatives TMP-C 4a markedly inhibited PDGF-BB-induced VSMCs proliferation in a time and dose-dependent manner, which is more potent than Ligustrazine. Stimulation of contractile VSMCs with PDGF-BB significantly reduced the contractile marker protein α-smooth muscle actin expression and increased the synthetic marker proteins osteopontin expression. However, TMP-C 4a effectively reversed this phenotypic switch, which was accompanied by a decreased expression of Matrix metalloproteinase 2 and 9 (MMP2 and MMP9) and cell cycle related proteins, including cyclin D1 and CDK4. In conclusion, the present study showed that a new Ligustrazine stilbene derivative TMP-C 4a suppressed PDGF-induced VSMC proliferation and phenotypic switch, indicating that it has a potential to become a promising therapeutic agent for treating VSMC-related atherosclerosis and restenosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulation of neuroblastoma differentiation by forkhead transcription factors FOXO1/3/4 through the receptor tyrosine kinase PDGFRA

PubMed Central

Mei, Yang; Wang, Zhanxiang; Zhang, Lei; Zhang, Yiru; Li, Xiaoyu; Liu, Huihui; Ye, Jing; You, Han

2012-01-01

Neuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial early event in neuroblastoma pathogenesis is arrested differentiation of neuroblasts at various stages. Treatment of neuroblastoma with TPA and PDGF-BB leads to terminal differentiation of neuroblastoma cells. However, the signaling pathways that are involved in this process remain largely unknown. Here, we report that inhibition of endogenous FOXO proteins attenuated TPA/PDGF-BB mediated differentiation of neuroblastoma cells. Activated FOXO transcription factors acted on PDGFRA promoter to direct its basal mRNA expression as well as its induction upon serum deprivation. Depletion of endogenous PDGFRA in neuroblastoma cells significantly diminished neurite formation and extension under TPA/PDGF-BB treatment. Furthermore, ectopic expression of PDGFRA abolished the blockage of neuroblastoma differentiation by FOXOs inhibition. These findings define the FOXO–PDGFRA axis as crucial mechanistic components that govern TPA-induced neuroblastoma differentiation. PMID:22411791

HIV-1 Tat-mediated induction of Platelet-derived Growth Factor in Astrocytes: Role of Early Growth Response Gene 1

PubMed Central

Bethel-Brown, Crystal; Yao, Honghong; Callen, Shannon; Lee, Young Han; Dash, Prasanta K; Kumar, Anil; Buch, Shilpa

2011-01-01

HIV-associated neurological disorders (HAND) are estimated to affect almost 60% of HIV infected individuals. HIV-encephalitis (HIVE), the pathological correlate of the most severe form of HAND is often characterized by glial activation, cytokine/chemokine dysregulation, and neuronal damage and loss. However, the severity of HIVE correlates better with glial activation rather than viral load. Using the macaque model, it has been demonstrated that simian immunodeficiency virus encephalitis (SIVE) correlates with increased expression of the mitogen platelet-derived growth factor-B (PDGF-B) chain in the brain. The present study was aimed at exploring the role of PDGF-B chain in HIV-associated activation and proliferation of astrocytes. Specifically, the data herein demonstrate that exposure of rat and human astrocytes to the HIV-1 protein, Tat resulted in the induction of PDGF at both the mRNA and protein levels. Furthermore, PDGF-BB induction was regulated by activation of ERK1/2 and JNK signaling pathways and the downstream transcription factor, early growth response 1(Egr-1). Chromatin immunoprecipitation (ChIP) assays demonstrated binding of Egr-1 to the PDGF-B promoter. Exposure of astrocytes to PDGF-BB, in turn, led to both increased proliferation and release of pro-inflammatory cytokines MCP-1 and IL-1β. Since astrogliosis is linked to disease severity, understanding its regulation by PDGF-BB could aid in the development of therapeutic intervention strategies for HAND. PMID:21368226

Inhibitory effect of PDGF-BB and serum-stimulated responses in vascular smooth muscle cell proliferation by hinokitiol via up-regulation of p21 and p53.

PubMed

Li, Jiun-Yi; Liu, Chun-Ping; Shiao, Wei-Cheng; Jayakumar, Thanasekaran; Li, Yi-Shin; Chang, Nen-Chung; Huang, Shih-Yi; Hsieh, Cheng-Ying

2018-04-01

Vascular smooth muscle cell (VSMC) proliferation plays a major role in the progression of vascular diseases. In the present study, we established the efficacy and the mechanisms of action of hinokitiol, a tropolone derivative found in Chamaecyparis taiwanensis , Cupressaceae, in relation to platelet-derived growth factor-BB (PDGF-BB) and serum-dependent VSMC proliferation. Primary cultured rat VSMCs were pre-treated with hinokitiol and then stimulated by PDGF-BB (10 ng/ml) or serum (10% fetal bovine serum). Cell proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactose dehydrogenase assay, respectively. The degree of DNA synthesis was evaluated by BrdU-incorporation measurements and observed using confocal microscopy. Immunoblotting was utilized to determine the protein level of p-extracellular signal-regulated kinase (ERK) 1/2, p-Akt, p-phosphoinositide 3-kinase (PI3K), p-Janus kinase 2 (JAK2), p-p53, and p21 Cip1 . The promoter activity of p21 and p53 activity were measured by dual luciferase reporter assay. Treatment with hinokitiol (1-10 μM) inhibited PDGF-BB and serum-induced VSMC proliferation and DNA synthesis in a concentration-dependent manner. Cytotoxicity was not observed in hinokitiol-treated VSMCs at the studied concentrations. Pre-incubation of VSMCs with hinokitiol did not alter PDGF-BB-induced phosphorylation of ERK1/2, Akt, PI3K or JAK2. Interestingly, hinokitiol induced promoter activity of p21 and p21 protein expression in VSMCs. Furthermore, hinokitiol augmented p53 protein phosphorylation and subsequently led to enhanced p53 activity. These data suggest that the anti-proliferative effects of hinokitiol in VSMCs may be mediated by activation of p21 and p53 signaling pathways, and it may contribute to the prevention of vascular diseases associated with VSMC proliferation.

Inhibitory effect of PDGF-BB and serum-stimulated responses in vascular smooth muscle cell proliferation by hinokitiol via up-regulation of p21 and p53

PubMed Central

Li, Jiun-Yi; Liu, Chun-Ping; Shiao, Wei-Cheng; Jayakumar, Thanasekaran; Li, Yi-Shin; Chang, Nen-Chung

2018-01-01

Introduction Vascular smooth muscle cell (VSMC) proliferation plays a major role in the progression of vascular diseases. In the present study, we established the efficacy and the mechanisms of action of hinokitiol, a tropolone derivative found in Chamaecyparis taiwanensis, Cupressaceae, in relation to platelet-derived growth factor-BB (PDGF-BB) and serum-dependent VSMC proliferation. Material and methods Primary cultured rat VSMCs were pre-treated with hinokitiol and then stimulated by PDGF-BB (10 ng/ml) or serum (10% fetal bovine serum). Cell proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactose dehydrogenase assay, respectively. The degree of DNA synthesis was evaluated by BrdU-incorporation measurements and observed using confocal microscopy. Immunoblotting was utilized to determine the protein level of p-extracellular signal-regulated kinase (ERK) 1/2, p-Akt, p-phosphoinositide 3-kinase (PI3K), p-Janus kinase 2 (JAK2), p-p53, and p21Cip1. The promoter activity of p21 and p53 activity were measured by dual luciferase reporter assay. Results Treatment with hinokitiol (1–10 μM) inhibited PDGF-BB and serum-induced VSMC proliferation and DNA synthesis in a concentration-dependent manner. Cytotoxicity was not observed in hinokitiol-treated VSMCs at the studied concentrations. Pre-incubation of VSMCs with hinokitiol did not alter PDGF-BB-induced phosphorylation of ERK1/2, Akt, PI3K or JAK2. Interestingly, hinokitiol induced promoter activity of p21 and p21 protein expression in VSMCs. Furthermore, hinokitiol augmented p53 protein phosphorylation and subsequently led to enhanced p53 activity. Conclusions These data suggest that the anti-proliferative effects of hinokitiol in VSMCs may be mediated by activation of p21 and p53 signaling pathways, and it may contribute to the prevention of vascular diseases associated with VSMC proliferation. PMID:29765446

Corynoxeine isolated from the hook of Uncaria rhynchophylla inhibits rat aortic vascular smooth muscle cell proliferation through the blocking of extracellular signal regulated kinase 1/2 phosphorylation.

PubMed

Kim, Tack-Joong; Lee, Ju-Hyun; Lee, Jung-Jin; Yu, Ji-Yeon; Hwang, Bang-Yeon; Ye, Sang-Kyu; Shujuan, Li; Gao, Li; Pyo, Myoung-Yun; Yun, Yeo-Pyo

2008-11-01

The proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis. Uncaria rhynchophylla is traditional Chinese herb that has been applied to the treatment of convulsive disorders, such as epilepsy, in China. In the present study, we examined whether corynoxeine exerts inhibitory effects on platelet-derived growth factor (PDGF)-BB-induced rat aortic VSMC proliferation and the possible mechanism of such effects. Pre-treatment of VSMCs with corynoxeine (5-50 microM) for 24 h resulted in significant decreases in cell number without any cytotoxicity; the inhibition percentages were 25.0+/-12.5, 63.0+/-27.5 and 88.0+/-12.5% at 5, 20 and 50 microM, respectively. Also, corynoxeine significantly inhibited the 50 ng/ml PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without any cytotoxicity; the inhibitions were 32.8+/-11.0, 51.8+/-8.0 and 76.9+/-7.4% at concentrations of 5, 20 and 50 microM, respectively. Pre-incubation of VSMCs with corynoxeine significantly inhibited PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, whereas corynoxeine had no effects on mitogen-activated protein kinase (MAPK/ERK)-activating kinase 1 and 2 (MEK1/2), Akt, or phospholipase C (PLC)gamma1 activation or on PDGF receptor beta (PDGF-Rbeta) phosphorylation. These results suggest that corynoxeine is a potent ERK1/2 inhibitor of key PDGF-BB-induced VSMC proliferation and may be useful in the prevention and treatment of vascular diseases and restenosis after angioplasty.

Effect of PDGF-BB and beta-tricalcium phosphate (β-TCP) on bone formation around dental implants: a pilot study in sheep.

PubMed

Choo, Tina; Marino, Victor; Bartold, P Mark

2013-02-01

The aim of this investigation was to examine the effect of a combination of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (β-TCP) on bone healing around dental implants with critical size circumferential defects. Three critical size circumferential defects were prepared in the ilium of six sheep. Three dental implants were placed into the centre of each defect and the 3.25 mm circumferential gap was filled with (a) blood clot alone; (b) β-TCP; (c) rhPDGF-BB (0.3 mg/ml) with β-TCP. All the defects in each group were covered with a Bio-Gide(®) resorbable barrier membrane. The sheep were sacrificed at 2 and 4 weeks and histological and histomorphometric analyses were performed to determine the percentage of new mineralized bone formation and residual β-TCP graft particles in the defects. Defects filled with rhPDGF-BB/β-TCP showed the highest rate of bone formation after 2 and 4 weeks with limited degradation of the β-TCP particles over 4 weeks. Defects filled with β-TCP showed the least bone fill after 2 and 4 weeks, and faster degradation of the β-TCP particles over 4 weeks compared with defects filled with rhPDGF-BB/β-TCP. Percentage of new mineralized bone was comparable in defects to blood clot alone and β-TCP after 4 weeks of healing, but there was a collapse in the defect area in defects with blood clot alone. In comparison, the space was maintained when β-TCP was used in defects at 4 weeks. Defects which had β-TCP alone showed an inhibition in bone healing at 2 and 4 weeks; however, the combination of rhPDGF-BB with β-TCP enhanced bone regeneration in these peri-implant bone defects at the same time intervals. © 2011 John Wiley & Sons A/S.

Growth factors in porcine full and partial thickness burn repair. Differing targets and effects of keratinocyte growth factor, platelet-derived growth factor-BB, epidermal growth factor, and neu differentiation factor.

PubMed Central

Danilenko, D. M.; Ring, B. D.; Tarpley, J. E.; Morris, B.; Van, G. Y.; Morawiecki, A.; Callahan, W.; Goldenberg, M.; Hershenson, S.; Pierce, G. F.

1995-01-01

The topical application of recombinant growth factors such as epidermal growth factor, platelet-derived growth factor-BB homodimer (rPDGF-BB), keratinocyte growth factor (rKGF), and neu differentiation factor has resulted in significant acceleration of healing in several animal models of wound repair. In this study, we established highly reproducible and quantifiable full and deep partial thickness porcine burn models in which burns were escharectomized 4 or 5 days postburn and covered with an occlusive dressing to replicate the standard treatment in human burn patients. We then applied these growth factors to assess their efficacy on several parameters of wound repair: extracellular matrix and granulation tissue production, percent reepithelialization, and new epithelial area. In full thickness burns, only rPDGF-BB and the combination of rPDGF-BB and rKGF induced significant changes in burn repair. rPDGF-BB induced marked extracellular matrix and granulation tissue production (P = 0.013) such that the burn defect was filled within several days of escharectomy, but had no effect on new epithelial area or reepithelialization. The combination of rPDGF-BB and rKGF in full thickness burns resulted in a highly significant increase in extracellular matrix and granulation tissue area (P = 0.0009) and a significant increase in new epithelial area (P = 0.007), but had no effect on reepithelialization. In deep partial thickness burns, rKGF induced the most consistent changes. Daily application of rKGF induced a highly significant increase in new epithelial area (P < 0.0001) but induced only a modest increase in reepithelialization (83.7% rKGF-treated versus 70.2% control; P = 0.016) 12 days postburn. rKGF also doubled the number of fully reepithelialized burns (P = 0.02) at 13 days postburn, at least partially because of marked stimulation of both epidermal and follicular proliferation as assessed by proliferating cell nuclear antigen expression. In situ hybridization for KGFR in porcine burns revealed strong expression of KGFR on hair follicles and basal epidermis, confirming direct rKGF action on follicular as well as epidermal keratinocytes. Although the epithelial proliferation induced by rKGF resulted in marked neoepidermal psoriasiform hyperplasia with exaggerated rete ridges and neoepidermal and follicular maturation as assessed by expression of cytokeratin 10, a marker of keratinocyte terminal differentiation was not delayed and appeared to be accelerated in some rKGF-treated burns. Recombinant epidermal growth factor induced a trend toward increased new epithelial area in deep partial thickness burns, but had no effect on reepithelialization. The recombinant neu differentiation factor-alpha 2 isoform had no significant biological effects in either full or deep partial thickness burns.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 2 Figure 4 Figure 7 Figure 8 PMID:7485390

Short term storage stability at room temperature of two different platelet-rich plasma preparations from equine donors and potential impact on growth factor concentrations.

PubMed

Hauschild, Gregor; Geburek, Florian; Gosheger, Georg; Eveslage, Maria; Serrano, Daniela; Streitbürger, Arne; Johannlükens, Sara; Menzel, Dirk; Mischke, Reinhard

2017-01-05

The increasing interest in platelet-rich plasma (PRP) based therapies is as yet accompanied by inconsistent information regarding nearly all aspects of handling and application. Among these storage stability of processed platelet-rich products may be the basis for a more flexible application mode. The objective of this study was (1) to estimate the storage stability of growth factors platelet derived growth factor BB (PDGF-BB) and transforming growth factor ß1 (TGF-ß1) in both, a single-step softspin centrifugation-based pure-PRP (P-PRP, ACP®), and a gravity filtration system-based leukocyte-rich-PRP (L-PRP, E-PET), over a six hours time span after preparation at room temperature and (2) to identify possible factors influencing these growth factor concentrations in an equine model. Growth factor concentrations remained stable over the entire investigation period in L-PRP as well as P-PRP preparations revealing a mean of 3569 pg/ml PDGF-BB for E-PET and means of 1276 pg/ml PDGF-BB and 5086 pg/ml TGF-ß1 for ACP®. Pearson correlations yielded no significant impact of whole blood platelet (PLT), white blood cell (WBC) and red blood cell (RBC) counts on resulting cytokine values. In case of ACP® no significant dependencies between PLT, WBC and RBC counts of the processed platelet-rich product and resulting cytokine content occurred with exception of TGF-ß1 concentrations showing a strong correlation with the WBC content. PDGF-BB content of E-PET preparations showed a strong positive correlation with PLT and a strong negative with WBC of these preparations but not with RBC. L-PRP ad modum E-PET and P-PRP ad modum ACP® are applicable over at least a six hours time span at room temperature without loss of growth factor content. Based on the results of this study factors influencing the resulting growth factor concentrations still remain questionable. Additional studies implicating a further standardization of preparation protocols are necessary to identify consistent impact on cytokine content after PRP processing.

Expression of platelet-derived growth factor B is upregulated in patients with thoracic aortic dissection.

PubMed

Meng, Weixin; Liu, Shangdian; Li, Dandan; Liu, Zonghong; Yang, Hui; Sun, Bo; Liu, Hongyu

2018-04-20

Thoracic aortic dissection (TAD) is a serious condition requiring urgent treatment to avoid catastrophic consequences. The inflammatory response is involved in the occurrence and development of TAD, possibly potentiated by platelet-derived growth factors (PDGFs). This study aimed to determine whether expression of PDGF-B (a subunit of PDGF-BB) was increased in TAD patients and to explore the factors responsible for its upregulation and subsequent effects on TAD. Full-thickness ascending aorta wall specimens from TAD patients (n = 15) and control patients (n = 10) were examined for expression of PDGF-B and its receptor (PDGFRB) and in terms of morphology, inflammation, and fibrosis. Blood samples from TAD and control patients were collected to detect plasma levels of PDGF-BB and soluble elastins. Expression levels of PDGF-B, PDGFRB, and collagen I were significantly enhanced in ascending aorta wall specimens from TAD patients compared with controls. Furthermore, soluble elastic fragments and PDGF-BB were significantly increased in plasma from TAD patients compared with controls, and numerous irregular elastic fibers and macrophages were seen in the ascending aorta wall in TAD patients. An increase in elastic fragments in the aorta wall might be responsible for inducing the activation and migration of macrophages to injured sites, leading to elevated expression of PDGF-B, which in turn induces deposition of collagen, disrupts extracellular matrix homeostasis, and increases the stiffness of the aorta wall, resulting in compromised aorta compliance. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

TRPM7 channel regulates PDGF-BB-induced proliferation of hepatic stellate cells via PI3K and ERK pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Ling, E-mail: fangling_1984@126.com; Zhan, Shuxiang; Huang, Cheng

2013-11-01

TRPM7, a non-selective cation channel of the TRP channel superfamily, is implicated in diverse physiological and pathological processes including cell proliferation. Recently, TRPM7 has been reported in hepatic stellate cells (HSCs). Here, we investigated the contribution role of TRPM7 in activated HSC-T6 cell (a rat hepatic stellate cell line) proliferation. TRPM7 mRNA and protein were measured by RT-PCR and Western blot in rat model of liver fibrosis in vivo and PDGF-BB-activated HSC-T6 cells in vitro. Both mRNA and protein of TRPM7 were dramatically increased in CCl{sub 4}-treated rat livers. Stimulation of HSC-T6 cells with PDGF-BB resulted in a time-dependent increasemore » of TRPM7 mRNA and protein. However, PDGF-BB-induced HSC-T6 cell proliferation was inhibited by non-specific TRPM7 blocker 2-aminoethoxydiphenyl borate (2-APB) or synthetic siRNA targeting TRPM7, and this was accompanied by downregulation of cell cycle proteins, cyclin D1, PCNA and CDK4. Blockade of TRPM7 channels also attenuated PDGF-BB induced expression of myofibroblast markers as measured by the induction of α-SMA and Col1α1. Furthermore, the phosphorylation of ERK and AKT, associated with cell proliferation, decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TRPM7 channels contribute to perpetuated fibroblast activation and proliferation of PDGF-BB induced HSC-T6 cells via the activation of ERK and PI3K pathways. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 mRNA and protein in the fibrotic livers from CCl{sub 4}-treated rats. • Increasing expression of TRPM7 mRNA and protein during HSC activation. • Blockade of TRPM7 inhibited the PDGF-BB induced proliferation of HSC-T6 cells. • Blockade of TRPM7 decreased α-SMA and Col1α1 expressions in activated HSC-T6 cells. • TRPM7 up-regulation contributes to the activation of ERK and AKT pathways.« less

Synergistic interaction of platelet derived growth factor (PDGF) with the surface of PLLA/Col/HA and PLLA/HA scaffolds produces rapid osteogenic differentiation.

PubMed

Raghavendran, Hanumantha Rao Balaji; Mohan, Saktiswaren; Genasan, Krishnamurithy; Murali, Malliga Raman; Naveen, Sangeetha Vasudevaraj; Talebian, Sepehr; McKean, Robert; Kamarul, Tunku

2016-03-01

Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

Amplified amperometric aptasensor for selective detection of protein using catalase-functional DNA-PtNPs dendrimer as a synergetic signal amplification label.

PubMed

Zhang, Juan; Yuan, Yali; biXie, Shun; Chai, Yaqin; Yuan, Ruo

2014-10-15

In this work, we present a new strategy to construct an electrochemical aptasensor for sensitive detection of platelet-derived growth factor BB (PDGF-BB) based on the synergetic amplification of a three-dimensional (3D) nanoscale catalase (CAT) enzyme-functional DNA-platinum nanoparticles (PtNPs) dendrimer through autonomous layer-by-layer assembly. Firstly, polyamidoaminedendrimer (PAMAM) with a hyper-branched and three-dimensional structure was served as nanocarriers to coimmobilize a large number of PDGF-BB binding aptamer (PBA II) and ssDNA 1 (S1) to form PBA II-PAMAM-S1 bioconjugate. In the presence of PDGF-BB, the bioconjugate was self-assembled on the electrode by sandwich assay. Following that, the carried S1 propagated a chain reaction of hybridization events between CAT-PtNPs-S1 and CAT-PtNPs-ssDNA 2 (S2) to form a 3D nanoscale CAT-functional PtNPs-DNA dendrimer, which successfully immobilized substantial CAT enzyme and PtNPs with superior catalysis activity. In this process, the formed negatively charged double-helix DNA could cause the intercalation of hexaammineruthenium(III) chloride (RuHex) into the groove via electrostatic interactions. Thus, numerous RuHex redox probes and CAT were decorated inside/outside of the dendrimer. In the presence of H2O2 in electrolytic cell, the synergistic reaction of CAT and PtNPs towards electrocatalysis could further amplify electrochemical signal. Under optimal condition, the CAT-PtNPs-DNA dendrimer-based sensing system presented a linear dependence between the reduction peak currents and logarithm of PDGF-BB concentrations in the range of 0.00005-35 nM with a relatively low detection limit of 0.02 pM. Copyright © 2014 Elsevier B.V. All rights reserved.

Regenerative Endodontic Treatment of an Immature Necrotic Molar with Arrested Root Development by Using Recombinant Human Platelet-derived Growth Factor: A Case Report.

PubMed

Zhujiang, Annie; Kim, Sahng G

2016-01-01

Regenerative endodontic treatment has provided a treatment option that aims to allow root maturation. The present report describes the regenerative endodontic treatment of a necrotic, immature molar by using recombinant human platelet-derived growth factor (rhPDGF-BB) and shows the continued root maturation in the tooth with arrested root development. A regenerative endodontic procedure that used a growth factor was performed for a necrotic molar with arrested root formation in a 20-year-old patient. Thorough disinfection by using mechanical instrumentation and copious irrigation of antimicrobial agents as well as intracanal medication with calcium hydroxide was performed throughout the first 2 appointments. At the third appointment, the root canals were irrigated with an antimicrobial solution and 17% EDTA, and bleeding was evoked by passing sterile paper points beyond the apex in each canal. Small pieces of a collagen membrane saturated with rhPDGF-BB solution from GEM 21S were packed into each canal. Mineral trioxide aggregate was placed, and Cavit and composite resin were used to restore the tooth. Complete root maturation and resolution of a periapical radiolucency were observed at the 15-month follow-up. The present report presents a regenerative endodontic procedure that uses rhPDGF-BB for a necrotic molar with arrested root development. The finding of continued root development in the present case suggests that regenerative endodontic treatment may be able to resume the root maturation process in teeth with arrested root formation. Further clinical studies are required to investigate the efficacy of rhPDGF-BB in regenerative endodontic treatment. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Platelet-Derived Growth Factor Promotes Periodontal Regeneration in Localized Osseous Defects: 36-Month Extension Results From a Randomized, Controlled, Double-Masked Clinical Trial

PubMed Central

Nevins, Myron; Kao, Richard T.; McGuire, Michael K.; McClain, Pamela K.; Hinrichs, James E.; McAllister, Bradley S.; Reddy, Michael S.; Nevins, Marc L.; Genco, Robert J.; Lynch, Samuel E.; Giannobile, William V.

2017-01-01

Background Recombinant human platelet-derived growth factor (rhPDGF) is safe and effective for the treatment of periodontal defects in short-term studies up to 6 months in duration. We now provide results from a 36-month extension study of a multicenter, randomized, controlled clinical trial evaluating the effect and long-term stability of PDGF-BB treatment in patients with localized severe periodontal osseous defects. Methods A total of 135 participants were enrolled fromsix clinical centers for an extension trial. Eighty-three individuals completed the study at 36 months and were included in the analysis. The study investigated the local application of β-tricalcium phosphate scaffold matrix with or without two different dose levels of PDGF (0.3 or 1.0 mg/mL PDGF-BB) in patients possessing one localized periodontal osseous defect. Composite analysis for clinical and radiographic evidence of treatment success was defined as percentage of cases with clinical attachment level (CAL) ≥2.7mmand linear bone growth (LBG) ≥1.1 mm. Results The participants exceeding this composite outcome benchmark in the 0.3 mg/mL rhPDGF-BB group went from 62.2% at 12 months, 75.9% at 24 months, to 87.0% at 36 months compared with 39.5%, 48.3%, and 53.8%, respectively, in the scaffold control group at these same time points (P <0.05). Although there were no significant increases in CAL and LBG at 36 months among all groups, there were continued increases in CAL gain, LBG, and percentage bone fill over time, suggesting overall stability of the regenerative response. Conclusion PDGF-BB in a synthetic scaffold matrix promotes long-term stable clinical and radiographic improvements as measured by composite outcomes for CAL gain and LBG for patients possessing localized periodontal defects (ClinicalTrials.gov no. CT01530126). PMID:22612364

Evaluation of human recession defects treated with coronally advanced flaps and either purified recombinant human platelet-derived growth factor-BB with beta tricalcium phosphate or connective tissue: a histologic and microcomputed tomographic examination.

PubMed

McGuire, Michael K; Scheyer, Todd; Nevins, Myron; Schupbach, Peter

2009-02-01

The current study examined the histologic and microcomputed tomographic (micro CT) outcomes of the treatment of gingival recession defects with either a subepithelial connective tissue graft (CTG) or 0.3 mg/mL recombinant human platelet-derived growth factor (rhPDGF-BB) on a beta tricalcium phosphate (beta-TCP) matrix. Gingival recession defects were surgically created in six premolar teeth with no more than 3 mm of keratinized marginal tissue, an osseous crest 2 to 3 mm apical to the newly created gingival margin, and recession depth of at least 3 mm. The defects were left untouched for 2 months; then, four defects were grafted with rhPDGF-BB + beta-TCP + a wound healing dressing, and two defects received CTGs. A coronally advanced flap covered each grafted site. Nine months later, sections were obtained for examination. All four sites treated with rhPDGF-BB + beta-TCP showed connective tissue fibers (Sharpey fibers) perpendicularly inserting into newly formed cementum and alveolar bone. In the two sites treated with CTGs, a long junctional epithelium was seen coronal to the osseous crest and connective tissue fibers ran parallel to the adjacent root surfaces, with no evidence of insertion into cementum or bone. There was no evidence of regeneration of cementum, inserting connective tissue fibers, or supporting alveolar bone. Regeneration of the periodontium in gingival recession defects is possible through growth factor-mediated therapy.

Differential growth factor control of bone formation through osteoprogenitor differentiation.

PubMed

Chaudhary, L R; Hofmeister, A M; Hruska, K A

2004-03-01

The osteogenic factors bone morphogenetic protein (BMP-7), platelet-derived growth factor (PDGF)-BB, and fibroblast growth factor (FGF-2) regulate the recruitment of osteoprogenitor cells and their proliferation and differentiation into mature osteoblasts. However, their mechanisms of action on osteoprogenitor cell growth, differentiation, and bone mineralization remain unclear. Here, we tested the hypothesis that these osteogenic agents were capable of regulating osteoblast differentiation and bone formation in vitro. Normal human bone marrow stromal (HBMS) cells were treated with BMP-7 (40 ng ml(-1)), PDGF-BB (20 ng ml(-1)), FGF-2 (20 ng ml(-1)), or FGF-2 plus BMP-7 for 28 days in a serum-containing medium with 10 mM beta-glycerophosphate and 50 microg ml(-1) ascorbic acid. BMP-7 stimulated a morphological change to cuboidal-shaped cells, increased alkaline phosphatase (ALKP) activity, bone sialoprotein (BSP) gene expression, and alizarin red S positive nodule formation. Hydroxyapatite (HA) crystal deposition in the nodules was demonstrated by Fourier transform infrared (FTIR) spectroscopy only in BMP-7- and dexamethasone (DEX)-treated cells. DEX-treated cells appeared elongated and fibroblast-like compared to BMP-7-treated cells. FGF-2 did not stimulate ALKP, and cell morphology was dystrophic. PDGF-BB had little or no effect on ALKP activity and biomineralization. Alizarin Red S staining of cells and calcium assay indicated that BMP-7, DEX, and FGF-2 enhanced calcium mineral deposition, but FTIR spectroscopic analysis demonstrated no formation of HA similar to human bone in control, PDGF-BB-, and FGF-2-treated samples. Thus, FGF-2 stimulated amorphous octacalcium phosphate mineral deposition that failed to mature into HA. Interestingly, FGF-2 abrogated BMP-7-induced ALKP activity and HA formation. Results demonstrate that BMP-7 was competent as a sole factor in the differentiation of human bone marrow stromal cells to bone-forming osteoblasts confirmed by FTIR examination of mineralized matrix. Other growth factors, PDGF, and FGF-2 were incompetent as sole factors, and FGF-2 inhibited BMP-7-stimulated osteoblast differentiation.

PDGF-BB induces PRMT1 expression through ERK1/2 dependent STAT1 activation and regulates remodeling in primary human lung fibroblasts.

PubMed

Sun, Qingzhu; Liu, Li; Mandal, Jyotshna; Molino, Antonio; Stolz, Daiana; Tamm, Michael; Lu, Shemin; Roth, Michael

2016-04-01

Tissue remodeling of sub-epithelial mesenchymal cells is a major pathology occurring in chronic obstructive pulmonary disease (COPD) and asthma. Fibroblasts, as a major source of interstitial connective tissue extracellular matrix, contribute to the fibrotic and inflammatory changes in these airways diseases. Previously, we described that protein arginine methyltransferase-1 (PRMT1) participates in airway remodeling in a rat model of pulmonary inflammation. In this study we investigated the mechanism by which PDGF-BB regulates PRMT1 in primary lung fibroblasts, isolated from human lung biopsies. Fibroblasts were stimulated with PDGF-BB for up-to 48h and the regulatory and activation of signaling pathways controlling PRMT1 expression were determined. PRMT1 was localized by immuno-histochemistry in human lung tissue sections and by immunofluorescence in isolated fibroblasts. PRMT1 activity was suppressed by the pan-PRMT inhibitor AMI1. ERK1/2 mitogen activated protein kinase (MAPK) was blocked by PD98059, p38 MAPK by SB203580, and STAT1 by small interference (si) RNA treatment. The results showed that PDGF-BB significantly increased PRMT1 expression after 1h lasting over 48h, through ERK1/2 MAPK and STAT1 signaling. The inhibition of ERK1/2 MAPK or of PRMT1 activity decreased PDGF-BB induced fibroblast proliferation, COX2 production, collagen-1A1 secretion, and fibronectin production. These findings suggest that PRMT1 is a central regulator of tissue remodeling and that the signaling sequence controlling its expression in primary human lung fibroblast is PDGF-ERK-STAT1. Therefore, PRMT1 presents a novel therapeutic and diagnostic target for the control of airway wall remodeling in chronic lung diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer.

PubMed

Kahlert, Christoph; Fiala, Maria; Musso, Gabriel; Halama, Niels; Keim, Sophia; Mazzone, Massimiliano; Lasitschka, Felix; Pecqueux, Mathieu; Klupp, Fee; Schmidt, Thomas; Rahbari, Nuh; Schölch, Sebastian; Pilarsky, Christian; Ulrich, Alexis; Schneider, Martin; Weitz, Juergen; Koch, Moritz

2014-12-30

Pancreatic cancer consists of a heterogenous bulk of tumor cells and stroma cells which contribute to tumor progression by releasing angiogenic factors. Those factors can be detected as circulating serum factors. We performed a compartment-specific analysis of tumor-derived and stroma-derived angiogenic factors to identify biomarkers and molecular targets for the treatment of pancreatic cancer. Kryo-frozen tissue from primary ductal adenocarcinomas (n = 51) was laser-microdissected to isolate tumor and stroma tissue. Expression of 17 angiogenic factors (angiopoietin-2, follistatin, GCSF, HGF, interleukin-8, leptin, PDGF-BB, PECAM-1, VEGF, matrix metalloproteinase -1, -2, -3, -7, -9, -10, -12, and -13) was analyzed using a multiplex elisa assay for tissue-derived proteins and corresponding serum. Our study reveals a compartment-specific expression profile for several angiogenic factors and matrix metalloproteinases. ROC analysis of corresponding serum samples reveals MMP-7 and MMP-12 as strong classifiers for the diagnosis of patients with pancreatic cancer vs. healthy control donors. High expression of tumor-derived PDGF-BB and MMP-1 correlates with prolonged survival in univariate and multivariate analysis. In conclusion, a distinct expression patterns for angiogenic cytokines and MMPs in pancreatic cancer and surrounding stroma may implicate them as novel targets for cancer treatment. Tumor-derived PDGF-BB and MMP-1 are significant and independent prognostic markers for poor survival.

rhPDGF-BB promotes early healing in a rat rotator cuff repair model.

PubMed

Kovacevic, David; Gulotta, Lawrence V; Ying, Liang; Ehteshami, John R; Deng, Xiang-Hua; Rodeo, Scott A

2015-05-01

Tendon-bone healing after rotator cuff repair occurs by fibrovascular scar tissue formation, which is weaker than a normal tendon-bone insertion site. Growth factors play a role in tissue formation and have the potential to augment soft tissue healing in the perioperative period. Our study aim was to determine if rhPDGF-BB delivery on a collagen scaffold can improve tendon-to-bone healing after supraspinatus tendon repair compared with no growth factor in rats as measured by (1) gross observations; (2) histologic analysis; and (3) biomechanical testing. Ninety-five male Sprague-Dawley rats underwent acute repair of the supraspinatus tendon. Rats were randomized into one of five groups: control (ie, repair only), scaffold only, and three different platelet-derived growth factor (PDGF) doses on the collagen scaffold. Animals were euthanized 5 days after surgery to assess cellular proliferation and angiogenesis. The remaining animals were analyzed at 4 weeks to assess repair site integrity by gross visualization, fibrocartilage formation with safranin-O staining, and collagen fiber organization with picrosirius red staining, and to determine the biomechanical properties (ie, load-to-failure testing) of the supraspinatus tendon-bone construct. The repaired supraspinatus tendon was in continuity with the bone in all animals. At 5 days, rhPDGF-BB delivery on a scaffold demonstrated a dose-dependent response in cellular proliferation and angiogenesis compared with the control and scaffold groups. At 28 days, with the numbers available, rhPDGF-BB had no effect on increasing fibrocartilage formation or improving collagen fiber maturity at the tendon-bone insertion site compared with controls. The control group had higher tensile loads to failure and stiffness (35.5 ± 8.8 N and 20.3 ± 4.5 N/mm) than all the groups receiving the scaffold, including the PDGF groups (scaffold: 27 ± 6.4 N, p = 0.021 and 13 ± 5.7 N/mm, p = 0.01; 30 µg/mL PDGF: 26.5 ± 7.5 N, p = 0.014 and 13.3 ± 3.2 N/mm, p = 0.01; 100 µg/mL PDGF: 25.7 ± 6.1 N, p = 0.005 and 11.6 ± 3.3 N/mm, p = 0.01; 300 µg/mL PDGF: 27 ± 6.9 N, p = 0.014 and 12.7 ± 4.1 N/mm, p = 0.01). rhPDGF-BB delivery on a collagen scaffold enhanced cellular proliferation and angiogenesis during the early phase of healing, but this did not result in either a more structurally organized or stronger attachment site at later stages of healing. The collagen scaffold had a detrimental effect on healing strength at 28 days, and its relatively larger size compared with the rat tendon may have caused mechanical impingement and extrinsic compression of the healing tendon. Future studies should be performed in larger animal models where healing occurs more slowly. Augmenting the healing environment to improve the structural integrity and to reduce the retear rate after rotator cuff repair may be realized with continued understanding and optimization of growth factor delivery systems.

Rat mesothelioma cell proliferation requires p38δ mitogen activated protein kinase and C/EBP-α.

PubMed

Zhong, Jun; Lardinois, Didier; Szilard, John; Tamm, Michael; Roth, Michael

2011-08-01

Pleural malignant mesothelioma is a rare but deadly tumour mainly induced by asbestos inhalation. Despite the ban of asbestos in 1990 in 52 countries, mesothelioma cases still increase worldwide. In pleural mesothelioma, p38 mitogen activated protein kinases (MAPK) have been suggested to play a major role in carcinogenesis and aggressiveness of tumours. The aim of this study was to determine the role of the different four p38 MAPK isoforms and their effect on proliferation together with the underlying signalling pathways in a rat pleural mesothelioma cell line. Rat pleural mesothelioma cells were stimulated with platelet-derived growth factor (PDGF)-BB and/or transforming growth factor beta (TGF)-β. MAPK and transcription factor expression and activation was monitored in the cytosol and nucleus by immuno-blotting. Proliferation was determined by manual cell count and siRNAs were used to control MAPK and transcription factor expression and action. Only PDGF-BB, but not TGF-β1 induced proliferation via activated Erk1/2 and p38 MAPK. The p38α and δ isoforms were expressed in the cytosol, and upon activation p38δ translocated into the nucleus, while p38α remained in the cytosol. No other p38 isoform was expressed by rat mesothelioma cells. C/EBP-α was found in both the cytosol and the nucleus, while C/EBP-β was not expressed at all. PDGF-BB induced proliferation was suppressed by down-regulation of either Erk1/2, or p38δ MAPK, or C/EBP-α. Furthermore, TGF-β inhibited PDGF-BB induced proliferation by interruption of p38 MAPK signalling. From this rat model, we conclude that in pleural mesothelioma, p38δ in C/EBP-α mediate proliferation and thus may represent new targets in mesothelioma therapy. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wenrui; Kong, Hui; Zeng, Xiaoning

Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (K{sub ATP}) channels have been identified in ASMCs. Mount evidence has suggested that K{sub ATP} channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K{sup +} channels triggers K{sup +} efflux, which leading to membrane hyperpolarization, preventing Ca{sup 2+}entry through closing voltage-operated Ca{sup 2+} channels. Intracellular Ca{sup 2+} is the most important regulator of muscle contraction, cell proliferation and migration. K{sup +} efflux decreases Ca{sup 2+} influx, which consequently influences ASMCs proliferation andmore » migration. As a K{sub ATP} channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca{sup 2+}/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective K{sub ATP} channel antagonist. These findings provide a strong evidence to support that Ipt antagonize the proliferating and migrating effects of PDGF-BB on human ASMCs through opening K{sub ATP} channels. Altogether, our results highlighted a novel profile of Ipt as a potent option against the airway remodeling in chronic airway diseases. - Highlights: Iptakalim is a novel ATP-sensitive potassium channel opener. Iptakalim showed anti-proliferation and anti-migration effects on PDGF-BB-induced human airway smooth muscle cells. Inhibitory effects of Iptakalim could be abolished by glibenclamide, a selective K{sub ATP} channel antagonist. Inhibitory effects of Iptakalim involved the signaling pathways of CaMKII, ERK1/2 and Akt, as well as their downstream, CREB.« less

Effects of sodium citrate and acid citrate dextrose solutions on cell counts and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel.

PubMed

Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

2015-03-14

There is a lack information on the effects of the most commonly used anticoagulants for equine platelet rich plasmas (PRPs) elaboration on cell counts and growth factor release from platelet rich gels (PRGs). The aims of this study were 1) to compare the effects of the anticoagulants sodium citrate (SC), acid citrate dextrose solution A (ACD-A) and ACD-B on platelet (PLT), leukocyte (WBC) and on some parameters associated to platelet activation including mean platelet volume (MPV) and platelet distribution width (PDW) between whole blood, pure PRP (P-PRP) and platelet-poor plasma (PPP); 2) to compare transforming growth factor beta 1 (TGF-β(1)) and platelet-derived growth factor isoform BB (PDGF-BB) concentrations in supernatants from pure PRG (P-PRG), platelet-poor gel (PPG), P-PRP lysate (positive control) and plasma (negative control); 3) to establish the possible correlations between all the studied cellular and molecular parameters. In all cases the three anticoagulants produced P-PRPs with significantly higher PLT counts compared with whole blood and PPP. The concentrations of WBCs were similar between P-PRP and whole blood, but significantly lower in PPP. The type of anticoagulant did not significantly affect the cell counts for each blood component. The anticoagulants also did not affect the MPV and PDW parameters. Independently of the anticoagulant used, all blood components presented significantly different concentrations of PDGF-BB and TGF-β(1). The highest growth factor (GF) concentrations were observed from P-PRP lysates, followed by PRG supernatants, PPP lysates, PPG supernatants and plasma. Significant correlations were observed between PLT and WBC counts (ρ = 0.80), PLT count and TGF-β(1) concentration (ρ = 0.85), PLT count and PDGF-BB concentration (ρ = 0.80) and PDGF-BB and TGF-β(1) concentrations (ρ = 0.75). The type of anticoagulant was not correlated with any of the variables evaluated. The anticoagulants did not significantly influence cell counts or GF concentrations in equine PRP. However, ACD-B was apparently the worst anticoagulant evaluated. It is necessary to perform additional research to determine the effect of anticoagulants on the kinetics of GF elution from P-PRG.

A potential oncogenic activity of platelet-derived growth factor d in prostate cancer progression.

PubMed

Ustach, Carolyn V; Taube, Marcus E; Hurst, Newton J; Bhagat, Sunita; Bonfil, R Daniel; Cher, Michael L; Schuger, Lucia; Kim, Hyeong-Reh Choi

2004-03-01

The platelet-derived growth factor (PDGF) proteins are potent stimulators of cell proliferation/transformation and play a major role in cell-cell communication. For over two decades, PDGFs were thought to exist as three dimeric polypeptides (the homodimers AA and BB and the heterodimer AB). Recently, however, the PDGF C and D chains were discovered in a BLAST search of the expressed sequence tag databases. The PDGF CC and DD dimers have a unique two-domain structure with an NH(2)-terminal CUB (compliment subcomponents C1r/C1s, Uegf, and Bmp1) domain and a COOH-terminal PDGF/vascular endothelial growth factor domain. Whereas secreted PDGF AA, BB, and AB readily activate their cell surface receptors, it was suggested that extracellular proteolytic removal of the CUB domain is required for the PDGF/vascular endothelial growth factor domain of PDGF CC and DD to activate PDGF receptors. In the present study, we examined the processing of latent PDGF D into its active form and the effects of PDGF D expression on prostate cancer progression. We show that LNCaP cells auto-activate latent PDGF DD into the active PDGF domain, which can induce phosphorylation of the beta-PDGF receptor and stimulates LNCaP cell proliferation in an autocrine manner. Additionally, LNCaP-PDGF D-conditioned medium induces migration of the prostate fibroblast cell line 1532-FTX, indicating LNCaP-processed PDGF DD is active in a paracrine manner as well. In a severe combined immunodeficient mouse model, PDGF DD expression accelerates early onset of prostate tumor growth and drastically enhances prostate carcinoma cell interaction with surrounding stromal cells. These demonstrate a potential oncogenic activity of PDGF DD in the development and/or progression of prostate cancer.

A Potential Oncogenic Activity of Platelet-Derived Growth Factor D in Prostate Cancer Progression

PubMed Central

Ustach, Carolyn V.; Taube, Marcus E.; Hurst, Newton J.; Bhagat, Sunita; Bonfil, R. Daniel; Cher, Michael L.; Schuger, Lucia; Kim, Hyeong-Reh Choi

2014-01-01

The platelet-derived growth factor (PDGF) proteins are potent stimulators of cell proliferation/transformation and play a major role in cell-cell communication. For over two decades, PDGFs were thought to exist as three dimeric polypeptides (the homodimers AA and BB and the heterodimer AB). Recently, however, the PDGF C and D chains were discovered in a BLAST search of the expressed sequence tag databases. The PDGF CC and DD dimers have a unique two-domain structure with an NH2-terminal CUB (compliment subcomponents C1r/C1s, Uegf, and Bmp1) domain and a COOH-terminal PDGF/vascular endothelial growth factor domain. Whereas secreted PDGF AA, BB, and AB readily activate their cell surface receptors, it was suggested that extracellular proteolytic removal of the CUB domain is required for the PDGF/vascular endothelial growth factor domain of PDGF CC and DD to activate PDGF receptors. In the present study, we examined the processing of latent PDGF D into its active form and the effects of PDGF D expression on prostate cancer progression. We show that LNCaP cells auto-activate latent PDGF DD into the active PDGF domain, which can induce phosphorylation of the β-PDGF receptor and stimulates LNCaP cell proliferation in an autocrine manner. Additionally, LNCaP-PDGF D-conditioned medium induces migration of the prostate fibroblast cell line 1532-FTX, indicating LNCaP-processed PDGF DD is active in a paracrine manner as well. In a severe combined immunodeficient mouse model, PDGF DD expression accelerates early onset of prostate tumor growth and drastically enhances prostate carcinoma cell interaction with surrounding stromal cells. These demonstrate a potential oncogenic activity of PDGF DD in the development and/or progression of prostate cancer. PMID:14996732

Ketamine, a Clinically Used Anesthetic, Inhibits Vascular Smooth Muscle Cell Proliferation via PP2A-Activated PI3K/Akt/ERK Inhibition

PubMed Central

Chang, Yi; Li, Jiun-Yi; Jayakumar, Thanasekaran; Hung, Shou-Huang; Lee, Wei-Cheng; Manubolu, Manjunath; Sheu, Joen-Rong; Hsu, Ming-Jen

2017-01-01

Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, resulting in modulation of blood pressure. Ketamine has been used for many years in the intensive care unit (ICU) for sedation, and has recently been considered for adjunctive therapy. In the present study, we investigated the effects of ketamine on platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation and the associated mechanism. Ketamine concentration-dependently inhibited PDGF-BB-induced VSMC proliferation without cytotoxicity, and phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated protein kinase (ERK) inhibitors, LY294002 and PD98059, respectively, have similar inhibitory effects. Ketamine was shown to attenuate PI3K, Akt, and ERK1/2 phosphorylation induced by PDGF-BB. Okadaic acid, a selective protein phosphatase 2A (PP2A) inhibitor, significantly reversed ketamine-mediated PDGF-BB-induced PI3K, Akt, and ERK1/2 phosphorylation; a transfected protein phosphatse 2a (pp2a) siRNA reversed Akt and ERK1/2 phosphorylation; and 3-O-Methyl-sphingomyeline (3-OME), an inhibitor of sphingomyelinase, also significantly reversed ERK1/2 phosphorylation. Moreover, ketamine alone significantly inhibited tyrosine phosphorylation and demethylation of PP2A in a concentration-dependent manner. In addition, the pp2a siRNA potently reversed the ketamine-activated catalytic subunit (PP2A-C) of PP2A. These results provide evidence of an anti-proliferating effect of ketamine in VSMCs, showing activation of PP2A blocks PI3K, Akt, and ERK phosphorylation that subsequently inhibits the proliferation of VSMCs. Thus, ketamine may be considered a potential effective therapeutic agent for reducing atherosclerotic process by blocking the proliferation of VSMCs. PMID:29186909

Ketamine, a Clinically Used Anesthetic, Inhibits Vascular Smooth Muscle Cell Proliferation via PP2A-Activated PI3K/Akt/ERK Inhibition.

PubMed

Chang, Yi; Li, Jiun-Yi; Jayakumar, Thanasekaran; Hung, Shou-Huang; Lee, Wei-Cheng; Manubolu, Manjunath; Sheu, Joen-Rong; Hsu, Ming-Jen

2017-11-27

Abnormal proliferation of vascular smooth muscle cells (VSMCs) gives rise to major pathological processes involved in the development of cardiovascular diseases. The use of anti-proliferative agents for VSMCs offers potential for the treatment of vascular disorders. Intravenous anesthetics are firmly established to have direct effects on VSMCs, resulting in modulation of blood pressure. Ketamine has been used for many years in the intensive care unit (ICU) for sedation, and has recently been considered for adjunctive therapy. In the present study, we investigated the effects of ketamine on platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation and the associated mechanism. Ketamine concentration-dependently inhibited PDGF-BB-induced VSMC proliferation without cytotoxicity, and phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated protein kinase (ERK) inhibitors, LY294002 and PD98059, respectively, have similar inhibitory effects. Ketamine was shown to attenuate PI3K, Akt, and ERK1/2 phosphorylation induced by PDGF-BB. Okadaic acid, a selective protein phosphatase 2A (PP2A) inhibitor, significantly reversed ketamine-mediated PDGF-BB-induced PI3K, Akt, and ERK1/2 phosphorylation; a transfected protein phosphatse 2a ( pp2a ) siRNA reversed Akt and ERK1/2 phosphorylation; and 3-O-Methyl-sphingomyeline (3-OME), an inhibitor of sphingomyelinase, also significantly reversed ERK1/2 phosphorylation. Moreover, ketamine alone significantly inhibited tyrosine phosphorylation and demethylation of PP2A in a concentration-dependent manner. In addition, the pp2a siRNA potently reversed the ketamine-activated catalytic subunit (PP2A-C) of PP2A. These results provide evidence of an anti-proliferating effect of ketamine in VSMCs, showing activation of PP2A blocks PI3K, Akt, and ERK phosphorylation that subsequently inhibits the proliferation of VSMCs. Thus, ketamine may be considered a potential effective therapeutic agent for reducing atherosclerotic process by blocking the proliferation of VSMCs.

Human buccal plate extraction socket regeneration with recombinant human platelet-derived growth factor BB or enamel matrix derivative.

PubMed

Nevins, Marc L; Camelo, Marcelo; Schupbach, Peter; Nevins, Myron; Kim, Soo-Woo; Kim, David M

2011-01-01

The objective of this study was to assess the osseous healing of buccal plate extraction socket defects. There were four cohorts: group A (mineral collagen bone substitute [MCBS] scaffold alone), group B (MCBS with recombinant human platelet-derived growth factor BB [rhPDGF-BB; 0.3 mg/mL]), group C (MCBS with enamel matrix derivative [EMD]), and group D (combination of EMD with bone ceramic). The primary outcome of bone quality was evaluated using light microscopy, backscatter scanning electron microscopy, and histomorphometrics. Reentry surgery provided an opportunity for clinical observation of the healed ridge morphology. Sixteen patients with buccal wall extraction socket defects were randomized into four treatment groups of equal size. Grafting was provided at the time of extraction with advancement of the buccal flap for primary closure. A trephine core biopsy of the implant site preparation was performed after 5 months for implant placement. Histologic examination identified new bone healing around the biomaterial scaffolds. Statistically significant differences in new bone formation were not observed among the treatment groups. There was a histomorphometric trend toward more new bone for the rhPDGF-BB-treated group (group B). This group had the most favorable ridge morphology for optimal implant placement.

TRAF6-Mediated SM22α K21 Ubiquitination Promotes G6PD Activation and NADPH Production, Contributing to GSH Homeostasis and VSMC Survival In Vitro and In Vivo.

PubMed

Dong, Li-Hua; Li, Liang; Song, Yu; Duan, Zhi-Li; Sun, Shao-Guang; Lin, Yan-Ling; Miao, Sui-Bing; Yin, Ya-Juan; Shu, Ya-Nan; Li, Huan; Chen, Peng; Zhao, Li-Li; Han, Mei

2015-09-25

Vascular smooth muscle cell (VSMC) survival under stressful conditions is integral to promoting vascular repair, but facilitates plaque stability during the development of atherosclerosis. The cytoskeleton-associated smooth muscle (SM) 22α protein is involved in the regulation of VSMC phenotypes, whereas the pentose phosphate pathway plays an essential role in cell proliferation through the production of dihydronicotinamide adenine dinucleotide phosphate. To identify the relationship between dihydronicotinamide adenine dinucleotide phosphate production and SM22α activity in the development and progression of vascular diseases. We showed that the expression and activity of glucose-6-phosphate dehydrogenase (G6PD) are promoted in platelet-derived growth factor (PDGF)-BB-induced proliferative VSMCs. PDGF-BB induced G6PD membrane translocation and activation in an SM22α K21 ubiquitination-dependent manner. Specifically, the ubiquitinated SM22α interacted with G6PD and mediated G6PD membrane translocation. Furthermore, we found that tumor necrosis factor receptor-associated factor (TRAF) 6 mediated SM22α K21 ubiquitination in a K63-linked manner on PDGF-BB stimulation. Knockdown of TRAF6 decreased the membrane translocation and activity of G6PD, in parallel with reduced SM22α K21 ubiquitination. Elevated levels of activated G6PD consequent to PDGF-BB induction led to increased dihydronicotinamide adenine dinucleotide phosphate generation through stimulation of the pentose phosphate pathway, which enhanced VSMC viability and reduced apoptosis in vivo and in vitro via glutathione homeostasis. We provide evidence that TRAF6-induced SM22α ubiquitination maintains VSMC survival through increased G6PD activity and dihydronicotinamide adenine dinucleotide phosphate production. The TRAF6-SM22α-G6PD pathway is a novel mechanism underlying the association between glucose metabolism and VSMC survival, which is beneficial for vascular repair after injury but facilitates atherosclerotic plaque stability. © 2015 American Heart Association, Inc.

Hyaluronic acid/Chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB.

PubMed

Parajó, Yolanda; D'Angelo, Ivana; Welle, Alexander; Garcia-Fuentes, Marcos; Alonso, María José

2010-11-01

The development of a vascular network in tissue-engineered constructs is a fundamental bottleneck of bioregenerative medicine, particularly when the size of the implant exceeds a certain limit given by diffusion lengths and/or if the host tissue shows a very active metabolism. One of the approaches to achieve the vascularization of tissue constructs is generating a sustained release of proangiogenic factors from the ischemic site. This work describes the formation and characterization of hyaluronic acid-chitosan (HA/CS) nanoparticles for the delivery of two pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF-BB). These nanoparticles were prepared by an ionic gelification technique, and different formulations were developed by encapsulating the growth factors in association with two stabilizing agents: bovine serum albumin or heparin sodium salt. These carriers were characterized with regard to their physicochemical properties, their stability in biological media, and their cytotoxicity in the C3a hepatoma cell line. The results show that nanoparticles around 200 nm can be prepared by this method. HA/CS nanoparticles were stable when incubated in EMEM cell culture medium or in water at 37°C for 24 h. Cell culture tests confirmed that HA/CS nanoparticles are not cytotoxic within the concentration range used for growth factor delivery. Moreover, HA/CS nanoparticles were able to entrap efficiently both growth factors, reaching association values of 94% and 54% for VEGF and PDGF, respectively. In vitro release studies confirm that PDGF-BB is released from HA/CS nanoparticles in a sustained manner over approximately 1 week. On the other hand, VEGF is completely released within the first 24 h.

Influence of cryopreservation and mechanical stimulation on equine Autologous Conditioned Plasma (ACP®).

PubMed

Mageed, M; Ionita, C; Kissich, C; Brehm, W; Winter, K; Ionita, J-C

2015-01-01

To determine the influence of cryopreservation at two different temperatures on platelet concentration, growth factor (GF) levels and platelet activation parameters in equine ACP®; moreover, to determine if adding mechanical ACP® stimulation to freeze-thaw activation amplifies GF release from platelets. Firstly, blood from five horses was used to prepare ACP®. Platelet, platelet derived growth factor BB (PDGF-BB) and transforming growth factor β1 (TGF-β1) concentrations as well as mean platelet volume (MPV) and mean platelet component (MPC) were determined in fresh and corresponding ACP® samples after 2 months cryopreservation at -20 °C and -80 °C, respectively. Secondly, ACP® was prepared from blood of nine horses. Half of ACP® was activated using one freeze-thaw-cycle at -20 °C, whereas the rest was first vortexed. Their PDGF-BB and TGF-β1 concentrations were subsequently determined. Platelet concentration significantly decreased after -80 °C cryopreservation. PDGF-BB level augmented significantly after both storage methods, whereas TGF-β1 concentration was not significantly altered. MPV significantly increased after -20 °C cryopreservation. Both storage regimens induced a significant MPC decrease. No significant differences in GF concentrations between the vortexed and non-vortexed samples were detected. Both cryopreservation methods induced platelet activation, but storage at -80 °C apparently harmed the platelets without generating higher GF release than -20 °C. The mechanical stimulation process could not enhance GF release in subsequently frozen-thawed ACP®. Storage of ACP® at -20 °C could be useful in equine practice, but, before this procedure can be recommended, further qualitative tests are needed. The mechanical stimulation technique should be adjusted in order to increase platelet activation.

Local Application of Gelatin Hydrogel Sheets Impregnated With Platelet-Derived Growth Factor BB Promotes Tendon-to-Bone Healing After Rotator Cuff Repair in Rats.

PubMed

Tokunaga, Takuya; Ide, Junji; Arimura, Hitoshi; Nakamura, Takayuki; Uehara, Yusuke; Sakamoto, Hidetoshi; Mizuta, Hiroshi

2015-08-01

To determine whether the local application of platelet-derived growth factor BB (PDGF-BB) in hydrogel sheets would promote healing and improve histologic characteristics and biomechanical strength after rotator cuff (RC) repair in rats. To assess the effect of PDGF-BB on tendon-to-bone healing we divided 36 adult male Sprague-Dawley rats treated with bilateral surgery to repair the supraspinatus tendon at its insertion site into 3 groups: group 1 = suture-only group; group 2 = suture and gelatin hydrogel sheets impregnated with phosphate-buffered saline (PBS); and group 3 = suture and gelatin hydrogel sheets impregnated with PDGF-BB (0.5 μg). Semiquantitative histologic evaluation was carried out 2, 6, and 12 weeks later; cell proliferation was assessed 2 and 6 weeks postoperatively by immunostaining for proliferating cell nuclear antigen (PCNA), and biomechanical testing, including ultimate load to failure, stiffness, and ultimate stress to failure, was performed 12 weeks after the operation. At 2 weeks, the average percentage of PCNA-positive cells at the insertion site was significantly higher in group 3 (40.5% ± 2.4%) than in group 1 (32.1% ± 6.9%; P = .03) and group 2 (31.9% ± 3.7%; P = .02). At 2 and 6 weeks, the histologic scores were similar among the 3 groups. At 12 weeks, the histologic score was significantly higher in group 3 (10.3 ± 0.8) than in group 1 (8.5 ± 0.5; P = .002) or group 2 (8.8 ± 0.8; P = .009), whereas ultimate load to failure, stiffness, and ultimate load to stress (normal control population, 44.73 ± 9.75 N, 27.59 ± 4.32 N/mm, and 21.33 ± 4.65 N/mm(2), respectively) were significantly higher in group 3 (28.28 ± 6.28 N, 11.05 ± 2.37 N/mm, and 7.99 ± 2.13 N/mm(2), respectively) than in group 1 (10.44 ± 1.98 N, 4.74 ± 1.31 N/mm, and 3.28 ± 1.27 N/mm(2), respectively; all P < .001) or group 2 (11.85 ± 2.89 N, 5.86 ± 1.75 N/mm, and 3.31 ± 0.80 N/mm(2), respectively; all P < .001). The placement of a PDGF-BB-impregnated hydrogel sheet just lateral to a transected and acutely reattached supraspinatus tendon produced significantly more PCNA-positive cells at 2 weeks and greater collagen fiber orientation, ultimate failure loads, stiffness, and stress to failure at 12 weeks than did a PBS-impregnated hydrogel sheet. No differences in vascularity or cellularity were observed. The local application of PDGF-BB-impregnated gelatin hydrogel may help to promote tendon-to-bone healing after RC repair in humans. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

PubMed Central

Yang, Lu; Chen, Xufeng; Simet, Samantha M.; Hu, Guoku; Cai, Yu; Niu, Fang; Kook, Yeonhee

2016-01-01

Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell–substrate impedance sensing and FITC-dextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1α. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2–related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1α/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF-1α and PDGF-BB. Pharmacological blocking of HIF-1α significantly abrogated cocaine-mediated loss of Zo-1. Understanding the mechanism(s) by which cocaine mediates barrier dysfunction could provide insights into the development of potential therapeutic targets for cocaine-mediated pulmonary hypertension. PMID:27391108

Diffractometric Detection of Proteins using Microbead-based Rolling Circle Amplification

PubMed Central

Lee, Joonhyung; Icoz, Kutay; Roberts, Ana; Ellington, Andrew D.; Savran, Cagri A.

2010-01-01

We present a robust, sensitive, fluorescent or radio label-free self-assembled optical diffraction biosensor that utilizes rolling circle amplification (RCA) and magnetic microbeads as a signal enhancement method. An aptamer-based sandwich assay was performed on microcontact-printed streptavidin arranged in 15-μm-wide alternating lines, and could specifically capture and detect platelet-derived growth factor B-chain (PDGF-BB). An aptamer served as a template for the ligation of a padlock probe and the circularized probe could in turn be used as a template for RCA. The concatameric RCA product hybridized to biotinylated oligonuclotides which then captured streptavidin-labeled magnetic beads. In consequence, the signal from the captured PDGF-BB was amplified via the concatameric RCA product, and the diffraction gratings on the printed areas produced varying intensities of diffraction modes. The detected diffraction intensity and the density of the microbeads on the surface varied as a function of PDGF-BB concentration. Our results demonstrate a robust biosensing platform that is easy to construct and use, and devoid of fluorescence microscopy. The self-assembled bead patterns allow both a visual analysis of the molecular binding events under an ordinary bright-field microscope and serve as a diffraction grating biosensor. PMID:19947589

ICAM-1-Targeted Liposomes Loaded with Liver X Receptor Agonists Suppress PDGF-Induced Proliferation of Vascular Smooth Muscle Cells

NASA Astrophysics Data System (ADS)

Huang, Xu; Xu, Meng-Qi; Zhang, Wei; Ma, Sai; Guo, Weisheng; Wang, Yabin; Zhang, Yan; Gou, Tiantian; Chen, Yundai; Liang, Xing-Jie; Cao, Feng

2017-05-01

The proliferation of vascular smooth muscle cells (VSMCs) is one of the key events during the progress of atherosclerosis. The activated liver X receptor (LXR) signalling pathway is demonstrated to inhibit platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation. Notably, following PDGF-BB stimulation, the expression of intercellular adhesion molecule-1 (ICAM-1) by VSMCs increases significantly. In this study, anti-ICAM-1 antibody-conjugated liposomes were fabricated for targeted delivery of a water-insoluble LXR agonist (T0901317) to inhibit VSMC proliferation. The liposomes were prepared by filming-rehydration method with uniform size distribution and considerable drug entrapment efficiency. The targeting effect of the anti-ICAM-T0901317 liposomes was evaluated by confocal laser scanning microscope (CLSM) and flow cytometry. Anti-ICAM-T0901317 liposomes showed significantly higher inhibition effect of VSMC proliferation than free T0901317 by CCk8 proliferation assays and BrdU staining. Western blot assay further confirmed that anti-ICAM-T0901317 liposomes inhibited retinoblastoma (Rb) phosphorylation and MCM6 expression. In conclusion, this study identified anti-ICAM-T0901317 liposomes as a promising nanotherapeutic approach to overcome VSMC proliferation during atherosclerosis progression.

Inhibition of Vascular Smooth Muscle Cell Proliferation by Gentiana lutea Root Extracts

PubMed Central

Kesavan, Rushendhiran; Potunuru, Uma Rani; Nastasijević, Branislav; T, Avaneesh; Joksić, Gordana; Dixit, Madhulika

2013-01-01

Gentiana lutea belonging to the Gentianaceae family of flowering plants are routinely used in traditional Serbian medicine for their beneficial gastro-intestinal and anti-inflammatory properties. The aim of the study was to determine whether aqueous root extracts of Gentiana lutea consisting of gentiopicroside, gentisin, bellidifolin-8-O-glucoside, demethylbellidifolin-8-O-glucoside, isovitexin, swertiamarin and amarogentin prevents proliferation of aortic smooth muscle cells in response to PDGF-BB. Cell proliferation and cell cycle analysis were performed based on alamar blue assay and propidium iodide labeling respectively. In primary cultures of rat aortic smooth muscle cells (RASMCs), PDGF-BB (20 ng/ml) induced a two-fold increase in cell proliferation which was significantly blocked by the root extract (1 mg/ml). The root extract also prevented the S-phase entry of synchronized cells in response to PDGF. Furthermore, PDGF-BB induced ERK1/2 activation and consequent increase in cellular nitric oxide (NO) levels were also blocked by the extract. These effects of extract were due to blockade of PDGF-BB induced expression of iNOS, cyclin D1 and proliferating cell nuclear antigen (PCNA). Docking analysis of the extract components on MEK1, the upstream ERK1/2 activating kinase using AutoDock4, indicated a likely binding of isovitexin to the inhibitor binding site of MEK1. Experiments performed with purified isovitexin demonstrated that it successfully blocks PDGF-induced ERK1/2 activation and proliferation of RASMCs in cell culture. Thus, Gentiana lutea can provide novel candidates for prevention and treatment of atherosclerosis. PMID:23637826

Inhibition of vascular smooth muscle cell proliferation by Gentiana lutea root extracts.

PubMed

Kesavan, Rushendhiran; Potunuru, Uma Rani; Nastasijević, Branislav; T, Avaneesh; Joksić, Gordana; Dixit, Madhulika

2013-01-01

Gentiana lutea belonging to the Gentianaceae family of flowering plants are routinely used in traditional Serbian medicine for their beneficial gastro-intestinal and anti-inflammatory properties. The aim of the study was to determine whether aqueous root extracts of Gentiana lutea consisting of gentiopicroside, gentisin, bellidifolin-8-O-glucoside, demethylbellidifolin-8-O-glucoside, isovitexin, swertiamarin and amarogentin prevents proliferation of aortic smooth muscle cells in response to PDGF-BB. Cell proliferation and cell cycle analysis were performed based on alamar blue assay and propidium iodide labeling respectively. In primary cultures of rat aortic smooth muscle cells (RASMCs), PDGF-BB (20 ng/ml) induced a two-fold increase in cell proliferation which was significantly blocked by the root extract (1 mg/ml). The root extract also prevented the S-phase entry of synchronized cells in response to PDGF. Furthermore, PDGF-BB induced ERK1/2 activation and consequent increase in cellular nitric oxide (NO) levels were also blocked by the extract. These effects of extract were due to blockade of PDGF-BB induced expression of iNOS, cyclin D1 and proliferating cell nuclear antigen (PCNA). Docking analysis of the extract components on MEK1, the upstream ERK1/2 activating kinase using AutoDock4, indicated a likely binding of isovitexin to the inhibitor binding site of MEK1. Experiments performed with purified isovitexin demonstrated that it successfully blocks PDGF-induced ERK1/2 activation and proliferation of RASMCs in cell culture. Thus, Gentiana lutea can provide novel candidates for prevention and treatment of atherosclerosis.

Dual growth factor-immobilized asymmetrically porous membrane for bone-to-tendon interface regeneration on rat patellar tendon avulsion model.

PubMed

Kim, Joong-Hyun; Oh, Se Heang; Min, Hyun Ki; Lee, Jin Ho

2018-01-01

Insufficient repair of the bone-to-tendon interface (BTI) with structural/compositional gradients has been a significant challenge in orthopedics. In this study, dual growth factor (platelet-derived growth factor-BB [PDGF-BB] and bone morphogenetic protein-2 [BMP-2])-immobilized polycaprolactone (PCL)/Pluronic F127 asymmetrically porous membrane was fabricated to estimate its feasibility as a potential strategy for effective regeneration of BTI injury. The growth factors immobilized (via heparin-intermediated interactions) on the membrane were continuously released for up to ∼80% of the initial loading amount after 5 weeks without a significant initial burst. From the in vivo animal study using a rat patellar tendon avulsion model, it was observed that the PDGF-BB/BMP-2-immobilized membrane accelerates the regeneration of the BTI injury, probably because of the continuous release of both growth factors (biological stimuli) and their complementary effect to create a multiphasic structure (bone, fibrocartilage, and tendon) like a native structure, as well as the role of the asymmetrically porous membrane as a physical barrier (nanopore side; prevention of fibrous tissue invasion into the defect site) and scaffold (micropore side; guidance for tissue regeneration). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 115-125, 2018. © 2017 Wiley Periodicals, Inc.

Clinical assessment of bone quality of human extraction sockets after conversion with growth factors.

PubMed

Ntounis, Athanasios; Geurs, Nico; Vassilopoulos, Philip; Reddy, Michael

2015-01-01

The study was conducted to evaluate the effect of mineralized freeze-dried bone allograft (FDBA), alone or in combination with growth factors in extraction sockets, on subjective assessment of bone quality during implant placement. Forty-one patients whose treatment plan involved extraction of anterior or premolar teeth were randomized into four groups: Group 1, collagen plug (control); Group 2, FDBA/β-tricalcium phosphate (β-TCP)/collagen plug; Group 3, FDBA/β-TCP/platelet-rich plasma (PRP)/collagen plug; Group 4, FDBA/β-TCP/recombinant human platelet-derived growth factor BB (rhPDGF-BB)/collagen plug. After 8 weeks of healing, implants were placed. The clinicians assessed bone quality according to the Misch classification. A benchtop calibration exercise test was conducted to evaluate agreement and accuracy of operators in recognizing different bone qualities. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means (LS means). Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. P < .05 was considered statistically significant. A simple (not weighted) kappa statistic was used to assess the agreement between raters. To assess accuracy in identifying bone quality, a chi-square test was used to compare the percent correct for each rater. The benchtop calibration exercise test demonstrated agreement among clinicians (0.75 and 0.92 between raters 1 and 2 and raters 1 and 3, respectively). Raters were more likely to identify the correct bone quality (P > .05). Inclusion of bone grafting is associated with a shift from D4 quality to D3 quality bone. Inclusion of PRP in bone grafting eliminates the incidence of D4 bone, establishing D3 and D2 quality bone as prevalent (56% vs. 42%, respectively). Inclusion of rhPDGF-BB and β-TCP in combination with the bone grafting has the same effect, although D2 quality is less prevalent. When compared to sockets grafted with FDBA/β-TCP/collagen plug alone, the sockets with growth factors demonstrated fewer residual bone graft particles. (1) Inclusion of bone grafting enhanced bone quality as assessed during implant placement. (2) Overall inclusion of PRP and rhPDGF-BB enhanced subjective bone quality, eliminating incidence of D4 quality in human extraction sockets. (3) The use of PRP or rhPDGF-BB may enhance healing within extraction sockets and decrease the healing time prior to dental implant placement.

Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

PubMed

Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

2014-01-01

In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, p<0.001), TGF-β1 (r=0.85, p<0.001), VEGF (r=0.46, p<0.01) and PDGF-bb (r=0.9, p<0.001). Our results demonstrate that selected growth factors are present in the platelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

Effects of the breed, sex and age on cellular content and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel.

PubMed

Giraldo, Carlos E; López, Catalina; Álvarez, María E; Samudio, Ismael J; Prades, Marta; Carmona, Jorge U

2013-02-12

There is no information on the effects of the breed, gender and age on the cellular content and growth factor (GF) release from equine pure-platelet rich plasma (P-PRP) and pure-platelet rich gel (P-PRG). The objectives of this study were: 1) to compare the cellular composition of P-PRP with whole blood and platelet poor plasma (PPP); 2) to compare the concentration of transforming GF beta 1 (TGF-β1) and platelet derived GF isoform BB (PDGF-BB) between P-PRP treated with non-ionic detergent (P-PRP+NID), P-PRG (activated with calcium gluconate -CG-), PPP+NID, PPP gel (PPG), and plasma and; 3) to evaluate and to correlate the effect of the breed, gender and age on the cellular and GF concentration for each blood component. Forty adult horses, 20 Argentinean Creole Horses (ACH) and, 20 Colombian Creole Horses (CCH) were included. Data were analyzed by parametric (i.e.: t-test, one way ANOVA) and non parametric (Kruskal-Wallis test, Wilcoxon test) tests. Correlation analysis was also performed by using the Spearman and Pearson tests. A p ≤ 0.05 was set as significant for all tests. All the blood components were compared for platelet (PLT), leukocyte (WBC), TGF-β1 and PDGF-BB concentrations. The effect of the breed, gender and age on these variables was analyzed. A P ≤ 0.05 was accepted as significant for all the tests. PLT counts were 1.8 and 0.6 times higher in P-PRP than in whole blood and PPP, respectively; WBC counts were 0.5 and 0.1 times lower in P-PRP, in comparison with whole blood and PPP, respectively. TGF-β1 and PDGF-BB concentrations were 2.3 and 262 times higher, respectively, in P-PRG than in plasma, and 0.59 and 0.48 times higher, respectively, in P-PRG than in PPG. P-PRG derived from CCH females or young horses presented significantly (P < 0.001) higher PDGF-BB concentrations than P-PRG derived from ACH males or older horses. Our results indicated that P-PRP obtained by a manual method was affected by intrinsic factors such as the breed, gender and age. Equine practitioners should be aware that cellular and GF release from P-PRP/P-PRG could change according with the intrinsic variables associated with a patient in particular.

A novel role for cathepsin K in periosteal osteoclast precursors during fracture repair.

PubMed

Walia, Bhavita; Lingenheld, Elizabeth; Duong, Le; Sanjay, Archana; Drissi, Hicham

2018-03-01

Osteoporosis management is currently centered around bisphosphonates, which inhibit osteoclast (OC) bone resorption but do not affect bone formation. This reduces fracture risk, but fails to restore healthy bone remodeling. Studies in animal models showed that cathepsin K (CatK) inhibition by genetic deletion or chemical inhibitors maintained bone formation while abrogating resorption during bone remodeling and stimulated periosteal bone modeling. Recently, periosteal mononuclear tartrate-resistant acid phosphatase-positive (TRAP + ) osteoclast precursors (OCPs) were shown to augment angiogenesis-coupled osteogenesis. CatK gene deletion increased osteoblast differentiation via enhanced OCP and OC secretion of platelet-derived growth factor (PDGF)-BB and sphingosine 1 phosphate. The effects of periosteum-derived OCPs on bone remodeling are unknown, particularly with regard to fracture repair. We hypothesized that periosteal OCPs derived from CatK-null (Ctsk -/- ) mice may enhance periosteal bone formation during fracture repair. We found fewer periosteal OCPs in Ctsk -/- mice under homeostatic conditions; however, after fracture, this population increased in number relative to that seen in wild-type (WT) mice. Enhanced TRAP staining and greater expression of PDGF-BB were observed in fractured Ctsk -/- femurs relative to WT femurs. This early pattern of augmented PDGF-BB expression in Ctsk -/- mice may contribute to improved fracture healing by enhancing callus mineralization in Ctsk -/- mice. © 2018 New York Academy of Sciences.

Computational model of mesenchymal migration in 3D under chemotaxis.

PubMed

Ribeiro, F O; Gómez-Benito, M J; Folgado, J; Fernandes, P R; García-Aznar, J M

2017-01-01

Cell chemotaxis is an important characteristic of cellular migration, which takes part in crucial aspects of life and development. In this work, we propose a novel in silico model of mesenchymal 3D migration with competing protrusions under a chemotactic gradient. Based on recent experimental observations, we identify three main stages that can regulate mesenchymal chemotaxis: chemosensing, dendritic protrusion dynamics and cell-matrix interactions. Therefore, each of these features is considered as a different module of the main regulatory computational algorithm. The numerical model was particularized for the case of fibroblast chemotaxis under a PDGF-bb gradient. Fibroblasts migration was simulated embedded in two different 3D matrices - collagen and fibrin - and under several PDGF-bb concentrations. Validation of the model results was provided through qualitative and quantitative comparison with in vitro studies. Our numerical predictions of cell trajectories and speeds were within the measured in vitro ranges in both collagen and fibrin matrices. Although in fibrin, the migration speed of fibroblasts is very low, because fibrin is a stiffer and more entangling matrix. Testing PDGF-bb concentrations, we noticed that an increment of this factor produces a speed increment. At 1 ng mL -1 a speed peak is reached after which the migration speed diminishes again. Moreover, we observed that fibrin exerts a dampening behavior on migration, significantly affecting the migration efficiency.

Dual-primer self-generation SERS signal amplification assay for PDGF-BB using label-free aptamer.

PubMed

Ye, SuJuan; Zhai, XiaoMo; Wu, YanYing; Kuang, ShaoPing

2016-05-15

Highly sensitive detection of proteins, especially those associated with cancers, is essential to biomedical research as well as clinical diagnosis. In this work, a simple and novel one-two-three signal amplification surface-enhanced Raman scattering (SERS) method for the detection of protein is fabricated by using label-free aptamer and dual-primer self-generation. Platelet-derived growth factor B-chain (PDGF-BB) is selected as the model protein. The one-two-three cascade DNA amplification means one target-aptamer binding event, two hairpin DNA switches and three DNA amplification reactions. This strategy possesses some remarkable features compared to conventional signal amplification methods: (i) A smart probe including a label-free aptamer is fabricated, for suitable hybridization without hindering the affinity of the aptamer toward its target. (ii) Using the unique structure switch of the aptamer and cooperator, a one-two-three working mode is developed to amplify the SERS signal. The amplification efficiency is enhanced. Given the unique and attractive characteristics, a simple and universal strategy is designed to accomplish ultrasensitive detection of proteins. The detection limit of PDGF-BB via SERS detection is 0.42 pM, with the linear range from 1.0×10(-12)M to 10(-8)M. It is potentially universal because the aptamer can be easily designed for biomolecules whose aptamers undergo similar conformational changes. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of electrospun bone-mimetic matrices for bone regenerative applications

NASA Astrophysics Data System (ADS)

Phipps, Matthew Christopher

Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein show that BMMs supported great-er adhesion, proliferation, and integrin activation of mesenchymal stem cells (MSCs), the multipotent bone-progenitor cells within bone marrow and the periosteum, in comparison to electrospun PCL alone. These cellular responses, which are essential early steps in the process of bone regeneration, highlight the benefits of presenting cells with natural bone molecules. Subsequently, evaluation of new bone formation in a rat cortical tibia defect showed that BMMs are highly osteoconductive. However, these studies also revealed the inability of endogenous cells to migrate within electrospun matrices due to the inherently small pore sizes. To address this limitation, which will negatively impact the rate of scaf-fold-to-bone turnover and inhibit vascularization, sacrificial fibers were added to the ma-trix. The removal of these fibers after fabrication resulted in BMMs with larger pores, leading to increased infiltration of MSCs and endogenous bone cells. Lastly, we evaluat-ed the potential of our matrices to stimulate the recruitment of MSCs, a vital step in bone healing, through the sustained delivery of platelet derived growth factor-BB (PDGF-BB). BMMs were found to adsorb and subsequently release greater quantities of PDGF-BB, compared to PCL scaffolds, over an 8-week interval. The released PDGF-BB retained its bioactivity, stimulating MSC chemotaxis in two separate assays. Collectively, these re-sults suggest that electrospun matrices incorporating the bone matrix molecules collagen I and HA, with sacrificial fibers, provide a favorable scaffold for MSC survival and infil-tration as well as the ability to sequester PDGF-BB from solution, leading to sustained local delivery and MSC chemotaxis.

In vitro comparison of the efficacy of TGF-β1 and PDGF-BB in combination with freeze-dried bone allografts for induction of osteogenic differentiation in MG-63 osteoblast-like cells.

PubMed

Vahabi, Surena; Torshabi, Maryam; Esmaeil Nejad, Azadeh

2016-12-01

Predictable regeneration of alveolar bone defects has always been a challenge in implant dentistry. Bone allografts are widely used bone substitutes with controversial osteoinductive activity. This in vitro study aimed to assess the osteogenic potential of some commercially available freeze-dried bone allografts supplemented with human recombinant platelet-derived growth factor-BB and transforming growth factor beta-1. Cell viability, mineralization, and osteogenic gene expression of MG-63 osteoblast-like cells were compared among the allograft alone, allograft/platelet-derived growth factor-BB, allograft/transforming growth factor beta-1, and allograft/platelet-derived growth factor-BB/transforming growth factor beta-1 groups. The methyl thiazol tetrazolium assay, real-time quantitative reverse transcription polymerase chain reaction and alizarin red staining were performed, respectively, for assessment of cell viability, differentiation, and mineralization at 24-72 h post treatment. The allograft with greater cytotoxic effect on MG-63 cells caused the lowest differentiation among the groups. In comparison with allograft alone, allograft/transforming growth factor beta-1, and allograft/transforming growth factor beta-1/platelet-derived growth factor-BB caused significant upregulation of bone sialoprotein and osteocalcin osteogenic mid-late marker genes, and resulted in significantly higher amounts of calcified nodules especially in mineralized non-cytotoxic allograft group. Supplementation of platelet-derived growth factor-BB alone in 5 ng/mL concentration had no significant effect on differentiation or mineralization markers. According to the results, transforming growth factor beta-1 acts synergistically with bone allografts to enhance the osteogenic differentiation potential. Therefore, this combination may be useful for rapid transformation of undifferentiated cells into bone-forming cells for bone regeneration. However, platelet-derived growth factor-BB supplementation did not support this synergistic ability to enhance osteogenic differentiation and thus, further investigations are required.

Platelet-Derived Growth Factor in the Ovarian Follicle Attracts the Stromal Cells of the Fallopian Tube Fimbriae

PubMed Central

Chen, Chiu-Hua; Hsu, Che-Fang; Huang, Rui-Len; Ding, Dah-Ching; Chu, Tang-Yuan

2016-01-01

During human ovulation, the fallopian tube fimbriae must move to the ovulation site to catch the oocyte. As the tissue-of-origin of the majority of ovarian high-grade serous carcinoma (HGSC), the fallopian tube fimbriae carrying a precursor cancer lesion may also approach the ovulatory site for metastasis. We hypothesize that platelet-derived growth factor (PDGF) in mature follicle fluid (FF) attracts the migration of PDGFR-expressing fimbriae toward the ovulating follicle. We observed that more PDGFR-β was expressed in the distal part than in the proximal parts of the fallopian tube, particularly in stromal cells in the lamina propria. The stromal cells, but not the epithelial cells, from normal fimbriae and fallopian tube HGSC were highly chemotactic to mature FF. The chemotactic activities were positively correlated with PDGF-BB and estradiol levels in FF and were abolished by a blocking antibody of PDGFR-β and by tyrosine kinase inhibitor imatinib. When PDGF-BB/AB was depleted from the FF, more than 80% of chemotaxis activities were diminished. This study suggests an ovarian follicle-directed and PDGF-dependent attraction of fallopian tube fimbriae before ovulation. The same mechanism may also be crucial for the ovarian homing of HGSC, which largely originates in the fimbriae. PMID:27379403

Treatment of periodontal intrabony defects using β-TCP alone or in combination with rhPDGF-BB: a randomized controlled clinical and radiographic study.

PubMed

Maroo, Sneha; Murthy, K Raja V

2014-01-01

The need to increase the predictability of periodontal regeneration has encouraged clinicians and researchers to employ cell-stimulating proteins in combination with osteoconductive scaffolds, based on the principles of tissue engineering. The purpose of this clinical and radiographic study was to compare the regenerative potential of the combination of β-tricalcium phosphate (β-TCP) and recombinant human platelet-derived growth factor BB (rhPDGF-BB) in the grafting of intraosseous defects with the established technique of bone grafting with (β-TCP alone. A total of 30 sites from 15 patients with infrabony defects in two different quadrants were selected, and the sites were randomly divided into test sites (rhPDGF + β-TCP) and control sites (β-TCP alone) using a split-mouth design. Clinical parameters, including probing pocket depth, clinical attachment level, and gingival recession, were recorded at baseline, 6 months, and 9 months. Radiographic evaluation was carried out to evaluate defect fill, change in alveolar crest height, and percentage of defect fill at baseline, 6 months, and 9 months. Both the experimental groups showed statistically significant reduction in probing pocket depth and gain in clinical attachment level. On intergroup comparison, sites treated with rhPDGF + β-TCP demonstrated a significantly greater pocket depth reduction (P < .05) and greater gain in clinical attachment level (P < .01). Mean percentage defect fill was significantly greater in test sites as compared with control sites at 6 and 9 months (P < .01). rhPDGF + β-TCP-treated sites demonstrated a significant gain in mean alveolar crest height at 6 and 9 months (P < .05), while β-TCP-treated sites demonstrated crestal resorption. Both groups demonstrated potential in enhancing periodontal regeneration; however, on comparison between the two groups, the results obtained by rhPDGF + β-TCP were significantly better with respect to both clinical and radiographic parameters.

PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis.

PubMed

Cho, John S; Fang, Terry C; Reynolds, Taylor L; Sofia, Daniel J; Hamann, Stefan; Burkly, Linda C

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disorder that can result in extensive tissue damage in the skin and, in advanced cases, internal organs. Vasculopathy, aberrant immune activation, and tissue fibrosis are three hallmarks of the disease that have been identified, with vasculopathy and aberrant immunity being amongst the earliest events. However, a mechanistic link between these processes has not been established. Here, we have identified a novel role of platelet derived growth factor-BB (PDGF-BB)/PDGFRβ activation in combination with dermal injury induced by bleomycin as a driver of early, aberrant expression of interferon stimulatory genes (ISGs) and inflammatory monocyte infiltration. Activation of PDGFRβ in combination with bleomycin-induced dermal injury resulted in increased dermal thickness, vascular density, monocyte/macrophage infiltration, and exacerbation of tissue injury. Many of these features were dependent on IFNAR-signaling, and an increase in the number of interferon-beta (IFN-β) producing monocytes cells was found in the skin lesions. Taken together, these results identify a novel link between PDGFRβ activation, and Type I IFN-driven vascular maintenance and monocyte/macrophage cell recruitment, and provide a potential explanation linking key features of SSc that were previously thought to be unrelated.

PI3K is involved in PDGF-beta receptor upregulation post-PDGF-BB treatment in mouse HSC.

PubMed

Lechuga, Carmen G; Hernández-Nazara, Zamira H; Hernández, Elizabeth; Bustamante, Marcia; Desierto, Gregory; Cotty, Adam; Dharker, Nachiket; Choe, Moran; Rojkind, Marcos

2006-12-01

Increased expression of PDGF-beta receptors is a landmark of hepatic stellate cell activation and transdifferentiation into myofibroblasts. However, the molecular mechanisms that regulate the fate of the receptor are lacking. Recent studies suggested that N-acetylcysteine enhances the extracellular degradation of PDGF-beta receptor by cathepsin B, thus suggesting that the absence of PDGF-beta receptors in quiescent cells is due to an active process of elimination and not to a lack of expression. In this communication we investigated further molecular mechanisms involved in PDGF-beta receptor elimination and reappearance after incubation with PDGF-BB. We showed that in culture-activated hepatic stellate cells there is no internal protein pool of receptor, that the protein is maximally phosphorylated by 5 min and completely degraded after 1 h by a lysosomal-dependent mechanism. Inhibition of receptor autophosphorylation by tyrphostin 1296 prevented its degradation, but several proteasomal inhibitors had no effect. We also showed that receptor reappearance is time and dose dependent, being more delayed in cells treated with 50 ng/ml (48 h) compared with 10 ng/ml (24 h).

PAR-2 inhibition reverses experimental pulmonary hypertension.

PubMed

Kwapiszewska, Grazyna; Markart, Philipp; Dahal, Bhola Kumar; Kojonazarov, Baktybek; Marsh, Leigh Matthew; Schermuly, Ralph Theo; Taube, Christian; Meinhardt, Andreas; Ghofrani, Hossein Ardeschir; Steinhoff, Martin; Seeger, Werner; Preissner, Klaus Theo; Olschewski, Andrea; Weissmann, Norbert; Wygrecka, Malgorzata

2012-04-27

A hallmark of the vascular remodeling process underlying pulmonary hypertension (PH) is the aberrant proliferation and migration of pulmonary arterial smooth muscle cells (PASMC). Accumulating evidence suggests that mast cell mediators play a role in the pathogenesis of PH. In the present study we investigated the importance of protease-activated receptor (PAR)-2 and its ligand mast cell tryptase in the development of PH. Our results revealed strong increase in PAR-2 and tryptase expression in the lungs of idiopathic pulmonary arterial hypertension (IPAH) patients, hypoxia-exposed mice, and monocrotaline (MCT)-treated rats. Elevated tryptase levels were also detected in plasma samples from IPAH patients. Hypoxia and platelet-derived growth factor (PDGF)-BB upregulated PAR-2 expression in PASMC. This effect was reversed by HIF (hypoxia inducible factor)-1α depletion, PDGF-BB neutralizing antibody, or the PDGF-BB receptor antagonist Imatinib. Attenuation of PAR-2 expression was also observed in smooth muscle cells of pulmonary vessels of mice exposed to hypoxia and rats challenged with MCT in response to Imatinib treatment. Tryptase induced PASMC proliferation and migration as well as enhanced synthesis of fibronectin and matrix metalloproteinase-2 in a PAR-2- and ERK1/2-dependent manner, suggesting that PAR-2-dependent signaling contributes to vascular remodeling by various mechanisms. Furthermore, PAR-2(-/-) mice were protected against hypoxia-induced PH, and PAR-2 antagonist application reversed established PH in the hypoxia mouse model. Our study identified a novel role of PAR-2 in vascular remodeling in the lung. Interference with this pathway may offer novel therapeutic options for the treatment of PH.

Herbal composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra prevents atherosclerosis by upregulating p27 (Kip1) expression.

PubMed

Lee, Jung-Jin; Lee, Ji-Hye; Cho, Won-Kyung; Han, Joo-Hui; Ma, Jin Yeul

2016-07-28

Kiom-18 is a novel composition of Cinnamomum cassia, Pinus densiflora, Curcuma longa and Glycyrrhiza glabra. Curcuma longa and Glycyrrhiza glabra, which are traditional medicines in Asia, have been reported to demonstrate preventive effects against atherosclerosis; however, they have not yet been developed into functional atherosclerosis treatments. We therefore studied the anti-atherosclerotic effects and possible molecular mechanisms of Kiom-18 using vascular smooth muscle cells (VSMCs). To assess the anti-proliferative effect of Kiom-18 in vitro, we performed thymidine incorporation, cell cycle progression, immunoblotting and immunofluorescence assays in VSMCs stimulated by platelet derived-growth factor (PDGF)-BB. In addition, we used LDLr knockout mice to identify the effects of Kiom-18 as a preliminary result in an atherosclerosis animal model. Kiom-18 inhibited platelet-derived growth factor (PDGF)-BB-stimulated-VSMC proliferation and DNA synthesis. Additionally, Kiom-18 arrested the cell cycle transition of G0/G1 stimulated by PDGF-BB and its cell cycle-related proteins. Correspondingly, the level of p27(kip1) expression was upregulated in the presence of the Kiom-18 extract. Moreover, in an atherosclerosis animal model of LDLr knockout mice, Kiom-18 extract showed a preventive effect for the formation of atherosclerotic plaque and suppressed body weight, fat weight, food treatment efficiency, neutrophil count, and triglyceride level. These results indicate that Kiom-18 exerts anti-atherosclerotic effects by inhibiting VSMC proliferation via G0/G1 arrest, which upregulates p27(Kip1) expression.

Growth factors and chronic wound healing: past, present, and future.

PubMed

Goldman, Robert

2004-01-01

Growth substances (cytokines and growth factors) are soluble signaling proteins affecting the process of normal wound healing. Cytokines govern the inflammatory phase that clears cellular and extracellular matrix debris. Wound repair is controlled by growth factors (platelet-derived growth factor [PDGF], keratinocyte growth factor, and transforming growth factor beta). Endogenous growth factors communicate across the dermal-epidermal interface. PDGF is important for most phases of wound healing. Becaplermin (PDGF-BB), the only growth factor approved by the Food and Drug Administration, requires daily application for neuropathic wound healing. Gene therapy is under development for more efficient growth factor delivery; a single application will induce constitutive growth factor expression for weeks. Based on dramatic preclinical animal studies, a phase 1 clinical trial planned on a PDGF genetic construct appears promising.

Comparative Analysis of Cellular and Growth Factor Composition in Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma.

PubMed

Sugaya, Hisashi; Yoshioka, Tomokazu; Kato, Toshiki; Taniguchi, Yu; Kumagai, Hiroshi; Hyodo, Kojiro; Ohneda, Osamu; Yamazaki, Masashi; Mishima, Hajime

2018-01-01

The purpose of this study was to quantify the stem cell and growth factor (GF) contents in the bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) prepared from whole blood using a protocol established in our laboratory. We examined 10 patients with osteonecrosis of the femoral head who were treated by autologous BMAC transplantation at our hospital between January 2015 and June 2015. We quantified CD34+ and CD31-CD45-CD90+CD105+ cells in BMAC and PRP by flow cytometry. Additionally, we measured various GFs, that is, basic fibroblast growth factor (b-FGF), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), transforming growth factor- β 1 (TGF- β 1), and bone morphogenetic protein-2 (BMP-2) in BMAC and PRP using enzyme-linked immunosorbent assays and statistical analyses. CD34+ and CD31-45-90+105+ cells accounted for approximately 1.9% and 0.03% of cells in BMAC and no cells in PRP. The concentration of b-FGF was higher in BMAC than in PRP ( P < 0.001), whereas no significant differences in the levels of PDGF-BB, VEGF, TGF- β 1, and BMP-2 were observed between the two types of sample. BMAC had an average of 1.9% CD34+ and 0.03% CD31-45-90+105+ cells and higher levels of b-FGF than those of PRP.

Serum Markers of Neurodegeneration in Maple Syrup Urine Disease.

PubMed

Scaini, Giselli; Tonon, Tássia; de Souza, Carolina F Moura; Schuk, Patricia F; Ferreira, Gustavo C; Neto, Joao Seda; Amorin, Tatiana; Schwartz, Ida Vanessa D; Streck, Emilio L

2017-09-01

Maple syrup urine disease (MSUD) is an inherited disorder caused by deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their respective α-keto-acids. Patients affected by MSUD present severe neurological symptoms and brain abnormalities, whose pathophysiology is poorly known. However, preclinical studies have suggested alterations in markers involved with neurodegeneration. Because there are no studies in the literature that report the neurodegenerative markers in MSUD patients, the present study evaluated neurodegenerative markers (brain-derived neurotrophic factor (BDNF), cathepsin D, neural cell adhesion molecule (NCAM), plasminogen activator inhibitor-1 total (PAI-1 (total)), platelet-derived growth factor AA (PDGF-AA), PDGF-AB/BB) in plasma from 10 MSUD patients during dietary treatment. Our results showed a significant decrease in BDNF and PDGF-AA levels in MSUD patients. On the other hand, NCAM and cathepsin D levels were significantly greater in MSUD patients compared to the control group, while no significant changes were observed in the levels of PAI-1 (total) and PDGF-AB/BB between the control and MSUD groups. Our data show that MSUD patients present alterations in proteins involved in the neurodegenerative process. Thus, the present findings corroborate previous studies that demonstrated that neurotrophic factors and lysosomal proteases may contribute, along with other mechanisms, to the intellectual deficit and neurodegeneration observed in MSUD.

Study of a Two-Step Centrifugation Protocol for Concentrating Cells and Growth Factors in Bovine Platelet-Rich Plasma

PubMed Central

Gutiérrez, Claudia M.; López, Catalina

2017-01-01

There is a lack of information about the methods used for bovine platelet-rich plasma (PRP)/platelet-rich gel (PRG) procurement, including information on platelet (PLT), white blood cell (WBC) in PRP, and growth factor release from PRG supernatants. The aims of this study were to compare and to correlate the PLT, WBC, transforming growth factor beta-1 (TGF-β1), and platelet-derived growth factor BB (PDGF-BB) concentrations in bovine whole blood, plasma, and four PRP layers and their respective PRG supernatants: A and B (obtained by a single centrifugation tube method at 720g/5 min) and C and D (obtained by a double centrifugation tube method, by using two centrifugation episodes at 720g/5 min). PLT and WBC counts were significantly higher in PRP-C, followed by whole blood, PRP-A, PRP-B, and PRP-D. TGF-β1 concentrations were significantly higher in PRG-B supernatants and its correspondent PRP-B lysate when compared to the other PRG supernatants and plasma. Supernatants from PRG-A, PRG-B, and PRG-D had equivalent TGF-β1 concentrations. PDGF-BB concentrations were not statistically different between the hemoderivatives. Significant Pearson correlations were noted between PLT counts and WBC counts (0.8) and between PLT counts and PLT distribution width (0.6). Further studies should be performed to assess the potential clinical applications of these PRPs. PMID:29214094

Localized bone regeneration around dental implants using recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB in the canine.

PubMed

Thoma, Daniel S; Cha, Jae-Kook; Sapata, Vitor M; Jung, Ronald E; Hüsler, Juerg; Jung, Ui-Won

2017-11-01

To test whether or not one of two biological mediators (recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor (rhPDGF-BB)) is superior to the other and compared with control groups for bone regeneration around implants based on histomorphometrical outcome measures. Box-type defects (10 × 5 × 5 mm) were prepared on the buccal sides of the left and right edentulous ridge in ten mongrel dogs. Implants were placed at each site, the defects either received (i) bovine-derived particulated bone mineral (DBBM) mixed with rhBMP-2 and a collagen membrane (CM) (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB and CM (DBBM/PDGF), (iii) DBBM and CM (DBBM) and (iv) empty control (control). Animals were euthanized post-surgery at 8 weeks and 16 weeks. Histomorphometrical analyses were performed. The mean percentages of regenerated area within total defect area amounted to 56.95% for DBBM/BMP-2, 48.86% for DBBM/PDFG, 33.44% for DBBM and 1.59% for control at 8 weeks, and 26.79% for DBBM/BMP-2, 23.78% for DBBM/PDFG, 30.21% for DBBM and 5.07% for control at 16 weeks with no statistically significant differences between the groups (P > 0.05). The mean amount of regenerated bone was 26.97% for DBBM/BMP-2, 22.02% for DBBM/PDFG, 5.03% for DBBM and 1.25% for control at 8 weeks, and at 16 weeks, these values were lower in the two groups with biological mediators (DBBM/BMP-2 = 13.35%; DBBM/PDGF = 6.96%) and only slightly increased in group DBBM (10.68%) and the control group (4.95%) compared with 8 weeks. The first bone-to-implant contact values on the buccal side were minimal for DBBM/BMP-2 (0.57 mm) and maximal for control (3.72 mm) at 8 weeks. The use of biological mediators (rhBMP-2 and rhPDGF-BB) can increase the amount of bone regeneration at dehiscence-type defects compared with controls at 8 weeks, but not at 16 weeks due to enhanced hard tissue remodeling processes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression of platelet-derived growth factor BB, erythropoietin and erythropoietin receptor in canine and feline osteosarcoma.

PubMed

Meyer, F R L; Steinborn, R; Grausgruber, H; Wolfesberger, B; Walter, I

2015-10-01

The discovery of expression of the erythropoietin receptor (EPO-R) on neoplastic cells has led to concerns about the safety of treating anaemic cancer patients with EPO. In addition to its endocrine function, the receptor may play a role in tumour progression through an autocrine mechanism. In this study, the expression of EPO, EPO-R and platelet-derived growth factor BB (PDGF-BB) was analysed in five feline and 13 canine osteosarcomas using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). EPO expression was positive in all tumours by IHC, but EPO mRNA was only detected in 38% of the canine and 40% of the feline samples. EPO-R was expressed in all samples by quantitative RT-PCR (RT-qPCR) and IHC. EPO-R mRNA was expressed at higher levels in all feline tumours, tumour cell lines, and kidney when compared to canine tissues. PDGF-BB expression was variable by IHC, but mRNA was detected in all samples. To assess the functionality of the EPO-R on tumour cells, the proliferation of canine and feline osteosarcoma cell lines was evaluated after EPO administration using an alamarBlue assay and Ki67 immunostaining. All primary cell lines responded to EPO treatment in at least one of the performed assays, but the effect on proliferation was very low indicating only a weak responsiveness of EPO-R. In conclusion, since EPO and its receptor are expressed by canine and feline osteosarcomas, an autocrine or paracrine tumour progression mechanism cannot be excluded, although in vitro data suggest a minimal role of EPO-R in osteosarcoma cell proliferation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Expression of platelet-derived growth factor BB, erythropoietin and erythropoietin receptor in canine and feline osteosarcoma

PubMed Central

Meyer, F.R.L.; Steinborn, R.; Grausgruber, H.; Wolfesberger, B.; Walter, I.

2015-01-01

The discovery of expression of the erythropoietin receptor (EPO-R) on neoplastic cells has led to concerns about the safety of treating anaemic cancer patients with EPO. In addition to its endocrine function, the receptor may play a role in tumour progression through an autocrine mechanism. In this study, the expression of EPO, EPO-R and platelet-derived growth factor BB (PDGF-BB) was analysed in five feline and 13 canine osteosarcomas using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). EPO expression was positive in all tumours by IHC, but EPO mRNA was only detected in 38% of the canine and 40% of the feline samples. EPO-R was expressed in all samples by quantitative RT-PCR (RT-qPCR) and IHC. EPO-R mRNA was expressed at higher levels in all feline tumours, tumour cell lines, and kidney when compared to canine tissues. PDGF-BB expression was variable by IHC, but mRNA was detected in all samples. To assess the functionality of the EPO-R on tumour cells, the proliferation of canine and feline osteosarcoma cell lines was evaluated after EPO administration using an alamarBlue assay and Ki67 immunostaining. All primary cell lines responded to EPO treatment in at least one of the performed assays, but the effect on proliferation was very low indicating only a weak responsiveness of EPO-R. In conclusion, since EPO and its receptor are expressed by canine and feline osteosarcomas, an autocrine or paracrine tumour progression mechanism cannot be excluded, although in vitro data suggest a minimal role of EPO-R in osteosarcoma cell proliferation. PMID:26189892

Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration.

PubMed

Kesavan, R; Chandel, S; Upadhyay, S; Bendre, R; Ganugula, R; Potunuru, U R; Giri, H; Sahu, G; Kumar, P Uday; Reddy, G Bhanuprakash; Joksic, G; Bera, A K; Dixit, Madhulika

2016-04-01

Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-α induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-γ activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Pore Interconnectivity Influences Growth Factor-Mediated Vascularization in Sphere-Templated Hydrogels

PubMed Central

Somo, Sami I.; Akar, Banu; Bayrak, Elif S.; Larson, Jeffery C.; Appel, Alyssa A.; Mehdizadeh, Hamidreza; Cinar, Ali

2015-01-01

Rapid and controlled vascularization within biomaterials is essential for many applications in regenerative medicine. The extent of vascularization is influenced by a number of factors, including scaffold architecture. While properties such as pore size and total porosity have been studied extensively, the importance of controlling the interconnectivity of pores has received less attention. A sintering method was used to generate hydrogel scaffolds with controlled pore interconnectivity. Poly(methyl methacrylate) microspheres were used as a sacrificial agent to generate porous poly(ethylene glycol) diacrylate hydrogels with interconnectivity varying based on microsphere sintering conditions. Interconnectivity levels increased with sintering time and temperature with resultant hydrogel structure showing agreement with template structure. Porous hydrogels with a narrow pore size distribution (130–150 μm) and varying interconnectivity were investigated for their ability to influence vascularization in response to gradients of platelet-derived growth factor-BB (PDGF-BB). A rodent subcutaneous model was used to evaluate vascularized tissue formation in the hydrogels in vivo. Vascularized tissue invasion varied with interconnectivity. At week 3, higher interconnectivity hydrogels had completely vascularized with twice as much invasion. Interconnectivity also influenced PDGF-BB transport within the scaffolds. An agent-based model was used to explore the relative roles of steric and transport effects on the observed results. In conclusion, a technique for the preparation of hydrogels with controlled pore interconnectivity has been developed and evaluated. This method has been used to show that pore interconnectivity can independently influence vascularization of biomaterials. PMID:25603533

Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Haipeng; Zhang, Xin; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012

Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has longmore » been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and attenuate pulmonary vascular remodeling after MCT induction. These beneficial effects were at least through the inhibition of PDGF-Rβ phosphorylation and its downstream signaling pathways. Therefore, IRN might be a potential candidate for the treatment of PAH.« less

MicroRNA-24 regulates vascular remodeling via inhibiting PDGF-BB pathway in diabetic rat model.

PubMed

Yang, Jian; Zeng, Ping; Yang, Jun; Liu, Xiaowen; Ding, Jiawang; Wang, Huibo; Chen, Lihua

2018-06-15

Hyperglycemia is the high risk factor of vascular remodeling induced by angioplasty, and neointimal hyperplasia is strongly implicated in the pathogenesis of vascular remodeling caused by carotid artery balloon injury. Studies have shown that MicroRNA 24 (miR-24) plays an important role in angiocardiopathy, However, the role of miR-24 is far from thorough research. In this study, we investigate whether up-regulation of miR-24 by using miR-24 recombinant adenovirus (Ad-miR-24-GFP) can inhibit PDGF-BB signaling pathway and attenuate vascular remodeling in the diabetic rat model. Male Sprague-Dawley rats (n = 60) were randomly divided into 5 groups and fed with high sugar and high fat diet (Sham, Saline, Scramble, Ad-miR-24 groups), or ordinary diet (Control group). The front four groups were treated with streptozotocin (STZ) four weeks later and the blood glucose level was closely monitored. After the successful establishment of diabetic rats, the external carotid artery was injured by pressuring balloon 1.5 after internal carotid artery ligation, then the blood vessels were harvested 14 days later and indexes were detected including the following: HE staining for the level of vascular intima thickness, immunohistochemical detection for PCNA and P27 to test the proliferative degree of vascular smooth muscle cells (VSMCs), qRT-PCR for the level of miR-24, RAS,PDGF-R, western blot for the protein levels of JNK1/2, p- JNK1/2, ERK1/2, p-ERK1/2, RAS, PDGF-R, AP-1,P27 and PCNA. Serological detection was conducted for TNF-α, IL-6, IL-8. The delivery of Ad-miR-24 into balloon injury site has significantly increased the level of miR-24. Up-regulation of miR-24 could regulate vascular remodeling effectively, lower the level of inflammatory factors, inhibit the expression of mRNA and protein levels of JNK1/2, ERK1/2, RAS, PDGF-R, AP-1, P27, PCNA. miR-24 can inhibit the expression of AP-1 via the inhibition of PDGF-BB signaling pathway, thus inhibit VSMCs proliferation and vascular remodeling. Copyright © 2018. Published by Elsevier B.V.

Loop III region of platelet-derived growth factor (PDGF) B-chain mediates binding to PDGF receptors and heparin.

PubMed Central

Schilling, D; Reid IV, J D; Hujer, A; Morgan, D; Demoll, E; Bummer, P; Fenstermaker, R A; Kaetzel, D M

1998-01-01

Site-directed mutagenesis of the platelet-derived growth factor (PDGF) B-chain was conducted to determine the importance of cationic amino acid residues (Arg160-Lys161-Lys162; RKK) located within the loop III region in mediating the biological and cell-association properties of the molecule. Binding to both PDGF alpha-and beta-receptors was inhibited by the conversion of all three cationic residues into anionic glutamates (RKK-->EEE), whereas an RKK-->SSS mutant also exhibited a modest loss in affinity for beta-receptors. Replacements with serine at either Arg160 (RKK-->SKK) or at all three positions (RKK-->SSS) had little effect on binding to alpha-receptors. Replacements with either glutamic or serine residues at any of the three positions also resulted in significant inhibition of heparin-binding activity. Furthermore, the RKK-->EEE mutant exhibited decreased association with the cell surface and accumulated in the culture medium as 29-32 kDa forms. Stable transfection of U87 astrocytoma cells with RKK-->EEE mutants of either the A-chain or the B-chain inhibited malignant growth in athymic nude mice. Despite altered receptor-binding activities, each of the loop III mutants retained full mitogenic activity when applied to cultured Swiss 3T3 cells. CD spectrophotometric analysis of the RKK-->EEE mutant revealed a secondary structure indistinguishable from the wild type, with a high degree of beta-sheet structure and random coil content (50% and 43% respectively). These findings indicate an important role of the Arg160-Lys161-Lys162 sequence in mediating the biological and cell-associative activities of the PDGF-BB homodimer, and reveal that the mitogenic activity of PDGF-BB is insufficient to mediate its full oncogenic properties. PMID:9677323

Focal Adhesion Kinase Regulates Fibroblast Migration via Integrin beta-1 and Plays a Central Role in Fibrosis

PubMed Central

Zhao, Xue-Ke; Cheng, Yiju; Liang Cheng, Ming; Yu, Lei; Mu, Mao; Li, Hong; Liu, Yang; Zhang, Baofang; Yao, Yumei; Guo, Hui; Wang, Rong; Zhang, Quan

2016-01-01

Lung fibrosis is a major medical problem for the aging population worldwide. Fibroblast migration plays an important role in fibrosis. Focal Adhesion Kinase (FAK) senses the extracellular stimuli and initiates signaling cascades that promote cell migration. This study first examined the dose and time responses of FAK activation in human lung fibroblasts treated with platelet derived growth factor BB (PDGF-BB). The data indicate that FAK is directly recruited by integrin β1 and the subsequent FAK activation is required for fibroblast migration on fibronectin. In addition, the study has identified that α5β1 and α4β1 are the major integrins for FAK-mediated fibroblast migration on fibronect. In contrast, integrins αvβ3, αvβ6, and αvβ8 play a minor but distinct role in fibroblast migration on fibronectin. FAK inhibitor significantly reduces PDGF-BB stimulated fibroblast migration. Importantly, FAK inhibitor protects bleomycin-induced lung fibrosis in mice. FAK inhibitor blocks FAK activation and significantly reduces signaling cascade of fibroblast migration in bleomycin-challenged mice. Furthermore, FAK inhibitor decreases lung fibrotic score, collagen accumulation, fibronectin production, and myofibroblast differentiation in in bleomycin-challenged mice. These data demonstrate that FAK mediates fibroblast migration mainly via integrin β1. Furthermore, the findings suggest that targeting FAK signaling is an effective therapeutic strategy against fibrosis. PMID:26763945

Phenotypic transformation of smooth muscle cells from porcine coronary arteries is associated with connexin 43

PubMed Central

ZHANG, XUMIN; WANG, XIAODONG; ZHOU, XIAOHUI; MA, XIAOYE; YAO, YIAN; LIU, XUEBO

2016-01-01

The current study aimed to investigate the relevance of the gap junction protein connexin Cx43 in coronary artery smooth muscle cell (SMC) heterogeneity and coronary artery restenosis. SMCs were isolated from the coronary artery of 3-month-old pigs using enzymatic digestion. Two distinct SMC populations were isolated: Rhomboid (R) and spindle-shaped (S) cells. S-SMCs exhibited relatively lower rates of proliferation, exhibiting a classic ''hills-and valleys'' growth pattern; R-SMCs displayed increased proliferation rates, growing as mono- or multi-layers. Immunofluorescent staining, polymerase chain reaction and western blotting were used to assess the expression of Cx40 and Cx43 in SMCs. For further evaluation, cultured SMCs were treated with 10 ng/ml platelet-derived growth factor (PDGF)-BB with or without the gap junction blocker 18α-glycyrrhetinic acid. Stent-induced restenosis was assessed in vivo. Different expression patterns were observed for Cx40 and Cx43 in R- and S-SMCs. Cx40 was the most abundant Cx in S-SMCs, whereas CX43 was identified at relatively higher levels than Cx40 in R-SMCs. Notably, PDGF-BB converted S-SMCs to R-SMCs, with increased Cx43 expression, while 18α-glycyrrhetinic acid inhibited the PDGF-BB-induced phenotypic alterations in S-SMCs. Additionally, restenosis was confirmed in pigs 1-month subsequent to stent placement. R-SMCs were the major cell population isolated from stent-induced restenosis artery tissues, and exhibited markedly increased Cx43 expression, in accordance with the in vitro data described above. In conclusion, the phenotypic transformation of coronary artery SMCs is closely associated with Cx43, which is involved in restenosis. These observations provide a basis for the use of Cx43 as a novel target in restenosis prevention. PMID:27175888

Pericyte–fibroblast transition promotes tumor growth and metastasis

PubMed Central

Hosaka, Kayoko; Yang, Yunlong; Seki, Takahiro; Fischer, Carina; Dubey, Olivier; Fredlund, Erik; Hartman, Johan; Religa, Piotr; Ishii, Yoko; Sasahara, Masakiyo; Larsson, Ola; Cossu, Giulio; Cao, Renhai; Lim, Sharon; Cao, Yihai

2016-01-01

Vascular pericytes, an important cellular component in the tumor microenvironment, are often associated with tumor vasculatures, and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte–fibroblast transition (PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that PDGF-BB-PDGFRβ signaling promotes PFT both in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB–activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFRβ ablate the PDGF-BB–induced PFT. Genetic tracing of pericytes with two independent mouse strains, TN-AP-CreERT2:R26R-tdTomato and NG2-CreERT2:R26R-tdTomato, shows that PFT cells gain stromal fibroblast and myofibroblast markers in tumors. Importantly, coimplantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells and metastasis. Our findings reveal a mechanism of vascular pericytes in PDGF-BB–promoted cancer invasion and metastasis by inducing PFT, and thus targeting PFT may offer a new treatment option of cancer metastasis. PMID:27608497

Long-term cytokine and growth factor release from equine platelet-rich fibrin clots obtained with two different centrifugation protocols.

PubMed

Jiménez-Aristizabal, Román F; López, Catalina; Álvarez, María E; Giraldo, Carlos; Prades, Marta; Carmona, Jorge U

2017-09-01

To compare the temporal release (over three weeks) of tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-1 receptor antagonist (IL-1ra), platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta-1 (TGF-β 1 ) from two platelet-rich fibrin (PRF) preparations from equine blood obtained at either 240g/8min or 416g/10min. Whole blood from 10 horses was used to obtain PRF clots by two different centrifugation protocols. After 1h of rest, PRF clots were deposited in wells with culture medium, which was changed at 6h, 24h and then every 48h to 21days. Cytokines and GFs were measured by ELISA at 1h (serum supernatants from PRF clots) and all time points of culture medium change. A negative control (plasma) and a positive control (blood lysate) were also included. There were no relevant differences between the two protocols for the temporal release of proteins. However, a significant (p=0.01) effect of time was noted. All cytokines were detected after 6h of PRF clot culture until day 21. GF were detected at 1h until day 21. The concentrations for these proteins diminished gradually over time. A highly significant (p=0.01) correlation was noticed between all the proteins evaluated. Leukocytes enmeshed in PRF clots were able to produce cytokines, TGF-β 1 and PDGF-BB. These findings demonstrate a paramount role of leukocytes in wound healing induced or modified by PRF clots in mammals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimisation of a double-centrifugation method for preparation of canine platelet-rich plasma.

PubMed

Shin, Hyeok-Soo; Woo, Heung-Myong; Kang, Byung-Jae

2017-06-26

Platelet-rich plasma (PRP) has been expected for regenerative medicine because of its growth factors. However, there is considerable variability in the recovery and yield of platelets and the concentration of growth factors in PRP preparations. The aim of this study was to identify optimal relative centrifugal force and spin time for the preparation of PRP from canine blood using a double-centrifugation tube method. Whole blood samples were collected in citrate blood collection tubes from 12 healthy beagles. For the first centrifugation step, 10 different run conditions were compared to determine which condition produced optimal recovery of platelets. Once the optimal condition was identified, platelet-containing plasma prepared using that condition was subjected to a second centrifugation to pellet platelets. For the second centrifugation, 12 different run conditions were compared to identify the centrifugal force and spin time to produce maximal pellet recovery and concentration increase. Growth factor levels were estimated by using ELISA to measure platelet-derived growth factor-BB (PDGF-BB) concentrations in optimised CaCl 2 -activated platelet fractions. The highest platelet recovery rate and yield were obtained by first centrifuging whole blood at 1000 g for 5 min and then centrifuging the recovered platelet-enriched plasma at 1500 g for 15 min. This protocol recovered 80% of platelets from whole blood and increased platelet concentration six-fold and produced the highest concentration of PDGF-BB in activated fractions. We have described an optimised double-centrifugation tube method for the preparation of PRP from canine blood. This optimised method does not require particularly expensive equipment or high technical ability and can readily be carried out in a veterinary clinical setting.

Use of a Cyclooxygenase-2 Inhibitor Does Not Inhibit Platelet Activation or Growth Factor Release From Platelet-Rich Plasma.

PubMed

Ludwig, Hilary C; Birdwhistell, Kate E; Brainard, Benjamin M; Franklin, Samuel P

2017-12-01

It remains unestablished whether use of cyclooxygenase (COX)-2 inhibitors impairs platelet activation and anabolic growth factor release from platelets in platelet-rich plasma (PRP). The purpose of this study was to assess the effects of a COX-2 inhibitor on platelet activation and anabolic growth factor release from canine PRP when using a clinically applicable PRP activator and to determine whether a 3-day washout would be sufficient to abrogate any COX-2 inhibitor-related impairment on platelet function. Controlled laboratory study. Ten healthy dogs underwent blood collection and PRP preparation. Dogs were then administered a COX-2 inhibitor for 7 days, after which PRP preparation was repeated. The COX-2 inhibitor was continued for 4 more days and PRP preparation performed a third time, 3 days after discontinuation of the COX-2 inhibitor. Immediately after PRP preparation, the PRP was divided into 4 aliquots: 2 unactivated and 2 activated using human γ-thrombin (HGT). One activated and 1 unactivated sample were assessed using flow cytometry for platelet expression of CD62P and platelet-bound fibrinogen using the canine activated platelet-1 (CAP1) antibody. The 2 remaining samples were centrifuged and the supernatant assayed for transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-BB (PDGF-BB), and thromboxane B2 (TXB2) concentrations. Differences in platelet activation and TGF-β1, PDGF-BB, and TXB2 concentrations over the 3 study weeks were evaluated using a 1-way repeated-measures ANOVA, and comparisons between activated and unactivated samples within a study week were assessed with paired t tests. There were no statistically significant ( P > .05) effects of the COX-2 inhibitor on percentage of platelets positive for CD62P or CAP1 or on concentrations of TGF-β1, PDGF-BB, or TXB2. All unactivated samples had low levels of activation or growth factor concentrations and significantly ( P < .05) greater activation and growth factor concentrations in HGT-activated samples. This COX-2 inhibitor did not impair platelet activation, growth factor release, or TXB2 production in this canine PRP when using HGT as an activator. Studies are warranted to determine whether COX-2 inhibitors affect platelet activation and growth factor release from human PRPs. These results suggest that there is no need to withhold a COX-2 inhibitor before PRP preparation, particularly if thrombin is going to be used to activate the PRP. This is clinically relevant information because many patients who are candidates for PRP therapy for treatment of musculoskeletal injury are also using COX-2 inhibitors.

Comparison of Tear cytokines and clinical outcomes between off-flap and on-flap epi-LASIK with mitomycin C.

PubMed

Zhang, Yu; Chen, Yue-Guo; Xia, Ying-Jie; Qi, Hong

2012-09-01

To compare tear cytokines and clinical outcomes between off-flap and on-flap epi-LASIK eyes and explore the possible mechanism for the clinical differences. This double-masked, randomized study enrolled 18 myopic patients who underwent off-flap epi-LASIK with mitomycin C (MMC) in 1 eye and on-flap epi-LASIK with MMC in the contralateral eye. Tears were collected from each eye preoperatively and 2 hours, 1 day, and 5 days postoperatively. Concentrations of multiple tear cytokines were measured by a multiplex immunobead assay. Uncorrected distance visual acuity (UDVA), refraction, haze scores, pain scores, and percentage of corneal epithelial healing were evaluated. Compared with the on-flap group, the off-flap group had outcomes of better UDVA and higher percentages of epithelial healing at 5 days after surgery (P<.001) and lower levels of haze at 1 month after surgery (P=.049). Preoperatively, no significant differences were noted in the release rate of all tear cytokines between groups. At 2 hours postoperatively, the release rate of tear basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF-BB), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in the off-flap group were significantly lower than those in the on-flap group (P=.011, .017, .048, and .041, respectively). Off-flap epi-LASIK with MMC offers faster corneal epithelial healing and visual recovery, and temporary less haze than on-flap epi-LASIK with MMC. The lower tear levels of bFGF, PDGF-BB, IL-8, and TNF-α in the offflap group 2 hours after surgery may suggest a possible mechanism for the clinical differences. Copyright 2012, SLACK Incorporated.

Effects of Non-Collagenous Proteins, TGF-β1, and PDGF-BB on Viability and Proliferation of Dental Pulp Stem Cells

PubMed Central

Tabatabaei, Fahimeh Sadat

2016-01-01

ABSTRACT Objectives The dentin matrix servers as a reservoir of growth factors, sequestered during dentinogenesis. The aim of this study was to assess the viability and proliferation of dental pulp stem cells in the presence of dentin matrix-derived non-collagenous proteins and two growth factors; platelet-derived growth factor BB and transforming growth factor beta 1. Material and Methods The dental pulp cells were isolated and cultured. The dentin proteins were extracted and purified. The MTT assay was performed for assessment of cell viability and proliferation in the presence of different concentrations of dentin proteins and growth factors during 24 - 72 h post-treatment. Results The cells treated with 250 ng/mL dentin proteins had the best viability and proliferation ability in comparison with other concentrations (P < 0.05). The MTT assay demonstrated that cells cultured with 5 ng/mL platelet-derived growth factor BB had the highest viability at each time point as compared to other groups (P < 0.05). However, in presence of platelet-derived growth factor BB alone and in combination with transforming growth factor beta 1 and dentin proteins (10 ng/mL), significant higher viability was seen at all time points (P < 0.05). The least viability and proliferation at each growth factor concentration was seen in cells treated with combination of transforming growth factor beta 1 and dentin proteins at 72 h (P < 0.05). Conclusions The results indicated that the triple combination of growth factors and matrix-derived non-collagenous proteins (especially at 10 ng/mL concentration) has mitogenic effect on dental pulp stem cells. PMID:27099698

Specific growth stimulation of cultured smooth muscle cells from spontaneously hypertensive rats by platelet-derived growth factor A-chain homodimer.

PubMed Central

Resink, T J; Scott-Burden, T; Hahn, A W; Rouge, M; Hosang, M; Powell, J S; Bühler, F R

1990-01-01

Cultured vascular smooth muscle cells (VSMC)1 from spontaneously hypertensive rats (SHR) possess specific cell surface receptors for both homodimeric forms of platelet-derived growth factor (PDGF-AA and PDGF-BB), in contrast to cells from normotensive Wistar Kyoto (WKY) animals, which express receptors only for the B-chain form of PDGF. Stimulation of quiescent VSMC from SHR with PDGF-AA resulted in activation of S6-kinase and induction of phosphoinositide catabolism, as well as cellular proliferation when cultures were maintained for prolonged periods with daily supplementation of the growth factor. WKY-derived VSMC showed no response to PDGF-AA, which was consistent with their lack of specific receptors for this homodimer. The responsiveness of quiescent cells from SHR and WKY to the B-chain homodimer was similar. The enhanced growth responsiveness of SHR-derived cells to fetal calf serum, as compared with cells from their normotensive counterparts, may be accounted for in part by their expression of receptors for the AA homodimer of PDGF. PMID:1965150

Effect of chitosan and coagulation factors on the wound repair phenotype of bioengineered blood clots.

PubMed

Hoemann, Caroline D; Marchand, Catherine; Rivard, Georges-Etienne; El-Gabalawy, Hani; Poubelle, Patrice E

2017-11-01

Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B 4 (LTB 4 ) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB 4 or inflammatory factors. Only 80% DDA chitosan clots produced around 15-fold more LTB 4 over other clots including 95% DDA chitosan clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots produced very low type I cytokines compared to lipopolysaccharide clots, with even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots. Coagulation factors had no detectable effect on clot phenotype. Conclusion In blood clots from healthy individuals, 80% DDA chitosan has a unique influence of inducing more LTB 4 , a potent neutrophil chemoattractant, with similar production of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical evaluation of GEM 21S® and a collagen membrane with a coronally advanced flap as a root coverage procedure in the treatment of gingival recession defects: A comparative study

PubMed Central

Singh, Preetinder; Suresh, D. K.

2012-01-01

Aim: Clinical evaluation of efficacy of rhPDGF-BB plus beta tricalcium phosphate (GEM 21S®) along with a collagen membrane in root coverage using a coronally advanced flap. Materials and Methods: This human case series evaluated the clinical outcome of rhPDGF-BB with beta-tricalcium phosphate (GEM 21S®) and a collagen membrane in the treatment of recession defects using a coronally advanced flap. Patients were followed postoperatively, and healing was evaluated at 1, 3, and 6 months, with recession depth as the primary outcome measure. Results: This pioneer case series revealed a favorable tissue response to GEM 21S® and collagen membrane from both clinical and esthetic point of view in regenerative periodontal surgery. PMID:23493720

Antiproliferation effect of imatinib mesylate on MCF7, T-47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR-β, PDGF-BB, c-Kit and SCF genes

PubMed Central

Kadivar, Ali; Kamalidehghan, Behnam; Akbari Javar, Hamid; Karimi, Benyamin; Sedghi, Reihaneh; Noordin, Mohamed Ibrahim

2017-01-01

Recent cancer molecular therapies are targeting main functional molecules to control applicable process of cancer cells. Attractive targets are established by receptor tyrosine kinases, such as platelet-derived growth factor receptors (PDGFRs) and c-Kit as mostly irregular signaling, which is due to either over expression or mutation that is associated with tumorigenesis and cell proliferation. Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-β and c-Kit. In this research, we studied how imatinib mesylate would exert effect on MCF7 and T-47D breast cancer and MCF 10A epithelial cell lines, the gene and protein expression of PDGFR-β, c-Kit and their relevant ligands platelet-derived growth factor (PDGF)-BB and stem cell factor (SCF). The MTS assay was conducted in therapeutic relevant concentration of 2–10 µM for 96, 120 and 144 h treatment. In addition, apoptosis induction and cytostatic activity of imatinib mesylate were investigated with the terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL and cell cycle assays, respectively, in a time-dependent manner. Comparative real-time PCR and Western blot analysis were conducted to evaluate the expression and regulation of imatinib target genes and proteins. Our finding revealed that imatinib mesylate antiproliferation effect, apoptosis induction and cytostatic activity were significantly higher in breast cancer cell lines compared to MCF 10A. This effect might be due to the expression of PDGFR-β, PDGF-BB, c-Kit and SCF, which was expressed by all examined cell lines, except the T-47D cell line which was not expressed c-Kit. However, examined gene and proteins expressed more in cancer cell lines. Therefore, imatinib mesylate was more effective on them. It is concluded that imatinib has at least two potential targets in both examined breast cancer cell lines and can be a promising drug for targeted therapy to treat breast cancer. PMID:28260860

AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaguin, Marie; Fardel, Olivier; Pôle Biologie, Centre Hospitalier Universitaire

2015-06-15

Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantlymore » increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. - Highlights: • PDGF-B expression and secretion are increased by DEPe exposure in human M1 and M2 MΦ. • DEPe-induced PDGF-B expression is aryl-hydrocarbon-dependent. • DEPe-exposed M1 MΦ secrete sufficient PDGF-B to increase lung fibroblast proliferation.« less

Activated platelet-derived growth factor autocrine pathway drives the transformed phenotype of a human glioblastoma cell line.

PubMed

Vassbotn, F S; Ostman, A; Langeland, N; Holmsen, H; Westermark, B; Heldin, C H; Nistér, M

1994-02-01

Human glioblastoma cells (A172) were found to concomitantly express PDGF-BB and PDGF beta-receptors. The receptors were constitutively autophosphorylated in the absence of exogenous ligand, suggesting the presence of an autocrine PDGF pathway. Neutralizing PDGF antibodies as well as suramin inhibited the autonomous PDGF receptor tyrosine kinase activity and resulted in up-regulation of receptor protein. The interruption of the autocrine loop by the PDGF antibodies reversed the transformed phenotype of the glioblastoma cell, as determined by (1) diminished DNA synthesis, (2) inhibition of tumor colony growth, and (3) reversion of the transformed morphology of the tumor cells. The PDGF antibodies showed no effect on the DNA synthesis of another glioblastoma cells line (U-343MGa 31L) or on Ki-ras-transformed fibroblasts. The present study demonstrates an endogenously activated PDGF pathway in a spontaneous human glioblastoma cell line. Furthermore, we provide evidence that the autocrine PDGF pathway drives the transformed phenotype of the tumor cells, a process that can be blocked by extracellular antagonists.

Mechanical strain stimulates vasculogenesis and expression of angiogenesis guidance molecules of embryonic stem cells through elevation of intracellular calcium, reactive oxygen species and nitric oxide generation.

PubMed

Sharifpanah, Fatemeh; Behr, Sascha; Wartenberg, Maria; Sauer, Heinrich

2016-12-01

Differentiation of embryonic stem (ES) cells may be regulated by mechanical strain. Herein, signaling molecules underlying mechanical stimulation of vasculogenesis and expression of angiogenesis guidance cues were investigated in ES cell-derived embryoid bodies. Treatment of embryoid bodies with 10% static mechanical strain using a Flexercell strain system significantly increased CD31-positive vascular structures and the angiogenesis guidance molecules plexinB1, ephrin B2, neuropilin1 (NRP1), semaphorin 4D (sem4D) and robo4 as well as vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-BB (PDGF-BB) as evaluated by Western blot and real time RT-PCR. In contrast ephrin type 4 receptor B (EphB4) expression was down-regulated upon mechanical strain, indicating an arterial-type differentiation. Robo1 protein expression was modestly increased with no change in mRNA expression. Mechanical strain increased intracellular calcium as well as reactive oxygen species (ROS) and nitric oxide (NO). Mechanical strain-induced vasculogenesis was abolished by the NOS inhibitor L-NAME, the NADPH oxidase inhibitor VAS2870, upon chelation of intracellular calcium by BAPTA as well as upon siRNA inactivation of ephrin B2, NRP1 and robo4. BAPTA blunted the strain-induced expression of angiogenic growth factors, the increase in NO and ROS as well as the expression of NRP1, sem4D and plexinB1, whereas ephrin B2, EphB4 as well as robo1 and robo4 expression were not impaired. Mechanical strain stimulates vasculogenesis of ES cells by the intracellular messengers ROS, NO and calcium as well as by upregulation of angiogenesis guidance molecules and the angiogenic growth factors VEGF, FGF-2 and PDGF-BB. Copyright © 2016 Elsevier B.V. All rights reserved.

TNF-{alpha} similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Lars, E-mail: lars.mueller@uksh-kiel.de; Seggern, Lena von; Schumacher, Jennifer

2010-07-02

Cancer-associated fibroblasts (CAFs) represent the predominant cell type of the neoplastic stroma of solid tumors, yet their biology and functional specificity for cancer pathogenesis remain unclear. We show here that primary CAFs from colorectal liver metastases express several inflammatory, tumor-enhancing factors, including interleukin (IL)-6 and monocyte-chemoattractant protein (MCP)-1. Both molecules were intensely induced by TNF-{alpha} on the transcript and protein level, whereas PDGF-BB, TGF-{beta}1 and EGF showed no significant effects. To verify their potential specialization for metastasis progression, CAFs were compared to fibroblasts from non-tumor liver tissue. Interestingly, these liver fibroblasts (LFs) displayed similar functions. Further analyses revealed a comparablemore » up-regulation of intercellular adhesion molecule-1 (ICAM-1) by TNF-{alpha}, and of alpha-smooth muscle actin, by TGF-{beta}1. Moreover, the proliferation of both cell types was induced by PDGF-BB, and CAFs and LFs displayed an equivalent migration towards HT29 colon cancer cells in Boyden chamber assays. In conclusion, colorectal liver metastasis may be supported by CAFs and resident fibroblastic cells competent to generate a prometastatic microenvironment through inflammatory activation of IL-6 and MCP-1.« less

Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation

PubMed Central

Tang, Zhongshu; Arjunan, Pachiappan; Lee, Chunsik; Li, Yang; Kumar, Anil; Hou, Xu; Wang, Bin; Wardega, Piotr; Zhang, Fan; Dong, Lijin; Zhang, Yongqing; Zhang, Shi-Zhuang; Ding, Hao; Fariss, Robert N.; Becker, Kevin G.; Lennartsson, Johan; Nagai, Nobuo; Cao, Yihai

2010-01-01

Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine–induced Parkinson’s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3β phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC–PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions. PMID:20231377

Proangiogenic hydrogels within macroporous scaffolds enhance islet engraftment in an extrahepatic site.

PubMed

Brady, Ann-Christina; Martino, Mikaël M; Pedraza, Eileen; Sukert, Steve; Pileggi, Antonello; Ricordi, Camillo; Hubbell, Jeffrey A; Stabler, Cherie L

2013-12-01

The transplantation of allogeneic islets in recent clinical trials has shown substantial promise as a therapy for type 1 diabetes; however, long-term insulin independence remains inadequate. This has been largely attributed to the current intravascular, hepatic transplant site, which exposes islets to mechanical and inflammatory stresses. A highly macroporous scaffold, housed within an alternative transplant site, can support an ideal environment for islet transplantation by providing three-dimensional distribution of islets, while permitting the infiltration of host vasculature. In the present study, we sought to evaluate the synergistic effect of a proangiogenic hydrogel loaded within the void space of a macroporous poly(dimethylsiloxane) (PDMS) scaffold on islet engraftment. The fibrin-based proangiogenic hydrogel tested presents platelet derived growth factor (PDGF-BB), via a fibronectin (FN) fragment containing growth factor and major integrin binding sites in close proximity. The combination of the proangiogenic hydrogel with PDMS scaffolds resulted in a significant decrease in the time to normoglycemia for syngeneic mouse islet transplants. This benefit was associated with an observed increase in competent vessel branching, as well as mature intraislet vessels. Overall, the addition of the proangiogenic factor PDGF-BB, delivered via the FN fragment-functionalized hydrogel, positively influenced the efficiency of engraftment. These characteristics, along with its ease of retrieval, make this combination of a biostable macroporous scaffold and a degradable proangiogenic hydrogel a supportive structure for insulin-producing cells implanted in extrahepatic sites.

Niemann-Pick Type C2 Protein Regulates Free Cholesterol Accumulation and Influences Hepatic Stellate Cell Proliferation and Mitochondrial Respiration Function.

PubMed

Wang, Yuan-Hsi; Twu, Yuh-Ching; Wang, Chung-Kwe; Lin, Fu-Zhen; Lee, Chun-Ya; Liao, Yi-Jen

2018-06-05

Liver fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and hepatocellular carcinoma. A high-cholesterol diet is associated with liver fibrosis via the accumulation of free cholesterol in hepatic stellate cells (HSCs). Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular free cholesterol homeostasis via direct binding with free cholesterol. Previously, we reported that NPC2 was downregulated in liver cirrhosis tissues. Loss of NPC2 enhanced the accumulation of free cholesterol in HSCs and made them more susceptible to transforming growth factor (TGF)-β1. In this study, we showed that knockdown of NPC2 resulted in marked increases in platelet-derived growth factor BB (PDGF-BB)-induced HSC proliferation through enhanced extracellular signal-regulated kinases (ERK), p38, c-Jun N-terminal kinases (JNK), and protein kinase B (AKT) phosphorylation. In contrast, NPC2 overexpression decreased PDGF-BB-induced cell proliferation by inhibiting p38, JNK, and AKT phosphorylation. Although NPC2 expression did not affect caspase-related apoptosis, the autophagy marker light chain 3β (LC3B) was decreased in NPC2 knockdown, and free cholesterol accumulated in the HSCs. The mitochondrial respiration functions (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were decreased in NPC2 knockdown, and free cholesterol accumulated in the HSCs, while NPC2-overexpressed cells remained normal. In addition, NPC2 expression did not affect the susceptibility of HSCs to lipopolysaccharides (LPS), and U18666A treatment induced free cholesterol accumulation, which enhanced LPS-induced Toll-like receptor 4 (TLR4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 phosphorylation, interleukin (IL)-1 and IL-6 expression. Our study demonstrated that NPC2-mediated free cholesterol homeostasis controls HSC proliferation and mitochondrial function.

The future of recombinant growth factors in wound healing.

PubMed

Robson, M C; Mustoe, T A; Hunt, T K

1998-08-01

For more than a decade, clinical trials have been conducted of the application of topical exogenous recombinant growth factors in attempts to accelerate the healing of chronic wounds. Although the results of some of these trials have been encouraging, overall the results have been somewhat discouraging. Much of the difficulty lies in the paucity of carefully controlled clinical trials of wound healing. Since wound healing is a complex process that can be influenced, both positively and negatively, by many factors, designing these trials has proved difficult. To date, only a single recombinant growth factor-recombinant human platelet-derived growth factor-BB (rhPDGF-BB)- has been approved by the US Food and Drug Administration; and that only for use in diabetic foot ulcers. It is unlikely, however, that a single growth factor will be able to resolve all issues of repair or strengthen all vulnerabilities of chronic wounds. Our expectation, therefore, is that growth factors, cytokines, and other biologic agents will be used more specifically in the future, for example, by targeting growth factor therapy at those specific components or processes that a given wound uses to heal.

Supernatants from culture of type I collagen-stimulated PBMC from patients with cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression of MMP-1 by fibroblasts.

PubMed

Brown, Monica; Postlethwaite, Arnold E; Myers, Linda K; Hasty, Karen A

2012-06-01

Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous studies have shown that compared to healthy or diseased controls, the peripheral blood mononuclear cells (PBMC) from patients with SSc produce a variety of cytokines or proliferate when cultured with solubilized type I collagen (CI) or constituent α1(II) and α2(I) polypeptide chains. The purpose of this study was to determine whether PBMC isolated from patients with SSc and cultured in vitro with soluble CI elaborated soluble mediators that inhibit the production of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts. Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous (dc)SSc patients significantly reduced MMP-1 production by SSc dermal fibroblasts, while supernatants of CI-stimulated PBMC from patients with localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from patients with dcSSc in contrast to patients with LS exhibited increased levels of platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-α, IL-13, and EGF. Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13 inhibited the induction of MMP-1 in response to subsequent TNF-α stimulation. These data suggest that therapies aimed at reducing these cytokines may decrease collagen accumulation in SSc, preventing the development of chronic fibrosis.

Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation.

PubMed

Chen, Rui; Zhong, Wei; Shao, Chen; Liu, Peijing; Wang, Cuiping; Wang, Zhongqun; Jiang, Meiping; Lu, Yi; Yan, Jinchuan

2018-02-01

Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed that docosahexaenoic acid (DHA) could improve hypoxia-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Our aims were, therefore, to evaluate the effects and molecular mechanisms of DHA on MCT-induced PH in rats. Rat PH was induced by MCT. Rats were treated with DHA daily in the prevention group (following MCT injection) and the reversal group (after MCT injection for 2 wk) by gavage. After 4 wk, mean pulmonary arterial pressure (mPAP), right ventricular (RV) hypertrophy index, and morphological and immunohistochemical analyses were evaluated. Rat pulmonary artery smooth muscle cells (PASMCs) were used to investigate the effects of DHA on cell proliferation stimulated by platelet-derived growth factor (PDGF)-BB. DHA decreased mPAP and attenuated pulmonary vascular remodeling and RV hypertrophy, which were associated with suppressed ER stress. DHA blocked the mitogenic effect of PDGF-BB on PASMCs and arrested the cell cycle via inhibiting nuclear factor of activated T cells-1 (NFATc1) expression and activation and regulating cell cycle-related proteins. Moreover, DHA ameliorated inflammation in lung and suppressed macrophage and T lymphocyte accumulation in lung and adventitia of resistance pulmonary arteries. These findings suggest that DHA could protect against MCT-induced PH by reducing ER stress, suppressing cell proliferation and inflammation.

In Vivo Tracking of Mesechymal Stem Cells Using Fluorescent Nanoparticles in an Osteochondral Repair Model

PubMed Central

Lee, Jong Min; Kim, Byung-Soo; Lee, Haeshin; Im, Gun-Il

2012-01-01

We devised and tested an in vivo system to monitor the migration of mesenchymal stem cells (MSCs) within the marrow cavity. In vitro studies confirmed that platelet-derived growth factor (PDGF)-AA had the most potent chemotactic effect of the tested factors, and possessed the greatest number of receptors in MSCs. MSCs were labeled with fluorescent nanoparticles and injected into the marrow cavity of nude rats through osteochondral defects created in the distal femur. The defects were sealed with HCF (heparin-conjugated fibrin) or PDGF-AA-loaded HCF. In the HCF-only group, the nanoparticle-labeled MSCs dispersed outside the marrow cavity within 3 days after injection. In the PDGF-AA-loaded HCF group, the labeled cells moved time-dependently for 14 days toward the osteochondral defect. HCF-PDGF in low dose (LD; 8.5 ng/µl) was more effective than HCF-PDGF in high dose (HD; 17 ng/µl) in recruiting the MSCs to the osteochondral defect. After 21 days, the defects treated with PDGF and transforming growth factor (TGF)-β1-loaded HCF showed excellent cartilage repair compared with other groups. Further studies confirmed that this in vivo osteochondral MSCs tracking system (IOMTS) worked for other chemoattractants (chemokine (C-C motif) ligand 2 (CCL2) and PDGF-BB). IOMTS can provide a useful tool to examine the effect of growth factors or chemokines on endogenous cartilage repair. PMID:22491215

Patients with IgA nephropathy exhibit high systemic PDGF-DD levels.

PubMed

Boor, Peter; Eitner, Frank; Cohen, Clemens D; Lindenmeyer, Maja T; Mertens, Peter R; Ostendorf, Tammo; Floege, Jürgen

2009-09-01

Platelet-derived growth factor (PDGF) is a central mediator of mesangioproliferative glomerulonephritis (GN). In experimental mesangioproliferative GN, PDGF-DD serum levels, unlike PDGF-BB, increased up to 1000-fold. We assessed disease activity in 72 patients with GN, established a novel PDGF-D ELISA and then determined their PDGF-DD levels. In parallel, we studied renal PDGF-DD mRNA expression by RT-PCR. PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 +/- 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 +/- 0.86 ng/ml) compared to healthy controls (1.17 +/- 0.46 ng/ml), while patients with focal segmental glomerulosclerosis, membranous GN and ANCA-positive vasculitis did not differ from controls. The subgroup of IgAN patients with elevated PDGF-DD levels (27% of samples) did not differ in their clinical features from those with normal PDGF-DD levels. In IgAN patients with repetitive PDGF-DD determinations, most exhibited only minor fluctuations of serum levels over time. Intrarenal PDGF-DD mRNA expression did not differ between controls and patients, suggesting an extrarenal source of the elevated PDGF-DD in IgAN. Serum PDGF-DD levels were specifically elevated in patients with IgAN, in particular in those with early disease, i.e. preserved renal function. Our data support the rationale for anti-PDGF-DD therapy in mesangioproliferative GN.

MiR-137 inhibited cell proliferation and migration of vascular smooth muscle cells via targeting IGFBP-5 and modulating the mTOR/STAT3 signaling

PubMed Central

Li, Kai; Huang, Wei; Zhang, Xiaoqing

2017-01-01

Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of cardiovascular diseases. Studies have shown the great impact of microRNAs (miRNAs) on the cell proliferation of VSMCs. This study examined the effects of miR-137 on the cell proliferation and migration of VSMCs and also explored the underlying molecular mechanisms. The mRNA and protein expression levels were determined by qRT-PCR and western blot assays, respectively. The CCK-8 assay, wound healing assay and transwell migration assay were performed to measure cell proliferation and migration of VSMCs. The miR-137-targeted 3’untranslated region of insulin-like growth factor-binding protein-5 (IGFBP-5) was confirmed by luciferase reporter assay. Platelet-derived growth factor-bb (PDGF-bb) treatment enhanced cell proliferation and suppressed the expression of miR-137 in VSMCs. The gain-of-function and loss-of-function assays showed that overexpression of miR-137 suppressed the cell proliferation and migration, and also inhibited the expression of matrix genes of VSMCs; down-regulation of miR-137 had the opposite effects on VSMCs. Bioinformatics analysis and luciferase report assay results showed that IGFBP-5 was a direct target of miR-137, and miR-137 overexpression suppressed the IGFBP-5 expression and down-regulation of miR-137 increased the IGFBP-5 expression in VSMCs. PDGF-bb treatment also increased the IGFBP-5 mRNA expression. In addition, enforced expression of IGFBP-5 reversed the inhibitory effects of miR-137 on cell proliferation and migration of VSMCs. More importantly, overexpression of miR-137 also suppressed the activity of mTOR/STAT3 signaling in VSMCs. Taken together, the results suggest that miR-137 may suppress cell proliferation and migration of VSMCs via targeting IGFBP-5 and modulating mTOR/STAT3 signaling pathway. PMID:29016699

The inhibition of activated hepatic stellate cells proliferation by arctigenin through G0/G1 phase cell cycle arrest: persistent p27(Kip1) induction by interfering with PI3K/Akt/FOXO3a signaling pathway.

PubMed

Li, Ao; Wang, Jun; Wu, Mingjun; Zhang, Xiaoxun; Zhang, Hongzhi

2015-01-15

Proliferation of hepatic stellate cells (HSCs) is vital for the development of fibrosis during liver injury. In this study, we describe that arctigenin (ATG), a major bioactive component of Fructus Arctii, exhibited selective cytotoxic activity via inhibiting platelet-derived growth factor-BB (PDGF-BB)-activated HSCs proliferation and arrested cell cycle at G0/G1 phase, which could not be observed in normal human hepatocytes in vitro. The cyclin-dependent kinase (CDK) 4/6 activities could be strongly inhibited by ATG through down-regulation of cyclin D1 and CDK4/6 expression in early G1 phase arrest. In the ATG-treated HSCs, the expression level of p27(Kip1) and the formation of CDK2-p27(Kip1) complex were also increased. p27(Kip1) silencing significantly attenuated the effect of ATG, including cell cycle arrest and suppression of proliferation in activated HSCs. We also found that ATG suppressed PDGF-BB-induced phosphorylation of Akt and its downstream transcription factor Forkhead box O 3a (FOXO3a), decreased binding of FOXO3a to 14-3-3 protein, and stimulated nuclear translocation of FOXO3a in activated HSCs. Furthermore, knockdown of FOXO3a expression by FOXO3a siRNA attenuated ATG-induced up-regulation of p27(Kip1) in activated HSCs. All the above findings suggested that ATG could increase the levels of p27(Kip1) protein through inhibition of Akt and improvement of FOXO3a activity, in turn inhibited the CDK2 kinase activity, and eventually caused an overall inhibition of HSCs proliferation. Copyright © 2014 Elsevier B.V. All rights reserved.

CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism.

PubMed

Wilhelm, Annika; Aldridge, Victoria; Haldar, Debashis; Naylor, Amy J; Weston, Christopher J; Hedegaard, Ditte; Garg, Abhilok; Fear, Janine; Reynolds, Gary M; Croft, Adam P; Henderson, Neil C; Buckley, Christopher D; Newsome, Philip N

2016-07-01

CD248 (endosialin) is a stromal cell marker expressed on fibroblasts and pericytes. During liver injury, myofibroblasts are the main source of fibrotic matrix. To determine the role of CD248 in the development of liver fibrosis in the rodent and human setting. CD248 expression was studied by immunostaining and quantitative PCR in both normal and diseased human and murine liver tissue and isolated hepatic stellate cells (HSCs). Hepatic fibrosis was induced in CD248(-/-) and wild-type controls with carbon tetrachloride (CCl4) treatment. Expression of CD248 was seen in normal liver of humans and mice but was significantly increased in liver injury using both immunostaining and gene expression assays. CD248 was co-expressed with a range of fibroblast/HSC markers including desmin, vimentin and α-smooth muscle actin (α-SMA) in murine and human liver sections. CD248 expression was restricted to isolated primary murine and human HSC. Collagen deposition and α-SMA expression, but not inflammation and neoangiogenesis, was reduced in CD248(-/-) mice compared with wild-type mice after CCl4 treatment. Isolated HSC from wild-type and CD248(-/-) mice expressed platelet-derived growth factor receptor α (PDGFR-α) and PDGFR-β at similar levels. As expected, PDGF-BB stimulation induced proliferation of wild-type HSC, whereas CD248(-/-) HSC did not demonstrate a proliferative response to PDGF-BB. Abrogated PDGF signalling in CD248(-/-) HSC was confirmed by significantly reduced c-fos expression in CD248(-/-) HSC compared with wild-type HSC. Our data show that deletion of CD248 reduces susceptibility to liver fibrosis via an effect on PDGF signalling, making it an attractive clinical target for the treatment of liver injury. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Insights into the Effects of Complement Factor H on the Assembly and Decay of the Alternative Pathway C3 Proconvertase and C3 Convertase*

PubMed Central

Bettoni, Serena; Bresin, Elena; Remuzzi, Giuseppe; Noris, Marina; Donadelli, Roberta

2016-01-01

The activated fragment of C3 (C3b) and factor B form the C3 proconvertase (C3bB), which is cleaved by factor D to C3 convertase (C3bBb). Older studies (Conrad, D. H., Carlo, J. R., and Ruddy, S. (1978) J. Exp. Med. 147, 1792–1805; Pangburn, M. K., and Müller-Eberhard, H. J. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 2416–2420; Kazatchkine, M. D., Fearon, D. T., and Austen, K. F. (1979) J. Immunol. 122, 75–81) indicated that the complement alternative pathway regulator factor H (FH) competes with factor B for C3b binding; however, the capability of FH to prevent C3bB assembly has not been formally investigated. Moreover, in the few published studies FH did not favor C3bB dissociation. Whether FH may affect C3bBb formation from C3bB is unknown. We set up user-friendly assays based on combined microplate/Western blotting techniques that specifically detect either C3bB or C3bBb, with the aim of investigating the effect of FH on C3bB assembly and decay and C3bBb formation and decay. We document that FH does not affect C3bB assembly, indicating that FH does not efficiently compete with factor B for C3b binding. We also found that FH does not dissociate C3bB. FH showed a strong C3bBb decay-accelerating activity, as reported previously, and also exerted an apparent inhibitory effect on C3bBb formation. The latter effect was not fully attributable to a rapid FH-mediated dissociation of C3bBb complexes, because blocking decay with properdin and C3 nephritic factor did not restore C3bBb formation. FH almost completely prevented release of the smaller cleavage subunit of FB (Ba), without modifying the amount of C3bB complexes, suggesting that FH inhibits the conversion of C3bB to C3bBb. Thus, the inhibitory effect of FH on C3bBb formation is likely the sum of inhibition of C3bB conversion to C3bBb and of C3bBb decay acceleration. Further studies are required to confirm these findings in physiological cell-based settings. PMID:26903516

The platelet-derived growth factor receptor/STAT3 signaling pathway regulates the phenotypic transition of corpus cavernosum smooth muscle in rats.

PubMed

Yan, Jun-Feng; Huang, Wen-Jie; Zhao, Jian-Feng; Fu, Hui-Ying; Zhang, Gao-Yue; Huang, Xiao-Jun; Lv, Bo-Dong

2017-01-01

Erectile dysfunction (ED) is a common clinical disease that is difficult to treat. We previously found that hypoxia modulates the phenotype of primary corpus cavernosum smooth muscle cells (CCSMCs) in rats, but the underlying molecular mechanism is still unknown. Platelet-derived growth factor receptor (PDGFR)-related signaling pathways are correlated with cell phenotypic transition, but research has been focused more on vascular smooth muscle and tracheal smooth muscle and less on CCSMCs. Here, we investigated the role of PDGFR-related signaling pathways in penile CCSMCs, which were successfully isolated from rats and cultured in vitro. PDGF-BB at 5, 10, or 20 ng/ml altered CCSMC morphology from the original elongated, spindle shape to a broader shape and promoted the synthetic phenotype and expression of the related proteins vimentin and collagen-I, while inhibiting the contractile phenotype and expression of the related proteins smooth muscle (SM) α-actin (α-SMA) and desmin. Inhibition of PDGFR activity via siRNA or the PDGFR inhibitor crenolanib inhibited vimentin and collagen-I expression, increased α-SMA and desmin expression, and considerably inhibited serine-threonine protein kinase (AKT) and signal transducer and activator of transcription 3 (STAT3) phosphorylation. STAT3 knockdown promoted the contractile phenotype, inhibited vimentin and collagen-I expression, and increased α-SMA and desmin expression, whereas AKT knockdown did not affect phenotype-associated proteins. STAT3 overexpression in CCSMC cells weakened the suppressive effect of PDGFR inhibition on the morphology and phenotypic transformation induced by PDGF-BB. Through activation of the PDGFR/STAT3 signaling pathway, PDGF promoted the synthetic phenotype transition; thus, regulation of this pathway might contribute to ED therapy.

PDGF-DD, a novel mediator of smooth muscle cell phenotypic modulation, is upregulated in endothelial cells exposed to atherosclerosis-prone flow patterns.

PubMed

Thomas, James A; Deaton, Rebecca A; Hastings, Nicole E; Shang, Yueting; Moehle, Christopher W; Eriksson, Ulf; Topouzis, Stavros; Wamhoff, Brian R; Blackman, Brett R; Owens, Gary K

2009-02-01

Platelet-derived growth factor (PDGF)-BB is a well-known smooth muscle (SM) cell (SMC) phenotypic modulator that signals by binding to PDGF alphaalpha-, alphabeta-, and betabeta-membrane receptors. PDGF-DD is a recently identified PDGF family member, and its role in SMC phenotypic modulation is unknown. Here we demonstrate that PDGF-DD inhibited expression of multiple SMC genes, including SM alpha-actin and SM myosin heavy chain, and upregulated expression of the potent SMC differentiation repressor gene Kruppel-like factor-4 at the mRNA and protein levels. On the basis of the results of promoter-reporter assays, changes in SMC gene expression were mediated, at least in part, at the level of transcription. Attenuation of the SMC phenotypic modulatory activity of PDGF-DD by pharmacological inhibitors of ERK phosphorylation and by a small interfering RNA to Kruppel-like factor-4 highlight the role of these two pathways in this process. PDGF-DD failed to repress SM alpha-actin and SM myosin heavy chain in mouse SMCs lacking a functional PDGF beta-receptor. Importantly, PDGF-DD expression was increased in neointimal lesions in the aortic arch region of apolipoprotein C-deficient (ApoE(-/-)) mice. Furthermore, human endothelial cells exposed to an atherosclerosis-prone flow pattern, as in vascular regions susceptible to the development of atherosclerosis, exhibited a significant increase in PDGF-DD expression. These findings demonstrate a novel activity for PDGF-DD in SMC biology and highlight the potential contribution of this molecule to SMC phenotypic modulation in the setting of disturbed blood flow.

Release of growth factors and the effect of age, sex, and severity of injury after long bone fracture. A preliminary report.

PubMed

Pountos, Ippokratis; Georgouli, Theodora; Henshaw, Karen; Bird, Howard; Giannoudis, Peter V

2013-02-01

The systemic response after fracture is regulated by a complex mechanism involving numerous growth factors. In this study, we analyzed the kinetics of key growth factors following lower-limb long bone fracture. Human serum was isolated from 15 patients suffering from lower-limb long bone fracture (tibia/femur) requiring surgical fixation. The levels of platelet-derived growth factor (PDGF-BB), vascular edothelial growth factor (VEGF), insulin growth factor-I (IGF-I), and transforming growth factor β1 (TGF-β1) were assayed by colorimetric ELISA at different time points during the first week after fracture. 10 healthy volunteers made up the control group of the study. Serum levels of the growth factors measured were compared to age, sex, and injury severity score. We found that there was a decline in the levels of PDGF-BB, IGF-I and TGF-β1 during the first 3 days after fracture. However, VEGF levels remained unchanged. The levels of all the growth factors studied then increased, with the highest concentrations noted at day 7 after surgery. No correlation was found between circulating levels of growth factors and age, injury severity score (ISS), blood loss, or fluid administration. There are systemic mitogenic and osteogenic signals after fracture. Important growth factors are released into the peripheral circulation, but early after surgery it appears that serum levels of key growth factors fall. By 7 days postoperatively, the levels had increased considerably. Our findings should be considered in cases where autologous serum is used for ex vivo expansion of mesenchymal stem cells. There should be further evaluation of the use of these molecules as biomarkers of bone union.

Regulation of cell growth by redox-mediated extracellular proteolysis of platelet-derived growth factor receptor beta.

PubMed

Okuyama, H; Shimahara, Y; Kawada, N; Seki, S; Kristensen, D B; Yoshizato, K; Uyama, N; Yamaoka, Y

2001-07-27

Redox-regulated processes are important elements in various cellular functions. Reducing agents, such as N-acetyl-l-cysteine (NAC), are known to regulate signal transduction and cell growth through their radical scavenging action. However, recent studies have shown that reactive oxygen species are not always involved in ligand-stimulated intracellular signaling. Here, we report a novel mechanism by which NAC blocks platelet-derived growth factor (PDGF)-induced signaling pathways in hepatic stellate cells, a fibrogenic player in the liver. Unlike in vascular smooth muscle cells, we found that reducing agents, including NAC, triggered extracellular proteolysis of PDGF receptor-beta, leading to desensitization of hepatic stellate cells toward PDGF-BB. This effect was mediated by secreted mature cathepsin B. In addition, type II transforming growth factor-beta receptor was also down-regulated. Furthermore, these events seemed to cause a dramatic improvement of rat liver fibrosis. These results indicated that redox processes impact the cell's response to growth factors by regulating the turnover of growth factor receptors and that "redox therapy" is promising for fibrosis-related disease.

PDGF-AA promotes osteogenic differentiation and migration of mesenchymal stem cell by down-regulating PDGFRα and derepressing BMP-Smad1/5/8 signaling.

PubMed

Li, Anna; Xia, Xuechun; Yeh, James; Kua, Huiyi; Liu, Huijuan; Mishina, Yuji; Hao, Aijun; Li, Baojie

2014-01-01

Platelet-derived growth factors (PDGFs) play important roles in skeletal development and bone fracture healing, yet how PDGFs execute their functions remains incompletely understood. Here we show that PDGF-AA, but not -AB or -BB, could activate the BMP-Smad1/5/8 pathway in mesenchymal stem cells (MSCs), which requires BMPRIA as well as PDGFRα. PDGF-AA promotes MSC osteogenic differentiation through the BMP-Smad1/5/8-Runx2/Osx axis and MSC migration via the BMP-Smad1/5/8-Twist1/Atf4 axis. Mechanistic studies show that PDGF-AA activates BMP-Smad1/5/8 signaling by feedback down-regulating PDGFRα, which frees BMPRI and allows for BMPRI-BMPRII complex formation to activate smad1/5/8, using BMP molecules in the microenvironment. This study unravels a physical and functional interaction between PDGFRα and BMPRI, which plays an important role in MSC differentiation and migration, and establishes a link between PDGF-AA and BMPs pathways, two essential regulators of embryonic development and tissue homeostasis.

RP-1551s, a family of azaphilones produced by Penicillium sp., inhibit the binding of PDGF to the extracellular domain of its receptor.

PubMed

Toki, S; Tanaka, T; Uosaki, Y; Yoshida, M; Suzuki, Y; Kita, K; Mihara, A; Ando, K; Lokker, N A; Giese, N A; Matsuda, Y

1999-03-01

Nine azaphilones designated RP-1551-1, -2, -3, -4, -5, -6, -7, -M1, and -M2 were isolated from the culture broth of Penicillium sp. SPC-21609 as inhibitors of PDGF binding to its receptor. RP-1551s inhibit the binding of PDGF AA to the extracellular domain of PDGF alpha-receptor with IC50 values ranging from 0.1 to 2 microM without affecting PDGF BB binding to the extracellular domain of PDGF beta-receptor. PDGF binding was not restored after the PDGF alpha-receptor extracellular domain was washed in an attempt to remove the RP-1551-1 bound to the receptor. This result suggests that RP-1551-1 may irreversibly interact with the PDGF alpha-receptor. Since many azaphilone compounds possess high reactivity with an amino group, RP-1551-1 may prevent PDGF AA binding by reacting with amino groups on the alpha-receptor extracellular domain.

3,3′Diindolylmethane Suppresses Vascular Smooth Muscle Cell Phenotypic Modulation and Inhibits Neointima Formation after Carotid Injury

PubMed Central

Guan, Hongjing; Zhu, Lihua; Fu, Mingyue; Yang, Da; Tian, Song; Guo, Yuanyuan; Cui, Changping; Wang, Lang; Jiang, Hong

2012-01-01

Background 3, 3′diindolylmethane (DIM), a natural phytochemical, has shown inhibitory effects on the growth and migration of a variety of cancer cells; however, whether DIM has similar effects on vascular smooth muscle cells (VSMCs) remains unknown. The purpose of this study was to assess the effects of DIM on the proliferation and migration of cultured VSMCs and neointima formation in a carotid injury model, as well as the related cell signaling mechanisms. Methodology/Principal Findings DIM dose-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs without cell cytotoxicity. This inhibition was caused by a G0/G1 phase cell cycle arrest demonstrated by fluorescence-activated cell-sorting analysis. We also showed that DIM-induced growth inhibition was associated with the inhibition of the expression of cyclin D1 and cyclin-dependent kinase (CDK) 4/6 as well as an increase in p27Kip1 levels in PDGF-stimulated VSMCs. Moreover, DIM was also found to modulate migration of VSMCs and smooth muscle-specific contractile marker expression. Mechanistically, DIM negatively modulated PDGF-BB-induced phosphorylation of PDGF-recptorβ (PDGF-Rβ) and the activities of downstream signaling molecules including Akt/glycogen synthase kinase(GSK)3β, extracellular signal-regulated kinase1/2 (ERK1/2), and signal transducers and activators of transcription 3 (STAT3). Our in vivo studies using a mouse carotid arterial injury model revealed that treatment with 150 mg/kg DIM resulted in significant reduction of the neointima/media ratio and proliferating cell nuclear antigen (PCNA)-positive cells, without affecting apoptosis of vascular cells and reendothelialization. Infiltration of inflammatory cells was also inhibited by DIM administration. Conclusion These results demonstrate that DIM can suppress the phenotypic modulation of VSMCs and neointima hyperplasia after vascular injury. These beneficial effects on VSMCs were at least partly mediated by the inhibition of PDGF-Rβ and the activities of downstream signaling pathways. The results suggest that DIM has the potential to be a candidate for the prevention of restenosis. PMID:22506059

Anti-proliferative actions of 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone in vascular smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jung-Jin; Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764; Zhang, Wei-Yun

2011-07-22

Highlights: {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner with no apparent cytotoxicity. {yields} 2-Decylamino-DMNQ inhibited PDGF-BB-induced phosphorylation of Erk1/2 and PLC{gamma}1. {yields} 2-Decylamino-DMNQ arrested a G{sub 0}/G{sub 1} cell cycle progression in association with pRb phosphorylation and PCNA expression. {yields} Both U0126, an Erk inhibitor, and U73122, a PLC{gamma} inhibitor, arrested a G{sub 0}/G{sub 1} phase of the cell cycle. -- Abstract: Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferationmore » and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-R{beta} or Akt, it did inhibit the phosphorylation of Erk1/2 and PLC{gamma}1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G{sub 0}/G{sub 1} phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and U73122, a PLC{gamma} inhibitor, increased the proportion of cells in the G{sub 0}/G{sub 1} phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G{sub 0}/G{sub 1} phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation.« less

Effect of PDGF-B aptamer on PDGFRβ/PDGF-B interaction: Molecular dynamics study.

PubMed

Vu, Cong Quang; Rotkrua, Pichayanoot; Soontornworajit, Boonchoy; Tantirungrotechai, Yuthana

2018-06-01

PDGFRβ/PDGF-B interaction plays a role in angiogenesis, and is mandatory in wound healing and cancer treatment. It has been reported that the PDGF-B aptamer was able to bind to PDGF-B, thus regulating the angiogenesis. However, the binding interaction between the aptamer and the growth factor, including the binding sites, has not been well investigated. This study applied a molecular dynamics (MD) simulation to investigate the aptamer-growth factor interaction in the presence or absence of a receptor (PDGFRβ). Characterization of the structure of an aptamer-growth factor complex revealed binding sites from each section in the complex. Upon the complex formation, PDGF-B and its aptamer exhibited less flexibility in their molecular movement, as indicated by the minimum values of RMSD, RMSF, loop-to-loop distance, and the summation of PCA eigenvalues. Our study of residue pairwise interaction demonstrated that the binding interaction was mainly contributed by electrostatic interaction between the positively-charged amino acid and the negatively-charged phosphate backbone. The role of the PDGF-B aptamer in PDGFRβ/PDGF-B interaction was also investigated. We demonstrated that the stability of the Apt-PDGF-B complex could prevent the presence of a competitor, of PDGFRβ, interrupting the binding process. Because the aptamer was capable of binding with PDGF-B, and blocking the growth factor from the PDGFRβ, it could down regulate the consequent signaling pathway. We provide evidence that the PDGF-BB aptamer is a promising molecule for regulation of angiogenesis. The MD study provides a molecular understanding to modification of the aptamer binding interaction, which could be used in a number of medical applications. Copyright © 2018 Elsevier Inc. All rights reserved.

Platelet-derived growth factor BB and DD and angiopoietin1 are altered in follicular fluid from polycystic ovary syndrome patients.

PubMed

Scotti, Leopoldina; Parborell, Fernanda; Irusta, Griselda; De Zuñiga, Ignacio; Bisioli, Claudio; Pettorossi, Hernan; Tesone, Marta; Abramovich, Dalhia

2014-08-01

Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age, and is characterized by abnormalities in ovarian angiogenesis, among other features. Consistent with this association, follicular fluid (FF) concentration and ovarian expression of vascular endothelial growth factor (VEGF) are increased in PCOS patients. In this study, we examined the protein levels of platelet-derived growth factor (PDGF) BB and DD (PDGFBB and PDGFDD), angiopoietin 1 and 2 (ANGPT1 and ANGPT2), and their soluble receptor sTIE2 in FF from PCOS and control patients undergoing assisted reproductive techniques. We also analyzed the effect of FF from PCOS and control patients on tight and adherens junction protein expression in an endothelial cell line. PDGFBB and PDGFDD were significantly lower whereas ANGPT1 concentration was significantly higher in FF from PCOS patients than from control patients. No changes were found in the concentration of ANGPT2 or sTIE2. Expression of claudin-5 was significantly increased in endothelial cells incubated for 24 hr in the presence of FF from PCOS versus from control patients, while vascular-endothelial cadherin, β-catenin, and zonula occludens 1 expression were unchanged. The changes observed in the levels of PDGF isoforms and ANGPT1 may prevent VEGF-induced vascular permeability in the PCOS ovary by regulating endothelial-cell-junction protein levels. Restoring the levels of angiogenic factors may provide new insights into PCOS treatment and the prevention of ovarian hyperstimulation syndrome in affected women. © 2014 Wiley Periodicals, Inc.

The effects of plasma rich in growth factors (PRGF-Endoret) on healing of medial collateral ligament of the knee.

PubMed

Yoshioka, Tomokazu; Kanamori, Akihiro; Washio, Toshikatsu; Aoto, Katsuya; Uemura, Kenta; Sakane, Masataka; Ochiai, Naoyuki

2013-08-01

Platelet-rich plasma (PRP) has been increasingly used in sports-related injuries for therapeutic applications. However, there are numerous manufacturing procedures and treatment protocols of PRP use, which make difficult to assess its real efficacy for tissue healing. This study addressed to evaluate the therapeutic effects of locally delivered plasma rich in growth factors (PRGF-Endoret) on the early healing of medial collateral ligament (MCL) in rabbit knees. Thirty-one Japanese white rabbits were subjected to a mop-end tear in the MCL of the left knee. PRGF-Endoret was prepared using Anitua's technique. Two groups were set up. In 17 knees, prepared 1.0 ml of PRGF-Endoret after clotting was applied on the tear site, while in 14 knees the tear site was untreated serving as a control. Quantitative aspects of PRGF-Endoret, the concentration of platelets, leukocytes and erythrocytes and therapeutic growth factors such as PDGF-BB and TGF-β1 were measured. Rabbits were sacrificed at 3 and 6 weeks after the operation and histological and biomechanical evaluation were performed. No leukocytes were measured and certain amount of growth factors such as PDGF-BB and TGF-β1 were confirmed in the PRGF-Endoret. PRGF-Endoret stimulated proliferation of fibroblasts and neovascularization, and induced statistically better structural properties in repaired MCL. Our findings provide evidence that local administration of PRGF-Endoret promotes early steps in ligament healing and the repair of structural properties in a rabbit model. PRGF-Endoret would be a useful product in clinical treatment of ligament injuries.

Understanding the role of growth factors in modulating stem cell tenogenesis.

PubMed

Gonçalves, Ana I; Rodrigues, Márcia T; Lee, Sang-Jin; Atala, Anthony; Yoo, James J; Reis, Rui L; Gomes, Manuela E

2013-01-01

Current treatments for tendon injuries often fail to fully restore joint biomechanics leading to the recurrence of symptoms, and thus resulting in a significant health problem with a relevant social impact worldwide. Cell-based approaches involving the use of stem cells might enable tailoring a successful tendon regeneration outcome. As growth factors (GFs) powerfully regulate the cell biological response, their exogenous addition can further stimulate stem cells into the tenogenic lineage, which might eventually depend on stem cells source. In the present study we investigate the tenogenic differentiation potential of human- amniotic fluid stem cells (hAFSCs) and adipose-derived stem cells (hASCs) with several GFs associated to tendon development and healing; namely, EGF, bFGF, PDGF-BB and TGF-β1. Stem cells response to biochemical stimuli was studied by screening of tendon-related genes (collagen type I, III, decorin, tenascin C and scleraxis) and proteins found in tendon extracellular matrix (ECM) (Collagen I, III, and Tenascin C). Despite the fact that GFs did not seem to influence the synthesis of tendon ECM proteins, EGF and bFGF influenced the expression of tendon-related genes in hAFSCs, while EGF and PDGF-BB stimulated the genetic expression in hASCs. Overall results on cellular alignment morphology, immunolocalization and PCR analysis indicated that both stem cell source can be biochemically induced towards tenogenic commitment, validating the potential of hASCs and hAFSCs for tendon regeneration strategies.

A virally inactivated functional growth factor preparation from human platelet concentrates.

PubMed

Su, C-Y; Kuo, Y P; Lin, Y C; Huang, C-T; Tseng, Y H; Burnouf, T

2009-08-01

Human platelet growth factors (HPGF) are essential for tissue regeneration and may replace fetal bovine serum (FBS) in cell therapy. No method for the manufacture of standardized virally inactivated HPGF has been developed yet. Platelet concentrates (PC) were subjected to solvent/detergent (S/D) treatment (1% TnBP/1% Triton X-45), oil extraction, hydrophobic interaction chromatography and sterile filtration. Platelet-derived growth factor (PDGF)-AB, -BB and -AA, transforming growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1) and vascular endothelium growth factor (VEGF) were measured by ELISA. Composition in proteins and lipids was determined, protein profiles were obtained by SDS-PAGE, and TnBP and Triton X-45 were assessed by gas chromatography and high-performance liquid chromatography, respectively. Cell growth promoting activity of HPGF was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay using human embryonic kidney (HEK293A) fibroblast and Statens Seruminstitute rabbit corneal (SIRC) epithelial cell lines. The GF preparation contained a mean of 16.66, 2.04, 1.53, 72.19, 0.33, 48.59 and 0.44 ng/ml of PDGF-AB, -BB, -AA, TGF-beta1, EGF, IGF-1 and VEGF, respectively. The protein profile was typical of platelet releasates and had less than 2 p.p.m. of residual S/D agents. MTS assay of HEK293A and SIRC cultures showed that the GF preparation at 10% and 0.1% (v/v), respectively, could successfully replace 10% FBS for cell proliferation. Cell-stimulating activity of HPGF on HEK293A was over twice that of PC releasates. STANDARDIZED and functional virally inactivated HPGF can be prepared from human PC for possible applications in cell therapy and regenerative medicine.

Selective Expression of an Endogenous Inhibitor of FAK Regulates Proliferation and Migration of Vascular Smooth Muscle Cells

PubMed Central

Taylor, Joan M.; Mack, Christopher P.; Nolan, Kate; Regan, Christopher P.; Owens, Gary K.; Parsons, J. Thomas

2001-01-01

Extracellular matrix signaling via integrin receptors is important for smooth muscle cell (SMC) differentiation during vasculogenesis and for phenotypic modulation of SMCs during atherosclerosis. We previously reported that the noncatalytic carboxyl-terminal protein binding domain of focal adhesion kinase (FAK) is expressed as a separate protein termed FAK-related nonkinase (FRNK) and that ectopic expression of FRNK can attenuate FAK activity and integrin-dependent signaling (A. Richardson and J. T. Parsons, Nature 380:538–540, 1996). Herein we report that in contrast to FAK, which is expressed ubiquitously, FRNK is expressed selectively in SMCs, with particularly high levels observed in conduit blood vessels. FRNK expression was low during embryonic development, was significantly upregulated in the postnatal period, and returned to low but detectable levels in adult tissues. FRNK expression was also dramatically upregulated following balloon-induced carotid artery injury. In cultured rat aortic smooth muscle cells, overexpression of FRNK attenuated platelet-derived growth factor (PDGF)-BB-induced migration and also dramatically inhibited [3H]thymidine incorporation upon stimulation with PDGF-BB or 10% serum. These effects were concomitant with a reduction in SMC proliferation. Taken together, these data indicate that FRNK acts as an endogenous inhibitor of FAK signaling in SMCs. Furthermore, increased FRNK expression following vascular injury or during development may alter the SMC phenotype by negatively regulating proliferative and migratory signals. PMID:11238893

Does Platelet-Rich Plasma Freeze-Thawing Influence Growth Factor Release and Their Effects on Chondrocytes and Synoviocytes?

PubMed Central

Cavallo, Carola; Cenacchi, Annarita; Facchini, Andrea; Grigolo, Brunella; Kon, Elizaveta; Mariani, Erminia; Pratelli, Loredana; Marcacci, Maurilio

2014-01-01

PRP cryopreservation remains a controversial point. Our purpose was to investigate the effect of freezing/thawing on PRP molecule release, and its effects on the metabolism of chondrocytes and synoviocytes. PRP was prepared from 10 volunteers, and a half volume underwent one freezing/thawing cycle. IL-1β, HGF, PDGF AB/BB, TGF-β1, and VEGF were assayed 1 hour and 7 days after activation. Culture media of chondrocytes and synoviocytes were supplemented with fresh or frozen PRP, and, at 7 days, proliferation, gene expression, and secreted proteins levels were evaluated. Results showed that in the freeze-thawed PRP the immediate and delayed molecule releases were similar or slightly lower than those in fresh PRP. TGF-β1 and PDGF AB/BB concentrations were significantly reduced after freezing both at 1 hour and at 7 days, whereas HGF concentration was significantly lower in frozen PRP at 7 days. In fresh PRP IL-1β and HGF concentrations underwent a significant further increase after 7 days. Similar gene expression was found in chondrocytes cultured with both PRPs, whereas in synoviocytes HGF gene expression was higher in frozen PRP. PRP cryopreservation is a safe procedure, which sufficiently preserves PRP quality and its ability to induce proliferation and the production of ECM components in chondrocytes and synoviocytes. PMID:25136613

Specificity of EIA immunoassay for complement factor Bb testing.

PubMed

Pavlov, Igor Y; De Forest, Nikol; Delgado, Julio C

2011-01-01

During the alternative complement pathway activation, factor B is cleaved in two fragments, Ba and Bb. Concentration of those fragments is about 2 logs lower than of factor B present in the blood, which makes fragment detection challenging because of potential cross-reactivity. Lack of information on Bb assay cross-reactivity stimulated the authors to investigate this issue. We ran 109 healthy donor EDTA plasmas and 80 sera samples with both factor B immunodiffusion (The Binding Site) and Quidel Bb EIA assays. During the study it was shown that physiological concentrations of gently purified factor B demonstrated approximately 0.15% cross-reactivity in the Quidel Bb EIA assay. We also observed that Bb concentration in serum is higher than in plasma due to complement activation during clot formation which let us use sera as samples representing complement activated state. Our study demonstrated that despite the potential 0.15% cross-reactivity between endogenous factor B and cleaved Bb molecule, measuring plasma concentrations of factor Bb is adequate to evaluate the activation of the alternative complement pathway.

Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant.

PubMed Central

Vassbotn, F S; Andersson, M; Westermark, B; Heldin, C H; Ostman, A

1993-01-01

A non-receptor-binding mutant of the platelet-derived growth factor (PDGF) A chain, PDGF-0, was generated by exchanging 7 amino acids in the sequence. The mutant chains formed dimers that were similar to wild-type PDGF-AA with regard to stability and rate of processing to the mature 30-kDa secreted forms. Moreover, the mutant chains formed disulfide-bonded heterodimers with the PDGF B chain in NIH 3T3 cells heterodimer underwent the same processing and secretion as PDGF-AB. Transfection of c-sis-expressing 3T3 cells with PDGF-0 significantly inhibited the transformed phenotype of these cells, as determined by the following criteria. (i) Compared with PDGF-0-negative clones, PDGF-0-producing clones showed a reverted morphology. (ii) Clones producing PDGF-0 grew more slowly than PDGF-0-negative clones, with a fivefold difference in cell number after 14 days in culture. (iii) The expression of PDGF-0 completely inhibited the ability of the c-sis-expressing 3T3 cells to form colonies in soft agar; this inhibition was overcome by the addition of recombinant PDGF-BB to the culture medium, showing that the lack of colony formation of these cells was not due to a general unresponsiveness to PDGF. The specific expression of a PDGF-0/PDGF wild-type heterodimer in COS cells revealed that the affinity of the mutant heterodimer for the PDGF alpha receptor was decreased by approximately 50-fold compared with that of PDGF-AA. Thus, we show that a non-receptor-binding PDGF A-chain mutant neutralizes in a trans-dominant manner the autocrine transforming potential of the c-sis/PDGF B chain by forming low-affinity heterodimers with wild-type PDGF chains. This method of specifically antagonizing the effect of PDGF may be useful in investigations of the role of PDGF in normal and pathological conditions. Images PMID:8321214

Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant.

PubMed

Vassbotn, F S; Andersson, M; Westermark, B; Heldin, C H; Ostman, A

1993-07-01

A non-receptor-binding mutant of the platelet-derived growth factor (PDGF) A chain, PDGF-0, was generated by exchanging 7 amino acids in the sequence. The mutant chains formed dimers that were similar to wild-type PDGF-AA with regard to stability and rate of processing to the mature 30-kDa secreted forms. Moreover, the mutant chains formed disulfide-bonded heterodimers with the PDGF B chain in NIH 3T3 cells heterodimer underwent the same processing and secretion as PDGF-AB. Transfection of c-sis-expressing 3T3 cells with PDGF-0 significantly inhibited the transformed phenotype of these cells, as determined by the following criteria. (i) Compared with PDGF-0-negative clones, PDGF-0-producing clones showed a reverted morphology. (ii) Clones producing PDGF-0 grew more slowly than PDGF-0-negative clones, with a fivefold difference in cell number after 14 days in culture. (iii) The expression of PDGF-0 completely inhibited the ability of the c-sis-expressing 3T3 cells to form colonies in soft agar; this inhibition was overcome by the addition of recombinant PDGF-BB to the culture medium, showing that the lack of colony formation of these cells was not due to a general unresponsiveness to PDGF. The specific expression of a PDGF-0/PDGF wild-type heterodimer in COS cells revealed that the affinity of the mutant heterodimer for the PDGF alpha receptor was decreased by approximately 50-fold compared with that of PDGF-AA. Thus, we show that a non-receptor-binding PDGF A-chain mutant neutralizes in a trans-dominant manner the autocrine transforming potential of the c-sis/PDGF B chain by forming low-affinity heterodimers with wild-type PDGF chains. This method of specifically antagonizing the effect of PDGF may be useful in investigations of the role of PDGF in normal and pathological conditions.

Composition of growth factors and cytokines in lysates obtained from fresh versus stored pathogen-inactivated platelet units.

PubMed

Sellberg, Felix; Berglund, Erik; Ronaghi, Martin; Strandberg, Gabriel; Löf, Helena; Sommar, Pehr; Lubenow, Norbert; Knutson, Folke; Berglund, David

2016-12-01

Platelet lysate is a readily available source of growth factors, and other mediators, which has been used in a variety of clinical applications. However, the product remains poorly standardized and the present investigation evaluates the composition of platelet lysate obtained from either fresh or stored pathogen-inactivated platelet units. Platelet pooled units (n = 10) were obtained from healthy blood donors and tested according to standard procedures. All units were pathogen inactivated using amotosalen hydrochloride and UVA exposure. Platelet lysate was subsequently produced at two separate time-points, either from fresh platelet units or after 5 days of storage, by repeated freeze-thaw cycles. The following mediators were determined at each time-point: EGF, FGF-2, VEGF, IGF-1, PDGF-AB/BB, BMP-2, PF4, TGF-β isoform 1, IL-1β, IL-2, IL-6, IL-10, IL-12p70, 1L-17A, TNF-α, and IFN-γ. The concentration of growth factors and cytokines was affected by time in storage. Notably, TGF-β, PDGF-AB/BB, and PF4 showed an increase of 27.2% (p < 0.0001), 29.5% (p = 0.04) and 8.2% (p = 0.0004), respectively. A decrease was seen in the levels of IGF-1 and FGF-2 with 22% (p = 0.041) and 11% (p = 0.01), respectively. Cytokines were present only in very low concentrations and all other growth factors remained stable with time in storage. The composition of mediators in platelet lysate obtained from pathogen-inactivated platelet units differs when produced from fresh and stored platelet units, respectively. This underscores the need for further standardization and optimization of this important product, which potentially may influence the clinical effects. Copyright © 2016. Published by Elsevier Ltd.

miRNA-21 is developmentally regulated in mouse brain and is co-expressed with SOX2 in glioma

PubMed Central

2012-01-01

Background MicroRNAs (miRNAs) and their role during tumor development have been studied in great detail during the last decade, albeit their expression pattern and regulation during normal development are however not so well established. Previous studies have shown that miRNAs are differentially expressed in solid human tumors. Platelet-derived growth factor (PDGF) signaling is known to be involved in normal development of the brain as well as in malignant primary brain tumors, gliomas, but the complete mechanism is still lacking. We decided to investigate the expression of the oncogenic miR-21 during normal mouse development and glioma, focusing on PDGF signaling as a potential regulator of miR-21. Methods We generated mouse glioma using the RCAS/tv-a system for driving PDGF-BB expression in a cell-specific manner. Expression of miR-21 in mouse cell cultures and mouse brain were assessed using Northern blot analysis and in situ hybridization. Immunohistochemistry and Western blot analysis were used to investigate SOX2 expression. LNA-modified siRNA was used for irreversible depletion of miR-21. For inhibition of PDGF signaling Gleevec (imatinib mesylate), Rapamycin and U0126, as well as siRNA were used. Statistical significance was calculated using double-sided unpaired Student´s t-test. Results We identified miR-21 to be highly expressed during embryonic and newborn brain development followed by a gradual decrease until undetectable at postnatal day 7 (P7), this pattern correlated with SOX2 expression. Furthermore, miR-21 and SOX2 showed up-regulation and overlapping expression pattern in RCAS/tv-a generated mouse brain tumor specimens. Upon irreversible depletion of miR-21 the expression of SOX2 was strongly diminished in both mouse primary glioma cultures and human glioma cell lines. Interestingly, in normal fibroblasts the expression of miR-21 was induced by PDGF-BB, and inhibition of PDGF signaling in mouse glioma primary cultures resulted in suppression of miR-21 suggesting that miR-21 is indeed regulated by PDGF signaling. Conclusions Our data show that miR-21 and SOX2 are tightly regulated already during embryogenesis and define a distinct population with putative tumor cell of origin characteristics. Furthermore, we believe that miR-21 is a mediator of PDGF-driven brain tumors, which suggests miR-21 as a promising target for treatment of glioma. PMID:22931209

The tick-over theory revisited: formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb).

PubMed

Bexborn, Fredrik; Andersson, Per Ola; Chen, Hui; Nilsson, Bo; Ekdahl, Kristina N

2008-04-01

The molecular interactions between the components of the C3 convertase of the alternative pathway (AP) of complement and its regulators, in both surface-bound and fluid-phase form, are still incompletely understood. The fact that the AP convertase is labile makes studies difficult to perform. According to the so called tick-over theory, hydrolyzed C3, called C3(H(2)O), forms the initial convertase in fluid phase together with factor B. In the present study, we have applied western blot analysis and ELISA together with fluorescence resonance energy transfer (FRET) to study the formation of the fluid-phase AP convertases C3(H(2)O)Bb and C3bBb and their regulation by factor H and factor I at specific time points and, with FRET, in real time. In our hands, factor B showed a higher affinity for C3(H(2)O) than for C3b, although in both cases it was readily activated to Bb. However, the convertase activity of C3bBb was approximately twice that of C3(H(2)O)Bb, as monitored by the generation of C3a. But in contrast, the C3(H(2)O)Bb convertase was more resistant to inactivation by factor H and factor I than was the C3bBb convertase. Under conditions that totally inactivated C3bBb, C3(H(2)O)Bb still retained approximately 25% of its initial activity.

The Tick-Over Theory Revisited: Formation and Regulation of the Soluble Alternative Complement C3 Convertase (C3(H2O)Bb)

PubMed Central

Bexborn, Fredrik; Andersson, Per Ola; Chen, Hui; Nilsson, Bo; Ekdahl, Kristina N.

2009-01-01

The molecular interactions between the components of the C3 convertase of the alternative pathway (AP) of complement and its regulators, in both surface-bound and fluid-phase form, are still incompletely understood. The fact that the AP convertase is labile makes studies difficult to perform. According to the so called tick-over theory, hydrolyzed C3, called C3(H2O), forms the initial convertase in fluid phase together with factor B. In the present study, we have applied western blot analysis and ELISA together with fluorescence resonance energy transfer (FRET) to study the formation of the fluid-phase AP convertases C3(H2O)Bb and C3bBb and their regulation by factor H and factor I at specific time points and, with FRET, in real time. In our hands, factor B showed a higher affinity for C3(H2O) than for C3b, although in both cases it was readily activated to Bb. However, the convertase activity of C3bBb was approximately twice that of C3(H2O)Bb, as monitored by the generation of C3a. But in contrast, the C3(H2O)Bb convertase was more resistant to inactivation by factor H and factor I than was the C3bBb convertase. Under conditions that totally inactivated C3bBb, C3(H2O)Bb still retained approximately 25% of its initial activity. PMID:18096230

Interactome analysis of transcriptional coactivator multiprotein bridging factor 1 unveils a yeast AP-1-like transcription factor involved in oxidation tolerance of mycopathogen Beauveria bassiana.

PubMed

Chu, Xin-Ling; Dong, Wei-Xia; Ding, Jin-Li; Feng, Ming-Guang; Ying, Sheng-Hua

2018-02-01

Oxidation tolerance is an important determinant to predict the virulence and biocontrol potential of Beauveria bassiana, a well-known entomopathogenic fungus. As a transcriptional coactivator, multiprotein bridging factor 1 mediates the activity of transcription factor in diverse physiological processes, and its homolog in B. bassiana (BbMBF1) contributes to fungal oxidation tolerance. In this study, the BbMBF1-interactomes under oxidative stress and normal growth condition were deciphered by mass spectrometry integrated with the immunoprecipitation. BbMBF1p factor has a broad interaction with proteins that are involved in various cellular processes, and this interaction is dynamically regulated by oxidative stress. Importantly, a B. bassiana homolog of yeast AP-1-like transcription factor (BbAP-1) was specifically associated with the BbMBF1-interactome under oxidation and significantly contributed to fungal oxidation tolerance. In addition, qPCR analysis revealed that several antioxidant genes are jointly controlled by BbAP-1 and BbMBF1. Conclusively, it is proposed that BbMBF1p protein mediates BbAP-1p factor to transcribe the downstream antioxidant genes in B. bassiana under oxidative stress. This study demonstrates for the first time a proteomic view of the MBF1-interactome in fungi, and presents an initial framework to probe the transcriptional mechanism involved in fungal response to oxidation, which will provide a new strategy to improve the biocontrol efficacy of B. bassiana.

PDGF-AA-induced filamentous mitochondria benefit dermal papilla cells in cellular migration.

PubMed

Mifude, C; Kaseda, K

2015-06-01

Human dermal papilla cells (HDPCs) play essential roles in hair follicular morphogenesis and postnatal hair growth cycles. Previous reports demonstrated that platelet-derived growth factor-AA (PDGF-AA) enhanced the formation of dermal condensates in hair follicular development. Additionally, PDGF-AA induces/maintains the anagen phase of the hair cycle. It is likely that mitochondrial morphology and functions are tightly coupled with maintenance of these energy-demanding activities. However, little is known about the mitochondrial regulation in HDPCs. Thus, we investigated the PDGF-involved mitochondrial regulation in HDPCs. The mitochondrial morphologies of HDPCs were examined in the presence or absence of PDGF-AA under a fluorescent microscope. ATP production and cellular motility were investigated. The relationship between mitochondrial morphology and the cellular functions was discussed. We observed that primary HDPCs contained mitochondria with filamentous and/or rounded morphologies. Both types of mitochondria showed similar membrane potentials. Interestingly, in the presence of PDGF-AA, but not PDGF-BB, the balance between the two morphologies shifted towards the filamentous form. Concomitantly, both mitochondrial enzymatic activity and total cellular ATP level were augmented by PDGF-AA. These two parameters were closely correlated, suggesting the mitochondrial involvement in the PDGF-augmented ATP production. Moreover, PDGF-AA accelerated the migration of HDPCs in a gap-filling assay, but did not change the rate of cellular proliferation. Notably, filamentous mitochondria dominated migrating HDPCs. PDGF-AA benefits HDPCs in the process of migration, by increasing the number of filamentous mitochondria. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Effect of volatile oil from Blumea Balsamifera (L.) DC. leaves on wound healing in mice.

PubMed

Pang, Yuxin; Wang, Dan; Hu, Xuan; Wang, Hui; Fu, Wanjin; Fan, Zuowang; Chen, Xiaolu; Yu, Fulai

2014-12-01

To assess the effectiveness of violate oil from Blumea Balsamifera (L.) DC. leaves (BB oil) on wound healing in mice. Undiluted BB oil and its diluted solutions with olive oil to 1/5 and 1/10 to yield BB oil1/5 and BB oil1/10 were applied to the wounded skin before wound healing conditions were assessed by healing rate, histopathology, and contents of collagen, hydroxyproline, and Neuropeptide Substance P (SP). All above results were compared with the efficacies of the control, pure olive oil, basic fibroblast growth factor (BFGF), and cream of Jing Wan Hong (JWH). BB oil1/5 and BB oil1/10 improved wound contraction and closure. Histopathology study further confirmed a desirable histological organization of wound tissues. BB oil1/5 and BB oil1/10 reduced the number of inflammatory cells, increased wound-healing rates, and significantly increased the hydroxyproline content. Both BB oil1/5 and BB oil1/10 improved formation of collagen, and reduced the frequency of fibroblasts. Moreover, BB oil1/5 and BB oil1/10 markedly promoted SP expression. However, undiluted BB oil may induce skin thickening and hardening, inhibite collagen synthesis and delay complete skin wound healing. The BB oil1/5 and BB oil1/10 promoted capillary regeneration, blood circulation, collagen deposition, granular tissue formation, epithelial deposition, and wound contraction. The mechanism underlying the action might be related to induction of SP secretion, and the proliferation and differentiation of mesenchymal cells.

Ultrasensitive sensing platform for platelet-derived growth factor BB detection based on layered molybdenum selenide-graphene composites and Exonuclease III assisted signal amplification.

PubMed

Huang, Ke-Jing; Shuai, Hong-Lei; Zhang, Ji-Zong

2016-03-15

A highly sensitive and ultrasensitive electrochemical aptasensor for platelet-derived growth factor BB (PDGF-BB) detection is fabricated based on layered molybdenum selenide-graphene (MoSe2-Gr) composites and Exonuclease III (Exo III)-aided signal amplification. MoSe2-Gr is prepared by a simple hydrothermal method and used as a promising sensing platform. Exo III has a specifical exo-deoxyribonuclease activity for duplex DNAs in the direction from 3' to 5' terminus, however its activity is limited on the duplex DNAs with more than 4 mismatched terminal bases at 3' ends. Herein, aptamer and complementary DNA (cDNA) sequences are designed with four thymine bases on 3' ends. In the presence of target protein, the aptamer associates with it and facilitates the formation of duplex DNA between cDNA and signal DNA. The duplex DNA then is digested by Exo III and releases cDNA, which hybridizes with signal DNA to perform a new cleavage process. Nevertheless, in the absence of target protein, the aptamer hybridizes with cDNA will inhibit the Exo III-assisted nucleotides cleavage. The signal DNA then hybridizes with capture DNA on the electrode. Subsequently, horse radish peroxidase is fixed on electrode by avidin-biotin reaction and then catalyzes hydrogen peroxide and hydroquinone to produce electrochemical response. Therefore, a bridge can be established between the concentration of target protein and the degree of the attenuation of the obtained signal, providing a quantitative measure of target protein with a broad detection range of 0.0001-1 nM and a detection limit of 20 fM. Copyright © 2015 Elsevier B.V. All rights reserved.

Platelet-rich plasma as treatment for persistent ocular epithelial defects.

PubMed

Ronci, Corrado; Ferraro, Angelo Salvatore; Lanti, Alessandro; Missiroli, Filippo; Sinopoli, Silvia; Del Proposto, Gianpaolo; Cipriani, Chiara; De Felici, Cecilia; Ricci, Federico; Ciotti, Marco; Cudillo, Laura; Arcese, William; Adorno, Gaspare

2015-06-01

Platelet- rich plasma (PRP) exhibits regenerative proprieties in wound healing but the biochemical mechanisms are unclear. In this study, autologous PRP with a mean value of 338 × 10(3) platelets/µL was used to treat corneal lesions of different aetiology, while homologous PRP with 1 × 10(6) platelets/µL was used to treat cornel lesions induced by a graft versus host disease. The impact of platelet count on the levels of PDGF AA and BB, VEGF, and EGF in the two PRPs was evaluated after a cycle of freezing/thawing. Treated corneal lesions healed or improved. The levels of PDGF AA and BB, VEGF, and EGF in the autologous PRP raised from 296 ± 61; 201.8 ± 24; 53 ± 14 and 8.9 ± 2 to 1017 ± 253; 924.7 ± 222; 101 ± 46.5 and 174 ± 15.5 pg/mL, while in the homologous PRP were 3.4, 4.5, 3.2 and 2 folds higher, respectively. High level of platelet counts seems not required to treat corneal lesions. Copyright © 2014 Elsevier Ltd. All rights reserved.

4-1BB regulates NKG2D costimulation in human cord blood CD8+ T cells.

PubMed

Kim, Young-June; Han, Myung-Kwan; Broxmeyer, Hal E

2008-02-01

Ligation of NKG2D, a potent costimulatory receptor, can be either beneficial or detrimental to CD8(+) cytotoxic T cell (CTL) responses. Factors for these diverse NKG2D effects remain elusive. In this study, we demonstrate that 4-1BB, another costimulatory receptor, is an essential regulator of NKG2D in CD8(+) T cells. Costimulation of NKG2D caused down-modulation of NKG2D, but induced 4-1BB expression on the cell surface, even in the presence of TGF-beta1, which inhibits 4-1BB expression. Resulting NKG2D(-)4-1BB(+) cells were activated but still in an immature state with low cytotoxic activity. However, subsequent 4-1BB costimulation induced cytotoxic activity and restored down-modulated NKG2D. The cytotoxic activity and NKG2D expression induced by 4-1BB on NKG2D(+)4-1BB(+) cells were refractory to TGF-beta1 down-modulation. Such 4-1BB effects were enhanced by IL-12. In contrast, in the presence of IL-4, 4-1BB effects were abolished because IL-4 down-modulated NKG2D and 4-1BB expression in cooperation with TGF-beta1, generating another CD8(+) T-cell type lacking both NKG2D and 4-1BB. These NKG2D(-)4-1BB(-) cells were inert and unable to gain cytotoxic activity. Our results suggest that 4-1BB plays a critical role in protecting NKG2D from TGF-beta1-mediated down-modulation. Co-expression of NKG2D and 4-1BB may represent an important biomarker for defining competency of tumor infiltrating CD8(+) T cells.

Temporal growth factor release from platelet-rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression.

PubMed

McCarrel, Taralyn; Fortier, Lisa

2009-08-01

Platelet-rich plasma (PRP) has generated substantial interest for tendon and ligament regeneration because of the high concentrations of growth factors in platelet alpha-granules. This study compared the temporal release of growth factors from bone marrow aspirate (BMA), PRP, and lyophilized platelet product (PP), and measured their effects on tendon and ligament gene expression. Blood and BMA were collected and processed to yield PRP and plasma. Flexor digitorum superficialis tendon (FDS) and suspensory ligament (SL) explants were cultured in 10% plasma in DMEM (control), BMA, PRP, or PP. TGF-beta1 and PDGF-BB concentrations were determined at 0, 24, and 96 h of culture using ELISA. Quantitative RT-PCR for collagen types I and III (COL1A1, COL3A1), cartilage oligomeric matrix protein (COMP), decorin, and matrix metalloproteinases-3 and 13 (MMP-3, MMP-13) was performed. TGF-beta1 and PDGF-BB concentrations were highest in PRP and PP. Growth factor quantity was unchanged in BMA, increased in PRP, and decreased in PP over 4 days. TGF-beta1 and platelet concentrations were positively correlated. Lyophilized PP and PRP resulted in increased COL1A1:COL3A1 ratio, increased COMP, and decreased MMP-13 expression. BMA resulted in decreased COMP and increased MMP-3 and MMP-13 gene expression. Platelet concentration was positively correlated with COL1A1, ratio of COL1A1:COL3A1, and COMP, and negatively correlated with COL3A1, MMP-13, and MMP-3. White blood cell concentration was positively correlated with COL3A1, MMP3, and MMP13, and negatively correlated with a ratio of COL1A1:COL3A1, COMP, and decorin. These findings support further in vivo investigation of PRP and PP for treatment of tendonitis and desmitis. Copyright 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Nckβ Adapter Regulates Actin Polymerization in NIH 3T3 Fibroblasts in Response to Platelet-Derived Growth Factor bb

PubMed Central

Chen, Min; She, Hongyun; Kim, Airie; Woodley, David T.; Li, Wei

2000-01-01

The SH3-SH3-SH3-SH2 adapter Nck represents a two-gene family that includes Nckα (Nck) and Nckβ (Grb4/Nck2), and it links receptor tyrosine kinases to intracellular signaling networks. The function of these mammalian Nck genes has not been established. We report here a specific role for Nckβ in platelet-derived growth factor (PDGF)-induced actin polymerization in NIH 3T3 cells. Overexpression of Nckβ but not Nckα blocks PDGF-stimulated membrane ruffling and formation of lamellipoda. Mutation in either the SH2 or the middle SH3 domain of Nckβ abolishes its interfering effect. Nckβ binds at Tyr-1009 in human PDGF receptor β (PDGFR-β) which is different from Nckα's binding site, Tyr-751, and does not compete with phosphatidylinositol-3 kinase for binding to PDGFR. Microinjection of an anti-Nckβ but not an anti-Nckα antibody inhibits PDGF-stimulated actin polymerization. Constitutively membrane-bound Nckβ but not Nckα blocks Rac1-L62-induced membrane ruffling and formation of lamellipodia, suggesting that Nckβ acts in parallel to or downstream of Rac1. This is the first report of Nckβ's role in receptor tyrosine kinase signaling to the actin cytoskeleton. PMID:11027258

Topical application of recombinant platelet-derived growth factor increases the rate of healing and the level of proteins that regulate this response.

PubMed

Gowda, Santosh; Weinstein, David A; Blalock, Timothy D; Gandhi, Kavita; Mast, Bruce A; Chin, Gloria; Schultz, Gregory S

2015-10-01

A bipedicle ischaemic rat skin flap model was used to study the effects of daily topical applications of platelet-derived growth factor (PDGF) on the healing of ischaemic wounds. Levels of tumour necrosis factor-alpha (TNFA), interleukin 1-beta (IL1B) and both the latent and active forms of matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were measured. Full-thickness wounds were made on a total of 72 adult male Sprague-Dawley rats. Each group of 18 rats with normal and ischaemic wounds received either vehicle or 0·01% recombinant PDGF-BB. Additional applications were made on the wounds on a daily basis. Wound areas were measured at 0, 1, 3, 5, 7 9 and 13 days after wounding. Ischaemia caused a delay in wound healing as well as an increase in TNFA, IL1B and both the pro and active forms of MMP2 and MMP9. PDGF accelerated the rate of wound healing in both normal and ischaemic wounds and negated the effect of ischaemia. PDGF reduced the TNFA concentration in both normal and ischaemic wounds, and the rate of wound healing closely resembled the pattern of TNFA protein expression. PDGF also reduced both the magnitude and duration of the increases in IL1B and both the pro and active forms of MMP2 and MMP9 induced by ischaemia. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Microtubule-actin crosslinking factor 1 (Macf1) domain function in Balbiani body dissociation and nuclear positioning.

PubMed

Escobar-Aguirre, Matias; Zhang, Hong; Jamieson-Lucy, Allison; Mullins, Mary C

2017-09-01

Animal-vegetal (AV) polarity of most vertebrate eggs is established during early oogenesis through the formation and disassembly of the Balbiani Body (Bb). The Bb is a structure conserved from insects to humans that appears as a large granule, similar to a mRNP granule composed of mRNA and proteins, that in addition contains mitochondria, ER and Golgi. The components of the Bb, which have amyloid-like properties, include germ cell and axis determinants of the embryo that are anchored to the vegetal cortex upon Bb disassembly. Our lab discovered in zebrafish the only gene known to function in Bb disassembly, microtubule-actin crosslinking factor 1a (macf1a). Macf1 is a conserved, giant multi-domain cytoskeletal linker protein that can interact with microtubules (MTs), actin filaments (AF), and intermediate filaments (IF). In macf1a mutant oocytes the Bb fails to dissociate, the nucleus is acentric, and AV polarity of the oocyte and egg fails to form. The cytoskeleton-dependent mechanism by which Macf1a regulates Bb mRNP granule dissociation was unknown. We found that disruption of AFs phenocopies the macf1a mutant phenotype, while MT disruption does not. We determined that cytokeratins (CK), a type of IF, are enriched in the Bb. We found that Macf1a localizes to the Bb, indicating a direct function in regulating its dissociation. We thus tested if Macf1a functions via its actin binding domain (ABD) and plectin repeat domain (PRD) to integrate cortical actin and Bb CK, respectively, to mediate Bb dissociation at the oocyte cortex. We developed a CRISPR/Cas9 approach to delete the exons encoding these domains from the macf1a endogenous locus, while maintaining the open reading frame. Our analysis shows that Macf1a functions via its ABD to mediate Bb granule dissociation and nuclear positioning, while the PRD is dispensable. We propose that Macf1a does not function via its canonical mechanism of linking two cytoskeletal systems together in dissociating the Bb. Instead our results suggest that Macf1a functions by linking one cytoskeletal system, cortical actin, to another structure, the Bb, where Macf1a is localized. Through this novel linking process, it dissociates the Bb at the oocyte cortex, thus specifying the AV axis of the oocyte and future egg. To our knowledge, this is also the first study to use genome editing to unravel the module-dependent function of a cytoskeletal linker.

Microtubule-actin crosslinking factor 1 (Macf1) domain function in Balbiani body dissociation and nuclear positioning

PubMed Central

Zhang, Hong; Jamieson-Lucy, Allison

2017-01-01

Animal-vegetal (AV) polarity of most vertebrate eggs is established during early oogenesis through the formation and disassembly of the Balbiani Body (Bb). The Bb is a structure conserved from insects to humans that appears as a large granule, similar to a mRNP granule composed of mRNA and proteins, that in addition contains mitochondria, ER and Golgi. The components of the Bb, which have amyloid-like properties, include germ cell and axis determinants of the embryo that are anchored to the vegetal cortex upon Bb disassembly. Our lab discovered in zebrafish the only gene known to function in Bb disassembly, microtubule-actin crosslinking factor 1a (macf1a). Macf1 is a conserved, giant multi-domain cytoskeletal linker protein that can interact with microtubules (MTs), actin filaments (AF), and intermediate filaments (IF). In macf1a mutant oocytes the Bb fails to dissociate, the nucleus is acentric, and AV polarity of the oocyte and egg fails to form. The cytoskeleton-dependent mechanism by which Macf1a regulates Bb mRNP granule dissociation was unknown. We found that disruption of AFs phenocopies the macf1a mutant phenotype, while MT disruption does not. We determined that cytokeratins (CK), a type of IF, are enriched in the Bb. We found that Macf1a localizes to the Bb, indicating a direct function in regulating its dissociation. We thus tested if Macf1a functions via its actin binding domain (ABD) and plectin repeat domain (PRD) to integrate cortical actin and Bb CK, respectively, to mediate Bb dissociation at the oocyte cortex. We developed a CRISPR/Cas9 approach to delete the exons encoding these domains from the macf1a endogenous locus, while maintaining the open reading frame. Our analysis shows that Macf1a functions via its ABD to mediate Bb granule dissociation and nuclear positioning, while the PRD is dispensable. We propose that Macf1a does not function via its canonical mechanism of linking two cytoskeletal systems together in dissociating the Bb. Instead our results suggest that Macf1a functions by linking one cytoskeletal system, cortical actin, to another structure, the Bb, where Macf1a is localized. Through this novel linking process, it dissociates the Bb at the oocyte cortex, thus specifying the AV axis of the oocyte and future egg. To our knowledge, this is also the first study to use genome editing to unravel the module-dependent function of a cytoskeletal linker. PMID:28880872

Corneal Protection for Burn Patients

DTIC Science & Technology

2014-11-01

multiplex immunoassays utilizing the Luminex bead array were procured. Tested chemokines/cytokines include EGF, FGF-2, Eotaxin, IFN, GRO, MDC, PDGF-BB, IL...17A, IL-1RA, IL- 3, IL-6, IL-8, MP-1a and VEGF. A separate assay was used to test for matrix metalloproteinase 9 (MMP 9) given its known up...regulation in dry eye models and clinical scenarios. The tested cytokines were chosen based on their reported prevalence in dry eye states and the

Effect of PDGF-BB combined with EDTA gel on adhesion and proliferation to the root surface.

PubMed

Belal, Mahmoud Helmy; Watanabe, Hisashi; Ichinose, Shizuko; Ishikawa, Isao

2012-07-01

Periodontal regeneration using EDTA or PDGF showed promising results, but the effect of combined application was still unclear. This study aimed to verify the effect of EDTA and/or PDGF application on root adhesion and proliferation of PDL fibroblast cells. Eighty specimens were prepared from forty periodontitis teeth and made five groups: (1) diseased (untreated), (2) SRP (scaling root planing), (3) EDTA (24%), (4) PDGF (25 ng/ml) and (5) Combined application of EDTA and PDGF. Periodontal ligament cells were cultured on the above conditioned dentin plate, and SEM examination was preformed and cells were counted within a representative standard area for both cell morphology and density. All groups including untreated showed significantly increase of adhered cells from baseline to 7 days. Among them, rate of increase was much higher in EDTA, PDGF, and combined groups. ANOVA test indicated that the number of cells in PDGF and combined groups was significantly higher than diseased group at 1 day. On day 7, PDGF and combined groups showed significantly higher number of adhesion cells than that found in the diseased, SRP and EDTA groups. Thus, root conditioning with EDTA enhanced cell adhesion more than SRP alone. There was no significant difference of cell number between PDGF and combined group. Combined application of EDTA and PDGF increased significantly PDL cell adhesion than EDTA alone. PDGF alone, however, also showed comparable effect to combined application at all periods. Thus, synergistic effect between PDGF and EDTA was not observed.

Increasing platelet concentrations in leukocyte-reduced platelet-rich plasma decrease collagen gene synthesis in tendons.

PubMed

Boswell, Stacie G; Schnabel, Lauren V; Mohammed, Hussni O; Sundman, Emily A; Minas, Tom; Fortier, Lisa A

2014-01-01

Platelet-rich plasma (PRP) is used for the treatment of tendinopathy. There are numerous PRP preparations, and the optimal combination of platelets and leukocytes is not known. Within leukocyte-reduced PRP (lrPRP), there is a plateau effect of platelet concentration, with increasing platelet concentrations being detrimental to extracellular matrix synthesis. Controlled laboratory study. Different formulations of lrPRP with respect to the platelet:leukocyte ratio were generated from venous blood of 8 horses. Explants of the superficial digital flexor tendon were cultured in lrPRP products for 96 hours. Platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin-1β (IL-1β) concentrations were determined in the media by enzyme-linked immunosorbent assay. Gene expression in tendon tissue for collagen type I and III (COL1A1 and COL3A1, respectively), matrix metalloproteinase-3 and -13 (MMP-3 and MMP-13, respectively), cartilage oligomeric matrix protein (COMP), and IL-1β was determined. Data were divided into 3 groups of lrPRP based on the ratio of platelets:leukocytes and evaluated to determine the effect of platelet concentration. Complete blood counts verified leukocyte reduction and platelet enrichment in all PRP preparations. In the lrPRP preparation, the anabolic growth factors PDGF-BB and TGF-β1 were increased with increasing platelet concentrations, and the catabolic cytokine IL-1β was decreased with increasing platelet concentrations. Increasing the platelet concentration resulted in a significant reduction in COL1A1 and COL3A1 synthesis in tendons. Increasing the platelet concentration within lrPRP preparations results in the delivery of more anabolic growth factors and less proinflammatory cytokines, but the biological effect on tendons is diminished metabolism as indicated by a decrease in the synthesis of both COL1A1 and COL3A1. Together, this information suggests that minimizing leukocytes in PRP is more important than maximizing platelet numbers with respect to decreasing inflammation and enhancing matrix gene synthesis. This study suggests that reducing leukocytes to minimize catabolic signaling appears to be more important than increasing platelets in an effort to maximize anabolic signaling. Further, a maximum biological threshold of benefit was demonstrated with regard to the number of platelets beyond which further increases in platelet concentration did not result in further anabolic upregulation. In vivo investigations documenting the use of platelets for the treatment of tendinopathy are justified as well as further in vitro characterization of the ideal PRP product for the treatment of tendinopathy and other musculoskeletal applications.

Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts.

PubMed

Nagaoka, Aya; Yoshida, Hiroyuki; Nakamura, Sachiko; Morikawa, Tomohiko; Kawabata, Keigo; Kobayashi, Masaki; Sakai, Shingo; Takahashi, Yoshito; Okada, Yasunori; Inoue, Shintaro

2015-12-25

Regulation of hyaluronan (HA) synthesis and degradation is essential to maintenance of extracellular matrix homeostasis. We recently reported that HYBID (HYaluronan-Binding protein Involved in hyaluronan Depolymerization), also called KIAA1199, plays a key role in HA depolymerization in skin and arthritic synovial fibroblasts. However, regulation of HA metabolism mediated by HYBID and HA synthases (HASs) under stimulation with growth factors remains obscure. Here we report that TGF-β1, basic FGF, EGF, and PDGF-BB commonly enhance total amount of HA in skin fibroblasts through up-regulation of HAS expression, but molecular size of newly produced HA is dependent on HYBID expression levels. Stimulation of HAS1/2 expression and suppression of HYBID expression by TGF-β1 were abrogated by blockade of the MAPK and/or Smad signaling and the PI3K-Akt signaling, respectively. In normal human skin, expression of the TGF-β1 receptors correlated positively with HAS2 expression and inversely with HYBID expression. On the other hand, TGF-β1 up-regulated HAS1/2 expression but exerted only a slight suppressive effect on HYBID expression in synovial fibroblasts from the patients with osteoarthritis or rheumatoid arthritis, resulting in the production of lower molecular weight HA compared with normal skin and synovial fibroblasts. These data demonstrate that although TGF-β1, basic FGF, EGF, and PDGF-BB enhance HA production in skin fibroblasts, TGF-β1 most efficiently contributes to production of high molecular weight HA by HAS up-regulation and HYBID down-regulation and suggests that inefficient down-regulation of HYBID by TGF-β1 in arthritic synovial fibroblasts may be linked to accumulation of depolymerized HA in synovial fluids in arthritis patients. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Sphingosine-1-phosphate receptor expression in cardiac fibroblasts is modulated by in vitro culture conditions.

PubMed

Landeen, Lee K; Aroonsakool, Nakon; Haga, Jason H; Hu, Betty S; Giles, Wayne R

2007-06-01

The bioactive molecule sphingosine-1-phosphate (S1P) binds with high affinity to five recognized receptors (S1P(1-5)) to affect various tissues, including cellular responses of cardiac fibroblasts (CFbs) and myocytes. CFbs are essential components of myocardium, and detailed study of their cell signaling and physiology is required for a number of emerging disciplines. Meaningful studies on CFbs, however, necessitate methods for selective, reproducible cell isolations. Macrophages reside within normal cardiac tissues and often are isolated with CFbs. A protocol was therefore developed that significantly reduces macrophage levels and utilizes more CFb-specific markers (discoidin domain receptor-2) instead of, or in addition to, more commonly used cytoskeletal markers. Our results demonstrate that primary isolated, purified CFbs express predominantly S1P(1-3); however, the relative levels of these receptor subtypes are modulated with time and by culture conditions. In coculture experiments, macrophages altered CFb S1P receptor levels relative to controls. Further investigations using known macrophage-secreted factors showed that S1P and H(2)O(2) had minimal effects on CFb S1P(1-3) expression, whereas transforming growth factor-beta1, TNF-alpha, and PDGF-BB significantly altered all S1P receptor subtypes. Lowering FBS concentrations from 10% to 0.1% increased S1P(2), whereas supplementation with either PDGF-BB or Rho-associated protein kinase inhibitor Y-27632 significantly elevated S1P(3) levels. S1P(2) and S1P(3) receptor levels are known to regulate cell migration. Using cells isolated from either normal or S1P(3)-null mice, we demonstrate that S1P(3) is important and necessary for CFb migration. These results highlight the importance of demonstrating CFb culture purity in functional studies of S1P and also identify conditions that modulate S1P receptor expression in CFbs.

Whole Blood Profiling of Bacillus Calmette–Guérin-Induced Trained Innate Immunity in Infants Identifies Epidermal Growth Factor, IL-6, Platelet-Derived Growth Factor-AB/BB, and Natural Killer Cell Activation

PubMed Central

Smith, Steven G.; Kleinnijenhuis, Johanneke; Netea, Mihai G.; Dockrell, Hazel M.

2017-01-01

Vaccination of infants with bacillus Calmette–Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli. Our aim was to examine an extensive panel of secreted immune biomarkers to characterize the profile of trained innate immunity in infants. Stimulation of whole blood for 48 h was performed 4 months after BCG vaccination, or in control unvaccinated infants. Stimulants were lipopolysaccharide; Pam3Cys (P3C); heat-killed Candida albicans, Staphylococcus aureus, Escherichia coli, and a lysate of Mycobacterium tuberculosis. Culture supernatants were tested for secreted cytokines and chemokines by 42-plex bead array and monocytes and natural killer (NK) cells assessed for expression of activation markers by flow cytometry. BCG-vaccinated infants displayed increases in 11 cytokines and chemokines in response to different non-specific innate immunity stimuli: epidermal growth factor (EGF); eotaxin; IL-6; IL-7; IL-8; IL-10; IL-12p40; monocyte chemotactic protein-3; macrophage inflammatory protein-1α; soluble CD40 ligand and platelet-derived growth factor (PDGF)-AB/BB. Although each stimulant induced a distinct response profile, three analytes, EGF, IL-6, and PDGF-AB/BB, were commonly higher after stimulation with Pam3Cys, C. albicans, and S. aureus. Conversely, certain cytokines such as interferon gamma-inducible protein-10, IL-2, IL-13, IL-17, GM-CSF, and GRO were suppressed in BCG-vaccinated infants, while no increases in TNFα or IL-1β production were detected. We did not observe a concomitant, BCG-associated change in monocyte surface activation markers in response to non-specific stimuli, but we detected a significant increase in CD69 expression on NK cells in response to Pam3Cys. Pam3Cys-induced NK cell activation correlated with the magnitude of IL-12p40 and IL-10 responses to the same stimulant. This study reveals a novel cytokine/chemokine biomarker signature of BCG-induced trained innate immunity in infants and the involvement of NK cells in these responses. PMID:28634479

Influence of calcareous soil on Cry3Bb1 expression and efficacy in the field.

PubMed

Wangila, David S; Valencia J, Arnubio; Wang, Haichuan; Siegfried, Blair D; Meinke, Lance J

2017-06-01

Greater than expected injury by western corn rootworm (WCR) (Diabrotica virgifera virgifera LeConte) to Cry3Bb1 expressing maize hybrids (Zea mays L.) has been reported in southwestern Nebraska. Affected areas of some fields are often associated with high pH calcareous soils where maize growth is poor and iron chlorosis is common. As part of a comprehensive study to understand potential causes of unexpected injury, experiments were conducted during 2013 and 2014 to ascertain whether the calcareous soil conditions and associated poor maize growth negatively affect the expression of Cry3Bb1. Quantitative determination of Cry3Bb1 protein expression levels in root tissues was carried out on plants at V5-V6 growth stage using the enzyme-linked immunosorbent assay. Cry3Bb1 and non-Bt near isoline maize hybrids were artificially infested with Cry3Bb1-susceptible WCR eggs to measure survival and efficacy of Cry3Bb1 maize in calcareous and non-calcareous soils. Results showed that there was not a significant difference in expression of Cry3Bb1 protein between plants from calcareous and non-calcareous soils (18.9-21.2 µg/g fresh weight). Western corn rootworm survival was about sevenfold greater from the non-Bt isoline than Cry3Bb1 maize indicating that Cry3Bb1 performed as expected when infested with a Cry3Bb1 susceptible rootworm population. When survival from calcareous and non-calcareous soils was compared, no significant differences were observed in each soil. A significant positive correlation between soil pH and expression of Cry3Bb1 protein in roots was detected from samples collected in 2014 but not in 2013. No such correlation was found between soil pH and survival of WCR. Results suggest that Cry3Bb1 expression levels were sufficient to provide adequate root protection against WCR regardless of soil environment, indicating that lowered Cry3Bb1 expression is not a contributing factor to the greater than expected WCR injury observed in some southwestern Nebraska maize fields.

Selection of single chain antibody fragments binding to the extracellular domain of 4-1BB receptor by phage display technology.

PubMed

Bagheri, Salman; Yousefi, Mehdi; Safaie Qamsari, Elmira; Riazi-Rad, Farhad; Abolhassani, Mohsen; Younesi, Vahid; Dorostkar, Ruhollah; Movassaghpour, Ali Akbar; Sharifzadeh, Zahra

2017-03-01

The 4-1BB is a surface glycoprotein that pertains to the tumor necrosis factor-receptor family. There is compelling evidence suggesting important roles for 4-1BB in the immune response, including cell activation and proliferation and also cytokine induction. Because of encouraging results of different agonistic monoclonal antibodies against 4-1BB in the treatment of cancer, infectious, and autoimmune diseases, 4-1BB has been suggested as an attractive target for immunotherapy. In this study, single chain variable fragment phage display libraries, Tomlinson I+J, were screened against specific synthetic oligopeptides (peptides I and II) designed from 4-1BB extracellular domain. Five rounds of panning led to selection of four 4-1BB specific single chain variable fragments (PI.12, PI.42, PII.16, and PII.29) which showed specific reaction to relevant peptides in phage enzyme-linked immunosorbent assay. The selected clones were successfully expressed in Escherichia coli Rosetta-gami 2, and their expression was confirmed by western blot analysis. Enzyme-linked immunosorbent assay experiments indicated that these antibodies were able to specifically recognize 4-1BB without any cross-reactivity with other antigens. Flow cytometry analysis demonstrated an acceptable specific binding of the single chain variable fragments to 4-1BB expressed on CCRF-CEM cells, while no binding was observed with an irrelevant antibody. Anti-4-1BB single chain variable fragments enhanced surface CD69 expression and interleukin-2 production in stimulated CCRF-CEM cells which confirmed the agonistic effect of the selected single chain variable fragments. The data from this study have provided a rationale for further experiments involving the biological functions of anti-4-1BB single chain variable fragments in future studies.

Minimally invasive esthetic ridge preservation with growth-factor enhanced bone matrix.

PubMed

Nevins, Marc L; Said, Sherif

2017-12-28

Extraction socket preservation procedures are critical to successful esthetic implant therapy. Conventional surgical approaches are technique sensitive and often result in alteration of the soft tissue architecture, which then requires additional corrective surgical procedures. This case series report presents the ability of flapless surgical techniques combined with a growth factor-enhanced bone matrix to provide esthetic ridge preservation at the time of extraction for compromised sockets. When considering esthetic dental implant therapy, preservation, or further enhancement of the available tissue support at the time of tooth extraction may provide an improved esthetic outcome with reduced postoperative sequelae and decreased treatment duration. Advances in minimally invasive surgical techniques combined with recombinant growth factor technology offer an alternative for bone reconstruction while maintaining the gingival architecture for enhanced esthetic outcome. The combination of freeze-dried bone allograft (FDBA) and rhPDGF-BB (platelet-derived growth factor-BB) provides a growth-factor enhanced matrix to induce bone and soft tissue healing. The use of a growth-factor enhanced matrix is an option for minimally invasive ridge preservation procedures for sites with advanced bone loss. Further studies including randomized clinical trials are needed to better understand the extent and limits of these procedures. The use of minimally invasive techniques with growth factors for esthetic ridge preservation reduces patient morbidity associated with more invasive approaches and increases the predictability for enhanced patient outcomes. By reducing the need for autogenous bone grafts the use of this technology is favorable for patient acceptance and ease of treatment process for esthetic dental implant therapy. © 2017 Wiley Periodicals, Inc.

Macropinocytosis of the PDGF β-receptor promotes fibroblast transformation by H-RasG12V

PubMed Central

Schmees, C.; Villaseñor, R.; Zheng, W.; Ma, H.; Zerial, M.; Heldin, C.-H.; Hellberg, C.

2012-01-01

Receptor tyrosine kinase (RTK) signaling is frequently increased in tumor cells, sometimes as a result of decreased receptor down-regulation. The extent to which the endocytic trafficking routes can contribute to such RTK hyperactivation is unclear. Here, we show for the first time that fibroblast transformation by H-RasG12V induces the internalization of platelet-derived growth factor β-receptor (PDGFRβ) by macropinocytosis, enhancing its signaling activity and increasing anchorage-independent proliferation. H-RasG12V transformation and PDGFRβ activation were synergistic in stimulating phosphatidylinositol (PI) 3-kinase activity, leading to receptor macropinocytosis. PDGFRβ macropinocytosis was both necessary and sufficient for enhanced receptor activation. Blocking macropinocytosis by inhibition of PI 3-kinase prevented the increase in receptor activity in transformed cells. Conversely, increasing macropinocytosis by Rabankyrin-5 overexpression was sufficient to enhance PDGFRβ activation in nontransformed cells. Simultaneous stimulation with PDGF-BB and epidermal growth factor promoted macropinocytosis of both receptors and increased their activation in nontransformed cells. We propose that H-Ras transformation promotes tumor progression by enhancing growth factor receptor signaling as a result of increased receptor macropinocytosis. PMID:22573884

Current concepts in periodontal bioengineering

PubMed Central

Taba, M.; Jin, Q.; Sugai, J.V.; Giannobile, W.V.

2008-01-01

Repair of tooth supporting alveolar bone defects caused by periodontal and peri-implant tissue destruction is a major goal of reconstructive therapy. Oral and craniofacial tissue engineering has been achieved with limited success by the utilization of a variety of approaches such as cell-occlusive barrier membranes, bone substitutes and autogenous block grafting techniques. Signaling molecules such as growth factors have been used to restore lost tooth support because of damage by periodontal disease or trauma. This paper will review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Several different polymer delivery systems that aid in the targeting of proteins, genes and cells to periodontal and peri-implant defects will be highlighted. Results from preclinical and clinical trials will be reviewed using the topical application of bone morphogenetic proteins (BMP-2 and BMP-7) and platelet-derived growth factor-BB (PDGF) for periodontal and peri-implant regeneration. The paper concludes with recent research on the use of ex vivo and in vivo gene delivery strategies via gene therapy vectors encoding growth promoting and inhibiting molecules (PDGF, BMP, noggin and others) to regenerate periodontal structures including bone, periodontal ligament and cementum. PMID:16238610

The autophagy-related genes BbATG1 and BbATG8 have different functions in differentiation, stress resistance and virulence of mycopathogen Beauveria bassiana

PubMed Central

Ying, Sheng-Hua; Liu, Jing; Chu, Xin-Ling; Xie, Xue-Qin; Feng, Ming-Guang

2016-01-01

Autophagy-related proteins play significantly different roles in eukaryotes. In the entomopathogenic fungus Beauveria bassiana, autophagy is associated with fungal growth and development. BbATG1 (a serine/threonine protein kinase) and BbATG8 (a ubiquitin-like protein) have similar roles in autophagy, but different roles in other processes. Disruption mutants of BbATG1 and BbATG8 had impaired conidial germination under starvation stress. The mutant ΔBbATG8 exhibited enhanced sensitivity to oxidative stress, while a ΔBbATG1 mutant did not. BbATG1 and BbATG8 showed different roles in spore differentiation. The blastospore yield was reduced by 70% and 92% in ΔBbATG1 and ΔBbATG8 mutants, respectively, and the double mutant had a reduction of 95%. Conidial yield was reduced by approximately 90% and 50% in ΔBbATG1 and ΔBbATG8 mutants, respectively. A double mutant had a reduction similar to ΔBbATG1. Additionally, both BbATG1 and BbATG8 affected the levels of conidial protein BbCP15p required for conidiation. The virulence of each autophagy-deficient mutant was considerably weakened as indicated in topical and intrahemocoel injection assays, and showed a greater reduction in topical infection. However, BbATG1 and BbATG8 had different effects on fungal virulence. Our data indicate that these autophagy-related proteins have different functions in fungal stress response, asexual development and virulence. PMID:27197558

Sustained functional improvement by hepatocyte growth factor-like small molecule BB3 after focal cerebral ischemia in rats and mice

PubMed Central

Chaparro, Rafael E; Izutsu, Miwa; Sasaki, Toshihiro; Sheng, Huaxin; Zheng, Yi; Sadeghian, Homa; Qin, Tao; von Bornstadt, Daniel; Herisson, Fanny; Duan, Bin; Li, Jing-Song; Jiang, Kai; Pearlstein, Molly; Pearlstein, Robert D; Smith, David E; Goldberg, Itzhak D; Ayata, Cenk; Warner, David S

2015-01-01

Hepatocyte growth factor (HGF), efficacious in preclinical models of acute central nervous system injury, is burdened by administration of full-length proteins. A multiinstitutional consortium investigated the efficacy of BB3, a small molecule with HGF-like activity that crosses the blood–brain barrier in rodent focal ischemic stroke using Stroke Therapy Academic Industry Roundtable (STAIR) and Good Laboratory Practice guidelines. In rats, BB3, begun 6 hours after temporary middle cerebral artery occlusion (tMCAO) reperfusion, or permanent middle cerebral artery occlusion (pMCAO) onset, and continued for 14 days consistently improved long-term neurologic function independent of sex, age, or laboratory. BB3 had little effect on cerebral infarct size and no effect on blood pressure. BB3 increased HGF receptor c-Met phosphorylation and synaptophysin expression in penumbral tissue consistent with a neurorestorative mechanism from HGF-like activity. In mouse tMCAO, BB3 starting 10 minutes after reperfusion and continued for 14 days improved neurologic function that persisted for 8 weeks in some, but not all measures. Study in animals with comorbidities and those exposed to common stroke drugs are the next steps to complete preclinical assessment. These data, generated in independent, masked, and rigorously controlled settings, are the first to suggest that the HGF pathway can potentially be harnessed by BB3 for neurologic benefit after ischemic stroke. PMID:25712497

A wildland fire emission inventory for the western United States - uncertainty across spatial and temporal scales

Treesearch

Shawn Urbanski; WeiMin Hao

2010-01-01

Emissions of trace gases and aerosols by biomass burning (BB) have a significant influence on the chemical composition of the atmosphere, air quality, and climate. BB emissions depend on a range of variables including burned area, fuels, meteorology, combustion completeness, and emission factors (EF). Emission algorithms provide BB emission inventories (EI) which serve...

Identification of two Th1 cell epitopes on the Babesia bovis-encoded 77-kilodalton merozoite protein (Bb-1) by use of truncated recombinant fusion proteins.

PubMed Central

Brown, W C; Zhao, S; Woods, V M; Tripp, C A; Tetzlaff, C L; Heussler, V T; Dobbelaere, D A; Rice-Ficht, A C

1993-01-01

Previous studies have demonstrated the serologic and T-cell immunogenicity for cattle of a recombinant form of the apical complex-associated 77-kDa merozite protein of Babesia bovis, designated Bb-1. The present study characterizes the immunogenic epitopes of the Bb-1 protein. A series of recombinant truncated fusion proteins spanning the majority of the Bb-1 protein were expressed in Escherichia coli, and their reactivities with bovine peripheral blood mononuclear cells and T-cell clones derived from B. bovis-immune cattle and with rabbit antibodies were determined. Lymphocytes from two immune cattle were preferentially stimulated by the N-terminal half of the Bb-1 protein (amino acids 23 to 266, termed Bb-1A), localizing the T-cell epitopes to the Bb-1A portion of the molecule. CD4+ T-cell clones derived by stimulation with the intact Bb-1 fusion protein were used to identify two T-cell epitopes in the Bb-1A protein, consisting of amino acids SVVLLSAFSGN VWANEAEVSQVVK and FSDVDKTKSTEKT (residues 23 to 46 and 82 to 94). In contrast, rabbit antiserum raised against the intact fusion protein reacted only with the C-terminal half of the protein (amino acids 267 to 499, termed Bb-1B), which contained 28 tandem repeats of the tetrapeptide PAEK or PAET. Biological assays and Northern (RNA) blot analyses for cytokines revealed that following activation with concanavalin A, T-cell clones reactive against the two Bb-1A epitopes produced interleukin-2, gamma interferon, and tumor necrosis factors beta and alpha, but not interleukin-4, suggesting that the Bb-1 antigen preferentially stimulates the Th1 subset of CD4+ T cells in cattle. The studies described here report for the first time the characterization, by cytokine production, of the Th1 subset of bovine T cells and show that, as in mice, protozoal antigens can induce Th1 cells in ruminants. This first demonstration of B. bovis-encoded Th1 cell epitopes provides a rationale for incorporation of all or part of the Bb-1 protein into a recombinant vaccine. Images PMID:7678098

[Roles of Y box-binding protein 1 in SK-BR-3 breast cancer proliferation].

PubMed

Shi, Jianhong; Lü, Xinrui; Wang, Bing; Daudan, Lin; Yanan, Wang; Yuhui, Bu; Zhenfeng, Ma

2014-09-30

To explore the roles of Y box-binding protein 1 (YB-1) in breast cancer cell proliferation. Twenty cases of surgical removal of breast cancer tissue (diagnosed with invasive ductal carcinoma, stage II, by postoperative paraffin pathology) and normal breast tissues adjacent to carcinoma were collected during June 2013 to August 2013.Quantitative real-time PCR (qRT-PCR) was performed to detect the YB1 mRNA levels. Cultured mammary epithelial cells (HBL-100) and breast cancer cells (MCF7, MDA-MB-231 & SK-BR-3 cells) were harvested and qRT-PCR was performed to detect the YB1 mRNA levels.SK-BR-3 cells were stimulated with various concentrations of PDGF-BB and YB1 expression levels were detected by qRT-PCR. Down-regulation or over-expression of YB1 by si-YB1 or Ad-GFP-YB1 was detected in SK-BR-3 cells. And MTS cell proliferation assay kit was used to detect cell proliferation. YB1 mRNA levels were significantly higher in breast cancer tissues and MDA-MB-231 and SK-BR-3 breast cancer cell lines than that in adjacent normal breast tissues and HBL-100 mammary epithelial cells respectively (P < 0.05).YB1 expression levels increased in PDGF-BB stimulated SK-BR-3 cells in a dose-dependent manner. A down-regulation of endogenous YB1 decreases and an over-expression of exogenous YB1 promotes the proliferation activity in SK-BR-3 cells.

Glucagon-like peptide-1 inhibits vascular smooth muscle cell dedifferentiation through mitochondrial dynamics regulation.

PubMed

Torres, Gloria; Morales, Pablo E; García-Miguel, Marina; Norambuena-Soto, Ignacio; Cartes-Saavedra, Benjamín; Vidal-Peña, Gonzalo; Moncada-Ruff, David; Sanhueza-Olivares, Fernanda; San Martín, Alejandra; Chiong, Mario

2016-03-15

Glucagon-like peptide-1 (GLP-1) is a neuroendocrine hormone produced by gastrointestinal tract in response to food ingestion. GLP-1 plays a very important role in the glucose homeostasis by stimulating glucose-dependent insulin secretion, inhibiting glucagon secretion, inhibiting gastric emptying, reducing appetite and food intake. Because of these actions, the GLP-1 peptide-mimetic exenatide is one of the most promising new medicines for the treatment of type 2 diabetes. In vivo treatments with GLP-1 or exenatide prevent neo-intima layer formation in response to endothelial damage and atherosclerotic lesion formation in aortic tissue. Whether GLP-1 modulates vascular smooth muscle cell (VSMC) migration and proliferation by controlling mitochondrial dynamics is unknown. In this report, we showed that GLP-1 increased mitochondrial fusion and activity in a PKA-dependent manner in the VSMC cell line A7r5. GLP-1 induced a Ser-637 phosphorylation in the mitochondrial fission protein Drp1, and decreased Drp1 mitochondrial localization. GLP-1 inhibited PDGF-BB-induced VSMC migration and proliferation, actions inhibited by overexpressing wild type Drp1 and mimicked by the Drp1 inhibitor Mdivi-1 and by overexpressing dominant negative Drp1. These results show that GLP-1 stimulates mitochondrial fusion, increases mitochondrial activity and decreases PDGF-BB-induced VSMC dedifferentiation by a PKA/Drp1 signaling pathway. Our data suggest that GLP-1 inhibits vascular remodeling through a mitochondrial dynamics-dependent mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

Silencing heat shock protein 27 (HSP27) inhibits the proliferation and migration of vascular smooth muscle cells in vitro.

PubMed

Huang, Jie; Xie, Liang-di; Luo, Li; Zheng, Su-Li; Wang, Hua-Jun; Xu, Chang-Sheng

2014-05-01

The objective of this study was to examine the role of heat shock protein 27 (HSP27) in proliferation and migration of vascular smooth muscle cells (VSMCs). Three complementary DNA sequences targeting rat HSP27 gene were designed, synthesized, and subcloned into lentiviral vector. The interfering efficiency was detected by reverse transcriptase-polymerase chain reaction and Western blot. Methyl thiazolyl tetrazolium bromide assay was used for examining cell proliferation. F-actin polymerization was detected by FITC-Phalloidin staining using confocal microscopy. Modified Boyden chamber technique was used to assess VSMCs migration. The recombinant lentivirus containing RNAi targeting HSP27 gene significantly inhibited expression of HSP27 at both mRNA and protein levels. The interfering efficiencies of pNL-HSP27-EGFP-1, pNL-HSP27-EGFP-2, and pNL-HSP27-EGFP-3 were 71 %, 77 %, and 43 %, respectively. Reorganization of actin stimulated by PDGF-BB was markedly blocked by pretreatment with pNL-HSP27-EGFP-2. Proliferation and migration rates of VSMCs induced by PDGF-BB were inhibited by 30.8 % and 45.6 %, respectively, by pNL-HSP27-EGFP-2 (all P < 0.01). To conclude, these data indicate that HSP27 may regulate the proliferation, actin reorganization, and the migration of VSMCs. RNAi targeting at HSP27 may be a potential approach for inhibition of cell migration involved in pathogenesis of proliferative vascular diseases.

Feeding Blueberry Diets to Young Rats Dose-Dependently Inhibits Bone Resorption through Suppression of RANKL in Stromal Cells

PubMed Central

Zhang, Jian; Lazarenko, Oxana P.; Kang, Jie; Blackburn, Michael L.; Ronis, Martin J. J.; Badger, Thomas M.; Chen, Jin-Ran

2013-01-01

Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB) powder for two weeks beginning on postnatal day 21 (PND21) significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is, as yet, unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5%) for 35 days beginning on PND25 on bone quality, and osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT) of tibia, demonstrated that bone mineral density (BMD) and content (BMC) were dose-dependently increased in BB-fed rats compared to controls (P<0.05). Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition) rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-κB ligand) a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPARγ (peroxisome proliferator-activated receptor γ) which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption. PMID:23936431

Burning of olive tree branches: a major organic aerosol source in the Mediterranean

NASA Astrophysics Data System (ADS)

Kostenidou, E.; Kaltsonoudis, C.; Tsiflikiotou, M.; Louvaris, E.; Russell, L. M.; Pandis, S. N.

2013-09-01

Aerosol produced during the burning of olive tree branches was characterized with both direct source sampling (using a mobile smog chamber) and with ambient measurements during the burning season. The fresh particles were composed of 80% organic matter, 8-10% black carbon (BC), 5% potassium, 3-4% sulfate, 2-3% nitrate and 0.8% chloride. Almost half of the fresh olive tree branches burning organic aerosol (otBB-OA) consisted of alkane groups. Their mode diameter was close to 70 nm. The oxygen to carbon (O : C) ratio of the fresh otBB-OA was 0.29 ± 0.04. The mass fraction of levoglucosan in PM1 was 0.034-0.043, relatively low in comparison with most fuel types. This may lead to an underestimation of the otBB-OA contribution if levoglucosan is being used as a wood burning tracer. Chemical aging was observed during smog chamber experiments, as f44 and O : C ratio increased, due to reactions with OH radicals and O3. The otBB-OA AMS mass spectrum differs from the other published biomass burning spectra, with a main difference at m/z 60, used as levoglucosan tracer. In addition to particles, volatile organic compounds (VOCs) such as methanol, acetonitrile, acrolein, benzene, toluene and xylenes are also emitted. Positive matrix factorization (PMF) was applied to the ambient organic aerosol data and 3 factors could be identified: OOA (oxygenated organic aerosol, 55%), HOA (hydrocarbon-like organic aerosol, 11.3%) and otBB-OA 33.7%. The fresh chamber otBB-OA AMS spectrum is close to the PMF otBB-OA spectrum and resembles the ambient mass spectrum during olive tree branches burning periods. We estimated an otBB-OA emission factor of 3.5 ± 0.9 g kg-1. Assuming that half of the olive tree branches pruned is burned in Greece, 2300 ± 600 tons of otBB-OA are emitted every year. This activity is one of the most important fine aerosol sources during the winter months in Mediterranean countries.

Burning of olive tree branches: a major organic aerosol source in the Mediterranean

NASA Astrophysics Data System (ADS)

Kostenidou, E.; Kaltsonoudis, C.; Tsiflikiotou, M.; Louvaris, E.; Russell, L. M.; Pandis, S. N.

2013-03-01

Aerosol produced during the burning of olive tree branches was characterized with both direct source-sampling (using a mobile smog chamber) and with ambient measurements during the burning season. The fresh particles were composed of 80% organic matter, 8-10% black carbon (BC), 5% potassium, 3-4% sulfate, 2-3% nitrate and 0.8% chloride. Almost half of the fresh olive tree branches burning organic aerosol (otBB-OA) consisted of alkane groups. Their mode diameter was close to 70 nm. The oxygen to carbon (O:C) ratio of the fresh otBB-OA was 0.29 ± 0.04. The mass fraction of levoglucosan in PM1 was 0.034-0.043, relatively low in comparison with most fuel types. This may lead to an underestimation of the otBB-OA contribution if levoglucosan is being used as a wood burning tracer. Chemical aging was observed during smog chamber experiments, as f44 and O:C ratio increased, due to reactions with OH radicals and O3. The otBB-OA AMS mass spectrum differs from the other published biomass burning spectra, with a main difference at m/z 60, used as levoglucosan tracer. In addition to particles, volatile organic compounds (VOCs) such as methanol, acetonitrile, acrolein, benzene, toluene and xylenes are also emitted. Positive matrix factorization (PMF) was applied to the ambient organic aerosol data and 3 factors could be identified: OOA (oxygenated organic aerosol, 55%), HOA (hydrocarbon-like organic aerosol, 11.3%) and otBB-OA 33.7%. The fresh chamber otBB-OA AMS spectrum is close to the PMF otBB-OA spectrum and resembles the ambient mass spectrum during olive tree branches burning periods. We estimated an otBB-OA emission factor of 3.5 ± 0.2 g kg-1. Assuming that half of the olive tree branches pruned is burned in Greece 2280 ± 140 tons of otBB-OA are emitted every year. This activity is one of the most important fine aerosol sources during the winter months in the Mediterranean countries.

Platelet-Poor and Platelet-Rich Plasma Stimulate Bone Lineage Differentiation in Periodontal Ligament Stem Cells.

PubMed

Martínez, Constanza E; González, Sergio A; Palma, Verónica; Smith, Patricio C

2016-02-01

Plasma-derived fractions have been used as an autologous source of growth factors; however, limited knowledge concerning their biologic effects has hampered their clinical application. In this study, the authors analyze the content and specific effect of both platelet-rich plasma (PRP) and platelet-poor plasma (PPP) on osteoblastic differentiation using primary cultures of human periodontal ligament stem cells (HPLSCs). The authors evaluated the growth factor content of PRP and PPP using a proteome profiler array and enzyme-linked immunosorbent assay. HPLSCs were characterized by flow cytometry and differentiation assays. The effect of PRP and PPP on HPLSC bone differentiation was analyzed by quantifying calcium deposition after 14 and 21 days of treatment. Albeit at different concentrations, the two fractions had similar profiles of growth factors, the most representative being platelet-derived growth factor (PDGF) isoforms (PDGF-AA, -BB, and -AB), insulin-like growth factor binding protein (IGFBP)-2, and IGFBP-6. Both formulations exerted a comparable stimulus on osteoblastic differentiation even at low doses (2.5%), increasing calcium deposits in HPLSCs. PRP and PPP showed a similar protein profile and exerted comparable effects on bone differentiation. Further studies are needed to characterize and compare the effects of PPP and PRP on bone healing in vivo.

Performance of Nursing Awassi Ewes Fed Different Levels of Bread By-product

PubMed Central

Obeidat, B. S.; Haddad, S. G.; Titi, H. H.; Abu Ishmais, M. A.; Telfah, B. T.

2012-01-01

Objective of this experiment was to evaluate the effect of partial substitution of barley grain with bread by-product (BB) on performance of Awassi ewes and their lambs. Forty Awassi ewes rearing single lambs were randomly allotted into four experimental diets containing various levels of BB. The experimental diets contained 0 (BB0), 10 (BB10), 15 (BB15), and 20% (BB20) of BB on dietary dry matter (DM). The study lasted for eight weeks, in which the first week was used as an adaptation period and seven weeks of data collection. Ewes and their lambs were penned individually where they were fed their lactating diets ad libitum. Ewes and lambs body weights were measured at the beginning and at the end of the experiment. However, milk production and composition were evaluated biweekly. Feeding BB had no effect (p>0.05) on dry matter (DM), organic matter (OM), and crude protein (CP) intakes. However, neutral detergent fiber (NDF) intake was the lowest (p<0.05) for the BB20 and BB15 diets followed to BB10 diet (i.e., 640, 677, 772 g/d, respectively) while the highest NDF intake was for the BB0 diet (i.e., 825 g/d). Similarly, NDF intake decreased linearly (p<0.001) as the BB content increased. Acid detergent fiber (ADF) intake was highest (p<0.05) for the BB0 and BB10 diets (425 and 416 g/d, respectively) followed by the BB15 and BB20 diets (359 and 342 g/d, respectively). Moreover, a linear (p<0.001), quadratic (p = 0.04), and cubic (p = 0.04) effects were observed in ADF intake among diets. Nutrient digestibility was similar among different diets. Bread by-product had no effect (p>0.05) on ewes body weight change and on lamb performance (i.e., weaning body weight and average daily gain). Similarly, no differences (p>0.05) were observed either in milk production or composition by the BB substitution. Inclusion of BB reduced feed cost by 9, 14, and 18% for the BB10, BB15, and BB20 diets, respectively. No differences were observed in milk efficiency (DM intake: milk production; p>0.05) among diets. However, cost of milk production ($US/kg milk) was the lowest (p<0.05) in the diet containing BB20. Results of the present study indicate that feeding bread by-product up to 20% of the diet DM had no effect on performance of Awassi ewes and their lambs and reduced feed cost. PMID:25049672

Prospects of discovering stable double-heavy tetraquarks at a Tera-Z factory

NASA Astrophysics Data System (ADS)

Ali, Ahmed; Parkhomenko, Alexander Ya.; Qin, Qin; Wang, Wei

2018-07-01

Motivated by a number of theoretical considerations, predicting the deeply bound double-heavy tetraquarks T[ u bar d bar ]{ bb }, T[ u bar s bar ]{ bb } and T[ d bar s bar ]{ bb }, we explore the potential of their discovery at Tera-Z factories. Using the process Z → b b bar b b bar , we calculate, employing the Monte Carlo generators MadGraph5_aMC@NLO and Pythia6, the phase space configuration in which the bb pair is likely to fragment as a diquark. In a jet-cone, defined by an invariant mass interval mbb < M T[ q bar qbar‧ ]{ bb } + ΔM, the sought-after tetraquarks T[ q bar qbar‧ ]{ bb } as well as the double-bottom baryons, Ξbb0,-, and Ωbb- , can be produced. Using the heavy quark-diquark symmetry, we estimate B (Z → T[ u bar d bar ]{ bb } + b bar b bar) = (1.2-0.3+1.0) ×10-6, and about a half of this for the T[ u bar s bar ]{ bb } and T[ d bar s bar ]{ bb } . We also present an estimate of their lifetimes using the heavy quark expansion, yielding τ (T[ q bar qbar‧ ]{ bb }) ≃ 800 fs. Measuring the tetraquark masses would require decays, such as T[ u bar d bar ]{ bb } - →B-D-π+, T [ u bar d bar ]{ bb } - → J / ψK‾0B-, T[ u bar d bar ]{ bb } - → J / ψK-B‾0, T[ u bar s bar ]{ bb } - → Ξbc0 Σ-, and T[ d bar s bar ]{ bb } 0 → Ξbc0 Σbar0, with subsequent decay chains in exclusive non-leptonic final states. We estimate a couple of the decay widths and find that the product branching ratios do not exceed 10-5. Hence, a good fraction of these modes will be required for a discovery of T[ q bar qbar‧ ]{ bb } at a Tera-Z factory.

Abnormal TNF-alpha production in diabetes-prone BB rats: enhanced TNF-alpha expression and defective PGE2 feedback inhibition.

PubMed Central

Rothe, H; Ongören, C; Martin, S; Rösen, P; Kolb, H

1994-01-01

Upon stimulation with lipopolysaccharide (LPS), peritoneal macrophages from diabetes-prone Bio-Breeding (BB) rats secrete more tumour necrosis factor-alpha (TNF-alpha) than macrophages from diabetes-resistant BB or normal Wistar rats. Enhanced transcription was demonstrated by Northern blot analysis and at the single cell level by mRNA: RNA hybridization. Cytofluorometry analysis showed 2-4 times more plasma membrane and total cell-associated TNF-alpha in macrophages of diabetes-prone BB rats. The analysis of fluorescence intensity showed a single peak, and TNF-alpha mRNA was found in > 90% of macrophages. These findings exclude TNF hypersecretion as being due to an abnormal subfraction of cells. TNF-alpha gene hyperexpression in diabetes-prone BB rats was not due to mutations in the regulatory regions of the promoter, which could be shown by cloning and sequencing of the TNF-alpha promoter in the three rat strains. When searching for other regulatory defects we found the production of prostaglandin E2 (PGE2) in response to LPS to be up to 10 times lower in macrophages from diabetes-prone BB rats than from Wistar rats. Furthermore, BB rats macrophages required significantly higher concentrations of PGE2 for suppression of TNF-alpha secretion. We conclude that abnormal TNF-alpha production in macrophages from diabetes-prone BB rats is due to enhanced gene transcription and translation and that this is associated with defective PGE2 feedback inhibition. Images Figure 1 Figure 2 PMID:8206514

Intrinsic Deregulation of Vascular Smooth Muscle and Myofibroblast Differentiation in Mesenchymal Stromal Cells from Patients with Systemic Sclerosis.

PubMed

Hegner, Björn; Schaub, Theres; Catar, Rusan; Kusch, Angelika; Wagner, Philine; Essin, Kirill; Lange, Claudia; Riemekasten, Gabriela; Dragun, Duska

2016-01-01

Obliterative vasculopathy and fibrosis are hallmarks of systemic sclerosis (SSc), a severe systemic autoimmune disease. Bone marrow-derived mesenchymal stromal cells (MSCs) from SSc patients may harbor disease-specific abnormalities. We hypothesized disturbed vascular smooth muscle cell (VSMC) differentiation with increased propensity towards myofibroblast differentiation in response to SSc-microenvironment defining growth factors and determined responsible mechanisms. We studied responses of multipotent MSCs from SSc-patients (SSc-MSCs) and healthy controls (H-MSCs) to long-term exposure to CTGF, b-FGF, PDGF-BB or TGF-β1. Differentiation towards VSMC and myofibroblast lineages was analyzed on phenotypic, biochemical, and functional levels. Intracellular signaling studies included analysis of TGF-β receptor regulation, SMAD, AKT, ERK1/2 and autocrine loops. VSMC differentiation towards both, contractile and synthetic VSMC phenotypes in response to CTGF and b-FGF was disturbed in SSc-MSCs. H-MSCs and SSc-MSCs responded equally to PDGF-BB with prototypic fibroblastic differentiation. TGF-β1 initiated myofibroblast differentiation in both cell types, yet with striking phenotypic and functional differences: In relation to H-MSC-derived myofibroblasts induced by TGF-β1, those obtained from SSc-MSCs expressed more contractile proteins, migrated towards TGF-β1, had low proliferative capacity, and secreted higher amounts of collagen paralleled by reduced MMP expression. Higher levels of TGF-β receptor 1 and enhanced canonical and noncanonical TGF-β signaling in SSc-MSCs accompanied aberrant differentiation response of SSc-MSCs in comparison to H-MSCs. Deregulated VSMC differentiation with a shift towards myofibroblast differentiation expands the concept of disturbed endogenous regenerative capacity of MSCs from SSc patients. Disease related intrinsic hyperresponsiveness to TGF-β1 with increased collagen production may represent one responsible mechanism. Better understanding of repair barriers and harnessing beneficial differentiation processes in MSCs could widen options of autologous MSC application in SSc patients.

Temporal and diurnal variations of carbonaceous aerosols and major ions in biomass burning influenced aerosols over Mt. Tai in the North China Plain during MTX2006

NASA Astrophysics Data System (ADS)

Boreddy, Suresh K. R.; Kawamura, Kimitaka; Okuzawa, Kazuhiro; Kanaya, Yugo; Wang, Zifa

2017-04-01

To better understand the impact of agricultural waste burning on the air quality of free troposphere over the North China Plain (NCP), we collected total suspended particles (TSP) at the summit of Mt. Tai, located in the NCP using a high volume air sampler during 29 May to 28 June 2006, when the field burning of agricultural residue was intense. Temporal variations of all measured species showed that their concentration increases from late May to mid June (major BB period), peaking during 12-14 June, and then significantly decreased towards late June (minor BB period). We noticed that a significant reduction in the concentrations of carbonaceous aerosols during the period of 8-11 June, when the wind direction shifted from southerly to northerly. We found that concentrations of carbonaceous aerosols and some major ions showed several times higher during major BB period than those of minor BB period. We also found that nighttime concentrations are higher than daytime during major BB period, suggesting that a long-range atmospheric transport of biomass burning plumes in the free troposphere, which arrived at the summit of Mt. Tai. In contrast, daytime concentrations are higher than nighttime during minor BB period. We found higher concentrations of secondary organic carbon (SOC) during major BB period, suggesting that formation of secondary organic aerosols through aqueous phase chemistry under high NOx conditions during a long-range atmospheric transport. nss-K+ showed about four times higher concentrations during major BB than those of minor BB. Concentrations of nss-Ca2+ are higher in nighttime during major BB period, implying that a significant long-range atmospheric transport of mineral dust over the sampling site. These results are further supported by the positive matrix factorization (PMF) analysis, which showed that biomass burning was a major source for the carbonaceous aerosols followed by mineral dust sources over the summit of Mt. Tai.

β-Blocker Therapy Prior to Admission for Acute Coronary Syndrome in Patients Without Heart Failure or Left Ventricular Dysfunction Improves In-Hospital and 12-Month Outcome: Results From the GULF-RACE 2 (Gulf Registry of Acute Coronary Events-2).

PubMed

Abi Khalil, Charbel; AlHabib, Khalid F; Singh, Rajvir; Asaad, Nidal; Alfaleh, Hussam; Alsheikh-Ali, Alawi A; Sulaiman, Kadhim; Alshamiri, Mostafa; Alshaer, Fayez; AlMahmeed, Wael; Al Suwaidi, Jassim

2017-12-20

The prognostic impact of β-blockers (BB) in acute coronary syndrome (ACS) patients without heart failure (HF) or left ventricular dysfunction is controversial, especially in the postreperfusion era. We sought to determine whether a BB therapy before admission for ACS has a favorable in-hospital outcome in patients without HF, and whether they also reduce 12-month mortality if still prescribed on discharge. The GULF-RACE 2 (Gulf Registry of Acute Coronary Events-2) is a prospective multicenter study of ACS in 6 Middle Eastern countries. We studied in-hospital cardiovascular events in patients hospitalized for ACS without HF in relation to BB on admission, and 1-year mortality in relation to BB on discharge. Among the 7903 participants, 7407 did not have HF, of whom 5937 (80.15%) patients were on BB. Patients on BB tended to be older and have more comorbidities. However, they had a lower risk of in-hospital mortality, mitral regurgitation, HF, cardiogenic shock, and ventricular tachycardia/ventricular fibrillation. Furthermore, 4208 patients were discharged alive and had an ejection fraction ≥40%. Among those, 84.1% had a BB prescription. At 12 months, they also had a reduced risk of mortality as compared with the non-BB group. Even after correcting for confounding factors in 2 different models, in-hospital and 12-month mortality risk was still lower in the BB group. In this cohort of ACS, BB therapy before admission for ACS is associated with decreased in-hospital mortality and major cardiovascular events, and 1-year mortality in patients without HF or left ventricular dysfunction if still prescribed on discharge. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Dinosaur bone beds and mass mortality: Implications for the K-T extinction

NASA Technical Reports Server (NTRS)

Carpenter, Kenneth

1988-01-01

Mass accumulations of fossilized large terrestrial vertebrate skeletons (bone beds: BB) provide a test for K-T catastrophic extinction hypotheses. The two major factors contributing to BB formation are mode of death and sedimentation rate. Catastrophic mass mortality (CMM) is the sudden death of numerous individuals where species, age, health, gender, or social ranking offer no survivorship advantage. Noncatastrophic mass mortality (NCMM) occurs over time and is strongly influenced by species, age, or gender. In addition to cause of death, sedimentation rate is also important in BB formation. Models of BBs can be made. The CMM drops all individuals in their tracks, therefore, the BB should reflect the living population with respect to species, age, or gender. The NCMM results in monospecific BBs skewed in the direction of the less fit, usually the very young or very old, or towards a specific gender. The NCMM and AM BBs may become more similar the more spread out over time NCMM deaths occur because carcasses are widely scattered requiring hydraulic accumulation, and the greater time allows for more disarticulation and weathering. The CMM and NCMM BB appear to be dominated by social animals. Applying this and the characteristics of mortality patterns to the uppermost Cretaceous Hell Creek Formation indicates that only NCMM and AM BB occur. Furthermore, NCMM BB are rare in the upper third of the Hell Creek. Near the K-T boundary, only AM BB are known. The absence of CMM and NCMM BB appears to be real reflecting a decrease in population levels of some dinosaurs prior to the K-T event. The absence of CMM suggests that the K-T event did not lead to an instantaneous extinction of dinosaurs. Nor was there a protracted die-off due to an asteroid impact winter, because no NCMM BB are known at or near the K-T boundary.

Radiative response of biomass-burning aerosols over an urban atmosphere in northern peninsular Southeast Asia.

PubMed

Pani, Shantanu Kumar; Lin, Neng-Huei; Chantara, Somporn; Wang, Sheng-Hsiang; Khamkaew, Chanakarn; Prapamontol, Tippawan; Janjai, Serm

2018-08-15

A large concentration of finer particulate matter (PM 2.5 ), the primary air-quality concern in northern peninsular Southeast Asia (PSEA), is believed to be closely related to large amounts of biomass burning (BB) particularly in the dry season. In order to quantitatively estimate the contributions of BB to aerosol radiative effects, we thoroughly investigated the physical, chemical, and optical properties of BB aerosols through the integration of ground-based measurements, satellite retrievals, and modelling tools during the Seven South East Asian Studies/Biomass-burning Aerosols & Stratocumulus Environment: Lifecycles & Interactions Experiment (7-SEAS/BASELInE) campaign in 2014. Clusters were made on the basis of measured BB tracers (Levoglucosan, nss-K + , and NO 3 - ) to classify the degree of influence from BB over an urban atmosphere, viz., Chiang Mai (18.795°N, 98.957°E, 354m.s.l.), Thailand in northern PSEA. Cluster-wise contributions of BB to PM 2.5 , organic carbon, and elemental carbon were found to be 54-79%, 42-79%, and 39-77%, respectively. Moreover, the cluster-wise aerosol optical index (aerosol optical depth at 500nm≈0.98-2.45), absorption (single scattering albedo ≈0.87-0.85; absorption aerosol optical depth ≈0.15-0.38 at 440nm; absorption Ångström exponent ≈1.43-1.57), and radiative impacts (atmospheric heating rate ≈1.4-3.6Kd -1 ) displayed consistency with the degree of BB. PM 2.5 during Extreme BB (EBB) was ≈4 times higher than during Low BB (LBB), whereas this factor was ≈2.5 for the magnitude of radiative effects. Severe haze (visibility≈4km) due to substantial BB loadings (BB to PM 2.5 ≈79%) with favorable meteorology can significantly impact the local-to-regional air quality and the, daily life of local inhabitants as well as become a respiratory health threat. Additionally, such enhancements in atmospheric heating could potentially influence the regional hydrological cycle and crop productivity over Chiang Mai in northern PSEA. Copyright © 2018 Elsevier B.V. All rights reserved.

The role of small molecule platelet-derived growth factor receptor (PDGFR) inhibitors in the treatment of neoplastic disorders.

PubMed

Roskoski, Robert

2018-03-01

Platelet-derived growth factor (PDGF) was discovered as a serum-derived component necessary for the growth of smooth muscle cells, fibroblasts, and glial cells. The PDGF family is a product of four gene products and consists of five dimeric isoforms: PDGF-AA, PDGF-BB, PDGF-CC, PDGF-DD, and the PDGF-AB heterodimer. This growth factor family plays an essential role in embryonic development and in wound healing in the adult. These growth factors mediate their effects by binding to and activating their receptor protein-tyrosine kinases, which are encoded by two genes: PDGFRA and PDGFRB. The functional receptors consist of the PDGFRα/α and PDGFRβ/β homodimers and the PDGFRα/β heterodimer. Although PDGF signaling is most closely associated with mesenchymal cells, PDGFs and PDGF receptors are widely expressed in the mammalian central nervous system. The PDGF receptors contain an extracellular domain that is made up of five immunoglobulin-like domains (Ig-d1/2/3/4/5), a transmembrane segment, a juxtamembrane segment, a protein-tyrosine kinase domain that contains an insert of about 100 amino acid residues, and a carboxyterminal tail. Although uncommon, activating mutations in the genes for PDGF or PDGF receptors have been documented in various neoplasms including dermatofibrosarcoma protuberans (DFSP) and gastrointestinal stromal tumors (GIST). In most neoplastic diseases, PDGF expression and action appear to involve the tumor stroma. Moreover, this family is pro-angiogenic. More than ten PDGFRα/β multikinase antagonists have been approved by the FDA for the treatment of several neoplastic disorders and interstitial pulmonary fibrosis (www.brimr.org/PKI/PKIs.htm). Type I protein kinase inhibitors interact with the active enzyme form with DFG-D of the proximal activation segment directed inward toward the active site (DFG-D in ). In contrast, type II inhibitors bind to their target with the DFG-D pointing away from the active site (DFG-D out ). We used the Schrödinger induced-fit docking protocol to model the interaction of several antagonists with PDGFRα including imatinib, sorafenib, and sunitinib. The results indicate that these antagonists are able to bind to the DFG-D out conformation of the receptor and are thus classified as type II inhibitors. Owing to the multiplicity of less active protein kinase conformations when compared with the canonical more active conformation, it was hypothesized that type II drugs would be less promiscuous than type I drugs which bind to the typical active conformation. Although type II inhibitors may be more selective, most - if not all - inhibit more than one target protein kinase and the differences are a matter of degree only. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparing the impact of personal and parental risk factors, and parental lifespan on all-cause mortality and cardiovascular disease: findings from the Midspan Family cohort study.

PubMed

Hart, Carole; McCartney, Gerry; Gruer, Laurence; Watt, Graham

2015-10-01

We aimed to identify which personal and parental factors best explained all-cause mortality and cardiovascular disease (CVD). In 1996, data were collected on 2338 adult offspring of the participants in the 1972-1976 Renfrew and Paisley prospective cohort study. Recorded risk factors were assigned to 5 groups: mid-life biological and behavioural (BB), mid-life socioeconomic, parental BB, early-life socioeconomic and parental lifespan. Participants were followed up for mortality and hospital admissions to the end of 2011. Cox proportional hazards models were used to analyse how well each group explained all-cause mortality or CVD. Akaike's Information Criterion (AIC), a measure of goodness-of-fit, identified the most important groups. For all-cause mortality (1997 participants with complete data, 111 deaths), decreases in AIC from the null model (adjusting for age and sex) to models including mid-life BB, mid-life socioeconomic, parental BB, early-life socioeconomic and parental lifespan were 55.8, 21.6, 10.3, 7.3 and 5.9, respectively. For the CVD models (1736 participants, 276 with CVD), decreases were 37.8, 3.7, 6.7, 17.3 and 0.4. Mid-life BB factors were the most important for both all-cause mortality and CVD; mid-life socioeconomic factors were important for all-cause mortality, and early-life socioeconomic factors were important for CVD. Parental lifespan was the weakest factor. As mid-life BB risk factors best explained all-cause mortality and CVD, continued action to reduce these is warranted. Targeting adverse socioeconomic factors in mid-life and early life may contribute to reducing all-cause mortality and CVD risk, respectively. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A cytokine axis regulates elastin formation and degradation

PubMed Central

Sproul, Erin P.; Argraves, W. Scott

2013-01-01

Underlying the dynamic regulation of tropoelastin expression and elastin formation in development and disease are transcriptional and post-transcriptional mechanisms that have been the focus of much research. Of particular importance is the cytokine–governed elastin regulatory axis in which the pro-elastogenic activities of transforming growth factor β-1 (TGFβ1) and insulin-like growth factor-I (IGF-I) are opposed by anti-elastogenic activities of basic fibroblast growth factor (bFGF/FGF-2), heparin-binding epidermal growth factor-like growth factor (HB-EGF), EGF, PDGF-BB, TGFα, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and noncanonical TGFβ1 signaling. A key mechanistic feature of the regulatory axis is that cytokines influence elastin formation through effects on the cell cycle involving control of cyclin–cyclin dependent kinase complexes and activation of the Ras/MEK/ERK signaling pathway. In this article we provide an overview of the major cytokines/growth factors that modulate elastogenesis and describe the underlying molecular mechanisms for their action on elastin production. PMID:23160093

Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy.

PubMed

Chacon, Jessica Ann; Pilon-Thomas, Shari; Sarnaik, Amod A; Radvanyi, Laszlo G

2013-09-01

Co-stimulation through members of the tumor necrosis factor receptor (TNFR) family appears to be critical for the generation of T cells with optimal effector-memory properties for adoptive cell therapy. Our work suggests that continuous 4-1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal therapeutic profile and that the administration of 4-1BB agonists upon adoptive cell transfer further improves antitumor T-cell functions.

Particulate-phase mercury emissions from biomass burning ...

EPA Pesticide Factsheets

Mercury (Hg) emissions from biomass burning (BB) are an important source of atmospheric Hg and a major factor driving the interannual variation of Hg concentrations in the troposphere. The greatest fraction of Hg from BB is released in the form of elemental Hg (Hg0(g)). However, little is known about the fraction of Hg bound to particulate matter (HgP) released from BB, and the factors controlling this fraction are also uncertain. In light of the aims of the Minamata Convention to reduce intentional Hg use and emissions from anthropogenic activities, the relative importance of Hg emissions from BB will have an increasing impact on Hg deposition fluxes. Hg speciation is one of the most important factors determining the redistribution of Hg in the atmosphere and the geographical distribution of Hg deposition. Using the latest version of the Global Fire Emissions Database (GFEDv4.1s) and the global Hg chemistry transport model, ECHMERIT, the impact of Hg speciation in BB emissions, and the factors which influence speciation, on Hg deposition have been investigated for the year 2013. The role of other uncertainties related to physical and chemical atmospheric processes involving Hg and the influence of model parametrisations were also investigated, since their interactions with Hg speciation are complex. The comparison with atmospheric HgP concentrations observed at two remote sites, Amsterdam Island (AMD) and Manaus (MAN), in the Amazon showed a significant improve

Developmental GPR mine detection technology known as Balanced Bridge

NASA Astrophysics Data System (ADS)

Sherbondy, Kelly D.; Lang, David A.

1995-06-01

The Balanced Bridge (BB) detection concept was developed just after the end of WWII. It has been researched for many years since then but it has never truly overcome the following inherent problems: sensitivity to antenna height and tilt variations, detectability of flush mines, sensitivity to soil moisture content, high false alarms, and most importantly, the inability to detect small anti-personnel (AP) mines. Even with all of these shortcomings, the BB sensor technology is still one of the most promising electrmagnetic mine detection systems. This paper will address a new BB detector and its preliminary field performance compared to earlier BB research. The new BB detector has superior capabilities compared to earlier BB efforts involving single frequency or single octave excitation because the new BB operates over a multi-octave bandwidth. The new BB detector also incorporates audio and visual presentations of digitally processed signals where earlier versions only had an audible announcement derived from a simple thresholding algorithm. New BB designs addressing previous BB deficiencies will also be discussed. Design changes include using a broadband printed circuit board antenna, RF transmit and receive components, and a digital signal processor. This new BB detector will be tested at an Advanced Technology Demonstration (ATD) evaluation in FY95. The ATD exit criteria will be discussed and compared to recent field testing of the new BB detector. Preliminary results with the new BB system have demonstrated encouraging results which will be incorporated in this paper.

Protocatechuic aldehyde inhibits migration and proliferation of vascular smooth muscle cells and intravascular thrombosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moon, Chang Yoon; Endocrinology, Brain Korea 21 Project for Medical Science, Institute of Endocrine Research, and Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University College of Medicine, Seoul; Ku, Cheol Ryong

2012-06-22

Highlights: Black-Right-Pointing-Pointer Protocatechuic aldehyde (PCA) inhibits ROS production in VSMCs. Black-Right-Pointing-Pointer PCA inhibits proliferation and migration in PDGF-induced VSMCs. Black-Right-Pointing-Pointer PCA has anti-platelet effects in ex vivo rat whole blood. Black-Right-Pointing-Pointer We report the potential therapeutic role of PCA in atherosclerosis. -- Abstract: The migration and proliferation of vascular smooth muscle cells (VSMCs) and formation of intravascular thrombosis play crucial roles in the development of atherosclerotic lesions. This study examined the effects of protocatechuic aldehyde (PCA), a compound isolated from the aqueous extract of the root of Salvia miltiorrhiza, an herb used in traditional Chinese medicine to treat a varietymore » of vascular diseases, on the migration and proliferation of VSMCs and platelets due to platelet-derived growth factor (PDGF). DNA 5-bromo-2 Prime -deoxy-uridine (BrdU) incorporation and wound-healing assays indicated that PCA significantly attenuated PDGF-induced proliferation and migration of VSMCs at a pharmacologically relevant concentration (100 {mu}M). On a molecular level, we observed down-regulation of the phosphatidylinositol 3-kinase (PI3K)/Akt and the mitogen-activated protein kinase (MAPK) pathways, both of which regulate key enzymes associated with migration and proliferation. We also found that PCA induced S-phase arrest of the VSMC cell cycle and suppressed cyclin D2 expression. In addition, PCA inhibited PDGF-BB-stimulated reactive oxygen species production in VSMCs, indicating that PCA's antioxidant properties may contribute to its suppression of PDGF-induced migration and proliferation in VSMCs. Finally, PCA exhibited an anti-thrombotic effect related to its inhibition of platelet aggregation, confirmed with an aggregometer. Together, these findings suggest a potential therapeutic role of PCA in the treatment of atherosclerosis and angioplasty-induced vascular restenosis.« less

Air pressure changes in the creation and bursting of the type-1 big bubble in deep anterior lamellar keratoplasty: an ex vivo study.

PubMed

AlTaan, S L; Mohammed, I; Said, D G; Dua, H S

2018-01-01

PurposeTo measure the pressure and volume of air required to create a big bubble (BB) in simulated deep anterior lamellar keratoplasty (DALK) in donor eyes and ascertain the bursting pressure of the BB.Patients and methodsTwenty-two human sclera-corneal discs were used. Air was injected into the corneal stroma to create a BB and the pressure measured by means of a pressure converter attached to the system via a side port. A special clamp was designed to prevent air leak from the periphery of the discs. The pressure at which air emerged in the corneal tissue; the bursting pressure measured after advancing the needle into the bubble cavity and injecting more air; the volume of air required to create a BB and the volume of the BB were ascertained.ResultsType-1 BB were achieved in 19 and type-2 BB in 3 eyes. The maximum pressure reached to create a BB was 96.25+/- 21.61 kpa; the mean type-1 intrabubble pressure was 10.16 +/- 3.65 kpa. The mean bursting pressure of a type-1 BB was 66.65 +/- 18.65 kpa, while that of a type-2 BB was 14.77 +/- 2.44 kpa. The volume of air required to create a type-1 BB was 0.54 ml and the volume of a type-1 BB was consistently 0.1 ml.ConclusionsDua's layer baring DALK can withstand high intraoperative pressures compared to Descemet's membrane baring DALK. The study suggests that it could be safe to undertake procedures such as DALK-triple with a type-1 BB but not with a type-2 BB.

Doses from beta radiation in sensitive layers of human lung and dose conversion factors due to 222Rn/220Rn progeny.

PubMed

Markovic, V M; Stevanovic, N; Nikezic, D

2011-08-01

Great deal of work has been devoted to determine doses from alpha particles emitted by (222)Rn and (220)Rn progeny. In contrast, contribution of beta particles to total dose has been neglected by most of the authors. The present work describes a study of the detriment of (222)Rn and (220)Rn progeny to the human lung due to beta particles. The dose conversion factor (DCF) was introduced to relate effective dose and exposure to radon progeny; it is defined as effective dose per unit exposure to inhaled radon or thoron progeny. Doses and DCFs were determined for beta radiation in sensitive layers of bronchi (BB) and bronchioles (bb), taking into account inhaled (222)Rn and (220)Rn progeny deposited in mucus and cilia layer. The nuclei columnar secretory and short basal cells were considered to be sensitive target layers. For dose calculation, electron-absorbed fractions (AFs) in the sensitive layers of the BB and bb regions were used. Activities in the fast and slow mucus of the BB and bb regions were obtained using the LUNGDOSE software developed earlier. Calculated DCFs due to beta radiation were 0.21 mSv/WLM for (222)Rn and 0.06 mSv/WLM for (220)Rn progeny. In addition, the influence of Jacobi room parameters on DCFs was investigated, and it was shown that DCFs vary with these parameters by up to 50%.

Lithospheric structure of an incipient rift basin: Results from receiver function analysis of Bransfield Strait, NW Antarctic Peninsula

NASA Astrophysics Data System (ADS)

Biryol, C. Berk; Lee, Stephen J.; Lees, Jonathan M.; Shore, Michael J.

2018-06-01

Bransfield Basin (BB), located northwest of the Antarctic Peninsula (AP) and southeast of the South Shetland Islands (SSI), is the most active section of the Antarctic continental margin. The region has long been (50 Ma) a convergent plate boundary where the Phoenix plate was subducting beneath the Antarctic Plate and is characterized by long-lived arc magmatism and accretion. However, the collision of the Antarctic-Phoenix spreading center with the subduction front near SSI (ca. 4 Ma) gave way to the opening of slab windows and dramatic decrease in the subduction rate of the Phoenix plate beneath AP and SSI. Consequently, the Phoenix slab began to rollback slowly along the South Shetland Trench (SST), giving way to slow extension in the back-arc region and rifting along the BB. Although there is consensus on the factors that control the current deformation and extension of the BB, the origin of the BB and the tectonic configuration of the basin are still unclear. Most of the controversy stems from uncertainties regarding the crustal thickness of the BB. Hence, we computed teleseismic receiver functions for 10 broadband stations in the region that belong to existing permanent and temporary deployments in order obtain robust constraints on the lithospheric structure and crustal thickness of the BB, as well as the AP and SSI. Our results indicate that the crust is thinning from 30 km to 26 km from the AP towards the South Shetland trench and Central BB showing the asymmetrical character of the rift basin. The crustal thickness and Vp/Vs variations are less pronounced along the AP but very significant across the SSB indicating the lithospheric scale segmentation of the South Shetland Block (SSB) and the incipient rift basin under the control of the opening of slab window and the roll-back of stalled Phoenix slab. High Vp/Vs ratios (∼1.9) beneath BB and SSI, agree well with the nascent rift character of BB, the presence of a steep Phoenix slab and consequently a wider mantle wedge characterized by the presence of underplating partial melts beneath SSI and BB.

AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists

PubMed Central

Moody, Terry W.; Tashakkori, Nicole; Mantey, Samuel A.; Moreno, Paola; Ramos-Alvarez, Irene; Leopoldo, Marcello; Jensen, Robert T.

2017-01-01

While peptide antagonists for the gastrin-releasing peptide receptor (BB2R), neuromedin B receptor (BB1R), and bombesin (BB) receptor subtype-3 (BRS-3) exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA)1 binds with high affinity to the BB1R, BB2R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB1R, BB2R, and BRS-3 with similar affinity (Ki = 1.4–10.8 µM). AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca2+ in human lung cancer cells transfected with BB1R, BB2R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists. PMID:28785244

AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists.

PubMed

Moody, Terry W; Tashakkori, Nicole; Mantey, Samuel A; Moreno, Paola; Ramos-Alvarez, Irene; Leopoldo, Marcello; Jensen, Robert T

2017-01-01

While peptide antagonists for the gastrin-releasing peptide receptor (BB 2 R), neuromedin B receptor (BB 1 R), and bombesin (BB) receptor subtype-3 (BRS-3) exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA)1 binds with high affinity to the BB 1 R, BB 2 R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB 1 R, BB 2 R, and BRS-3 with similar affinity ( K i = 1.4-10.8 µM). AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca 2+ in human lung cancer cells transfected with BB 1 R, BB 2 R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists.

Metastasis Risk Reduction Related with Beta-Blocker Treatment in Mexican Women with Breast Cancer.

PubMed

Parada-Huerta, E; Alvarez-Dominguez, Tp; Uribe-Escamilla, R; Rodriguez-Joya, Jf; Ponce-Medrano, Ja Diaz; Padron-Lucio, S; Alfaro-Rodriguez, A; Bandala, C

2016-01-01

Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked β2-adrenergic receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel- Haenszel, Student t, and ANOVA tests were performed for data analysis. On average, patients were 54.8±11.8 years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for β1 - and β2 -adrenergic-receptors did not present metastasis globally, but patients treated with β1 BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. In Mexican patients with BCa and SAH treated with non-selective (β1- and β2-adrenergic receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.

Flocculation of high purity wheat straw soda lignin.

PubMed

Piazza, G J; Lora, J H; Garcia, R A

2014-01-01

In industrial process, acidification causes non-sulfonated lignin insolubility. The flocculants poly(diallyldimethylammonium chloride) (pDADMAC) and bovine blood (BB) also caused lignin insolubility while cationic polyacrylamide, chitosan, and soy protein PF 974 were ineffective. Turbidity determined optimal flocculant, but turbidity magnitude with BB was greater than expected. pDADMAC caused negative lignin Zeta potential to became positive, but BB-lignin Zeta potential was always negative. Insoluble lignin did not gravity sediment, and flocculant-lignin mixtures were centrifuged. Pellet and supernatant dry mass and corrected spectroscopic results were in good agreement for optimal pDADMAC and BB. Spectroscopy showed 87-92% loss of supernatant lignin. Nitrogen analysis showed BB concentrated in the pellet until the pellet became saturated with BB. Subtracting ash and BB mass from pellet and supernatant mass confirmed optimal BB. Low levels of alum caused increased lignin flocculation at lower levels of pDADMAC and BB, but alum did not affect optimal flocculant. Published by Elsevier Ltd.

Association between vitamin D receptor BsmI polymorphism and bone mineral density in pediatric patients: A meta-analysis and systematic review of observational studies.

PubMed

Bao, Li; Chen, Mingzhi; Lei, Yong; Zhou, Zemin; Shen, Huiping; Le, Feng

2017-04-01

Vitamin D and the vitamin D receptor (VDR) are important in the metabolic processes that affect bone mineral density (BMD). However, the effect of VDR BsmI polymorphism on BMD in pediatric patients is still unclear. Eligible studies were identified from the following electronic databases: PubMed, Embase, the Cochrane Library, and the Chinese CNKI and Wanfang databases before October 1, 2016. Data were extracted from the eligible studies, and associations between VDR BsmI polymorphism and BMD in pediatric patients were estimated with weighted mean differences (WMDs) and 95% confidence intervals (CIs). Subgroup analysis of ethnicity and sensitivity analyses were used to identify sources of heterogeneity. A significant difference was observed between VDR BsmI polymorphism and pediatric BMD levels of the lumbar spine (LS) in the corecessive model (bb vs BB + Bb: WMD = -0.23, 95% CI [-0.35, -0.11], P < 0.01). No significant relationship was found in the dominant, recessive, or codominant models for LS BMD (BB vs Bb: WMD = -0.56, 95% CI [-1.58, 0.46], P = 0.29; BB vs bb: WMD = -0.54, 95% CI [-1.49, 0.41], P = 0.27; and BB vs Bb + bb: WMD = -0.45, 95% CI [-1.71, 0.26], P = 0.22). In addition, we found no remarkable association between the BsmI polymorphism and BMD levels of the femoral neck (FN) in children (BB vs Bb: WMD = -1.08, 95% CI [-3.13, 0.96], P = 0.30; BB vs bb: WMD = 0.98, 95% CI [-0.89, 2.85], P = 0.31; BB vs Bb + bb: WMD = -0.061, 95% CI [-0.30, 0.17], P = 0.61; and bb vs BB + Bb: WMD = 0.82, 95% CI [-0.59, 2.32], P = 0.25). Our meta-analysis found that the VDR BsmI genetic polymorphism was correlated with LS BMD level in pediatric patients: compared with those with the B allele, children with the bb genotype were less likely to have lower BMD levels. No significant difference was identified in the pediatric FN BMD levels.

Precision blackbody sources for radiometric standards.

PubMed

Sapritsky, V I; Khlevnoy, B B; Khromchenko, V B; Lisiansky, B E; Mekhontsev, S N; Melenevsky, U A; Morozova, S P; Prokhorov, A V; Samoilov, L N; Shapoval, V I; Sudarev, K A; Zelener, M F

1997-08-01

The precision blackbody sources developed at the All-Russian Institute for Optical and Physical Measurements (Moscow, Russia) and their characteristics are analyzed. The precision high-temperature graphite blackbody BB22p, large-area high-temperature pyrolytic graphite blackbody BB3200pg, middle-temperature graphite blackbody BB2000, low-temperature blackbody BB300, and gallium fixed-point blackbody BB29gl and their characteristics are described.

Demonstration of 1-year duration of immunity for attenuated Bordetella bronchiseptica vaccines in dogs.

PubMed

Lehar, Craig; Jayappa, Huchappa; Erskine, Jason; Brown, Alicia; Sweeney, Diane; Wassmoen, Terri

2008-01-01

Three groups of healthy dogs with low antibody titers to Bordetella bronchiseptica (Bb), canine parainfluenza virus (CPI), and canine adenovirus type 2 (CAV-2) were used in this study. One group was vaccinated with a single dose of monovalent attenuated Bb vaccine and one group with a trivalent vaccine containing attenuated Bb, CPI, and CAV-2; dogs were vaccinated intranasally with a single dose of the respective vaccines. The third group served as unvaccinated controls. All vaccinated dogs subsequently developed serum antibody titers to Bb that persisted for at least 1 year. Following Bb challenge 1 year after vaccination, all vaccinated dogs, regardless of group, showed significantly fewer clinical signs and shed significantly fewer challenge organisms than unvaccinated controls. These results demonstrate that intranasal administration of a single dose of monovalent attenuated Bb vaccine or trivalent vaccine containing attenuated Bb, CPI, and CAV-2 provides 1 year of protection against Bb.

Velocity specificity of training in bodybuilders.

PubMed

Bell, D G; Jacobs, I

1992-03-01

This study investigated the effects of many years of bodybuilding on muscular strength and endurance. Eight bodybuilders (BB), 4 males and 4 females, and 8 controls (C), 4 males and 4 females, performed a muscle fatigue test (MFT) consisting of 25 maximal leg extensions at angular velocities of 180 and 300 degrees/s. The results for strength showed that at both the slow and fast contraction speeds, BB were significantly stronger than C and males were significantly stronger than females. For muscular endurance the results showed that at the slow contraction speed the torques and torque decline were greater in the BB than in the C, and greater in the males than the females. At the faster contraction speed, torque decline was similar in all groups while torques for the BB and male-C were similar and significantly greater than the torques for the female-C. The ratio of torques (fast/slow) for both strength and muscular endurance showed a main effect due to training status which supported the velocity specificity hypothesis. However, when the relative torques over the 25 contractions at both speeds were looked at, no velocity specificity occurred for muscular endurance. The data suggest a definite velocity specificity for the strength factor in BB whereas the same conclusion is not as clear for the muscular endurance factor.

4-1BB Aptamer-Based Immunomodulation Enhances the Therapeutic Index of Radiation Therapy in Murine Tumor Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benaduce, Ana Paula; Brenneman, Randall; Schrand, Brett

Purpose: To report a novel strategy using oligonucleotide aptamers to 4-1BB as an alternate method for costimulation, and show that combinatorial therapy with radiation improves the therapeutic ratio over equivalent monoclonal antibodies. Methods and Materials: Subcutaneous 4T1 (mouse mammary carcinoma) tumors were established (approximately 100 mm{sup 3}), and a radiation therapy (RT) dose/fractionation schedule that optimally synergizes with 4-1BB monoclonal antibody (mAb) was identified. Comparable tumor control and animal survival was observed when either 4-1BB antibody or aptamer were combined with RT using models of breast cancer and melanoma (4T1 and B16-F10). Off-target CD8{sup +} T-cell toxicity was evaluated by quantification ofmore » CD8{sup +} T cells in livers and spleens of treated animals. Results: When combined with 4-1BB mAb, significant differences in tumor control were observed by varying RT dose and fractionation schedules. Optimal synergy between RT and 4-1BB mAb was observed at 5 Gy × 6. Testing 4-1BB mAb and aptamer independently using the optimal RT (5 Gy × 6 for 4T1/Balb/c and 12 Gy × 1 for B16/C57BL6J mouse models) revealed equivalent tumor control using 4-1BB aptamer and 4-1BB mAb. 4-1BB mAb, but not 4-1BB aptamer-treated animals, exhibited increased lymphocytic liver infiltrates and increased splenic and liver CD8{sup +} T cells. Conclusions: Radiation therapy synergizes with 4-1BB mAb, and this effect is dependent on RT dose and fractionation. Tumor control by 4-1BB aptamer is equivalent to 4-1BB mAb when combined with optimal RT dose, without eliciting off-target liver and spleen CD8{sup +} expansion. 4-1BB aptamer-based costimulation affords a comparable and less toxic strategy to augment RT-mediated tumor control.« less

Feeder-free differentiation of cells exhibiting characteristics of corneal endothelium from human induced pluripotent stem cells.

PubMed

Wagoner, Michael D; Bohrer, Laura R; Aldrich, Benjamin T; Greiner, Mark A; Mullins, Robert F; Worthington, Kristan S; Tucker, Budd A; Wiley, Luke A

2018-05-08

The purpose of this study was to devise a strategy for the derivation of corneal endothelial cells (CEnCs) from adult fibroblast-derived induced pluripotent stem cells (iPSCs). IPSCs were generated from an adult human with normal ocular history via expression of OCT4 , SOX2 , KLF4 and c-MYC Neural crest cells (NCCs) were differentiated from iPSCs via addition of CHIR99021 and SB4315542. NCCs were driven toward a CEnC fate via addition of B27, PDGF-BB and DKK-2 to CEnC media. Differentiation of NCCs and CEnCs was evaluated via rt-PCR, morphological and immunocytochemical analysis. At 17 days post-NCC induction, there were notable changes in cell morphology and upregulation of the neural crest lineage transcripts PAX3 , SOX9 , TFAP2A , SOX10 and p75NTR and the proteins p75/NGFR and SOX10. Exposure of NCCs to B27, PDGF-BB and DKK-2 induced a shift in morphology from a spindle-shaped neural phenotype to a tightly-packed hexagonal appearance and increased expression of the transcripts ATP1A1 , COL8A1 , COL8A2 , AQP1 and CDH2 and the proteins ZO-1, N-Cad, AQP-1 and Na + /K + ATPase. Replacement of NCC media with CEnC media on day 3, 5 or 8 reduced the differentiation time needed to yield CEnCs. IPSC-derived CEnCs could be used for evaluation of cornea endothelial disease pathophysiology and for testing of novel therapeutics. © 2018. Published by The Company of Biologists Ltd.

Transferrin Receptor 1 in Chronic Hypoxia-Induced Pulmonary Vascular Remodeling.

PubMed

Naito, Yoshiro; Hosokawa, Manami; Sawada, Hisashi; Oboshi, Makiko; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Nishimura, Koichi; Soyama, Yuko; Fujii, Kenichi; Mano, Toshiaki; Ishihara, Masaharu; Tsujino, Takeshi; Masuyama, Tohru

2016-06-01

Iron is associated with the pathophysiology of several cardiovascular diseases, including pulmonary hypertension (PH). In addition, disrupted pulmonary iron homeostasis has been reported in several chronic lung diseases. Transferrin receptor 1 (TfR1) plays a key role in cellular iron transport. However, the role of TfR1 in the pathophysiology of PH has not been well characterized. In this study, we investigate the role of TfR1 in the development of hypoxia-induced pulmonary vascular remodeling. PH was induced by exposing wild-type (WT) mice and TfR1 hetero knockout mice to hypoxia for 4 weeks and evaluated via assessment of pulmonary vascular remodeling, right ventricular (RV) systolic pressure, and RV hypertrophy. In addition, we assessed the functional role of TfR1 in pulmonary artery smooth muscle cells in vitro. The morphology of pulmonary arteries did not differ between WT mice and TfR1 hetero knockout mice under normoxic conditions. In contrast, TfR1 hetero knockout mice exposed to 4 weeks hypoxia showed attenuated pulmonary vascular remodeling, RV systolic pressure, and RV hypertrophy compared with WT mice. In addition, the depletion of TfR1 by RNA interference attenuated human pulmonary artery smooth muscle cells proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in vitro. These results suggest that TfR1 plays an important role in the development of hypoxia-induced pulmonary vascular remodeling. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Association between VDR gene polymorphisms and HOMA index for prediabetes in Ningxia].

PubMed

Liao, Sha; He, Jun; Li, Xiaoxia; Xu, Honexia; Liu, Xiuying; Zhao, Yi; Zhang, Yuhong

2016-03-01

To explore the association between the vitamin D receptor (VDR) gene polymorphisms and HOMA index in prediabetes. On the basis of a cross-sectional study which was conducted in Ningxia during 2008-2012, 339 controls and 468 subjects with prediabetes were selected according to ADA diabetes diagnosis standards. Anthropometric data and blood samples were collected in the field investigation. Blood biochemistry analyses and insulin determination were carried out in the laboratory. The whole blood DNA was extracted for genotyping. The BMI, WC, FPG and HOMA-IR of individuals with prediabetes were higher than those of the controls, while the HOMA-B and HOMA-S in cases were lower than those of the controls (P < 0.05). In BsmI, individuals with prediabetes carrying genotype BB/Bb showed lower HOMA-B than bb carrier, and they showed significantly higher HOMA-S than bb carriers (P < 0.05). After adjusting age, sex, BMI, TC, TG and SBP, low level HOMA-B index was the risk factor of prediabetes in individuals who carried genotype BB/Bb for BsmI and genotype FF/Ff/ff for FokI (OR > 1 , P < 0.05 ), and the genotype ff got the highest risk level (OR = 10.59). In FokI, the Ff carriers with low level HOMA-S and HOM-IR were also the risk factors of prediabetes (OR > 1, P < 0.05). The VDR gene polymorphisms appeared to be associated with HOMA index in prediabetes. The BsmI polymorphism seemed to influence HOMA-B, while the FokI polymorphism influence HOMA-B and HOMA-IR at different levels.

Emission factors for open and domestic biomass burning for use in atmospheric models

Treesearch

S. K. Akagi; R. J. Yokelson; C. Wiedinmyer; M. J. Alvarado; J. S. Reid; T. Karl; J. D. Crounse; P. O. Wennberg

2010-01-01

Biomass burning (BB) is the second largest source of trace gases and the largest source of primary fine carbonaceous particles in the global troposphere. Many recent BB studies have provided new emission factor (EF) measurements. This is especially 5 true for non methane organic compounds (NMOC), which influence secondary organic aerosol (SOA) and ozone formation. New...

Effects of Bobath-based therapy on depression, shoulder pain and health-related quality of life in patients after stroke.

PubMed

Hafsteinsdóttir, Thóra B; Kappelle, Jaap; Grypdonck, Maria H F; Algra, Ale

2007-10-01

To measure the effects of Bobath-based (BB) therapy on depression, shoulder pain and health-related quality of life (HRQoL) of patients during one year after stroke. In a prospective, non-randomized design, the use of BB therapy was compared with a more task-oriented therapy and no BB therapy. A total of 324 patients in 12 hospitals. Patients in the intervention group received BB therapy, whereas patients in the control group received no BB therapy and a more task-oriented therapy. HRQoL was measured using the SF-36; depression was measured with the Center of Epidemiological Studies Depression Scale and shoulder pain was measured with the Visual Analogue Scale at discharge, 6 and 12 months. Linear and logistic regression analyses were performed. No effects of BB therapy on HRQoL or shoulder pain were found. After one year fewer patients were depressed in the BB group (30%) than in the non-BB group (43%); the adjusted odds ratio was 0.6 (95% confidence interval 0.3-1.0). BB therapy did not have any effect on HRQoL or shoulder pain in stroke patients. Healthcare professionals should reconsider the use of BB therapy in the care of stroke patients.

Small molecule receptor tyrosine kinase inhibitor of platelet-derived growth factor signaling (SU9518) modifies radiation response in fibroblasts and endothelial cells

PubMed Central

Li, Minglun; Ping, Gong; Plathow, Christian; Trinh, Thuy; Lipson, Kenneth E; Hauser, Kai; Krempien, Robert; Debus, Juergen; Abdollahi, Amir; Huber, Peter E

2006-01-01

Background Several small receptor tyrosine kinase inhibitors (RTKI) have entered clinical cancer trials alone and in combination with radiotherapy or chemotherapy. The inhibitory spectrum of these compounds is often not restricted to a single target. For example Imatinib/Gleevec (primarily a bcr/abl kinase inhibitor) or SU11248 (mainly a VEGFR inhibitor) are also potent inhibitors of PDGFR and other kinases. We showed previously that PDGF signaling inhibition attenuates radiation-induced lung fibrosis in a mouse model. Here we investigate effects of SU9518, a PDGFR inhibitor combined with ionizing radiation in human primary fibroblasts and endothelial cells in vitro, with a view on utilizing RTKI for antifibrotic therapy. Methods Protein levels of PDGFR-α/-β and phosphorylated PDGFR in fibroblasts were analyzed using western and immunocytochemistry assays. Functional proliferation and clonogenic assays were performed (i) to assess PDGFR-mediated survival and proliferation in fibroblasts and endothelial cells after SU9518 (small molecule inhibitor of PDGF receptor tyrosine kinase); (ii) to test the potency und selectivity of the PDGF RTK inhibitor after stimulation with PDGF isoforms (-AB, -AA, -BB) and VEGF+bFGF. In order to simulate in vivo conditions and to understand the role of radiation-induced paracrine PDGF secretion, co-culture models consisting of fibroblasts and endothelial cells were employed. Results In fibroblasts, radiation markedly activated PDGF signaling as detected by enhanced PDGFR phosphorylation which was potently inhibited by SU9518. In fibroblast clonogenic assay, SU9518 reduced PDGF stimulated fibroblast survival by 57%. Likewise, SU9518 potently inhibited fibroblast and endothelial cell proliferation. In the co-culture model, radiation of endothelial cells and fibroblast cells substantially stimulated proliferation of non irradiated fibroblasts and vice versa. Importantly, the RTK inhibitor significantly inhibited this paracrine radiation-induced fibroblast and endothelial cell activation. Conclusion Radiation-induced autocrine and paracrine PDGF signaling plays an important role in fibroblast and endothelial cell proliferation. SU9518, a PDGFR tyrosine kinase inhibitor, reduces radiation-induced fibroblast and endothelial cell activation. This may explain therapeutic anticancer effects of Imatinib/Gleevec, and at the same time it could open a way of attenuating radiation-induced fibrosis. PMID:16556328

Improved survival of baby boomer women with early-stage uterine cancer: A Surveillance, Epidemiology and End Results (SEER) Study.

PubMed

Elshaikh, Mohamed A; Ruterbusch, Julie; Cote, Michele L; Cattaneo, Richard; Munkarah, Adnan R

2013-11-01

To study the prognostic impact of baby boomer (BB) generation on survival end-points of patients with early-stage endometrial carcinoma (EC). Data were obtained from the SEER registry between 1988-2009. Inclusion criteria included women who underwent hysterectomy for stage I-II EC. Patients were divided into two birth cohorts: BB (women born between 1946 and 1964) and pre-boomers (PB) (born between 1926 and 1945). A total of 30,956 patients were analyzed. Considering that women in the PB group were older than those of the BB generation, the statistical analysis was limited to women 50-59 years of age at the time of diagnosis (n=11,473). Baby boomers had a significantly higher percentage of endometrioid histology (p<0.0001), higher percentage of African American women (p<0.0001), lower tumor grade (p<0.0001), higher number of dissected lymph nodes (LN) (p<0.0001), and less utilization of adjuvant radiation therapy (p=0.0003). Overall survival was improved in women in the BB generation compared to the PB generation (p=0.0003) with a trend for improved uterine cancer-specific survival (p=0.0752). On multivariate analysis, birth cohort (BB vs. PB) was not a significant predictor of survival end-points. Factors predictive of survival included: tumor grade, FIGO stage, African-American race, and increased number of dissected LN. Our study suggests that the survival of BB women between 50-60 years of age is better compared to women in the PB generation. As more BB patients are diagnosed with EC, further research is warranted.

Bone repair of critical size defects treated with mussel powder associated or not with bovine bone graft: histologic and histomorphometric study in rat calvaria.

PubMed

Trotta, Daniel Rizzo; Gorny, Clayton; Zielak, João César; Gonzaga, Carla Castiglia; Giovanini, Allan Fernando; Deliberador, Tatiana Miranda

2014-09-01

The objective of this study was to evaluate the bone repair of critical size defects treated with mussel powder with or without additional bovine bone. Critical size defects of 5 mm were realized in the calvaria of 70 rats, which were randomly divided in 5 groups - Control (C), Autogenous Bone (AB), Mussel Powder (MP), Mussel Powder and Bovine Bone (MP-BB) and Bovine Bone (BB). Histological and histomorphometric analysis were performed 30 and 90 days after the surgical procedures (ANOVA e Tukey p < 0.05). After 30 days, the measures of remaining particles were: 28.36% (MP-BB), 26.63% (BB) and 8.64% (MP) with a statistically significant difference between BB and MP. The percentage of osseous matrix after 30 days was, AB (55.17%), 23.31% (BB), 11.66% (MP) and 10.71% (MP-BB) with statistically significant differences among all groups. After 90 days the figures were 25.05% (BB), 21.53% (MP-BB) and 1.97% (MP) with statistically significant differences between MP-BB and MP. Percentages of new bone formation after 90 days were 89.47% (AB), 35.70% (BB), 26.48% (MP-BB) and 7.37% (MP) with statistically significant differences between AB and the other groups. Within the limits of this study, we conclude that mussel powder, with or without additional bovine bone, did not induce new bone formation and did not repair critical size defects in rat calvaria. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Optical coherence tomography characteristics of different types of big bubbles seen in deep anterior lamellar keratoplasty by the big bubble technique

PubMed Central

AlTaan, S L; Termote, K; Elalfy, M S; Hogan, E; Werkmeister, R; Schmetterer, L; Holland, S; Dua, H S

2016-01-01

Purpose To define optical coherence tomography (OCT) characteristics of type-1, type-2, and mixed big bubbles (BB) seen in deep anterior lamellar keratoplasty. Methods Human sclero-corneal discs were obtained from UK (30) and Canada (16) eye banks. Air was injected into corneal stroma until a BB formed. UK samples were fixed in formalin before scanning with Fourier-domain (FD-OCT). One pair of each type of BB was scanned fresh. All BB obtained from Canada were scanned fresh with time-domain (TD-OCT). For each OCT machine used, type-1 BB from which Descemets membrane (DM) was partially peeled, were also scanned. The morphological characteristics of the scans were studied. Results FD-OCT of the posterior wall of type-1 (Dua's layer (DL) with DM) and type-2 BB (DM alone) both revealed a double-contour hyper-reflective curvilinear image with a hypo-reflective zone in between. The anterior line of type-2 BB was thinner than that seen with type-1 BB. In mixed BB, FD-OCT showed two separate curvilinear images. The anterior image was a single hyper-reflective line (DL), whereas the posterior image, representing the posterior wall of type-2 BB (DM) was made of two hyper-reflective lines with a dark space in between. TD-OCT images were similar with less defined component lines, but the entire extent of the BB could be visualised. Conclusion On OCT examination the DM and DL present distinct features, which can help identify type-1, type-2, and mixed BB. These characteristics will help corneal surgeons interpret intraoperative OCT during lamellar corneal surgery. PMID:27472215

Validation of Improved Broadband Shortwave and Longwave Fluxes Derived From GOES

NASA Technical Reports Server (NTRS)

Khaiyer, Mandana M.; Nordeen, Michele L.; Palikonda, Rabindra; Yi, Yuhong; Minnis, Patrick; Doelling, David R.

2009-01-01

Broadband (BB) shortwave (SW) and longwave (LW) fluxes at TOA (Top of Atmosphere) are crucial parameters in the study of climate and can be monitored over large portions of the Earth's surface using satellites. The VISST (Visible Infrared Solar Split-Window Technique) satellite retrieval algorithm facilitates derivation of these parameters from the Geostationery Operational Environmental Satellites (GOES). However, only narrowband (NB) fluxes are available from GOES, so this derivation requires use of narrowband-to-broadband (NB-BB) conversion coefficients. The accuracy of these coefficients affects the validity of the derived broadband (BB) fluxes. Most recently, NB-BB fits were re-derived using the NB fluxes from VISST/GOES data with BB fluxes observed by the CERES (Clouds and the Earth's Radiant Energy Budget) instrument aboard Terra, a sun-synchronous polar-orbiting satellite that crosses the equator at 10:30 LT. Subsequent comparison with ARM's (Atmospheric Radiation Measurement) BBHRP (Broadband Heating Rate Profile) BB fluxes revealed that while the derived broadband fluxes agreed well with CERES near the Terra overpass times, the accuracy of both LW and SW fluxes decreased farther away from the overpass times. Terra's orbit hampers the ability of the NB-BB fits to capture diurnal variability. To account for this in the LW, seasonal NB-BB fits are derived separately for day and night. Information from hourly SW BB fluxes from the Meteosat-8 Geostationary Earth Radiation Budget (GERB) is employed to include samples over the complete solar zenith angle (SZA) range sampled by Terra. The BB fluxes derived from these improved NB-BB fits are compared to BB fluxes computed with a radiative transfer model.

Spatial and temporal variability of carbonaceous aerosols: Assessing the impact of biomass burning in the urban environment.

PubMed

Titos, G; Del Águila, A; Cazorla, A; Lyamani, H; Casquero-Vera, J A; Colombi, C; Cuccia, E; Gianelle, V; Močnik, G; Alastuey, A; Olmo, F J; Alados-Arboledas, L

2017-02-01

Biomass burning (BB) is a significant source of atmospheric particles in many parts of the world. Whereas many studies have demonstrated the importance of BB emissions in central and northern Europe, especially in rural areas, its impact in urban air quality of southern European countries has been sparsely investigated. In this study, highly time resolved multi-wavelength absorption coefficients together with levoglucosan (BB tracer) mass concentrations were combined to apportion carbonaceous aerosol sources. The Aethalometer model takes advantage of the different spectral behavior of BB and fossil fuel (FF) combustion aerosols. The model was found to be more sensitive to the assumed value of the aerosol Ångström exponent (AAE) for FF (AAE ff ) than to the AAE for BB (AAE bb ). As result of various sensitivity tests the model was optimized with AAE ff =1.1 and AAE bb =2. The Aethalometer model and levoglucosan tracer estimates were in good agreement. The Aethalometer model was further applied to data from three sites in Granada urban area to evaluate the spatial variation of CM ff and CM bb (carbonaceous matter from FF or BB origin, respectively) concentrations within the city. The results showed that CM bb was lower in the city centre while it has an unexpected profound impact on the CM levels measured in the suburbs (about 40%). Analysis of BB tracers with respect to wind speed suggested that BB was dominated by sources outside the city, to the west in a rural area. Distinguishing whether it corresponds to agricultural waste burning or with biomass burning for domestic heating was not possible. This study also shows that although traffic restrictions measures contribute to reduce carbonaceous concentrations, the extent of the reduction is very local. Other sources such as BB, which can contribute to CM as much as traffic emissions, should be targeted to reduce air pollution. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative efficacy of intranasal and injectable vaccines in stimulating Bordetella bronchiseptica-reactive anamnestic antibody responses in household dogs

PubMed Central

Ellis, John A.; Gow, Sheryl P.; Lee, Lindsey B.; Lacoste, Stacey; Ball, Eileen C.

2017-01-01

In order to determine the comparative efficacy of injectable and intranasal vaccines to stimulate Bordetella bronchiseptica (Bb)-reactive anamnestic antibodies, a trial was conducted using 144 adult household dogs of various breeds and ages, which had been previously administered intranasal Bb vaccine approximately 12 months before enrollment. Dogs were randomized into 2 groups and blood, nasal swabs, and pharyngeal swabs were collected prior to the administration of single component Bb vaccines intranasally or parenterally. Ten to 14 days later all dogs were resampled to measure changes in systemic and local antibody to Bb. There were no differences in the changes in Bb-reactive serum IgG and nasal IgA between the groups, whereas intranasally vaccinated dogs had significantly higher Bb-reactive serum IgA. These data indicate that both of the current generation of intranasal (modified-live) and injectable (acellular) Bb vaccines can stimulate anamnestic local and systemic antibody responses in previously vaccinated, Bb-seropositive adult household dogs. PMID:28761185

Management of BB shot wounds to the heart.

PubMed

Thompson, E C; Block, E F; Mancini, M C

1996-01-01

The aim of this study was to review our experience with BB shot injuries to the heart. This is a retrospective chart review. Three patients were found to have BB injuries to the heart. All patients were stable upon presentation. Echocardiography localized the BB pellets to the muscular septum. All patients were treated with nonoperative therapy. There was not mortality. One patient developed an interventricular conduction delay that resolved before discharge. Nonoperative management of stable patients who present with BB wounds to the heart is safe and effective if the BB is intramuscular. An echocardiogram should be used to localize the pellets and evaluate the pericardium.

Electroluminescent TCC, C3dg and fB/Bb epitope assays for profiling complement cascade activation in vitro using an activated complement serum calibration standard.

PubMed

van Vuuren, B Jansen; Bergseth, G; Mollnes, T E; Shaw, A M

2014-01-15

Electroluminescent assays for epitopes on the complement components C3dg, terminal complement complex (TCC) and factor B/Bb (fB/Bb) have been developed with capture and detection antibodies to produce detection limits C3dg=91±9ng/mL, TCC=3±0.1ng/mL and fB=55.7±0.1ng/mL. The assay performance was assessed against a series of zymosan and heat aggregated IgG (HAIgG) in vitro activations of complement using a calibrated activated complement serum (ACS) as calibration standard. The ACS standard was stable within 20% accuracy over a 6-month period with freeze-thaw cycles as required. Differential activation of the complement cascade was observed for TCC showing a pseudo-first order formation half-life of 3.5h after activation with zymosan. The C3dg activation fragment indicates a 10% total activation for both activation agents. The kinetic-epitope analysis for fB indicates that the capture epitope is on the fB/Bb protein fragment which can then become covered by the formation of C3bBb or C3bBbP complexes during the time course of the cascade. Copyright © 2013 Elsevier B.V. All rights reserved.

[Creatine kinase BB and lactate in the cerebrospinal fluid of neonates and infants with perinatal injuries of the CNS].

PubMed

Alatyrtsev, V V; Iakunin, Iu A; Burkova, A S; Podkopaev, V N; Afonina, L G

1989-01-01

A study was made of the content of creatine kinase-BB (CK-BB) and lactate in cerebrospinal fluid (CSF) of 202 neonates and infants with perinatal CNS injuries. The relationship was found between the rise of the CK-BB content and the gravity of perinatal CNS injuries. The highest content of CK-BB in CSF was marked in neonates with cerebral disorders complicated by infectious and inflammatory diseases (pneumonia, sepsis). Within the first 5 days of life, the children of this group demonstrated the relationship between the content of CK-BB and lactate of CSF. The measurement of the content of CK-BB in CSF should be used for early diagnosis, assessment of the gravity and course of perinatal CNS injuries in neonates and in infants.

Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice.

PubMed

Almeida-Reis, Rafael; Theodoro-Junior, Osmar A; Oliveira, Bruno T M; Oliva, Leandro V; Toledo-Arruda, Alessandra C; Bonturi, Camila R; Brito, Marlon V; Lopes, Fernanda D T Q S; Prado, Carla M; Florencio, Ariana C; Martins, Mílton A; Owen, Caroline A; Leick, Edna A; Oliva, Maria L V; Tibério, Iolanda F L C

2017-01-01

Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.  C57BL / 6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNF α -, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2 α , collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNF α -positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease.

Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice

PubMed Central

Theodoro-Junior, Osmar A.; Oliveira, Bruno T. M.; Oliva, Leandro V.; Toledo-Arruda, Alessandra C.; Bonturi, Camila R.; Brito, Marlon V.; Prado, Carla M.; Florencio, Ariana C.; Martins, Mílton A.; Owen, Caroline A.; Oliva, Maria L. V.

2017-01-01

Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.  C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNFα-, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2α, collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNFα-positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease. PMID:28466019

Regulation of a phenylalanine ammonia lyase (BbPAL) by calmodulin in response to environmental changes in the entomopathogenic fungus Beauveria bassiana.

PubMed

Kim, Jiyoung; Park, Hyesung; Han, Jae-Gu; Oh, Junsang; Choi, Hyung-Kyoon; Kim, Seong Hwan; Sung, Gi-Ho

2015-11-01

Phenylalanine ammonia lyase (PAL, E.C. 4.3.1.5) catalyses the deamination of L -phenylalanine to trans-cinnamic acid and ammonia, facilitating a critical step in the phenylpropanoid pathway that produces a variety of secondary metabolites. In this study, we isolated BbPAL gene in the entomopathogenic fungus Beauveria bassiana. According to multiple sequence alignment, homology modelling and in vitro PAL activity, we demonstrated that BbPAL acts as a typical PAL enzyme in B. bassiana. BbPAL interacted with calmodulin (CaM) in vitro and in vivo, indicating that BbPAL is a novel CaM-binding protein. The functional role of CaM in BbPAL action was to negatively regulate the BbPAL activity in B. bassiana. High-performance liquid chromatography analysis revealed that L -phenylalanine was reduced and trans-cinnamic acid was increased in response to the CaM inhibitor W-7. Dark conditions suppressed BbPAL activity in B. bassiana, compared with light. In addition, heat and cold stresses inhibited BbPAL activity in B. bassiana. Interestingly, these negative effects of BbPAL activity by dark, heat and cold conditions were recovered by W-7 treatment, suggesting that the inhibitory mechanism is mediated through stimulation of CaM activity. Therefore, this work suggests that BbPAL plays a role in the phenylpropanoid pathway mediated by environmental stimuli via the CaM signalling pathway. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Comparison of MODIS and VIIRS On-board Blackbody Performance

NASA Technical Reports Server (NTRS)

Xiong, Jack; Butler, Jim; Wu, Aisheng; Chiang, Vincent; McIntire, Jeff; Oudari, Hassan

2012-01-01

MODIS has 16 thermal emissive bands (TEBs), covering wavelengths from 3.7 to 14.4 microns. MODIS TEBs are calibrated on-orbit by a v-grooved blackbody (BB) on a scan-by-scan basis. The BB temperatures are measured by a set of 12 thennistors. As expected, the BB temperature uncertainty and stability have direct impact on the quality of TEB calibration and, therefore, the quality of the science products derived from TEB observations. Since launch, Terra and Aqua MODIS have successfully operated for more than 12 and 10 years, respectively. Their on-board BB performance has been satisfactory in meeting the TEB calibration requirements. The first VIIRS, launched on-board the Suomi NPP spacecraft on October 28, 2011, has successfully completed its initial Intensive Calibration and Validation (ICV) phase. VIIRS has 7 thermal emissive bands (TEBs), covering wavelengths from 3.7 to 12.4 microns. Designed with strong MODIS heritage, VIIRS uses a similar BB for its TEB calibration. Like MODIS, VIIRS BB is nominally controlled at a pre-determined temperature (set point). Periodically, a BB Warm-Up and Cool-Down (WUCD) operation is performed, during which the BB temperatures vary from instrument ambient (temperature) to 315K. This paper examines NPP VIIRS BB on-orbit performance. It focuses on its BB temperature scan-to-scan variations at nominally controlled temperature as well as during its WUCD operation and their impact on TEB calibration uncertainty. Comparisons of VIIRS (NPP) and MODIS (Terra and Aqua) BB on-orbit performance and lessons learned for future improvements are also presented in this paper.

Dietary Blueberry Attenuates Whole-Body Insulin Resistance in High Fat-Fed Mice by Reducing Adipocyte Death and Its Inflammatory Sequelae1–3

PubMed Central

DeFuria, Jason; Bennett, Grace; Strissel, Katherine J.; Perfield, James W.; Milbury, Paul E.; Greenberg, Andrew S.; Obin, Martin S.

2009-01-01

Adipose tissue (AT) inflammation promotes insulin resistance (IR) and other obesity complications. AT inflammation and IR are associated with oxidative stress, adipocyte death, and the scavenging of dead adipocytes by proinflammatory CD11c+ AT macrophages (ATMΦ). We tested the hypothesis that supplementation of an obesitogenic (high-fat) diet with whole blueberry (BB) powder protects against AT inflammation and IR. Male C57Bl/6j mice were maintained for 8 wk on 1 of 3 diets: low-fat (10% of energy) diet (LFD), high-fat (60% of energy) diet (HFD) or the HFD containing 4% (wt:wt) whole BB powder (1:1 Vaccinium ashei and V. corymbosum) (HFD+B). BB supplementation (2.7% of total energy) did not affect HFD-associated alterations in energy intake, metabolic rate, body weight, or adiposity. We observed an emerging pattern of gene expression in AT of HFD mice indicating a shift toward global upregulation of inflammatory genes (tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein 1, inducible nitric oxide synthase), increased M1-polarized ATMΦ (CD11c+), and increased oxidative stress (reduced glutathione peroxidase 3). This shift was attenuated or nonexistent in HFD+B-fed mice. Furthermore, mice fed the HFD+B were protected from IR and hyperglycemia coincident with reductions in adipocyte death. Salutary effects of BB on adipocyte physiology and ATMΦ gene expression may reflect the ability of BB anthocyanins to alter mitogen-activated protein kinase and nuclear factor-κB stress signaling pathways, which regulate cell fate and inflammatory genes. These results suggest that cytoprotective and antiinflammatory actions of dietary BB can provide metabolic benefits to combat obesity-associated pathology. PMID:19515743

Particulate-phase mercury emissions from biomass burning and impact on resulting deposition: a modelling assessment

EPA Science Inventory

Mercury (Hg) emissions from biomass burning (BB) are an important source of atmospheric Hg and a major factor driving the interannual variation of Hg concentrations in the troposphere. The greatest fraction of Hg from BB is released in the form of elemental Hg (Hg0(g)). However, ...

Biodegradable electrospun nanofibers coated with platelet-rich plasma for cell adhesion and proliferation

PubMed Central

Díaz-Gómez, Luis; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Silva, Maite; Dominguez, Fernando; Sheikh, Faheem A.; Cantu, Travis; Desai, Raj; Garcia, Vanessa L.; Macossay, Javier

2014-01-01

Biodegradable electrospun poly(ε-caprolactone) (PCL) scaffolds were coated with platelet-rich plasma (PRP) to improve cell adhesion and proliferation. PRP was obtained from human buffy coat, and tested on human adipose-derived mesenchymal stem cells (MSC) to confirm cell proliferation and cytocompatibility. Then, PRP was adsorbed on the PCL scaffolds via lyophilization, which resulted in uniform sponge-like coating of 2.85 (s.d. 0.14) mg/mg. The scaffolds were evaluated regarding mechanical properties (Young’s modulus, tensile stress and tensile strain), sustained release of total protein and growth factors (PDGF-BB, TGF-β1 and VEGF), and hemocompatibility. MSC seeded on the PRP-PCL nanofibers showed an increased adhesion and proliferation compared to pristine PCL fibers. Moreover, the adsorbed PRP enabled angiogenesis features observed as neovascularization in a chicken chorioallantoic membrane (CAM) model. Overall, these results suggest that PRP-PCL scaffolds hold promise for tissue regeneration applications. PMID:24857481

Immunization with a Borrelia burgdorferi BB0172-Derived Peptide Protects Mice against Lyme Disease

PubMed Central

Small, Christina M.; Ajithdoss, Dharani K.; Rodrigues Hoffmann, Aline; Mwangi, Waithaka; Esteve-Gassent, Maria D.

2014-01-01

Lyme disease is the most prevalent arthropod borne disease in the US and it is caused by the bacterial spirochete Borrelia burgdorferi (Bb), which is acquired through the bite of an infected Ixodes tick. Vaccine development efforts focused on the von Willebrand factor A domain of the borrelial protein BB0172 from which four peptides (A, B, C and D) were synthesized and conjugated to Keyhole Limpet Hemocyanin, formulated in Titer Max® adjuvant and used to immunize C3H/HeN mice subcutaneously at days 0, 14 and 21. Sera were collected to evaluate antibody responses and some mice were sacrificed for histopathology to evaluate vaccine safety. Twenty-eight days post-priming, protection was evaluated by needle inoculation of half the mice in each group with 103 Bb/mouse, whereas the rest were challenged with 105Bb/mouse. Eight weeks post-priming, another four groups of similarly immunized mice were challenged using infected ticks. In both experiments, twenty-one days post-challenge, the mice were sacrificed to determine antibody responses, bacterial burdens and conduct histopathology. Results showed that only mice immunized with peptide B were protected against challenge with Bb. In addition, compared to the other the treatment groups, peptide B-immunized mice showed very limited inflammation in the heart and joint tissues. Peptide B-specific antibody titers peaked at 8 weeks post-priming and surprisingly, the anti-peptide B antibodies did not cross-react with Bb lysates. These findings strongly suggest that peptide B is a promising candidate for the development of a new DIVA vaccine (Differentiate between Infected and Vaccinated Animals) for protection against Lyme disease. PMID:24505447

Clinical and Genetic Modifiers of Long-term Survival in Heart Failure

PubMed Central

Cresci, Sharon; Kelly, Reagan J; Cappola, Thomas P; ScM; Diwan, Abhinav; Dries, Daniel; Kardia, Sharon LR; Dorn, Gerald W

2009-01-01

Objective To identify genetic modifiers of β-blocker (BB) response and long-term survival in heart failure (HF). Background Differences in BB treatment effect between Caucasians and African Americans with HF have been reported. Methods Prospective cohort study of 2,460 patients (711 African American; 1,749 Caucasian) enrolled between 1999 and 2007. 2039 (81.7%) were treated with BB. Each was genotyped for β1-adrenergic receptor (ADRB1) Arg389>Gly and G-protein receptor kinase 5 (GRK5) Gln41>Leu polymorphisms, which are more prevalent among African Americans than Caucasians. Primary endpoint was survival time from HF onset. Results There were 765 deaths during follow up (median 46 months). BB treatment increased survival in Caucasians (Log Rank P=0.00038) but not African Americans (Log Rank P=0.327). Among patients not taking BB, ADRB1 Gly389 was associated with decreased survival in Caucasians (HR = 1.98, 95% CI = 1.1 − 3.7, P = 0.03) while GRK5 Leu41 was associated with improved survival in African Americans (HR = 0.325, CI = 0.133 − 0.796, P = 0.01). ADRB1 Gly389 GRK5 Gln41Gln African Americans derived similar survival benefit from BB therapy (HR = 0.385 95% CI = 0.182 − 0.813, P = 0.012) as ADRB1 Gly389 GRK5 Gln41Gln Caucasians (HR = 0.529, 95% CI = 0.326 − 0.858, P=0.0098). Conclusions These data demonstrate that differences caused by β-adrenergic receptor signaling pathway gene polymorphisms, rather than race, are the major factors contributing to apparent differences in BB treatment effect between Caucasians and African Americans; proper evaluation of treatment response should account for genetic variance. PMID:19628119

Biomass burning emissions of trace gases and particles in marine air at Cape Grim, Tasmania

NASA Astrophysics Data System (ADS)

Lawson, S. J.; Keywood, M. D.; Galbally, I. E.; Gras, J. L.; Cainey, J. M.; Cope, M. E.; Krummel, P. B.; Fraser, P. J.; Steele, L. P.; Bentley, S. T.; Meyer, C. P.; Ristovski, Z.; Goldstein, A. H.

2015-12-01

Biomass burning (BB) plumes were measured at the Cape Grim Baseline Air Pollution Station during the 2006 Precursors to Particles campaign, when emissions from a fire on nearby Robbins Island impacted the station. Measurements made included non-methane organic compounds (NMOCs) (PTR-MS), particle number size distribution, condensation nuclei (CN) > 3 nm, black carbon (BC) concentration, cloud condensation nuclei (CCN) number, ozone (O3), methane (CH4), carbon monoxide (CO), hydrogen (H2), carbon dioxide (CO2), nitrous oxide (N2O), halocarbons and meteorology. During the first plume strike event (BB1), a 4 h enhancement of CO (max ~ 2100 ppb), BC (~ 1400 ng m-3) and particles > 3 nm (~ 13 000 cm-3) with dominant particle mode of 120 nm were observed overnight. A wind direction change lead to a dramatic reduction in BB tracers and a drop in the dominant particle mode to 50 nm. The dominant mode increased in size to 80 nm over 5 h in calm sunny conditions, accompanied by an increase in ozone. Due to an enhancement in BC but not CO during particle growth, the presence of BB emissions during this period could not be confirmed. The ability of particles > 80 nm (CN80) to act as CCN at 0.5 % supersaturation was investigated. The ΔCCN / ΔCN80 ratio was lowest during the fresh BB plume (56 ± 8 %), higher during the particle growth period (77 ± 4 %) and higher still (104 ± 3 %) in background marine air. Particle size distributions indicate that changes to particle chemical composition, rather than particle size, are driving these changes. Hourly average CCN during both BB events were between 2000 and 5000 CCN cm-3, which were enhanced above typical background levels by a factor of 6-34, highlighting the dramatic impact BB plumes can have on CCN number in clean marine regions. During the 29 h of the second plume strike event (BB2) CO, BC and a range of NMOCs including acetonitrile and hydrogen cyanide (HCN) were clearly enhanced and some enhancements in O3 were observed (ΔO3 / ΔCO 0.001-0.074). A short-lived increase in NMOCs by a factor of 10 corresponded with a large CO enhancement, an increase of the NMOC / CO emission ratio (ER) by a factor of 2-4 and a halving of the BC / CO ratio. Rainfall on Robbins Island was observed by radar during this period which likely resulted in a lower fire combustion efficiency, and higher emission of compounds associated with smouldering. This highlights the importance of relatively minor meteorological events on BB emission ratios. Emission factors (EFs) were derived for a range of trace gases, some never before reported for Australian fires, (including hydrogen, phenol and toluene) using the carbon mass balance method. This provides a unique set of EFs for Australian coastal heathland fires. Methyl halide EFs were higher than EFs reported from other studies in Australia and the Northern Hemisphere which is likely due to high halogen content in vegetation on Robbins Island. This work demonstrates the substantial impact that BB plumes can have on the composition of marine air, and the significant changes that can occur as the plume interacts with terrestrial, aged urban and marine emission sources.

A Bilobalide-Producing Endophytic Fungus, Pestalotiopsis uvicola from Medicinal Plant Ginkgo biloba.

PubMed

Qian, Yi-Xin; Kang, Ji-Chuan; Luo, Yi-Kai; Zhao, Jun-Jie; He, Jun; Geng, Kun

2016-08-01

For screening bilobalide (BB)-producing endophytic fungi from medicinal plant Ginkgo biloba, a total of 57 fungal isolates were isolated from the internal stem, root, leaf, and bark of the plant G. biloba. Fermentation processes using BB-producing fungi other than G. biloba may become a novel way to produce BB, which is a terpene trilactones exhibiting neuroprotective effects. In this study, a BB-producing endophytic fungal strain GZUYX13 was isolated from the leaves of G. biloba grown in the campus of Guizhou University, Guiyang city, Guizhou province, China. The strain produced BB when grown in potato dextrose liquid medium. The amount of BB produced by this endophytic fungus was quantified to be 106 μg/L via high-performance liquid chromatography (HPLC), substantially lower than that produced by the host tissue. The fungal BB which was analyzed by thin layer chromatography (TLC) and HPLC was proven to be identical to authentic BB. The strain GZUYX13 was identified as Pestalotiopsis uvicola via morphology and ITS rDNA phylogeny. To the best of our knowledge, this is the first report concerning the isolation and identification of endophytic BB-producing Pestalotiopsis spp. from the host plant, which further proved that endophytic fungi have the potential to produce bioactive compounds.

First measurement of the charge asymmetry in beauty-quark pair production.

PubMed

Aaij, R; Adeva, B; Adinolfi, M; Affolder, A; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Anderson, J; Andreassen, R; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Borsato, M; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brodzicka, J; Brook, N H; Brown, H; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carranza-Mejia, H; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chen, S; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Corvo, M; Counts, I; Couturier, B; Cowan, G A; Craik, D C; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Dalseno, J; David, P; David, P N Y; Davis, A; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Donleavy, S; Dordei, F; Dorigo, M; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dreimanis, K; Dujany, G; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Ely, S; Esen, S; Evans, H-M; Evans, T; Falabella, A; Färber, C; Farinelli, C; Farley, N; Farry, S; Fay, Rf; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Fu, J; Furfaro, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; García Pardiñas, J; Garofoli, J; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gavardi, L; Gavrilov, G; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianelle, A; Giani', S; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gordon, H; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grillo, L; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Henry, L; Hernando Morata, J A; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hoballah, M; Hombach, C; Hulsbergen, W; Hunt, P; Hussain, N; Hutchcroft, D; Hynds, D; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jalocha, J; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Karodia, S; Kelsey, M; Kenyon, I R; Ketel, T; Khanji, B; Khurewathanakul, C; Klaver, S; Klimaszewski, K; Kochebina, O; Kolpin, M; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Langhans, B; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Liles, M; Lindner, R; Linn, C; Lionetto, F; Liu, B; Liu, G; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lowdon, P; Lu, H; Lucchesi, D; Luo, H; Lupato, A; Luppi, E; Lupton, O; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Manca, G; Mancinelli, G; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marino, P; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M-N; Moggi, N; Molina Rodriguez, J; Monteil, S; Morandin, M; Morawski, P; Mordà, A; Morello, M J; Moron, J; Morris, A-B; Mountain, R; Muheim, F; Müller, K; Muresan, R; Mussini, M; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, G; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palombo, F; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrignani, C; Pazos Alvarez, A; Pearce, A; Pellegrino, A; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Petridis, K; Petrolini, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Pistone, A; Playfer, S; Plo Casasus, M; Polci, F; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Price, E; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rachwal, B; Rademacker, J H; Rakotomiaramanana, B; Rama, M; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Reichert, S; Reid, M M; Dos Reis, A C; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rotondo, M; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrie, M; Savrina, D; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Sepp, I; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Shires, A; Silva Coutinho, R; Simi, G; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, N A; Smith, E; Smith, E; Smith, J; Smith, M; Snoek, H; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, M; Stahl, S; Steinkamp, O; Stenyakin, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Stracka, S; Straticiuc, M; Straumann, U; Stroili, R; Subbiah, V K; Sun, L; Sutcliffe, W; Swientek, K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szilard, D; Szumlak, T; T'Jampens, S; Teklishyn, M; Tellarini, G; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vagnoni, V; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vieites Diaz, M; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; de Vries, J A; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Websdale, D; Whitehead, M; Wicht, J; Wiedner, D; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Xu, Z; Yang, Z; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

2014-08-22

The difference in the angular distributions between beauty quarks and antiquarks, referred to as the charge asymmetry, is measured for the first time in bb pair production at a hadron collider. The data used correspond to an integrated luminosity of 1.0 fb(-1) collected at 7 TeV center-of-mass energy in proton-proton collisions with the LHCb detector. The measurement is performed in three regions of the invariant mass of the bb system. The results obtained are A(C)(bb))(40 105 GeV/c(2)) = 1.6 ± 1.7 ± 0.6%, where A(C)(bb)) is defined as the asymmetry in the difference in rapidity between jets formed from the beauty quark and antiquark, where in each case the first uncertainty is statistical and the second systematic. The beauty jets are required to satisfy 2 < η < 4, E(T) >20 GeV, and have an opening angle in the transverse plane Δ ϕ > 2.6 rad. These measurements are consistent with the predictions of the standard model.

Analysis of EEG activity in response to binaural beats with different frequencies.

PubMed

Gao, Xiang; Cao, Hongbao; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Wang, Xiaolu; Chen, Runge; Zhou, Peng

2014-12-01

When two coherent sounds with nearly similar frequencies are presented to each ear respectively with stereo headphones, the brain integrates the two signals and produces a sensation of a third sound called binaural beat (BB). Although earlier studies showed that BB could influence behavior and cognition, common agreement on the mechanism of BB has not been reached yet. In this work, we employed Relative Power (RP), Phase Locking Value (PLV) and Cross-Mutual Information (CMI) to track EEG changes during BB stimulations. EEG signals were acquired from 13 healthy subjects. Five-minute BBs with four different frequencies were tested: delta band (1 Hz), theta band (5 Hz), alpha band (10 Hz) and beta band (20 Hz). We observed RP increase in theta and alpha bands and decrease in beta band during delta and alpha BB stimulations. RP decreased in beta band during theta BB, while RP decreased in theta band during beta BB. However, no clear brainwave entrainment effect was identified. Connectivity changes were detected following the variation of RP during BB stimulations. Our observation supports the hypothesis that BBs could affect functional brain connectivity, suggesting that the mechanism of BB-brain interaction is worth further study. Copyright © 2014. Published by Elsevier B.V.

Synthesis, electrochemistry, and electrogenerated chemiluminescence of two BODIPY-appended bipyridine homologues.

PubMed

Qi, Honglan; Teesdale, Justin J; Pupillo, Rachel C; Rosenthal, Joel; Bard, Allen J

2013-09-11

Two new 2,2'-bipyridine (bpy) derivatives containing ancillary BODIPY chromophores attached at the 5- and 5'-positions (BB3) or 6- and 6'-positions (BB4) were prepared and characterized. In this work, the basic photophysics, electrochemistry, and electrogenerated chemiluminescence (ECL) of BB3 and BB4 are compared with those previously reported for a related bpy-BODIPY derivative (BB2) (J. Phys. Chem. C 2011, 115, 17993-18001). Cyclic voltammetry revealed that BB3 and BB4 display reversible 2e(-) oxidation and reduction waves, which consist of two closely spaced (50-70 mV) 1e(-) events. This redox behavior is consistent with the frontier molecular orbitals calculated for BB3 and BB4 and indicates that the 2,2'-bipyridine spacer of each bpy-BODIPY homologue does not facilitate efficient electronic communication between the tethered indacene units. In the presence of a coreactant such as tri-n-propylamine (TPA) or benzoyl peroxide (BPO), BB3 and BB4 exhibit strong ECL and produce spectra that are very similar to their corresponding photoluminescence profiles. The ECL signal obtained under annihilation conditions, however, is significantly different and is characterized by two distinct bands. One of these bands is centered at ∼570 nm and is attributed to emission via an S- or T-route. The second band occurs at longer wavelengths and is centered around ∼740 nm. The shape and concentration dependence of this long-wavelength ECL signal is not indicative of emission from an excimer or aggregate, but rather it suggests that a new emissive species is formed from the bpy-BODIPY luminophores during the annihilation process.

Losartan added to β-blockade therapy for aortic root dilation in Marfan syndrome: a randomized, open-label pilot study.

PubMed

Chiu, Hsin-Hui; Wu, Mei-Hwan; Wang, Jou-Kou; Lu, Chun-Wei; Chiu, Shuenn-Nan; Chen, Chun-An; Lin, Ming-Tai; Hu, Fu-Chang

2013-03-01

To assess the tolerability and efficacy of the investigational use of the angiotensin II receptor blocker losartan added to β-blockade (BB) to prevent progressive aortic root dilation in patients with Marfan syndrome (MFS). Between May 1, 2007, and September 31, 2011, 28 patients with MFS (11 males [39%]; mean ± SD age, 13.1±6.3 years) with recognized aortic root dilation (z score >2.0) and receiving BB (atenolol or propranolol) treatment were enrolled. They were randomized to receive BB (BB: 13 patients) or β-blockade and losartan (BB-L: 15 patients) for 35 months. In the BB-L group, aortic root dilation was reduced with treatment, and the annual dilation rate of the aortic root was significantly lower than that of the BB group (0.10 mm/yr vs 0.89 mm/yr; P=.02). The absolute aortic diameters at the sinus of Valsalva, annulus, and sinotubular junction showed similar trends, with a reduced rate of dilation in the BB-L group (P=.02, P=.03, and P=.03, respectively). Five patients (33%) treated with BB-L were noted to have a reduced aortic root diameter. However, the differences between the groups regarding changes in aortic stiffness and cross-sectional compliance were not statistically significant. This randomized, open-label, active controlled trial mostly based on a pediatric population demonstrated for the first time that losartan add-on BB therapy is safe and provides more effective protection to slow the progression of aortic root dilation than does BB treatment alone in patients with MFS. clinicaltrials.gov Identifier: NCT00651235. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Synthesis, Electrochemistry and Electrogenerated Chemiluminesce of two BODIPY-Appended Bipyridine Homologues

PubMed Central

Qi, Honglan; Teesdale, Justin J.; Pupillo, Rachel C.

2014-01-01

Two new 2,2’-bipyridine (bpy) derivatives containing ancillary BODIPY chromophores attached at the 5- and 5’-positions (BB3) or 6- and 6’-positions (BB4) were prepared and characterized. In this work, the basic photophysics, electrochemistry and electrogenerated chemiluminescence (ECL) of BB3 and BB4 are compared with those previously reported for a related bpy-BODIPY derivative (BB2) (J. Phys. Chem. C 2011, 115, 17993–18001). Cyclic voltammetry revealed that BB3 and BB4 display reversible 2e− oxidation and reduction waves, which consist of two closely spaced (50 – 70 mV) 1e− events. This redox behavior is consistent with the frontier molecular orbitals calculated for BB3 and BB4 and indicates that the 2,2’-bipyridine spacer of each bpy- BODIPY homologue does not facilitate efficient electronic communication between the tethered indacene units. In the presence of a coreactant such as tri-n-propylamine (TPA) or benzoyl peroxide (BPO), BB3 and BB4 exhibit strong ECL and produce spectra that are very similar to their corresponding photoluminescence profiles. The ECL signal obtained under annihilation conditions, however, is significantly different and is characterized by two distinct bands. One of these bands is centered at ~570 nm and is attributed to emission via an S- or T-route. The second band, occurs at longer wavelengths and is centered around ~740 nm. The shape and concentration dependence of this long-wavelength ECL signal is not indicative of emission from an excimer or aggregate, but rather is suggests that a new emissive species is formed from the bpy-BODIPY luminophores during the annihilation process. PMID:23980850

Lack of association between vitamin D receptor genotypes and osteoporosis in Koreans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Sung Kil; Park, Young Suk; Park, Jae Min

To evaluate whether common allelic variants in the gene encoding the vitamin D receptor (VDR) were useful in predicting differences in bone mineral density (BMD) and bone turnover rate in Koreans, we analyzed the restriction pattern of the polymerase chain reaction product of the VDR gene with the Bsm1 enzyme and serum osteocalcin in patients with osteoporosis. The prevalence of the BB genotype in the controls was extremely low when compared with that in other reports: the BB, Bb, and bb genotypes accounted for 1.4%, 12.9%, and 85.7%, respectively. Only 2.8% of those patients with osteoporosis had the BB genotype.more » In contrast, 12.5% had the Bb genotype, and 84.7% had the bb genotype. The prevalence of the BB genotype in patients with severe osteoporosis was also extremely low: the BB, Bb and bb genotypes accounted for 0%, 12.4%, and 87.6%, respectively. Compared with the mean serum osteocalcin level of the pre- and post-menopausal controls, the levels in patients with severe osteoporosis was higher, and this was statistically significant. As expected, a negative correlation was observed between the serum osteocalcin levels and the age-matched Z scores for spinal BMD. However, no correlation was found in the femoral neck BMD. These results suggest that restriction fragment length polymorphism analysis of the VDR gene with a Bsm1 restriction enzyme in Koreans is not helpful for early detection of patients at risk of developing osteoporosis. This is true even in patients with a high rate of bone turnover. Our data suggest extreme ethnic differences in the pattern of prevalence of the VDR allele. 19 refs., 5 figs., 2 tabs.« less

Intrinsic and Extrinsic Modifiers of the Regulative Capacity of the Developing Liver

PubMed Central

Shin, Donghun; Weidinger, Gilbert; Moon, Randall T.; Stainier, Didier Y.R.

2012-01-01

Zebrafish wnt2bb mutants initially fail to form a liver, but surprisingly the liver eventually forms in a majority of these embryos which then develop into fertile adults. This unexpected result raised the possibility that identifying the mechanisms of liver formation in wnt2bb mutants could provide insights into the poorly understood yet general principle of regulative development, a process by which some cells can change fate in order to compensate for a deficiency. Here, we identify two factors that underlie the regulative capacity of endodermal tissues: an intrinsic factor, Sox32, a transcription factor of the SoxF subfamily, and an extrinsic factor, Fgf10a. sox32 is expressed in the extrahepatic duct primordium which is not affected in wnt2bb mutants. Blocking Sox32 function prevented liver formation in most wnt2bb mutants. fgf10a, which is expressed in the mesenchyme surrounding non-hepatic endodermal cells, negatively impacts the regulative capacity of endodermal tissues. In Wnt/β-catenin signaling deficient embryos, in which the liver completely fails to form, the repression of Fgf10a function allowed liver formation. Altogether, these studies reveal that there is more than one way to form a liver, and provide molecular insights into the phenomenon of tissue plasticity. PMID:22313811

Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine.

PubMed

Cowley, Daniel; Boniface, Karen; Bogdanovic-Sakran, Nada; Kirkwood, Carl D; Bines, Julie E

2017-08-03

The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0-5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0-5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3-7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3-7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4-5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3-7 was the result of replication rather than passage through the gastrointestinal tract.

Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells.

PubMed

Adam, Rosalyn M; Eaton, Samuel H; Estrada, Carlos; Nimgaonkar, Ashish; Shih, Shu-Ching; Smith, Lois E H; Kohane, Isaac S; Bägli, Darius; Freeman, Michael R

2004-12-15

Application of mechanical stimuli has been shown to alter gene expression in bladder smooth muscle cells (SMC). To date, only a limited number of "stretch-responsive" genes in this cell type have been reported. We employed oligonucleotide arrays to identify stretch-sensitive genes in primary culture human bladder SMC subjected to repetitive mechanical stimulation for 4 h. Differential gene expression between stretched and nonstretched cells was assessed using Significance Analysis of Microarrays (SAM). Expression of 20 out of 11,731 expressed genes ( approximately 0.17%) was altered >2-fold following stretch, with 19 genes induced and one gene (FGF-9) repressed. Using real-time RT-PCR, we tested independently the responsiveness of 15 genes to stretch and to platelet-derived growth factor-BB (PDGF-BB), another hypertrophic stimulus for bladder SMC. In response to both stimuli, expression of 13 genes increased, 1 gene (FGF-9) decreased, and 1 gene was unchanged. Six transcripts (HB-EGF, BMP-2, COX-2, LIF, PAR-2, and FGF-9) were evaluated using an ex vivo rat model of bladder distension. HB-EGF, BMP-2, COX-2, LIF, and PAR-2 increased with bladder stretch ex vivo, whereas FGF-9 decreased, consistent with expression changes observed in vitro. In silico analysis of microarray data using the FIRED algorithm identified c-jun, AP-1, ATF-2, and neurofibromin-1 (NF-1) as potential transcriptional mediators of stretch signals. Furthermore, the promoters of 9 of 13 stretch-responsive genes contained AP-1 binding sites. These observations identify stretch as a highly selective regulator of gene expression in bladder SMC. Moreover, they suggest that mechanical and growth factor signals converge on common transcriptional regulators that include members of the AP-1 family.

Mississippi River: Study of Alternatives for Rehabilitation of Lock and Dam Number 1. Minneapolis, Minnesota. Volume 4. Appendices G-M.

DTIC Science & Technology

1976-04-01

juniper (Juniperus chinensis, var. pfitzeriana), globe juniper (Juni]erus virginiana , var. globosa), dwarf Japanese yew (Taxus cuspidata, var. nana) and...excessively, compacted after planting. Heavy pruning of the tree’s upper branches is recommended at this point, to reduce the load put on root functioning...8217 5@9 BB 500.00 Shrubs-2 Juniperus chinensis 4𔃻 BB 42.00 Juniperus virginiana 31- BB 48.70 Taxus cuspidata 31 BB 38.40 *Cotoneaster apiculata 5’ BB

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Huan, E-mail: wanghuan7@126.com; Institute for Liver Diseases of Anhui Medical University; Wang, Ying-hong

Metabolic syndrome characterized by hyperglycemia contributes to nonalcoholic steatohepatitis-associated liver fibrosis. This study was to investigate the effects of Acid-sensing ion Channel 1a (ASIC1a) on the process of liver fibrosis under hyperglycemia. Results showed that high glucose significantly worsen the pathology of liver fibrosis in vivo. In vitro, high glucose stimulated proliferation, activation and extracellular matrix (ECM) production in HSCs, and enhanced the effect of PDGF-BB on the activation and proliferation of HSCs. These effects could be attenuated by ASIC1a specific inhibitor Psalmotoxin-1(PcTx1) or specific ShRNA for ASIC1a through Notch1/Hes-1 pathways. These data indicate that ASIC1a plays an important role in diabetesmore » complication liver fibrosis. - Highlights: • Hyperglycemia is a risk factor for the process of liver fibrosis. • ASIC1a may be a key factor linking between high glucose and liver fibrosis. • Notch1/Hes-1 may involve to the process of liver fibrosis under hyperglycemia.« less

Better Efficacy of Synchrotron Spatially Microfractionated Radiation Therapy Than Uniform Radiation Therapy on Glioma.

PubMed

Bouchet, Audrey; Bräuer-Krisch, Elke; Prezado, Yolanda; El Atifi, Michèle; Rogalev, Léonid; Le Clec'h, Céline; Laissue, Jean Albert; Pelletier, Laurent; Le Duc, Géraldine

2016-08-01

Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood. Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control and on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis. MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P<.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT. These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Better Efficacy of Synchrotron Spatially Microfractionated Radiation Therapy Than Uniform Radiation Therapy on Glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bouchet, Audrey, E-mail: audrey.m.bouchet@gmail.com; Biomedical Beamline, European Synchrotron Radiation Facility, Grenoble; Bräuer-Krisch, Elke

Purpose: Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood. Methods and Materials: Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control andmore » on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis. Results: MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P<.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT. Conclusions: These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses.« less

Effect of shear stress on the migration of hepatic stellate cells.

PubMed

Sera, Toshihiro; Sumii, Tateki; Fujita, Ryosuke; Kudo, Susumu

2018-01-01

When the liver is damaged, hepatic stellate cells (HSCs) can change into an activated, highly migratory state. The migration of HSCs may be affected by shear stress due not only to sinusoidal flow but also by the flow in the space of Disse because this space is filled with blood plasma. In this study, we evaluated the effects of shear stress on HSC migration in a scratch-wound assay with a parallel flow chamber. At regions upstream of the wound area, the migration was inhibited by 0.6 Pa and promoted by 2.0 Pa shear stress, compared to the static condition. The platelet-derived growth factor (PDGF)-BB receptor, PDGFR-β, was expressed in all conditions and the differences were not significant. PDGF increased HSC migration, except at 0.6 Pa shear stress, which was still inhibited. These results indicate that another molecular factor, such as PDGFR-α, may act to inhibit the migration under low shear stress. At regions downstream of the wound area, the migration was smaller under shear stress than under the static condition, although the expression of PDGFR-β was significantly higher. In particular, the migration direction was opposite to the wound area under high shear stress; therefore, migration might be influenced by the intercellular environment. Our results indicate that HSC migration was influenced by shear stress intensity and the intercellular environment.

Biomass burning in Indo-China peninsula and its impacts on regional air quality and global climate change-a review.

PubMed

Yadav, Ishwar Chandra; Linthoingambi Devi, Ningombam; Li, Jun; Syed, Jabir Hussain; Zhang, Gan; Watanabe, Hirozumi

2017-08-01

Although, many biomass burning (BB) emissions products (particulate matter and trace gases) are believed to be trans-boundary pollutants that originates from India and China (the two most populous countries in Asia), the information about BB emission and related contents is limited for Indo-China Peninsula (ICP) region. This motivated us to review this region pertaining to BB emission. The main objective of the review is to document the current status of BB emission in ICP region. In order to highlight the impact of BB on regional air quality and global climate change, the role of BB emission in ICP region is also discussed. Based on the available literature and modeling simulations studies, it is evidenced that ICP is one of the hotspot regional source for aerosols in terms of BB emissions. In addition, regional emissions through BB have significant implications for regional air quality especially in the neighboring countries such as China, Taiwan and India. Our assessment highlight that there is still a general lack of reliable data and research studies addressing BB related issues in context of environmental and human health. There is therefore a critical need to improve the current knowledge base, which should build upon the research experience and further research into these issues is considered vital to help inform future policies/control strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Light-absorbing organic carbon from prescribed and laboratory biomass burning and gasoline vehicle emissions.

PubMed

Xie, Mingjie; Hays, Michael D; Holder, Amara L

2017-08-04

Light-absorbing organic carbon (OC), also termed brown carbon (BrC), from laboratory-based biomass burning (BB) has been studied intensively to understand the contribution of BB to radiative forcing. However, relatively few measurements have been conducted on field-based BB and even fewer measurements have examined BrC from anthropogenic combustion sources like motor vehicle emissions. In this work, the light absorption of methanol-extractable OC from prescribed and laboratory BB and gasoline vehicle emissions was examined using spectrophotometry. The light absorption of methanol extracts showed a strong wavelength dependence for both BB and gasoline vehicle emissions. The mass absorption coefficients at 365 nm (MAC 365 , m 2 g -1 C) - used as a measurement proxy for BrC - were significantly correlated (p < 0.05) to the elemental carbon (EC)/OC ratios when examined by each BB fuel type. No significant correlation was observed when pooling fuels, indicating that both burn conditions and fuel types may impact BB BrC characteristics. The average MAC 365 of gasoline vehicle emission samples is 0.62 ± 0.76 m 2  g -1 C, which is similar in magnitude to the BB samples (1.27 ± 0.76 m 2  g -1 C). These results suggest that in addition to BB, gasoline vehicle emissions may also be an important BrC source in urban areas.

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2013-02-28

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Measurement of the branching fractions of exclusive _B-->D(*)(pi)l-_nu l decays in events with a fully reconstructed B meson.

PubMed

Aubert, B; Bona, M; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Wenzel, W A; del Amo Sanchez, P; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Gary, J W; Liu, F; Long, O; Shen, B C; Vitug, G M; Yasin, Z; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Ayad, R; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Karbach, M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Playfer, S; Robertson, A I; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Nash, J A; Panduro Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Firmino da Costa, J; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Alwyn, K E; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Hertzbach, S S; Li, X; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Morganti, M; Mazur, M A; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Biesiada, J; Lau, Y P; Lopes Pegna, D; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Cavoto, G; del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Roethel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Yi, K; Young, C C; Ziegler, V; Burchat, P R; Edwards, A J; Majewski, S A; Miyashita, T S; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Vuosalo, C O; Wu, S L

2008-04-18

We report a measurement of the branching fractions for _B-->D(*)(pi)l- _nu(l) decays based on 341.1 fb(-1) of data collected at the Upsilon(4S) resonance with the BABAR detector at the SLAC PEP-II e+ e- storage rings. Events are tagged by fully reconstructing one of the B mesons in a hadronic decay mode. We obtain B(B- -->D(0)l-_nu(l)=(2.33+/-0.09(stat)+/-0.09(syst)%, B(B- -->D(*0)l-_nu(l)=(5.83+/-0.15(stat) +/-0.30(syst) %, B(_B(0)-->D+l-_nu(l)=(2.21+/-0.11(stat) +/-0.12(syst)%, B(_B(0)-->D(*)l-_nu(l)=(5.49+/-0.16(stat)+/-0.25(syst)%, B(B- -->D+pi-l-_nu(l)=(0.42+/-0.06(stat)+/-0.03(syst)%, B(B- -->D(*)+pi-l-_nu(l)=(0.59+/-0.05(stat)+/-0.04(syst)%, B(_B(0)-->D(0)pi+l-_nu(l)=(0.43+/-0.08(stat)+/-0.03(syst)%, and B(_B(0)-->D(*0)pi+l-_nu(l)=(0.48+/-0.08(stat)+/-0.04(syst)%.

Characterizing Atmospheric Processing of Aerosols from Forest Fires at the Mt. Bachelor Observatory during BBOP

NASA Astrophysics Data System (ADS)

Zhou, S.; Collier, S.; Hee, J.; Wigder, N. L.; Jaffe, D. A.; Zhang, Q.

2014-12-01

This study investigates the physical and chemical characteristics and atmospheric processing of aerosols from uncontrolled forest fires across the Pacific Northwest. The measurements were made at the Mt. Bachelor Observatory (MBO) located at the summit of Mt. Bachelor in central Oregon (43.9794° N, 121.6885° W, 2,763 m asl) in summer 2013 during the DOE sponsored Biomass Burning Observation Project (BBOP) field campaign. We utilized an Aerodyne High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) coupled with a thermodenuder. Observations during periods affected by biomass burning (BB) pollution showed elevated non-refractory submicron aerosol (NR-PM1) concentration up to 140 μg/m3. NR-PM1 correlated well with PM light scattering (up to ~ 600 Mm-1 at 550 nm) and gas phase CO (up to ~0.4 ppmv). The AMS BB tracer, f60, i.e., fraction of organic signals at m/z = 60, was also enhanced with a maximum of ~ 2%. Organic aerosol (OA) dominated the PM composition in BB plumes (94.1% of the NR-PM1 mass) with an average concentration of 13.9 μg/m3. Three distinctive BBOA factors were identified by Positive Matrix Factorization (PMF): a fresh BBOA-I factor (O/C=0.27, H/C=1.52, f60 = 2.26%) that correlates well with ammonium nitrate; an intermediately oxidized BBOA-II (O/C=0.52, H/C=1.47, f60 = 1.05%), and a highly oxidized BBOA-III (O/C=0.95, H/C=1.02) with a low f60 (< 0.01%) and enhanced tracer ions for carboxylic acids (e.g., CHO2+). During persistent BB plume events from fixed fire sources, fresh BBOA-I initially dominated the OA composition, but decreased as the more oxidized BBOA-II increased while BBOA-III remained unchanged. These events shed light on the chemical transformation of BB aerosol during atmospheric aging. We will examine the enhancement of different BBOA factors relative to CO to investigate secondary organic aerosol (SOA) formation processes in BB plumes.

Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia

PubMed Central

Lynch, Anne M.; Murphy, James R.; Byers, Tim; Gibbs, Ronald S.; Neville, Margaret C.; Giclas, Patricia C.; Salmon, Jane E.; Holers, V. Michael

2008-01-01

OBJECTIVE Preeclampsia is a multisystem disease classically defined on the basis of hypertension and proteinuria. As shown in animal studies, complement activation is associated with inflammation in the placenta and adverse pregnancy outcomes. The association between complement activation in humans and adverse pregnancy outcomes is unclear. The purpose of this study was to determine whether elevated levels of the activation fragment Bb in early pregnancy are predictive of preeclampsia. STUDY DESIGN This prospective study of 701 women was conducted in Denver, CO. A single plasma sample was obtained from each woman before 20 weeks’ gestation. The cohort was followed up throughout pregnancy for the development of preeclampsia. Analysis included multivariate logistic regression to adjust for established risk factors for preeclampsia. RESULTS Preeclampsia developed in 4.6% of the cohort. Women with elevated Bb (90th or greater percentile) were substantially more likely to develop preeclampsia than women who had levels less than the 90th percentile (unadjusted relative risk [RR], 3.3, 95% confidence interval [CI] 1.6 to 7, P = .0009). Other significant risk factors for preeclampsia included nulliparity (RR, 2.1, 95% CI, 1–4), a high body mass index (P = .006 for trend), and maternal medical (preexisting maternal hypertension, type 1 diabetes, systemic lupus erythematosus) disease (RR, 4.4, 95% CI, 2–10). Significant risk factors among multiparous women included a history of hypertension in a previous pregnancy (RR, 5, 95% CI, 1.6 to 16) and a change of paternity (RR, 5.1, 95% CI, 1.6 to 15). Adjustment for risk factors did not attenuate the association between an elevated Bb and preeclampsia (adjusted odds ratio [OR], 3.8, 95% CI, 1.6 to 9, P = .002) in the cohort. After removing women with plasma obtained before 10 weeks, the adjusted OR of Bb in the top decile for preeclampsia was 6.1 (95% CI 2.2, 17, P = .0005). CONCLUSION The complement activation product Bb in early pregnancy is a biomarker for elevated risk of preeclampsia. This observation suggests that events linked to activation of complement in early pregnancy are associated with the pathogenesis of preeclampsia. PMID:18221926

[Effect of vitamin D receptor gene polymorphism and lifestyle on bone mineral density and bone mineral density decrement rate].

PubMed

Yamagata, Z; Miyamura, T; Iijima, S; Asaka, A

1995-12-01

The effects of genetic and environmental factors on bone mineral density (BMD) were investigated in 108 healthy Japanese women. Of the 108 subjects, BMD (from the second to forth lumbar vertebrae) was measured in 1992 in 103, in 1993 in 100, and in both years in 95 by dual energy X-ray absorptiometry. Vitamin D receptor (VDR) gene polymorphism in intron 8 was used as a genetic marker. Information on menstruation, health status, lifestyle, quantities of nutrient intake and frequencies of food intake was obtained by questionnaire. The frequency of allele B (825bp), whose polymerase chain reaction (PCR) products cannot be cut with BsmI, was 0.259 and the frequency of allele b (650bp), whose PCR products can be cut with BsmI, was 0.741. The subjects in our study obeyed the Hardy-Weinberg law. While the frequency of allele B was 0.448 in European whites as reported by Morrison et al, it was 0.259 in our Japanese subjects, suggesting a racial difference. Z score values (average value 0, standard deviation 1) increased in the order BB, Bb and bb. This result indicates that allele B is associated with the lower BMD in Japanese, as in European whites. The BMD decrement rate increased in the order bb, Bb and BB, indicating that VDR gene polymorphism may be a regulatory factor for losing BMD. Most of lifestyle variables, calcium intake and vitamin D intake were not correlated with BMD, but the food frequency score (which was defined as values weighted in each of three food categories obtained by factor analysis) was significantly correlated with BMD. Multiple regression analysis showed significant influences of years after menopause, the food frequency score and VDR genotype on BMD. VDR genotype and years after menopause influenced the BMD decrement rate significantly in multiple regression analysis. Neither a relationship between BMD and calcium intake nor between BMD and vitamin D intake by VDR genotype was found. These results suggest that the VDR gene is a genetic factor in BMD and the BMD decrement rate in Japanese.

Cry3Bb1-Resistant Western Corn Rootworm, Diabrotica virgifera virgifera (LeConte) Does Not Exhibit Cross-Resistance to DvSnf7 dsRNA.

PubMed

Moar, William; Khajuria, Chitvan; Pleau, Michael; Ilagan, Oliver; Chen, Mao; Jiang, Changjian; Price, Paula; McNulty, Brian; Clark, Thomas; Head, Graham

2017-01-01

There is a continuing need to express new insect control compounds in transgenic maize against western corn rootworm, Diabrotica virgifera virgifera (LeConte) (WCR). In this study three experiments were conducted to determine cross-resistance between the new insecticidal DvSnf7 dsRNA, and Bacillus thuringiensis (Bt) Cry3Bb1; used to control WCR since 2003, with field-evolved resistance being reported. Laboratory susceptible and Cry3Bb1-resistant WCR were evaluated against DvSnf7 dsRNA in larval diet-incorporation bioassays. Additionally, the susceptibility of seven field and one field-derived WCR populations to DvSnf7 (and Cry3Bb1) was assessed in larval diet-overlay bioassays. Finally, beetle emergence of laboratory susceptible and Cry3Bb1-resistant WCR was evaluated with maize plants in the greenhouse expressing Cry3Bb1, Cry34Ab1/Cry35Ab1, or DvSnf7 dsRNA singly, or in combination. The Cry3Bb1-resistant colony had slight but significantly (2.7-fold; P<0.05) decreased susceptibility to DvSnf7 compared to the susceptible colony, but when repeated using a field-derived WCR population selected for reduced Cry3Bb1 susceptibility, there was no significant difference (P<0.05) in DvSnf7 susceptibility compared to that same susceptible population. Additionally, this 2.7-fold difference in susceptibility falls within the range of DvSnf7 susceptibility among the seven field populations tested. Additionally, there was no correlation between susceptibility to DvSnf7 and Cry3Bb1 for all populations evaluated. In greenhouse studies, there were no significant differences (P<0.05) between beetle emergence of susceptible and Cry3Bb1-resistant colonies on DvSnf7 and Cry34Ab1/Cry35Ab1, and between DvSnf7 and MON 87411 (DvSnf7 + Cry3Bb1) for the Cry3Bb1-resistant colony. These results demonstrate no cross-resistance between DvSnf7 and Cry3Bb1 against WCR. Therefore, pyramiding DvSnf7 with Bt proteins such as Cry3Bb1 and Cry34Ab1/Cry35Ab1 will provide a valuable IRM tool against WCR that will increase the durability of these Bt proteins. These results also illustrate the importance of using appropriate bioassay methods when characterizing field-evolved resistant WCR populations.

Cry3Bb1-Resistant Western Corn Rootworm, Diabrotica virgifera virgifera (LeConte) Does Not Exhibit Cross-Resistance to DvSnf7 dsRNA

PubMed Central

Khajuria, Chitvan; Pleau, Michael; Ilagan, Oliver; Chen, Mao; Jiang, Changjian; Price, Paula; McNulty, Brian; Clark, Thomas; Head, Graham

2017-01-01

Background and Methodology There is a continuing need to express new insect control compounds in transgenic maize against western corn rootworm, Diabrotica virgifera virgifera (LeConte) (WCR). In this study three experiments were conducted to determine cross-resistance between the new insecticidal DvSnf7 dsRNA, and Bacillus thuringiensis (Bt) Cry3Bb1; used to control WCR since 2003, with field-evolved resistance being reported. Laboratory susceptible and Cry3Bb1-resistant WCR were evaluated against DvSnf7 dsRNA in larval diet-incorporation bioassays. Additionally, the susceptibility of seven field and one field-derived WCR populations to DvSnf7 (and Cry3Bb1) was assessed in larval diet-overlay bioassays. Finally, beetle emergence of laboratory susceptible and Cry3Bb1-resistant WCR was evaluated with maize plants in the greenhouse expressing Cry3Bb1, Cry34Ab1/Cry35Ab1, or DvSnf7 dsRNA singly, or in combination. Principal Findings and Conclusions The Cry3Bb1-resistant colony had slight but significantly (2.7-fold; P<0.05) decreased susceptibility to DvSnf7 compared to the susceptible colony, but when repeated using a field-derived WCR population selected for reduced Cry3Bb1 susceptibility, there was no significant difference (P<0.05) in DvSnf7 susceptibility compared to that same susceptible population. Additionally, this 2.7-fold difference in susceptibility falls within the range of DvSnf7 susceptibility among the seven field populations tested. Additionally, there was no correlation between susceptibility to DvSnf7 and Cry3Bb1 for all populations evaluated. In greenhouse studies, there were no significant differences (P<0.05) between beetle emergence of susceptible and Cry3Bb1-resistant colonies on DvSnf7 and Cry34Ab1/Cry35Ab1, and between DvSnf7 and MON 87411 (DvSnf7 + Cry3Bb1) for the Cry3Bb1-resistant colony. These results demonstrate no cross-resistance between DvSnf7 and Cry3Bb1 against WCR. Therefore, pyramiding DvSnf7 with Bt proteins such as Cry3Bb1 and Cry34Ab1/Cry35Ab1 will provide a valuable IRM tool against WCR that will increase the durability of these Bt proteins. These results also illustrate the importance of using appropriate bioassay methods when characterizing field-evolved resistant WCR populations. PMID:28060922

Simple and efficient generation of virus-specific T cells for adoptive therapy using anti-4-1BB antibody.

PubMed

Imahashi, Nobuhiko; Nishida, Tetsuya; Goto, Tatsunori; Terakura, Seitaro; Watanabe, Keisuke; Hanajiri, Ryo; Sakemura, Reona; Imai, Misa; Kiyoi, Hitoshi; Naoe, Tomoki; Murata, Makoto

2015-01-01

Although recent studies of virus-specific T-cell (VST) therapy for viral infections after allogeneic hematopoietic stem cell transplantation have shown promising results, simple and less time-intensive and labor-intensive methods are required to generate VSTs for the wider application of VST therapy. We investigated the efficacy of anti-CD28 and anti-4-1BB antibodies, which can provide T cells with costimulatory signals similar in strength to those of antigen-presenting cells, in generating VSTs. When peripheral blood mononuclear cells were stimulated with viral peptides together with isotype control, anti-CD28, or anti-4-1BB antibodies, anti-4-1BB antibodies yielded the highest numbers of VSTs, which were on an average 7.9 times higher than those generated with isotype control antibody. The combination of anti-CD28 and anti-4-1BB antibodies did not result in increased numbers of VSTs compared with anti-4-1BB antibody alone. Importantly, the positive effect of anti-4-1BB antibody was observed regardless of the epitopes of the VSTs. In contrast, the capacity of dendritic cells (DCs) to generate VSTs differed considerably depending on the epitopes of the VSTs. Furthermore, the numbers of VSTs generated with DCs were at most similar to those generated with the anti-4-1BB antibody. Generation of VSTs with anti-4-1BB antibody did not result in excessive differentiation or deteriorated function of the generated VSTs compared with those generated with control antibody or DCs. In conclusion, VSTs can be generated rapidly and efficiently by simply stimulating peripheral blood mononuclear cells with viral peptide and anti-4-1BB antibody without using antigen-presenting cells. We propose using anti-4-1BB antibody as a novel strategy to generate VSTs for adoptive therapy.

Pseudomonas syringae Type III Effector HopBB1 Promotes Host Transcriptional Repressor Degradation to Regulate Phytohormone Responses and Virulence.

PubMed

Yang, Li; Teixeira, Paulo José Pereira Lima; Biswas, Surojit; Finkel, Omri M; He, Yijian; Salas-Gonzalez, Isai; English, Marie E; Epple, Petra; Mieczkowski, Piotr; Dangl, Jeffery L

2017-02-08

Independently evolved pathogen effectors from three branches of life (ascomycete, eubacteria, and oomycete) converge onto the Arabidopsis TCP14 transcription factor to manipulate host defense. However, the mechanistic basis for defense control via TCP14 regulation is unknown. We demonstrate that TCP14 regulates the plant immune system by transcriptionally repressing a subset of the jasmonic acid (JA) hormone signaling outputs. A previously unstudied Pseudomonas syringae (Psy) type III effector, HopBB1, interacts with TCP14 and targets it to the SCF COI1 degradation complex by connecting it to the JA signaling repressor JAZ3. Consequently, HopBB1 de-represses the TCP14-regulated subset of JA response genes and promotes pathogen virulence. Thus, HopBB1 fine-tunes host phytohormone crosstalk by precisely manipulating part of the JA regulon to avoid pleiotropic host responses while promoting pathogen proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of beta-blocker therapy on heart rate response in patients with hypertension and newly diagnosed untreated obstructive sleep apnea syndrome.

PubMed

Wolf, Jacek; Drozdowski, Jacek; Czechowicz, Krzysztof; Winklewski, Paweł J; Jassem, Ewa; Kara, Tomas; Somers, Virend K; Narkiewicz, Krzysztof

2016-01-01

Beta1-receptor antagonists (BBs) are commonly administered in the treatment of cardiovascular disease (CVD). The reported benefits of BB use in CVD patients with concomitant obstructive sleep apnea (OSA) may be limited by their impact on apnea-induced bradycardias. Therefore the aim of the study was to test the influence of BBs on periapneic heart rate (HR) fluctuations in hypertensive patients with newly-detected and untreated OSA. We studied 88 hypertensive patients (56 on BBs and 32 BB naive) with newly-diagnosed moderate-to-severe OSA who were free of major pulmonary comorbidities and did not require antiarrhythmic therapy. ECGs recorded during sleep were investigated for heart rate (HR) responses to apneas allowing to compare extreme HR accelerations and decelerations between the groups. Average sleep-time HR was comparable in BB-naive (BB-) and BB-treated (BB+) patients. Direct comparisons showed that HR decelerations were also similar in the two subgroups (53.8±9.6 vs. 54.4±7.8 bpm; P=0.78, for BB- and BB+, respectively) however, BBs blunted the OSA-induced HR accelerations (82.3±12.2 vs. 74.3±10.0; P=0.003). After adjusting for baseline HR and magnitude of desaturations, HR decelerations were more evident in BB-naive group whereas tachycardic responses remained blunted in the BB+ group. The incidence of ectopies and conduction abnormalities were comparable across two groups. Beta-blockers do not potentiate apnea-induced HR decelerations, attenuate apnea-induced increases in heart rate and do not influence incidence of ectopies and conduction abnormalities in patients with hypertension and moderate-to-severe, untreated OSA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study.

PubMed

Merenstein, Daniel J; Tan, Tina P; Molokin, Aleksey; Smith, Keisha Herbin; Roberts, Robert F; Shara, Nawar M; Mete, Mihriye; Sanders, Mary Ellen; Solano-Aguilar, Gloria

2015-01-01

Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states.

Global biomass burning - Atmospheric, climatic, and biospheric implications

NASA Technical Reports Server (NTRS)

Levine, Joel S.

1990-01-01

Topics discussed at the March 1990 American Geophysical Union's Conference on biomass burning which was attended by more than 175 participants representing 19 countries are presented. Conference highlights include discussion of remote sensing data concerning biomass burning (BB), gaseous and particle emissions resulting from BB in the tropics, BB in temperate and boreal ecosystems, the historic and prehistoric perspectives on BB, BB and global budgets for carbon, nitrogen, and oxygen, and the BB and the greenhouse effect. Global estimates of annual amounts of biomass burning and of the resulting release of carbon to the atmosphere and the mean gaseous emission ratios for fires in wetlands, chaparral, and boreal ecosystems are given. An overview is presented of some conference discussions including global burning from 1850-1980, the global impact of biomass burning, the great Chinese/Soviet fire of 1987, and burning and biogenic emissions.

Olive Tree Branches Burning: A major pollution source in the Mediterranean

NASA Astrophysics Data System (ADS)

Kostenidou, Evangelia; Kaltsonoudis, Christos; Tsiflikiotou, Maria; Louvaris, Evangelos; Russell, Lynn; Pandis, Spyros

2013-04-01

Olive tree branches burning is a common agricultural waste management practice after the annual pruning of olive trees from November to February. Almost 1 billion (90%) of the olive trees in our planet are located around the Mediterranean, so the corresponding emissions of olive tree branches burning can be a significant source of fine aerosols during the cold months. Organic aerosol produced during the burning of olive tree branches (otBB-OA) was characterized with both direct source-sampling (using a mobile smog chamber) and ambient measurements during the burning season in the area of Patras, Greece. The aerosol emitted consists of organics, black carbon (BC), potassium, chloride, nitrate and sulfate. In addition to NOx, O3, CO and CO2, Volatile Organic Compounds (VOCs) such as methanol, acetonitrile, benzene and toluene were also produced. The Aerosol Mass Spectrometry (AMS) mass spectrum of otBB-OA is characterized by the m-z's27, 29, 39, 41, 43, 44, 55, 57, 67, 69 and 91 and changes as the emissions react with OH and O3. Fourier Transform Infrared Spectroscopy (FTIR) analysis showed that otBB-OA was composed of 48% alkane groups, 27% organic hydroxyl groups, 11% carboxylic acid groups, 11% primary amine groups and 4% carbonyl groups. The oxygen to carbon (O:C) ratio is 0.29±0.04. The otBB-OA AMS mass spectrum differs from the other published biomass burning spectra. The m-z60, used as levoglucosan tracer, is lower than in most biomass burning sources. This is confirmed by Gas Chromatography Mass Spectroscopy (GC-MS) analysis on filters where the levoglucosan to OC mass ratio was between 0.034 and 0.043, close to the lower limit of the reported values for most fuel types. This may lead to an underestimation of the otBB-OA contribution in Southern Europe if levoglucosan is being used as a wood burning tracer. During the olive tree branches burning season, 20 days of ambient measurements were performed. Applying positive matrix factorization (PMF) to the ambient organic data 3 factors could be identified: OOA (oxygenated organic aerosol), HOA (hydrocarbon-like organic aerosol) and otBB-OA. The chamber organic AMS spectrum resembles the ambient mass spectrum during olive tree branches burning events. We estimated an otBB-OA emission factor of 3.45±0.2 g kg-1. Assuming that half of the olive trees branches are burned 2,300 tons of otBB-OA are emitted in Greece each winter. This is one of the most important fine aerosol emission sources during the winter months in the Mediterranean countries in which this activity is prevalent.

An Investigation of Hierachical Protein Recruitment to the Inhibitory Platelet Receptor, G6B-b

PubMed Central

Coxon, Carmen H.; Sadler, Amanda J.; Huo, Jiandong; Campbell, R. Duncan

2012-01-01

Platelet activation is regulated by both positive and negative signals. G6B-b is an inhibitory platelet receptor with an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM). The molecular basis of inhibition by G6B-b is currently unknown but thought to involve the SH2 domain-containing tyrosine phosphatase SHP-1. Here we show that G6B-b also associates with SHP-2, as well as SHP-1, in human platelets. Using a number of biochemical approaches, we found these interactions to be direct and that the tandem SH2 domains of SHP-2 demonstrated a binding affinity for G6B-b 100-fold higher than that of SHP-1. It was also observed that while SHP-1 has an absolute requirement for phosphorylation at both motifs to bind, SHP-2 can associate with G6B-b when only one motif is phosphorylated, with the N-terminal SH2 domain and the ITIM being most important for the interaction. A number of other previously unreported SH2 domain-containing proteins, including Syk and PLCγ2, also demonstrated specificity for G6B-b phosphomotifs and may serve to explain the observation that G6B-b remains inhibitory in the absence of both SHP-1 and SHP-2. In addition, the presence of dual phosphorylated G6B-b in washed human platelets can reduce the EC50 for both CRP and collagen. PMID:23185356

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect.

PubMed

Yin, Juntao; Hou, Yantao; Yin, Yuyun; Song, Xiaoyong

2017-01-01

Diabetes mellitus is an incurable metabolic disorder that seriously threatens human health. At present, there is no effective medication available to defeat it. This work intended to develop selenium-coated nanostructured lipid carriers (SeNLCs) for enhancing the oral bioavailability and the curative effect of berberine, an antidiabetic phytomedicine. Berberine-loaded SeNLCs (BB-SeNLCs) were prepared by hot-melt dispersion/homogenization procedure followed by in situ reduction. BB-SeNLCs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Pharmacokinetics of berberine solution, berberine-loaded NLCs (BB-NLCs) and BB-SeNLCs were studied in Sprague Dawley rats administered by oral gavage. The prepared BB-SeNLCs were around 160 nm in particle size with an EE of 90%. In addition, BB-SeNLCs exhibited a better sustained release of berberine compared to the plain NLCs. After oral administration, BB-SeNLCs greatly enhanced the oral bioavailability of berberine, which was approximately 6.63 times as much as that of berberine solution. The hypoglycemic effect of BB-SeNLCs was also significantly superior to that of BB-NLCs and berberine solution. It turned out that sustained drug release and good intestinal absorption, plus the synergy of selenium, were basically responsible for enhanced oral bioavailability and hypoglycemic effect. Our findings show that SeNLCs are promising nanocarriers for oral delivery of berberine to strengthen the antidiabetic action.

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect

PubMed Central

Yin, Juntao; Hou, Yantao; Yin, Yuyun; Song, Xiaoyong

2017-01-01

Diabetes mellitus is an incurable metabolic disorder that seriously threatens human health. At present, there is no effective medication available to defeat it. This work intended to develop selenium-coated nanostructured lipid carriers (SeNLCs) for enhancing the oral bioavailability and the curative effect of berberine, an antidiabetic phytomedicine. Berberine-loaded SeNLCs (BB-SeNLCs) were prepared by hot-melt dispersion/homogenization procedure followed by in situ reduction. BB-SeNLCs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Pharmacokinetics of berberine solution, berberine-loaded NLCs (BB-NLCs) and BB-SeNLCs were studied in Sprague Dawley rats administered by oral gavage. The prepared BB-SeNLCs were around 160 nm in particle size with an EE of 90%. In addition, BB-SeNLCs exhibited a better sustained release of berberine compared to the plain NLCs. After oral administration, BB-SeNLCs greatly enhanced the oral bioavailability of berberine, which was approximately 6.63 times as much as that of berberine solution. The hypoglycemic effect of BB-SeNLCs was also significantly superior to that of BB-NLCs and berberine solution. It turned out that sustained drug release and good intestinal absorption, plus the synergy of selenium, were basically responsible for enhanced oral bioavailability and hypoglycemic effect. Our findings show that SeNLCs are promising nanocarriers for oral delivery of berberine to strengthen the antidiabetic action. PMID:29263662

A plant Kunitz-type inhibitor mimics bradykinin-induced cytosolic calcium increase and intestinal smooth muscle contraction.

PubMed

Andrade, Sheila Siqueira; Smaili, Soraya Soubhi; Monteforte, Priscila Totarelli; Miranda, Antônio; Kouyoumdjian, Maria; Sampaio, Misako Uemura; Lopes, Guiomar Silva; Oliva, Maria Luiza V

2012-09-01

BbKI is a kallikrein inhibitor with a reactive site sequence similar to that of kinins, the vasoactive peptides inserted in kininogen moieties. This structural similarity probably contributes to the strong interaction with plasma kallikrein, the enzyme that releases, from high-molecular weight kininogen (HMWK), the proinflammatory peptide bradykinin, which acts on B(2) receptors (B(2)R). BbKI was examined on smooth muscle contraction and Ca(2+) mobilization, in which the kallikrein-kinin system is involved. Contrary to expectations, BbKI (1.8 μm) increased [Ca(2+)](c) and contraction, as observed with BK (2.0 μm). Not blocked by B(1) receptors (B(1)R), the BbKI agonistic effect was blocked by the B(2)R antagonist, HOE-140 (6 μm), and the involvement of B(2)R was confirmed in B(2)R-knockout mice intestine. The same tissue response was obtained using a synthetic peptide derived from the BbKI reactive site structure, more resistant than BK to angiotensin I-converting enzyme (ACE) hydrolysis. Depending on the concentration, BbKI has a dual effect. At a low concentration, BbKI acts as a potent kallikrein inhibitor; however, due to the similarity to BK, in high concentrations, BbKI greatly increases Ca(2+) release from internal storages, as a consequence of its interaction with B(2)R. Therefore, the antagonistic and agonistic effects of BbKI may be considered in conditions of B(2)R involvement.

Platelet-Derived Growth Factor-BB Stimulates Fibronectin Gene Expression in Fibroblasts Isolated from Rat Thoracic Aorta

DTIC Science & Technology

1994-06-13

MARYLAND 20814-4799 TEACHING HOSPITALS WALTER REED ARMY MEDtCA L CENTER APPROVAL SHEET NAVAL HOSPITAL. BETHESDA MALCOLM GROW AIR FORCE MEDICAL ...CENTER WILFORD HALL "IR FORCE MEDICAL CENTER Title of Dissertation: "Platelet-derived growth factor-BB stimulates fibronectin gene expression in...fascinating world of basic medical science. His dedication and pursuit of excellence in all facets of his work are standards by which I will guide my own

Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of α-adrenergic/imidazoline receptor ligands, and QSPR analysis.

PubMed

Vucicevic, J; Popovic, M; Nikolic, K; Filipic, S; Obradovic, D; Agbaba, D

2017-03-01

For this study, 31 compounds, including 16 imidazoline/α-adrenergic receptor (IRs/α-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log k BMC and log k wRP , respectively). Based on the retention factor (log k wRP ) and slope of the linear curve (S) the isocratic parameter (φ 0 ) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds. High correlations were obtained between logarithm of biopartitioning micellar chromatography (BMC) retention factor and effective permeability (r(log k BMC /log BB): 0.77), while for RP-HPLC system the correlations were lower (r(log k wRP /log BB): 0.58; r(S/log BB): -0.50; r(φ 0 /P e ): 0.61). Based on the log k BMC retention data and calculated molecular parameters of the examined compounds, quantitative structure-permeability relationship (QSPR) models were developed using partial least squares, stepwise multiple linear regression, support vector machine and artificial neural network methodologies. A high degree of structural diversity of the analysed IRs/α-ARs ligands and CNS drugs provides wide applicability domain of the QSPR models for estimation of blood-brain barrier penetration of the related compounds.

Standardization of a Protocol for Obtaining Platelet Rich Plasma from blood Donors; a Tool for Tissue Regeneration Procedures.

PubMed

Gómez, Lina Andrea; Escobar, Magally; Peñuela, Oscar

2015-01-01

To develop a protocol for obtaining autologous platelet rich plasma in healthy individuals and to determine the concentration of five major growth factors before platelet activation. This protocol could be integrated into the guidelines of good clinical practice and research in regenerative medicine. Platelet rich plasma was isolated by centrifugation from 38 healthy men and 42 women ranging from 18 to 59 years old. The platelet count and quantification of growth factors were analyzed in eighty samples, stratified for age and gender of the donor. Analyses were performed using parametric the t-test or Pearson's analysis for non-parametric distribution. P < 0.05 was considered statistically significant. Our centrifugation protocol allowed us to concentrate basal platelet counts from 1.6 to 4.9 times (mean = 2.8). There was no correlation between platelet concentration and the level of the following growth factors: VEGF-D (r = 0.009, p = 0.4105), VEGF-A (r = 0.0068, p = 0.953), PDGF subunit AA (p = 0.3618; r = 0.1047), PDGF-BB (p = 0.5936; r = 0.6095). In the same way, there was no correlation between donor gender and growth factor concentrations. Only TGF-β concentration was correlated to platelet concentration (r = 0.3163, p = 0.0175). The procedure used allowed us to make preparations rich in platelets, low in leukocytes and red blood cells, and sterile. Our results showed biological variations in content of growth factors in PRP. The factors influencing these results should be further studied.

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

Aviation System Safety Risk Management Tool Analysis. Volume 2: Appendices

DTIC Science & Technology

1993-10-01

Part Number FY AMC Case Number BATERY BB433AA 81 E 810421201 E’ BATTERY BB433AA 81 E 810421181 [’ BATTERY BB433AA 81 E 810514141 [’ BATIERY BB433AA 81...830520061 [- BAT=ERY NOT REC 83 E 830514071 -l BATTERY NOT REC 82 E 811102131 El BATERY NOT REC 82 E 820715191 " BATTERY NOT REC 82 E 820902051 "- BATERY NOT

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

Health behaviors associated with use of body building, weight loss, and performance enhancing supplements.

PubMed

Kao, Tzu-Cheg; Deuster, Patricia A; Burnett, Daniel; Stephens, Mark

2012-05-01

To identify health-related behaviors associated with potentially harmful dietary supplements (DS) - body building (BB), weight loss (WL) and performance enhancing (PE), explore common reasons and sources of information for DS use. Based on the 2005 Survey of 16,146 U.S. military personnel, BB users were dichotomized as yes (regular use - taking any supplement of BB at least once a week in past 12 months) or no; similarly defined for WL and PE. Weighted logistic regression models are used. BB, WL and PE were used by 19.4%, 17.0%, and 8.0% of participants, respectively. Significantly more users were overweight or obese: BMI ≥25 (vs. BMI<25); heavy drinkers (vs. abstainers); and users of taking steroids in their lifetime (vs. not). Most common reasons of BB, WL, and PE users wanted to increase muscle mass, lose weight, and improve physical performance (BB: 45.8%, WL: 54.8%, PE: 38.5%). Fewer than 30% discussed dietary supplements use with their healthcare providers. The leading source of dietary supplements information (BB: 27.8%, WL: 23.6%, PE: 30.0%) was magazines. The dietary supplements: BB, WL and PE were used by significant proportions of service members, and associated with risk-taking behaviors that may affect overall military readiness and public health. Published by Elsevier Inc.

Search for Stellar Streams Based on Data from the RAVE5 and Gaia TGAS Catalogues

NASA Astrophysics Data System (ADS)

Bajkova, A. T.; Bobylev, V. V.

2018-03-01

We have analyzed the space velocities of stars with the proper motions and trigonometric parallaxes from the Gaia TGAS catalogue in combination with the line-of-sight velocities from the RAVE5 catalogue. In the V, √ {{U^2} + 2{V^2}} velocity plane we have identified three clumps, BB17-1, BB17-2, and BB17-3, in the region of large velocities ( V<-150 km s-1). The stars of the BB17-1 and BB17-2 clumps are associated with the kinematic groups VelHel-6 and VelHel-7 detected previously by Helmi et al. We give the greatest attention to the BB17-3 clump. The latter is shown to be most closely linked with the debris of the globular cluster ω Cen. In the BB17-3 clump we have identified 28 stars with a low velocity dispersion with respect to the center of their distribution. All these stars have very close individual age estimates: log t ≈ 10. The distribution of metallicity indices in this sample is typical for the stars of the globular cluster ω Cen. In our opinion, the BB17-3 clump can be described as a homogeneous stream in the debris of the cluster ω Cen.

On the Vertical Nature of Biomass Burning Plumes by the California Coast and Their Relationship with Marine Boundary Layer Clouds

NASA Astrophysics Data System (ADS)

Hu, L.; Montzka, S. A.; Godwin, D.; Andrews, A. E.; Thoning, K. W.; Miller, B. R.; Sweeney, C.; Miller, J. B.; Lehman, S.; Siso, C.; Mondeel, D. J.; Hall, B. D.; Nance, J. D.; Tans, P. P.; Elkins, J. W.

2016-12-01

Biomass burning (BB) plumes can significantly impact stratocumulus clouds (Sc), the dominant cloud type by global area, by altering their microphysical properties. The California (CA) coast is home to one of the three major semi-permanent stratocumulus (Sc) cloud decks in the world and BB emissions are of growing concern in the western United States, owing to both a warmer climate and fire-control strategies over recent decades. The thickness and vertical position of BB plumes, especially relative to clouds, is critical to understand how the aerosol will affect the thermodynamic structure of the atmosphere, cloud properties, and radiative forcing. This study reports on the characterization of the vertical, spatial, and temporal nature of BB aerosol over coastal CA, based on airborne data collected in the months of July and August for 2013 and 2016. Results from over 100 soundings indicate that multiple BB plume layers exist above clouds, with the thickness of BB plumes and their vertical position relative to cloud top varying significantly as a function of distance from coastline. Comparison of soundings at a given location at two different times of day reveals significant variation in BB characteristics. Intercomparisons for BB plume characteristics are explored between the field data, NAAPS, and CALIPSO.

On the Vertical Nature of Biomass Burning Plumes by the California Coast and Their Relationship with Marine Boundary Layer Clouds

NASA Astrophysics Data System (ADS)

Hossein Mardi, A.; MacDonald, A. B.; Dadashazar, H.; Crosbie, E.; WANG, Z.; Lynch, P.; Campbell, J. R.; Jonsson, H.; Sorooshian, A.

2017-12-01

Biomass burning (BB) plumes can significantly impact stratocumulus clouds (Sc), the dominant cloud type by global area, by altering their microphysical properties. The California (CA) coast is home to one of the three major semi-permanent stratocumulus (Sc) cloud decks in the world and BB emissions are of growing concern in the western United States, owing to both a warmer climate and fire-control strategies over recent decades. The thickness and vertical position of BB plumes, especially relative to clouds, is critical to understand how the aerosol will affect the thermodynamic structure of the atmosphere, cloud properties, and radiative forcing. This study reports on the characterization of the vertical, spatial, and temporal nature of BB aerosol over coastal CA, based on airborne data collected in the months of July and August for 2013 and 2016. Results from over 100 soundings indicate that multiple BB plume layers exist above clouds, with the thickness of BB plumes and their vertical position relative to cloud top varying significantly as a function of distance from coastline. Comparison of soundings at a given location at two different times of day reveals significant variation in BB characteristics. Intercomparisons for BB plume characteristics are explored between the field data, NAAPS, and CALIPSO.

Statistical molecular design of building blocks for combinatorial chemistry.

PubMed

Linusson, A; Gottfries, J; Lindgren, F; Wold, S

2000-04-06

The reduction of the size of a combinatorial library can be made in two ways, either base the selection on the building blocks (BB's) or base it on the full set of virtually constructed products. In this paper we have investigated the effects of applying statistical designs to BB sets compared to selections based on the final products. The two sets of BB's and the virtually constructed library were described by structural parameters, and the correlation between the two characterizations was investigated. Three different selection approaches were used both for the BB sets and for the products. In the first two the selection algorithms were applied directly to the data sets (D-optimal design and space-filling design), while for the third a cluster analysis preceded the selection (cluster-based design). The selections were compared using visual inspection, the Tanimoto coefficient, the Euclidean distance, the condition number, and the determinant of the resulting data matrix. No difference in efficiency was found between selections made in the BB space and in the product space. However, it is of critical importance to investigate the BB space carefully and to select an appropriate number of BB's to result in an adequate diversity. An example from the pharmaceutical industry is then presented, where selection via BB's was made using a cluster-based design.

Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity

PubMed Central

Li, Wenpeng; Guo, Linjie; Rathi, Purva; Marinova, Ekaterina; Gao, Xiuhua; Wu, Meng-Feng; Liu, Hao; Dotti, Gianpietro; Gottschalk, Stephen; Metelitsa, Leonid S.; Heczey, Andras

2017-01-01

T cells engineered to express CD19-specific chimeric antigen receptors (CARs) have shown breakthrough clinical successes in patients with B-cell lymphoid malignancies. However, similar therapeutic efficacy of CAR T cells in solid tumors is yet to be achieved. In this study we systematically evaluated a series of CAR constructs targeting glypican-3 (GPC3), which is selectively expressed on several solid tumors. We compared GPC3-specific CARs that encoded CD3ζ (Gz) alone or with costimulatory domains derived from CD28 (G28z), 4-1BB (GBBz), or CD28 and 4-1BB (G28BBz). All GPC3-CARs rendered T cells highly cytotoxic to GPC3-positive hepatocellular carcinoma, hepatoblastoma, and malignant rhabdoid tumor cell lines in vitro. GBBz induced the preferential production of Th1 cytokines (interferon γ/granulocyte macrophage colony-stimulating factor) while G28z preferentially induced Th2 cytokines (interleukin-4/interleukin-10). Inclusion of 4-1BB in G28BBz could only partially ameliorate the Th2-polarizing effect of CD28. 4-1BB induced superior expansion of CAR T cells in vitro and in vivo. T cells expressing GPC3-CARs incorporating CD28, 4-1BB, or both induced sustained tumor regressions in two xenogeneic tumor models. Thus, GBBz CAR endows T cells with superior proliferative potential, potent antitumor activity, and a Th1-biased cytokine profile, justifying further clinical development of GBBz CAR for immunotherapy of GPC3-positive solid tumors. PMID:27530312

Does more favourable handling of the cerebrospinal fluid increase the diagnostic sensitivity of Borrelia burgdorferi sensu lato-specific PCR in Lyme neuroborreliosis?

PubMed

Forselv, Kristine J N; Lorentzen, Åslaug R; Ljøstad, Unn; Mygland, Åse; Eikeland, Randi; Kjelland, Vivian; Noraas, Sølvi; Quarsten, Hanne

2018-04-01

Tests for direct detection of Borrelia burgdorferi sensu lato (Bb) in Lyme neuroborreliosis (LNB) are needed. Detection of Bb DNA using PCR is promising, but clinical utility is hampered by low diagnostic sensitivity. We aimed to examine whether diagnostic sensitivity can be improved by the use of larger cerebrospinal fluid (CSF) volumes and faster handling of samples. Patients who underwent CSF examination for LNB were included. We collected two millilitres of CSF for PCR analysis, extracted DNA from the pellets within 24 h and analysed the eluate by two real-time PCR protocols (16S rRNA and OspA). Patients who fulfilled diagnostic criteria for LNB were classified as LNB cases and the rest as controls. Bb DNA in CSF was detected by PCR in seven of 28 adults with LNB. Two were Bb antibody negative. No Bb DNA was detected in CSF from 137 controls. Diagnostic sensitivity was 25% and specificity 100%. There was a non-significant trend towards larger CSF sample volume, faster handling of the sample, shorter duration of symptoms, and higher CSF cell count in the PCR-positive cases. We did not find that optimized handling of CSF increased diagnostic sensitivity of PCR in adults with LNB. However, our case series is small and we hypothesize that the importance of these factors will be clarified in further studies with larger case series and altered study design. PCR for diagnosis of LNB may be useful in cases without Bb antibodies due to short duration of symptoms.

Foreign Body Ingestion in Children: Should Button Batteries in the Stomach Be Urgently Removed?

PubMed

Lee, Jun Hee; Lee, Jee Hoo; Shim, Jung Ok; Lee, Jung Hwa; Eun, Baik-Lin; Yoo, Kee Hwan

2016-03-01

Foreign body (FB) ingestion is common in children, and button battery (BB) ingestion has been increasing in recent years. This study was to identify factors related to outcomes of FB ingestion, particularly BBs in the stomach. We evaluated whether the current recommendations are appropriate and aimed to suggest indications for endoscopic removal of BB in the stomach in young children. We investigated patient age, shape, size, location of FBs, spontaneous passage time and resulting complications among 76 children. We observed types, size, location of BB and outcomes, and analyzed their associations with complications. Coins and BB were the two most common FBs. Their shapes and sizes were not associated with the spontaneous passage time. Size, spontaneous passage time, and age were also not associated with any specific complications. For BB ingestion, all 5 cases with lithium batteries (≥1.5 cm, 3 V) presented moderate to major complications in the esophagus and stomach without any symptoms, even when the batteries were in the stomach and beyond the duodenum, while no complications were noted in 7 cases with alkaline batteries (<1.5 cm, 1.5 V) (p=0.001). All endoscopies were conducted within 24 hours after ingestion. The type and voltage of the battery should be considered when determining whether endoscopy is required to remove a BB in the stomach. For lithium battery ingestion in young children, urgent endoscopic removal might be important in order to prevent complications, even if the child is asymptomatic and the battery is smaller than 2 cm.

Influence of biomass burning on mixing state of sub-micron aerosol particles in the North China Plain

NASA Astrophysics Data System (ADS)

Kecorius, Simonas; Ma, Nan; Teich, Monique; van Pinxteren, Dominik; Zhang, Shenglan; Gröβ, Johannes; Spindler, Gerald; Müller, Konrad; Iinuma, Yoshiteru; Hu, Min; Herrmann, Hartmut; Wiedensohler, Alfred

2017-09-01

Particulate emissions from crop residue burning decrease the air quality as well as influence aerosol radiative properties on a regional scale. The North China Plain (NCP) is known for the large scale biomass burning (BB) of field residues, which often results in heavy haze pollution episodes across the region. We have been able to capture a unique BB episode during the international CAREBeijing-NCP intensive field campaign in Wangdu in the NCP (38.6°N, 115.2°E) from June to July 2014. It was found that aerosol particles originating from this BB event showed a significantly different mixing state compared with clean and non-BB pollution episodes. BB originated particles showed a narrower probability density function (PDF) of shrink factor (SF). And the maximum was found at shrink factor of 0.6, which is higher than in other episodes. The non-volatile particle number fraction during the BB episode decreased to 3% and was the lowest measured value compared to all other predefined episodes. To evaluate the influence of particle mixing state on aerosol single scattering albedo (SSA), SSA at different RHs was simulated using the measured aerosol physical-chemical properties. The differences between the calculated SSA for biomass burning, clean and pollution episodes are significant, meaning that the variation of SSA in different pollution conditions needs to be considered in the evaluation of aerosol direct radiative effects in the NCP. And the calculated SSA was found to be quite sensitive on the mixing state of BC, especially at low-RH condition. The simulated SSA was also compared with the measured values. For all the three predefined episodes, the measured SSA are very close to the calculated ones with assumed mixing states of homogeneously internal and core-shell internal mixing, indicating that both of the conception models are appropriate for the calculation of ambient SSA in the NCP.

40 CFR Appendix A to Subpart Bb of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart BB

Code of Federal Regulations, 2010 CFR

2010-07-01

... additional requirements. 63.7(f) Alternative Test Method Yes. 63.7(g) Data Analysis Yes. 63.7(h) Waiver of....8(g)(1) Data Reduction Yes. 63.8(g)(2) No Subpart BB does not require COMS or CEMS. 63.8(g)(3... Data Reports No Subpart BB does not require COMS. 63.10(f) Recordkeeping/Reporting Waiver Yes. 63.11(a...

Precision-cut liver slices as a model for the early onset of liver fibrosis to test antifibrotic drugs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westra, Inge M.; Oosterhuis, Dorenda; Groothuis, Geny M.M.

Induction of fibrosis during prolonged culture of precision-cut liver slices (PCLS) was reported. In this study, the use of rat PCLS was investigated to further characterize the mechanism of early onset of fibrosis in this model and the effects of antifibrotic compounds. Rat PCLS were incubated for 48 h, viability was assessed by ATP and gene expression of PDGF-B and TGF-β1 and the fibrosis markers Hsp47, αSma and Pcol1A1 and collagen1 protein expressions were determined. The effects of the antifibrotic drugs imatinib, sorafenib and sunitinib, PDGF-pathway inhibitors, and perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone, TGFβ-pathway inhibitors, were determined.more » After 48 h of incubation, viability of the PCLS was maintained and gene expression of PDGF-B was increased while TGF-β1 was not changed. Hsp47, αSma and Pcol1A1 gene expressions were significantly elevated in PCLS after 48 h, which was further increased by PDGF-BB and TGF-β1. The increased gene expression of fibrosis markers was inhibited by all three PDGF-inhibitors, while TGFβ-inhibitors showed marginal effects. The protein expression of collagen 1 was inhibited by imatinib, perindopril, tetrandrine and pirfenidone. In conclusion, the increased gene expression of PDGF-B and the down-regulation of fibrosis markers by PDGF-pathway inhibitors, together with the absence of elevated TGF-β1 gene expression and the limited effect of the TGFβ-pathway inhibitors, indicated the predominance of the PDGF pathway in the early onset of fibrosis in PCLS. PCLS appear a useful model for research of the early onset of fibrosis and for testing of antifibrotic drugs acting on the PDGF pathway. - Highlights: • During culture, fibrosis markers increased in precision-cut liver slices (PCLS). • Gene expression of PDGF-β was increased, while TGFβ was not changed in rat PCLS. • PDGF-pathway inhibitors down-regulated this increase of fibrosis markers. • TGFβ-pathway inhibitors had only minor effects on fibrosis markers. • Rat PCLS can be used to study the early onset of fibrosis.« less

Difference in production routes of water-soluble organic carbon in PM2.5 observed during non-biomass and biomass burning periods in Gwangju, Korea.

PubMed

Yu, Geun-Hye; Cho, Sung-Yong; Bae, Min-Suk; Park, Seung-Shik

2014-07-01

4 h integrated PM2.5 samples were collected from an urban site of Gwangju, Korea, for five days and analyzed for organic carbon and elemental carbon (OC and EC), total water-soluble OC (WSOC), hydrophilic and hydrophobic WSOC fractions (WSOCHPI and WSOCHPO), oxalate, and inorganic ionic species (sodium (Na(+)), ammonium (NH4(+)), potassium (K(+)), calcium (Ca(2+)), magnesium (Mg(2+)), chloride (Cl(-)), nitrate (NO3(-)), and sulfate (SO4(2-))) to investigate the possible sources of water-soluble organic aerosols. Two types of sampling periods were classified according to the regression relationship between black carbon (BC) concentrations measured at wavelengths of 370 nm (BC370nm) and 880 nm (BC880nm) using an aethalometer; the first period was traffic emission influence ("non-biomass burning (BB) period") and the second was biomass burning influence ("BB period"). The slope of the regression equation (BC370nm/BC880nm) was 0.95 for the non-BB period and 1.29 for the BB period. However, no noticeable difference in the WSOC/OC ratio, which can be used to infer the extent of secondary organic aerosol (SOA) formation, was found between the non-BB (0.61, range = 0.43-0.75) and BB (0.61, range = 0.52-0.68) periods, due to significant contribution of primary BB emissions to the WSOC. The concentrations of OC, WSOC and K(+), which were used as the BB emission markers, were 15.7 μg C m(-3) (11.5-24.3), 9.4 μg C m(-3) (7.0-12.7), and 1.2 μg m(-3) (0.6-2.7), respectively, during the BB period, and these results were approximately 1.7, 1.7, and 3.9 times higher than those during the non-BB period. During the non-BB period, good correlations among WSOC, SO4(2-) and oxalate, and poor correlations among WSOC, EC, and K(+) suggest that SOA is probably an important source of WSOC (and WSOCHPI) concentration. For the WSOC fractions, better correlations among WSOCHPI, oxalate (R(2) = 0.52), and SO4(2-) (R(2) = 0.57) were found than among WSOCHPO, oxalate (R(2) = 0.23), and SO4(2-) (R(2) = 0.20), suggesting that a significant proportion of the WSOCHPI fraction of OC could be produced through processes (gas-phase and heterogeneous oxidations) such as SOA formation. However, during the BB period, the BB emission source accounted for the high correlations between total WSOC (and WSOC fractions) and other relevant atmospheric parameters (EC, Na(+), Cl(-), K(+), and oxalate), with higher correlations in WSOCHPI than in WSOCHPO. These results suggest a significant contribution of BB emissions to WSOC.

Skeletal muscle hypertrophy and structure and function of skeletal muscle fibres in male body builders

PubMed Central

D'Antona, Giuseppe; Lanfranconi, Francesca; Pellegrino, Maria Antonietta; Brocca, Lorenza; Adami, Raffaella; Rossi, Rosetta; Moro, Giorgio; Miotti, Danilo; Canepari, Monica; Bottinelli, Roberto

2006-01-01

Needle biopsy samples were taken from vastus lateralis muscle (VL) of five male body builders (BB, age 27.4 ± 0.93 years; mean ±s.e.m.), who had being performing hypertrophic heavy resistance exercise (HHRE) for at least 2 years, and from five male active, but untrained control subjects (CTRL, age 29.9 ± 2.01 years). The following determinations were performed: anatomical cross-sectional area and volume of the quadriceps and VL muscles in vivo by magnetic resonance imaging (MRI); myosin heavy chain isoform (MHC) distribution of the whole biopsy samples by SDS-PAGE; cross-sectional area (CSA), force (Po), specific force (Po/CSA) and maximum shortening velocity (Vo) of a large population (n= 524) of single skinned muscle fibres classified on the basis of MHC isoform composition by SDS-PAGE; actin sliding velocity (Vf) on pure myosin isoforms by in vitro motility assays. In BB a preferential hypertrophy of fast and especially type 2X fibres was observed. The very large hypertrophy of VL in vivo could not be fully accounted for by single muscle fibre hypertrophy. CSA of VL in vivo was, in fact, 54% larger in BB than in CTRL, whereas mean fibre area was only 14% larger in BB than in CTRL. MHC isoform distribution was shifted towards 2X fibres in BB. Po/CSA was significantly lower in type 1 fibres from BB than in type 1 fibres from CTRL whereas both type 2A and type 2X fibres were significantly stronger in BB than in CTRL. Vo of type 1 fibres and Vf of myosin 1 were significantly lower in BB than in CTRL, whereas no difference was observed among fast fibres and myosin 2A. The findings indicate that skeletal muscle of BB was markedly adapted to HHRE through extreme hypertrophy, a shift towards the stronger and more powerful fibre types and an increase in specific force of muscle fibres. Such adaptations could not be fully accounted for by well known mechanisms of muscle plasticity, i.e. by the hypertrophy of single muscle fibre (quantitative mechanism) and by a regulation of contractile properties of muscle fibres based on MHC isoform content (qualitative mechanism). Two BB subjects took anabolic steroids and three BB subjects did not. The former BB differed from the latter BB mostly for the size of their muscles and muscle fibres. PMID:16339176

Short-term blueberry-enriched diet prevents and reverses object recognition memory loss in aging rats.

PubMed

Malin, David H; Lee, David R; Goyarzu, Pilar; Chang, Yu-Hsuan; Ennis, Lalanya J; Beckett, Elizabeth; Shukitt-Hale, Barbara; Joseph, James A

2011-03-01

Previously, 4 mo of a blueberry-enriched (BB) antioxidant diet prevented impaired object recognition memory in aging rats. Experiment 1 determined whether 1- and 2-mo BB diets would have a similar effect and whether the benefits would disappear promptly after terminating the diets. Experiment 2 determined whether a 1-mo BB diet could subsequently reverse existing object memory impairment in aging rats. In experiment 1, Fischer-344 rats were maintained on an appropriate control diet or on 1 or 2 mo of the BB diet before testing object memory at 19 mo postnatally. In experiment 2, rats were tested for object recognition memory at 19 mo and again at 20 mo after 1 mo of maintenance on a 2% BB or control diet. In experiment 1, the control group performed no better than chance, whereas the 1- and 2-mo BB diet groups performed similarly and significantly better than controls. The 2-mo BB-diet group, but not the 1-mo group, maintained its performance over a subsequent month on a standard laboratory diet. In experiment 2, the 19-mo-old rats performed near chance. At 20 mo of age, the rats subsequently maintained on the BB diet significantly increased their object memory scores, whereas the control diet group exhibited a non-significant decline. The change in object memory scores differed significantly between the two diet groups. These results suggest that a considerable degree of age-related object memory decline can be prevented and reversed by brief maintenance on BB diets. Copyright © 2011 Elsevier Inc. All rights reserved.

Exposure of a distinct PDCA-1+ (CD317) B cell population to agonistic anti-4-1BB (CD137) inhibits T and B cell responses both in vitro and in vivo.

PubMed

Vinay, Dass S; Lee, Seung J; Kim, Chang H; Oh, Ho Sik; Kwon, Byoung S

2012-01-01

4-1BB (CD137) is an important T cell activating molecule. Here we report that it also promotes development of a distinct B cell subpopulation co-expressing PDCA-1. 4-1BB is expressed constitutively, and its expression is increased when PDCA-1(+) B cells are activated. We found that despite a high level of surface expression of 4-1BB on PDCA-1(+) B cells, treatment of these cells with agonistic anti-4-1BB mAb stimulated the expression of only a few activation markers (B7-2, MHC II, PD-L2), cytokines (IL-12p40/p70), and chemokines (MCP-1, RANTES), as well as sTNFR1, and the immunosuppressive enzyme, IDO. Although the PDCA-1(+) B cells stimulated by anti-4-1BB expressed MHC II at high levels and took up antigens efficiently, Ig class switching was inhibited when they were pulsed with T-independent (TI) or T-dependent (TD) Ags and adoptively transferred into syngeneic recipients. Furthermore, when anti-4-1BB-treated PDCA-1(+) B cells were pulsed with OVA peptide and combined with Vα2(+)CD4(+) T cells, Ag-specific cell division was inhibited both in vitro and in vivo. Our findings suggest that the 4-1BB signal transforms PDCA-1(+) B cells into propagators of negative immune regulation, and establish an important role for 4-1BB in PDCA-1(+) B cell development and function.

Essential oils and Beauveria bassiana against Dermanyssus gallinae (Acari: Dermanyssidae): Towards new natural acaricides.

PubMed

Immediato, Davide; Figueredo, Luciana Aguiar; Iatta, Roberta; Camarda, Antonio; de Luna, Rafaela Lira Nogueira; Giangaspero, Annunziata; Brandão-Filho, Sinval Pinto; Otranto, Domenico; Cafarchia, Claudia

2016-10-15

Essential oils (EOs) and entomopathogenic fungi such as Beauveria bassiana (Bb) strains have the potential to be used as alternative insecticides and acaricides for controlling ectoparasites as Dermanyssus gallinae. These compounds have some limitations in their use: the acaricidal effect of EOs is rapid, but short-lived, whilst that of Bb is delayed, but long-lived. To evaluate the effect of both compounds combined against D. gallinae, the non-toxic dose of Eucalyptus globulus, Eucalyptus citriodora, Thymus vulgaris and Eugenia caryophyllata essential oils were firstly calculated for "native" strains of Bb. Subsequently, the effects of the combination of selected EOs with Bb against nymph and adult poultry red mites (PRMs) was assessed. EO concentrations ranging from 0.0015 to 8% v/v (i.e., nine double dilutions) were used to evaluate their effect on germination, sporulation and vegetative growth rates of native strains of Bb. A total of 1440 mites (720 nymphs and 720 adults) were divided into three-treated group (TGs) and one control group (CG). In TGs, mites were exposed to Bb in combination with the selected EO (TG1), EO alone (TG2) or Bb (TG3) alone. In the CG, mites were exposed to 0.1% tween 80 plus EO solvent (CG). E. globulus and E. citriodora were toxic for Bb in concentrations higher than 0.2% and 0.003% respectively, whilst E. caryophyllata and T. vulgaris were toxic at all concentrations tested against Bb. Based on the results of the toxicity assays against Bb, E. globulus was chosen to be tested as acaricide resulting non-toxic for Bb at concentration lower than 0.4%. Increased mortality of D. gallinae adults was recorded in TG1 than those in other TGs from 4days post-infection (T+4DPI). A 100% mortality of D. gallinae was recorded in adults at T+9DPI and at T+10DPI in nymphs in TG1 and later than T+11DPI in the other TGs. Used in combination with E. globulus, Bb displayed an earlier acaricidal effect towards both haematophagous D. gallinae stages. The combination of B. bassiana and E. globulus at 0.2% might be used for controlling arthropods of medical and veterinary importance as D. gallinae. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of carotid stenosis with axial high-resolution black-blood MR imaging.

PubMed

U-King-Im, Jean M; Trivedi, Rikin A; Sala, Evis; Graves, Martin J; Gaskarth, Mathew; Higgins, Nicholas J; Cross, Justin C; Hollingworth, William; Coulden, Richard A; Kirkpatrick, Peter J; Antoun, Nagui M; Gillard, Jonathan H

2004-07-01

High-resolution axial black-blood MR imaging (BB MRI) has been shown to be able to characterise carotid plaque morphology. The aim of this study was to explore the accuracy of this technique in quantifying the severity of carotid stenosis. A prospective study of 54 patients with symptomatic carotid disease was conducted, comparing BB MRI to the gold standard, conventional digital subtraction X-ray angiography (DSA). The BB MRI sequence was a fast-spin echo acquisition (TE = 42 ms, ETL = 24, field of view = 100 x 100 mm, slice thickness = 3.0 mm) at 1.5 T using a custom-built phased-array coil. Linear measurements of luminal and outer carotid wall diameter were made directly from the axial BB MRI slices by three independent blinded readers and stenosis was calculated according to European Carotid Surgery Trial (ECST) criteria. There was good agreement between BB MRI and DSA (intraclass correlation = 0.83). Inter-observer agreement was good (average kappa = 0.77). BB MRI was accurate for detection of severe stenosis (> or = 80%) with sensitivity and specificity of 87 and 81%, respectively. Eight cases of "DSA-defined" moderate stenosis were overestimated as severe by BB MRI and this may be related to non-circular lumens. Axial imaging with BB MRI could potentially be used to provide useful information about severity of carotid stenosis. Copyright 2004 Springer-Verlag

Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system.

PubMed

Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S; Philipp, Mario T

2017-02-02

Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi (Bb), affects both the central and peripheral nervous systems. Previously, we reported that in a model of acute LNB in rhesus monkeys, treatment with the anti-inflammatory drug dexamethasone significantly reduced both pleocytosis and levels of cerebrospinal fluid (CSF) immune mediators that were induced by Bb. Dexamethasone also inhibited the formation of inflammatory, neurodegenerative, and demyelinating lesions in the brain and spinal cord of these animals. In contrast, these signs were evident in the infected animals that were left untreated or in those that were treated with meloxicam, a non-steroidal anti-inflammatory drug. To address the differential anti-inflammatory effects of dexamethasone and meloxicam in the central nervous system (CNS), we evaluated the potential of these drugs to alter the levels of Bb-induced inflammatory mediators in culture supernatants of rhesus frontal cortex (FC) explants, primary rhesus astrocytes and microglia, and human oligodendrocytes. We also ascertained the potential of dexamethasone to modulate Bb-induced apoptosis in rhesus FC explants. As meloxicam is a known COX-2 inhibitor, we evaluated whether meloxicam altered the levels of COX-2 as induced by live Bb in cell lysates of primary rhesus astrocytes and microglia. Dexamethasone but not meloxicam significantly reduced the levels of several Bb-induced immune mediators in culture supernatants of FC explants, astrocytes, microglia, and oligodendrocytes. Dexamethasone also had a protective effect on Bb-induced neuronal and oligodendrocyte apoptosis in rhesus FC explants. Further, meloxicam significantly reduced the levels of Bb-induced COX-2 in microglia, while both Bb and meloxicam were unable to alter the constitutive levels of COX-2 in astrocytes. These data indicate that dexamethasone and meloxicam have differential anti-inflammatory effects on Bb-induced inflammation in glial and neuronal cells of the CNS and help explain the in vivo findings of significantly reduced inflammatory mediators in the CSF and lack of inflammatory neurodegenerative lesions in the brain and spinal cord of Bb-infected animals that were treated with dexamethasone but not meloxicam. Signaling cascades altered by dexamethasone could serve as possible therapeutic targets for limiting CNS inflammation and tissue damage in LNB.

[Experimental research on the effects of different activators on the formation of platelet-rich gel and the release of bioactive substances in human platelet-rich plasma].

PubMed

Yang, Y; Zhang, W; Cheng, B

2017-01-20

Objective: To explore the effects of calcium gluconate and thrombin on the formation of platelet-rich gel (PRG) and the release of bioactive substances in human platelet-rich plasma (PRP) and the clinical significance. Methods: Six healthy blood donors who met the inclusion criteria were recruited in our unit from May to August in 2016. Platelet samples of each donor were collected for preparation of PRP. (1) PRP in the volume of 10 mL was collected from each donor and divided into thrombin activation group (TA, added with 0.5 mL thrombin solution in dose of 100 U/mL) and calcium gluconate activation group (CGA, added with 0.5 mL calcium gluconate solution in dose of 100 g/L) according to the random number table, with 5 mL PRP in each group. Then the PRP of the two groups was activated in water bath at 37 ℃ for 1 h. The formation time of PRG was recorded, and the formation situation of PRG was observed within 1 hour of activation. After being activated for 1 h, one part of PRG was collected to observe the distribution of fibrous protein with HE staining, and another part of PRG was collected to observe platelet ultrastructure under transmission electron microscope (TEM). After being activated for 1 h, the supernatant was collected to determine the content of transforming growth factor β(1, )platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor, basic fibroblast growth factor (bFGF), epidermal growth factor, and insulin-like growth factorⅠby enzyme-linked immunosorbent assay. (2) Another 10 mL PRP from each donor was collected and grouped as above, and the platelet suspension was obtained after two times of centrifugation and resuspension with phosphate buffered saline, respectively. And then they were treated with corresponding activator for 1 h as that in experiment (1). Nanoparticle tracking analyzer was used to detect the concentrations of microvesicles with different diameters and total microvesicles derived from platelet. Data were processed with t test. Results: (1) The formation time of PRG in group TA was (228±40) s, and the PRG volume reached the maximum at this moment. The PRG volume shrunk to the minimum after 30 minutes of activation. The formation time of PRG in group CGA was (690±71) s, and the PRG volume reached the maximum at this moment. After 55 minutes of activation, the PRG volume shrunk to the minimum. The formation time of PRG in group TA was obviously shorter than that in group CGA ( t =15.17, P <0.01). (2) HE staining showed that after 1 hour of activation, the red-stained area of fibrous protein in PRG of group TA was large and densely distributed, while that of group CGA was small and loosely distributed. TEM revealed that after 1 hour of activation, the platelets in PRG of group TA were fragmented, while lysing platelet structure, lysing α granule structure, intact α granule structure, and intact dense body structure were observed in PRG of group CGA. (3) The content of PDGF-BB released by PRP in group TA was (7.4±0.8) ng/mL, which was obviously higher than that in group CGA [(4.9±0.5) ng/mL, t =5.41, P <0.01]. The content of bFGF released by PRP in group CGA was (960±151) pg/mL, which was significantly higher than that in group TA [(384±56) pg/mL, t =8.75, P <0.01]. The content of the other 4 growth factors released by PRP in the two groups was close (with t values from 0.11 to 1.97, P values above 0.05). (4) The concentrations of total microvesicles, microvesicles with diameter more than 100 nm, and exosomes with diameter less than or equal to 100 nm derived from platelet in group CGA were (165.8±15.1)×10(8)/mL, (142.4±12.3)×10(8)/mL, and (23.4±2.9)×10(8)/mL respectively, which were significantly higher than those in group TA [(24.7±4.6)×10(8)/mL, (22.6±4.0)×10(8)/mL, and (2.1±0.7)×10(8)/mL, with t values from 17.36 to 22.66, P values below 0.01]. Conclusions: Calcium gluconate can slowly activate PRP, resulting in slowly shrunk PRG with high content of bFGF and high concentration of microvesicles, which is suitable for repairing articular cavity and sinus tract wound. Thrombin can rapidly activate PRP, resulting in quickly shrunk PRG with high content of PDGF-BB and a certain concentration of microvesicles, which is suitable for repairing acute trauma.

Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study

PubMed Central

Merenstein, Daniel J; Tan, Tina P; Molokin, Aleksey; Smith, Keisha Herbin; Roberts, Robert F; Shara, Nawar M; Mete, Mihriye; Sanders, Mary Ellen; Solano-Aguilar, Gloria

2015-01-01

Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states. PMID:25569274

Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults.

PubMed

Meng, Huicui; Ba, Zhaoyong; Lee, Yujin; Peng, Jiayu; Lin, Junli; Fleming, Jennifer A; Furumoto, Emily J; Roberts, Robert F; Kris-Etherton, Penny M; Rogers, Connie J

2017-03-01

Probiotic bacteria modulate immune parameters and inflammatory outcomes. Emerging evidence demonstrates that the matrix used to deliver probiotics may influence the efficacy of probiotic interventions in vivo. The aims of the current study were to evaluate (1) the effect of one species, Bifidobacterium animalis subsp. lactis BB-12 at a dose of log10 ± 0.5 CFUs/day on immune responses in a randomized, partially blinded, 4-period crossover, free-living study, and (2) whether the immune response to BB-12 differed depending on the delivery matrix. Healthy adults (n = 30) aged 18-40 years were recruited and received four treatments in a random order: (A) yogurt smoothie alone; smoothie with BB-12 added (B) before or (C) after yogurt fermentation, or (D) BB-12 given in capsule form. At baseline and after each 4-week treatment, peripheral blood mononuclear cells (PBMCs) were isolated, and functional and phenotypic marker expression was assessed. BB-12 interacted with peripheral myeloid cells via Toll-like receptor 2 (TLR-2). The percentage of CD14 + HLA-DR + cells in peripheral blood was increased in male participants by all yogurt-containing treatments compared to baseline (p = 0.0356). Participants who consumed yogurt smoothie with BB-12 added post-fermentation had significantly lower expression of TLR-2 on CD14 + HLA-DR + cells (p = 0.0186) and reduction in TNF-α secretion from BB-12- (p = 0.0490) or LPS-stimulated (p = 0.0387) PBMCs compared to baseline. These findings not only demonstrate a potential anti-inflammatory effect of BB-12 in healthy adults, but also indicate that the delivery matrix influences the immunomodulatory properties of BB-12.

Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta-analysis.

PubMed

Albillos, Agustín; Zamora, Javier; Martínez, Javier; Arroyo, David; Ahmad, Irfan; De-la-Peña, Joaquin; Garcia-Pagán, Juan-Carlos; Lo, Gin-Ho; Sarin, Shiv; Sharma, Barjesh; Abraldes, Juan G; Bosch, Jaime; Garcia-Tsao, Guadalupe

2017-10-01

Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013). Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231). © 2017 by the American Association for the Study of Liver Diseases.

Measurement of |V(cb)| and the form-factor slope in B --> Dl- nu(l) decays in events tagged by a fully reconstructed B meson.

PubMed

Aubert, B; Karyotakis, Y; Lees, J P; Poireau, V; Prencipe, E; Prudent, X; Tisserand, V; Garra Tico, J; Grauges, E; Martinelli, M; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Battaglia, M; Brown, D N; Kerth, L T; Kolomensky, Yu G; Lynch, G; Osipenkov, I L; Tackmann, K; Tanabe, T; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Asgeirsson, D J; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Randle-Conde, A; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Atmacan, H; Gary, J W; Liu, F; Long, O; Vitug, G M; Yasin, Z; Zhang, L; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Mazur, M A; Richman, J D; Beck, T W; Eisner, A M; Heusch, C A; Kroseberg, J; Lockman, W S; Martinez, A J; Schalk, T; Schumm, B A; Seiden, A; Wang, L; Winstrom, L O; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Bloom, P C; Ford, W T; Gaz, A; Hirschauer, J F; Nagel, M; Nauenberg, U; Smith, J G; Wagner, S R; Ayad, R; Toki, W H; Wilson, R J; Feltresi, E; Hauke, A; Jasper, H; Karbach, T M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Kobel, M J; Nogowski, R; Schubert, K R; Schwierz, R; Volk, A; Bernard, D; Latour, E; Verderi, M; Clark, P J; Playfer, S; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Fioravanti, E; Franchini, P; Luppi, E; Munerato, M; Negrini, M; Petrella, A; Piemontese, L; Santoro, V; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Contri, R; Guido, E; Lo Vetere, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Tosi, S; Chaisanguanthum, K S; Morii, M; Adametz, A; Marks, J; Schenk, S; Uwer, U; Bernlochner, F U; Klose, V; Lacker, H M; Bard, D J; Dauncey, P D; Tibbetts, M; Behera, P K; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Derkach, D; da Costa, J Firmino; Grosdidier, G; Le Diberder, F; Lepeltier, V; Lutz, A M; Malaescu, B; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; Clarke, C K; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Paramesvaran, S; Wren, A C; Brown, D N; Davis, C L; Denig, A G; Fritsch, M; Gradl, W; Hafner, A; Alwyn, K E; Bailey, D; Barlow, R J; Jackson, G; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Henderson, S W; Sciolla, G; Spitznagel, M; Yamamoto, R K; Zhao, M; Patel, P M; Robertson, S H; Schram, M; Lazzaro, A; Lombardo, V; Palombo, F; Stracka, S; Bauer, J M; Cremaldi, L; Godang, R; Kroeger, R; Sonnek, P; Summers, D J; Zhao, H W; Simard, M; Taras, P; Nicholson, H; De Nardo, G; Lista, L; Monorchio, D; Onorato, G; Sciacca, C; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Wang, W F; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Gagliardi, N; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Sanchez, P del Amo; Ben-Haim, E; Bonneaud, G R; Briand, H; Chauveau, J; Hamon, O; Leruste, Ph; Marchiori, G; Ocariz, J; Perez, A; Prendki, J; Sitt, S; Gladney, L; Biasini, M; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Calderini, G; Carpinelli, M; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Pegna, D Lopes; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Anulli, F; Baracchini, E; Cavoto, G; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Wilson, F F; Emery, S; Esteve, L; de Monchenault, G Hamel; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Allen, M T; Aston, D; Bartoldus, R; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Sevilla, M Franco; Gabareen, A M; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; West, C A; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Young, C C; Ziegler, V; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Burchat, P R; Edwards, A J; Miyashita, T S; Ahmed, S; Alam, M S; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Soffer, A; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Wray, B C; Drummond, B W; Izen, J M; Lou, X C; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Choi, H H F; Hamano, K; King, G J; Kowalewski, R; Lewczuk, M J; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Puccio, E M T; Band, H R; Chen, X; Dasu, S; Flood, K T; Pan, Y; Prepost, R; Vuosalo, C O; Wu, S L

2010-01-08

We present a measurement of the Cabibbo-Kobayashi-Maskawa matrix element |V(cb)| and the form-factor slope rho2 in B --> Dl- nu(l) decays based on 460x10(6) BB events recorded at the Upsilon(4S) resonance with the BABAR detector. B --> Dl- nu(l) decays are selected in events in which a hadronic decay of the second B meson is fully reconstructed. We measure B(B- --> D0 l- nu(l))/B(B- --> Xl- nu(l)) = (0.255+/-0.009+/-0.009) and B(B0 --> D+ l- nu(l))/B(B0 --> Xl- nu(l)) = (0.230+/-0.011+/-0.011), along with the differential decay distribution in B --> Dl- nu(l) decays. We then determine G(1)|V(cb)| = (42.3+/-1.9+/-1.4)x10(-3) and rho2 = 1.20+/-0.09+/-0.04, where G(1) is the hadronic form factor at the point of zero recoil.

Nonradioactive Screening Method for Isolation of Disease-Specific Probes To Diagnose Plant Diseases Caused by Mycoplasmalike Organisms

PubMed Central

Lee, Ing-Ming; Davis, Robert E.; DeWitt, Natalie D.

1990-01-01

DNA fragments of tomato big bud (BB) mycoplasmalike organism (MLO) in diseased periwinkle plants (Catharanthus roseus L.) were cloned to pSP6 plasmid vectors and amplified in Escherichia coli JM83. A nonradioactive method was developed and used to screen for MLO-specific recombinants. Cloned DNA probes were prepared by nick translation of the MLO recombinant plasmids by using biotinylated nucleotides. The probes all hybridized with nucleic acid from BB MLO-infected, but not healthy, plants. Results from dot hybridization analyses indicated that several MLOs, e.g., those of Italian tomato big bud, periwinkle little leaf, and clover phyllody, are closely related to BB MLO. The Maryland strain of aster yellows and maize bushy stunt MLOs are also related to BB MLO. Among the remaining MLOs used in this study, Vinca virescence and elm yellows MLOs may be very distantly related, if at all, to BB MLO. Potato witches' broom, clover proliferation, ash yellows, western X, and Canada X MLOs are distantly related to BB MLO. Southern hybridization analyses revealed that BB MLO contains extrachromosomal DNA that shares sequence homologies with extrachromosomal DNAs from aster yellows and periwinkle little leaf MLOs. Images PMID:16348195

Percolation analysis for cosmic web with discrete points

NASA Astrophysics Data System (ADS)

Zhang, Jiajun; Cheng, Dalong; Chu, Ming-Chung

2016-03-01

Percolation analysis has long been used to quantify the connectivity of the cosmic web. Unlike most of the previous works using density field on grids, we have studied percolation analysis based on discrete points. Using a Friends-of-Friends (FoF) algorithm, we generate the S-bb relation, between the fractional mass of the largest connected group (S) and the FoF linking length (bb). We propose a new model, the Probability Cloud Cluster Expansion Theory (PCCET) to relate the S-bb relation with correlation functions. We show that the S-bb relation reflects a combination of all orders of correlation functions. We have studied the S-bb relation with simulation and find that the S-bb relation is robust against redshift distortion and incompleteness in observation. From the Bolshoi simulation, with Halo Abundance Matching (HAM), we have generated a mock galaxy catalogue. Good matching of the projected two-point correlation function with observation is confirmed. However, comparing the mock catalogue with the latest galaxy catalogue from SDSS DR12, we have found significant differences in their S-bb relations. This indicates that the mock catalogue cannot accurately recover higher order correlation functions than the two-point correlation function, which reveals the limit of HAM method.

Respiratory muscle adaptations: a comparison between bodybuilders and endurance athletes.

PubMed

Hackett, D A; Johnson, N; Chow, C

2013-04-01

The purpose of this study was to compare the respiratory muscle and lung function measures of bodybuilders (BB) and endurance athletes (EA). Forty-two male subjects (22 BB and 20 EA) aged 20-35 years underwent respiratory muscle strength measurements (MIP and MEP), lung function testing (FEV1, FVC, FEV1/FVC%, IC, ERV, FRC, RV, and TLC), hydrostatic weighing and VO2max testing. One-repetition maximum (1RM) for bench press, squat and deadlift was performed by BB. BB had significantly greater MIP and MEP compared to EA by 43% and 53% respectively (P<0.01). Moderate correlation was found for MEP and 1RM bench press (P<0.01), and weak correlations found for the squat and deadlift (P<0.01). Fat-free mass was significantly greater for BB compared with EA (P<0.01), while VO2max was significantly greater for EA compared with BB (P<0.01). No differences in lung function indices were observed between groups. When compared to EA, BB exhibited significantly greater respiratory muscle strength. The maximal load lifted for bench press predicted expiratory muscle strength gain. Lung function measures did not differ between the groups.

The effects of energetic and informational masking on The Words-in-Noise Test (WIN).

PubMed

Wilson, Richard H; Trivette, Cristine P; Williams, Daniel A; Watts, Kelly L

2012-01-01

In certain masking paradigms, the masker can have two components, energetic and informational. Energetic masking is the traditional peripheral masking, whereas informational masking involves confusions (uncertainty) between the signal and masker that originate more centrally in the auditory system. Sperry et al (1997) used Northwestern University Auditory Test No. 6 (NU-6) words in multitalker babble to study the differential effects of energetic and informational masking using babble played temporally forward (FB) and backward (BB). The FB and BB are the same except BB is void of the contextual and semantic content cues that are available in FB. It is these informational cues that are thought to fuel informational masking. Sperry et al found 15% better recognition performance (∼3 dB) on BB than on FB, which can be interpreted as the presence of informational masking in the FB condition and not in the BB condition (Dirks and Bower, 1969). The Words-in-Noise Test (WIN) (Wilson, 2003; Wilson and McArdle, 2007) uses NU-6 words as the signal and multitalker babble as the masker, which is a combination of stimuli that potentially could produce informational masking. The WIN presents 5 or 10 words at each of seven signal-to-noise ratios (S/N, SNR) from 24 to 0 dB in 4 dB decrements with the 50% correct point being the metric of interest. The same recordings of the NU-6 words and multitalker babble used by Sperry et al are used in the WIN. To determine whether informational masking was involved with the WIN. Descriptive, quasi-experimental designs were conducted in three experiments using FB and BB in various paradigms in which FB and BB varied from 4.3 sec concatenated segments to essentially continuous. Eighty young adults with normal hearing and 64 older adults with sensorineural hearing losses participated in a series of three experiments. Experiment 1 compared performance on the normal WIN (FB) with performance on the WIN in which the babble segment with each word was reversed temporally (BB). Experiment 2 examined the effects of continuous FB and BB segments on WIN performance. Experiment 3 replicated the Sperry et al (1997) experiment at 4 and 0 dB S/N using NU-6 words in the FB and BB conditions. Experiment 1-with the WIN paradigm, recognition performances on FB and BB were the same for listeners with normal hearing and listeners with hearing loss, except at the 0 dB S/N with the listeners with normal hearing at which performance was significantly better on BB than FB. Experiment 2-recognition performances on FB and BB were the same at all SNRs for listeners with normal hearing using a slightly modified WIN paradigm. Experiment 3-there was no difference in performances on the FB and BB conditions with either of the two SNRs. Informational masking was not involved in the WIN paradigm. The Sperry et al results were not replicated, which is thought to be related to the way in which the Sperry et al BB condition was produced. American Academy of Audiology.

Baseline Field Testing of BB-2590 Lithium-Ion Batteries using an iRobot FasTac 510 Robot

DTIC Science & Technology

2010-09-17

No. 21320 Baseline Field Testing of BB-2590 Lithium - Ion Batteries using an iRobot FasTac 510 Robot U.S. Army Tank...SEP 2010 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Baseline Field Testing of BB-2590 Lithium - Ion Batteries using an iRobot...COVERED (From - To) Baseline Field Testing of BB-2590 Lithium - Ion Batteries using an 4. TITLE AND SUBTITLE iRobot FasTac 510 Robot 5a. CONTRACT

Firing rate modulation of human motor units in different muscles during isometric contraction with various forces.

PubMed

Seki, K; Narusawa, M

1996-05-06

To examine the factors affecting the control of human motor units, rate coding strategies of the motor units were investigated in upper limb and intrinsic hand muscles during voluntary isometric contraction of steady force levels up to 80% of maximal voluntary contraction. Numerous spike trains from single motor units were recorded from the m. first dorsal interosseous (FDI) and the m. biceps brachii (BB) of eight human subjects by means of tungsten micro-electrodes, and the mean firing rate (MFR) was calculated for each subject and inter-individual comparisons made. The MFRs of the FDI were larger than that of the BB at the higher force level, and substantial differences were not found between these muscles at the lower force level. The slope of the linear regression line of MFRs vs. exerted forces for the FDI was more than twice that for the BB. Therefore, isometric force control of the FDI depends more on the rate coding strategy. The difference in rate coding between the FDI and BB motor units may be determined by factors other than muscle fiber composition, because both muscles are known to possess a similar composition of fiber types. Possible mechanisms underlying these characteristics of rate coding strategy are considered in this report.

MODIS On-Board Blackbody Function and Performance

NASA Technical Reports Server (NTRS)

Xiaoxiong, Xiong; Wenny, Brian N.; Wu, Aisheng; Barnes, William

2009-01-01

Two MODIS instruments are currently in orbit, making continuous global observations in visible to long-wave infrared wavelengths. Compared to heritage sensors, MODIS was built with an advanced set of on-board calibrators, providing sensor radiometric, spectral, and spatial calibration and characterization during on-orbit operation. For the thermal emissive bands (TEB) with wavelengths from 3.7 m to 14.4 m, a v-grooved blackbody (BB) is used as the primary calibration source. The BB temperature is accurately measured each scan (1.47s) using a set of 12 temperature sensors traceable to NIST temperature standards. The onboard BB is nominally operated at a fixed temperature, 290K for Terra MODIS and 285K for Aqua MODIS, to compute the TEB linear calibration coefficients. Periodically, its temperature is varied from 270K (instrument ambient) to 315K in order to evaluate and update the nonlinear calibration coefficients. This paper describes MODIS on-board BB functions with emphasis on on-orbit operation and performance. It examines the BB temperature uncertainties under different operational conditions and their impact on TEB calibration and data product quality. The temperature uniformity of the BB is also evaluated using TEB detector responses at different operating temperatures. On-orbit results demonstrate excellent short-term and long-term stability for both the Terra and Aqua MODIS on-board BB. The on-orbit BB temperature uncertainty is estimated to be 10mK for Terra MODIS at 290K and 5mK for Aqua MODIS at 285K, thus meeting the TEB design specifications. In addition, there has been no measurable BB temperature drift over the entire mission of both Terra and Aqua MODIS.

Susceptibility to fatty acid-induced β-cell dysfunction is enhanced in prediabetic diabetes-prone biobreeding rats: a potential link between β-cell lipotoxicity and islet inflammation.

PubMed

Tang, Christine; Naassan, Anthony E; Chamson-Reig, Astrid; Koulajian, Khajag; Goh, Tracy T; Yoon, Frederick; Oprescu, Andrei I; Ghanim, Husam; Lewis, Gary F; Dandona, Paresh; Donath, Marc Y; Ehses, Jan A; Arany, Edith; Giacca, Adria

2013-01-01

β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity may be synergistic. Thus, β-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth (WF) rats. Rats received a 48-h iv infusion of saline or Intralipid plus heparin (IH) (to elevate free fatty acid levels ~2-fold) followed by hyperglycemic clamp or islet secretion studies ex vivo. IH significantly decreased β-cell function, assessed both by the disposition index (insulin secretion corrected for IH-induced insulin resistance) and in isolated islets, in dp-BB, but not in dr-BB or WF, rats, and the effect of IH was inhibited by the antioxidant N-acetylcysteine. Furthermore, IH significantly increased islet cytokine mRNA and plasma cytokine levels (monocyte chemoattractant protein-1 and IL-10) in dp-BB, but not in dr-BB or WF, rats. All dp-BB rats had mononuclear infiltration of islets, which was absent in dr-BB and WF rats. In conclusion, the presence of insulitis was permissive for IH-induced β-cell dysfunction in the BB rat, which suggests a link between β-cell lipotoxicity and islet inflammation.

The effect of music with and without binaural beat audio on operative anxiety in patients undergoing cataract surgery: a randomized controlled trial

PubMed Central

Wiwatwongwana, D; Vichitvejpaisal, P; Thaikruea, L; Klaphajone, J; Tantong, A; Wiwatwongwana, A

2016-01-01

Purpose To investigate the anxiolytic effects of binaural beat embedded audio in patients undergoing cataract surgery under local anesthesia. Methods This prospective RCT included 141 patients undergoing cataract surgery under local anesthesia. The patients were randomized into three groups; the Binaural beat music group (BB), the plain music intervention group (MI), and a control group (ear phones with no music). Blood pressure (BP) and heart rate were measured on admission, at the beginning of and 20 min after the start of the operation. Peri-operative anxiety level was assessed using the State-Trait Anxiety Inventory questionnaire (STAI). Results The BB and MI groups comprised 44 patients each and the control group 47. Patients in the MI group and BB group showed significant reduction of STAI state scores after music intervention compared with the control group (P<0.001) but the difference was not significant between the MI and BB group (STAI-S score MI group −7.0, BB group −9.0, P=0.085). Systolic BP was significantly lower in both MI (P=0.043) and BB (0.040) groups although there was no difference between the two groups (P=1.000). A significant reduction in heart rate was seen only in the BB group (BB vs control P=0.004, BB vs MI P=0.050, MI vs control P=0.303). Conclusion Music, both with and without binaural beat, was proven to decrease anxiety level and lower systolic BP. Patients who received binaural beat audio showed additional decrease in heart rate. Binaural beat embedded musical intervention may have benefit over musical intervention alone in decreasing operative anxiety. PMID:27740618

Motor unit potentials of the erector spinae muscle by concentric needle electromyography.

PubMed

Posa, Andreas; Niśkiewicz, Izabela; Emmer, Alexander; Kluge, Yorck; Kornhuber, Malte E

2017-03-01

The needle electromyography (EMG) serves to supply additional information in patients with suspected neuromuscular disorders. We aimed to provide motor unit potential (MUP) data by concentric needle EMG in the erector spinae (ES) in comparison with biceps brachii (BB) and lateral vastus (LV). Electromyography MUP data ( n ) were obtained in ES (517), BB (539), and LV (627) in 32 healthy volunteers (16f). Motor unit potential data: amplitude (μV) 393 ± 174 (ES), 375 ± 162 (BB), and 577 ± 304 (LV); duration (ms) 10.4 ± 2.4 (ES), 10.1 ± 2.1 (BB), and 11.1 ± 2.3 (LV), area (μV × ms) 585 ± 327 (ES), 538 ± 267 (BB), and 881 ± 492 (LV); phase number 3.23 ± 0.94 (ES), 2.98 ± 0.76 (BB), and 3.19 ± 0.81 (LV); size index 0.60 ± 0.56 (ES), 0.51 ± 0.53 (BB), and 0.96 ± 0.55 (LV). LV displayed higher values ( p at least <.001) for MUP amplitude, duration, area, and size index as compared to both, BB and ES. Concentric needle EMG investigations in healthy adult human subjects revealed similar MUP parameters in the ES and BB muscles, while in the LV muscle MUP amplitude, duration, area, and size index were significantly larger. Different neuromuscular disorders display a predominant involvement of proximally located muscles such as truncal muscles. The present results given here may facilitate the diagnosis of neuromuscular disorders.

The effect of music with and without binaural beat audio on operative anxiety in patients undergoing cataract surgery: a randomized controlled trial.

PubMed

Wiwatwongwana, D; Vichitvejpaisal, P; Thaikruea, L; Klaphajone, J; Tantong, A; Wiwatwongwana, A

2016-11-01

PurposeTo investigate the anxiolytic effects of binaural beat embedded audio in patients undergoing cataract surgery under local anesthesia.MethodsThis prospective RCT included 141 patients undergoing cataract surgery under local anesthesia. The patients were randomized into three groups; the Binaural beat music group (BB), the plain music intervention group (MI), and a control group (ear phones with no music). Blood pressure (BP) and heart rate were measured on admission, at the beginning of and 20 min after the start of the operation. Peri-operative anxiety level was assessed using the State-Trait Anxiety Inventory questionnaire (STAI).ResultsThe BB and MI groups comprised 44 patients each and the control group 47. Patients in the MI group and BB group showed significant reduction of STAI state scores after music intervention compared with the control group (P<0.001) but the difference was not significant between the MI and BB group (STAI-S score MI group -7.0, BB group -9.0, P=0.085). Systolic BP was significantly lower in both MI (P=0.043) and BB (0.040) groups although there was no difference between the two groups (P=1.000). A significant reduction in heart rate was seen only in the BB group (BB vs control P=0.004, BB vs MI P=0.050, MI vs control P=0.303).ConclusionMusic, both with and without binaural beat, was proven to decrease anxiety level and lower systolic BP. Patients who received binaural beat audio showed additional decrease in heart rate. Binaural beat embedded musical intervention may have benefit over musical intervention alone in decreasing operative anxiety.

Perceptions, opinions and knowledge of pharmacists towards the use of complementary medicines by people living with cancer.

PubMed

Harnett, Joanna; Le, Trong Quy; Smith, Lorraine; Krass, Ines

2018-05-09

Background Biologically-based complementary medicine (BB-CM) use is prevalent amongst people living with cancer. Pharmacists play an important role in the provision of standard treatments for cancer. Less is known about pharmacist's provision of BB-CM information. Objective This study investigated the opinions, perceptions and knowledge of pharmacists regarding the use of BB-CMs by people living with cancer and the facilitators and barriers to providing information and advice. Setting Australia. Method A cross-sectional 53-item survey was developed and the survey link distributed in two professional associations newsletters. The associations represent ~29,000 pharmacists. Questions were categories into pharmacist's perceptions, opinions, and knowledge towards the use of BB-CM in cancer. Main Outcome Measure Scores obtained from responses to perception, opinion and knowledge statements and responses to demographic questions Results Respondents (n=70) were predominantly female (73%), Caucasian (66%) and under 40 years of age (78%). Respondents estimated that 19% of daily inquiries related to BB-CMs. Seventy-two per cent of respondents believed they had a responsibility to advise about the concomitant use of BB-CM with standard cancer treatments despite 60% reporting a lack of confidence in their knowledge. There was a moderate positive association (Spearman's rho 0.41 p= 0.001) between a pharmacists confidence in their level of knowledge and their total knowledge scores. The main barriers to providing information about BB-CMs reported were inadequate training in BB-CMs (94%) and reservations about the evidence base for efficacy and safety (50%). Conclusion Pharmacists have a role to play in counselling people living with cancer about their use of BB-CMs and this role could be maximized with further training and education in this area.

Association of vitamin D receptor BsmI rs1544410 and ApaI rs7975232 polymorphisms with susceptibility to adolescent idiopathic scoliosis

PubMed Central

Yin, Xin; Wang, Huadong; Guo, Jidong; Zhang, Liang; Zhang, Yupeng; Li, Li; Hou, Shuxun

2018-01-01

Abstract Background: AIS is the most common spinal deformity disease, yet its etiology remains uncertain. Significant associations have been found between AIS risk and vitamin D receptor (VDR) gene polymorphisms; however, some of these results are controversial. The aim of this study was to determine whether VDR BsmI rs1544410 and ApaI rs7975232 polymorphisms are correlated with AIS. Methods: Databases, including PubMed, EMBASE, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Database, and the Wanfang Database, were systematically searched, and eligible case–control studies that explored the association of VDR (BsmI and ApaI) and the susceptibility to AIS were selected. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study population. Results: A total of 5 studies with 717 cases and 554 controls fulfilled the inclusion criteria after assessment by 2 reviewers. Generally, significant correlations were found between the BsmI polymorphism and AIS risk in overall populations and in Asian populations (overall population: B vs b: OR = 2.12, 95% CI = 1.21–3.75, P = .009; BB vs bb: OR = 3.38, 95% CI = 1.08–10.57, P = .036; Bb vs bb: OR = 2.50, 95% CI = 1.29–4.82, P = .006; BB/Bb vs bb: OR = 2.71, 95% CI = 1.31–5.63, P = .007; Asian population: B vs b: OR = 2.42, 95% CI = 1.27–4.61, P = .007; BB vs bb: OR = 4.09, 95% CI = 1.03–16.22, P = .045; Bb vs bb: OR =  2.94, 95% CI = 1.42–6.10, P = .004; BB/Bb vs bb: OR = 3.23, 95% CI = 1.42–7.35, P = .005). There was no significant association observed in Caucasian populations (all P > .05). With regard to the ApaI polymorphism, we found that it significantly decreased the risk of AIS (Aa vs AA: OR = 0.43, 95% CI = 0.24–0.77, P = .004; Aa/aa vs AA: OR = 0.52, 95% CI = 0.30–0.91, P = .023); however, we could not draw a definitive conclusion for Caucasian populations, as no studies have been conducted in this group to determine the role of the VDR ApaI polymorphism in AIS etiology and development. Conclusion: VDR BsmI was significantly associated with AIS susceptibility in the overall and Asian populations, while the VDR ApaI polymorphism only played a key role in AIS etiology and development in Asian populations. PMID:29480871

Measurement of the decays B--> phiK and B--> phiK*.

PubMed

Aubert, B; Boutigny, D; Gaillard, J M; Hicheur, A; Karyotakis, Y; Lees, J P; Robbe, P; Tisserand, V; Palano, A; Chen, G P; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Reinertsen, P L; Stugu, B; Abbott, B; Abrams, G S; Borgland, A W; Breon, A B; Brown, D N; Button-Shafer, J; Cahn, R N; Clark, A R; Fan, Q; Gill, M S; Gowdy, S J; Gritsan, A; Groysman, Y; Jacobsen, R G; Kadel, R W; Kadyk, J; Kerth, L T; Kluth, S; Kolomensky, Y G; Kral, J F; LeClerc, C; Levi, M E; Liu, T; Lynch, G; Meyer, A B; Momayezi, M; Oddone, P J; Perazzo, A; Pripstein, M; Roe, N A; Romosan, A; Ronan, M T; Shelkov, V G; Telnov, A V; Wenzel, W A; Bright-Thomas, P G; Harrison, T J; Hawkes, C M; Kirk, A; Knowles, D J; O'Neale, S W; Penny, R C; Watson, A T; Watson, N K; Deppermann, T; Koch, H; Krug, J; Kunze, M; Lewandowski, B; Peters, K; Schmuecker, H; Steinke, M; Andress, J C; Barlow, N R; Bhimji, W; Chevalier, N; Clark, P J; Cottingham, W N; De Groot, N; Dyce, N; Foster, B; Mass, A; McFall, J D; Wallom, D; Wilson, F F; Abe, K; Hearty, C; Mattison, T S; McKenna, J A; Thiessen, D; Camanzi, B; Jolly, S; McKemey, A K; Tinslay, J; Blinov, V E; Bukin, A D; Bukin, D A; Buzykaev, A R; Dubrovin, M S; Golubev, V B; Ivanchenko, V N; Korol, A A; Kravchenko, E A; Onuchin, A P; Salnikov, A A; Serednyakov, S I; Skovpen, Y I; Telnov, V I; Yushkov, A N; Lankford, A J; Mandelkern, M; McMahon, S; Stoker, D P; Ahsan, A; Arisaka, K; Buchanan, C; Chun, S; Branson, J G; MacFarlane, D B; Prell, S; Rahatlou, S; Raven, G; Sharma, V; Campagnari, C; Dahmes, B; Hart, P A; Kuznetsova, N; Levy, S L; Long, O; Lu, A; Richman, J D; Verkerke, W; Witherell, M; Yellin, S; Beringer, J; Dorfan, D E; Eisner, A M; Frey, A; Grillo, A A; Grothe, M; Heusch, C A; Johnson, R P; Kroeger, W; Lockman, W S; Pulliam, T; Sadrozinski, H; Schalk, T; Schmitz, R E; Schumm, B A; Seiden, A; Turri, M; Walkowiak, W; Williams, D C; Wilson, M G; Chen, E; Dubois-Felsmann, G P; Dvoretskii, A; Hitlin, D G; Metzler, S; Oyang, J; Porter, F C; Ryd, A; Samuel, A; Weaver, M; Yang, S; Zhu, R Y; Devmal, S; Geld, T L; Jayatilleke, S; Mancinelli, G; Meadows, B T; Sokoloff, M D; Bloom, P; Fahey, S; Ford, W T; Gaede, F; Johnson, D R; Michael, A K; Nauenberg, U; Olivas, A; Park, H; Rankin, P; Roy, J; Sen, S; Smith, J G; van Hoek, W C; Wagner, D L; Blouw, J; Harton, J L; Krishnamurthy, M; Soffer, A; Toki, W H; Wilson, R J; Zhang, J; Brandt, T; Brose, J; Colberg, T; Dahlinger, G; Dickopp, M; Dubitzky, R S; Maly, E; Müller-Pfefferkorn, R; Otto, S; Schubert, K R; Schwierz, R; Spaan, B; Wilden, L; Behr, L; Bernard, D; Bonneaud, G R; Brochard, F; Cohen-Tanugi, J; Ferrag, S; Roussot, E; T'Jampens, S; Thiebaux, C; Vasileiadis, G; Verderi, M; Anjomshoaa, A; Bernet, R; Di Lodovico, F; Khan, A; Muheim, F; Playfer, S; Swain, J E; Falbo, M; Bozzi, C; Dittongo, S; Folegani, M; Piemontese, L; Treadwell, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Falciai, D; Finocchiaro, G; Patteri, P; Peruzzi, I M; Piccolo, M; Xie, Y; Zallo, A; Bagnasco, S; Buzzo, A; Contri, R; Crosetti, G; Fabbricatore, P; Farinon, S; Lo Vetere, M; Macri, M; Monge, M R; Musenich, R; Pallavicini, M; Parodi, R; Passaggio, S; Pastore, F C; Patrignani, C; Pia, M G; Priano, C; Robutti, E; Santroni, A; Morii, M; Bartoldus, R; Dignan, T; Hamilton, R; Mallik, U; Cochran, J; Crawley, H B; Fischer, P A; Lamsa, J; Meyer, W T; Rosenberg, E I; Benkebil, M; Grosdidier, G; Hast, C; Höcker, A; Lacker, H M; LePeltier, V; Lutz, A M; Plaszczynski, S; Schune, M H; Trincaz-Duvoid, S; Valassi, A; Wormser, G; Bionta, R M; Brigljevic, V; Fackler, O; Fujino, D; Lange, D J; Mugge, M; Shi, X; van Bibber, K; Wenaus, T J; Wright, D M; Wuest, C R; Carroll, M; Fry, J R; Gabathuler, E; Gamet, R; George, M; Kay, M; Payne, D J; Sloane, R J; Touramanis, C; Aspinwall, M L; Bowerman, D A; Dauncey, P D; Egede, U; Eschrich, I; Gunawardane, N J; Martin, R; Nash, J A; Sanders, P; Smith, D; Azzopardi, D E; Back, J J; Dixon, P; Harrison, P F; Potter, R J; Shorthouse, H W; Strother, P; Vidal, P B; Williams, M I; Cowan, G; George, S; Green, M G; Kurup, A; Marker, C E; McGrath, P; McMahon, T R; Ricciardi, S; Salvatore, F; Scott, I; Vaitsas, G; Brown, D; Davis, C L; Allison, J; Barlow, R J; Boyd, J T; Forti, A; Fullwood, J; Jackson, F; Lafferty, G D; Savvas, N; Simopoulos, E T; Weatherall, J H; Farbin, A; Jawahery, A; Lillard, V; Olsen, J; Roberts, D A; Schieck, J R; Blaylock, G; Dallapiccola, C; Flood, K T; Hertzbach, S S; Kofler, R; Lin, C S; Moore, T B; Staengle, H; Willocq, S; Wittlin, J; Brau, B; Cowan, R; Sciolla, G; Taylor, F; Yamamoto, R K; Britton, D I; Milek, M; Patel, P M; Trischuk, J; Lanni, F; Palombo, F; Bauer, J M; Booke, M; Cremaldi, L; Eschenburg, V; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Martin, J P; Nief, J Y; Seitz, R; Taras, P; Zacek, V; Nicholson, H; Sutton, C S; Cartaro, C; Cavallo, N; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Paolucci, P; Piccolo, D; Sciacca, C; LoSecco, J M; Alsmiller, J R; Gabriel, T A; Handler, T; Brau, J; Frey, R; Iwasaki, M; Sinev, N B; Strom, D; Colecchia, F; Dal Corso, F; Dorigo, A; Galeazzi, F; Margoni, M; Michelon, G; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Torassa, E; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; De La Vaissière, C; Del Buono, L; Hamon, O; Le Diberder, F; Leruste, P; Lory, J; Roos, L; Stark, J; Versillé, S; Manfredi, P F; Re, V; Speziali, V; Frank, E D; Gladney, L; Guo, Q H; Panetta, J H; Angelini, C; Batignani, G; Bettarini, S; Bondioli, M; Carpinelli, M; Forti, F; Giorgi, M A; Lusiani, A; Martinez-Vidal, F; Morganti, M; Neri, N; Paoloni, E; Rama, M; Rizzo, G; Sandrelli, F; Simi, G; Triggiani, G; Walsh, J; Haire, M; Judd, D; Paick, K; Turnbull, L; Wagoner, D E; Albert, J; Bula, C; Lu, C; McDonald, K T; Miftakov, V; Schaffner, S F; Smith, A J; Tumanov, A; Varnes, E W; Cavoto, G; del Re, D; Faccini, R; Ferrarotto, F; Ferroni, F; Fratini, K; Lamanna, E; Leonardi, E; Mazzoni, M A; Morganti, S; Piredda, G; Safai Tehrani, F; Serra, M; Voena, C; Christ, S; Waldi, R; Adye, T; Franek, B; Geddes, N I; Gopal, G P; Xella, S M; Aleksan, R; De Domenico, G; Emery, S; Gaidot, A; Ganzhur, S F; Giraud, P F; Hamel De Monchenault, G; Kozanecki, W; Langer, M; London, G W; Mayer, B; Serfass, B; Vasseur, G; Yeche, C; Zito, M; Copty, N; Purohit, M V; Singh, H; Yumiceva, F X; Adam, I; Anthony, P L; Aston, D; Baird, K; Bartelt, J; Bloom, E; Boyarski, A M; Bulos, F; Calderini, G; Claus, R; Convery, M R; Coupal, D P; Coward, D H; Dorfan, J; Doser, M; Dunwoodie, W; Field, R C; Glanzman, T; Godfrey, G L; Grosso, P; Himel, T; Huffer, M E; Innes, W R; Jessop, C P; Kelsey, M H; Kim, P; Kocian, M L; Langenegger, U; Leith, D W; Luitz, S; Luth, V; Lynch, H L; Manzin, G; Marsiske, H; Menke, S; Messner, R; Moffeit, K C; Mount, R; Muller, D R; O'Grady, C P; Petrak, S; Quinn, H; Ratcliff, B N; Robertson, S H; Rochester, L S; Roodman, A; Schietinger, T; Schindler, R H; Schwiening, J; Serbo, V V; Snyder, A; Soha, A; Spanier, S M; Stahl, A; Stelzer, J; Su, D; Sullivan, M K; Talby, M; Tanaka, H A; Trunov, A; Va'vra, J; Wagner, S R; Weinstein, A J; Wisniewski, W J; Young, C C; Burchat, P R; Cheng, C H; Kirkby, D; Meyer, T I; Roat, C; De Silva, A; Henderson, R; Bugg, W; Cohn, H; Hart, E; Weidemann, A W; Benninger, T; Izen, J M; Kitayama, I; Lou, X C; Turcotte, M; Bianchi, F; Bona, M; Di Girolamo, B; Gamba, D; Smol, A; Zanin, D; Bosisio, L; Della Ricca, G; Lanceri, L; Pompili, A; Poropat, P; Prest, M; Vallazza, E; Vuagnin, G; Panvini, R S; Brown, C M; Kowalewski, R; Roney, J M; Band, H R; Charles, E; Dasu, S; Elmer, P; Hu, H; Johnson, J R; Liu, R; Nielsen, J; Orejudos, W; Pan, Y; Prepost, R; Scott, I J; Sekula, S J; von Wimmersperg-Toeller, J H; Wu, S L; Yu, Z; Zobering, H; Kordich, T M; Neal, H

2001-10-08

We have observed the decays B--> phiK and phiK(*) in a sample of over 45 million B mesons collected with the BABAR detector at the PEP-II collider. The measured branching fractions are B(B+--> phiK+) = (7.7(+1.6)(-1.4)+/-0.8)x10(-6), B(B0--> phiK0) = (8.1(+3.1)(-2.5)+/-0.8)x10(-6), B(B+--> phiK(*+)) = (9.7(+4.2)(-3.4)+/-1.7)x10(-6), and B(B0--> phiK(*0)) = (8.7(+2.5)(-2.1)+/-1.1)x10(-6). We also report the upper limit B(B+--> phipi(+))<1.4x10(-6) ( 90% C.L.).

Growth factor and proteinase profile of Vivostat® platelet-rich fibrin linked to tissue repair.

PubMed

Agren, M S; Rasmussen, K; Pakkenberg, B; Jørgensen, B

2014-07-01

Autologous platelet-rich fibrin (PRF(®)) is prepared by the automatic Vivostat(®) system. Conflicting results with Vivostat PRF in acute wound healing prompted us to examine its cellular and biomolecular composition. Specifically, platelets, selected growth factors and matrix metalloproteinase (MMP)-9 were quantified using novel analytical methods. Ten healthy non-thrombocytopenic volunteers donated blood for generation of intermediate fibrin-I and final PRF. Anticoagulated whole blood and serum procured in parallel served as baseline controls. Leucocyte, erythrocyte and platelet counts in whole blood and fibrin-I were determined by automated haematology analyser. Platelet concentration in PRF was quantified manually by stereologic analysis of Giemsa-stained tissue sections, and the total content of five growth factors and MMP-9 by enzyme-linked immunosorbent assays. The number of leucocytes and erythrocytes was reduced (P < 0·001), whereas platelets increased (P < 0·001) in fibrin-I versus whole blood. PRF contained 982 ± 206 × 10(9) platelets/l representing 3·9-fold (P < 0·001) enrichment relative to whole blood. Growth factor abundance in Vivostat PRF and serum was in descending order: transforming growth factor-β1 [5·1-fold higher in PRF than serum, P < 0·001] > platelet-derived growth factor (PDGF)-AB [2·5-fold, P < 0·01] > PDGF-BB [1·6-fold, P < 0·05] > vascular endothelial growth factor > basic fibroblast growth factor [75-fold, P < 0·001]. MMP-9 was reduced 139-fold (P < 0·001) compared with serum, reflecting leucocyte depletion in PRF. The gained knowledge on platelet enrichment and biomolecular constituents may guide clinicians in their optimal use of Vivostat PRF for tissue regenerative applications. © 2013 International Society of Blood Transfusion.

32 CFR 552.102 - Requirements for possession and use.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-defined and privately-owned firearms, ammunition, BB and pellet guns, knives, bows and arrows, and crossbows under the following conditions: (a) Privately-owned firearms, crossbows, BB and pellet guns..., registered crossbows, registered BB and pellet guns and registered firearms within their quarters. (c...

Flattop regulates basal body docking and positioning in mono- and multiciliated cells

PubMed Central

Gegg, Moritz; Böttcher, Anika; Burtscher, Ingo; Hasenoeder, Stefan; Van Campenhout, Claude; Aichler, Michaela; Walch, Axel; Grant, Seth G N; Lickert, Heiko

2014-01-01

Planar cell polarity (PCP) regulates basal body (BB) docking and positioning during cilia formation, but the underlying mechanisms remain elusive. In this study, we investigate the uncharacterized gene Flattop (Fltp) that is transcriptionally activated during PCP acquisition in ciliated tissues. Fltp knock-out mice show BB docking and ciliogenesis defects in multiciliated lung cells. Furthermore, Fltp is necessary for kinocilium positioning in monociliated inner ear hair cells. In these cells, the core PCP molecule Dishevelled 2, the BB/spindle positioning protein Dlg3, and Fltp localize directly adjacent to the apical plasma membrane, physically interact and surround the BB at the interface of the microtubule and actin cytoskeleton. Dlg3 and Fltp knock-outs suggest that both cooperatively translate PCP cues for BB positioning in the inner ear. Taken together, the identification of novel BB/spindle positioning components as potential mediators of PCP signaling might have broader implications for other cell types, ciliary disease, and asymmetric cell division. DOI: http://dx.doi.org/10.7554/eLife.03842.001 PMID:25296022

On-Orbit Operation and Performance of MODIS Blackbody

NASA Technical Reports Server (NTRS)

Xiong, X.; Chang, T.; Barnes, W.

2009-01-01

MODIS collects data in 36 spectral bands, including 20 reflective solar bands (RSB) and 16 thermal emissive bands (TES). The TEB on-orbit calibration is performed on a scan-by-scan basis using a quadratic algorithm that relates the detector response with the calibration radiance from the sensor on-board blackbody (BB). The calibration radiance is accurately determined each scan from the BB temperature measured using a set of 12 thermistors. The BB thermistors were calibrated pre-launch with traceability to the NIST temperature standard. Unlike many heritage sensors, the MODIS BB can be operated at a constant temperature or with the temperature continuously varying between instrument ambient (about 270K) and 315K. In this paper, we provide an overview of both Terra and Aqua MODIS on-board BB operations, functions, and on-orbit performance. We also examine the impact of key calibration parameters, such as BB emissivity and temperature (stability and gradient) determined from its thermistors, on the TEB calibration and Level I (LIB) data product uncertainty.

Safety of Bifidobacterium animalis Subsp. Lactis (B. lactis) Strain BB-12-Supplemented Yogurt in Healthy Children.

PubMed

Tan, Tina P; Ba, Zhaoyong; Sanders, Mary E; D'Amico, Frank J; Roberts, Robert F; Smith, Keisha H; Merenstein, Daniel J

2017-02-01

Probiotics are live microorganisms that may provide health benefits to the individual when consumed in sufficient quantities. For studies conducted on health or disease endpoints on probiotics in the United States, the Food and Administration has required those studies to be conducted as investigational new drugs. This phase I, double-blinded, randomized, controlled safety study represents the first requirement of this pathway. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp. lactis (B lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of children. The secondary aim was to assess the effect of BB-12-supplemented yogurt on the gut microbiota of the children. Sixty children ages 1 to 5 years were randomly assigned to consume 4 ounces of either BB-12-supplemented yogurt or nonsupplemented control yogurt daily for 10 days. The primary outcome was to assess safety and tolerability, as determined by the number of reported adverse events. A total of 186 nonserious adverse events were reported, with no significant differences between the control and BB-12 groups. No significant changes due to probiotic treatment were observed in the gut microbiota of the study cohort. BB-12-supplemented yogurt is safe and well-tolerated when consumed by healthy children. The present study will form the basis for future randomized clinical trials investigating the potential effects of BB-12-supplemented yogurt in different disease states.

Delivering Beauveria bassiana with electrostatic powder for the control of stored-product beetles.

PubMed

Athanassiou, Christos G; Rumbos, Christos I; Sakka, Maria; Potin, Olivier; Storm, Clare; Dillon, Aoife B

2017-08-01

The efficacy of a Beauveria bassiana-based formulation (Bb38) with Entostat, an electrostatically charged powder, was investigated as a surface treatment against Cryptolestes ferrugineus, Oryzaephilus surinamensis and Sitophilus granarius adults. In lab bioassays, the efficacy of Bb38 against the aforementioned species was examined on concrete, plywood, steel and ceramic, whereas its residual efficacy against the same species was assessed on concrete and steel in the presence or absence of illumination. Finally, the efficacy of Bb38 against O. surinamensis and S. granarius adults was assessed in a commercial grain storage facility under realistic field conditions. In the lab trials, O. surinamensis and C. ferrugineus were much more susceptible to Bb38 than S. granarius on all types of surfaces. Moreover, Bb38 was, at least for O. surinamensis and C. ferrugineus, as effective as the chemical standard (deltamethrin) for at least 2 months after the application, regardless of the presence or absence of illumination. Finally, in the field trial Bb38 provided a satisfactory level of control against O. surinamensis. Bb38 is an effective surface treatment, but its efficacy varies according to the target species, the type of surface and the time post-application. This is the first published report that examines the efficacy of Bb38 as a surface treatment for wider uses in empty warehouses and related storage facilities. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Investigation of the CCN Activity, BC and UVBC Mass Concentrations of Biomass Burning Aerosols during the 2013 BASELInE Campaign

NASA Technical Reports Server (NTRS)

Hsiao, Ta-Chih; Ye, Wei-Cheng; Wang, Sheng-Hsiang; Tsay, Si-Chee; Chen, Wei-Nai; Lin, Neng-Huei; Lee, Chung-Te; Hung, Hui-Ming; Chuang, Ming-Tung; Chantara, Somporn

2015-01-01

Biomass-burning (BB) aerosols, acting as cloud condensation nuclei (CCN), can influence cloud microphysical and radiative properties. In this study, we present CCN measured near the BB source regions over northern Southeast Asia (Doi Ang Khang, Thailand) and at downwind receptor areas (Lulin Atmospheric Background Station, Taiwan), focusing exclusively on 13-20 March 2013 as part of 2013 spring campaign of the Seven SouthEast Asian Studies (7-SEAS) intensive observation. One of the campaigns objectives is to characterize BB aerosols serving as CCN in SouthEast Asia (SEA). CCN concentrations were measured by a CCN counter at 5 supersaturation (SS) levels: 0.15%, 0.30%, 0.45%, 0.60%, and 0.75%. In addition, PM2.5 and black carbon mass concentrations were analyzed by using a tapered element oscillating microbalance and an aethalometer. It was found the number-size distributions and the characteristics of hygroscopicity (e.g., activation ratio and k) of BB aerosols in SEA have a strong diurnal pattern, and different behaviors of patterns were characterized under two distinct weather systems. The overall average value was low (0.05-0.1) but comparable with previous CCN studies in other BB source regions. Furthermore, a large fraction of UV-absorbing organic material (UVBC) and high Delta-C among BB aerosols were also observed, which suggest the existence of substantial particulate organic matter in fresh BB aerosols. These data provide the most extensive characterization of BB aerosols in SEA until now.

Biomass burning emissions of trace gases and particles in marine air at Cape Grim, Tasmania, 41° S

NASA Astrophysics Data System (ADS)

Lawson, S. J.; Keywood, M. D.; Galbally, I. E.; Gras, J. L.; Cainey, J. M.; Cope, M. E.; Krummel, P. B.; Fraser, P. J.; Steele, L. P.; Bentley, S. T.; Meyer, C. P.; Ristovski, Z.; Goldstein, A. H.

2015-07-01

Biomass burning (BB) plumes were measured at the Cape Grim Baseline Air Pollution Station during the 2006 Precursors to Particles campaign, when emissions from a fire on nearby Robbins Island impacted the station. Measurements made included non methane organic compounds (NMOCs) (PTR-MS), particle number size distribution, condensation nuclei (CN) > 3 nm, black carbon (BC) concentration, cloud condensation nuclei (CCN) number, ozone (O3), methane (CH4), carbon monixide (CO), hydrogen (H2), carbon dioxide (CO2), nitrous oxide (N2O), halocarbons and meteorology. During the first plume strike event (BB1), a four hour enhancement of CO (max ~ 2100 ppb), BC (~ 1400 ng m-3) and particles > 3 nm (~ 13 000 cm-3) with dominant particle mode of 120 nm were observed overnight. Dilution of the plume resulted in a drop in the dominant particle mode to 50 nm, and then growth to 80 nm over 5 h. This was accompanied by an increase in O3, suggesting that photochemical processing of air and condensation of low volatility oxidation products may be driving particle growth. The ability of particles > 80 nm (CN80) to act as CCN at 0.5 % supersaturation was investigated. The ΔCCN / ΔCN80 ratio was lowest during the fresh BB plume (56 %), higher during the particle growth event (77 %) and higher still (104 %) in background marine air. Particle size distributions indicate that changes to particle chemical composition, rather than particle size, are driving these changes. Hourly average CCN during both BB events were between 2000-5000 CCN cm-3, which were enhanced above typical background levels by a factor of 6-34, highlighting the dramatic impact BB plumes can have on CCN number in clean marine regions. During the 29 h of the second plume strike event (BB2) CO, BC and a range of NMOCs including acetonitrile and hydrogen cyanide (HCN) were clearly enhanced and some enhancements in O3 were observed (ΔO3 / ΔCO 0.001-0.074). A shortlived increase in NMOCs by a factor of 10 corresponded with a large CO enhancement, an increase of the NMOC / CO emission ratio (ER) by a factor of 2-4 and a halving of the BC / CO ratio. Rainfall on Robbins Island was observed by radar during this period which likely resulted in a lower fire combustion efficiency, and higher emission of compounds associated with smouldering. This highlights the importance of relatively minor meterological events on BB emissions. Emission factors (EF) were derived for a range of trace gases, some never before reported for Australian conditions, (including hydrogen, phenol and toluene) using a calculated ER to CO and a published CO EF. The EF derived for most species are comparable to other temperate Australian studies but lower than Northern Hemisphere temperate studies. This work demonstrates the substantial impact that BB plumes have on the composition of marine air, and the significant changes that can occur as the plume is diluted and interacts with other emission sources. We also provide new trace gas and particle EF for temperate southern Australia.

Examining the Influence of Beta Blockers and ACE Inhibitors on the Risk for Breast Cancer Recurrence: Results from the LACE Cohort

PubMed Central

Ganz, Patricia A.; Habel, Laurel A.; Weltzien, Erin K.; Caan, Bette J.; Cole, Steven W.

2011-01-01

There is increasing interest in the relationship between host lifestyle factors and the outcomes of cancer treatment. Behavioral factors, comorbid conditions, and non-cancer related pharmaceutical exposures may affect breast cancer (BC) outcomes. We used observational data from the LACE Study cohort (women with early stage BC from the Kaiser Permanente Northern California Cancer Registry) to examine the association between beta-blockers (BB) and/or angiotensin converting enzyme inhibitors (ACEi) and BC recurrence, BC-specific mortality, and overall mortality. Among 1,779 women, there were 292 BC recurrences, 174 BC deaths, and 323 total deaths. 23% were exposed to either a BB and/or an ACEi. These drugs were associated with older age, postmenopausal status, tamoxifen therapy, greater pre-diagnosis BMI, hypertension, and diabetes. In Cox proportional hazards models, ACEi exposure was associated with BC recurrence (HR 1.56, 95% CI 1.02, 2.39, p=0.04), but not cause-specific mortality or overall mortality. Combined ACEi and BB was associated with overall mortality (HR 1.94, 95% CI 1.22, 3.10, p=0.01). BB exposure was associated with lower hazard of recurrence and cause-specific mortality. However, there was no evidence of a dose response with either medication. For recurrence and cause-specific mortality, BB combined with ACEi was associated with a lower HR for the outcome than when ACEi alone was used. These hypothesis generating findings suggest that BC recurrence and survival were associated with exposure to two commonly used classes of anti-hypertensive medications. These observations need to be confirmed and suggest that greater attention should focus on the potential role of these commonly used medications in BC outcomes. PMID:21479924

Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance.

PubMed

Krzystek-Korpacka, Malgorzata; Diakowska, Dorota; Kapturkiewicz, Bartosz; Bębenek, Marek; Gamian, Andrzej

2013-08-28

Alternate colorectal cancer (CRC) screening and surveillance strategies are needed to pre-select candidates for invasive methods. We compared systemic inflammatory profiles in CRC (n=99), health (n=98), high CRC-risk conditions (n=48) and overt inflammation (n=69) by multiplexed analysis of IL-1β, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-B and CEA. Cytokines corresponded with CRC advancement. FGF2, GM-CSF, IL-1β, IL-6, MIP-1α, PDGF-BB, TNF-α, and VEGF-A were higher than in controls already in stage I CRC with FGF2, IL1-β, and MIP-1α higher than in high CRC-risk individuals as well. Cytokine panels devised to differentiate early CRC from controls, adenomas, or inflammatory bowel disease patients (IBD) had good accuracy but only IBD panel had promising specificity at 95% sensitivity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

32 CFR 552.128 - Requirements for possession and use.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., ammunition, pellet and BB guns, knives, bows and arrows, and crossbows under the following conditions: (a) Privately-owned firearms, crossbows, pellet and BB guns possessed or stored on the installation must be... pellet and BB guns, and registered firearms within their quarters. (c) Personnel residing in troop...

Human basal body basics.

PubMed

Vertii, Anastassiia; Hung, Hui-Fang; Hehnly, Heidi; Doxsey, Stephen

2016-01-01

In human cells, the basal body (BB) core comprises a ninefold microtubule-triplet cylindrical structure. Distal and subdistal appendages are located at the distal end of BB, where they play indispensable roles in cilium formation and function. Most cells that arrest in the G0 stage of the cell cycle initiate BB docking at the plasma membrane followed by BB-mediated growth of a solitary primary cilium, a structure required for sensing the extracellular environment and cell signaling. In addition to the primary cilium, motile cilia are present in specialized cells, such as sperm and airway epithelium. Mutations that affect BB function result in cilia dysfunction. This can generate syndromic disorders, collectively called ciliopathies, for which there are no effective treatments. In this review, we focus on the features and functions of BBs and centrosomes in Homo sapiens.

Suppression of a methionine synthase by calmodulin under environmental stress in the entomopathogenic fungus Beauveria bassiana.

PubMed

Kim, Jiyoung; Oh, Junsang; Yoon, Deok-Hyo; Sung, Gi-Ho

2017-10-01

Methionine synthase (MetE, EC 2.1.1.14) catalyses the final step in the methionine biosynthetic pathway. Methionine biosynthesis plays a major role in protein biogenesis and is the source of S-adenosyl methionine (SAM), the universal donor of methyl groups. In this study, we demonstrated that BbMetE acts as a typical MetE enzyme in the entomopathogenic fungus Beauveria bassiana. In addition, we found that BbMetE binds to calmodulin (CaM) in vitro and in vivo. The functional role of CaM binding to BbMetE was to negatively regulate BbMetE activity in B. bassiana. Our proton-nuclear magnetic resonance data revealed that CaM inhibitor W-7 increases methionine content in B. bassiana, suggesting that CaM negatively regulates the BbMetE activity. Environmental stress stimuli such as salt, H 2 O 2 and heat suppressed BbMetE activity in B. bassiana. W-7 reversed this effect, suggesting that the inhibitory mechanism is mediated through stimulation of CaM activity. Therefore, this work suggests that BbMetE plays an important role in methionine biosynthesis, which is mediated by environmental stress stimuli via the CaM signalling pathway. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice.

PubMed

Lee, Sang Kyu; Lee, Dong Ju; Jeon, Tae Won; Ko, Gyu Sub; Yoo, Se Hyun; Ha, Hyun Woo; Kang, Mi Jeong; Kang, Wonku; Kim, Sang Kyum; Jeong, Tae Cheon

2010-06-01

Halogenated organic compounds, such as 1-bromobutane (1-BB) , have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

Blueberries improve glucose tolerance and lipid handling without altering body composition in obese postmenopausal mice

PubMed Central

Elks, Carrie M.; Terrebonne, Jennifer D.; Ingram, Donald K.; Stephens, Jacqueline M.

2014-01-01

Objective Metabolic syndrome (MetS) risk increases significantly during menopause and remains elevated post-menopause. Several botanicals, including blueberries (BB), have been shown to delay MetS progression, but few studies have been conducted in postmenopausal animal models. Here, we examined the effects of BB supplementation on obese postmenopausal mice using a chemically-induced menopause model. Design and Methods After induction of menopause, mice were fed a high-fat diet or the same diet supplemented with 4% BB powder for 12 weeks. Body weight and body composition were measured, and mice were subjected to glucose and insulin tolerance tests. Serum triglycerides and adiponectin were measured, and liver histology and hepatic gene expression were assessed. Results: Menopausal and BB-supplemented mice had significantly higher body weights and fat mass than control mice, while menopausal mice had impaired glucose tolerance and higher serum triglycerides when compared with control and BB-supplemented mice. Menopausal mice also had hepatic steatosis that was prevented by BB supplementation and correlated with expression of genes involved in hepatic fatty acid oxidation. Conclusions We conclude that BB supplementation prevents the glucose intolerance and hepatic steatosis that occur in obese postmenopausal mice, and that these effects are independent of body weight. PMID:25611327

Air-to-Air Target Acquisition: Factors and Means of Improvement.

DTIC Science & Technology

1980-03-01

and an atmospheric modelo B t - Bb VISTARAQ C - b derived from input quantities and an B atmospheric model Bt Bb RAE/BAC C B derived from input...seair ’ h task in a !static, fielId. I" Osi c r r, I’lut ion is, dependi- ent upon the angle of’ t hr vi:i x is, -ft wh iih -wilil1y is measured and th

The regime of biomass burning aerosols over the Mediterranean basin based on satellite observations

NASA Astrophysics Data System (ADS)

Kalaitzi, Nikoleta; Gkikas, Antonis; Papadimas, Christos. D.; Hatzianastassiou, Nikolaos; Torres, Omar; Mihalopoulos, Nikolaos

2016-04-01

Biomass burning (BB) aerosol particles have significant effects on global and regional climate, as well as on regional air quality, visibility, cloud processes and human health.Biomass burning contributes by about 40% to the global emission of black carbonBC, and BB aerosols can exert a significant positive radiative forcing. The BB aerosols can originate from natural fires and human induced burning, such as wood or agricultural waste. However, the magnitude, but also the sign of the radiative forcing of BB aerosols is still uncertain, according to the third assessment report of IPCC (2013). Moreover, there are significant differences between different models as to their representation (inventories) of BB aerosols, more than for others, e.g. of fossil fuel origin. Therefore, it is important to better understand the spatial and temporal regime of BB aerosols. This is attempted here for the broader Mediterranean basin, which is a very interesting study area for aerosols, also being one of the most climaticallysensitive world regions. The determination of spatial and temporal regime of Mediterranean BB aerosols premises the identification of these particles at a complete spatial and long temporal coverage. Such a complete coverage is only ensured by contemporary satellite observations, which offer a challenging ability to characterize the existence of BB aerosols. This is possible thanks to the current availability of derived satellite products offering information on the size and absorption/scattering ability of aerosol particles. A synergistic use of such satellite aerosol data is made here, in conjunction with a developed algorithm, in order to identify the existence of BB aerosols over the Mediterranean basin over the 11-year period from 2005 to 2015. The algorithm operates, on a daily basis and at 1°×1°latitude-longitude resolution, setting threshold values (criteria) for specific physical and optical properties, which are representative of BB aerosols. More specifically, the algorithm examines the fulfillment of these criteria for Ångström Exponent (AE), Fine Fraction (FF) and Aerosol Index (AI). The AE and FF data, which are characteristic of the aerosol size, are derived from multispectralCollection 006 MODIS-AquaAerosol Optical Depth (AOD) data, whereas the AI data, that characterize the absorption ability of aerosols, are taken from the OMI-Aura database. The algorithm enables the identification of BB aerosols over specific geographical cells (pixels) throughout the study region, over both sea and land surfaces, during days of the 2005-2015 period. The results make possible the construction of a climatological-like database of Mediterranean BB aerosols, permitting to perceive the geographical patterns of their regime, namely the areas in which they occur, in relation to their timing, i.e. the months and seasons of their occurrence. This regime is quantified, which means that the frequency (absolute and percent) of occurrence of BB aerosols is calculated, along with the associated computed AOD values. The year by year variability of BB aerosols is also investigated over the period 2005-2015, with emphasis to inter-annual and seasonal tendencies.

Cell Population Kinetics of Collagen Scaffolds in Ex Vivo Oral Wound Repair

PubMed Central

Agis, Hermann; Collins, Amy; Taut, Andrei D.; Jin, Qiming; Kruger, Laura; Görlach, Christoph; Giannobile, William V.

2014-01-01

Biodegradable collagen scaffolds are used clinically for oral soft tissue augmentation to support wound healing. This study sought to provide a novel ex vivo model for analyzing healing kinetics and gene expression of primary human gingival fibroblasts (hGF) within collagen scaffolds. Sponge type and gel type scaffolds with and without platelet-derived growth factor-BB (PDGF) were assessed in an hGF containing matrix. Morphology was evaluated with scanning electron microscopy, and hGF metabolic activity using MTT. We quantitated the population kinetics within the scaffolds based on cell density and distance from the scaffold border of DiI-labled hGFs over a two-week observation period. Gene expression was evaluated with gene array and qPCR. The sponge type scaffolds showed a porous morphology. Absolute cell number and distance was higher in sponge type scaffolds when compared to gel type scaffolds, in particular during the first week of observation. PDGF incorporated scaffolds increased cell numbers, distance, and formazan formation in the MTT assay. Gene expression dynamics revealed the induction of key genes associated with the generation of oral tissue. DKK1, CYR61, CTGF, TGFBR1 levels were increased and integrin ITGA2 levels were decreased in the sponge type scaffolds compared to the gel type scaffold. The results suggest that this novel model of oral wound healing provides insights into population kinetics and gene expression dynamics of biodegradable scaffolds. PMID:25397671

Sulfur dioxide inhibits vascular smooth muscle cell proliferation via suppressing the Erk/MAP kinase pathway mediated by cAMP/PKA signaling

PubMed Central

Liu, D; Huang, Y; Bu, D; Liu, A D; Holmberg, L; Jia, Y; Tang, C; Du, J; Jin, H

2014-01-01

The present study was designed to investigate the role of endogenous sulfur dioxide (SO2) in vascular smooth muscle cell (VSMC) proliferation, and explore the possible role of cross-talk between cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) pathways in this action. By cell counting, growth curve depict, flow cytometry and bromodeoxyuridine (BrdU) labeling assays, we found that SO2 inhibited VSMC proliferation by preventing cell cycle progression from G1 to S phase and by reducing DNA synthesis. SO2 synthase aspartate aminotransferase (AAT1 and AAT2) overexpression significantly inhibited serum-induced proliferating cell nuclear antigen (PCNA) protein expression in VSMCs, demonstrated by western blot analysis. Moreover, overexpression of AAT1 or AAT2 markedly reduced incorporation of BrdU in serum-treated VSMCs. By contrast, either AAT1 or AAT2 knockdown significantly exacerbated serum-stimulated VSMC proliferation. Thus, both exogenous- and endogenous-derived SO2 suppressed serum-induced VSMC proliferation. However, annexin V-propidium iodide (PI) staining and cell cycle analysis demonstrated that SO2 did not influence VSMC apoptosis in the serum-induced proliferation model. In a platelet-derived growth factor (PDGF)-BB-stimulated VSMC proliferation model, SO2 dephosphorylated the active sites of Erk1/2, MAPK kinase 1/2 and RAF proto-oncogene serine/threonine-protein kinase (c-Raf) induced by PDGF-BB. However, the inactivation of the three kinases of the Erk/MAPK pathway was not due to the separate interferences on them by SO2 simultaneously, but a consequence of the influence on the upstream activity of the c-Raf molecule. Hence, we examined the cAMP/PKA pathway, which could inhibit Erk/MAPK transduction in VSMCs. The results showed that SO2 could stimulate the cAMP/PKA pathway to block c-Raf activation, whereas the Ser259 site on c-Raf had an important role in SO2-induced suppression of Erk/MAPK pathway. The present study firstly demonstrated that SO2 exerted a negative regulation of VSMC proliferation via suppressing the Erk/MAPK pathway mediated by cAMP/PKA signaling. PMID:24853429

Survey of selected tick-borne diseases in dogs in Finland.

PubMed

Pérez Vera, Cristina; Kapiainen, Suvi; Junnikkala, Sami; Aaltonen, Kirsi; Spillmann, Thomas; Vapalahti, Olli

2014-06-23

Due to climate changes during the last decades, ticks have progressively spread into higher latitudes in northern Europe. Although some tick borne diseases are known to be endemic in Finland, to date there is limited information with regard to the prevalence of these infections in companion animals. We determined the antibody and DNA prevalence of the following organisms in randomly selected client-owned and clinically healthy hunting dogs living in Finland: Ehrlichia canis (Ec), Anaplasma phagocytophilum (Ap), Borrelia burgdorferi (Bb) and Bartonella. Anti-Ap, -Bb and -Ec antibodies were determined in 340 Finnish pet dogs and 50 healthy hunting dogs using the 4DX Snap®Test (IDEXX Laboratories). In addition, PCRs for the detection of Ap and Bartonella DNA were performed. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with seropositivity to a vector borne agent. The overall seroprevalence was highest for Ap (5.3%), followed by Bb (2.9%), and Ec (0.3%). Seropositivities to Ap and Bb were significantly higher in the Åland Islands (p <0.001), with prevalence of Ap and Bb antibodies of 45 and 20%, respectively. In healthy hunting dogs, seropositivity rates of 4% (2/50) and 2% (1/50) were recorded for Ap and Bb, respectively. One client-owned dog and one hunting dog, both healthy, were infected with Ap as determined by PCR, while being seronegative. For Bartonella spp., none of the dogs tested was positive by PCR. This study represents the first data of seroprevalence to tick borne diseases in the Finnish dog population. Our results indicate that dogs in Finland are exposed to vector borne diseases, with Ap being the most seroprevalent of the diseases tested, followed by Bb. Almost 50% of dogs living in Åland Islands were Ap seropositive. This finding suggests the possibility of a high incidence of Ap infection in humans in this region. Knowing the distribution of seroprevalence in dogs may help predict the pattern of a tick borne disease and may aid in diagnostic and prevention efforts.

Importance of compensatory heart rate increase during myocardial ischemia to preserve appropriate oxygen kinetics.

PubMed

Yoshida, Sadamitsu; Adachi, Hitoshi; Murata, Makoto; Tomono, Junichi; Oshima, Shigeru; Kurabayashi, Masahiko

2017-09-01

Myocardial ischemia induces cardiac dysfunction, resulting in insufficient oxygen supply to peripheral tissues and mismatched energy production during exercise. To relieve the insufficient oxygen supply, heart rate (HR) response is augmented; however, beta-adrenergic receptor blockers (BB) restrict HR response. Although BB are essential drugs for angina pectoris, the effect of BB on exercise tolerance in patients with angina has not been studied. The aim of this study was to clarify the importance of HR augmentation to preserve exercise tolerance in patients with angina pectoris. Forty-two subjects who underwent cardiopulmonary exercise testing (CPX) to detect myocardial ischemia were enrolled. CPX was performed until exhaustion or onset of significant myocardial ischemia using a ramp protocol. Subjects were assigned to three groups (Group A: with ST depression during CPX with significant coronary stenosis and taking BB; Group B: with ST depression and not taking BB; Group C: without ST depression and not taking BB). HR response to exercise was evaluated during the following two periods: below and above ischemic threshold (IT). In Group C, it was evaluated during the first 2min and the last 2min of a ramp exercise. No significant differences were observed among the three groups with regard to patients' basic characteristics. Below IT, there were no differences in oxygen pulse/watt (O 2 pulse increasing rate), HR/watt (ΔHR/ΔWR), and ΔV˙O 2 /ΔWR. Above IT, O 2 pulse increasing rate was greater in Group A than in Group B. ΔHR/ΔWR was smaller in Group A than in Group B. ΔV˙O 2 /ΔWR became smaller in Group A than in Group B. There was no difference in anaerobic threshold, and peak V˙O 2 was smaller in Group A than in Group B. Restriction of HR response by a BB is shown to be one of the important factors in diminished exercise tolerance. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Uncoupling of the ITIM receptor G6b-B from the tyrosine phosphatases Shp1 and Shp2 disrupts platelet homeostasis in mice.

PubMed

Geer, Mitchell J; van Geffen, Johanna P; Gopalasingam, Piraveen; Vögtle, Timo; Smith, Christopher W; Heising, Silke; Kuijpers, Marijke J E; Tullemans, Bibian M E; Jarvis, Gavin E; Eble, Johannes A; Jeeves, Mark; Overduin, Michael; Heemskerk, Johan W M; Mazharian, Alexandra; Senis, Yotis A

2018-06-11

The immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptor G6b-B has emerged as a key regulator of platelet homeostasis. However, it remains unclear how it mediates its effects. Tyrosine phosphorylation of the ITIM and immunoreceptor tyrosine-based switch motif (ITSM) within the cytoplasmic tail of G6b-B provides a docking site for SH2 domain-containing protein-tyrosine phosphatases Shp1 and Shp2, which are also critical regulators of platelet production and function. In this study, we investigate the physiological consequences of uncoupling G6b-B from Shp1 and Shp2. To address this, we generated a transgenic mouse model expressing a mutant form of G6b-B in which tyrosine (Y) residues 212 and 238 within the ITIM and ITSM were mutated to phenylalanine (F), respectively. Mice homozygous for the mutation (G6b-B diY/F) were macrothrombocytopenic, due to a reduction in platelet production, had large clusters of megakaryocytes and myelofibrosis at sites of hematopoiesis, similar to that observed in G6b knockout (G6b KO) mice. Platelets from G6b-B diY/F mice were hypo-responsive to collagen, due to a significant reduction in expression of the immunoreceptor tyrosine-based activation motif (ITAM)-containing collagen receptor complex GPVI-FcR γ-chain, and thrombin, that could be partially rescued by co-stimulating the platelets with ADP. In contrast, platelets from G6b-B diY/F, G6b KO and megakaryocyte-specific Shp2 KO mice were hyper-responsive to antibody-mediated cross-linking of the hemi-ITAM-containing podoplanin receptor CLEC-2, suggesting that G6b-B inhibits CLEC-2-mediated platelet activation through Shp2. Findings from this study demonstrate that G6b-B must engage with Shp1 and Shp2 in order to mediate its regulatory effects on platelet homeostasis. Copyright © 2018 American Society of Hematology.

Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine.

PubMed

Danchin, M; Kirkwood, C D; Lee, K J; Bishop, R F; Watts, E; Justice, F A; Clifford, V; Cowley, D; Buttery, J P; Bines, J E

2013-05-28

RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth. A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis. The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant. A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12®-supplemented yogurt in healthy children

PubMed Central

Tan, Tina P.; Ba, Zhaoyong; Sanders, Mary Ellen; D’Amico, Frank J.; Roberts, Robert F.; Smith, Keisha Herbin; Merenstein, Daniel J.

2016-01-01

Objectives Probiotics are live microorganisms that may provide health benefits to the individual when consumed in sufficient quantities. For studies conducted on health or disease endpoints on probiotics in the United States, the Food and Administration (FDA) has required those studies to be conducted as investigational new drugs. This phase I, double-blinded, randomized, controlled safety study represents the first requirement of this pathway. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12® (BB-12®)-supplemented yogurt when consumed by a generally healthy group of children. The secondary aim was to assess the effect of BB-12®-supplemented yogurt on the gut microbiota of the children. Methods Sixty children aged 1–5 years were randomly assigned to consume four ounces of either BB-12®-supplemented yogurt or non-supplemented control yogurt daily for 10 days. The primary outcome was to assess safety and tolerability, as determined by the number of reported adverse events. Results A total of 186 non-serious adverse events were reported, with no significant differences between the control and BB-12® groups. No significant changes due to probiotic treatment were observed in the gut microbiota of the study cohort. Conclusions BB-12®-supplemented yogurt is safe and well-tolerated when consumed by healthy children. This study will form the basis for future randomized clinical trials investigating the potential effects of BB-12®-supplemented yogurt in different disease states. PMID:28114246

Fragment Bb in Amniotic Fluid: Evidence for complement activation by the alternative pathway in women with Intra-amniotic Infection/Inflammation

PubMed Central

Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Tovi, Shali Mazaki; Pedro, Kusanovic Juan; Soto, Eleazar; Gotsch, Francesca; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Mittal, Pooja; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.

2013-01-01

Objective Fragment Bb is an activator of the alternative pathway of the complement system. Recently, increased first trimester maternal plasma concentrations of this fragment were reported in patients destined to have a spontaneous preterm delivery before 34 weeks of gestation. The aim of this study was to determine whether the amniotic fluid (AF) concentrations of fragment Bb change with gestational age, spontaneous labor (term and preterm), and in the presence of intra-amniotic infection/ inflammation (IAI). Study design This cross-sectional study included patients in the following groups: 1) midtrimester (n=64); 2) term in spontaneous labor (n=70); 3) term not in labor (n=43); 4) spontaneous preterm labor (PTL) who delivered at term (n=76); 5) PTL without IAI who delivered preterm (n=73); 6) PTL with IAI (n=76); 7) prelabor rupture of the membranes (preterm PROM) without IAI (n=71); and 8) preterm PROM with IAI (n=71). Fragment Bb concentration in amniotic fluid was determined by an enzyme-linked immunoassay. Non-parametric statistics were used for analyses. Results 1) Fragment Bb was detected in all AF samples (n=544); 2) The median AF concentration of fragment Bb in patients at term not in labor was significantly higher than that of those in the mid-trimester [2.42 μg/mL, interquartile range (IQR) 1.78-3.22 vs. 1.64 μg/mL, IQR 1.06-3.49; p<0.001]; 3) Among patients with PTL, those with IAI had a higher median AF fragment Bb concentration than that of woman without IAI who delivered preterm (4.82 μg/mL, IQR 3.32-6.08 vs. 3.67 μg/mL, IQR 2.35-4.57; p<0.001) and than that of women with an episode of PTL who delivered at term (3.21 μg/mL, IQR 2.39-4.16; p<0.001); 4) Similarly, among patients with preterm PROM, the median AF fragment Bb concentration was higher in individuals with IAI than in those without IAI (4.24 μg/mL, IQR 2.58-5.79 vs. 2.79 μg/mL, IQR 2.09-3.89; p<0.001). 5) Among patients at term, the median AF fragment Bb concentration did not differ between women with spontaneous labor and those without labor (term in labor: 2.47 μg/mL, IQR 1.86-3.22; p=0.97). Conclusions 1) Fragment Bb, an activator of the alternative complement pathway, is a physiologic constituent of the amniotic fluid, and its concentration increases with advancing gestational age; 2) Amniotic fluid concentrations of fragment Bb are higher in pregnancies complicated with IAI; and 3) Labor at term is not associated with changes in the amniotic fluid concentrations of fragment Bb. These findings suggest a role for fragment Bb in the host immune response against IAI. PMID:19603351

Text-Based Conferencing: Features vs. Functionality

ERIC Educational Resources Information Center

Anderson, Lynn; McCarthy, Cathy

2005-01-01

This report examines three text-based conferencing products: "WowBB", "Invision Power Board", and "vBulletin". Their selection was prompted by a feature-by-feature comparison of the same products on the "WowBB" website. The comparison chart painted a misleading impression of "WowBB's" features in relation to the other two products; so the…

40 CFR Appendix A to Subpart Bb of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart BB

Code of Federal Regulations, 2011 CFR

2011-07-01

... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants From Phosphate Fertilizers Production Plants Pt. 63, Subpart BB, App. A Appendix A...

40 CFR Appendix A to Subpart Bb of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart BB

Code of Federal Regulations, 2012 CFR

2012-07-01

... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants From Phosphate Fertilizers Production Plants Pt. 63, Subpart BB, App. A Appendix A...

40 CFR Appendix A to Subpart Bb of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart BB

Code of Federal Regulations, 2013 CFR

2013-07-01

... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants From Phosphate Fertilizers Production Plants Pt. 63, Subpart BB, App. A Appendix A...

Comparison of phenolic acid profiles and anti-inflammatory effects of two major species of blueberries in the US

USDA-ARS?s Scientific Manuscript database

Blueberries (BB) contain high levels of polyphenols. Among them, phenolic acids (PAs) have been recently suggested as a group of important bioactive compounds. Highbush BB (Vaccinium corymbosum) and lowbush “wild" BB (Vaccinium angustifolium) are two predominant species in North America. The first o...

Integrating marker-assisted background analysis with foreground selection for pyramiding bacterial blight resistance genes into Basmati rice.

PubMed

Baliyan, Nikita; Malik, Rekha; Rani, Reema; Mehta, Kirti; Vashisth, Urvashi; Dhillon, Santosh; Boora, Khazan Singh

2018-01-01

Bacterial leaf blight (BB), caused by the bacterium Xanthomonas oryzae pv. Oryzae (Xoo), is the major constraint amongst rice diseases in India. CSR-30 is a very popular high-yielding, salt-tolerant Basmati variety widely grown in Haryana, India, but highly susceptible to BB. In the present study, we have successfully introgressed three BB resistance genes (Xa21, xa13 and xa5) from BB-resistant donor variety IRBB-60 into the BB-susceptible Basmati variety CSR-30 through marker-assisted selection (MAS) exercised with stringent phenotypic selection without compromising the Basmati traits. Background analysis using 131 polymorphic SSR markers revealed that recurrent parent genome (RPG) recovery ranged up to 97.1% among 15 BC 3 F 1 three-gene-pyramided genotypes. Based on agronomic evaluation, BB reaction, aroma, percentage recovery of RPG, and grain quality evaluation, four genotypes, viz., IC-R28, IC-R68, IC-R32, and IC-R42, were found promising and advanced to BC 3 F 2 generation. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Complement activation fragment Bb in early pregnancy and spontaneous preterm birth.

PubMed

Lynch, Anne M; Gibbs, Ronald S; Murphy, James R; Byers, Tim; Neville, Margaret C; Giclas, Patricia C; Salmon, Jane E; Van Hecke, Trisha M; Holers, V Michael

2008-10-01

The objective of this study was to determine whether an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks' gestation or SPTB between 34 and 37 weeks' gestation (late SPTB). This was a prospective study of 784 women enrolled at less than 20 weeks' gestation. Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks' gestation and 25 (3.2%) a SPTB between 34 and 37 weeks' gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks' gestation as compared with women who had levels of Bb in the lower 3 quartiles (95% confidence interval [CI] 1.5-14, P = .003). There was no association between Bb and late SPTB (relative risk 0.8, 95% CI 0.3-2). A significant relationship was found between an elevated Bb in early pregnancy and SPTB less than 34 weeks' gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition.

COMPLEMENT ACTIVATION FRAGMENT Bb IN EARLY PREGNANCY AND SPONTANEOUS PRETERM BIRTH

PubMed Central

LYNCH, ANNE M.; GIBBS, RONALD S.; MURPHY, JAMES R.; BYERS, TIM; NEVILLE, MARGARET C.; GICLAS, PATRICIA C.; SALMON, JANE E.; VAN HECKE, TRISHA M; MICHAEL HOLERS, V.

2008-01-01

Objective To determine if an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks gestation or SPTB between 34 and 37 weeks gestation (late SPTB). Study Design Prospective study of 784 women enrolled at < 20 weeks gestation. Results Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks gestation and 25 (3.2%) a SPTB between 34 and 37 weeks gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks gestation as compared with women who had levels of Bb in the lower three quartiles (95% CI 1.5 to 14, P = 0.003). There was no association between Bb and late SPTB (RR= 0.8, 95% CI = 0.3 to 2). Conclusions A significant relationship was found between an elevated Bb in early pregnancy and SPTB < 34 weeks gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition. PMID:18928972

Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice

PubMed Central

Huang, Yan-Feng; Qu, Chang; Xu, Lie-Qiang; Su, Zi-Ren; Zeng, Hui-Fang; Zheng, Lin; Yi, Tie-Gang; Li, Hui-Lin; Chen, Jian-Ping

2018-01-01

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC. PMID:29538417

Breed differences of bull frozen-thawed semen.

PubMed

Ntemka, A; Tsousis, G; Brozos, C; Kiossis, E; Boscos, C M; Tsakmakidis, I A

2016-12-01

The objective of this study was to investigate the quality of frozen-thawed semen from different bull breeds. Commercial frozen-thawed bull semen samples (26 per breed, 130 totally) of five breeds (Holstein [Η], Brown Swiss [BS], Limousin [L], Belgian Blue [BB], Blonde d' Aquitaine [BA]) were used. After thawing, each semen sample was subjected to thermal resistance test (TR) for 0.5 and 1 hr at 38°C and hypo-osmotic swelling test (HOST) for 1 hr at 150 mOsm at 37°C. Additionally, all samples were evaluated at times 0 hr (thawing), 0.5 hr (TR), 1 hr (TR) for kinetics by CASA [progressive, immotile, rapid, medium, slow moving spermatozoa, curvilinear velocity (VCL), average path velocity (VAP), straight line velocity (VSL), linearity (LIN), straightness (STR), beat cross-frequency (BCF), amplitude of lateral head displacement (ALH), wobble (WOB)]. Moreover, directly after thawing, all semen samples were evaluated for morphometry, morphology, viability and DNA fragmentation. Statistical analysis was conducted using a mixed model for repeated measures. The results showed (a) higher VCL after thawing in H, L breeds compared to BB and BA, (b) higher VAP after thawing in L compared to BB, BA, (c) higher values of progressive spermatozoa after TR in H, BS compared to BB, BA, (d) higher values of rapid spermatozoa after thawing and 0.5 hr of TR in H, BS, L compared to BB, BA, (e) lower viability in BA after thawing compared to H, BS, BB, (f) lower morphological abnormalities in H compared to L, BB, (g) higher head length in Η compared to BB. No significant differences were observed in the results from HOST and DNA fragmentation between breeds. In conclusion, quality characteristics of frozen-thawed bull semen are dependent on the breed. Frozen semen from BB and BA breeds should be handled more carefully after thawing, as it is more sensitive to stress. © 2016 Blackwell Verlag GmbH.

SU-F-T-92: Clinical Benefit for Breast and Chest Wall Setup in Using a Breast Board

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, S; Miyamoto, C; Serratore, D

Purpose: To validate benefit of using a breast board (BB) by analyzing the geometry and dosimetry changes of the regions of interest (ROIs) between CT scans with and without BB. Methods: Seven patients, two chest walls (CW) and five breasts, use BB at CT simulation and no BB at diagnostic CT were included. By using deformable image registration software (Velocity AI), diagnostic CT and planning CT were rigidly co-registered according to the thoracic cage at the target. The heart and the target were then deformedly matched and the contours of the planned ROIs were transferred to the diagnostic CT. Whichmore » were brought back to the planning CT data set though the initial rigid co-registration in order to keep the deformed ROIs redefined in the diagnostic CT. Anatomic shifts and volume changes of a ROI beyond the rigid translation were recorded and dosimetry changes to ROIs were compared with recalculated DVHs. Results: Patient setup without the BB had small but systematic heart shifts superiorly by ∼5 mm. Torso rotations in two cases moved the heart in opposite directions by ∼10 mm. The breast target volume, shape, and locations were significantly changed with arm extension over the head but not in cases with the arm extended laterally. Breast setup without BB could increase the mean dose to the heart and the maximal dose to the anterior ventricle wall by 1.1 and 6.7 Gy, respectively. Conclusion: A method for evaluation of breast setup technique is introduced and applied for patients. Results of systematic heart displacement without using the BB and the potential increase of heart doses encourage us to further investigate the current trend of not using a BB for easy setup and CT scans. Using a BB would likely increase patient sag during prolonged IMRT and real-time patient position monitoring is clinically desired.« less

Differences in acid tolerance between Bifidobacterium breve BB8 and its acid-resistant derivative B. breve BB8dpH, revealed by RNA-sequencing and physiological analysis.

PubMed

Yang, Xu; Hang, Xiaomin; Tan, Jing; Yang, Hong

2015-06-01

Bifidobacteria are common inhabitants of the human gastrointestinal tract, and their application has increased dramatically in recent years due to their health-promoting effects. The ability of bifidobacteria to tolerate acidic environments is particularly important for their function as probiotics because they encounter such environments in food products and during passage through the gastrointestinal tract. In this study, we generated a derivative, Bifidobacterium breve BB8dpH, which displayed a stable, acid-resistant phenotype. To investigate the possible reasons for the higher acid tolerance of B. breve BB8dpH, as compared with its parental strain B. breve BB8, a combined transcriptome and physiological approach was used to characterize differences between the two strains. An analysis of the transcriptome by RNA-sequencing indicated that the expression of 121 genes was increased by more than 2-fold, while the expression of 146 genes was reduced more than 2-fold, in B. breve BB8dpH. Validation of the RNA-sequencing data using real-time quantitative PCR analysis demonstrated that the RNA-sequencing results were highly reliable. The comparison analysis, based on differentially expressed genes, suggested that the acid tolerance of B. breve BB8dpH was enhanced by regulating the expression of genes involved in carbohydrate transport and metabolism, energy production, synthesis of cell envelope components (peptidoglycan and exopolysaccharide), synthesis and transport of glutamate and glutamine, and histidine synthesis. Furthermore, an analysis of physiological data showed that B. breve BB8dpH displayed higher production of exopolysaccharide and lower H(+)-ATPase activity than B. breve BB8. The results presented here will improve our understanding of acid tolerance in bifidobacteria, and they will lead to the development of new strategies to enhance the acid tolerance of bifidobacterial strains. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi.

PubMed

Cordes, Frank S; Kraiczy, Peter; Roversi, Pietro; Simon, Markus M; Brade, Volker; Jahraus, Oliver; Wallis, Russell; Goodstadt, Leo; Ponting, Chris P; Skerka, Christine; Zipfel, Peter F; Wallich, Reinhard; Lea, Susan M

2006-05-01

Borrelia burgdorferi, a spirochaete transmitted to human hosts during feeding of infected Ixodes ticks, is the causative agent of Lyme disease, the most frequent vector-borne disease in Eurasia and North America. Sporadically Lyme disease develops into a chronic, multisystemic disorder. Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). The atomic structure of BbCRASP-1, the key FHL-1/FH-binding protein of B. burgdorferi, has recently been determined. Our analysis indicates that its protein topology apparently evolved to provide a high affinity interaction site for FH/FHL-1 and leads to an atomic-level hypothesis for the functioning of BbCRASP-1. This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design.

Genome-wide analysis of basic/helix-loop-helix gene family in peanut and assessment of its roles in pod development.

PubMed

Gao, Chao; Sun, Jianlei; Wang, Chongqi; Dong, Yumei; Xiao, Shouhua; Wang, Xingjun; Jiao, Zigao

2017-01-01

The basic/helix-loop-helix (bHLH) proteins constitute a superfamily of transcription factors that are known to play a range of regulatory roles in eukaryotes. Over the past few decades, many bHLH family genes have been well-characterized in model plants, such as Arabidopsis, rice and tomato. However, the bHLH protein family in peanuts has not yet been systematically identified and characterized. Here, 132 and 129 bHLH proteins were identified from two wild ancestral diploid subgenomes of cultivated tetraploid peanuts, Arachis duranensis (AA) and Arachis ipaensis (BB), respectively. Phylogenetic analysis indicated that these bHLHs could be classified into 19 subfamilies. Distribution mapping results showed that peanut bHLH genes were randomly and unevenly distributed within the 10 AA chromosomes and 10 BB chromosomes. In addition, 120 bHLH gene pairs between the AA-subgenome and BB-subgenome were found to be orthologous and 101 of these pairs were highly syntenic in AA and BB chromosomes. Furthermore, we confirmed that 184 bHLH genes expressed in different tissues, 22 of which exhibited tissue-specific expression. Meanwhile, we identified 61 bHLH genes that may be potentially involved in peanut-specific subterranean. Our comprehensive genomic analysis provides a foundation for future functional dissection and understanding of the regulatory mechanisms of bHLH transcription factors in peanuts.

(-)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana prevents diabetes and dyslipidemia in streptozotocin-induced diabetic mice.

PubMed

Lin, Cheng-Hsiu; Wu, Jin-Bin; Jian, Jia-Ying; Shih, Chun-Ching

2017-01-01

The objective of this study was to evaluate the effects and molecular mechanism of (-)-epicatechin-3-O-β-D-allopyranoside from Davallia formosana (BB) (also known as Gu-Sui-Bu) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. This plant was demonstrated to display antioxidant activities and possess polyphenol contents. Diabetic mice were randomly divided into six groups and were given daily oral gavage doses of either BB (at three dosage levels), metformin (Metf) (at 0.3 g/kg body weight), fenofibrate (Feno) (at 0.25 g/kg body weight) or vehicle (distilled water) and a group of control (CON) mice were gavaged with vehicle over a period of 4 weeks. Treatment with BB led to reduced levels of blood glucose, HbA1C, triglycerides and leptin and to increased levels of insulin and adiponectin compared with the vehicle-treated STZ group. The diabetic islets showed retraction from their classic round-shaped as compared with the control islets. The BB-treated groups (at middle and high dosages) showed improvement in islets size and number of Langerhans islet cells. The membrane levels of skeletal muscular glucose transporter 4 (GLUT4) were significantly higher in BB-treated mice. This resulted in a net glucose lowering effect among BB-treated mice. Moreover, BB enhanced the expression of skeletal muscle phospho-AMPK in treated mice. BB-treated mice increased expression of fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα) and mRNA levels of carnitine palmitoyl transferase Ia (CPT1a). These mice also expressed lower levels of lipogenic genes such as fatty acid synthase (FAS), as well as lower mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and liver adipocyte fatty acid binding protein 2 (aP2). This resulted in a reduction in plasma triglyceride levels. BB-treated mice also expressed lower levels of PPARγ and FAS protein. This led to reduced adipogenesis, fatty acid synthesis and lipid accumulation within adipose tissue, and consequently, to lower triglyceride levels in liver, blood, and adipose tissue. Moreover, BB treatment not only displayed the activation Akt in liver tissue and skeletal muscle, but also in C2C12 myotube to cause an increase in phosphorylation of Akt in the absence of insulin. These results demonstrated that BB act as an activator of AMPK and /or regulation of insulin pathway (Akt), and the antioxidant activity within the pancreas. Therefore, BB treatment ameliorated the diabetic and dyslipidemic state in STZ-induced diabetic mice.

Maternal and fetal alternative complement pathway activation in early severe preeclampsia.

PubMed

Hoffman, M Camille; Rumer, Kristen K; Kramer, Anita; Lynch, Anne M; Winn, Virginia D

2014-01-01

We sought to determine whether alternative complement activation fragment Bb (Bb) levels are elevated in the maternal, fetal, and placental blood in cases of severe preeclampsia (PE) compared with normotensive controls. This was a cross-sectional study of women admitted at ≥24 weeks gestation with or without severe PE. Maternal plasma was collected at the time of enrollment. Umbilical venous cord and intervillous space blood were collected at delivery. Plasma Bb levels were assessed using ELISA. Bb levels were compared between cases and controls. Median Bb levels were higher in the maternal plasma of severe PE subjects (n = 24) than in controls (n = 20), 1.45 ± 1.03 versus 0.65 ± 0.23 μg/mL, P < 0.001. In umbilical venous plasma, Bb levels were higher in severe PE subjects (n = 15) compared with controls (n = 15), 2.48 ± 1.40 versus 1.01 ± 0.57 μg/mL, P = 0.01. Activation fragment Bb is increased in the maternal and umbilical venous blood of cases of severe PE when compared with normotensive controls. These data provide support for alternative complement pathway involvement in the pathogenesis of severe PE and demonstrate that alternative complement activation occurs not only in the maternal but also in the fetal compartment. © 2013 John Wiley & Sons Ltd.

Comparison of fluence-to-dose conversion coefficients for deuterons, tritons and helions.

PubMed

Copeland, Kyle; Friedberg, Wallace; Sato, Tatsuhiko; Niita, Koji

2012-02-01

Secondary radiation in aircraft and spacecraft includes deuterons, tritons and helions. Two sets of fluence-to-effective dose conversion coefficients for isotropic exposure to these particles were compared: one used the particle and heavy ion transport code system (PHITS) radiation transport code coupled with the International Commission on Radiological Protection (ICRP) reference phantoms (PHITS-ICRP) and the other the Monte Carlo N-Particle eXtended (MCNPX) radiation transport code coupled with modified BodyBuilder™ phantoms (MCNPX-BB). Also, two sets of fluence-to-effective dose equivalent conversion coefficients calculated using the PHITS-ICRP combination were compared: one used quality factors based on linear energy transfer; the other used quality factors based on lineal energy (y). Finally, PHITS-ICRP effective dose coefficients were compared with PHITS-ICRP effective dose equivalent coefficients. The PHITS-ICRP and MCNPX-BB effective dose coefficients were similar, except at high energies, where MCNPX-BB coefficients were higher. For helions, at most energies effective dose coefficients were much greater than effective dose equivalent coefficients. For deuterons and tritons, coefficients were similar when their radiation weighting factor was set to 2.

Functional characterization of a serine-threonine protein kinase from Bambusa balcooa that implicates in cellulose overproduction and superior quality fiber formation

PubMed Central

2013-01-01

Background Molecular markers allow rapid identification of biologically important germplasm/s having desired character. Previously we have reported a genotype specific molecular marker, Balco1128 [GenBank ID EU258678] of Bambusa balcooa containing an ORF (375 bp) having high similarity with receptor like cytoplasmic kinase of Arabidopsis and Oryza. Balco1128 was found to be associated only with bamboo genotypes endowed with high cellulose and low lignin contents of fibers. Under the above backdrop, it was necessitated to characterize this genetic marker for better understanding of its biological significance in context of superior quality fiber development. Results The full length cDNA (3342 bp) of BbKst, a serine-threonine protein kinase was isolated from B. balcooa comprising of six LRR domains at the N-terminal end and a kinase domain at the C-terminal end. Bacteria-expressed BbKst-kinase domain (3339 bp long) showed Mg2+ dependent kinase activity at pH 7.0, 28°C. Bioinformatics study followed by phospho-amino analysis further confirmed that BbKst-kinase belongs to the serine/threonine protein kinase family. Transcript analysis of the BbKst gene following RNA slot blot hybridization and qPCR revealed higher expression of BbKst during initiation and elongation stages of fiber development. Tissue specific expression studies showed much higher expression of BbKst transcript in stems and internodes of B. balcooa than in leaves and rhizomes. Southern analysis revealed single copy insertion of BbKst in most of the Agrobacterium mediated transgenic tobacco plants. Real-time PCR detected 150-200 fold enhanced expression of BbKst in different T1 tobacco lines than that of the vector transformed plants. Heterologous expression of BbKst under control of 35S promoter in transgenic tobacco showed high cellulose deposition in the xylem fibers. Number of xylary fibers was higher in transgenic T0 and T1 plants than that of empty-vector transformed tobacco plants offering enhanced mechanical strength to the transgenic plants, which was also substantiated by their strong upright phenotypes, significantly higher cellulose contents, flexibility coefficient, slenderness ratio, and lower Runkel ratio of the fibers. Conclusions This finding clearly demonstrated that BbKst gene (GenBank ID JQ432560) encodes a serine/threonine protein kinase. BbKst induced higher cellulose deposition/synthesis in transgenic tobacco plants, an important attribute of fiber quality bestowing additional strength to the plant. PMID:24015925

Early snow melts and biomass burning over Eastern Eurasia and their impacts on the air quality in Northern Japan

NASA Astrophysics Data System (ADS)

Yasunari, T. J.; daSilva, A.; Akiyama, M.; Hayasaki, M.; Murao, N.; Kim, K. M.

2016-12-01

We investigated monthly characteristics including a couple of large biomass burnings (BB) in Eastern Eurasia during 2003 and 2014, and the smoke impacts on Northern Japan. The new re-analyses data including the aerosol data assimilation, called MERRA-2, which was produced by the NASA's Global Modeling and Assimilation Office (GMAO), the monthly mean MODIS snow cover fraction (SCF) data (MOD10CM; further re-gridded), and the observations on PM2.5, elemental carbon (EC), and organic carbon (OC) in Sapporo city (Hokkaido, Japan), were used in our analyses. For the MERRA-2 and MODIS SCF data, we calculated 12-year climatology for each month and these anomalies from the climatology on the focused variables. Three-month means of the anomalies for the last three months until the BB months were calculated except for the SCF. For the SCF, the three-month mean anomalies until the one month before the BB months were also calculated. Here we start especially focusing on the identified fire months with the MERRA-2 data (May 2003, April 2008, and July 2014) in terms of these smoke impacts on the air qualities in Northern Japan (i.e., Hokkaido). We identified two types of biomass burning patterns within these three months. For the BBs in May 2003 and April 2008, the main BB areas were seen in the eastern part of the Lake Baikal. In July 2014, the main BB area was in the Sakha Republic and close to the Arctic region. Then, the MERRA-2 data overestimated the observations (EC, OC, and PM2.5) in Sapporo (Hokkaido, Japan) during the smoke transports, but the elevated timings were well reproduced. For all the three BB cases, abnormally reduced SCF were seen by the one month before the Eurasian BB generations (i.e., earlier than the BB generations). The positive and negative anomalies of 2-m temperature and surface soil wetness, covering the three-month until the BB months, were identified. These suggest that early snow-melting anomalies for these three years could make the following BB-ready environmental conditions around the regions where warmer temperature and dryer soil conditions were also maintained until setting on fire there. Therefore, the accurate grasp of Eurasian snow cover conditions in spring would be essential to project the following BB generations from spring to summer and the smoke impact from the fires on surrounding and remote areas.

Impact of inulin and okara on Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 viability in a fermented soy product and probiotic survival under in vitro simulated gastrointestinal conditions.

PubMed

Bedani, Raquel; Rossi, Elizeu Antonio; Isay Saad, Susana Marta

2013-06-01

The effect of inulin and/or okara flour on Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 viability in a fermented soy product (FSP) and on probiotic survival under in vitro simulated gastrointestinal conditions were investigated throughout 28 days of storage at 4 °C. Employing a 2(2) design, four FSP trials were produced from soymilk fermented with ABT-4 culture (La-5, Bb-12, and Streptococcus thermophilus): FSP (control); FSP-I (with inulin, 3 g/100 mL of soymilk); FSP-O (with okara, 5 g/100 mL); FSP-IO (with inulin + okara, ratio 3:5 g/100 mL). Probiotic viabilities ranged from 8 to 9 log cfu/g during the 28 days of storage, and inulin and/or okara flour did not affect the viability of La-5 and Bb-12. Bb-12 resistance to the artificial gastrointestinal juices was higher than for La-5, since the Bb-12 and La-5 populations decreased approximately 0.6 log cfu/g and 3.8 log cfu/g, respectively, throughout storage period. Even though the protective effect of inulin and/or okara flour on probiotic microorganisms was not significant, when compared to a fresh culture, the FSP matrix improved Bb-12 survival on day 1 of storage and may be considered a good vehicle for Bb-12 and could play an important role in probiotic protection against gastrointestinal juices. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of the biomass burning on methane variability during dry years in the Amazon measured from an aircraft and the AIRS sensor.

PubMed

Ribeiro, Igor Oliveira; Andreoli, Rita Valéria; Kayano, Mary Toshie; de Sousa, Thaiane Rodrigues; Medeiros, Adan Sady; Guimarães, Patrícia Costa; Barbosa, Cybelli G G; Godoi, Ricardo H M; Martin, Scot T; de Souza, Rodrigo Augusto Ferreira

2018-05-15

The present study examines the spatiotemporal variability and interrelations of the atmospheric methane (CH 4 ), carbon monoxide (CO) and biomass burning (BB) outbreaks retrieved from satellite data over the Amazon region during the 2003-2012 period. In the climatological context, we found consistent seasonal cycles of BB outbreaks and CO in the Amazon, both variables showing a peak during the dry season. The dominant CO variability mode features the largest positive loadings in the southern Amazon, and describes the interannual CO variations related to BB outbreaks along the deforestation arc during the dry season. In line with CO variability and BB outbreaks, the results show strong correspondence with the spatiotemporal variability of CH 4 in the southern Amazon during years of intense drought. Indeed, the areas with the largest positive CH 4 anomalies in southern Amazon overlap the areas with high BB outbreaks and positive CO anomalies. The analyses also showed that high (low) BB outbreaks in the southern Amazon occur during dry (wet) years. In consequence, the interannual climate variability modulates the BB outbreaks in the southern Amazon, which in turn have considerable impacts on CO and CH 4 interannual variability in the region. Therefore, the BB outbreaks might play a major role in modulating the CH 4 and CO variations, at least in the southern Amazon. This study also provides a comparison between the estimate of satellite and aircraft measurements for the CH 4 over the southern Amazon, which indicates relatively small differences from the aircraft measurements in the lower troposphere, with errors ranging from 0.18% to 1.76%. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of chemical fingerprints in long-range transport of burning induced upper tropospheric ozone from Colorado to the North Atlantic Ocean.

PubMed

Jeon, Wonbae; Choi, Yunsoo; Souri, Amir Hossein; Roy, Anirban; Diao, Lijun; Pan, Shuai; Lee, Hwa Woon; Lee, Soon-Hwan

2018-02-01

This study investigates a significant biomass burning (BB) event occurred in Colorado of the United States in 2012 using the Community Multi-scale Air Quality (CMAQ) model. The simulation reasonably reproduced the significantly high upper tropospheric O 3 concentrations (up to 145ppb) caused by BB emissions. We find the BB-induced O 3 was primarily affected by chemical reactions and dispersion during its transport. In the early period of transport, high NO x and VOCs emissions caused O 3 production due to reactions with the peroxide and hydroxyl radicals, HO 2 and OH. Here, NO x played a key role in O 3 formation in the BB plume. The results indicated that HO 2 in the BB plume primarily came from formaldehyde (HCHO+hv=2HO 2 +CO), a secondary alkoxy radical (ROR=HO 2 ). CO played an important role in the production of recycled HO 2 (OH+CO=HO 2 ) because of its abundance in the BB plume. The chemically produced HO 2 was largely converted to OH by the reactions with NO (HO 2 +NO=OH+NO 2 ) from BB emissions. This is in contrast to the surface, where HO 2 and OH are strongly affected by VOC and HONO, respectively. In the late stages of transport, the O 3 concentration was primarily controlled by dispersion. It stayed longer in the upper troposphere compared to the surface due to sustained depletion of NO x . Sensitivity analysis results support that O 3 in the BB plume is significantly more sensitive to NO x than VOCs. Copyright © 2017 Elsevier B.V. All rights reserved.

Crystal structure of the human 4-1BB/4-1BBL complex.

PubMed

Gilbreth, Ryan N; Oganesyan, Vaheh Y; Amdouni, Hamza; Novarra, Shabazz; Grinberg, Luba; Barnes, Arnita; Baca, Manuel

2018-05-02

4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4 Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Mycelial fungi completely remediate di(2-ethylhexyl)phthalate, the hazardous plasticizer in PVC blood storage bag.

PubMed

Pradeep, S; Benjamin, Sailas

2012-10-15

This pioneering work describes how simply, inexpensively and efficiently novel fungi utilize the alarming plasticizer, di(2-ethylhexyl)phthalate (DEHP) blended in PVC blood storage bags (BB). In order to quantify total DEHP (33.5%, w/w) present in BB, it was extracted using n-hexane and confirmed by GC-MS. Three mycelial fungi, viz., Aspergillus parasiticus, Fusarium subglutinans and Penicillium funiculosum isolated in our laboratory form heavily plastics-contaminated soil - either singly or in consortium - completely consumed intact DEHP physically bound to BB by static submerged growth (28 °C) in simple basal salt medium (BSM). A two-stage cultivation strategy was adopted for the complete removal of DEHP from BB in situ. During the first growth stage, almost 70% DEHP contained in the BB was consumed in 2 weeks, accompanied by increased fungal biomass (~0.15-0.35 g/g BB; OD ~7 at 600 nm) and a sharp declining (3.3) of initial pH (7.2). Spent BSM was replaced at this stagnant growth state (low pH), thus in the second stage, remaining DEHP bound to BB utilized completely (over 99%). Furthermore, A. parasiticus and F. subglutinans also grew well on scrapes of PVC water pipes in BSM. F. subglutinans was as efficient independently as consortium in completely utilizing the DEHP bound to BB, and these fungi offer great potentials for the inexpensive and eco-friendly bioremediation of phthalates in medical and allied PVC wastes on a large scale through a batch process in alleviating the plactics waste management issue. Copyright © 2012 Elsevier B.V. All rights reserved.

Deep anterior lamellar keratoplasty: dissection plane with viscoelastic and air can be different.

PubMed

Ross, Andrew R; Said, Dalia G; El-Amin, Abdalla; Altaan, Saif; Cabrerizo, Javier; Nubile, Mario; Hogan, Emily; Mastropasqua, Leonardo; Dua, Harminder Singh

2018-04-03

To investigate and define the nature of big bubbles (BB) formed by injection of viscoelastic in deep anterior lamellar keratoplasty. Intrastromal injections of 0.1 and 0.3 mL of sodium hyaluronate 1.2% and 0.6% were made into sclera-corneal discs (n = 32) at superficial (anterior-third), midstromal (middle-third) and deep (posterior-third) levels to simulate deep anterior lamellar keratoplasty. Postinjection optical coherence tomograms (OCT) were obtained with the needle in situ. The samples were sectioned and examined histologically. Twelve control samples were injected with air. With superficial injections (n=8) only intrastromal accumulation of viscoelastic was noted. With midstromal injections (n=10) intrastromal accumulation of viscoelastic (n=6) and intrastromal big bubbles (IBB) (n=4) with substantial and variable stromal tissue in the walls were noted. No type 1, type 2 or mixed BB were noted. With deep injections (n=14), type 1 BB (n=4), IBB (n=4) and mixed BB (n=6) were obtained.There was no difference in the results with the two different concentrations of viscoelastic used. With air injection (n=12), 10 type 1 and 1 type 2 BB and 1 mixed BB were obtained. No IBB was noted. BB obtained by injection of viscoelastic and air can be different. The former tends to occur at the site of injection, especially with midstromal injections, takes the form of tissue separation by stretch and tearing and does not cleave in a consistent plane like air. Surgeons should be aware of IBB created by viscodissection and not confuse it for a type1 BB. Intraoperative OCT should help identify IBB. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Influence of CO2 on growth and hydrocarbon production in Botryococcus braunii.

PubMed

Ranga Rao, A; Sarada, R; Ravishankar, G A

2007-03-01

Botryococcus braunii is a green colonial fresh water microalga and it is recognized as one of the renewable resources for production of liquid hydrocarbons. CFTRI-Bb-1 and CFTRI-Bb-2 have been reported for the first time and their performance with regard to growth and biochemical profile is presented here. The present study focused on effect of carbon dioxide (CO2) on biomass, hydrocarbon, carbohydrate production, fatty acid profile, and carotenoid content in various species of B. braunii (LB-572, SAG 30.81, MCRC-Bb, N-836, CFTRI-Bb-1, and CFTRI-Bb-2) at 0.5, 1.0, and 2.0% (v/v) levels using a two-tier flask. CO2 at 2.0% (v/v) level enhanced growth of the organism, and a two-fold increase in biomass and carotenoid contents was observed in all the B. braunii strains studied compared with control culture (without CO2 supplementation). At 1% and 2% (v/v) CO2 concentrations, palmitic acid and oleic acid levels increased by 2.5 to 3 folds in one of the strains of B. braunii (LB-572). Hydrocarbon content was found to be above 20% at 2% CO2 level in the B. braunii LB-572, CFTRI-Bb-2, CFTRI-Bb-1, and N-836 strains, whereas it was less than 20% in the SAG 30.81 and MCRC-Bb strains compared with control culture. This culture methodology will provide information on CO2 requirement for growth of algae and metabolite production. B. braunii spp. can be grown at the tested levels of CO2 concentration without much influence on culture pH.

A study on the levels of a polybrominated biphenyl in Chinese human milk samples collected in 2007 and 2011.

PubMed

Liu, Xiao; Wen, Sheng; Li, Jingguang; Zhang, Lei; Zhao, Yunfeng; Wu, Yongning

2016-09-01

The levels of a 2,2',4,4',5,5'-hexabromobiphenyl (BB-153) were measured in human milk samples collected in 2007 and 2011 from residents in China by high-resolution gas chromatography-high-resolution mass chromatography (HRGC-HRMS) with isotope dilution. The median concentrations of BB-153 from the samples collected in 2007 and 2011 were 8.3 and 7.2 pg/g lipid weight, respectively. The levels of BB-153 in the human milk collected from rural areas were not significantly different to those collected from the urban areas in China. Meanwhile, significant positive correlations were found between the levels of BB-153 in human milk and the consumption of animal-origin foods. In the present study, the mean levels of BB-153 in human milk from Chinese mothers were found to be lower than those from European and American mothers.

Observation of Z_{b}(10610) and Z_{b}(10650) Decaying to B Mesons.

PubMed

Garmash, A; Abdesselam, A; Adachi, I; Aihara, H; Asner, D M; Aushev, T; Ayad, R; Aziz, T; Babu, V; Badhrees, I; Bakich, A M; Behera, P; Bhardwaj, V; Bhuyan, B; Bobrov, A; Bondar, A; Bonvicini, G; Bozek, A; Bračko, M; Browder, T E; Červenkov, D; Chekelian, V; Chen, A; Cheon, B G; Chilikin, K; Cho, K; Chobanova, V; Choi, Y; Cinabro, D; Dalseno, J; Danilov, M; Dash, N; Doležal, Z; Drutskoy, A; Dutta, D; Eidelman, S; Epifanov, D; Farhat, H; Fast, J E; Ferber, T; Fulsom, B G; Gaur, V; Gabyshev, N; Gillard, R; Goh, Y M; Goldenzweig, P; Golob, B; Hara, T; Hayasaka, K; Hayashii, H; Iijima, T; Ishikawa, A; Itoh, R; Iwasaki, Y; Jaegle, I; Joffe, D; Joo, K K; Julius, T; Kang, K H; Kato, E; Kawasaki, T; Kim, D Y; Kim, J B; Kim, K T; Kim, M J; Kim, S H; Kim, Y J; Kinoshita, K; Korpar, S; Križan, P; Krokovny, P; Kuhr, T; Kuzmin, A; Kwon, Y-J; Lange, J S; Lee, I S; Li, C; Li, H; Li, L; Li Gioi, L; Libby, J; Liventsev, D; Lukin, P; Masuda, M; Matvienko, D; Miyabayashi, K; Miyata, H; Mizuk, R; Mohanty, G B; Moll, A; Mori, T; Mussa, R; Nakano, E; Nakao, M; Nanut, T; Natkaniec, Z; Nishida, S; Olsen, S L; Pakhlov, P; Pakhlova, G; Pal, B; Park, H; Pedlar, T K; Pestotnik, R; Petrič, M; Piilonen, L E; Pulvermacher, C; Ribežl, E; Ritter, M; Rostomyan, A; Sahoo, H; Sakai, Y; Sandilya, S; Sanuki, T; Savinov, V; Schneider, O; Schnell, G; Schwanda, C; Seino, Y; Semmler, D; Senyo, K; Seong, I S; Sevior, M E; Shebalin, V; Shen, C P; Shibata, T-A; Shiu, J-G; Shwartz, B; Simon, F; Sohn, Y-S; Solovieva, E; Starič, M; Sumiyoshi, T; Tamponi, U; Tanida, K; Teramoto, Y; Trabelsi, K; Uchida, M; Uehara, S; Uglov, T; Uno, S; Van Hulse, C; Vanhoefer, P; Varner, G; Vorobyev, V; Wagner, M N; Wang, C H; Wang, M-Z; Wang, P; Watanabe, Y; Williams, K M; Won, E; Yamamoto, H; Yamaoka, J; Yashchenko, S; Yelton, J; Yook, Y; Yuan, C Z; Zhang, Z P; Zhilich, V; Zhulanov, V; Zupanc, A

2016-05-27

We report the analysis of the three-body e^{+}e^{-}→BB[over ¯]π^{±}, BB[over ¯]^{*}π^{±}, and B^{*}B[over ¯]^{*}π^{±} processes, including the first observations of the Z_{b}^{±}(10610)→[BB[over ¯]^{*}+c.c.]^{±} and Z_{b}^{±}(10650)→[B^{*}B[over ¯]^{*}]^{±} transitions that are found to dominate the corresponding final states. We measure Born cross sections for the three-body production of σ(e^{+}e^{-}→[BB[over ¯]^{*}+c.c.]^{±}π^{∓})=[17.4±1.6(stat)±1.9(syst)]  pb and σ(e^{+}e^{-}→[B^{*}B[over ¯]^{*}]^{±}π^{∓})=[8.75±1.15(stat)±1.04(syst)]  pb and set a 90% C.L. upper limit of σ(e^{+}e^{-}→[BB[over ¯

Enhancing PC Cluster-Based Parallel Branch-and-Bound Algorithms for the Graph Coloring Problem

NASA Astrophysics Data System (ADS)

Taoka, Satoshi; Takafuji, Daisuke; Watanabe, Toshimasa

A branch-and-bound algorithm (BB for short) is the most general technique to deal with various combinatorial optimization problems. Even if it is used, computation time is likely to increase exponentially. So we consider its parallelization to reduce it. It has been reported that the computation time of a parallel BB heavily depends upon node-variable selection strategies. And, in case of a parallel BB, it is also necessary to prevent increase in communication time. So, it is important to pay attention to how many and what kind of nodes are to be transferred (called sending-node selection strategy). In this paper, for the graph coloring problem, we propose some sending-node selection strategies for a parallel BB algorithm by adopting MPI for parallelization and experimentally evaluate how these strategies affect computation time of a parallel BB on a PC cluster network.

The Behaviour of the Military Battery Type BB248/U Used to Start the Engine of the A.P.C.

DTIC Science & Technology

1979-12-01

UNCLASS IFIED I I ABSTRACT ~ ‘The performance of the lead—acid battery used to start the diesel engine ~~~~he Armoured Personnel Carrier...vehicle engines . One factor limiting the performance of this battery system is the very low Canadian winter temperatures, especially in Northern...information on the conditions of discharge inside the vehicle. For example, the military battery type BB248/U used to start the engine of the Armoured

2008/09 Baccalaureate and Beyond Longitudinal Study (B&B:08/09). Full-Scale Methodology Report. NCES 2014-041

ERIC Educational Resources Information Center

Wine, Jennifer; Janson, Natasha; Siegel, Peter; Bennett, Christopher

2013-01-01

This report documents the methodological procedures and evaluations of the 2008/09 Baccalaureate and Beyond Longitudinal Study (B&B:08/09). RTI, with the assistance of MPR, conducted B&B:08/09 for the National Center for Education Statistics (NCES) of the U.S. Department of Education. Chapter 1 describes the background, legislative…

76 FR 55720 - BB&T Capital Partners Mezzanine Fund II, L.P.; Notice Seeking Exemption Under Section 312 of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-08

... SMALL BUSINESS ADMINISTRATION [License No. 04/04-0311] BB&T Capital Partners Mezzanine Fund II, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that BB&T Capital Partners Mezzanine Fund II, 101 N. Cherry Street, Suite...

bb̅ud̅ four-quark systems in the Born-Oppenheimer approximation: prospects and challenges

NASA Astrophysics Data System (ADS)

Peters, Antje; Bicudo, Pedro; Wagner, Marc

2018-03-01

We summarize previous work on b̅b̅ud four-quark systems in the Born-Oppenheimer approximation and discuss first steps towards an extension to the theoretically more challenging bb̅ud̅ system. Strategies to identify a possibly existing bb̅ud̅ bound state are discussed and first numerical results are presented.

Backward Blocking and Interference between Cues Are Empirically Equivalent in Non-Causally Framed Learning Tasks

ERIC Educational Resources Information Center

Luque, David; Moris, Joaquin; Orgaz, Cristina; Cobos, Pedro L.; Matute, Helena

2011-01-01

Backward blocking (BB) and interference between cues (IbC) are cue competition effects produced by very similar manipulations. In a standard BB design, both effects might occur simultaneously, which implies a potential problem for studying BB. In the present study with humans, the magnitude of both effects was compared using a non-causal scenario…

Cosmological space-times with resolved Big Bang in Yang-Mills matrix models

NASA Astrophysics Data System (ADS)

Steinacker, Harold C.

2018-02-01

We present simple solutions of IKKT-type matrix models that can be viewed as quantized homogeneous and isotropic cosmological space-times, with finite density of microstates and a regular Big Bang (BB). The BB arises from a signature change of the effective metric on a fuzzy brane embedded in Lorentzian target space, in the presence of a quantized 4-volume form. The Hubble parameter is singular at the BB, and becomes small at late times. There is no singularity from the target space point of view, and the brane is Euclidean "before" the BB. Both recollapsing and expanding universe solutions are obtained, depending on the mass parameters.

Can the use of the Leggett-Garg inequality enhance security of the BB84 protocol?

NASA Astrophysics Data System (ADS)

Shenoy H., Akshata; Aravinda, S.; Srikanth, R.; Home, Dipankar

2017-08-01

Prima facie, there are good reasons to answer in the negative the question posed in the title: the Bennett-Brassard 1984 (BB84) protocol is provably secure subject to the assumption of trusted devices, while the Leggett-Garg-type inequality (LGI) does not seem to be readily adaptable to the device independent (DI) or semi-DI scenario. Nevertheless, interestingly, here we identify a specific device attack, which has been shown to render the standard BB84 protocol completely insecure, but against which our formulated LGI-assisted BB84 protocol (based on an appropriate form of LGI) is secure.

Role of mixed precipitating cloud systems on the typhoon rainfall

NASA Astrophysics Data System (ADS)

Pan, C. J.; Krishna Reddy, K.; Lai, H. C.; Yang, S. S.

2010-01-01

L-band wind profiler data are utilized to diagnose the vertical structure of the typhoon precipitating cloud systems in Taiwan. For several typhoons, a pronounced bright band (BB) around 5 km is commonly observed from the observation. Since strong convection within typhoon circulation may disturb and/or disrupt the melting layer, the BB shall not appear persistently. Hence, an understanding of the vertical structure of the BB region is important because it holds extensive hydrometeors information on the type of precipitation and its variability. Wind profiler observational results suggest that the mixture of convective and stratiform (embedded type) clouds are mostly associated with typhoons. In the case of one typhoon, BB is appeared around 5.5 km with embedded precipitation and also BB height of 1 km higher than ordinary showery precipitation. This is evident from the long-term observations of wind profiler and Tropical Rainfall Measuring Mission. The Doppler velocity profiles show hydrometers (ice/snow) at 6 km but liquid below 5 km for typhoons and 4 km for showery precipitation. In the BB region the melting particles accelerations of 5.8 ms-1 km-1 and 3.2 ms-1 km-1 are observed for typhoon and showery precipitation, respectively.

Identification and characterization of an insect toxin protein, Bb70p, from the entomopathogenic fungus, Beauveria bassiana, using Galleria mellonella as a model system.

PubMed

Khan, Sehroon; Nadir, Sadia; Lihua, Guo; Xu, Jianchu; Holmes, Keith A; Dewen, Qiu

2016-01-01

An insect-toxic protein, Bb70p, was purified from Beauveria bassiana 70 using ammonium sulfate precipitation, ion exchange chromatography, and gel filtration. Bb70p has a high affinity for anion exchangers and 2D electrophoresis results revealed a single spot with a molecular weight of 35.5 kDa and an iso-electric point of ∼4.5. Bb70p remains active from 4 to 60°C, within a pH range of 4-10, but is more active in slightly acidic pH. A pure protein, Bb70p does not have any carbohydrate side chains. The protein caused high mortality by intra-haemocelic injection into Galleria mellonella with LD50 of 334.4 μg/g body weight and activates the phenol oxidase cascade. With a partial amino acid sequence comparison using the NCBI database, we showed no homology to known toxin proteins of entomopathogenic fungi. Thus, Bb70p appears to be an insect toxin protein, demonstrating novelty. Identification of this insect-toxic protein presents potential to enhance the virulence of B. bassiana through genetic manipulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Exploration of a variation of the bottle buoyancy technique for the assessment of body composition.

PubMed

Gulick, Dawn T; Geigle, Paula Richley

2003-05-01

Hydrostatic weighing has long been recognized as a reliable and valid method for the assessment of body composition. An alternative method known as bottle buoyancy (BB) was introduced by Katch, Hortobagyi, and Denahan in 1989. The purpose of this clinical investigation was to determine the accuracy of the BB technique using an 11-L container. Sixteen individuals (8 men, 8 women) were weighed hydrostatically using a chair/scale and the BB technique. The overall intraclass correlation coefficient for the two techniques was 0.9537. A 2-variable ANOVA was significant for gender but not for technique, and there was no interaction between variables. Thus, the BB technique appears to be an accurate substitute for the chair/scale technique for hydrostatic weighing. The BB method does not involve elaborate equipment and is portable. It could be improved with the use of multiple bottles of various volumes or a calibrated bottle to minimize the number of trials needed for accurate measurements. BB is a valuable, simple clinical tool for assessing body composition based on the principles of hydrostatic weighing and can be performed in any high school, college, or community swimming pool.

X-Ray absorption spectroscopy quantitative analysis of biomimetic copper(II) complexes with tridentate nitrogen ligands mimicking the tris(imidazole) array of protein centres.

PubMed

Borghi, Elena; Casella, Luigi

2010-02-21

In this study copper(ii) complexes with the tridentate nitrogen ligand bis[2-(1-methylbenzimidazol-2-yl)ethyl]amine (2-BB) are considered as model compounds for the Cu-tris(imidazole) array found in several copper proteins. 2-BB chelates copper(ii) forming two six-membered rings and the complexes contain methanol, nitrite, azide and water as ancillary ligands; both the coordination numbers and stereochemistries differ in these complexes. Their key structural features were investigated by using full multiple-scattering theoretical analysis of the copper K-edge X-ray absorption spectrum with the MXAN code. We showed that using cluster sizes large enough to include all atoms of the ligand, the analysis of the XANES region can give both a structural model of the metal centre and map the structure of the 2-BB complexes. Complex [Cu(2-BB)(N(3))](+) provided a critical test through the comparison of the XANES simulation results with crystallographic data, thus permitting the extension of the method to the complex [Cu(2-BB)(H(2)O)(n)](+) (n = 1 or 2), for which crystallographic data are not available but is expected to bear a five-coordinated Cu(3N)(2O) core (n = 2). The structural data of [Cu(2-BB)(MeOH)(ClO(4))](+) and [Cu(2-BB)(NO(2))](+), both with a Cu(3N)(2O) core but with a different stereochemistry, were used as the starting parameters for two independent simulations of the XANES region of the [Cu(2-BB)(H(2)O)(2)](+) cation. The two structural models generated by simulation converge towards a structure for the aqua-cation with a lower coordination number. New calculations, where four-coordinated Cu(3N)(O) cores were considered as the starting structures, validated that the structure of the aqua-complex in the powder state has a copper(ii) centre with a four-coordinated Cu(3N)(O) core and a molecular formula [Cu(2-BB)(H(2)O)](ClO(4)).(H(2)O). A water solvation molecule, presumed to be disordered from the simulations with the two Cu(3N)(2O) cores, is present. The successful treatment of this Cu-2-BB complex system allows the extension of the method to other biomimetic compounds when a structural characterization is lacking.

Combination CTLA-4 Blockade and 4-1BB Activation Enhances Tumor Rejection by Increasing T-Cell Infiltration, Proliferation, and Cytokine Production

PubMed Central

Curran, Michael A.; Kim, Myoungjoo; Montalvo, Welby; Al-Shamkhani, Aymen; Allison, James P.

2011-01-01

Background The co-inhibitory receptor Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) attenuates immune responses and prevent autoimmunity, however, tumors exploit this pathway to evade the host T-cell response. The T-cell co-stimulatory receptor 4-1BB is transiently upregulated on T-cells following activation and increases their proliferation and inflammatory cytokine production when engaged. Antibodies which block CTLA-4 or which activate 4-1BB can promote the rejection of some murine tumors, but fail to cure poorly immunogenic tumors like B16 melanoma as single agents. Methodology/Principal Findings We find that combining αCTLA-4 and α4-1BB antibodies in the context of a Flt3-ligand, but not a GM-CSF, based B16 melanoma vaccine promoted synergistic levels of tumor rejection. 4-1BB activation elicited strong infiltration of CD8+ T-cells into the tumor and drove the proliferation of these cells, while CTLA-4 blockade did the same for CD4+ effector T-cells. Anti-4-1BB also depressed regulatory T-cell infiltration of tumors. 4-1BB activation strongly stimulated inflammatory cytokine production in the vaccine and tumor draining lymph nodes and in the tumor itself. The addition of CTLA-4 blockade further increased IFN-γ production from CD4+ effector T-cells in the vaccine draining node and the tumor. Anti 4-1BB treatment, with or without CTLA-4 blockade, induced approximately 75% of CD8+ and 45% of CD4+ effector T-cells in the tumor to express the killer cell lectin-like receptor G1 (KLRG1). Tumors treated with combination antibody therapy showed 1.7-fold greater infiltration by these KLRG1+CD4+ effector T-cells than did those treated with α4-1BB alone. Conclusions/Significance This study shows that combining T-cell co-inhibitory blockade with αCTLA-4 and active co-stimulation with α4-1BB promotes rejection of B16 melanoma in the context of a suitable vaccine. In addition, we identify KLRG1 as a useful marker for monitoring the anti-tumor immune response elicited by this therapy. These findings should aid in the design of future trials for the immunotherapy of melanoma. PMID:21559358

The enhancement of PM2.5 mass and water-soluble ions of biosmoke transported from Southeast Asia over the Mountain Lulin site in Taiwan

NASA Astrophysics Data System (ADS)

Lee, Chung-Te; Chuang, Ming-Tung; Lin, Neng-Huei; Wang, Jia-Lin; Sheu, Guey-Rong; Chang, Shuenn-Chin; Wang, Sheng-Hsiang; Huang, Hill; Chen, Horng-Wen; Liu, Yuan-Liang; Weng, Guo-Hau; Lai, Hsin-Yo; Hsu, Shao-Peng

2011-10-01

Biomass burning (BB) in Southeast Asia (Indochina and southern China) occurs frequently in March and April every year. The burning plume is ordinarily transported eastward by the prevailing westerly, further affecting downstream air quality in East Asia. In this study, atmospheric aerosols were collected at the downstream Lulin Atmospheric Background Station (LABS, 2862 m a.s.l., central Taiwan) from April 2003 to April 2009. Results show that monthly means of PM2.5 were highest during the BB period, especially in March. The PM2.5 mean for BB activity was 17.5 μg m-3, while the daily PM2.5 mean can sometimes be above 40 μg m-3. The background PM2.5 level in free troposphere of the West Pacific was at 3.7 ± 1.8 μg m-3. This mean is roughly the same regardless of the air masses moving from China, Pacific Ocean, and South China Sea toward LABS. In addition, the highest PM2.5 level occurred in 2004, making it the most active year of BB for the whole observation period. Greater amounts of nitrate and potassium ions were observed in the PM2.5 collected during the BB period compared to the non-BB (NBB) period. Linear regression analysis on PM2.5 water-soluble ions shows a moderate correlation (R2 = 0.59) between non-sea-salt potassium and nitrate ions during the BB period. Furthermore, for all trajectory source origins, ammonium ion had the best correlation (R2 = 0.84) with non-sea-salt sulfate when the air masses were influenced by anthropogenic sources during the NBB period. The enhancement ratios of nitrate ion during the BB period could reach 6.7 and 9.7 relative to air masses from the BB source region and from the pristine area during the NBB period, respectively. During the study period, ammonia gas was found to be insufficient to neutralize sulfuric and nitric gases. Therefore, most aerosols were more acidic than basic. Our long-term observation of atmospheric aerosols with inter-annual variability is valuable in providing data for verifying BB source inventory and model performance in East Asia.

Paracrine-Mediated Neuroprotection and Neuritogenesis of Axotomised Retinal Ganglion Cells by Human Dental Pulp Stem Cells: Comparison with Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells

PubMed Central

Mead, Ben; Logan, Ann; Berry, Martin

2014-01-01

We have investigated and compared the neurotrophic activity of human dental pulp stem cells (hDPSC), human bone marrow-derived mesenchymal stem cells (hBMSC) and human adipose-derived stem cells (hAMSC) on axotomised adult rat retinal ganglion cells (RGC) in vitro in order to evaluate their therapeutic potential for neurodegenerative conditions of RGC. Using the transwell system, RGC survival and length/number of neurites were quantified in coculture with stem cells in the presence or absence of specific Fc-receptor inhibitors to determine the role of NGF, BDNF, NT-3, VEGF, GDNF, PDGF-AA and PDGF-AB/BB in stem cell-mediated RGC neuroprotection and neuritogenesis. Conditioned media, collected from cultured hDPSC/hBMSC/hAMSC, were assayed for the secreted growth factors detailed above using ELISA. PCR array determined the hDPSC, hBMSC and hAMSC expression of genes encoding 84 growth factors and receptors. The results demonstrated that hDPSC promoted significantly more neuroprotection and neuritogenesis of axotomised RGC than either hBMSC or hAMSC, an effect that was neutralized after the addition of specific Fc-receptor inhibitors. hDPSC secreted greater levels of various growth factors including NGF, BDNF and VEGF compared with hBMSC/hAMSC. The PCR array confirmed these findings and identified VGF as a novel potentially therapeutic hDPSC-derived neurotrophic factor (NTF) with significant RGC neuroprotective properties after coculture with axotomised RGC. In conclusion, hDPSC promoted significant multi-factorial paracrine-mediated RGC survival and neurite outgrowth and may be considered a potent and advantageous cell therapy for retinal nerve repair. PMID:25290916

Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration

PubMed Central

2014-01-01

Background Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis. Methods Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model. Results Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process. Conclusions Taken together, these results demonstrate that dHACM grafts: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds. PMID:24817999

Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration.

PubMed

Koob, Thomas J; Lim, Jeremy J; Massee, Michelle; Zabek, Nicole; Rennert, Robert; Gurtner, Geoffrey; Li, William W

2014-01-01

Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis. Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model. Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process. TAKEN TOGETHER, THESE RESULTS DEMONSTRATE THAT DHACM GRAFTS: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds.

Modeling the Complex Photochemistry of Biomass Burning Plumes in Plume-Scale, Regional, and Global Air Quality Models

NASA Astrophysics Data System (ADS)

Alvarado, M. J.; Lonsdale, C. R.; Yokelson, R. J.; Travis, K.; Fischer, E. V.; Lin, J. C.

2014-12-01

Forecasting the impacts of biomass burning (BB) plumes on air quality is difficult due to the complex photochemistry that takes place in the concentrated young BB plumes. The spatial grid of global and regional scale Eulerian models is generally too large to resolve BB photochemistry, which can lead to errors in predicting the formation of secondary organic aerosol (SOA) and O3, as well as the partitioning of NOyspecies. AER's Aerosol Simulation Program (ASP v2.1) can be used within plume-scale Lagrangian models to simulate this complex photochemistry. We will present results of validation studies of the ASP model against aircraft observations of young BB smoke plumes. We will also present initial results from the coupling of ASP v2.1 into the Lagrangian particle dispersion model STILT-Chem in order to better examine the interactions between BB plume chemistry and dispersion. In addition, we have used ASP to develop a sub-grid scale parameterization of the near-source chemistry of BB plumes for use in regional and global air quality models. The parameterization takes inputs from the host model, such as solar zenith angle, temperature, and fire fuel type, and calculates enhancement ratios of O3, NOx, PAN, aerosol nitrate, and other NOy species, as well as organic aerosol (OA). We will present results from the ASP-based BB parameterization as well as its implementation into the global atmospheric composition model GEOS-Chem for the SEAC4RS campaign.

Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease.

PubMed

Cholankeril, George; Yoo, Eric R; Perumpail, Ryan B; Liu, Andy; Sandhu, Jeevin S; Nair, Satheesh; Hu, Menghan; Ahmed, Aijaz

2017-09-26

We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945-1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts-the BB and non-BB-with a secondary diagnosis of HCV, ALD, or NASH. From 2003-2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.

[Contained laparostomy with a Bogota bag. Results of case series].

PubMed

Manterola, Carlos; Moraga, Javier; Urrutia, Sebastián

2011-01-01

The «Bogota bag» (BB) is one of the options for contained laparostomy (CL). The aim of this study was to report the procedure associated hospital morbidity (PAHM) in patients undergoing relaparotomy followed by a laparostomy using the BB. Between 2002 and 2008, a prospective series of patients who underwent relaparotomy at the Hospital Hernán Henríquez, Temuco (Chile) was evaluated. The main end point was «development of PAHM». Secondary end points were: indications of the CL, time to first change of the BB, type of abdominal wall repair, hospital mortality and development of ventral hernia. Descriptive statistics were used, with the calculations of percentages and measures of central tendency and dispersion. The BB was used in 86 patients (median age of 53 years, 63% female). The PAHM was 38% (surgical-site infection and enterocutaneous fistula). The most frequent indication of CL was intra-abdominal sepsis (60%). The median time until the first change of the BB, the time period between surgical operations, and the time until removal of the BB were 65 hours, 2 days and 9 days, respectively. Laparostomy was repaired exclusively with skin, fascial closure or dermal-epidermal graft in 50, 39 and 10%, respectively. In hospital mortality was 12%. Sixty percent of the patients developed a ventral hernia within a 48 month follow-up. CL with a BB is associated with a high rate of PAHM and delayed complications. Copyright © 2010 AEC. Published by Elsevier Espana. All rights reserved.

Advanced Characterization of Semivolatile Organic Compounds Emitted from Biomass Burning

NASA Astrophysics Data System (ADS)

Hatch, L. E.; Liu, Y.; Rivas-Ubach, A.; Shaw, J. B.; Lipton, M. S.; Barsanti, K. C.

2016-12-01

Biomass burning (BB) emits large amounts of non-methane organic gases (NMOGs) and primary (directly emitted) particulate matter (PM). NMOGs also react in plume to form secondary PM (i.e., SOA) and ozone. BB-PM has been difficult to represent accurately in models used for chemistry and climate predictions, including for air quality and fire management purposes. Much recent research supports that many previously unconsidered SOA precursors exist, including oxidation of semivolatile compounds (SVOCs). Although many recent studies have characterized relatively volatile BB-derived NMOGs and relatively non-volatile particle-phase organic species, comparatively few studies have performed detailed characterization of SVOCs emitted from BB. Here we present efforts to expand the volatility and compositional ranges of compounds measured in BB smoke. In this work, samples of SVOCs in gas and particle phases were collected from 18 fires representing a range of fuel types during the 2016 FIREX fire laboratory campaign; samples were analyzed by two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC-TOFMS) and Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS). Hundreds of compounds were detectable in both gas and particle phases by GCxGC-TOFMS whereas thousands of peaks were present in the FTICR mass spectra. Data from both approaches highlight that chemical fingerprints of smoke are fuel/burn-dependent. These efforts support our continued research in building the understanding and model representation of BB emissions and BB-derived SOA.

Preparation of a specific bamboo based activated carbon and its application for ciprofloxacin removal.

PubMed

Wang, Y X; Ngo, H H; Guo, W S

2015-11-15

The studied bamboo based activated carbon (BbAC) with high specific surface area (SSA) and high micro pore volume was prepared from bamboo scraps by the combined activation of H3PO4 and K2CO3. The BbAC was characterized based on the N2 adsorption isotherm at 77K. The results showed that the SSA and pore volume of BbAC increased with increasing impregnation ratio and reached maxima at the impregnation ratio of 3:1 at 750°C. Under these optimal conditions, the BbAC obtained could have a maximum SSA of 2237 m(2)/g and a maximum total pore volume of 1.23 cm(3)/g with the micro pore ratio of more than 90%. The adsorption performance of ciprofloxacin (CIP) on the BbAC was determined at 298 K. The Langmuir and Freundlich models were employed to describe the adsorption equilibrium and the kinetic data were fitted by pseudo first-order and pseudo second-order kinetic models. The results showed that the Langmuir model and the pseudo second-order kinetic model presented better fittings for the adsorption equilibrium and kinetics data, respectively. The maximum adsorption amount of CIP (613 mg/g) on the BbAC was much higher than the report in the literature. Conclusively, the BbAC could be a promising adsorption material for CIP removal from water. Copyright © 2015 Elsevier B.V. All rights reserved.

Advanced Characterization of Semivolatile Organic Compounds Emitted from Biomass Burning

NASA Astrophysics Data System (ADS)

Hatch, L. E.; Liu, Y.; Rivas-Ubach, A.; Shaw, J. B.; Lipton, M. S.; Barsanti, K. C.

2017-12-01

Biomass burning (BB) emits large amounts of non-methane organic gases (NMOGs) and primary (directly emitted) particulate matter (PM). NMOGs also react in plume to form secondary PM (i.e., SOA) and ozone. BB-PM has been difficult to represent accurately in models used for chemistry and climate predictions, including for air quality and fire management purposes. Much recent research supports that many previously unconsidered SOA precursors exist, including oxidation of semivolatile compounds (SVOCs). Although many recent studies have characterized relatively volatile BB-derived NMOGs and relatively non-volatile particle-phase organic species, comparatively few studies have performed detailed characterization of SVOCs emitted from BB. Here we present efforts to expand the volatility and compositional ranges of compounds measured in BB smoke. In this work, samples of SVOCs in gas and particle phases were collected from 18 fires representing a range of fuel types during the 2016 FIREX fire laboratory campaign; samples were analyzed by two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC-TOFMS) and Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS). Hundreds of compounds were detectable in both gas and particle phases by GCxGC-TOFMS whereas thousands of peaks were present in the FTICR mass spectra. Data from both approaches highlight that chemical fingerprints of smoke are fuel/burn-dependent. These efforts support our continued research in building the understanding and model representation of BB emissions and BB-derived SOA.

A First-look Atmospheric Modeling Study of the Young Directly Imaged Planet-mass Companion, ROXs 42Bb

NASA Astrophysics Data System (ADS)

Currie, Thayne; Burrows, Adam; Daemgen, Sebastian

2014-06-01

We present and analyze JKsL' photometry and our previously published H-band photometry and K-band spectroscopy for ROXs 42Bb, an object Currie et al. first reported as a young directly imaged planet-mass companion. ROXs 42Bb exhibits IR colors redder than field L dwarfs but consistent with other planet-mass companions. From the H2O-2 spectral index, we estimate a spectral type of L0 ± 1; weak detections/non-detections of the CO bandheads, Na I, and Ca I support evidence for a young, low surface gravity object primarily derived from the H2(K) index. ROXs 42Bb's photometry/K-band spectrum are inconsistent with limiting cases of dust-free atmospheres (COND) and marginally inconsistent with the AMES/DUSTY models and the BT-SETTL models. However, ROXS 42Bb data are simultaneously fit by atmosphere models incorporating several micron-sized dust grains entrained in thick clouds, although further modifications are needed to better reproduce the K-band spectral shape. ROXs 42Bb's best-estimated temperature is T eff ~ 1950-2000 K, near the low end of the empirically derived range in Currie et al. For an age of ~1-3 Myr and considering the lifetime of the protostar phase, ROXs 42Bb's luminosity of log(L/L ⊙) ~ -3.07 ± 0.07 implies a mass of 9^{+3}_{-3} MJ , making it one of the lightest planetary-mass objects yet imaged.

Gut microbiota mediated benefits of barley kernel products on metabolism, gut hormones, and inflammatory markers as affected by co-ingestion of commercially available probiotics: a randomized controlled study in healthy subjects.

PubMed

Nilsson, Anne; Johansson-Boll, Elin; Sandberg, Jonna; Björck, Inger

2016-10-01

Barley kernel based products have been shown to induce benefits on blood glucose regulation, cardio-metabolic risk markers and appetite regulating hormones in a time perspective of 11-16 h after intake. The mechanisms have been assigned to gut fermentation of indigestible carbohydrates. The purpose of the present study was to evaluate if the modulatory effects of barley on markers of metabolic- and appetite regulation are affected by a dietary background including a mixture of commercially available probiotics. Barley kernel bread was included in the normal diet of 21 healthy subjects in two 4-day intervention periods; with (BB-pro) or without (BB) dietary supplement with a combination of probiotics (Bifidobacterium animalis DN-173 010, Lactobacillus reuteri DSM 17938, and Lactobacillus plantarum 299v). A white wheat flour based bread was included as a reference product (WWB-ref) in a separate 4-day bread intervention period. A cross-over design was applied concerning BB- and WWB-ref; the BB-pro intervention was last in the test sequence. The BB-pro intervention was preceded by 10 days priming with probiotics. The 4 day BB- and WWB-ref intervention periods included dietary supplementation with placebo, and the interventions were preceded with 10 days priming with the placebo. The day after each intervention period, blood samples were collected at fasting and postprandially after a standardized breakfast (0-210 min) for determination of markers of glucose metabolism (blood glucose, serum (s-) insulin), inflammation (s-IL-6, s-IL-18, s-CRP, PAI-1), and concentrations of gut derived hormones involved in satiety and glucose homeostasis (plasma (p-) PYY, p-GLP-1) and intestinal barrier integrity (p-GLP-2). Breath hydrogen was determined as a marker of colonic fermentation. Four days intervention with BB, in comparison to WWB-ref, lowered blood glucose response after a subsequent standardized breakfast (0-210 min, P < 0.05). BB and BB-pro interventions increased p-GLP-1 (0-120 min, P < 0.05) and breath H 2 (0-210 min, P < 0.05). BB-pro intervention, in comparison to BB and WWB-ref, increased levels of s-PAI-1 (P < 0.05), and p-GLP-2 (0-210 min, P < 0.05) after the standardized breakfast. With the exception of increased p-GLP-2 and an unexpected increase in s-PAI-1 concentrations, co-ingestion of a mixture of probiotics did not affect the metabolic outcome of BB; neither positively nor importantly negatively. The study was registered at: ClinicalTrials.gov, register number NCT01718418 (www.clinicaltrials.gov/ct2/show/NCT01718418). Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

77 FR 77040 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-31

... Laser Guided Bombs, 162 FMU-152 bomb fuzes, 150 BLU-111B/B 500-lb Conical Fin General Purpose Bombs (Freefall Tail), 60 BLU-111B/B 500-lb Retarded Fin General Purpose Bombs (Ballute Tail), and 32 CBU-105 Wind... (AMRAAM), 162 GBU-12 PAVEWAY II 500-lb Laser Guided Bombs, 162 FMU-152 bomb fuzes, 150 BLU- 111B/B 500-lb...

De Novo whole genome sequence of Xylella fastidiosa subsp. multiplex strain BB01 from blueberry in Georgia, USA

USDA-ARS?s Scientific Manuscript database

This study reports a de novo assembled draft genome sequence of Xylella fastidiosa subsp. multiplex strain BB01 causing blueberry bacterial leaf scorch in Georgia, USA. The BB01 genome is 2,517,579 bp with a G+C content of 51.8% and 2,943 open reading frames (ORFs) and 48 RNA genes....

Daily propranolol administration reduces persistent injury-associated anemia after severe trauma and chronic stress.

PubMed

Alamo, Ines G; Kannan, Kolenkode B; Bible, Letitia E; Loftus, Tyler J; Ramos, Harry; Efron, Philip A; Mohr, Alicia M

2017-04-01

After severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow (BM) erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators, such as ferroportin, transferrin, and transferrin receptor-1 (TFR-1), is unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a nonselective β blocker, restores BM function and improves iron homeostasis. Male Sprague-Dawley rats were subjected to LCHS ± BB and LCHS/CS ± BB. BB was achieved with propranolol (10 mg/kg) daily until the day of sacrifice. Hemoglobin, plasma EPO, plasma hepcidin, BM cellularity and BM erythroid colony growth were assessed. RNA was isolated to measure transferrin, TFR-1 and ferroportin expression. Data are presented as mean ± SD; *p < 0.05 versus untreated counterpart by t test. The addition of CS to LCHS leads to persistent anemia on posttrauma day 7, while the addition of BB improved hemoglobin levels (LCHS/CS: 10.6 ± 0.8 vs. LCHS/CS + BB: 13.9 ± 0.4* g/dL). Daily BB use after LCHS/CS improved BM cellularity, colony-forming units granulocyte, erythrocyte, monocyte megakaryocyte, burst-forming unit erythroid and colony-forming unit erythroid cell colony growth. LCHS/CS + BB significantly reduced plasma EPO levels and increased plasma hepcidin levels on day 7. The addition of CS to LCHS resulted in decreased liver ferroportin expression as well as decreased BM transferrin and TFR-1 expression, thus, blocking iron supply to erythroid cells. However, daily BB after LCHS/CS improved expression of all iron regulators. Daily propranolol administration after LCHS/CS restored BM function and improved anemia after severe trauma. In addition, iron regulators are significantly reduced after LCHS/CS, which may contribute to iron restriction after injury. However, daily propranolol administration after LCHS/CS improved iron homeostasis.

Probiotics Blunt the Anti-Hypertensive Effect of Blueberry Feeding in Hypertensive Rats without Altering Hippuric Acid Production.

PubMed

Blanton, Cynthia; He, Zhengcheng; Gottschall-Pass, Katherine T; Sweeney, Marva I

2015-01-01

Previously we showed that feeding polyphenol-rich wild blueberries to hypertensive rats lowered systolic blood pressure. Since probiotic bacteria produce bioactive metabolites from berry polyphenols that enhance the health benefits of berry consumption, we hypothesized that adding probiotics to a blueberry-enriched diet would augment the anti-hypertensive effects of blueberry consumption. Groups (n = 8) of male spontaneously hypertensive rats were fed one of four AIN '93G-based diets for 8 weeks: Control (CON); 3% freeze-dried wild blueberry (BB); 1% probiotic bacteria (PRO); or 3% BB + 1% PRO (BB+PRO). Blood pressure was measured at weeks 0, 2, 4, 6, and 8 by the tail-cuff method, and urine was collected at weeks 4 and 8 to determine markers of oxidative stress (F2-isoprostanes), nitric oxide synthesis (nitrites), and polyphenol metabolism (hippuric acid). Data were analyzed using mixed models ANOVA with repeated measures. Diet had a significant main effect on diastolic blood pressure (p = 0.046), with significantly lower measurements in the BB- vs. CON-fed rats (p = 0.035). Systolic blood pressure showed a similar but less pronounced response to diet (p = 0.220), again with the largest difference between the BB and CON groups. Absolute increase in blood pressure between weeks 0 and 8 tended to be smaller in the BB and PRO vs. CON and BB+PRO groups (systolic increase, p = 0.074; diastolic increase, p = 0.185). Diet had a significant main effect on hippuric acid excretion (p<0.0001), with 2- and ~1.5-fold higher levels at weeks 4 and 8, respectively, in the BB and BB+PRO vs. PRO and CON groups. Diet did not have a significant main effect on F2-isoprostane (p = 0.159) or nitrite excretion (p = 0.670). Our findings show that adding probiotics to a blueberry-enriched diet does not enhance and actually may impair the anti-hypertensive effect of blueberry consumption. However, probiotic bacteria are not interfering with blueberry polyphenol metabolism into hippuric acid.

Endometrial carcinoma in the baby boomer generation. Tumor characteristics and clinical outcome.

PubMed

Elshaikh, Mohamed A; Cattaneo, Richard; Shah, Mira; Patel, Suketu; Mahan, Meredith; Buekers, Thomas; Siddiqui, Farzan

2013-02-01

Baby boomers (BB) entering retirement represent a significant burden on medical resources. The unique lifestyle characteristics engendered by the BB may lead to different endometrial cancer characteristics that bear understanding. We sought to characterize BB with endometrioid carcinoma after hysterectomy and compare the results to those of prior to the baby boomers (PB). After reviewing our prospectively maintained database of 1,450 patients with endometrial cancer, we identified 595 patients who underwent hysterectomy for 1988 International Federation of Gynecologic Oncology (FIGO) stage I-II uterine endometrioid carcinomas, who were born between 1926 and 1964. Their medical records were reviewed in this Institutional review board (IRB)-approved study. Patients with non-endometrioid carcinoma and those who received preoperative therapy were excluded. Patients were defined as BB (born 1946-1964) or PB (born in 1926-1945). The two groups were compared regarding patients' demographics, tumor characteristics and survival. Following a univariate analysis, multivariable modeling was carried out using Cox regression analysis. All patients underwent hysterectomy with a minimum of two years' follow-up. There were 234 patients (39%) in the BB group and 361 patients (61%) in the PB group. Median follow-up for the study cohort was 56 months. BB had higher body mass index (p=0.027), lower tumor grade (p=0.002), earlier FIGO stage (p=0.023), higher number of dissected lymph nodes (p=0.008), less lymphvascular space involvement (p=<0.034), less utilization of adjuvant therapy (p=<0.001), and younger age at diagnosis (p=0.002). However, there was no significant difference found between the BB and PB in regards to local control, disease-specific survival and overall survival. For the study cohort, FIGO stage and tumor grade were independent predictors of recurrence-free and disease-specific survival. There was a trend towards shorter overall survival for the PB women (p=0.063). Although tumor characteristics were more favorable in the BB group of women, local control and survival end-points were not statistically different compared to those of the PB group. As more BB are diagnosed with endometrial carcinoma, further research is warranted to further elucidate the characteristic differences in endometrial carcinoma, if any, in this generation.

Daily propranolol administration reduces persistent injury-associated anemia following severe trauma and chronic stress

PubMed Central

Alamo, Ines G.; Kannan, Kolenkode B.; Bible, Letitia E.; Loftus, Tyler J.; Ramos, Harry; Efron, Philip A.; Mohr, Alicia M.

2017-01-01

Background Following severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators such as ferroportin, transferrin and transferrin receptor-1 (TFR-1) are unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a non-selective beta-blocker, restores bone marrow function and improves iron homeostasis. Methods Male Sprague-Dawley rats were subjected to LCHS±BB and LCHS/CS±BB. BB was achieved with propranolol (10mg/kg) daily until the day of sacrifice. Hemoglobin (Hgb), plasma EPO, plasma hepcidin, bone marrow cellularity and bone marrow erythroid colony growth were assessed. RNA was isolated to measure transferrin, TFR-1 and ferroportin expression. Data is presented as mean±SD; *p<0.05 vs. untreated counterpart by t-test. Results The addition of CS to LCHS leads to persistent anemia on post-trauma day 7, while the addition of BB improved Hgb levels (LCHS/CS: 10.6±0.8 vs. LCHS/CS+BB: 13.9±0.4* g/dL). Daily BB use following LCHS/CS improved BM cellularity, CFU-GEMM, BFU-E and CFU-E colony growth. LCHS/CS+BB significantly reduced plasma EPO levels and increased plasma hepcidin levels on day 7. The addition of CS to LCHS resulted in decreased liver ferroportin expression as well as decreased bone marrow transferrin and TFR-1 expression, thus, blocking iron supply to erythroid cells. However, daily BB after LCHS/CS improved expression of all iron regulators. Conclusions Daily propranolol administration following LCHS/CS restored bone marrow function and improved anemia after severe trauma. In addition, iron regulators are significantly reduced following LCHS/CS, which may contribute to iron restriction after injury. However, daily propranolol administration after LCHS/CS improved iron homeostasis. Level of Evidence Level II, therapeutic study PMID:28099381

Probiotics Blunt the Anti-Hypertensive Effect of Blueberry Feeding in Hypertensive Rats without Altering Hippuric Acid Production

PubMed Central

2015-01-01

Previously we showed that feeding polyphenol-rich wild blueberries to hypertensive rats lowered systolic blood pressure. Since probiotic bacteria produce bioactive metabolites from berry polyphenols that enhance the health benefits of berry consumption, we hypothesized that adding probiotics to a blueberry-enriched diet would augment the anti-hypertensive effects of blueberry consumption. Groups (n = 8) of male spontaneously hypertensive rats were fed one of four AIN ‘93G-based diets for 8 weeks: Control (CON); 3% freeze-dried wild blueberry (BB); 1% probiotic bacteria (PRO); or 3% BB + 1% PRO (BB+PRO). Blood pressure was measured at weeks 0, 2, 4, 6, and 8 by the tail-cuff method, and urine was collected at weeks 4 and 8 to determine markers of oxidative stress (F2-isoprostanes), nitric oxide synthesis (nitrites), and polyphenol metabolism (hippuric acid). Data were analyzed using mixed models ANOVA with repeated measures. Diet had a significant main effect on diastolic blood pressure (p = 0.046), with significantly lower measurements in the BB- vs. CON-fed rats (p = 0.035). Systolic blood pressure showed a similar but less pronounced response to diet (p = 0.220), again with the largest difference between the BB and CON groups. Absolute increase in blood pressure between weeks 0 and 8 tended to be smaller in the BB and PRO vs. CON and BB+PRO groups (systolic increase, p = 0.074; diastolic increase, p = 0.185). Diet had a significant main effect on hippuric acid excretion (p<0.0001), with 2- and ~1.5-fold higher levels at weeks 4 and 8, respectively, in the BB and BB+PRO vs. PRO and CON groups. Diet did not have a significant main effect on F2-isoprostane (p = 0.159) or nitrite excretion (p = 0.670). Our findings show that adding probiotics to a blueberry-enriched diet does not enhance and actually may impair the anti-hypertensive effect of blueberry consumption. However, probiotic bacteria are not interfering with blueberry polyphenol metabolism into hippuric acid. PMID:26544724

Role of Soluble ST2 Levels and Beta-Blockers Dosage on Cardiovascular Events of Patients with Unselected ST-Segment Elevation Myocardial Infarction

PubMed Central

Huang, Wei-Ping; Zheng, Xuan; He, Lei; Su, Xi; Liu, Cheng-Wei; Wu, Ming-Xiang

2018-01-01

Background: Serum soluble ST2 (sST2) levels are elevated early after acute myocardial infarction and are related to adverse left ventricular (LV) remodeling and cardiovascular outcomes in ST-segment elevation myocardial infarction (STEMI). Beta-blockers (BB) have been shown to improve LV remodeling and survival. However, the relationship between sST2, final therapeutic BB dose, and cardiovascular outcomes in STEMI patients remains unknown. Methods: A total of 186 STEMI patients were enrolled at the Wuhan Asia Heart Hospital between January 2015 and June 2015. All patients received standard treatment and were followed up for 1 year. Serum sST2 was measured at baseline. Patients were divided into four groups according to their baseline sST2 values (high >56 ng/ml vs. low ≤56 ng/ml) and final therapeutic BB dose (high ≥47.5 mg/d vs. low <47.5 mg/d). Cox regression analyses were performed to determine whether sST2 and BB were independent risk factors for cardiovascular events in STEMI. Results: Baseline sST2 levels were positively correlated with heart rate (r = 0.327, P = 0.002), Killip class (r = 0.408, P = 0.000), lg N-terminal prohormone B-type natriuretic peptide (r = 0.467, P = 0.000), lg troponin I (r = 0.331, P = 0.000), and lg C-reactive protein (r = 0.307, P = 0.000) and negatively correlated to systolic blood pressure (r = −0.243, P = 0.009) and LV ejection fraction (r = −0.402, P = 0.000). Patients with higher baseline sST2 concentrations who were not titrated to high-dose BB therapy (P < 0.0001) had worse outcomes. Baseline high sST2 (hazard ratio [HR]: 2.653; 95% confidence interval [CI]: 1.201–8.929; P = 0.041) and final low BB dosage (HR: 1.904; 95% CI, 1.084–3.053; P = 0.035) were independent predictors of cardiovascular events in STEMI. Conclusions: High baseline sST2 levels and final low BB dosage predicted cardiovascular events in STEMI. Hence, sST2 may be a useful biomarker in cardiac pathophysiology. PMID:29786039

The role of ENSO in determining the emission, the speciation and the resulting fate of Hg from Biomass Burning, a lesson from the recent past

NASA Astrophysics Data System (ADS)

De Simone, F.; Hedgecock, I. M.; Cinnirella, S.; Carbone, F.; Sprovieri, F.; Pirrone, N.

2017-12-01

The burning of vegetation is an environmental process that impacts the chemical composition of troposphere on a global scale, and has significant consequences on atmospheric pollution and climate. ENSO influences the alternating patterns of drier and wetter periods in almost all continents, therefore causing a rise in, and varying the timing of, fire activity in numerous regions and ecosystems (Le Page et al). A large amount of legacy Hg is currently buffered in different environmental compartments, including soil and vegetation, due to past and current anthropogenic processes and activities. Biomass Burning (BB) is a major source of atmospheric Hg, and a main driver in recycling this legacy Hg which is eventually re-deposited over land and oceans. Hg from BB is emitted mainly as Hg(0)(g), but a large fraction (up to 30% and more) is released as Hg bound to particulate matter, Hg(p), which is more likely to be deposited close to the fire activity (De Simone et al). Thus, speciation is one of the most important factors in determining the redistribution of Hg, and of the subsequent geographical distribution of its atmospheric deposition. Although the drivers controlling speciation remain uncertain, there is evidence that it depends on burn characteristics and fuel moisture content, which depends on the climatological characteristics of the regions where BB occurs (Obrist et al). The areas where atmospheric Hg is deposited depends ultimately on atmospheric transport, transformation and precipitation patterns, hence the fate of Hg emitted from BB is determined by a complex series of interacting processes and mechanisms, which begin with the release of Hg and continue until deposition. Many of these processes are influenced by ENSO. This modeling study analyses the deposition of Hg from BB using different satellite imagery based products, spanning a number of years, characterized by different ENSO regimes, to evaluate how it impacts BB, the speciation of emitted Hg, and ultimately the fate of Hg. The aim is to identify the key mechanism(s) involved in determining the final receptors of Hg recycled by BB changing climate. Le Page et al., https://doi.org/10.5194/acp-8-1911-2008, 2008 De Simone et al., https://doi.org/10.5194/acp-17-1881-2017, 2017 Obrist et al., https://doi.org/10.1021/es071279n

The ambient aerosol characterization during the prescribed bushfire season in Brisbane 2013.

PubMed

Milic, A; Miljevic, B; Alroe, J; Mallet, M; Canonaco, F; Prevot, A S H; Ristovski, Z D

2016-08-01

Prescribed burnings are conducted in Queensland each year from August until November aiming to decrease the impact of bushfire hazards and maintain the health of vegetation. This study reports chemical characteristics of the ambient aerosol, with a focus on source apportionment of the organic aerosol (OA) fraction, during the prescribed biomass burning (BB) season in Brisbane 2013. All measurements were conducted within the International Laboratory for Air Quality and Health (ILAQH) located in Brisbane's Central Business District. Chemical composition, degree of ageing and the influence of BB emission on the air quality of central Brisbane were characterized using a compact Time of Flight Aerosol Mass Spectrometer (cToF-AMS). AMS loadings were dominated by OA (64%), followed by, sulfate (17%), ammonium (14%) and nitrates (5%). Source apportionment was applied on the AMS OA mass spectra via the multilinear engine solver (ME-2) implementation within the recently developed Source Finder (SoFi) interface. Six factors were extracted including hydrocarbon-like OA (HOA), cooking-related OA (COA), biomass burning OA (BBOA), low-volatility oxygenated OA (LV-OOA), semivolatile oxygenated OA (SV-OOA), and nitrogen-enriched OA (NOA). The aerosol fraction that was attributed to BB factor was 9%, on average over the sampling period. The high proportion of oxygenated OA (72%), typically representing aged emissions, could possess a fraction of oxygenated species transfored from BB components on their way to the sampling site. Copyright © 2016 Elsevier B.V. All rights reserved.

Probing into the aging dynamics of biomass burning aerosol by using satellite measurements of aerosol optical depth and carbon monoxide

NASA Astrophysics Data System (ADS)

Konovalov, Igor B.; Beekmann, Matthias; Berezin, Evgeny V.; Formenti, Paola; Andreae, Meinrat O.

2017-04-01

Carbonaceous aerosol released into the atmosphere from open biomass burning (BB) is known to undergo considerable chemical and physical transformations (aging). However, there is substantial controversy about the nature and observable effects of these transformations. A shortage of consistent observational evidence on BB aerosol aging processes under different environmental conditions and at various temporal scales hinders development of their adequate representations in chemistry transport models (CTMs). In this study, we obtain insights into the BB aerosol dynamics by using available satellite measurements of aerosol optical depth (AOD) and carbon monoxide (CO). The basic concept of our method is to consider AOD as a function of the BB aerosol photochemical age (that is, the time period characterizing the exposure of BB aerosol emissions to atmospheric oxidation reactions) predicted by means of model tracers. We evaluate the AOD enhancement ratio (ER) defined as the ratio of optical depth of actual BB aerosol with respect to that of a modeled aerosol tracer that is assumed to originate from the same fires as the real BB aerosol but that is not affected by any aging processes. To limit possible effects of model transport errors, the AOD measurements are normalized to CO column amounts that are also retrieved from satellite measurements. The method is applied to the analysis of the meso- and synoptic-scale evolution of aerosol in smoke plumes from major wildfires that occurred in Siberia in summer 2012. AOD and CO retrievals from MODIS and IASI measurements, respectively, are used in combination with simulations performed with the CHIMERE CTM. The analysis indicates that aging processes strongly affected the evolution of BB aerosol in the situation considered, especially in dense plumes (with spatial average PM2. 5 concentration exceeding 100 µg m-3). For such plumes, the ER is found to increase almost 2-fold on the scale of ˜ 10 h of daytime aerosol evolution (after a few first hours of the evolution that are not resolved in our analysis). The robustness of this finding is corroborated by sensitivity tests and Monte Carlo experiments. Furthermore, a simulation using the volatility basis set framework suggests that a large part of the increase in the ER can be explained by atmospheric processing of semi-volatile organic compounds. Our results are consistent with findings of a number of earlier studies reporting considerable underestimation of AOD by CTMs in which BB aerosol aging processes have either been disregarded or simulated in a highly simplified way. In general, this study demonstrates the feasibility of using satellite measurements of AOD in biomass burning plumes in combination with aerosol tracer simulations for the investigation of BB aerosol evolution and validation of BB aerosol aging schemes in atmospheric models.

Carbonaceous aerosols in the air masses transported from Indochina to Taiwan: Long-term observation at Mt. Lulin

NASA Astrophysics Data System (ADS)

Chuang, Ming-Tung; Lee, Chung-Te; Chou, Charles C.-K.; Lin, Neng-Huei; Sheu, Guey-Rong; Wang, Jia-Lin; Chang, Shuenn-Chin; Wang, Sheng-Hsiang; Chi, Kai Hsien; Young, Chea-Yuan; Huang, Hill; Chen, Horng-Wen; Weng, Guo-Hau; Lai, Sin-Yu; Hsu, Shao-Peng; Chang, Yu-Jia; Chang, Jia-Hon; Wu, Xyue-Chang

2014-06-01

Eight carbonaceous fractions from aerosols were resolved using the Interagency Monitoring of Protected Visual Environments (IMPROVE) protocol (Chow et al., 1993). The aerosols were collected at the Mountain Lulin Atmospheric Background Station (Mt. Lulin, 2862 m a.s.l.) in Central Taiwan from April 2003 to April 2012. The monthly and yearly levels of organic carbon (OC) and elemental carbon (EC) varied consistently with PM2.5 mass concentrations during biomass burning (BB) period. The highest monthly carbonaceous content was observed in March and the highest yearly carbonaceous concentration was observed in 2007. This finding is consistent with the BB activity in Indochina and indicates that carbonaceous content is a major component of BB aerosols. Lee et al. (2011) classified four trajectory groups from the air masses transported to Mt. Lulin during the aerosol collection period. For the air masses transported from the BB area (the BB group) in Indochina, the carbonaceous content was greater than the water-soluble ions in PM2.5, and the OC/EC ratio (4.8 ± 1.5) was high. With EC as the indicator of primary emission sources, the air masses of the BB group were found to contain more primary than secondary OC. The Anthropogenic group (from the local and free troposphere below the 700-hPa pressure level over the Asian continent) probably contained more secondary than primary OC or the sources of OC and EC could be quite diverse. The average char-EC/soot-EC (low-temperature EC/high-temperature EC) ratios were 3.9 ± 3.5, 0.4 ± 0.4, 0.9 ± 0.8, and 0.3 ± 0.4 for the trajectory groups BB, SNBB (from BB source areas during the non-BB period), Anthropogenic, and FT (from the oceanic area and the free troposphere above the 700-hPa pressure level over the Asian continent), respectively. The presence of a high char-EC/soot-EC ratio confirmed the correct classification of the BB group, whereas the low ratios from the other groups indicated the strong influence of vehicle exhaust. It is noted that higher OC and EC levels were obtained at Mt. Lulin as compared with those obtained at other high-elevation sites. This difference suggested that the Indochina BB plume exhibited a more serious climatic impact on the background air in East Asia than in other places in Asia and Europe. On the basis of the carbonaceous levels of the SNBB and FT groups, the background OC and EC levels of approximately 3000 m in the West Pacific are around 1.33 μg m-3 and 0.35 μg m-3, respectively.

Association of Lyme Disease and Schizoaffective Disorder, Bipolar Type: Is it Inflammation Mediated?

PubMed

Mattingley, David William; Koola, Maju Mathew

2015-01-01

Lyme disease has been reported to be associated with various psychiatric presentations. Borreliaburgdorferi (Bb) can present with symptoms similar to schizophrenia and bipolar disorder. It has been suggested that inflammation incurred during the Bb infection leads to neurodegenerative changes that result in schizophrenia-like presentations. We report a case of a 41-year-old male with a past history of Bb infection who presents with psychosis. Later in the course of his hospitalization, he developed mood symptoms and was diagnosed with schizoaffective disorder, bipolar type. This case highlights the diagnosis and treatment of a patient with the unique presentation of schizoaffective disorder, bipolar type in the setting of previous Bb infection.

Refined Use of Satellite Aerosol Optical Depth Snapshots to Constrain Biomass Burning Emissions in the GOCART Model

NASA Astrophysics Data System (ADS)

Petrenko, Mariya; Kahn, Ralph; Chin, Mian; Limbacher, James

2017-10-01

Simulations of biomass burning (BB) emissions in global chemistry and aerosol transport models depend on external inventories, which provide location and strength for BB aerosol sources. Our previous work shows that to first order, satellite snapshots of aerosol optical depth (AOD) near the emitted smoke plume can be used to constrain model-simulated AOD, and effectively, the smoke source strength. We now refine the satellite-snapshot method and investigate where applying simple multiplicative emission adjustment factors alone to the widely used Global Fire Emission Database version 3 emission inventory can achieve regional-scale consistency between Moderate Resolution Imaging Spectroradiometer (MODIS) AOD snapshots and the Goddard Chemistry Aerosol Radiation and Transport model. The model and satellite AOD are compared globally, over a set of BB cases observed by the MODIS instrument during the 2004, and 2006-2008 biomass burning seasons. Regional discrepancies between the model and satellite are diverse around the globe yet quite consistent within most ecosystems. We refine our approach to address physically based limitations of our earlier work (1) by expanding the number of fire cases from 124 to almost 900, (2) by using scaled reanalysis-model simulations to fill missing AOD retrievals in the MODIS observations, (3) by distinguishing the BB components of the total aerosol load from background aerosol in the near-source regions, and (4) by including emissions from fires too small to be identified explicitly in the satellite observations. The small-fire emission adjustment shows the complimentary nature of correcting for source strength and adding geographically distinct missing sources. Our analysis indicates that the method works best for fire cases where the BB fraction of total AOD is high, primarily evergreen or deciduous forests. In heavily polluted or agricultural burning regions, where smoke and background AOD values tend to be comparable, this approach encounters large uncertainties, and in some regions, other model- or measurement-related factors might contribute significantly to model-satellite discrepancies. This work sets the stage for a larger study within the Aerosol Comparison between Observations and Models (AeroCOM) multimodel biomass burning experiment. By comparing multiple model results using the refined technique presented here, we aim to separate BB inventory from model-specific contributions to the remaining discrepancies.

Using new non-invasive quick method to detect Borrelia Burgdorferi (B.B.) infection from specific parts of the heart in "seemingly normal" ECGs, and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are found to have: 1) Significant B.B. infection, 2) Markedly increased ANP, 3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4 factors were mainly localized at infected areas of the SA node area, R-&L-Atria & pulmonary veins at the L-atrium.

PubMed

Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

2015-01-01

Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224-600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224-600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100-400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4-6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times/day + Taurine 175mg x 3 times/day, with or without EPA 180 mg & DHA 120 mg, to avoid serious current limitations in the use of Doxycycline 100 mg 2 times/day, for 4 weeks.

[Status of β-blocker use and heart rate control in Chinese patients with stable coronary artery disease].

PubMed

Sun, Yihong; Yu, Jinming; Hu, Dayi

2016-01-01

To observe the current status of β-blocker (BB) use and heart rate control in Chinese patients with stable coronary artery disease (SCAD) based on subgroup data of the prospective observational longitudinal registry of patients with stable coronary artery disease (CLARIFY). The CLARIFY study is an international prospective observational registry of outpatients with SCAD. From November 2009 to July 2010, patients with SCAD were enrolled, and demographic information, clinical indicators, medication and blood flow reconstruction were collected. Patients were divided in three mutually exclusive categories by baseline pulse palpation heart rate(HR)≤60 beats per minute (bpm)(n=397), 61-69 bpm(n=782), and ≥70 bpm(n=1 443). The patients were also divided into taking BB or not taking BB groups. The aim of present study is to describe and analyze the current status and factors related to the HR control and BB use in the Chinese subgroup of CLARIFY. A total of 2 622 patients were enrolled from 56 centers across China. The mean age was (63.6±10.3) years old with 75.6% (1 983) male patients, 55.0% (1 443) patients had HR≥70 bpm. Mean HR measure by electrocardiogram(ECG) was (69.4±10.2)bpm, 50.9% (1 334 cases) patients had myocardial infarction(MI) history. A total of 21.9%(575 cases) patients had anginal symptoms; coronary angiography was performed in 88.8%(2 327 cases) of the patients. 76.2%(1 997 cases) patients were treated with BB (any molecule and any dose), 2.7% (70 cases) with digoxin or derivatives, 3.9% (103 cases) with verapamil or diltiazem, and 1.8% (47 cases) with amiodarone or dronedarone and 0.1%(2 cases) received ivabradine. BB use was similar among 3 HR groups(P>0.05). The independent risk factors associated with HR≥70 bpm were diabetes(OR=1.31), current smoker(OR=1.57), chronic heart failure(CHF) with NYHA Ⅲ (OR=2.13) and increased diastolic blood pressure (OR=1.30). Conversely, high physical activity (OR=0.61), former smoker (OR=0.76) and history of percutaneous coronary intervention(PCI, OR=0.80) were associated with lower risk of HR≥70 bpm (all P<0.05). The independent risk factors associated with non-BB use were older age (OR=1.11, 95%CI 1.01-1.47, P=0.005), lower diastolic blood pressure (OR=1.47, 95%CI 1.32-1.68, P=0.012), no history of MI (OR=1.86, 95%CI 1.43-2.44, P<0.001) or PCI (OR=1.94, 95%CI 1.55-3.73, P<0.001), asthma/chronic obstructive pulmonary disease (OR=1.32, 95%CI 1.15-1.99, P<0.001). A total of 76.2% Chinese SCAD patients received BB medication but more than half of them did not reach the optimal HR. Clinical characteristics including diabetes, current smoker, CHF, increased diastolic blood pressure and no PCI were associated with poorly controlled HR(≥70 bpm). More efforts including adjusting the type and dose of heart rate lowering drugs are needed to achieve optimal HR control in Chinese SCAD patients. Clinical Trail Registry International Standard Randomized Controlled Trial, ISRCTN43070564.

Transcriptome Analysis Reveals Candidate Genes involved in Blister Blight defense in Tea (Camellia sinensis (L) Kuntze)

PubMed Central

Jayaswall, Kuldip; Mahajan, Pallavi; Singh, Gagandeep; Parmar, Rajni; Seth, Romit; Raina, Aparnashree; Swarnkar, Mohit Kumar; Singh, Anil Kumar; Shankar, Ravi; Sharma, Ram Kumar

2016-01-01

To unravel the molecular mechanism of defense against blister blight (BB) disease caused by an obligate biotrophic fungus, Exobasidium vexans, transcriptome of BB interaction with resistance and susceptible tea genotypes was analysed through RNA-seq using Illumina GAIIx at four different stages during ~20-day disease cycle. Approximately 69 million high quality reads were assembled de novo, yielding 37,790 unique transcripts with more than 55% being functionally annotated. Differentially expressed, 149 defense related transcripts/genes, namely defense related enzymes, resistance genes, multidrug resistant transporters, transcription factors, retrotransposons, metacaspases and chaperons were observed in RG, suggesting their role in defending against BB. Being present in the major hub, putative master regulators among these candidates were identified from predetermined protein-protein interaction network of Arabidopsis thaliana. Further, confirmation of abundant expression of well-known RPM1, RPS2 and RPP13 in quantitative Real Time PCR indicates salicylic acid and jasmonic acid, possibly induce synthesis of antimicrobial compounds, required to overcome the virulence of E. vexans. Compendiously, the current study provides a comprehensive gene expression and insights into the molecular mechanism of tea defense against BB to serve as a resource for unravelling the possible regulatory mechanism of immunity against various biotic stresses in tea and other crops. PMID:27465480

Transcriptome Analysis Reveals Candidate Genes involved in Blister Blight defense in Tea (Camellia sinensis (L) Kuntze)

NASA Astrophysics Data System (ADS)

Jayaswall, Kuldip; Mahajan, Pallavi; Singh, Gagandeep; Parmar, Rajni; Seth, Romit; Raina, Aparnashree; Swarnkar, Mohit Kumar; Singh, Anil Kumar; Shankar, Ravi; Sharma, Ram Kumar

2016-07-01

To unravel the molecular mechanism of defense against blister blight (BB) disease caused by an obligate biotrophic fungus, Exobasidium vexans, transcriptome of BB interaction with resistance and susceptible tea genotypes was analysed through RNA-seq using Illumina GAIIx at four different stages during ~20-day disease cycle. Approximately 69 million high quality reads were assembled de novo, yielding 37,790 unique transcripts with more than 55% being functionally annotated. Differentially expressed, 149 defense related transcripts/genes, namely defense related enzymes, resistance genes, multidrug resistant transporters, transcription factors, retrotransposons, metacaspases and chaperons were observed in RG, suggesting their role in defending against BB. Being present in the major hub, putative master regulators among these candidates were identified from predetermined protein-protein interaction network of Arabidopsis thaliana. Further, confirmation of abundant expression of well-known RPM1, RPS2 and RPP13 in quantitative Real Time PCR indicates salicylic acid and jasmonic acid, possibly induce synthesis of antimicrobial compounds, required to overcome the virulence of E. vexans. Compendiously, the current study provides a comprehensive gene expression and insights into the molecular mechanism of tea defense against BB to serve as a resource for unravelling the possible regulatory mechanism of immunity against various biotic stresses in tea and other crops.

1993/03 Baccalaureate and Beyond Longitudinal Study (B&B:93/03). Methodology Report. NCES 2006-166

ERIC Educational Resources Information Center

Wine, Jennifer S.; Cominole, Melissa B.; Wheeless, Sara; Dudley, Kristin; Franklin, Jeff

2005-01-01

This report describes the procedures and results of the full-scale implementation of the B&B:93/03 study. Students who earned a bachelor's degree in 1992-93 were first interviewed in 1993 and then subsequently in 1994 and 1997. This is the final follow-up interview of the B&B:93 cohort, 10 years following completion of the bachelor's…

77 FR 61797 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-11

..., MM, RP, 3, or 4 and removal flags are defined as Flags BB, MT, N, W, PI, PR, or 6. Where a Member..., BB and PI where they satisfy the volume tier requirements for the Mega Tier in Footnote 1. Currently... removing liquidity and the rate for Flags N, W, 6, BB, and PI subject to the volume thresholds in Footnotes...

Regulation of macrophage migration by products of the complement system.

PubMed Central

Bianco, C; Götze, O; Cohn, Z A

1979-01-01

Agents formerly shown to induce rapid macrophage spreading were examined for their ability to modify the migration of macrophages in the capillary tube assay. Products of the activation of the contact phase of blood coagulation as well as the purified component Bb, the large cleavage fragment of factor B of the alternative complement pathway produced a dose-dependent inhibition of migration. In addition, inflammatory macrophages elicited with either a lipopolysaccharide endotoxin or thioglycollate medium exhibited rapid spreading and inhibited migration, whereas resident cells did not. A close correlation existed, therefore, between enhanced spreading and inhibited migration under both in vitro induced and in vivo situations. Cleavage products of component C5 of the classical complement pathway enhanced macrophage migration and did not alter spreading. In mixtures of C5 cleavage products and Bb, the predominant peptide determined the outcome of the reaction. Factor B, a normal secretory product of macrophages, may represent a common substrate for several of the proteases that induce spreading, inhibit migration, and lead to the generation of the enzymatically active fragment Bb. PMID:284412

Recent applications of acoustic Doppler current profilers

USGS Publications Warehouse

Oberg, K.A.; Mueller, David S.

1994-01-01

A Broadband acoustic Doppler current profiler (BB-ADCP) is a new instrument being used by the U.S. Geological Survey (USGS) to measure stream discharge and velocities, and bathymetry. During the 1993 Mississippi River flood, more than 160 high-flow BB-ADCP measurements were made by the USGS at eight locations between Quincy and Cairo, Ill., from July 19 to August 20, 1993. A maximum discharge of 31,400 m3/s was measured at St. Louis, Mo., on August 2, 1993. A BB-ADCP also has been used to measure leakage through three control structures near Chicago, Ill. These measurements are unusual in that the average velocity for the measured section was as low as 0.03 m/s. BB-ADCP's are also used in support of studies of scour at bridges. During the recent Mississippi River flood, BB-ADCP's were used to measure water velocities and bathymetry upstream from, next to, and downstream from bridge piers at several bridges over the Mississippi River. Bathymetry data were collected by merging location data from Global Positioning System (GPS) receivers, laser tracking systems, and depths measured by the BB-ADCP. These techniques for collecting bathymetry data were used for documenting the channel formation downstream from the Miller City levee break and scour near two bridges on the Mississippi River.

Synthesis and electrical properties of BaBiO 3 and high resistivity BaTiO 3 –BaBiO 3 ceramics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Nitish; Golledge, Stephen L.; Cann, David P.

2016-12-01

Ceramics of the composition BaBiO3 (BB) were sintered in oxygen to obtain a single phase with monoclinic II2/mm symmetry as suggested by high-resolution X-ray diffraction. X-ray photoelectron spectroscopy confirmed the presence of bismuth in two valence states - 3+ and 5+. Optical spectroscopy showed presence of a direct bandgap at ~ 2.2eV and a possible indirect bandgap at ~ 0.9eV. This combined with determination of the activation energy for conduction of 0.25eV, as obtained from ac impedance spectroscopy, suggested that a polaron-mediated conduction mechanism was prevalent in BB. The BB ceramics were crushed, mixed with BaTiO3 (BT), and sintered tomore » obtain BT–BB solid solutions. All the ceramics had tetragonal symmetry and exhibited a normal ferroelectric-like dielectric response. Using ac impedance and optical spectroscopy, it was shown that resistivity values of BT–BB were orders of magnitude higher than BT or BB alone, indicating a change in the fundamental defect equilibrium conditions. A shift in the site occupancy of Bi to the A-site is proposed to be the mechanism for the increased electrical resistivity.« less

Hyoscine N-Butylbromide for Preventing Propofol Injection Pain: A Randomized, Placebo-Controlled and Double-Blind Study

PubMed Central

Sargın, Mehmet; Uluer, Mehmet Selçuk; Aydoğan, Eyüp

2018-01-01

Objective In this study, the aim was to investigate the effect of hyoscine N-butylbromide (HnBB) pretreatment on pain during propofol injection. Subjects and Methods In this prospective, randomized, placebo-controlled and double-blind trial, 60 patients scheduled to undergo routine outpatient surgery under general anesthesia were randomly allocated to 2 groups, the HnBB (n = 30) and sodium chloride (n = 30) groups. Twenty seconds after the injection of 20 mg HnBB or 0.9 % sodium chloride, a 50-mg dose of propofol was injected in 2–3 s. Ten seconds later, the pain intensity was assessed using a 4-point scale: no pain (0), mild (1), moderate (2), and severe (3) pain. The Student t test was used for the analysis of parametric data and the Pearson χ2 test for categorical data. Results The occurrence of pain in the HnBB group (43.3%) was significantly lower than the control group (73.3%) (p < 0.018). Of the 30 patients in each group, 10 in the control group and 3 in the HnBB group experienced severe pain (p = 0.001). Conclusions Pretreatment with 20 mg HnBB significantly reduced propofol injection pain compared to placebo. PMID:29402789

Characterization and antimicrobial spectrum of bacteriocins produced by lactic acid bacteria isolated from traditional Bulgarian dairy products.

PubMed

Simova, E D; Beshkova, D B; Dimitrov, Zh P

2009-02-01

To isolate bacteriocin-producing lactic acid bacteria (LAB) with high wide spectrum antibacterial activity and to characterize their inhibitory peptides. Seven LAB strains [Lactobacillus casei ssp. rhamnosus (PC5), Lactobacillus delbrueckii ssp. bulgaricus (BB18), Lactococcus lactis ssp. lactis (BCM5, BK15), Enterococcus faecium (MH3), Lactobacillus plantarum (BR12), Lactobacillus casei ssp. casei (BCZ2)], isolated from authentic Bulgarian dairy products were capable of producing bacteriocins, inhibiting the widest range of pathogenic bacteria. The bacteriocins were resistant to heating at 121 degrees C for 15 min, stable at pH 2-10, sensitive to protease, insensitive to alpha-amylase and lipase. Two of bacteriocins produced by Lact. bulgaricus BB18 (bulgaricin BB18) and E. faecium MH3 (enterocin MH3) were purified and the molecular masses were determined. The N-terminal amino acid sequence of bulgaricin BB18 did not show strong homology to other known bacteriocins. Lactobacillus bulgaricus BB18 and E. faecium MH3 produce two novel bacteriocins highly similar to the pediocin-like nonlantibiotics. The two bacteriocins are potential antimicrobial agents and, in conjunction with their producers, may have use in applications to contribute a positive effect on the balance of intestinal microflora. Furthermore, bulgaricin BB18 strongly inhibits Helicobacter pylori.

Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese.

PubMed

Shimada, Akira; Kanazawa, Yasuhiko; Motohashi, Yoshiko; Yamada, Satoru; Maruyama, Taro; Ikegami, Hiroshi; Awata, Takuya; Kawasaki, Eiji; Kobayashi, Tetsuro; Nakanishi, Koji; Kawabata, Yumiko; Kurihara, Susumu; Uga, Miho; Tanaka, Shoichiro

2008-06-01

Type 1 diabetes is considered to be T-helper 1 (Th1) type autoimmune disease. Because the vitamin D receptor is expressed on CD4+T cells and is known to affect cytokine responses, several groups have investigated the association between the vitamin D receptor gene BsmI polymorphism and type 1 diabetes. However, this issue is still controversial; therefore, we examined this gene polymorphism in a large number of type 1 diabetic patients as a multi-center collaborative study in Japan. A total of 1,373 subjects, including 774 cases and 599 control subjects of Japanese origin, were studied. The frequency of carriers of the BB genotype in type 1 diabetic patients was significantly higher than that in controls (p<0.01, odds ratio 3.65). Moreover, IFN-gamma production upon anti-CD3 stimulation in the BB genotype group was significantly higher than that in the Bb and bb genotype groups (p<0.05), suggesting that the polyclonal T cell response in BB genotype patients is Th1 dominant. Based upon these results, we propose that it may be worthwhile to focus on subjects with the BB genotype of this gene polymorphism as having high risk for type 1 diabetes.

Protective Effect of a Synbiotic against Multidrug-Resistant Acinetobacter baumannii in a Murine Infection Model

PubMed Central

Takahashi, Akira; Yuki, Norikatsu; Kaji, Rumi; Takahashi, Takuya; Nomoto, Koji

2016-01-01

This study investigated the ability of the probiotic Bifidobacterium breve strain Yakult (BbY) to protect against infection, as well as the potentiation of BbY activity by the synbiotic combination of BbY and prebiotic galactooligosaccharides (GOS). The study employed a mouse model of lethal intestinal multidrug-resistant Acinetobacter baumannii (MDRAb) infection. The endogenous intestinal microbiota was disrupted by the administration of multiple antibiotics, causing the loss of endogenous Bifidobacterium. Oral infection of these mice with MDRAb resulted in marked growth of this organism. Additional treatment of the infected mice with a sublethal dose of 5-fluorouracil (5-FU) induced systemic invasion by MDRAb and subsequent animal death. The continuous oral administration of BbY increased the survival rate and inhibited the intestinal growth and invasion by MDRAb in the infection model. Disruptions of the intestinal environment and barrier function in the infected mice were attenuated by BbY. Protection against the MDRAb infection was markedly potentiated by a synbiotic combination of BbY and GOS, although GOS by itself did not provide protection. Negative correlations were observed between intestinal MDRAb and BbY counts or acetic acid levels; positive correlations were observed between acetic acid levels and intestinal epithelium expression of tight-junction-related genes. These results demonstrated that the probiotic and synbiotic markedly potentiated protection against fatal intestinal infection caused by a multidrug-resistant bacterium. Probiotics and synbiotics are presumed to provide protection by compensation for the disrupted indigenous populations, thereby maintaining the intestinal environments and barrier functions otherwise targeted during opportunistic infection by MDRAb. PMID:26953197

Comparative performance of isolation methods using Preston broth, Bolton broth and their modifications for the detection of Campylobacter spp. from naturally contaminated fresh and frozen raw poultry meat.

PubMed

Seliwiorstow, T; De Zutter, L; Houf, K; Botteldoorn, N; Baré, J; Van Damme, I

2016-10-03

The performance of different isolation methods was evaluated for the detection of Campylobacter from naturally contaminated raw poultry meat. Therefore, fresh and frozen poultry meat samples were analysed using the standard procedure (ISO 10272-1:2006), enrichment in Preston broth, and enrichment in modified Bolton broth (supplemented with (i) potassium clavulanate (C-BB), (ii) triclosan (T-BB), (iii) polymyxin B (P-BB)). The enrichment cultures were streaked onto both modified charcoal cefoperazone deoxycholate agar (mCCDA) and RAPID'Campylobacter agar (RCA). Moreover, direct plating on mCCDA and RCA was performed to quantify Campylobacter. In total, 33 out of 59 fresh retail meat samples (55.9%) were Campylobacter positive. For both fresh and frozen poultry meat samples, enrichment in Bolton broth (ISO 10272-1:2006) resulted in a higher number of positive samples than enrichment in Preston broth. Supplementation of Bolton broth with potassium clavulanate (C-BB) and triclosan (T-BB) enhanced the Campylobacter recovery from fresh poultry meat compared to non-supplemented Bolton broth, although the use of C-BB was less applicable than T-BB for Campylobacter recovery from frozen samples. Additionally, the use of RCA resulted in a higher isolation rate compared to mCCDA. The present study demonstrates the impact of culture medium on the recovery of Campylobacter from fresh and frozen naturally contaminated poultry meat samples and can support laboratories in choosing the most appropriate culturing method to detect Campylobacter. Copyright © 2016 Elsevier B.V. All rights reserved.

Program BB for calculation of PEP corrector strengths for beam-bump excitation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kheifets, S.

Excitation of a beam-bump (BB) can be effectively used for a number of goals. Since BB is sensitive only to perturbations of elements which are located inside it, errors and their consequencies spaced separately can be singled out and studied one by one. This technique in principle can be used to study the uniformity of the quadrupole distribution around the ring, the beam stays clear size of the machine at different locations, the polarity and probably even the strength of sextupole magnets, alignments of different monitors, etc. It can be used also to increase the beam cross section if thatmore » appears to be desirable. Design of PEP correctors does not allow to use them for excitation of a halfwave BB. The minimum number of correctors which can be used in this situation is three. The situation for horizontal plane is aggravated still more since most of horizontal correctors are hooked in pairs. The presence of sextupole magnets interlacing the correctors makes it necessary to use iterative procedure to find the corrector strengths for BB, since a perturbed orbit is influenced by a field of a sextupole magnet which in turn depends on the perturbed orbit value in the sextupole. Since the strength of sextupoles are rather small as the first guess of corrector strengths for iterative procedure can be taken the linear solution neglecting sextupoles. This paper describes the program BB itself, and some results of calculations with BB for PEP. 3 refs., 4 figs., 6 tabs.« less

Practical estimates of field-saturated hydraulic conductivity of bedrock outcrops using a modified bottomless bucket method

USGS Publications Warehouse

Mirus, Benjamin B.; Perkins, Kim S.

2012-01-01

The bottomless bucket (BB) approach (Nimmo et al., 2009a) is a cost-effective method for rapidly characterizing field-saturated hydraulic conductivity Kfs of soils and alluvial deposits. This practical approach is of particular value for quantifying infiltration rates in remote areas with limited accessibility. A similar approach for bedrock outcrops is also of great value for improving quantitative understanding of infiltration and recharge in rugged terrain. We develop a simple modification to the BB method for application to bedrock outcrops, which uses a non-toxic, quick-drying silicone gel to seal the BB to the bedrock. These modifications to the field method require only minor changes to the analytical solution for calculating Kfs on soils. We investigate the reproducibility of the method with laboratory experiments on a previously studied calcarenite rock and conduct a sensitivity analysis to quantify uncertainty in our predictions. We apply the BB method on both bedrock and soil for sites on Pahute Mesa, which is located in a remote area of the Nevada National Security Site. The bedrock BB tests may require monitoring over several hours to days, depending on infiltration rates, which necessitates a cover to prevent evaporative losses. Our field and laboratory results compare well to Kfs values inferred from independent reports, which suggests the modified BB method can provide useful estimates and facilitate simple hypothesis testing. The ease with which the bedrock BB method can be deployed should facilitate more rapid in-situ data collection than is possible with alternative methods for quantitative characterization of infiltration into bedrock.

Reduction of Enteric Viruses by Blueberry Juice and Blueberry Proanthocyanidins.

PubMed

Joshi, Snehal S; Howell, Amy B; D'Souza, Doris H

2016-12-01

Blueberry and blueberry extracts are known for their health benefits and antimicrobial properties. Natural therapeutic or preventive options to decrease the incidences of foodborne viral illnesses are becoming popular and being researched. This study aimed to determine the antiviral effects of blueberry juice (BJ) and blueberry proanthocyanidins (BB-PAC, B-type PAC structurally different from A-type PAC found in cranberries) against the infectivity of hepatitis A virus (HAV) and human norovirus surrogates (feline calicivirus (FCV-F9) and murine norovirus (MNV-1)) at 37 °C over 24 h using standard plaque assays. Viruses at ~5 log PFU/ml were mixed with equal volumes of BJ (pH 2.8), neutralized BJ (pH 7.0), BB-PAC (1, 2, 4, and 10 mg/ml), malic acid (pH 3.0), or phosphate-buffered saline (pH 7.2) and incubated over 24 h at 37 °C. Each experiment was carried out in duplicate and replicated thrice. FCV-F9 titers were found to be reduced to undetectable levels with 1 and 2 mg/ml BB-PAC after 5 min, with 0.5 mg/ml BB-PAC after 1-h, and with BJ after 3-h. MNV-1 titers were reduced to undetectable levels after 3 h with 1, 2, and 5 mg/ml BB-PAC and after 6 h with BJ. HAV titers were reduced to undetectable levels after 30 min with 2 and 5 mg/ml BB-PAC, after 3 h with 1 mg/ml BB-PAC, and by ~2 log PFU/ml with BJ after 24-h. BB-PAC shows preventive potential against infection by the tested enteric viruses in a dose- and time-dependent manner, although further in vitro studies in model food systems and in vivo studies using animal models are warranted.

Derivation of Improved Surface and TOA Broadband Fluxes Using CERES-derived Narrowband-to-Broadband Coefficients

NASA Technical Reports Server (NTRS)

Khaiyer, Mandana M.; Doelling, David R.; Chan, Pui K.; Nordeen, MIchele L.; Palikonda, Rabindra; Yi, Yuhong; Minnis, Patrick

2006-01-01

Satellites can provide global coverage of a number of climatically important radiative parameters, including broadband (BB) shortwave (SW) and longwave (LW) fluxes at the top of the atmosphere (TOA) and surface. These parameters can be estimated from narrowband (NB) Geostationary Operational Environmental Satellite (GOES) data, but their accuracy is highly dependent on the validity of the narrowband-to-broadband (NB-BB) conversion formulas that are used to convert the NB fluxes to broadband values. The formula coefficients have historically been derived by regressing matched polarorbiting satellite BB fluxes or radiances with their NB counterparts from GOES (e.g., Minnis et al., 1984). More recently, the coefficients have been based on matched Earth Radiation Budget Experiment (ERBE) and GOES-6 data (Minnis and Smith, 1998). The Clouds and the Earth's Radiant Energy Budget (CERES see Wielicki et al. 1998)) project has recently developed much improved Angular Distribution Models (ADM; Loeb et al., 2003) and has higher resolution data compared to ERBE. A limited set of coefficients was also derived from matched GOES-8 and CERES data taken on Topical Rainfall Measuring Mission (TRMM) satellite (Chakrapani et al., 2003; Doelling et al., 2003). The NB-BB coefficients derived from CERES and the GOES suite should yield more accurate BB fluxes than from ERBE, but are limited spatially and seasonally. With CERES data taken from Terra and Aqua, it is now possible to derive more reliable NB-BB coefficients for any given area. Better TOA fluxes should translate to improved surface radiation fluxes derived using various algorithms. As part of an ongoing effort to provide accurate BB flux estimates for the Atmospheric Radiation Measurement (ARM) Program, this paper documents the derivation of new NB-BB coefficients for the ARM Southern Great Plains (SGP) domain and for the Darwin region of the Tropical Western Pacific (DTWP) domain.

Bauhinia bauhinioides cruzipain inhibitor reduces endothelial proliferation and induces an increase of the intracellular Ca2+ concentration.

PubMed

Bilgin, Mehmet; Neuhof, Christiane; Doerr, Oliver; Benscheid, Utz; Andrade, Sheila S; Most, Astrid; Abdallah, Yaser; Parahuleva, Mariana; Guenduez, Dursun; Oliva, Maria L; Erdogan, Ali

2010-12-01

Proteinase inhibitors, isolated from different types of Bauhinia, have an effect on apoptosis, angiogenesis and inflammation. The Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a Kunitz-type inhibitor and inactivates the cysteine proteinases cruzipain and cruzain from Trypanosoma cruzi. Cruzipain and tissue kallikrein have similar biochemical properties, e.g. the proteolytic cleavage of the kininogen precursor of lys-bradykinin. Tissue kallikrein stimulation in endothelial cells causes migration and capillary tube formation. The aim of this study was to examine whether the antiproliferative effect of BbCI is dependent on changes of the intracellular calcium concentration and membrane hyperpolarization. Endothelial cells were isolated from human umbilical cord veins (HUVEC). For proliferation experiments, HUVEC were incubated with BbCI (10-100 μmol/L) for 48 h. The proliferation was detected by cell counting with a Neubauer chamber. The effect of BbCI (10-100 μM) on the membrane potential was measured with the fluorescence dye DiBAC4(3) and the effect on [Ca+2]i with the fluorescence probe Fluo-3 AM. The change of the fluorescence intensity was determined with a GENios plate reader (Tecan). The experiments showed that BbCI (10-100 μmol/L) reduces the endothelial cell proliferation significantly in a concentration-dependent manner with a maximum effect at 100 μmol/L (35.1±1.8% as compared to control (p≤0.05; n=45)). As compared to the control, the addition of BbCI (100 μmol/L) caused a significant increase of systolic Ca2+ of 28.4±5.0% after 30 min incubation. HUVEC treatment with BbCI (100 μmol/L) showed a weak but significant decrease of the membrane potential of 9.5±0.9% as compared to control (p≤0.05; n=80). BbCI influenced significantly the endothelial proliferation, the intracellular Ca2+ concentration and the membrane potential.

Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing

PubMed Central

Koob, Thomas J; Rennert, Robert; Zabek, Nicole; Massee, Michelle; Lim, Jeremy J; Temenoff, Johnna S; Li, William W; Gurtner, Geoffrey

2013-01-01

Human amnion/chorion tissue derived from the placenta is rich in cytokines and growth factors known to promote wound healing; however, preservation of the biological activities of therapeutic allografts during processing remains a challenge. In this study, PURION® (MiMedx, Marietta, GA) processed dehydrated human amnion/chorion tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for the presence of growth factors, interleukins (ILs) and tissue inhibitors of metalloproteinases (TIMPs). Enzyme-linked immunosorbent assays (ELISA) were performed on samples of dHACM and showed quantifiable levels of the following growth factors: platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, transforming growth factor α (TGFα), TGFβ1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), placental growth factor (PLGF) and granulocyte colony-stimulating factor (GCSF). The ELISA assays also confirmed the presence of IL-4, 6, 8 and 10, and TIMP 1, 2 and 4. Moreover, the relative elution of growth factors into saline from the allograft ranged from 4% to 62%, indicating that there are bound and unbound fractions of these compounds within the allograft. dHACM retained biological activities that cause human dermal fibroblast proliferation and migration of human mesenchymal stem cells (MSCs) in vitro. An in vivo mouse model showed that dHACM when tested in a skin flap model caused mesenchymal progenitor cell recruitment to the site of implantation. The results from both the in vitro and in vivo experiments clearly established that dHACM contains one or more soluble factors capable of stimulating MSC migration and recruitment. In summary, PURION® processed dHACM retains its biological activities related to wound healing, including the potential to positively affect four distinct and pivotal physiological processes intimately involved in wound healing: cell proliferation, inflammation, metalloproteinase activity and recruitment of progenitor cells. This suggests a paracrine mechanism of action for dHACM when used for wound healing applications. PMID:23902526

PDGFBB promotes PDGFR{alpha}-positive cell migration into artificial bone in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshida, Shigeyuki; Center for Human Metabolomic Systems Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582; Iwasaki, Ryotaro

2012-05-18

Highlights: Black-Right-Pointing-Pointer We examined effects of PDGFBB in PDGFR{alpha} positive cell migration in artificial bones. Black-Right-Pointing-Pointer PDGFBB was not expressed in osteoblastic cells but was expressed in peripheral blood cells. Black-Right-Pointing-Pointer PDGFBB promoted PDGFR{alpha} positive cell migration into artificial bones but not osteoblast proliferation. Black-Right-Pointing-Pointer PDGFBB did not inhibit osteoblastogenesis. -- Abstract: Bone defects caused by traumatic bone loss or tumor dissection are now treated with auto- or allo-bone graft, and also occasionally by artificial bone transplantation, particularly in the case of large bone defects. However, artificial bones often exhibit poor affinity to host bones followed by bony union failure.more » Thus therapies combining artificial bones with growth factors have been sought. Here we report that platelet derived growth factor bb (PDGFBB) promotes a significant increase in migration of PDGF receptor {alpha} (PDGFR{alpha})-positive mesenchymal stem cells/pre-osteoblastic cells into artificial bone in vivo. Growth factors such as transforming growth factor beta (TGF{beta}) and hepatocyte growth factor (HGF) reportedly inhibit osteoblast differentiation; however, PDGFBB did not exhibit such inhibitory effects and in fact stimulated osteoblast differentiation in vitro, suggesting that combining artificial bones with PDGFBB treatment could promote host cell migration into artificial bones without inhibiting osteoblastogenesis.« less

Seasonal and regional differentiation of bio-optical properties within the north polar Atlantic

NASA Astrophysics Data System (ADS)

Stramska, Malgorzata; Stramski, Dariusz; Kaczmarek, SłAwomir; Allison, David B.; Schwarz, Jill

2006-08-01

Using field data from the north polar Atlantic, we examined seasonal variability of the spectral absorption, a(λ), and backscattering, bb(λ), coefficients of surface waters in relation to phytoplankton pigments. For a given chlorophyll a concentration, the concentrations of accessory pigments were lower in spring than in summer. This effect contributed to lower chlorophyll-specific absorption of phytoplankton and total particulate matter in spring. The spring values of the green-to-blue band ratio of a(λ) were higher than the summer ratios. The blue-to-green ratios of bb(λ) were also higher in spring. The higher bb values and lower blue-to-green bb ratios in summer were likely associated with higher concentrations of detrital particles in summer compared to spring. Because the product of these band ratios of a and bb is a proxy for the blue-to-green ratio of remote-sensing reflectance, the performance of ocean color band-ratio algorithms for estimating pigments is significantly affected by seasonal shifts in the relationships between absorption, backscattering, and chlorophyll a. Our results suggest that the algorithm for the spring season would predict chlorophyll a that is higher by as much as a factor of 4-6 compared to that predicted from the summer algorithm. This indicates a need for a seasonal approach in the north polar Atlantic. However, we also found that a fairly good estimate of the particulate beam attenuation coefficient at 660 nm (a proxy for total particulate matter or particulate organic carbon concentration) can be obtained by applying a single blue-to-green band-ratio algorithm regardless of the season.

Doctor says you are cured, but you still feel the pain. Borrelia DNA persistence in Lyme disease.

PubMed

Cervantes, Jorge

Lyme disease is a zoonosis caused by infection with Borrelia burgdorferi (Bb). A great amount of research has attempted to elucidate the mechanisms by which Bb causes inflammation and chronic symptomatology in some patients. Patients often seek unconventional treatments that lack scientific evidence, as medical care is unable to effectively explain and treat their illness. Bb-DNA can persist for long periods of time in some individuals, even after antibiotic therapy. Herein, scientific rationale is presented for a new therapeutic approach against remaining bacterial DNA, and/or increasing the ability of human macrophages to remove extracellular Bb DNA. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-β signaling.

PubMed

Nikolakopoulou, Angeliki Maria; Zhao, Zhen; Montagne, Axel; Zlokovic, Berislav V

2017-01-01

Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain. We asked whether these mice have a stable or progressive vascular phenotype after birth, and whether both pericyte and VSMCs populations are affected in the adult brain. We found an early and progressive region-dependent loss of brain pericytes, microvascular reductions and blood-brain barrier (BBB) breakdown, which were more pronounced in the cortex, hippocampus and striatum than in the thalamus, whereas VSMCs population remained unaffected at the time when pericyte loss was already established. For example, compared to age-matched controls, PdgfrβF7/F7 mice between 4-6 and 36-48 weeks of age developed a region-dependent loss in pericyte coverage (22-46, 24-44 and 4-31%) and cell numbers (36-49, 34-64 and 11-36%), reduction in capillary length (20-39, 13-46 and 1-30%), and an increase in extravascular fibrinogen-derived deposits (3.4-5.2, 2.8-4.1 and 0-3.6-fold) demonstrating BBB breakdown in the cortex, hippocampus and thalamus, respectively. Capillary reductions and BBB breakdown correlated with loss of pericyte coverage. Our data suggest that PdgfrβF7/F7 mice develop an aggressive and rapid vascular phenotype without appreciable early involvement of VSMCs, therefore providing a valuable model to study regional effects of pericyte loss on brain vascular and neuronal functions. This model could be a useful tool for future studies directed at understanding the role of pericytes in the pathogenesis of neurological disorders associated with pericyte loss such as vascular dementia, Alzheimer's disease, amyotrophic lateral sclerosis, stroke and human immunodeficiency virus-associated neurocognitive disorder.

Effect of blue-blocking glasses in major depressive disorder with sleep onset insomnia: A randomized, double-blind, placebo-controlled study.

PubMed

Esaki, Yuichi; Kitajima, Tsuyoshi; Takeuchi, Ippei; Tsuboi, Soji; Furukawa, Osamu; Moriwaki, Masatsugu; Fujita, Kiyoshi; Iwata, Nakao

2017-01-01

Blue wavelengths form the portion of the visible electromagnetic spectrum that most potently regulates circadian rhythm. We hypothesized that wearing blue-blocking (BB) glasses in the evening may influence circadian rhythm disturbances in patients with major depressive disorder (MDD), resulting in improved sleep and mood. We used a randomized placebo-controlled double-blinded design. Patients with MDD with sleep onset insomnia were randomly assigned to wearing either BB glasses or clear glasses (placebo). Patients were instructed to wear the glasses from 20:00 hours until bedtime for 2 weeks. We assessed sleep state (sleep quality on a visual analog scale, the Morningness-Eveningness Questionnaire [MEQ], and a sleep diary) and depressive symptoms at baseline and after 2 weeks. Data were analyzed with a full analysis set. In total, 20 patients were randomly assigned to the BB and placebo groups (BB group, n = 10; placebo group, n = 10). There were three dropouts (BB group, n = 1; placebo group, n = 2). At baseline, sleep quality, sleep latency (assessed via a sleep diary), and antipsychotics use differed between the groups. To take account of these differences, the baseline sleep state or depressive symptoms and antipsychotics use were used as covariates in the later analysis. The change scores for sleep quality did not show a significant improvement in the BB group compared with the placebo group (mean [standard deviation, SD] scores for BB versus placebo: 36.1 [31.7] versus 16.2 [15.1], p = 0.43), although half of the BB group showed a clear improvement in sleep quality. The change in MEQ scores did not significantly differ between the groups (p = 0.14), although there was a trend of a shift to morning type in the BB group (3.10 [4.95] points) and to evening type in the placebo group (0.50 [3.89] points). There were no statistically significant changes in depressive symptoms in either group. Across both groups, 40% of the participants reported pain or discomfort from wearing the glasses, which were available in only one size. Thus, the failure to find significant differences may have resulted from the glasses used in this study. Glasses fitted to individual patients may improve efficacy and safety. Replication of the study with a larger sample size and size-adjustable glasses is needed.

Effects of biomass smoke from southern Africa on stratocumulus over southeastern Atlantic Ocean based on satellite observations and WRF-Chem model simulations

NASA Astrophysics Data System (ADS)

Lu, Z.; Liu, X.; Zhang, Z.; Zhao, C.; Meyer, K.; Rajapakshe, C.; Wu, C.; Yang, Z.; Penner, J.

2017-12-01

Each year, large amount of biomass burning (BB) aerosols are emitted over southern Africa, and transported by the predominant circulation to the southeastern Atlantic Ocean (SEA), where they overly and potentially interact with the semi-permanent stratocumulus deck in the marine boundary layer (MBL). Many previous studies suggested that the aerosol plumes are well separated from the MBL clouds, and only focused on the radiative effects of BB aerosols (direct + semi-direct radiative effects); however, as shown in several recent satellite observational studies, BB aerosols are able to be frequently entrained into the underlying clouds, function as cloud condensation nuclei (CCN), and potentially cause microphysical effects. Based on satellite observations from CATS, we found that the mixing frequencies between above-cloud aerosols and MBL clouds are very high ( 50%) over both coastal and remote regions, suggesting that BB aerosols may likely contact MBL cloud top and function as CCN quickly after they are transported over SEA. Despite the potential importance of the microphysical effect of BB aerosols over SEA, its magnitude is not fully assessed by modeling studies. In this study, we employ WRF-Chem model to study the impacts of BB aerosols on MBL stratocumulus clouds over SEA during the fire season of 2014. By designing three cases, we are able to quantitatively determine the relative importance of microphysical and radiative effects of BB aerosols. Our modeling results show that, by serving as CCN, BB aerosols are able to alter cloud properties of stratocumulus (e.g. higher cloud droplet number concentration [CDNC], higher cloud liquid water path [LWP], and larger cloud fraction [CF] before noon) and exert significant cooling effect at TOA (-8.05 Wm-2) over SEA. The cooling is primarily caused by higher CDNC (the Twomey effect), and secondarily by the changes in LWP and CF (the cloud lifetime effect). The semi-direct effect estimated in this study is smaller in magnitude compared to previous modeling studies (e.g. Sakaeda et al., 2011), partially because of the heating in the boundary layer after BB aerosols entrained in MBL. The findings in our study are important because they may partially explain the underestimation of cloud radiative forcing as predicted by GCMs.

The interrelationship of complement-activation fragments and angiogenesis-related factors in early pregnancy and their association with pre-eclampsia

PubMed Central

Lynch, AM; Murphy, JR; Gibbs, RS; Levine, RJ; Giclas, PC; Salmon, JE; Holers, VM

2016-01-01

Objective To determine the interrelationships during early pregnancy of complement-activation fragments Bb, C3a and sC5b-9, and angiogenesis-related factors placental growth factor (PiGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and their associations with pre-eclampsia. Design Prospective cohort study. Setting Denver complement study (June 2005–June 2008). Population A total of 668 pregnant women with singleton gestations, recruited between 10 and 15 weeks of gestation. Methods Using univariable and multivariable logistic regression analysis, concentrations of complement-activation fragments and angiogenesis-related factors were compared between 10 and 15 weeks of gestation in women who subsequently did or did not develop pre-eclampsia. Interrelationships between these variables were tested using the non-parametric Spearman rank correlation coefficient. Main outcome measure Pre-eclampsia. The association of complement-activation fragments and angiogenesis-related factors with obesity was also examined. Results The mean (±SD) levels of complement Bb in early pregnancy among women who did and did not develop pre-eclampsia were 0.84 (±0.26) µg/ml and 0.69 (±0.2) µg/ml, respectively (P = 0.001). Concentrations of PiGF were significantly (P = 0.01) lower (31 ± 12 pg/ml) in early pregnancy in the pre-eclamptic group of women, as compared with the normotensive group (39 ± 32 pg/ml). The adjusted odds ratio (AOR) of Bb and PiGF were 2.1 (CI = 1.4–3.1, P < 0.0003) and 0.2 (CI = 0.07–0.7, P = 0.01), respectively. There was no significant difference in the levels of C3a, sC5b-9, sFlt-1 and sEng in early pregnancy among women who developed pre-eclampsia, compared with women who remained normotensive during pregnancy. Higher levels of Bb (P = 0.0001) and C3a (P = 0.03), and lower levels of sFlt-1 (P = 0.0002) and sEng (P = 0.0001) were found among women with obesity, compared with non-obese controls. No meaningful relationships were found between the complement-activation fragments and the angiogenesis-related factors. Conclusions In this cohort during early pregnancy, increased concentrations of complement-activation factor Bb and lower concentrations of PiGF were associated with the development of pre-eclampsia later in pregnancy. PMID:20074261

Not all Beta-Blockers are Equal in the Management of Long QT Syndrome Types 1 and 2: Higher Recurrence of Events under Metoprolol

PubMed Central

Chockalingam, Priya; Crotti, Lia; Girardengo, Giulia; Johnson, Jonathan N.; Harris, Katy M.; van der Heijden, Jeroen F.; Hauer, Richard N.W.; Beckmann, Britt M.; Spazzolini, Carla; Rordorf, Roberto; Rydberg, Annika; Clur, Sally-Ann B.; Fischer, Markus; van den Heuvel, Freek; Kääb, Stefan; Blom, Nico A.; Ackerman, Michael J.; Schwartz, Peter J.; Wilde, Arthur A.M.

2012-01-01

Objectives To compare the efficacy of beta-blockers (BB) in congenital long QT syndrome (LQTS). Background BB are the mainstay in managing LQTS. Studies comparing the efficacy of commonly-used BB are lacking and clinicians generally assume they are equally effective. Methods ECG and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n=134), metoprolol (n=147), and nadolol (n=101) were analyzed, excluding patients aged <1 year at BB initiation. Symptoms prior to therapy and the first breakthrough cardiac events (BCEs) were documented. Results Patients (56% females, 27% symptomatic, HR 76±16 bpm, QTc 472±46 ms) were started on BB therapy at a median age of 14 years (IQR 8–32 years). QTc-shortening with propranolol was significantly greater than with other BB in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n=101), 15 had BCEs (all syncopes). QTc-shortening was significantly less-pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of other two BB combined, after adjustment for genotype (OR 3.95, 95% CI 1.2–13.1, p=0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients on metoprolol compared to propranolol/nadolol. Conclusions Propranolol has a significantly better QTc-shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used in symptomatic LQT1 and LQT2 patients. PMID:23083782

SGR J1550-5418 Bursts Detected with the Fermi Gamma-Ray Burst Monitor during Its Most Prolific Activity

NASA Technical Reports Server (NTRS)

vanderHorst, A. J.; Kouveliotou, C.; Gorgone, N. M.; Kaneko, Y.; Baring, M. G.; Guiriec, S.; Gogus, E,; Granot, J.; Watts, A. L.; Lin, L.;

Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy

PubMed Central

Chacon, Jessica Ann; Sarnaik, Amod A; Chen, Jie Qing; Creasy, Caitlin; Kale, Charuta; Robinson, John; Weber, Jeffrey; Hwu, Patrick; Pilon-Thomas, Shari; Radvanyi, Laszlo

2014-01-01

Purpose Cultured tumor fragments from melanoma metastases have been used for years as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy. The expansion of tumor-reactive CD8+ T cells with IL-2 in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8+ T cells recently found to constitute the majority of tumor-specific T cells. Experimental Design We used an agonistic anti-4-1BB antibody added during the initial tumor fragment cultures to provide in situ 4-1BB co-stimulation. Results We found that addition of an agonistic anti-4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8+ TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFκB activation and the induction of T-cell survival and memory genes, as well as enhanced IL-2 responsiveness, in the CD8+ T cells in the fragments and emerging from the fragments. Early provision of 4-1BB co-stimulation also affected the dendritic cells (DC) by activating NFκB in DC and promoting their maturation inside the tumor fragments. Blocking HLA class I prevented the enhanced outgrowth of CD8+ T cells with anti-4-1BB, suggesting that an ongoing HLA class I-mediated antigen presentation in early tumor fragment cultures plays a role in mediating tumor-specific CD8+ TIL outgrowth. Conclusions Our results highlight a previously unrecognized concept in TIL adoptive cell therapy that the tumor microenvironment can be dynamically regulated in the initial tumor fragment cultures to regulate the types of T cells expanded and their functional characteristics. PMID:25472998

Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy.

PubMed

Chacon, Jessica Ann; Sarnaik, Amod A; Chen, Jie Qing; Creasy, Caitlin; Kale, Charuta; Robinson, John; Weber, Jeffrey; Hwu, Patrick; Pilon-Thomas, Shari; Radvanyi, Laszlo

2015-02-01

Cultured tumor fragments from melanoma metastases have been used for years as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy (ACT). The expansion of tumor-reactive CD8(+) T cells with interleukin-2 (IL2) in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8(+) T cells recently found to constitute the majority of tumor-specific T cells. We used an agonistic anti-4-1BB antibody added during the initial tumor fragment cultures to provide in situ 4-1BB costimulation. We found that addition of an agonistic anti-4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8(+) TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFκB activation and the induction of T-cell survival and memory genes, as well as enhanced IL2 responsiveness, in the CD8(+) T cells in the fragments and emerging from the fragments. Early provision of 4-1BB costimulation also affected the dendritic cells (DC) by activating NFκB in DC and promoting their maturation inside the tumor fragments. Blocking HLA class I prevented the enhanced outgrowth of CD8(+) T cells with anti-4-1BB, suggesting that an ongoing HLA class I-mediated antigen presentation in early tumor fragment cultures plays a role in mediating tumor-specific CD8(+) TIL outgrowth. Our results highlight a previously unrecognized concept in TIL ACT that the tumor microenvironment can be dynamically regulated in the initial tumor fragment cultures to regulate the types of T cells expanded and their functional characteristics. ©2014 American Association for Cancer Research.

Effects of Shock and Turbulence Properties on Electron Acceleration

NASA Astrophysics Data System (ADS)

Qin, G.; Kong, F.-J.; Zhang, L.-H.

2018-06-01

Using test particle simulations, we study electron acceleration at collisionless shocks with a two-component model turbulent magnetic field with slab component including dissipation range. We investigate the importance of the shock-normal angle θ Bn, magnetic turbulence level {(b/{B}0)}2, and shock thickness on the acceleration efficiency of electrons. It is shown that at perpendicular shocks the electron acceleration efficiency is enhanced with the decrease of {(b/{B}0)}2, and at {(b/{B}0)}2=0.01 the acceleration becomes significant due to a strong drift electric field with long time particles staying near the shock front for shock drift acceleration (SDA). In addition, at parallel shocks the electron acceleration efficiency is increasing with the increase of {(b/{B}0)}2, and at {(b/{B}0)}2=10.0 the acceleration is very strong due to sufficient pitch-angle scattering for first-order Fermi acceleration, as well as due to the large local component of the magnetic field perpendicular to the shock-normal angle for SDA. On the other hand, the high perpendicular shock acceleration with {(b/{B}0)}2=0.01 is stronger than the high parallel shock acceleration with {(b/{B}0)}2=10.0, the reason might be the assumption that SDA is more efficient than first-order Fermi acceleration. Furthermore, for oblique shocks, the acceleration efficiency is small no matter whether the turbulence level is low or high. Moreover, for the effect of shock thickness on electron acceleration at perpendicular shocks, we show that there exists the bendover thickness, L diff,b. The acceleration efficiency does not noticeably change if the shock thickness is much smaller than L diff,b. However, if the shock thickness is much larger than L diff,b, the acceleration efficiency starts to drop abruptly.

Forever Young: The Role of Ubiquitin Receptor DA1 and E3 Ligase BIG BROTHER in Controlling Leaf Growth and Development.

PubMed

Vanhaeren, Hannes; Nam, Youn-Jeong; De Milde, Liesbeth; Chae, Eunyoung; Storme, Veronique; Weigel, Detlef; Gonzalez, Nathalie; Inzé, Dirk

2017-02-01

The final size of plant organs is determined by a combination of cell proliferation and cell expansion. Leaves account for a large part of above-ground biomass and provide energy to complete the plant's life cycle. Although the final size of leaves is remarkably constant under fixed environmental conditions, several genes have been described to enhance leaf growth when their expression is modulated. In Arabidopsis (Arabidopsis thaliana), mutations in DA1 and BB increase leaf size, an effect that is synergistically enhanced in the double mutant. Here, we show that overexpression of a dominant-negative version of DA1 enhances leaf size in a broad range of natural accessions of this species, indicating a highly conserved role of this protein in controlling organ size. We also found that during early stages of development, leaves of da1-1 and bb/eod1-2 mutants were already larger than the isogenic Col-0 wild type, but this phenotype was triggered by different cellular mechanisms. Later during development, da1-1 and bb/eod1-2 leaves showed a prolonged longevity, which was enhanced in the double mutant. Conversely, ectopic expression of DA1 or BB restricted growth and promoted leaf senescence. In concert, shortly upon induction of DA1 and BB expression, several marker genes for the transition from proliferation to expansion were highly up-regulated. Additionally, multiple genes involved in maintaining the mitotic cell cycle were rapidly down-regulated and senescence genes were strongly up-regulated, particularly upon BB induction. With these results, we demonstrate that DA1 and BB restrict leaf size and promote senescence through converging and different mechanisms. © 2017 American Society of Plant Biologists. All Rights Reserved.

Prevention of abdominal aortic aneurysm progression by targeted inhibition of matrix metalloproteinase activity with batimastat-loaded nanoparticles.

PubMed

Nosoudi, Nasim; Nahar-Gohad, Pranjal; Sinha, Aditi; Chowdhury, Aniqa; Gerard, Patrick; Carsten, Christopher G; Gray, Bruce H; Vyavahare, Naren R

2015-11-06

Matrix metalloproteinases (MMPs)-mediated extracellular matrix destruction is the major cause of development and progression of abdominal aortic aneurysms. Systemic treatments of MMP inhibitors have shown effectiveness in animal models, but it did not translate to clinical success either because of low doses used or systemic side effects of MMP inhibitors. We propose a targeted nanoparticle (NP)-based delivery of MMP inhibitor at low doses to the abdominal aortic aneurysms site. Such therapy will be an attractive option for preventing expansion of aneurysms in patients without systemic side effects. Our previous study showed that poly(d,l-lactide) NPs conjugated with an antielastin antibody could be targeted to the site of an aneurysm in a rat model of abdominal aortic aneurysms. In the study reported here, we tested whether such targeted NPs could deliver the MMP inhibitor batimastat (BB-94) to the site of an aneurysm and prevent aneurysmal growth. Poly(d,l-lactide) NPs were loaded with BB-94 and conjugated with an elastin antibody. Intravenous injections of elastin antibody-conjugated BB-94-loaded NPs targeted the site of aneurysms and delivered BB-94 in a calcium chloride injury-induced abdominal aortic aneurysms in rats. Such targeted delivery inhibited MMP activity, elastin degradation, calcification, and aneurysmal development in the aorta (269% expansion in control versus 40% elastin antibody-conjugated BB-94-loaded NPs) at a low dose of BB-94. The systemic administration of BB-94 alone at the same dose was ineffective in producing MMP inhibition. Targeted delivery of MMP inhibitors using NPs may be an attractive strategy to inhibit aneurysmal progression. © 2015 American Heart Association, Inc.

Lactobacillus panisapium sp. nov., from honeybee Apis cerana bee bread.

PubMed

Wang, Cong; Huang, Yan; Li, Li; Guo, Jun; Wu, Zhengyun; Deng, Yu; Dai, Lirong; Ma, Shichun

2018-03-01

A novel facultatively anaerobic, Gram-stain-positive, non-motile, non-spore-forming, catalase-negative bacterium of the genus Lactobacillus, designated strain Bb 2-3 T , was isolated from bee bread of Apis cerana collected from a hive in Kunming, China. The strain was regular rod-shaped. Optimal growth occurred at 37 °C, pH 6.5 with 5.0 g l -1 NaCl. The predominant fatty acids were C18 : 1ω9c, C16 : 0 and C19 : 0 iso. Respiratory quinones were not detected. Seven glycolipids, three lipids, phosphatidylglycerol and diphosphatidylglycerol were detected. The peptidoglycan type A4α l-Lys-d-Asp was determined. Strain Bb 2-3 T was closely related to Lactobacillus bombicola DSM 28793 T , Lactobacillus apis LMG 26964 T and Lactobacillus helsingborgensis DSM 26265 T , with 97.8, 97.6 and 97.0 % 16S rRNA gene sequence similarity, respectively. A comparison of two housekeeping genes, rpoA and pheS, revealed that strain Bb 2-3 T was well separated from the reference strains of species of the genus Lactobacillus. The average nucleotide identity between strain Bb 2-3 T and the type strains of closely related species was lower than the 95-96 % threshold value for delineation of genomic prokaryotic species. The G+C content of the genomic DNA of strain Bb 2-3 T was 37.4 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analyses, strain Bb 2-3 T is proposed to represent a novel species of the genus Lactobacillus, for which we propose the name Lactobacillus panisapium sp. nov. The type strain is Bb 2-3 T (=DSM 102188 T =ACCC 19955 T ).

Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes

PubMed Central

Bogdani, Marika; Henschel, Angela M.; Kansra, Sanjay; Fuller, Jessica M.; Geoffrey, Rhonda; Jia, Shuang; Kaldunski, Mary L.; Pavletich, Scott; Prosser, Simon; Chen, Yi-Guang; Lernmark, Åke; Hessner, Martin J.

2014-01-01

Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating β cell duress. To identify genes/mechanisms involved with diabeto-genesis at the β cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and under-expressed numerous genes involved in ROS metabolism, including glutathione S-transferase (GST) family members (Gstm2, Gstm4, Gstm7, Gstt1, Gstp1, and Gstk1), superoxide dismutases (Sod2 and Sod3), peroxidases, and peroxiredoxins. This pattern of under-expression was not observed in brain, liver, or muscle. Compared with F344 rats, BB rat pancreata exhibited lower GST protein levels, while plasma GST activity was found significantly lower in BB rats. Systemic administration of the antioxidant N-acetyl cysteine to DRlyp/lyp rats altered abundances of peripheral eosinophils, reduced severity of insulitis, and significantly delayed but did not prevent diabetes onset. We find evidence of β cell dysfunction in BB rats independent of T1D progression, which includes lower expression of genes related to antioxidative defense mechanisms during the pre-onset period that may contribute to overall T1D susceptibility. PMID:23111281

Exploring the ameliorative potential of probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum on dextran sodium sulphate induced colitis in mice.

PubMed

Jadhav, Sagar R; Shandilya, Umesh Kr; Kansal, Vinod K

2013-02-01

Conventional medical therapies for ulcerative colitis (UC) are still limited due to the adverse side effects like dose-dependent diarrhoea and insufficient potency to keep in remission for long-term periods. So, new alternatives that provide more effective and safe therapies for ulcerative colitis are constantly being sought. In the present study, probiotic LaBb Dahi was selected for investigation of its therapeutic effect on DSS-induced colitis model in mice. LaBb Dahi was prepared by co-culturing Dahi culture of Lactococci along with selected strain of Lactobacillus acidophilus LaVK2 and Bifidobacterium bifidum BbVK3 in buffalo milk. Four groups of mice (12 each) were fed for 17 d with buffalo milk (normal control), buffalo milk plus DSS (Colitis control), Dahi plus DSS, and LaBb Dahi plus DSS, respectively, with basal diet. The disease activity scores, weight loss, organ weight, colon length, myeloperoxidase (MPO) and β-glucoronidase activity was assessed, and the histopathological picture of the colon of mice was studied. All colitis control mice evidenced significant increase in MPO, β-glucoronidase activity and showed high disease activity scores along with histological damage to colonic tissue. Feeding with LaBb Dahi offered significant reduction in MPO activity, β-glucoronidase activity and improved disease activity scores. We found significant decline in length of colon, organ weight and body weight in colitis induced controls which were improved significantly by feeding LaBb Dahi. The present study suggests that LaBb Dahi can be used as a potential nutraceutical intervention to combat UC related changes and may offer effective adjunctive treatment for management of UC.

Biomass Burning observed during IAGOS - CARIBIC

NASA Astrophysics Data System (ADS)

Neumaier, Marco; Förster, Eric; Bönisch, Harald; Fischbeck, Garlich; Safadi, Layal; Hermann, Markus; Assmann, Denise; Zahn, Andreas

2017-04-01

Since May 2005 the CARIBIC passenger aircraft (Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container - Lufthansa, Airbus 340-600) measures ˜100 trace gases and aerosol components in the UTLS (9-12 km altitude) on 4-6 consecutive long-distance flights per month. Volatile Organic Compounds (VOCs) are measured with a Proton-Transfer-Reaction Mass Spectrometer (PTR-MS). In 2017 the current instrument will be replaced by an improved version, similar to the one operated by our group onboard the HALO research aircraft. Worldwide ˜1.3 Tg/y of acetonitrile (CH3CN) is emitted into the atmosphere almost exclusively from biomass burning (BB) together with other VOCs (e.g. ketones, aldehydes, aromatics), CO, CO2, NOx and aerosol particles. Therefore, and due to its rather long tropospheric lifetime of ˜6 months, acetonitrile constitutes a reliable BB tracer. Based on the signal of acetonitrile and CO, we analyzed the IAGOS-CARIBIC data set with respect to signatures of BB. The most intense but relatively rare BB signals (up to ˜1200 pptV acetonitrile, i.e. ˜8 times the tropospheric background) were sampled ˜3 km above the thermal tropopause over North America and Greenland in boreal summer. However, the largest contribution of BB signatures (˜40%) was observed over the tropics in autumn and winter. In the tropics ECMWF back trajectory calculations show that the upward transport is driven by convection and we found hints for secondary O3 production in BB affected air masses leading to an enhancement of ˜25 ppb O3 relative to the tropospheric background. Based on our applied detection algorithm, ˜8% of the IAGOS-CARIBIC data were identified to be affected by BB.

Forever Young: The Role of Ubiquitin Receptor DA1 and E3 Ligase BIG BROTHER in Controlling Leaf Growth and Development1[OPEN

PubMed Central

Vanhaeren, Hannes; De Milde, Liesbeth

2017-01-01

The final size of plant organs is determined by a combination of cell proliferation and cell expansion. Leaves account for a large part of above-ground biomass and provide energy to complete the plant’s life cycle. Although the final size of leaves is remarkably constant under fixed environmental conditions, several genes have been described to enhance leaf growth when their expression is modulated. In Arabidopsis (Arabidopsis thaliana), mutations in DA1 and BB increase leaf size, an effect that is synergistically enhanced in the double mutant. Here, we show that overexpression of a dominant-negative version of DA1 enhances leaf size in a broad range of natural accessions of this species, indicating a highly conserved role of this protein in controlling organ size. We also found that during early stages of development, leaves of da1-1 and bb/eod1-2 mutants were already larger than the isogenic Col-0 wild type, but this phenotype was triggered by different cellular mechanisms. Later during development, da1-1 and bb/eod1-2 leaves showed a prolonged longevity, which was enhanced in the double mutant. Conversely, ectopic expression of DA1 or BB restricted growth and promoted leaf senescence. In concert, shortly upon induction of DA1 and BB expression, several marker genes for the transition from proliferation to expansion were highly up-regulated. Additionally, multiple genes involved in maintaining the mitotic cell cycle were rapidly down-regulated and senescence genes were strongly up-regulated, particularly upon BB induction. With these results, we demonstrate that DA1 and BB restrict leaf size and promote senescence through converging and different mechanisms. PMID:28003326

Radioimmunoassay measurement of creatine kinase bb in the serum of schizophrenic patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lerner, M.H.; Friedhoff, A.J.

1980-03-03

Brain type creatine kinase (BB) isoenzyme was measured using a highly sensitive and specific radioimmunoassay procedure in two schizophrenic populations. The data would indicate that in the schizophrenic populations examined there is insufficient tissue disruption to cause abnormal build-up of brain creatine kinase levels. However the possibility of a rapid removal of creatine kinase BB from the circulation exists. The elevated creatine kinase reported in acute schizophrenics is most likely not of brain origin.

The contributions of biomass burning to primary and secondary organics: A case study in Pearl River Delta (PRD), China.

PubMed

Wang, BaoLin; Liu, Ying; Shao, Min; Lu, SiHua; Wang, Ming; Yuan, Bin; Gong, ZhaoHeng; He, LingYan; Zeng, LiMin; Hu, Min; Zhang, YuanHang

2016-11-01

Synchronized online measurements of gas- and particle- phase organics including non-methane hydrocarbons (NMHCs), oxygenated volatile organic compounds (OVOCs) and submicron organic matters (OM) were conducted in November 2010 at Heshan, Guangdong provincial supersite, China. Several biomass burning events were identified by using acetonitrile as a tracer, and enhancement ratios (EnRs) of organics to carbon monoxide (CO) obtained from this work generally agree with those from rice straw burning in previous studies. The influences of biomass burning on NMHCs, OVOCs and OM were explored by comparing biomass burning impacted plumes (BB plumes) and non-biomass burning plumes (non-BB plumes). A photochemical age-based parameterization method was used to characterize primary emission and chemical behavior of those three organic groups. The emission ratios (EmRs) of NMHCs, OVOCs and OM to CO increased by 27-71%, 34-55% and 67% in BB plumes, respectively, in comparison with non-BB plumes. The estimated formation rate of secondary organic aerosol (SOA) in BB plumes was found to be 24% faster than non-BB plumes. By applying the above emission ratios to the whole PRD, the annual emissions of VOCs and OM from open burning of crop residues would be 56.4 and 3.8Gg in 2010 in PRD, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Incorporation of Bacterial Blight Resistance Genes Into Lowland Rice Cultivar Through Marker-Assisted Backcross Breeding.

PubMed

Pradhan, Sharat Kumar; Nayak, Deepak Kumar; Pandit, Elssa; Behera, Lambodar; Anandan, Annamalai; Mukherjee, Arup Kumar; Lenka, Srikanta; Barik, Durga Prasad

2016-07-01

Bacterial blight (BB) of rice caused by Xanthomonas oryzae pv. oryzae is a major disease of rice in many rice growing countries. Pyramided lines carrying two BB resistance gene combinations (Xa21+xa13 and Xa21+xa5) were developed in a lowland cultivar Jalmagna background through backcross breeding by integrating molecular markers. In each backcross generation, markers closely linked to the disease resistance genes were used to select plants possessing the target genes. Background selection was continued in those plants carrying resistant genes until BC(3) generation. Plants having the maximum contribution from the recurrent parent genome were selected in each generation and hybridized with the recipient parent. The BB-pyramided line having the maximum recipient parent genome recovery of 95% was selected among BC3F1 plants and selfed to isolate homozygous BC(3)F(2) plants with different combinations of BB resistance genes. Twenty pyramided lines with two resistance gene combinations exhibited high levels of tolerance against the BB pathogen. In order to confirm the resistance, the pyramided lines were inoculated with different X. oryzae pv. oryzae strains of Odisha for bioassay. The genotypes with combination of two BB resistance genes conferred high levels of resistance to the predominant X. oryzae pv. oryzae isolates prevalent in the region. The pyramided lines showed similarity with the recipient parent with respect to major agro-morphologic traits.

Vitamin D receptor levels in colorectal cancer. Possible role of BsmI polymorphism.

PubMed

Parisi, Eva; Reñé, Josep Maria; Cardús, Anna; Valcheva, Petya; Piñol-Felis, Carme; Valdivielso, José Manuel; Fernández, Elvira

2008-07-01

A high expression of vitamin D receptor (VDR) in colorectal cancer (CRC) tumoral tissue has been related to a good prognosis and it has been proposed that it could be a good biological marker of CRC progression. Nevertheless, there are no previous studies that compare the VDR expression in tumoral towards normal tissue of the same CRC patient in relation to VDR BsmI genotype. We collected normal and tumoral tissue samples, as well as blood samples, from CRC patients (n=170) and controls (n=122). VDR genotyping was performed and BsmI homozygous patients were selected (CRC=50, Cont=32). VDR mRNA and protein levels were analyzed. We also measured 25-Hydroxyvitamin D serum levels. We found no differences in the polymorphism distribution in tumoral versus normal tissue (control: BB=15.7%, bb=41.3%, Bb=43%; CRC: BB=14.2%, bb=41.9%, Bb=43.9%). Furthermore, VDR levels decreased in colonic cancer tissue (mean: 3.03) versus normal mucosa (11.62) from the same patient (p<0.001), but this decrease was similar in both genotypes. There were differences in 25-Hydroxyvitamin D(3) levels between the CRC and the control group (CRC=8.65 ng/ml, Cont=18.15 ng/ml). In conclusion, we found a decrease in VDR levels in tumoral compared with normal mucosa from the same patient. This difference is independent of the BsmI polymorphism.

B.B. Contracting & Remodeling Information Sheet

EPA Pesticide Factsheets

B.B. Contracting & Remodeling (the Company) is located in St. Louis, Missouri. The settlement involves renovation activities conducted at property constructed prior to 1978, located in St. Louis, Missouri.

γ–Butyrobetaine is a pro-atherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO

PubMed Central

Koeth, Robert A.; Levison, Bruce S.; Culley, Miranda K.; Buffa, Jennifer A.; Wang, Zeneng; Gregory, Jill C.; Org, Elin; Wu, Yuping; Li, Lin; Smith, Jonathan D.; Wilson Tang, W. H.; DiDonato, Joseph A.; Lusis, Aldons J.; Hazen, Stanley L.

2014-01-01

Summary L- Carnitine, a nutrient in red meat, was recently reported to accelerate atherosclerosis via a metaorganismal pathway involving gut microbial trimethylamine (TMA) formation and host hepatic conversion into trimethylamine-N-oxide (TMAO). Herein we show that following L-carnitine ingestion, γ-butyrobetaine (γBB) is produced as an intermediary metabolite by gut microbes at a site anatomically proximal to and at a rate ~1000-fold higher than the formation of TMA. Moreover, we show γBB is the major gut microbial metabolite formed from dietary L-carnitine in mice, and like dietary L-carnitine, in a gut microbiota-dependent manner is converted into TMA and TMAO, and accelerates atherosclerosis. Gut microbial composition and functional metabolic studies reveal distinct taxa are associated with the production of γBB versus TMA/TMAO from dietary L-carnitine. Moreover, despite their close structural similarity, chronic dietary exposure to L-carnitine versus γBB promotes development of functionally distinct microbial communities optimized for the metabolism of L-carnitine versus γBB, respectively. PMID:25440057

A direct force model for Galilean invariant lattice Boltzmann simulation of fluid-particle flows

NASA Astrophysics Data System (ADS)

Tao, Shi; He, Qing; Chen, Baiman; Yang, Xiaoping; Huang, Simin

The lattice Boltzmann method (LBM) has been widely used in the simulation of particulate flows involving complex moving boundaries. Due to the kinetic background of LBM, the bounce-back (BB) rule and the momentum exchange (ME) method can be easily applied to the solid boundary treatment and the evaluation of fluid-solid interaction force, respectively. However, recently it has been found that both the BB and ME schemes may violate the principle of Galilean invariance (GI). Some modified BB and ME methods have been proposed to reduce the GI error. But these remedies have been recognized subsequently to be inconsistent with Newton’s Third Law. Therefore, contrary to those corrections based on the BB and ME methods, a unified iterative approach is adopted to handle the solid boundary in the present study. Furthermore, a direct force (DF) scheme is proposed to evaluate the fluid-particle interaction force. The methods preserve the efficiency of the BB and ME schemes, and the performance on the accuracy and GI is verified and validated in the test cases of particulate flows with freely moving particles.

Lyme disease spirochaete Borrelia burgdorferi does not require thiamin.

PubMed

Zhang, Kai; Bian, Jiang; Deng, Yijie; Smith, Alexis; Nunez, Roy E; Li, Michael B; Pal, Utpal; Yu, Ai-Ming; Qiu, Weigang; Ealick, Steven E; Li, Chunhao

2016-11-21

Thiamin pyrophosphate (ThDP), the active form of thiamin (vitamin B 1 ), is believed to be an essential cofactor for all living organisms 1,2 . Here, we report the unprecedented result that thiamin is dispensable for the growth of the Lyme disease pathogen Borrelia burgdorferi (Bb) 3 . Bb lacks genes for thiamin biosynthesis and transport as well as known ThDP-dependent enzymes 4 , and we were unable to detect thiamin or its derivatives in Bb cells. We showed that eliminating thiamin in vitro and in vivo using BcmE, an enzyme that degrades thiamin, has no impact on Bb growth and survival during its enzootic infectious cycle. Finally, high-performance liquid chromatography analysis reveals that the level of thiamin and its derivatives in Ixodes scapularis ticks, the enzootic vector of Bb, is extremely low. These results suggest that by dispensing with use of thiamin, Borrelia, and perhaps other tick-transmitted bacterial pathogens, are uniquely adapted to survive in tick vectors before transmitting to mammalian hosts. To our knowledge, such a mechanism has not been reported previously in any living organisms.

A review of biomass burning: Emissions and impacts on air quality, health and climate in China.

PubMed

Chen, Jianmin; Li, Chunlin; Ristovski, Zoran; Milic, Andelija; Gu, Yuantong; Islam, Mohammad S; Wang, Shuxiao; Hao, Jiming; Zhang, Hefeng; He, Congrong; Guo, Hai; Fu, Hongbo; Miljevic, Branka; Morawska, Lidia; Thai, Phong; Lam, Yun Fat; Pereira, Gavin; Ding, Aijun; Huang, Xin; Dumka, Umesh C

2017-02-01

Biomass burning (BB) is a significant air pollution source, with global, regional and local impacts on air quality, public health and climate. Worldwide an extensive range of studies has been conducted on almost all the aspects of BB, including its specific types, on quantification of emissions and on assessing its various impacts. China is one of the countries where the significance of BB has been recognized, and a lot of research efforts devoted to investigate it, however, so far no systematic reviews were conducted to synthesize the information which has been emerging. Therefore the aim of this work was to comprehensively review most of the studies published on this topic in China, including literature concerning field measurements, laboratory studies and the impacts of BB indoors and outdoors in China. In addition, this review provides insights into the role of wildfire and anthropogenic BB on air quality and health globally. Further, we attempted to provide a basis for formulation of policies and regulations by policy makers in China. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

DisAp-dependent striated fiber elongation is required to organize ciliary arrays

PubMed Central

Galati, Domenico F.; Bonney, Stephanie; Kronenberg, Zev; Clarissa, Christina; Yandell, Mark; Elde, Nels C.; Jerka-Dziadosz, Maria; Giddings, Thomas H.; Frankel, Joseph

2014-01-01

Cilia-organizing basal bodies (BBs) are microtubule scaffolds that are visibly asymmetrical because they have attached auxiliary structures, such as striated fibers. In multiciliated cells, BB orientation aligns to ensure coherent ciliary beating, but the mechanisms that maintain BB orientation are unclear. For the first time in Tetrahymena thermophila, we use comparative whole-genome sequencing to identify the mutation in the BB disorientation mutant disA-1. disA-1 abolishes the localization of the novel protein DisAp to T. thermophila striated fibers (kinetodesmal fibers; KFs), which is consistent with DisAp’s similarity to the striated fiber protein SF-assemblin. We demonstrate that DisAp is required for KFs to elongate and to resist BB disorientation in response to ciliary forces. Newly formed BBs move along KFs as they approach their cortical attachment sites. However, because they contain short KFs that are rotated, BBs in disA-1 cells display aberrant spacing and disorientation. Therefore, DisAp is a novel KF component that is essential for force-dependent KF elongation and BB orientation in multiciliary arrays. PMID:25533842

A comparative rapid and sensitive method to screen l-asparaginase producing fungi.

PubMed

Dhale, Mohan A; Mohan-Kumari, H Puttananjaiah

2014-07-01

Fungi are well known to produce various industrial enzymes and secondary metabolites with different colours. Fungi producing l-asparaginase enzyme are conventionally screened on medium containing phenol red (PR). The contrast between enzyme-hydrolysed zone and unhydrolysed l-asparagine is not very evident and distinct in medium containing PR and bromothymol blue (BB) due to coloured secondary metabolite production. Thus, PR and BB limit and affect the detection and screening method. In the present investigation, an improved method for screening is reported by comparing with PR and BB, wherein methyl red (MR) is incorporated as pH indicator. The enzyme activity was distinctly observed (red and light-yellow) in MR incorporated medium compared to PR and BB. Copyright © 2014 Elsevier B.V. All rights reserved.

A pancreatic venular defect in the BB/Wor rat.

PubMed Central

Majno, G.; Joris, I.; Handler, E. S.; Desemone, J.; Mordes, J. P.; Rossini, A. A.

1987-01-01

BB rats develop spontaneous autoimmune diabetes mellitus characterized morphologically by insulitis, an inflammatory lymphocytic infiltration of the islets of Langerhans. To investigate the role of the vascular endothelium of the pancreas in this destructive process, the authors injected diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats as well as other nondiabetic strains of rats with Monastral blue B, a colloidal pigment that identifies leaky microvasculature. They found evidence of a venular defect limited to the pancreas that is specific to the BB rat. Light- and electron-microscopic evidence suggests that this defect is due to a population of trapped (marginating) intravascular monocytes, which may be activated by the colloidal pigment and release vasoactive mediators. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3618725

CUORE: The Three Towers Test

NASA Astrophysics Data System (ADS)

Sparks, Laura; Goodsell, Alison

2009-11-01

Cryogenic Underground Observatory for Rare Events (CUORE) will be part of the next generation of detectors used to search for neutrinoless double beta decay (0vBB). Located in Assergi, Italy at the Gran Sasso National Laboratory (LNGS), CUORE will be a large cryogenic bolometer composed of 988 tellurium dioxide (TeO2) detectors with a total mass of 750 kg, and will search for 0vBB in 130Te. As the experiment will monitor the extremely rare event of 0vBB, all factors contributing to background need to be minimized to effectively increase the sensitivity. We assisted the LNGS researchers over the summer of 2008 by supporting Research and Development efforts to reduce the radioactive background of the experiment. Activities involved decontaminating the copper frame of radon daughters, and chemically etching and lapping the TeO2 crystals with nitric acid and silicon dioxide, respectively, to remove surface contaminants that contribute to background counts. This work was supported in part by NSF grant PHY-0653284 and the California State Faculty Support Grant.

Improving bounds on flavor changing vertices in the two Higgs doublet model from B^0-bar{B}^0 mixing

NASA Astrophysics Data System (ADS)

Diaz, R. A.; Martinez, R.; Sandoval, C. E.

2006-05-01

We find some constraints on the flavor changing vertices of the two Higgs doublet model, from the {Δ}M_{B_{text{d}}} measurement. Although bounds from this observable have already been considered, this paper takes into account the role of a new operator not included previously, as well as the vertices ξ_{bb}, ξ_{tc} and ξ_{sb}. Using the Cheng Sher parametrization, we find that for a relatively light charged Higgs boson (200 300 GeV), we obtain \\vertλ_{tt}\\vertlesssim1, while the parameter λ_{bb} could have values up to about 50. In addition, we use bounds for λ_{tt} and λ_{bb} obtained from B^0rightarrow X_sγ at next to leading order, and study the case where the only vanishing vertex factors are the ones involving quarks from the first family. We obtain that {Δ} M_{B_{text{d}}} is not sensitive to the change of the parameter λ_{sb}, while \\vertλ_{tc}\\vertlesssim1.

BICEP2 III: Instrumental systematics

DOE PAGES

Ade, P. A. R.

2015-11-23

In a companion paper, we have reported a >5σ detection of degree scale B-mode polarization at 150 GHz by the Bicep2 experiment. Here we provide a detailed study of potential instrumental systematic contamination to that measurement. We focus extensively on spurious polarization that can potentially arise from beam imperfections. We present a heuristic classification of beam imperfections according to their symmetries and uniformities, and discuss how resulting contamination adds or cancels in maps that combine observations made at multiple orientations of the telescope about its boresight axis. We introduce a technique, which we call "deprojection," for filtering the leading ordermore » beam-induced contamination from time-ordered data, and show that it reduces power in Bicep2's actual and null-test BB spectra consistent with predictions using high signal-to-noise beam shape measurements. We detail the simulation pipeline that we use to directly simulate instrumental systematics and the calibration data used as input to that pipeline. Finally, we present the constraints on BB contamination from individual sources of potential systematics. We find that systematics contribute BB power that is a factor of ~10× below Bicep2's three-year statistical uncertainty, and negligible compared to the observed BB signal. Lastly, the contribution to the best-fit tensor/scalar ratio is at a level equivalent to r = (3–6) × 10 –3.« less

BICEP2 III: Instrumental systematics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ade, P. A. R.

In a companion paper, we have reported a >5σ detection of degree scale B-mode polarization at 150 GHz by the Bicep2 experiment. Here we provide a detailed study of potential instrumental systematic contamination to that measurement. We focus extensively on spurious polarization that can potentially arise from beam imperfections. We present a heuristic classification of beam imperfections according to their symmetries and uniformities, and discuss how resulting contamination adds or cancels in maps that combine observations made at multiple orientations of the telescope about its boresight axis. We introduce a technique, which we call "deprojection," for filtering the leading ordermore » beam-induced contamination from time-ordered data, and show that it reduces power in Bicep2's actual and null-test BB spectra consistent with predictions using high signal-to-noise beam shape measurements. We detail the simulation pipeline that we use to directly simulate instrumental systematics and the calibration data used as input to that pipeline. Finally, we present the constraints on BB contamination from individual sources of potential systematics. We find that systematics contribute BB power that is a factor of ~10× below Bicep2's three-year statistical uncertainty, and negligible compared to the observed BB signal. Lastly, the contribution to the best-fit tensor/scalar ratio is at a level equivalent to r = (3–6) × 10 –3.« less

Advanced Manufacturing Process for Lower Cost Rechargeable Lithium-ion Batteries for DOD Including the BB2590

DTIC Science & Technology

2013-11-30

Rechargeable Lithium-ion Batteries for DOD Including the BB2590 Contract #SP4701-10-C-0032 Submitted by LithChem Energy (Div. of Retriev...Lithium-ion Batteries for DOD Including the BB2590 5a. CONTRACT NUMBER AP4701-10-C-0032 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...automated lithium-ion bi-cell production machine to produce lower cost prismatic lithium-ion batteries for the DOD. This machine was completed and

Oocyte Polarization Is Coupled to the Chromosomal Bouquet, a Conserved Polarized Nuclear Configuration in Meiosis

PubMed Central

Elkouby, Yaniv M.; Jamieson-Lucy, Allison; Mullins, Mary C.

2016-01-01

The source of symmetry breaking in vertebrate oocytes is unknown. Animal—vegetal oocyte polarity is established by the Balbiani body (Bb), a conserved structure found in all animals examined that contains an aggregate of specific mRNAs, proteins, and organelles. The Bb specifies the oocyte vegetal pole, which is key to forming the embryonic body axes as well as the germline in most vertebrates. How Bb formation is regulated and how its asymmetric position is established are unknown. Using quantitative image analysis, we trace oocyte symmetry breaking in zebrafish to a nuclear asymmetry at the onset of meiosis called the chromosomal bouquet. The bouquet is a universal feature of meiosis where all telomeres cluster to one pole on the nuclear envelope, facilitating chromosomal pairing and meiotic recombination. We show that Bb precursor components first localize with the centrosome to the cytoplasm adjacent to the telomere cluster of the bouquet. They then aggregate around the centrosome in a specialized nuclear cleft that we identified, assembling the early Bb. We show that the bouquet nuclear events and the cytoplasmic Bb precursor localization are mechanistically coordinated by microtubules. Thus the animal—vegetal axis of the oocyte is aligned to the nuclear axis of the bouquet. We further show that the symmetry breaking events lay upstream to the only known regulator of Bb formation, the Bucky ball protein. Our findings link two universal features of oogenesis, the Bb and the chromosomal bouquet, to oocyte polarization. We propose that a meiotic—vegetal center couples meiosis and oocyte patterning. Our findings reveal a novel mode of cellular polarization in meiotic cells whereby cellular and nuclear polarity are aligned. We further reveal that in zygotene nests, intercellular cytoplasmic bridges remain between oocytes and that the position of the cytoplasmic bridge coincides with the location of the centrosome meiotic—vegetal organizing center. These results suggest that centrosome positioning is set by the last mitotic oogonial division plane. Thus, oocytes are polarized in two steps: first, mitotic divisions preset the centrosome with no obvious polarization yet, then the meiotic—vegetal center forms at zygotene bouquet stages, when symmetry is, in effect, broken. PMID:26741740

Linear α-(1 → 6)-d-glucan from Bifidobacterium bifidum BIM В-733D is low molecular mass biopolymer with unique immunochemical properties.

PubMed

Kiseleva, Elena P; Mikhailopulo, Konstantin I; Zdorovenko, Evelina L; Knirel, Yuriy A; Novik, Galina I

2017-12-20

Role of microorganisms in induction of/protection from autoimmune diseases is proven though molecular mechanisms and bacterial/viral/yeast biopolymers responsible for these effects are in the research stage. Autoantobodies (AAbs) to thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg) as well as AAbs to transglutaminase 2 (anti-TG2) and antibodies to gliadins (anti-gliadins) are serological markers of autoimmune thyroid disease and celiac disease, respectively, and players in pathogenesis of these autoimmune diseases. In current study, biopolymer of Bifidobacterium bifidum BIM В-733D that interacts selectively with anti-gliadins (Bb-G anti-gliadins ) was isolated by affinity chromatography with anti-gliadins, purified by size exclusion chromatography on TSK 40 gel and identified by NMR as linear α-(1 → 6)-d-glucan with molecular mass about 5000 Da. It was proven that compounds Bb-G anti-gliadins and Bb-G anti-TPO /Bb-G anti-Tg isolated early from the same strain [Kiseleva, E. P. et al., Benef Microbes.2013, 4, 375 -391] are the same substance designated G Bb . Its unique immunochemical property is the ability to interact selectively with anti-TPO, anti-Tg, anti-TG2 and anti-gliadins in presence of no less than 10-fold excess of total immunoglobulins of class G (tIgG), as it was proven by ELISA. Synthesis of G Bb -bovine serum albumin (G Bb -BSA) conjugate is an example of increasing the reliability and reproducibility of ELISA results by mediated immobilization of a polysaccharide covalently attached to a well-adsorbed protein. Taking into account that there are population of bispecific anti-gliadins (anti-gliadins and anti-TG2 simultaneously) we regard our data as first argument in favor of hypothesis that G Bb differentiates between human AAbs per se and other human Ig (e.g. antibodies to antigens of infectious agents) due to its binding with a yet unidentified site which is present in the molecules of all AAbs (independently on their specificity) and absent in other human Igs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Efficacy and tolerability of a new synergized pyrethrins thermofobic foam in comparison with benzyl benzoate in the treatment of scabies in convicts: the ISAC study (Studio Della scabbia in ambiente carcerario).

PubMed

Biele, M; Campori, G; Colombo, R; De Giorgio, G; Frascione, P; Sali, R; Starnini, G; Milani, M

2006-07-01

Scabies is a very common skin infection in convicts. The SIMSPE Society (Società Italiana di Medicina e Sanità Penitenziaria) has organized and conducted a multicentre, randomized, comparative, parallel group, investigator-blinded trial to evaluate the efficacy and tolerability of synergized pyrethrins foam (PF) in comparison with benzyl benzoate (BB) lotion. A total of 240 convicted patients, enrolled in eight National Jail Institutions, with a clinical diagnosis of scabies, were treated with PF (n = 120) for three consecutive days or BB (n = 120) for five consecutive days. Primary study endpoints were the clinical cure rate and the local tolerability. Secondary endpoints were clinical evolution of scabietic lesions and itching intensity. Study outcomes were assessed using appropriate semiquantitative scores at baseline and after 2 and 4 weeks. A second treatment cycle was applied if after 2 weeks the patient was not judged clinically cured. At week 2, a total of 75% (95% CI: 66-82%) and 71% (95% CI: 62-78%) of patients showed a complete clinical cure rate in the PF and BB groups, respectively. At week 4, the percentage of totally cured patients increased up to 95% (95% CI: 89-97%) and 91% (95% CI: 83-94%) in the PF and BB groups, respectively (P = NS between groups). At week 4, 5% in the PF group and 9% in the BB group complained of itching. Burning and irritation after treatment applications were more common in the BB group in comparison with the PF group. The tolerability score was better in the PF group in comparison with to BB group (2.9 vs. 2.2; P = 0.0001). A total of 95% of patients in the PV group had a good tolerability score (i.e. = 3) in comparison with 41% in the BB group. Our results show that a 3-day treatment with pyrethrins thermofobic foam is at least as effective as a 5-day treatment with benzyl benzoate lotion in convicted subjects with scabies. The foam formulation is better tolerated than the benzyl benzoate lotion.

Bifidobacterium breve C50 secretes lipoprotein with CHAP domain recognized in aggregated form by TLR2.

PubMed

Scuotto, Angelo; Djorie, Serge; Colavizza, Michel; Romond, Pierre-Charles; Romond, Marie-Bénédicte

2014-12-01

Extracellular components secreted by Bifidobacterium breve C50 can induce maturation, high IL-10 production and prolonged survival of dendritic cells via a TLR2 pathway. In this study, the components were isolated from the supernatant by gel filtration chromatography. Antibodies raised against the major compounds with molecular weight above 600 kDa (Bb C50BC) also recognized compounds of lower molecular weight (200–600 kDa). TLR2 and TLR6 bound to the components already recognized by the antibodies. Trypsin digestion of Bb C50BC released three major peptides whose sequences displayed close similarities to a putative secreted protein with a CHAP amidase domain from B. breve. The 1300-bp genomic region corresponding to the hypothetical protein was amplified by PCR. The deduced polypeptide started with an N-terminal signal sequence of 45 amino acids, containing the lipobox motif (LAAC) with the cysteine in position 25, and 2 positively charged residues within the first 14 residues of the signal sequence. Lipid detection in Bb C50BC by GC/MS further supported the implication of a lipoprotein. Sugars were also detected in Bb C50BC. Close similarity with the glucan-binding protein B from Bifidobacterium animalis of two released peptides from Bb C50BC protein suggested that glucose moieties, possibly in glucan form, could be bound to the lipoprotein. Finally, heating at 100 °C for 5 min led to the breakdown of Bb C50BC in compounds of molecular weight below 67 kDa, which suggested that Bb C50BC was an aggregate. One might assume that a basic unit was formed by the lipoprotein bound putatively to glucan. Besides the other sugars and hexosamines recognized by galectin 1 were localized at the surface of the Bb C50BC aggregate. In conclusion, the extracellular components secreted by B. breve C50 were constituted of a lipoprotein putatively associated with glucose moieties and acting in an aggregating form as an agonist of TLR2/TLR6.

Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study.

PubMed

García-Bailo, Bibiana; Roke, Kaitlin; Mutch, David M; El-Sohemy, Ahmed; Badawi, Alaa

2012-11-16

Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Participants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson's correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates. We observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA), interferon-γ (IFN-γ), and platelet-derived growth factor BB (PDGF-bb). After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES). We observed an unexpected positive association between ascorbic acid and IFN-γ. 25(OH)D was not associated with altered concentrations of any inflammatory biomarkers. These findings suggest that α-tocopherol, but not ascorbic acid or 25(OH)D, is inversely associated with inflammation in healthy young adults.

S-NPP VIIRS thermal emissive band gain correction during the blackbody warm-up-cool-down cycle

NASA Astrophysics Data System (ADS)

Choi, Taeyoung J.; Cao, Changyong; Weng, Fuzhong

2016-09-01

The Suomi National Polar orbiting Partnership (S-NPP) Visible Infrared Imaging Radiometer Suite (VIIRS) has onboard calibrators called blackbody (BB) and Space View (SV) for Thermal Emissive Band (TEB) radiometric calibration. In normal operation, the BB temperature is set to 292.5 K providing one radiance level. From the NOAA's Integrated Calibration and Validation System (ICVS) monitoring system, the TEB calibration factors (F-factors) have been trended and show very stable responses, however the BB Warm-Up-Cool-Down (WUCD) cycles provide detectors' gain and temperature dependent sensitivity measurements. Since the launch of S-NPP, the NOAA Sea Surface Temperature (SST) group noticed unexpected global SST anomalies during the WUCD cycles. In this study, the TEB Ffactors are calculated during the WUCD cycle on June 17th 2015. The TEB F-factors are analyzed by identifying the VIIRS On-Board Calibrator Intermediate Product (OBCIP) files to be Warm-Up or Cool-Down granules. To correct the SST anomaly, an F-factor correction parameter is calculated by the modified C1 (or b1) values which are derived from the linear portion of C1 coefficient during the WUCD. The F-factor correction factors are applied back to the original VIIRS SST bands showing significantly reducing the F-factor changes. Obvious improvements are observed in M12, M14 and M16, but corrections effects are hardly seen in M16. Further investigation is needed to find out the source of the F-factor oscillations during the WUCD.

Biodosimetric quantification of short-term synchrotron microbeam versus broad-beam radiation damage to mouse skin using a dermatopathological scoring system

PubMed Central

Priyadarshika, R C U; Crosbie, J C; Kumar, B; Rogers, P A W

2011-01-01

Objectives Microbeam radiotherapy (MRT) with wafers of microscopically narrow, synchrotron generated X-rays is being used for pre-clinical cancer trials in animal models. It has been shown that high dose MRT can be effective at destroying tumours in animal models, while causing unexpectedly little damage to normal tissue. The aim of this study was to use a dermatopathological scoring system to quantify and compare the acute biological response of normal mouse skin with microplanar and broad-beam (BB) radiation as a basis for biological dosimetry. Method The skin flaps of three groups of mice were irradiated with high entrance doses (200 Gy, 400 Gy and 800 Gy) of MRT and BB and low dose BB (11 Gy, 22 Gy and 44 Gy). The mice were culled at different time-points post-irradiation. Skin sections were evaluated histologically using the following parameters: epidermal cell death, nuclear enlargement, spongiosis, hair follicle damage and dermal inflammation. The fields of irradiation were identified by γH2AX-positive immunostaining. Results The acute radiation damage in skin from high dose MRT was significantly lower than from high dose BB and, importantly, similar to low dose BB. Conclusion The integrated MRT dose was more relevant than the peak or valley dose when comparing with BB fields. In MRT-treated skin, the apoptotic cells of epidermis and hair follicles were not confined to the microbeam paths. PMID:21849367

Multi-instrument comparison and compilation of non-methane organic gas emissions from biomass burning and implications for smoke-derived secondary organic aerosol precursors

NASA Astrophysics Data System (ADS)

Hatch, Lindsay E.; Yokelson, Robert J.; Stockwell, Chelsea E.; Veres, Patrick R.; Simpson, Isobel J.; Blake, Donald R.; Orlando, John J.; Barsanti, Kelley C.

2017-01-01

Multiple trace-gas instruments were deployed during the fourth Fire Lab at Missoula Experiment (FLAME-4), including the first application of proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOFMS) and comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS) for laboratory biomass burning (BB) measurements. Open-path Fourier transform infrared spectroscopy (OP-FTIR) was also deployed, as well as whole-air sampling (WAS) with one-dimensional gas chromatography-mass spectrometry (GC-MS) analysis. This combination of instruments provided an unprecedented level of detection and chemical speciation. The chemical composition and emission factors (EFs) determined by these four analytical techniques were compared for four representative fuels. The results demonstrate that the instruments are highly complementary, with each covering some unique and important ranges of compositional space, thus demonstrating the need for multi-instrument approaches to adequately characterize BB smoke emissions. Emission factors for overlapping compounds generally compared within experimental uncertainty, despite some outliers, including monoterpenes. Data from all measurements were synthesized into a single EF database that includes over 500 non-methane organic gases (NMOGs) to provide a comprehensive picture of speciated, gaseous BB emissions. The identified compounds were assessed as a function of volatility; 6-11 % of the total NMOG EF was associated with intermediate-volatility organic compounds (IVOCs). These atmospherically relevant compounds historically have been unresolved in BB smoke measurements and thus are largely missing from emission inventories. Additionally, the identified compounds were screened for published secondary organic aerosol (SOA) yields. Of the total reactive carbon (defined as EF scaled by the OH rate constant and carbon number of each compound) in the BB emissions, 55-77 % was associated with compounds for which SOA yields are unknown or understudied. The best candidates for future smog chamber experiments were identified based on the relative abundance and ubiquity of the understudied compounds, and they included furfural, 2-methyl furan, 2-furan methanol, and 1,3-cyclopentadiene. Laboratory study of these compounds will facilitate future modeling efforts.

Cytokine, chemokine, and growth factor profile of platelet-rich plasma.

PubMed

Mussano, F; Genova, T; Munaron, L; Petrillo, S; Erovigni, F; Carossa, S

2016-07-01

During wound healing, biologically active molecules are released from platelets. The rationale of using platelet-rich plasma (PRP) relies on the concentration of bioactive molecules and subsequent delivery to healing sites. These bioactive molecules have been seldom simultaneously quantified within the same PRP preparation. In the present study, the flexible Bio-Plex system was employed to assess the concentration of a large range of cytokines, chemokines, and growth factors in 16 healthy volunteers so as to determine whether significant baseline differences may be found. Besides IL-1b, IL-1ra, IL-4, IL-6, IL-8, IL-12, IL-13, IL-17, INF-γ, TNF-α, MCP-1, MIP-1a, RANTES, bFGF, PDGF, and VEGF that were already quantified elsewhere, the authors reported also on the presence of IL-2, IL-5, IL-7, IL-9, IL-10, IL-15 G-CSF, GM-CSF, Eotaxin, CXCL10 chemokine (IP-10), and MIP 1b. Among the most interesting results, it is convenient to mention the high concentrations of the HIV-suppressive and inflammatory cytokine RANTES and a statistically significant difference between males and females in the content of PDGF-BB. These data are consistent with previous reports pointing out that gender, diet, and test system affect the results of platelet function in healthy subjects, but seem contradictory when compared to other quantification assays in serum and plasma. The inconsistencies affecting the experimental results found in literature, along with the variability found in the content of bioactive molecules, urge further research, hopefully in form of randomized controlled clinical trials, in order to find definitive evidence of the efficacy of PRP treatment in various pathologic and regenerative conditions.

A comparison of the performance of two advanced restraint systems in frontal impacts.

PubMed

Lopez-Valdes, F J; Juste, O; Pipkorn, B; Garcia-Muñoz, I; Sunnevång, C; Dahlgren, M; Alba, J J

2014-01-01

The goal of the study is to compare the kinematics and dynamics of the THOR dummy in a frontal impact under the action of 2 state-of-the-art restraint systems. Ten frontal sled tests were performed with THOR at 2 different impact speeds (35 and 9 km/h). Two advanced restraint systems were used: a pretensioned force-limiting belt (PT+FL) and a pretensioned belt incorporating an inflatable portion (PT+BB). Dummy measurements included upper and lower neck reactions, multipoint thoracic deflection, and rib deformation. Data were acquired at 10,000 Hz. Three-dimensional motion of relevant dummy landmarks was tracked at 1,000 Hz. RESULTS are reported in a local coordinate system moving with the test buck. Average forward displacement of the head was greater when the PT+FL belt was used (35 km/h: 376.3±16.1 mm [PT+BB] vs. 393.6±26.1 mm [PT+FL]; 9 km/h: 82.1±26.0 mm [PT+BB] vs. 98.8±0.2 mm [PT+FL]). The forward displacement of T1 was greater for the PT+FL belt at 35 km/h but smaller at 9 km/h. The forward motion of the pelvis was greater when the PT+BB was used, exhibiting a difference of 82 mm in the 9 km/h tests and 95.5 mm in the 35 km/h test. At 35 km/h, upper shoulder belt forces were similar (PT+FL: 4,756.8±116.6 N; PT+BB: 4,957.7±116.4 N). At 9 km/h, the PT+BB belt force was significantly greater than the PT+FL one. Lower neck flexion moments were higher for the PT+BB at 35 km/h but lower at 9 km/h (PT+FL: 34.2±3.5 Nm; PT+BB: 26.8±2.1 Nm). Maximum chest deflection occurred at the chest upper left region for both belts and regardless of the speed. The comparison of the performance of different restraints requires assessing occupant kinematics and dynamics from a global point of view. Even if the force acting on the chest is similar, kinematics can be substantially different. The 2 advanced belts compared here showed that while the PT+BB significantly reduced peak and resultant chest deflection, the resulting kinematics indicated an increased forward motion of the pelvis and a reduced rotation of the occupant's torso. Further research is needed to understand how these effects can influence the protection of real occupants in more realistic vehicle environments.

Optical absorption characteristics of brown carbon aerosols during the KORUS-AQ campaign at an urban site

NASA Astrophysics Data System (ADS)

Park, Seungshik; Yu, Geun-Hye; Lee, Sangil

2018-05-01

This study investigates the absorption characteristics of brown carbon (BrC) obtained from water and methanol extracts of fine particulate matter measured at an urban site in Gwangju, Korea during the KOREA U.S. - Air Quality campaign (May 2-June 11, 2016). The measurement period was classified into two intervals: biomass burning (BB) and non-BB periods. During the non-BB period, water-soluble organic carbon (WSOC) and humic-like substances (HULIS) primarily resulted from secondary organic aerosol (SOA) formation and primary vehicle emissions. Water-soluble organic aerosols during the BB period, meanwhile, were closely related to SOA formation and regionally transported BB emissions. The light absorption coefficient measured at 365 nm (babs,365) by methanol extracts was 2.6 and 6.1 times higher than the coefficients from the water and HULIS extracts, respectively, indicating the importance of BrC absorption by water-insoluble organic carbon. This was demonstrated by a good correlation between the water-insoluble BrC absorption and the elemental carbon concentration. A comparison of babs,365 between the methanol- and water-extracted BrC indicated that water-insoluble BrC accounted for approximately 61% (33-86%) of the total BrC absorption. The contributions of SOA, primary BB emissions, and traffic emissions to the water extract babs,365 were estimated using a stepwise multiple linear regression (MLR) analysis and found to be 1.17 ± 0.55, 0.65 ± 0.62, and 0.25 ± 0.09 Mm- 1, respectively, accounting for 59.6, 26.1, and 14.3% of the absorption coefficient by the water-soluble BrC. Further, it was determined that the contribution of the BB emissions to the water-soluble BrC absorption was approximately two times higher in the BB period than in the non-BB period. The average absorption Ångstrӧm exponent was 4.8 ± 0.3, 5.3 ± 0.7, and 6.8 ± 0.8 for the methanol, water, and HULIS extracts, respectively. The average mass absorption efficiency (MAE365) of methanol extracted BrC was 1.3 ± 0.4 m2/g·C. Water- and HULIS-extracted BrC had a MAE365 of 1.0 ± 0.3 and 0.8 ± 0.3 m2/g·C, respectively. These results suggest that methanol-extracted BrC could provide a better estimation of BrC absorption compared to WSOC and HULIS.