Expression of the cell-surface heparan sulfate proteoglycan syndecan-2 in developing rat anterior pituitary gland.

PubMed

Horiguchi, Kotaro; Syaidah, Rahimi; Fujiwara, Ken; Tsukada, Takehiro; Ramadhani, Dini; Jindatip, Depicha; Kikuchi, Motoshi; Yashiro, Takashi

2013-09-01

In the anterior pituitary gland, folliculo-stellate cells and five types of hormone-producing cells are surrounded by an extracellular matrix (ECM) essential for these cells to perform their respective roles. Syndecans-type I transmembrane cell-surface heparan sulfate proteoglycans act as major ECM coreceptors via their respective heparan sulfate chains and efficiently transduce intracellular signals through the convergent action of their transmembrane and cytoplasmic domains. The syndecans comprise four family members in vertebrates: syndecan-1, -2, -3 and -4. However, whether syndecans are produced in the pituitary gland or whether they have a role as a coreceptor is not known. We therefore used (1) reverse transcription plus the polymerase chain reaction to analyze the expression of syndecan genes and (2) immunohistochemical techniques to identify the cells that produce the syndecans in the anterior pituitary gland of adult rat. Syndecan-2 mRNA expression was clearly detected in the corticotropes of the anterior pituitary gland. Moreover, the expression of syndecan-2 in the developing pituitary gland had a distinct temporospatial pattern. To identify the cells expressing syndecan-2 in the developing pituitary gland, we used double-immunohistochemistry for syndecan-2 and the cell markers E-cadherin (immature cells) and Ki-67 (proliferating cells). Some E-cadherin- and Ki-67-immunopositive cells expressed syndecan-2. Therefore, syndecan-2 expression occurs in developmentally regulated patterns and syndecan-2 probably has different roles in adult and developing anterior pituitary glands.

Perlecan and syndecan-4 in uterine tissues during the early pregnancy in mice.

PubMed

San Martin, S; Soto-Suazo, M; Zorn, T M T

2004-07-01

During early pregnancy in mice, there is recruitment of specific immune cells, remodeling of the endometrium, cell differentiation and synthesis of new molecules. Immunohistochemistry was used to determine the distribution of perlecan and syndecan-4 in the uteri before and after embryo implantation. During pre-implantation, perlecan was identified in basement membranes and extracellular spaces of the endometrial stroma. In contrast, expression of syndecan-4 was quite weak. In the peri-implantation period, perlecan remained in the basement membranes, and it was no longer observed in the stroma and it was identified in the embryonic cells. On day 4 of pregnancy, syndecan-4 increased in the fibroblasts of the subepithelial stroma. After implantation, syndecan-4 was pronounced in pre-decidual and mature decidual cells. The coordinate balance between the pre- and post-implantation periods suggests a role of these two molecules in the adaptive modification of the uterine microenvironment to receive and implant the embryo.

Distribution of syndecan-1 protein in developing mouse teeth

PubMed Central

Filatova, Anna; Pagella, Pierfrancesco; Mitsiadis, Thimios A.

2014-01-01

Syndecan-1 is a cell surface proteoglycan involved in the regulation of various biological processes such as proliferation, migration, condensation and differentiation of cells, intercellular communication, and morphogenesis. The extracellular domain of syndecan-1 can bind to extracellular matrix components and signaling molecules, while its intracellular domain interacts with cytoskeletal proteins, thus allowing the transfer of information about extracellular environment changes into the cell that consequently affect cellular behavior. Although previous studies have shown syndecan-1 expression during precise stages of tooth development, there is no equivalent study regrouping the expression patterns of syndecan-1 during all stages of odontogenesis. Here we examined the distribution of syndecan-1 protein in embryonic and post-natal developing mouse molars and incisors. Syndecan-1 distribution in mesenchymal tissues such as dental papilla and dental follicle was correlated with proliferating events and its expression was often linked to stem cell niche territories. Syndecan-1 was also expressed in mesenchymal cells that will differentiate into the dentin producing odontoblasts, but not in differentiated functional odontoblasts. In the epithelium, syndecan-1 was detected in all cell layers, by the exception of differentiated ameloblasts that form the enamel. Furthermore, syndecan-1 was expressed in osteoblast precursors and osteoclasts of the alveolar bone that surrounds the developing tooth germs. Taken together these results show the dynamic nature of syndecan-1 expression during odontogenesis and suggest its implication in various processes of tooth development and homeostasis. PMID:25642191

Syndecan-4 enhances PDGF-BB activity in diabetic wound healing.

PubMed

Das, Subhamoy; Majid, Marjan; Baker, Aaron B

2016-09-15

Non-healing ulcers are a common consequence of long-term diabetes and severe peripheral vascular disease. These non-healing wounds are a major source of morbidity in patients with diabetes and place a heavy financial burden on the healthcare system. Growth factor therapies are an attractive strategy for enhancing wound closure in non-healing wounds but have only achieved mixed results in clinical trials. Platelet derived growth factor-BB (PDGF-BB) is the only currently approved growth factor therapy for non-healing wounds. However, PDGF-BB therapy is not effective in many patients and requires high doses that increase the potential for side effects. In this work, we demonstrate that syndecan-4 delivered in a proteoliposomal formulation enhances PDGF-BB activity in diabetic wound healing. In particular, syndecan-4 proteoliposomes enhance the migration of keratinocytes derived from patients with diabetes. In addition, syndecan-4 proteoliposomes sensitize keratinocytes to PDGF-BB stimulation, enhancing the intracellular signaling response to PDGF-BB. We further demonstrated that co-therapy with syndecan-4 proteoliposomes enhanced wound closure in diabetic, hyperlipidemic ob/ob mice. Wounds treated with both syndecan-4 proteoliposomes and PDGF-BB had increased re-epithelization and angiogenesis in comparison to wounds treated with PDGF-BB alone. Moreover, the wounds treated with syndecan-4 proteoliposomes and PDGF-BB also had increased M2 macrophages and reduced M1 macrophages, suggesting syndecan-4 delivery induces immunomodulation within the healing wounds. Together our findings support that syndecan-4 proteoliposomes markedly improve PDGF-BB efficacy for wound healing and may be useful in enhancing treatments for non-healing wounds. Non-healing wounds are major healthcare issue for patients with diabetes and peripheral vascular disease. Growth factor therapies have potential for healing chronic wounds but have not been effective for many patients. PDGF-BB is currently the only approved growth factor for enhancing wound healing. However, it has not seen widespread adoption due to limited efficacy and high cost. In this work, we have developed an enhancing agent that improves the activity of PDGF-BB in promoting wound healing in animals with diabetes. This co-therapy may be useful in improving the efficacy of PDGFBB and enhance its safety through lowering the dose of growth factor needed to improve wound healing. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Analysis on the expression and function of syndecan in the Pacific white shrimp Litopenaeus vannamei.

PubMed

Yang, Hui; Li, Shihao; Li, Fuhua; Wen, Rong; Xiang, Jianhai

2015-08-01

Syndecan is considered to be a multifunctional protein which functions as a cell surface receptor involved in cell adhesion, migration, cytoskeleton organization and differentiation. Previous bioinformatic analysis has revealed that syndecan in shrimp might interact with white spot syndrome virus (WSSV). In the present study, we experimentally studied the function of syndecan in shrimp immunity. The syndecan from Litopenaeus vannamei (LvSDC) was cloned and analyzed. The full-length cDNA of LvSDC was 1005 bp, consisting of 59 bp 5'-UTR, 253 bp 3'-UTR, and 693 bp open reading frame encoding 230 amino acids. LvSDC consisted of an extracellular domain (ED), a transmembrane domain (TM) and a cytoplasmic domain (CD). TM and CD shared high similarities with those of syndecan proteins from other species. LvSDC was ubiquitously expressed in all tested tissues, with the highest level in Oka. After WSSV challenge, the transcription level of LvSDC in Oka was apparently up-regulated. Recombinant LvSDC protein and its rabbit polyclonal antibody were prepared for detecting the location of LvSDC in hemocytes using immunocytochemistry approach. Data showed that LvSDC mainly located at the cell membrane and the cytoplasm of hemocytes. After silencing of LvSDC with siRNA, the WSSV copy numbers and mortality of shrimp after WSSV infection were both significantly decreased. These data provide useful information for understanding the immune mechanism of shrimp to WSSV infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Syndecan-1 Is Required to Maintain Intradermal Fat and Prevent Cold Stress

PubMed Central

Wollny, Damian; Clark, Rod J.; Roopra, Avtar; Colman, Ricki J.; MacDougald, Ormond A.; Shedd, Timothy A.; Nelson, David W.; Yen, Mei-I; Yen, Chi-Liang Eric; Alexander, Caroline M.

2014-01-01

Homeostatic temperature regulation is fundamental to mammalian physiology and is controlled by acute and chronic responses of local, endocrine and nervous regulators. Here, we report that loss of the heparan sulfate proteoglycan, syndecan-1, causes a profoundly depleted intradermal fat layer, which provides crucial thermogenic insulation for mammals. Mice without syndecan-1 enter torpor upon fasting and show multiple indicators of cold stress, including activation of the stress checkpoint p38α in brown adipose tissue, liver and lung. The metabolic phenotype in mutant mice, including reduced liver glycogen, is rescued by housing at thermoneutrality, suggesting that reduced insulation in cool temperatures underlies the observed phenotypes. We find that syndecan-1, which functions as a facultative lipoprotein uptake receptor, is required for adipocyte differentiation in vitro. Intradermal fat shows highly dynamic differentiation, continuously expanding and involuting in response to hair cycle and ambient temperature. This physiology probably confers a unique role for Sdc1 in this adipocyte sub-type. The PPARγ agonist rosiglitazone rescues Sdc1−/− intradermal adipose tissue, placing PPARγ downstream of Sdc1 in triggering adipocyte differentiation. Our study indicates that disruption of intradermal adipose tissue development results in cold stress and complex metabolic pathology. PMID:25101993

Therapeutic Ultrasound Bypasses Canonical Syndecan-4 Signaling to Activate Rac1*S⃞

PubMed Central

Mahoney, Claire M.; Morgan, Mark R.; Harrison, Andrew; Humphries, Martin J.; Bass, Mark D.

2009-01-01

The application of pulsed, low intensity ultrasound is emerging as a potent therapy for the treatment of complex bone fractures and tissue damage. Ultrasonic stimuli accelerate fracture healing by up to 40% and enhance tendon and ligament healing by promoting cell proliferation, migration, and matrix synthesis through an unresolved mechanism. Ultrasound treatment also induces closure of nonunion fractures, at a success rate (85% of cases) similar to that of surgical intervention (68-96%) while avoiding the complications associated with surgery. The regulation of cell adhesion necessary for wound healing depends on cooperative engagement of the extracellular matrix receptors, integrin and syndecan, as exemplified by the wound healing defects observed in syndecan- and integrin-knock-out mice. This report distinguishes the influence of ultrasound on signals downstream of the prototypic fibronectin receptors, α5β1 integrin and syndecan-4, which cooperate to regulate Rac1 and RhoA. Ultrasonic stimulation fails to activate integrins or induce cell spreading on poor, electrostatic ligands. By contrast, ultrasound treatment overcomes the necessity of engagement or expression of syndecan-4 during the process of focal adhesion formation, which normally requires simultaneous engagement of both receptors. Ultrasound exerts an influence downstream of syndecan-4 and PKCα to specifically activate Rac1, itself a critical regulator of tissue repair, and to a lesser extent RhoA. The ability of ultrasound to bypass syndecan-4 signaling, which is known to facilitate efficient tissue repair, explains the reduction in healing times observed in ultrasound-treated patients. By substituting for one of the key axes of adhesion-dependent signaling, ultrasound therapy has considerable potential as a clinical technique. PMID:19147498

Syndecan-2 is upregulated in colorectal cancer cells through interactions with extracellular matrix produced by stromal fibroblasts.

PubMed

Vicente, Carolina Meloni; Ricci, Ritchelli; Nader, Helena Bonciani; Toma, Leny

2013-05-25

The extracellular matrix (ECM) influences the structure, viability and functions of cells and tissues. Recent evidence indicates that tumor cells and stromal cells interact through direct cell-cell contact, the production of ECM components and the secretion of growth factors. Syndecans are a family of transmembrane heparan sulfate proteoglycans that are involved in cell adhesion, motility, proliferation and differentiation. Syndecan-2 has been found to be highly expressed in colorectal cancer cell lines and appears to be critical for cancer cell behavior. We have examined the effect of stromal fibroblast-produced ECM on the production of proteoglycans by colorectal cancer cell lines. Our results showed that in a highly metastatic colorectal cancer cell line, HCT-116, syndecan-2 expression is enhanced by fibroblast ECM, while the expression of other syndecans decreased. Of the various components of the stromal ECM, fibronectin was the most important in stimulating the increase in syndecan-2 expression. The co-localization of syndecan-2 and fibronectin suggests that these two molecules are involved in the adhesion of HCT-116 cells to the ECM. Additionally, we demonstrated an increase in the expression of integrins alpha-2 and beta-1, in addition to an increase in the expression of phospho-FAK in the presence of fibroblast ECM. Furthermore, blocking syndecan-2 with a specific antibody resulted in a decrease in cell adhesion, migration, and organization of actin filaments. Overall, these results show that interactions between cancer cells and stromal ECM proteins induce significant changes in the behavior of cancer cells. In particular, a shift from the expression of anti-tumorigenic syndecans to the tumorigenic syndecan-2 may have implications in the migratory behavior of highly metastatic tumor cells.

Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy

PubMed Central

Xie, Jun; He, Guixin; Chen, Qinhua; Sun, Jiayin; Dai, Qin; Lu, Jianrong; Li, Guannan; Wu, Han; Li, Ran; Chen, Jianzhou; Xu, Wei; Xu, Biao

2016-01-01

Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4–/–) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4–/– compared with wild-type (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4-overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy. PMID:26835698

Syndecan-1 Acts as an Important Regulator of CXCL1 Expression and Cellular Interaction of Human Endometrial Stromal and Trophoblast Cells

PubMed Central

Altergot-Ahmad, Olga; Pour, Sarah Jean; Krüssel, Jan-Steffen; Markert, Udo Rudolf; Fehm, Tanja Natascha; Bielfeld, Alexandra Petra

2017-01-01

Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression. Western blot analyses of MAPK and Wnt members were performed, followed by analysis of spheroid interactions between human endometrial cells and extravillous trophoblast cells. By mimicking embryo contact using IL-1β, we showed less ERK and c-Jun activation by depletion of Syndecan-1 and less Frizzled 4 production as part of the canonical Wnt pathway. Additionally, more beta-catenin was phosphorylated and therefore degraded after depletion of Syndecan-1. Secretion of CXC motif ligand 1 depends on MEK-1 with respect to Syndecan-1. Regarding the interaction of endometrial and trophoblast cells, the spheroid center-to-center distances were smaller after depletion of Syndecan-1. Therefore, Syndecan-1 seems to affect signaling processes relevant to signaling and intercellular interaction at the trophoblast-decidual interface. PMID:28293067

Induction of Syndecan-4 by Organic-Inorganic Hybrid Molecules with a 1,10-Phenanthroline Structure in Cultured Vascular Endothelial Cells.

PubMed

Hara, Takato; Kojima, Takayuki; Matsuzaki, Hiroka; Nakamura, Takehiro; Yoshida, Eiko; Fujiwara, Yasuyuki; Yamamoto, Chika; Saito, Shinichi; Kaji, Toshiyuki

2017-02-08

Organic-inorganic hybrid molecules constitute analytical tools used in biological systems. Vascular endothelial cells synthesize and secrete proteoglycans, which are macromolecules consisting of a core protein and glycosaminoglycan side chains. Although the expression of endothelial proteoglycans is regulated by several cytokines/growth factors, there may be alternative pathways for proteoglycan synthesis aside from downstream pathways activated by these cytokines/growth factors. Here, we investigated organic-inorganic hybrid molecules to determine a variant capable of analyzing the expression of syndecan-4, a transmembrane heparan-sulfate proteoglycan, and identified 1,10-phenanthroline ( o -Phen) with or without zinc (Zn-Phen) or rhodium (Rh-Phen). Bovine aortic endothelial cells in culture were treated with these compounds, and the expression of syndecan-4 mRNA and core proteins was determined by real-time reverse transcription polymerase chain reaction and Western blot analysis, respectively. Our findings indicated that o -Phen and Zn-Phen specifically and strongly induced syndecan-4 expression in cultured vascular endothelial cells through activation of the hypoxia-inducible factor-1α/β pathway via inhibition of prolyl hydroxylase-domain-containing protein 2. These results demonstrated an alternative pathway involved in mediating induction of endothelial syndecan-4 expression and revealed organic-inorganic hybrid molecules as effective tools for analyzing biological systems.

Primordial odontogenic tumor: Subepithelial expression of Syndecan-1 and Ki-67 suggests origin during early odontogenesis.

PubMed

Bologna-Molina, R; Mikami, T; Pereira-Prado, V; Tapia-Repetto, G; Pires, F R; Carlos, R; Mosqueda-Taylor, A

2018-03-01

Primordial odontogenic tumor (POT) is composed of variably cellular myxoid connective tissue, surrounded by cuboidal to columnar odontogenic epithelium resembling the inner epithelium of the enamel organ, which often invaginates into the underlying connective tissue. The tumor is delimited at least partially by a thin fibrous capsule. It derives from the early stages of tooth development. Syndecan-1 is a heparan sulfate proteoglycan that has a physiological role in several cellular functions, including maintenance of the epithelial architecture, cell-to-cell adhesion and interaction of cells with extracellular matrix, and with diverse growth factors, stimulating cell proliferation. Ki-67 is considered the gold standard as a cell proliferation marker. The aim of this study was to examine the expression of Syndecan-1 and Ki-67 proliferation index in POT and normal tooth germs to better understand the biological behavior of this tumor. Results showed that Syndecan-1 was more intensely expressed in subepithelial mesenchymal areas of POT, in a pattern that resembles the early stages of tooth development. The cell proliferation index (4.1%) suggests that POT is a slow growing tumor. Syndecan-1 expression in tooth germs in late cap and early bell stages was similar to POT, showing immunopositivity in subepithelial mesenchymal condensed areas. The immunohistochemical findings showed a pattern in which the population of subepithelial mesenchymal cells exhibited greater proliferative activity than the central portion of the dental papilla. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis.

PubMed

Ohkawara, Bisei; Glinka, Andrei; Niehrs, Christof

2011-03-15

The R-Spondin (Rspo) family of secreted Wnt modulators is involved in development and disease and holds therapeutic promise as stem cell growth factors. Despite growing biological importance, their mechanism of action is poorly understood. Here, we show that Rspo3 binds syndecan 4 (Sdc4) and that together they activate Wnt/PCP signaling. In Xenopus embryos, Sdc4 and Rspo3 are essential for two Wnt/PCP-driven processes-gastrulation movements and head cartilage morphogenesis. Rspo3/PCP signaling during gastrulation requires Wnt5a and is transduced via Fz7, Dvl, and JNK. Rspo3 functions by inducing Sdc4-dependent, clathrin-mediated endocytosis. We show that this internalization is essential for PCP signal transduction, suggesting that endocytosis of Wnt-receptor complexes is a key mechanism by which R-spondins promote Wnt signaling. Copyright © 2011 Elsevier Inc. All rights reserved.

Proline-rich antimicrobial peptide, PR-39 gene transduction altered invasive activity and actin structure in human hepatocellular carcinoma cells

PubMed Central

Ohtake, T; Fujimoto, Y; Ikuta, K; Saito, H; Ohhira, M; Ono, M; Kohgo, Y

1999-01-01

PR-39 is an endogenous proline-rich antimicrobial peptide which induces the synthesis of syndecan-1, a transmembrane heparan sulphate proteoglycan involved in cell-to-matrix interactions and wound healing. Previously, we revealed that the expression of syndecan-1 was reduced in human hepatocellular carcinomas with high metastatic potential and speculated that syndecan-1 played an important role in inhibition of invasion and metastasis. It is assumed that a modification of this process with PR-39 and syndecan-1 may result in a new strategy by which it can inhibit the invasion and metastasis. Therefore, we transduced a gene of PR-39 into human hepatocellular carcinoma cell line HLF, which shows a low expression of syndecan-1 and a high in vitro invasive activity, and examined whether this procedure could reduce the invasive activity of tumour cells. In two transfectants with PR-39 gene, the syndecan-1 expression was induced and the invasive activity in type I collagen-coated chamber was inhibited. Moreover, these transfectants showed the suppression of motile activity assayed by phagokinetic tracks in addition to the disorganization of actin filaments observed by a confocal imaging system. In contrast, five transfectants with syndecan-1 gene in the HLF cells revealed suppression of invasive activity but did not alter the motile activity and actin structures of the cell. These results suggest that PR-39 has functions involved in the suppression of motile activity and alteration of actin structure on human hepatocellular carcinoma cells in addition to the suppression of invasive activity which might result from the induction of syndecan-1 expression. © 1999 Cancer Research Campaign PMID:10507762

Epithelial-mesenchymal status influences how cells deposit fibrillin microfibrils.

PubMed

Baldwin, Andrew K; Cain, Stuart A; Lennon, Rachel; Godwin, Alan; Merry, Catherine L R; Kielty, Cay M

2014-01-01

Here, we show that epithelial-mesenchymal status influences how cells deposit extracellular matrix. Retinal pigmented epithelial (RPE) cells that expressed high levels of E-cadherin and had cell-cell junctions rich in zona occludens (ZO)-1, β-catenin and heparan sulfate, required syndecan-4 but not fibronectin or protein kinase C α (PKCα) to assemble extracellular matrix (fibrillin microfibrils and perlecan). In contrast, RPE cells that strongly expressed mesenchymal smooth muscle α-actin but little ZO-1 or E-cadherin, required fibronectin (like fibroblasts) and PKCα, but not syndecan-4. Integrins α5β1 and/or α8β1 and actomyosin tension were common requirements for microfibril deposition, as was heparan sulfate biosynthesis. TGFβ, which stimulates epithelial-mesenchymal transition, altered gene expression and overcame the dependency on syndecan-4 for microfibril deposition in epithelial RPE cells, whereas blocking cadherin interactions disrupted microfibril deposition. Renal podocytes had a transitional phenotype with pericellular β-catenin but little ZO-1; they required syndecan-4 and fibronectin for efficient microfibril deposition. Thus, epithelial-mesenchymal status modulates microfibril deposition.

Reduction of Syndecan Transcript Levels in the Insulin-Producing Cells Affects Glucose Homeostasis in Adult Drosophila melanogaster.

PubMed

Warren, Jonathan L; Hoxha, Eneida; Jumbo-Lucioni, Patricia; De Luca, Maria

2017-11-01

Signaling by direct cell-matrix interactions has been shown to impact the transcription, secretion, and storage of insulin in mammalian β cells. However, more research is still needed in this area. Syndecans are transmembrane heparan sulfate proteoglycans that function independently and in synergy with integrin-mediated signaling to mediate cell adhesion to the extracellular matrix. In this study, we used the model organism Drosophila melanogaster to determine whether knockdown of the Syndecan (Sdc) gene expression specifically in the insulin-producing cells (IPCs) might affect insulin-like peptide (ILP) production and secretion. IPCs of adult flies produce three ILPs (ILP2, ILP3, and ILP5), which have significant homology to mammalian insulin. We report that flies with reduced Sdc expression in the IPCs did not show any difference in the expression of ilp genes compared to controls. However, they had significantly reduced levels of the circulating ILP2 protein, higher circulating carbohydrates, and were less glucose tolerant than control flies. Finally, we found that IPCs-specific Sdc knockdown led to reduced levels of head Glucose transporter1 gene expression, extracellular signal-regulated kinase phosphorylation, and reactive oxygen species. Taken together, our findings suggest a cell autonomous role for Sdc in insulin release in D. melanogaster.

Polymorphisms in the bovine ghrelin precursor (GHRL) and Syndecan-1 (SDC1) genes that are associated with growth traits in cattle.

PubMed

Sun, Jiajie; Jin, Qijiang; Zhang, Chunlei; Fang, Xingtang; Gu, Chuanwen; Lei, Chuzhao; Wang, Juqiang; Chen, Hong

2011-06-01

Transgenically expressed Syndecan-1 was found in the hypothalamic nuclei that control energy balance, and was associated with maturity-onset obesity, while ghrelin has been shown to play important roles in the control of food intake, gastric acid secretion, energy homeostasis, and glucose and lipid metabolism. However, the roles of genetic variations of Syndecan-1 and ghrelin on growth trait have few been reported in cattle. Herein, five Chinese cattle breeds were analyzed by PCR-SSCP and DNA sequencing methods. The bovine ghrelin gene showed eleven SNPs g.[267G>A, 271G>A, 290C>T, 326A>G, 327T>C, 420C>A, 569A>G, 945C>T, 993C>T, 4491A>G, 4644G>A] and three SNPs g.[420C>A, 569 A>G, 945C>T] were firstly detected in cattle. The bovine Syndecan-1 gene showed two SNPs. One SNP showed a transition C>G at position 21514, resulting in a synonymous mutation p.G(GGC)169G(GGG) and another showed a transversion C>T at position 22591, resulting in a synonymous mutation p.D(GAC)283D(GAT). In ghrelin gene, no significant associations were revealed between any variant sites and body weight, average daily gain, body sizes for different growth periods (6, 12, 18, and 24 months old), as well as for the milk yield at 305 days, milk protein rate and milk fat percentage. However, the polymorphism of Syndecan-1 gene was significantly associated with bovine birth weight and body length. Hence, we first suggested that Syndecan-1 gene could be regarded as molecular marker for superior birth weight and body length.

Matrix expansion and syncytial aggregation of syndecan-1+ cells underpin villous atrophy in coeliac disease.

PubMed

Salvestrini, Camilla; Lucas, Mark; Lionetti, Paolo; Torrente, Franco; James, Sean; Phillips, Alan D; Murch, Simon H

2014-01-01

We studied the expression of sulphated glycosaminoglycans (GAGs) in coeliac disease (CD) mucosa, as they are critical determinants of tissue volume, which increases in active disease. We also examined mucosal expression of IL-6, which stimulates excess GAG synthesis in disorders such as Grave's ophthalmopathy. We stained archival jejunal biopsies from 5 children with CD at diagnosis, on gluten-free diet and challenge for sulphated GAGs. We then examined duodenal biopsies from 9 children with CD compared to 9 histological normal controls, staining for sulphated GAGs, heparan sulphate proteoglycans (HSPG), short-chain HSPG (Δ-HSPG) and the proteoglycan syndecan-1 (CD138), which is expressed on epithelium and plasma cells. We confirmed findings with a second monoclonal in another 12 coeliac children. We determined mucosal IL-6 expression by immunohistochemistry and PCR in 9 further cases and controls, and used quantitative real time PCR for other Th17 pathway cytokines in an additional 10 cases and controls. In CD, HSPG expression was lost in the epithelial compartment but contrastingly maintained within an expanded lamina propria. Within the upper lamina propria, clusters of syndecan-1(+) plasma cells formed extensive syncytial sheets, comprising adherent plasma cells, lysed cells with punctate cytoplasmic staining and shed syndecan ectodomains. A dense infiltrate of IL-6(+) mononuclear cells was detected in active coeliac disease, also localised to the upper lamina propria, with significantly increased mRNA expression of IL-6 and IL-17A but not IL-23 p19. Matrix expansion, through syndecan-1(+) cell recruitment and lamina propria GAG increase, underpins villous atrophy in coeliac disease. The syndecan-1(+) cell syncytia and excess GAG production recapitulate elements of the invertebrate encapsulation reaction, itself dependent on insect transglutaminase and glutaminated early response proteins. As in other matrix expansion disorders, IL-6 is upregulated and represents a logical target for immunotherapy in patients with coeliac disease refractory to gluten-free diet.

Matrix Expansion and Syncytial Aggregation of Syndecan-1+ Cells Underpin Villous Atrophy in Coeliac Disease

PubMed Central

Salvestrini, Camilla; Lucas, Mark; Lionetti, Paolo; Torrente, Franco; James, Sean; Phillips, Alan D.; Murch, Simon H.

2014-01-01

Background We studied the expression of sulphated glycosaminoglycans (GAGs) in coeliac disease (CD) mucosa, as they are critical determinants of tissue volume, which increases in active disease. We also examined mucosal expression of IL-6, which stimulates excess GAG synthesis in disorders such as Grave's ophthalmopathy. Methods We stained archival jejunal biopsies from 5 children with CD at diagnosis, on gluten-free diet and challenge for sulphated GAGs. We then examined duodenal biopsies from 9 children with CD compared to 9 histological normal controls, staining for sulphated GAGs, heparan sulphate proteoglycans (HSPG), short-chain HSPG (Δ-HSPG) and the proteoglycan syndecan-1 (CD138), which is expressed on epithelium and plasma cells. We confirmed findings with a second monoclonal in another 12 coeliac children. We determined mucosal IL-6 expression by immunohistochemistry and PCR in 9 further cases and controls, and used quantitative real time PCR for other Th17 pathway cytokines in an additional 10 cases and controls. Results In CD, HSPG expression was lost in the epithelial compartment but contrastingly maintained within an expanded lamina propria. Within the upper lamina propria, clusters of syndecan-1+ plasma cells formed extensive syncytial sheets, comprising adherent plasma cells, lysed cells with punctate cytoplasmic staining and shed syndecan ectodomains. A dense infiltrate of IL-6+ mononuclear cells was detected in active coeliac disease, also localised to the upper lamina propria, with significantly increased mRNA expression of IL-6 and IL-17A but not IL-23 p19. Conclusions Matrix expansion, through syndecan-1+ cell recruitment and lamina propria GAG increase, underpins villous atrophy in coeliac disease. The syndecan-1+ cell syncytia and excess GAG production recapitulate elements of the invertebrate encapsulation reaction, itself dependent on insect transglutaminase and glutaminated early response proteins. As in other matrix expansion disorders, IL-6 is upregulated and represents a logical target for immunotherapy in patients with coeliac disease refractory to gluten-free diet. PMID:25198673

Evaluation of maternal serum hypoxia inducible factor-1α, progranulin and syndecan-1 levels in pregnancies with early- and late-onset preeclampsia.

PubMed

Alici Davutoğlu, Ebru; Akkaya Firat, Asuman; Ozel, Ayşegül; Yılmaz, Nevin; Uzun, Isil; Temel Yuksel, Ilkbal; Madazlı, Riza

2018-08-01

To determine the serum levels of HIF-1 α, progranulin, and syndecan-1 in preeclampsia (PE) and normal pregnancy, and to compare whether these markers demonstrate any difference between early-onset PE (EO-PE) and late-onset PE (LO-PE). This cross-sectional study was conducted on 27 women with EO-PE, 27 women with LO-PE, and 26 healthy normotensive pregnant controls matched for gestational age. Maternal levels of serum HIF-1 α, progranulin, and syndecan-1 were measured with the use of an enzyme-linked immunosorbent assay kit. Statistical analysis revealed significant differences between the control and the PE groups in progranulin (p < .001) and syndecan-1 (p <.001) levels. There were no significant differences in the serum HIF-1 α levels between these groups (p= .069). When PE patients were evaluated by considering subgroups; statistical analysis revealed significant inter-group differences in all biomarkers. Serum progranulin levels were significantly higher in LO-PE compared with the other two groups (EO-PE versus LO-PE and LO-PE versus controls p = .000). Control group presented significantly higher syndecan-1 levels, than EO and LO-PE (p < .001). HIF-1 α levels positively correlated with progranulin levels (r = .439, p= .000). Serum progranulin may have potential to be used as a biomarker for the differentiation of EO-PE and LO-PE. The co-operative action between HIF-1 α and progranulin might play a key role in the pathogenesis of LO-PE. The predominant feature of LO-PE seems to be an inflammatory process, whereas in EO-PE placentation problem seems to be the main pathology.

Perturbation of the endothelial glycocalyx in post cardiac arrest syndrome.

PubMed

Grundmann, Sebastian; Fink, Katrin; Rabadzhieva, Lyubomira; Bourgeois, Natascha; Schwab, Tilmann; Moser, Martin; Bode, Christoph; Busch, Hans-Joerg

2012-06-01

The prognosis of immediate survivors of cardiac arrest remains poor, as the majority of these patients develops an inflammatory disorder known as the post-cardiac arrest syndrome (PCAS). Recently, the endothelial glycocalyx has been shown to be a key modulator of vascular permeability and inflammation, but its role in PCAS remains unknown. Plasma levels of the glycocalyx components syndecan-1, heparan sulfate and hyaluronic acid were measured in 25 patients after immediate survival of cardiac arrest during different phases of PCAS. Twelve hemodynamically stable patients with acute coronary syndrome served as controls. Cardiac arrest resulted in a significant increase in syndecan-1, heparan sulfate and hyaluronic acid levels compared to controls, indicating a shedding of the endothelial glycocalyx as a pathophysiological component of the post cardiac arrest syndrome. The time course differed between the individual glycocalyx components, with a higher increase of syndecan-1 in the early phase of PCAS (2.8-fold increase vs. controls) and a later peak of heparan sulfate (1.7-fold increase) and hyaluronic acid (2-fold increase) in the intermediate phase. Only the plasma levels of syndecan-1 correlated positively with the duration of CPR and negatively with the glycocalyx-protective protease inhibitor antithrombin III. Plasma levels of both syndecan-1 and heparan sulfate were higher in eventual non-survivors than in survivors of cardiac arrest. Our data for the first time demonstrates a perturbation of the endothelial glycocalyx in immediate survivors of cardiac arrest and indicate a potential important role of this endothelial surface layer in the development of post-cardiac arrest syndrome. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Syndecan-4 inhibits Wnt/β-catenin signaling through regulation of low-density-lipoprotein receptor-related protein (LRP6) and R-spondin 3.

PubMed

Astudillo, Pablo; Carrasco, Héctor; Larraín, Juan

2014-01-01

Regulation of Wnt signaling is crucial for embryonic development and adult homeostasis. Here we study the role of Syndecan-4 (SDC4), a cell-surface heparan sulphate proteoglycan, and Fibronectin (FN), in Wnt/β-catenin signaling. Gain- and loss-of-function experiments in mammalian cell lines and Xenopus embryos demonstrate that SDC4 and FN inhibit Wnt/β-catenin signaling. Epistatic and biochemical experiments show that this inhibition occurs at the cell membrane level through regulation of LRP6. R-spondin 3, a ligand that promotes canonical and non-canonical Wnt signaling, is more prone to potentiate Wnt/β-catenin signaling when SDC4 levels are reduced, suggesting a model whereby SDC4 tunes the ability of R-spondin to modulate the different Wnt signaling pathways. Since SDC4 has been previously related to non-canonical Wnt signaling, our results also suggest that this proteoglycan can be a key component in the regulation of Wnt signaling. Copyright © 2013 Elsevier Ltd. All rights reserved.

Differences in E-Cadherin and Syndecan-1 Expression in Different Types of Ameloblastomas

PubMed Central

López-Verdín, Sandra; Pereira-Prado, Vanesa

2018-01-01

Ameloblastomas are a group of benign, locally aggressive, recurrent tumors characterized by their slow and infiltrative growth. E-Cadherin and syndecan-1 are cell adhesion molecules related to the behavior of various tumors, including ameloblastomas. Ninety-nine ameloblastoma samples were studied; the expression of E-cadherin and syndecan-1 were evaluated by immunohistochemistry. E-Cadherin and epithelial syndecan-1 were more highly expressed in intraluminal/luminal unicystic ameloblastoma than in mural unicystic ameloblastoma and solid/multicystic ameloblastoma, whereas the stromal expression of syndecan-1 was higher in mural unicystic ameloblastoma and solid/multicystic ameloblastoma. Synchronicity was observed between E-cadherin and epithelial syndecan-1; the expression was correlated with intensity in all cases. There was a strong association between expression and tumor size and recurrence. The evaluation of the expression of E-cadherin and syndecan-1 are important for determining the potential aggressiveness of ameloblastoma variants. Future studies are required to understand how the expression of these markers is related to tumor aggressiveness.

The effect of nutritional status and myogenic satellite cell age on turkey satellite cell proliferation, differentiation, and expression of myogenic transcriptional regulatory factors and heparan sulfate proteoglycans syndecan-4 and glypican-1.

PubMed

Harthan, Laura B; McFarland, Douglas C; Velleman, Sandra G

2014-01-01

Posthatch satellite cell mitotic activity is a critical component of muscle development and growth. Satellite cells are myogenic stem cells that can be induced by nutrition to follow other cellular developmental pathways, and whose mitotic activity declines with age. The objective of the current study was to determine the effect of restricting protein synthesis on the proliferation and differentiation, expression of myogenic transcriptional regulatory factors myogenic determination factor 1, myogenin, and myogenic regulatory factor 4, and expression of the heparan sulfate proteoglycans syndecan-4 and glypican-1 in satellite cells isolated from 1-d-, 7-wk-, and 16-wk-old turkey pectoralis major muscle (1 d, 7 wk, and 16 wk cells, respectively) by using variable concentrations of Met and Cys. Four Met concentrations-30 (control), 7.5, 3, or 0 mg/L with 3.2 mg/L of Cys per 1 mg/L of Met-were used for culture of satellite cells to determine the effect of nutrition and age on satellite cell behavior during proliferation and differentiation. Proliferation was reduced by lower Met and Cys concentrations in all ages at 96 h of proliferation. Differentiation was increased in the 1 d Met-restricted cells, whereas the 7 wk cells treated with 3 mg/L of Met had decreased differentiation. Reduced Met and Cys levels from the control did not significantly affect the 16 wk cells at 72 h of differentiation. However, medium with no Met or Cys suppressed differentiation at all ages. The expression of myogenic determination factor 1, myogenin, myogenic regulatory factor 4, syndecan-4, and glypican-1 was differentially affected by age and Met or Cys treatment. These data demonstrate the age-specific manner in which turkey pectoralis major muscle satellite cells respond to nutritional availability and the importance of defining optimal nutrition to maximize satellite cell proliferation and differentiation for subsequent muscle mass accretion.

Acute UV irradiation increases heparan sulfate proteoglycan levels in human skin.

PubMed

Jung, Ji-Yong; Oh, Jang-Hee; Kim, Yeon Kyung; Shin, Mi Hee; Lee, Dayae; Chung, Jin Ho

2012-03-01

Glycosaminoglycans are important structural components in the skin and exist as various proteoglycan forms, except hyaluronic acid. Heparan sulfate (HS), one of the glycosaminoglycans, is composed of repeated disaccharide units, which are glucuronic acids linked to an N-acetyl-glucosamine or its sulfated forms. To investigate acute ultraviolet (UV)-induced changes of HS and HS proteoglycans (HSPGs), changes in levels of HS and several HSPGs in male human buttock skin were examined by immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR) after 2 minimal erythema doses (MED) of UV irradiation (each n = 4-7). HS staining revealed that 2 MED of UV irradiation increased its expression, and staining for perlecan, syndecan-1, syndecan-4, CD44v3, and CD44 showed that UV irradiation increased their protein levels. However, analysis by real-time qPCR showed that UV irradiation did not change mRNA levels of CD44 and agrin, and decreased perlecan and syndecan-4 mRNA levels, while increased syndecan-1 mRNA level. As HS-synthesizing or -degrading enzymes, exostosin-1 and heparanase mRNA levels were increased, but exostosin-2 was decreased by UV irradiation. UV-induced matrix metalloproteinase-1 expression was confirmed for proper experimental conditions. Acute UV irradiation increases HS and HSPG levels in human skin, but their increase may not be mediated through their transcriptional regulation.

Syndecan-2 Attenuates Radiation-induced Pulmonary Fibrosis and Inhibits Fibroblast Activation by Regulating PI3K/Akt/ROCK Pathway via CD148.

PubMed

Tsoyi, Konstantin; Chu, Sarah G; Patino-Jaramillo, Nasly G; Wilder, Julie; Villalba, Julian; Doyle-Eisele, Melanie; McDonald, Jacob; Liu, Xiaoli; El-Chemaly, Souheil; Perrella, Mark A; Rosas, Ivan O

2018-02-01

Radiation-induced pulmonary fibrosis is a severe complication of patients treated with thoracic irradiation. We have previously shown that syndecan-2 reduces fibrosis by exerting alveolar epithelial cytoprotective effects. Here, we investigate whether syndecan-2 attenuates radiation-induced pulmonary fibrosis by inhibiting fibroblast activation. C57BL/6 wild-type mice and transgenic mice that overexpress human syndecan-2 in alveolar macrophages were exposed to 14 Gy whole-thoracic radiation. At 24 weeks after irradiation, lungs were collected for histological, protein, and mRNA evaluation of pulmonary fibrosis, profibrotic gene expression, and α-smooth muscle actin (α-SMA) expression. Mouse lung fibroblasts were activated with transforming growth factor (TGF)-β1 in the presence or absence of syndecan-2. Cell proliferation, migration, and gel contraction were assessed at different time points. Irradiation resulted in significantly increased mortality and pulmonary fibrosis in wild-type mice that was associated with elevated lung expression of TGF-β1 downstream target genes and cell death compared with irradiated syndecan-2 transgenic mice. In mouse lung fibroblasts, syndecan-2 inhibited α-SMA expression, cell contraction, proliferation, and migration induced by TGF-β1. Syndecan-2 attenuated phosphoinositide 3-kinase/serine/threonine kinase/Rho-associated coiled-coil kinase signaling and serum response factor binding to the α-SMA promoter. Syndecan-2 attenuates pulmonary fibrosis in mice exposed to radiation and inhibits TGF-β1-induced fibroblast-myofibroblast differentiation, migration, and proliferation by down-regulating phosphoinositide 3-kinase/serine/threonine kinase/Rho-associated coiled-coil kinase signaling and blocking serum response factor binding to the α-SMA promoter via CD148. These findings suggest that syndecan-2 has potential as an antifibrotic therapy in radiation-induced lung fibrosis.

Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration.

PubMed

Pisconti, Addolorata; Banks, Glen B; Babaeijandaghi, Farshad; Betta, Nicole Dalla; Rossi, Fabio M V; Chamberlain, Jeffrey S; Olwin, Bradley B

2016-01-01

The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells. Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts. Additionally, muscle aging is improved in syndecan-3 null mice. Since syndecan-3 null myofiber-associated satellite cells downregulate Pax7 and migrate away from the niche more readily than wild type cells, syxndecan-3 appears to regulate satellite cell homeostasis and satellite cell homing to the niche. Manipulating syndecan-3 provides a promising target for development of therapies to enhance muscle regeneration in muscular dystrophies and in aged muscle.

Loss of Syndecan-1 Abrogates the Pulmonary Protective Phenotype Induced by Plasma After Hemorrhagic Shock.

PubMed

Wu, Feng; Peng, Zhanglong; Park, Pyong Woo; Kozar, Rosemary A

2017-09-01

Syndecan-1 (Sdc1) is considered a biomarker of injury to the endothelial glycocalyx following hemorrhagic shock, with shedding of Sdc1 deleterious. Resuscitation with fresh frozen plasma (FFP) has been correlated with restitution of pulmonary Sdc1 and reduction of lung injury, but the precise contribution of Sdc1 to FFPs protection in the lung remains unclear. Human lung endothelial cells were used to assess the time and dose-dependent effect of FFP on Sdc1 expression and the effect of Sdc1 silencing on in vitro endothelial cell permeability and actin stress fiber formation. Wild-type and Sdc1 mice were subjected to hemorrhagic shock followed by resuscitation with lactated Ringers (LR) or FFP and compared with shock alone and shams. Lungs were harvested after 3 h for analysis of permeability, histology, and inflammation and for measurement of syndecan- 2 and 4 expression. In vitro, FFP enhanced pulmonary endothelial Sdc1 expression in time- and dose-dependent manners and loss of Sdc1 in pulmonary endothelial cells worsened permeability and stress fiber formation by FFP. Loss of Sdc1 in vivo led to equivalency between LR and FFP in restoring pulmonary injury, inflammation, and permeability after shock. Lastly, Sdc1 mice demonstrated a significant increase in pulmonary syndecan 4 expression after hemorrhagic shock and FFP-based resuscitation. Taken together, our findings support a key role for Sdc1 in modulating pulmonary protection by FFP after hemorrhagic shock. Our results also suggest that other members of the syndecan family may at least be contributing to FFP's effects on the endothelium, an area that warrants further investigation.

Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer.

PubMed

Yao, Jun; Zhang, Lu-Lin; Huang, Xu-Mei; Li, Wen-Yao; Gao, She-Gan

2017-06-07

To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. The expression rates of PTN and N-syndecan proteins were 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI ( P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites ( P = 0.009), liver metastasis ( P = 0.035), and decreased survival time ( P = 0.022). N-syndecan expression was significantly associated with tumor size ( P = 0.025), but not with survival time ( P = 0.539). High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer.

Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer

PubMed Central

Yao, Jun; Zhang, Lu-Lin; Huang, Xu-Mei; Li, Wen-Yao; Gao, She-Gan

2017-01-01

AIM To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). METHODS An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. RESULTS The expression rates of PTN and N-syndecan proteins were 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI (P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites (P = 0.009), liver metastasis (P = 0.035), and decreased survival time (P = 0.022). N-syndecan expression was significantly associated with tumor size (P = 0.025), but not with survival time (P = 0.539). CONCLUSION High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer. PMID:28638231

Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction.

PubMed

Murphy, Laura S; Wickersham, Nancy; McNeil, J Brennan; Shaver, Ciara M; May, Addison K; Bastarache, Julie A; Ware, Lorraine B

2017-10-06

Disruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured plasma levels of syndecan-1, a marker for glycocalyx degradation. The present study is a retrospective observational study of 262 ventilated medical ICU patients at risk of ARDS due to severe sepsis and APACHE II ≥ 25. Plasma syndecan-1 was measured at study enrollment. Primary analysis focused on the association between syndecan-1 levels and the development of ARDS, other organ dysfunction (Brussels criteria), or in-hospital mortality. Overall, 135 (52%) patients developed ARDS. In patients with non-pulmonary sepsis, syndecan-1 levels were associated with ARDS (p = 0.05). Regardless of etiology of sepsis, higher syndecan-1 levels were associated with hepatic (p < 0.001), renal (p = 0.003), coagulation (p = 0.001), and circulatory (p = 0.02) failure as well as in-hospital mortality (p = 0.001), and there was a significant association between syndecan-1 levels and the number of vasopressors required in the first 24 h (p < 0.001). In addition, elevated syndecan levels were independently predictive of mortality in multivariable logistic regression adjusted for age and APACHE II score (odds ratio 1.85 per log increase in syndecan-1, 95% CI 1.056-3.241, p = 0.03). The extent of endothelial glycocalyx degradation is associated with non-pulmonary organ dysfunction in subjects with sepsis and is associated with ARDS but only in the subgroup with non-pulmonary sepsis. Measurement of syndecan-1 levels in sepsis patients might be useful for identifying patients at high risk of organ dysfunction and mortality as well as those who could benefit from therapies targeted at protecting or restoring the glycocalyx.

A Conserved Role for Syndecan Family Members in the Regulation of Whole-Body Energy Metabolism

PubMed Central

De Luca, Maria; Klimentidis, Yann C.; Casazza, Krista; Moses Chambers, Michelle; Cho, Ruth; Harbison, Susan T.; Jumbo-Lucioni, Patricia; Zhang, Shaoyan; Leips, Jeff; Fernandez, Jose R.

2010-01-01

Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1), and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs) in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction) and nominally associated with fasting glucose levels (P = 0.01) and sleep duration (P = 0.044). On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035) and intra-abdominal fat (P = 0.049), and SNP rs2267871 with insulin sensitivity (P = 0.037). Collectively, our results in Drosophila and humans argue that syndecan family members play a key role in the regulation of body metabolism. PMID:20585652

A conserved role for syndecan family members in the regulation of whole-body energy metabolism.

PubMed

De Luca, Maria; Klimentidis, Yann C; Casazza, Krista; Chambers, Michelle Moses; Cho, Ruth; Harbison, Susan T; Jumbo-Lucioni, Patricia; Zhang, Shaoyan; Leips, Jeff; Fernandez, Jose R

2010-06-23

Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1), and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs) in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction) and nominally associated with fasting glucose levels (P = 0.01) and sleep duration (P = 0.044). On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035) and intra-abdominal fat (P = 0.049), and SNP rs2267871 with insulin sensitivity (P = 0.037). Collectively, our results in Drosophila and humans argue that syndecan family members play a key role in the regulation of body metabolism.

Syndecan defines precise spindle orientation by modulating Wnt signaling in C. elegans.

PubMed

Dejima, Katsufumi; Kang, Sukryool; Mitani, Shohei; Cosman, Pamela C; Chisholm, Andrew D

2014-11-01

Wnt signals orient mitotic spindles in development, but it remains unclear how Wnt signaling is spatially controlled to achieve precise spindle orientation. Here, we show that C. elegans syndecan (SDN-1) is required for precise orientation of a mitotic spindle in response to a Wnt cue. We find that SDN-1 is the predominant heparan sulfate (HS) proteoglycan in the early C. elegans embryo, and that loss of HS biosynthesis or of the SDN-1 core protein results in misorientation of the spindle of the ABar blastomere. The ABar and EMS spindles both reorient in response to Wnt signals, but only ABar spindle reorientation is dependent on a new cell contact and on HS and SDN-1. SDN-1 transiently accumulates on the ABar surface as it contacts C, and is required for local concentration of Dishevelled (MIG-5) in the ABar cortex adjacent to C. These findings establish a new role for syndecan in Wnt-dependent spindle orientation. © 2014. Published by The Company of Biologists Ltd.

A subset of high Gleason grade prostate carcinomas contain a large burden of prostate cancer syndecan-1 positive stromal cells.

PubMed

Sharpe, Benjamin; Alghezi, Dhafer A; Cattermole, Claire; Beresford, Mark; Bowen, Rebecca; Mitchard, John; Chalmers, Andrew D

2017-05-01

There is a pressing need to identify prognostic and predictive biomarkers for prostate cancer to aid treatment decisions in both early and advanced disease settings. Syndecan-1, a heparan sulfate proteoglycan, has been previously identified as a potential prognostic biomarker by multiple studies at the tissue and serum level. However, other studies have questioned its utility. Anti-Syndecan-1 immunohistochemistry was carried out on 157 prostate tissue samples (including cancerous, adjacent normal tissue, and non-diseased prostate) from three independent cohorts of patients. A population of Syndecan-1 positive stromal cells was identified and the number and morphological parameters of these cells quantified. The identity of the Syndecan-1-positive stromal cells was assessed by multiplex immunofluorescence using a range of common cell lineage markers. Finally, the burden of Syndecan-1 positive stromal cells was tested for association with clinical parameters. We identified a previously unreported cell type which is marked by Syndecan-1 expression and is found in the stroma of prostate tumors and adjacent normal tissue but not in non-diseased prostate. We call these cells Prostate Cancer Syndecan-1 Positive (PCSP) cells. Immunofluorescence analysis revealed that the PCSP cell population did not co-stain with markers of common prostate epithelial, stromal, or immune cell populations. However, morphological analysis revealed that PCSP cells are often elongated and displayed prominent lamellipodia, suggesting they are an unidentified migratory cell population. Analysis of clinical parameters showed that PCSP cells were found with a frequency of 20-35% of all tumors evaluated, but were not present in non-diseased normal tissue. Interestingly, a subset of primary Gleason 5 prostate tumors had a high burden of PCSP cells. The current study identifies PCSP cells as a novel, potentially migratory cell type, which is marked by Syndecan-1 expression and is found in the stroma of prostate carcinomas, adjacent normal tissue, but not in non-diseased prostate. A subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP cell burden, suggesting an association between this unidentified cell type and tumor aggressiveness. © 2017 Wiley Periodicals, Inc.

Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes.

PubMed

Strunz, Célia Maria Cássaro; Roggerio, Alessandra; Cruz, Paula Lázara; Pacanaro, Ana Paula; Salemi, Vera Maria Cury; Benvenuti, Luiz Alberto; Mansur, Antonio de Pádua; Irigoyen, Maria Cláudia

2017-02-01

Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Heparanase-2 and syndecan-1 in colon cancer: the ugly ducklings or the beautiful swans?

PubMed

Giordano, Ricardo José

2008-08-01

Syndecan expression, or the lack thereof by tumor cells, has been associated with poor prognosis in several types of cancer, including colorectal cancer. Syndecan is a heparan sulfate proteoglycan involved in tumor adhesion, invasion, and metastasis. In addition, the expression of the enzyme heparanase by cancer cells correlates with malignant transformation and metastasis. Given the prominent role of syndecan and heparanase in physiological and pathological processes, they are promising molecular targets in the development of diagnostic methods and drugs for cancer and other diseases. A study in this issue of the European Journal of Gastroenterology & Hepatology reports the expression of syndecan-1 (Syn-1) and HPA2 in human colorectal cancer samples. These results confirm earlier observations that Syn-1 is downregulated by colorectal carcinoma cells but raise questions about its prognostic value. This study is also the first report on the upregulation of HPA2 in human cancer samples. HPA2 and Syn-1 expression by colorectal cancer tumor cells and the possible implications in disease progression are discussed.

The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics.

PubMed

Liu, Xu; Shepherd, Tyson R; Murray, Ann M; Xu, Zhen; Fuentes, Ernesto J

2013-03-05

PDZ (PSD-95/Dlg/ZO-1) domains are protein-protein interaction modules often regulated by ligand phosphorylation. Here, we investigated the specificity, structure, and dynamics of Tiam1 PDZ domain/ligand interactions. We show that the PDZ domain specifically binds syndecan1 (SDC1), phosphorylated SDC1 (pSDC1), and SDC3 but not other syndecan isoforms. The crystal structure of the PDZ/SDC1 complex indicates that syndecan affinity is derived from amino acids beyond the four C-terminal residues. Remarkably, the crystal structure of the PDZ/pSDC1 complex reveals a binding pocket that accommodates the phosphoryl group. Methyl relaxation experiments of PDZ/SCD1 and PDZ/pSDC1 complexes reveal that PDZ-phosphoryl interactions dampen dynamic motions in a distal region of the PDZ domain by decoupling them from the ligand-binding site. Our data are consistent with a selection model by which specificity and phosphorylation regulate PDZ/syndecan interactions and signaling events. Importantly, our relaxation data demonstrate that PDZ/phospho-ligand interactions regulate protein dynamics and their coupling to distal sites. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inhibition of hair follicle growth by a laminin-1 G-domain peptide, RKRLQVQLSIRT, in an organ culture of isolated vibrissa rudiment.

PubMed

Hayashi, Kazuhiro; Mochizuki, Mayumi; Nomizu, Motoyoshi; Uchinuma, Eijyu; Yamashina, Shohei; Kadoya, Yuichi

2002-04-01

We established a serum-free organ culture system of isolated single vibrissa rudiments taken from embryonic day 13 mice. This system allowed us to test more than 30 laminin-derived cell adhesive peptides to determine their roles on the growth and differentiation of vibrissa hair follicles. We found that the RKRLQVQLSIRT sequence (designated AG-73), which mapped to the LG-4 module of the laminin-alpha1 chain carboxyl-terminal G domain, perturbed the growth of hair follicles in vitro. AG-73 is one of the cell-binding peptides identified from more than 600 systematically synthesized 12 amino acid peptides covering the whole amino acid sequence of the laminin-alpha1, -beta1, and -gamma1 chains, by cell adhesion assay. Other cell-adhesive laminin peptides and a control scrambled peptide, LQQRRSVLRTKI, however, failed to show any significant effects on the growth of hair follicles. The AG-73 peptide binds to syndecan-1, a transmembrane heparan-sulfate proteoglycan. Syndecan-1 was expressed in both the mesenchymal condensation and the epithelial hair peg of developing vibrissa, suggesting that AG-73 binding to the cell surface syndecan-1 perturbed the epithelial-mesenchymal interactions of developing vibrissa. The formation of hair bulbs was aberrant in the explants treated with AG-73. In addition, impaired basement membrane formation, an abnormal cytoplasmic bleb formation, and an unusual basal formation of actin bundles were noted in the AG-73-treated-hair matrix epithelium, indicating that AG-73 binding perturbs various steps of epithelial morphogenesis, including the basement membrane remodeling. We also found a region-specific loss of the laminin-alpha1 chain in the basement membrane at the distal region of the invading hair follicle epithelium, indicating that laminins play a part in hair morphogenesis.

Pleiotrophin promotes perineural invasion in pancreatic cancer.

PubMed

Yao, Jun; Hu, Xiu-Feng; Feng, Xiao-Shan; Gao, She-Gan

2013-10-21

Perineural invasion (PNI) in pancreatic cancer is an important cause of local recurrence, but little is known about its mechanism. Pleiotrophin (PTN) is an important neurotrophic factor. It is of interest that our recent experimental data showed its involvement in PNI of pancreatic cancer. PTN strongly presents in the cytoplasm of pancreatic cancer cells, and high expression of PTN and its receptor may contribute to the high PNI of pancreatic cancer. Correspondingly, PNI is prone to happen in PTN-positive tumors. We thus hypothesize that, as a neurite growth-promoting factor, PTN may promote PNI in pancreatic cancer. PTN is released at the time of tumor cell necrosis, and binds with its high-affinity receptor, N-syndecan on pancreatic nerves, to promote neural growth in pancreatic cancer. Furthermore, neural destruction leads to a distorted neural homeostasis. Neurons and Schwann cells produce more N-syndecan in an effort to repair the pancreatic nerves. However, the abundance of N-syndecan attracts further PTN-positive cancer cells to the site of injury, creating a vicious cycle. Ultimately, increased PTN and N-syndecan levels, due to the continuous nerve injury, may promote cancer invasion and propagation along the neural structures. Therefore, it is meaningful to discuss the relationship between PTN/N-syndecan signaling and PNI in pancreatic cancer, which may lead to a better understanding of the mechanism of PNI in pancreatic cancer.

Pleiotrophin promotes perineural invasion in pancreatic cancer

PubMed Central

Yao, Jun; Hu, Xiu-Feng; Feng, Xiao-Shan; Gao, She-Gan

2013-01-01

Perineural invasion (PNI) in pancreatic cancer is an important cause of local recurrence, but little is known about its mechanism. Pleiotrophin (PTN) is an important neurotrophic factor. It is of interest that our recent experimental data showed its involvement in PNI of pancreatic cancer. PTN strongly presents in the cytoplasm of pancreatic cancer cells, and high expression of PTN and its receptor may contribute to the high PNI of pancreatic cancer. Correspondingly, PNI is prone to happen in PTN-positive tumors. We thus hypothesize that, as a neurite growth-promoting factor, PTN may promote PNI in pancreatic cancer. PTN is released at the time of tumor cell necrosis, and binds with its high-affinity receptor, N-syndecan on pancreatic nerves, to promote neural growth in pancreatic cancer. Furthermore, neural destruction leads to a distorted neural homeostasis. Neurons and Schwann cells produce more N-syndecan in an effort to repair the pancreatic nerves. However, the abundance of N-syndecan attracts further PTN-positive cancer cells to the site of injury, creating a vicious cycle. Ultimately, increased PTN and N-syndecan levels, due to the continuous nerve injury, may promote cancer invasion and propagation along the neural structures. Therefore, it is meaningful to discuss the relationship between PTN/N-syndecan signaling and PNI in pancreatic cancer, which may lead to a better understanding of the mechanism of PNI in pancreatic cancer. PMID:24151381

Increased syndecan-4 expression in sera and skin of patients with atopic dermatitis.

PubMed

Nakao, Momoko; Sugaya, Makoto; Takahashi, Naomi; Otobe, Sayaka; Nakajima, Rina; Oka, Tomonori; Kabasawa, Miyoko; Suga, Hiraku; Morimura, Sohshi; Miyagaki, Tomomitsu; Fujita, Hideki; Asano, Yoshihide; Sato, Shinichi

2016-11-01

Syndecan-4 (SDC-4) is a cell surface proteoglycan, which participates in signaling during cell adhesion, migration, proliferation, endocytosis, and mechanotransduction, and is expressed on various cells, including endothelial cells, epithelial cells, T cells, and eosinophils. Emerging evidences have suggested that SDC-4 might contribute to Th2-driven allergic immune responses. Here, we examined the role of SDC-4 in patients with atopic dermatitis (AD). Serum SDC-4 levels in AD patients were significantly higher than in healthy individuals, and they increased according to the disease severity. Importantly, they positively correlated with Eczema Area and Severity Index and itch visual analogue scale scores. Furthermore, serum SDC-4 levels decreased after treatment. We also analyzed SDC-4 expression in AD lesional skin. SDC-4 mRNA levels in AD skin were significantly higher than those of normal skin. Immunohistochemical staining revealed that SDC-4 was highly expressed in the epidermis and endothelial cells in AD lesional skin. Taken together, our study has demonstrated that SDC-4 expression was increased in sera and skin of AD patients, suggesting that SDC-4 may contribute to the development of AD.

Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.

PubMed

Mundt, Filip; Nilsonne, Gustav; Arslan, Sertaç; Csürös, Karola; Hillerdal, Gunnar; Yildirim, Huseyin; Metintas, Muzaffer; Dobra, Katalin; Hjerpe, Anders

2013-01-01

Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39), N-ERC/mesothelin (4.81, 3.19-7.93), CERC/mesothelin (3.58, 2.43-5.59) and syndecan-1 (1.34, 1.03-1.77). A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) in the model generation dataset and 0.83 (0.74-0.91) in the validation dataset, respectively. A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.

PDGF-A suppresses contact inhibition during directional collective cell migration.

PubMed

Nagel, Martina; Winklbauer, Rudolf

2018-06-08

The leading edge mesendoderm (LEM) of the Xenopus gastrula moves as an aggregate by collective migration. However, LEM cells on fibronectin in vitro show contact inhibition of locomotion by quickly retracting lamellipodia upon mutual contact. We found that a fibronectin-integrin-syndecan module acts between p21-activated kinase-1 upstream and ephrinB1 downstream to promote the contact-induced collapse of lamellipodia. To function in this module, fibronectin has to be present as puncta on the surface of LEM cells. To overcome contact inhibition in LEM cell aggregates, PDGF-A deposited in the endogenous substratum of LEM migration blocks the fibronectin-integrin-syndecan module at the integrin level. This stabilizes lamellipodia preferentially in the direction of normal LEM movement and supports cell orientation and the directional migration of the coherent LEM cell mass. © 2018. Published by The Company of Biologists Ltd.

pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen

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

Matsumoto, Yasuyuki; Zhang, Qing; Akita, Kaoru

2012-03-02

Highlights: Black-Right-Pointing-Pointer ppGalNAc-T13 was up-regulated in high metastatic sublines of Lewis lung cancer. Black-Right-Pointing-Pointer ppGalNAc-T13 expression enhanced cell invasion activity in low metastatic sublines. Black-Right-Pointing-Pointer Trimeric Tn antigen was induced in the transfectant cells of ppGalNAc-T13 cDNA. Black-Right-Pointing-Pointer A major protein carrying trimeric Tn structure was identified as Syndecan-1. Black-Right-Pointing-Pointer Silencing of ppGalNAc-T13 resulted in the reduction of invasion and of metastasis.. -- Abstract: In order to analyze the mechanisms for cancer metastasis, high metastatic sublines (H7-A, H7-Lu, H7-O, C4-sc, and C4-ly) were obtained by repeated injection of mouse Lewis lung cancer sublines H7 and C4 into C57BL/6 mice. Thesemore » sublines exhibited increased proliferation and invasion activity in vitro. Ganglioside profiles exhibited lower expression of GM1 in high metastatic sublines than the parent lines. Then, we established GM1-Si-1 and GM1-Si-2 by stable silencing of GM1 synthase in H7 cells. These GM1-knockdown clones exhibited increased proliferation and invasion. Then, we explored genes that markedly altered in the expression levels by DNA microarray in the combination of C4 vs. C4-ly or H7 vs. H7 (GM1-Si). Consequently, pp-GalNAc-T13 gene was identified as up-regulated genes in the high metastatic sublines. Stable transfection of pp-GalNAc-T13 cDNA into C4 (T13-TF) resulted in increased invasion and motility. Then, immunoblotting and flow cytometry using various antibodies and lectins were performed. Only anti-trimeric Tn antibody (mAb MLS128), showed increased expression levels of trimeric Tn antigen in T13-TF clones. Moreover, immunoprecipitation/immunoblotting was performed by mAb MLS128, leading to the identification of an 80 kDa band carrying trimeric Tn antigen, i.e. Syndecan-1. Stable silencing of endogenous pp-GalNAc-T13 in C4-sc (T13-KD) revealed that primary tumors generated by subcutaneous injection of T13-KD clones showed lower coalescence to fascia and peritoneum, and significantly reduced lung metastasis than control clones. These data suggested that high expression of pp-GalNAc-T13 gene generated trimeric Tn antigen on Syndecan-1, leading to the enhanced metastasis.« less

Alterations in expression of mucin, tenascin-c and syndecan-1 in the conjunctiva following retinal surgery and plaque radiotherapy.

PubMed

Heimann, H; Coupland, S E; Gochman, R; Hellmich, M; Foerster, M H

2001-07-01

Disturbances of the ocular tear film layer and dry eye symptoms are common complications following retinal surgery and ocular tumour therapy. Examined were the histopathological changes of the conjunctiva following posterior segment surgery and plaque radiotherapy. Biopsy specimens of the superior bulbar conjunctiva were obtained during cataract surgery between 2 weeks and 7 years following vitrectomy (n=92) or plaque radiotherapy for uveal melanoma (n=20) and from control subjects without previous ocular surgery (n=29). These were examined using conventional histology (HE, PAS, Van Gieson) and immunochemistry [APAAP, using antibodies directed against MUC1, MUC5AC, syndecan-1 and tenascin-C (TN-C)]. The histopathological changes were graded and statistical analysis was performed using Wilcoxon and Kruskal-Wallis rank sum tests. Conjunctival specimens of patients following vitrectomy or plaque radiotherapy for uveal melanoma demonstrated increased epithelial stratification, a significant decrease in the number of PAS- and MUC5AC-positive goblet cells, and distributional changes in expression of MUC1, syndecan- and TN-C within conjunctival epithelium or stroma. These alterations - in particular the goblet cell reduction and stromal fibrosis - were most prominent in those patients who had undergone radiotherapy. Posterior segment surgery can lead to morphological alterations of the conjunctiva and distributional changes in ocular mucins, which may cause dry eye symptoms.

Loss of cell invasiveness through PKC-mediated syndecan-1 downregulation in melanoma cells under anchorage independency.

PubMed

Wang, ChiaChen; Tseng, TingTing; Jhang, Yaoyun; Tseng, JenChih; Hsieh, ChiaoHui; Wu, Wen-guey; Lee, ShaoChen

2014-11-01

Anchorage-independent survival is one of the key features for malignant tumor cells. Whether specific gene alterations contributed by anchorage independency would further affect metastatic phenotypes of melanoma cells was unclear. We adapted suspension culture of melanoma cells to establish anchorage independency. The suspended melanoma cells lost their invasive abilities in vitro. Specific loss of laminin-binding ability in suspended melanoma cells was observed, which was correlated with downregulation of syndecan-1 as revealed by microarray and validated by qPCR and Western blot. Modulation of syndecan-1 expression level affected laminin binding, transwell migration and matrix metalloproteinase-2 secretion in melanoma cells. SDC1 expression and transwell migration were correlated with activity or level of protein kinase Cδ as evidence by specific inhibitors and shRNA transfection. In this study, we compared metastatic phenotypes and gene expressions of adherent and suspended melanoma cells. The anchorage independency led to protein kinase Cδ-mediated syndecan-1 downregulation, which contributed to loss of laminin-binding ability, reduced metalloproteinase-2 secretion and loss of invasiveness. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

LDL receptor-related protein mediates cell-surface clustering and hepatic sequestration of chylomicron remnants in LDLR-deficient mice.

PubMed

Yu, K C; Chen, W; Cooper, A D

2001-06-01

It has been proposed that in the liver, chylomicron remnants (lipoproteins carrying dietary lipid) may be sequestered before being internalized by hepatocytes. To study this, chylomicron remnants labeled with a fluorescent dye were perfused into isolated livers of LDL receptor-deficient (LDLR-deficient) mice (Ldlr(-/-)) and examined by confocal microscopy. In contrast to livers from normal mice, there was clustering of the chylomicron remnants on the cell surface in the space of DISSE: These remnant clusters colocalized with clusters of LDLR-related protein (LRP) and could be eliminated by low concentrations of receptor-associated protein, an inhibitor of LRP. When competed with ligands of heparan sulfate proteoglycans (HSPGs), the remnant clusters still appeared but were fewer in number, although syndecans (membrane HSPGs) colocalized with the remnant clusters. This suggests that the clustering of remnants is not dependent on syndecans but that the syndecans may modify the binding of remnants. These results establish that sequestration is a novel process, the clustering of remnants in the space of DISSE: The clustering involves remnants binding to the LRP, and this may be stabilized by binding with syndecans, eventually followed by endocytosis.

Syndecan-1 and Metastasis Dormancy

DTIC Science & Technology

2015-09-01

Sdc1 WT vs Sdc1 KO mice (p = 0.36). - 5 - Major Task 2: Optimize 3D lung microenvironment assay Subtask 1: Transduce HMVEC-L with E4ORF1 and mCherry...micro-channel devices (see below) but have not yet transduced them with E4ORF1 nor labeled them. If we succeed in generating defined vascular

Soluble Syndecan-1: A Novel Biomarker of Small Bowel Mucosal Damage in Children with Celiac Disease.

PubMed

Yablecovitch, D; Oren, A; Ben-Horin, S; Fudim, E; Eliakim, R; Saker, T; Konikoff, F M; Kopylov, U; Matthias, T; Lerner, A

2017-03-01

Syndecan-1 (SDC1) is essential for maintaining normal epithelial barrier. Shedding of SDC1 ectodomain, reflected by serum soluble syndecan-1 (SSDC1) levels, is regulated by inflammation. Increased intestinal permeability plays a central role in celiac disease (CD). The association between SSDC1 levels and mucosal damage in CD has not been evaluated. To evaluate serum SSDC1 levels in children with CD and to determine its relationship with histological grading classified by modified Marsh criteria. This is a cross-sectional, pilot study, in which serum SSDC1 was analyzed by ELISA in a cohort of 49 untreated children with CD and 15 children with nonspecific abdominal pain (AP). CD was diagnosed based on positive celiac serology and small intestinal biopsy. SSDC1 levels at the time of biopsy were correlated with Marsh grading. Controls were defined by AP, negative celiac serology, normal upper endoscopy, and small intestinal biopsies. SSDC1 levels were significantly higher in CD patients compared to AP controls (116.2 ± 161 vs. 41.3 ± 17.5 ng/ml, respectively, p < 0.01). SSDC1 levels were significantly higher in patients with Marsh 3c lesion compared to AP controls (170.6 ± 201 vs. 41.3 ± 17.5 ng/ml, respectively, p < 0.05). SSDC1 concentrations displayed a significant correlation with mucosal damage defined by Marsh (r = 0.39, p < 0.05). This is the first study demonstrating elevated levels of serum SSDC1 in children with CD. Our results suggest that SSDC1 is a potentially novel marker of intestinal mucosal damage in patients with CD. Its applicability as a surrogate biomarker in CD remains to be determined.

A novel device to stretch multiple tissue samples with variable patterns: application for mRNA regulation in tissue-engineered constructs.

PubMed

Imsirovic, Jasmin; Derricks, Kelsey; Buczek-Thomas, Jo Ann; Rich, Celeste B; Nugent, Matthew A; Suki, Béla

2013-01-01

A broad range of cells are subjected to irregular time varying mechanical stimuli within the body, particularly in the respiratory and circulatory systems. Mechanical stretch is an important factor in determining cell function; however, the effects of variable stretch remain unexplored. In order to investigate the effects of variable stretch, we designed, built and tested a uniaxial stretching device that can stretch three-dimensional tissue constructs while varying the strain amplitude from cycle to cycle. The device is the first to apply variable stretching signals to cells in tissues or three dimensional tissue constructs. Following device validation, we applied 20% uniaxial strain to Gelfoam samples seeded with neonatal rat lung fibroblasts with different levels of variability (0%, 25%, 50% and 75%). RT-PCR was then performed to measure the effects of variable stretch on key molecules involved in cell-matrix interactions including: collagen 1α, lysyl oxidase, α-actin, β1 integrin, β3 integrin, syndecan-4, and vascular endothelial growth factor-A. Adding variability to the stretching signal upregulated, downregulated or had no effect on mRNA production depending on the molecule and the amount of variability. In particular, syndecan-4 showed a statistically significant peak at 25% variability, suggesting that an optimal variability of strain may exist for production of this molecule. We conclude that cycle-by-cycle variability in strain influences the expression of molecules related to cell-matrix interactions and hence may be used to selectively tune the composition of tissue constructs.

Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection

PubMed Central

Sasmono, R. Tedjo; Sinto, Robert; Ibrahim, Eppy; Suryamin, Maulana

2017-01-01

Abstract Background. The role of vascular endothelial (VE) components in dengue infection with plasma leakage is unknown. Therefore, we conducted a study to determine the adjusted association of the endothelial glycocalyx layer (EGL) and tight and adherens junction markers with plasma leakage. Methods. A prospective observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on the third day of fever from November 2013 through August 2015 were included in the study. Multiple regression analysis was used to determine the adjusted association of the VE biomarkers with the severity of the plasma leakage. Results. A total of 103 dengue-infected patients participated in the study. In the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence interval [CI] = 1.001–1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025–1.307) had an adjusted association with plasma leakage, whereas levels of syndecan-1 (OR = 1.004; 95% CI = 1.000–1.008) and claudin-5 (OR = 1.038; 95% CI = 1.004–1.074) had an adjusted association with severe plasma leakage. Conclusions. In dengue-infected patients, elevated levels of syndecan-1 and chondroitin sulfate are strongly associated with plasma leakage, and elevated levels of syndecan-1 and claudin-5 are strongly associated with severe plasma leakage. PMID:28453844

Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis

PubMed Central

Haddad, Oualid; Guyot, Erwan; Marinval, Nicolas; Chevalier, Fabien; Maillard, Loïc; Gadi, Latifa; Laguillier-Morizot, Christelle; Oudar, Olivier; Sutton, Angela; Charnaux, Nathalie; Hlawaty, Hanna

2015-01-01

Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4), in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC) migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases. PMID:26516869

SDN-1/syndecan regulates growth factor signaling in distal tip cell migrations in C. elegans.

PubMed

Schwabiuk, Megan; Coudiere, Ludivine; Merz, David C

2009-10-01

Mutations in the sdn-1/syndecan gene act as genetic enhancers of the ventral-to-dorsal distal tip cell (DTC) migration defects caused by a weak allele of the netrin receptor gene unc-5. The sdn-1(ev697) allele was identified in a genetic screen for enhancers of unc-5 DTC migration defects, and carried a nonsense mutation predicted to truncate the SDN-1 protein prior to the transmembrane domain. The enhancement of unc-5 caused by an sdn-1 mutation was rescued by expression of wild-type sdn-1 in the hypodermis or nervous system rather than the DTCs, indicating a cell non-autonomous function of sdn-1. The enhancement was also partially reversed by mutations in the egl-17/FGF or egl-20/Wnt genes, suggesting that sdn-1 affects UNC-5 function through a mis-regulation of signaling in growth factor pathways. egl-20 reporter constructs exhibited increased and mis-localized EGL-20 distribution in sdn-1 mutants compared to wild-type animals. Finally, using loss of function mutations, we show that egl-17/Fgf and egl-20/Wnt are partially redundant in regulating the migration pattern of the posterior DTC, as double mutants exhibit significant frequencies of defects in migration phases along both the anteroposterior and dorsoventral axes. Together these results suggest that SDN-1 affects UNC-5 function by regulating the proper extracellular distribution of growth factors.

A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis.

PubMed

Hartin, Samantha N; Hudson, Martin L; Yingling, Curtis; Ackley, Brian D

2015-01-01

The C. elegans proteins PTP-3/LAR-RPTP and SDN-1/Syndecan are conserved cell adhesion molecules. Loss-of-function (LOF) mutations in either ptp-3 or sdn-1 result in low penetrance embryonic developmental defects. Work from other systems has shown that syndecans can function as ligands for LAR receptors in vivo. We used double mutant analysis to test whether ptp-3 and sdn-1 function in a linear genetic pathway during C. elegans embryogenesis. We found animals with LOF in both sdn-1 and ptp-3 exhibited a highly penetrant synthetic lethality (SynLet), with only a small percentage of animals surviving to adulthood. Analysis of the survivors demonstrated that these animals had a synergistic increase in the penetrance of embryonic developmental defects. Together, these data strongly suggested PTP-3 and SDN-1 function in parallel during embryogenesis. We subsequently used RNAi to knockdown ~3,600 genes predicted to encode secreted and/or transmembrane molecules to identify genes that interacted with ptp-3 or sdn-1. We found that the Wnt ligand, lin-44, was SynLet with sdn-1, but not ptp-3. We used 4-dimensional time-lapse analysis to characterize the interaction between lin-44 and sdn-1. We found evidence that loss of lin-44 caused defects in the polarization and migration of endodermal precursors during gastrulation, a previously undescribed role for lin-44 that is strongly enhanced by the loss of sdn-1. PTP-3 and SDN-1 function in compensatory pathways during C. elegans embryonic and larval development, as simultaneous loss of both genes has dire consequences for organismal survival. The Wnt ligand lin-44 contributes to the early stages of gastrulation in parallel to sdn-1, but in a genetic pathway with ptp-3. Overall, the SynLet phenotype provides a robust platform to identify ptp-3 and sdn-1 interacting genes, as well as other genes that function in development, yet might be missed in traditional forward genetic screens.

A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis

PubMed Central

Hartin, Samantha N.; Hudson, Martin L.; Yingling, Curtis; Ackley, Brian D.

2015-01-01

Background The C. elegans proteins PTP-3/LAR-RPTP and SDN-1/Syndecan are conserved cell adhesion molecules. Loss-of-function (LOF) mutations in either ptp-3 or sdn-1 result in low penetrance embryonic developmental defects. Work from other systems has shown that syndecans can function as ligands for LAR receptors in vivo. We used double mutant analysis to test whether ptp-3 and sdn-1 function in a linear genetic pathway during C. elegans embryogenesis. Results We found animals with LOF in both sdn-1 and ptp-3 exhibited a highly penetrant synthetic lethality (SynLet), with only a small percentage of animals surviving to adulthood. Analysis of the survivors demonstrated that these animals had a synergistic increase in the penetrance of embryonic developmental defects. Together, these data strongly suggested PTP-3 and SDN-1 function in parallel during embryogenesis. We subsequently used RNAi to knockdown ~3,600 genes predicted to encode secreted and/or transmembrane molecules to identify genes that interacted with ptp-3 or sdn-1. We found that the Wnt ligand, lin-44, was SynLet with sdn-1, but not ptp-3. We used 4-dimensional time-lapse analysis to characterize the interaction between lin-44 and sdn-1. We found evidence that loss of lin-44 caused defects in the polarization and migration of endodermal precursors during gastrulation, a previously undescribed role for lin-44 that is strongly enhanced by the loss of sdn-1. Conclusions PTP-3 and SDN-1 function in compensatory pathways during C. elegans embryonic and larval development, as simultaneous loss of both genes has dire consequences for organismal survival. The Wnt ligand lin-44 contributes to the early stages of gastrulation in parallel to sdn-1, but in a genetic pathway with ptp-3. Overall, the SynLet phenotype provides a robust platform to identify ptp-3 and sdn-1 interacting genes, as well as other genes that function in development, yet might be missed in traditional forward genetic screens. PMID:25938228

Caenorhabditis elegans syndecan (SDN-1) is required for normal egg laying and associates with the nervous system and the vulva.

PubMed

Minniti, Alicia N; Labarca, Mariana; Hurtado, Claudia; Brandan, Enrique

2004-10-01

In Caenorhabditis elegans, the identification of many enzymes involved in the synthesis and modification of glycosaminoglycans (GAGs), essential components of proteoglycans, has attained special attention in recent years. Mutations in all the genes that encode for GAG biosynthetic enzymes show defects in the development of the vulva, specifically in the invagination of the vulval epithelium. Mutants for certain heparan sulfate modifying enzymes present axonal and cellular guidance defects in specific neuronal classes. Although most of the enzymes involved in the biosynthesis and modification of heparan sulfate have been characterized in C. elegans, little is known regarding the core proteins to which these GAGs covalently bind in proteoglycans. A single syndecan homologue (sdn-1) has been identified in the C. elegans genome through sequence analysis. In the present study, we show that C. elegans synthesizes sulfated proteoglycans, seen as three distinct species in western blot analysis. In the sdn-1 (ok449) deletion mutant allele we observed the lack of one species, which corresponds to a 50 kDa product after heparitinase treatment. The expression of sdn-1 mRNA and sequencing revealed that sdn-1 (ok449) deletion mutants lack two glycosylation sites. Hence, the missing protein in the western blot analysis probably corresponds to SDN-1. In addition, we show that SDN-1 localizes to the C. elegans nerve ring, nerve cords and to the vulva. SDN-1 is found specifically phosphorylated in nerve ring neurons and in the vulva, in both wild-type worms and sdn-1 (ok449) deletion mutants. These mutants show a defective egg-laying phenotype. Our results show for the first time, the identification, localization and some functional aspects of syndecan in the nematode C. elegans.

Pleiotrophin, a target of miR-384, promotes proliferation, metastasis and lipogenesis in HBV-related hepatocellular carcinoma.

PubMed

Bai, Pei-Song; Xia, Nan; Sun, Hong; Kong, Ying

2017-11-01

Hepatitis B virus (HBV) infection plays a crucial role and is a major cause of hepatocellular carcinoma (HCC) in China. microRNAs (miRNAs) have emerged as key players in hepatic steatosis and carcinogenesis. We found that down-regulation of miR-384 expression was a common event in HCC, especially HBV-related HCC. However, the possible function of miR-384 in HBV-related HCC remains unclear. The oncogene pleiotrophin (PTN) was a target of miR-384. HBx inhibited miR-384, increasing PTN expression. The PTN receptor N-syndecan was highly expressed in HCC. PTN induced by HBx acted as a growth factor via N-syndecan on hepatocytes and further promoted cell proliferation, metastasis and lipogenesis. PTN up-regulated sterol regulatory element-binding protein 1c (SREBP-1c) through the N-syndecan/PI3K/Akt/mTORC1 pathway and the expression of lipogenic genes, including fatty acid synthesis (FAS). PTN-mediated de novo lipid synthesis played an important role in HCC proliferation and metastasis. PI3K/AKT and an mTORC1 inhibitor diminished PTN-induced proliferation, metastasis and lipogenesis. Taken together, these data strongly suggest that the dysregulation of miR-384 could play a crucial role in HBV related to HCC, and the target gene of miR-384, PTN, represents a new potential therapeutic target for the prevention of hepatic steatosis and further progression to HCC after chronic HBV infection. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1

PubMed Central

Sgaramella, N; Coates, P J; Strindlund, K; Loljung, L; Colella, G; Laurell, G; Rossiello, R; Muzio, L L; Loizou, C; Tartaro, G; Olofsson, K; Danielsson, K; Fåhraeus, R; Nylander, K

2015-01-01

Background: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. Methods: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. Results: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. Conclusion: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged ⩽40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair. PMID:26057450

Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1

PubMed Central

Mao, Yang; Resende, Mafalda; Daugaard, Mads; Riis Kristensen, Anders; Damm, Peter; G. Theander, Thor; R. Hansson, Stefan; Salanti, Ali

2016-01-01

During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells. PMID:27556547

Syndecan-1 knockdown inhibits glioma cell proliferation and invasion by deregulating a c-src/FAK-associated signaling pathway.

PubMed

Shi, Shuang; Zhong, Dong; Xiao, Yao; Wang, Bing; Wang, Wentao; Zhang, Fu'an; Huang, Haoyang

2017-06-20

Recent studies have shown that increased syndecan-1 (SDC1) expression in human glioma is associated with higher tumor grades and poor prognoses, but its oncogenic functions and the underlying molecular mechanisms remain unknown. Here, we examined SDC1 expression in datasets from The Cancer Genome Atlas and the National Center for Biotechnology Information Gene Expression Omnibus. Elevated SDC1 expression in glioma was closely associated with increases in tumor progression and shorter survival. We also examined SDC1 expression and evaluated the effects of stable SDC1 knockdown in glioma cell lines. SDC1 knockdown attenuated proliferation and invasion by glioma cells and markedly decreased PCNA and MMP-9 mRNA and protein expression. In a xenograft model, SDC1 knockdown suppressed the tumorigenic effects of U87 cells in vivo. SDC1 knockdown decreased phosphorylation of the c-src/FAK complex and its downstream signaling molecules, Erk, Akt and p38 MAPK. These results suggest that SDC1 may be a novel therapeutic target in the treatment of glioma.

SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration.

PubMed

Sundararajan, Lakshmi; Norris, Megan L; Lundquist, Erik A

2015-05-28

The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration. Copyright © 2015 Sundararajan et al.

SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration

PubMed Central

Sundararajan, Lakshmi; Norris, Megan L.; Lundquist, Erik A.

2015-01-01

The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration. PMID:26022293

Matrix metalloproteinase 9-mediated shedding of syndecan 4 in response to tumor necrosis factor α: a contributor to endothelial cell glycocalyx dysfunction.

PubMed

Ramnath, Raina; Foster, Rebecca R; Qiu, Yan; Cope, George; Butler, Matthew J; Salmon, Andrew H; Mathieson, Peter W; Coward, Richard J; Welsh, Gavin I; Satchell, Simon C

2014-11-01

The endothelial surface glycocalyx is a hydrated mesh in which proteoglycans are prominent. It is damaged in diseases associated with elevated levels of tumor necrosis factor α (TNF-α). We investigated the mechanism of TNF-α-induced disruption of the glomerular endothelial glycocalyx. We used conditionally immortalized human glomerular endothelial cells (GEnCs), quantitative PCR arrays, Western blotting, immunoprecipitation, immunofluorescence, and dot blots to examine the effects of TNF-α. TNF-α induced syndecan 4 (SDC4) mRNA up-regulation by 2.5-fold, whereas cell surface SDC4 and heparan sulfate (HS) were reduced by 36 and 30%, respectively, and SDC4 and sulfated glycosaminoglycan in the culture medium were increased by 52 and 65%, respectively, indicating TNF-α-induced shedding. Small interfering (siRNA) knockdown of SDC4 (by 52%) caused a corresponding loss of cell surface HS of similar magnitude (38%), and immunoprecipitation demonstrated that SDC4 and HS are shed as intact proteoglycan ectodomains. All of the effects of TNF-α on SDC4 and HS were abrogated by the metalloproteinase (MMP) inhibitor batimastat. Also abrogated was the associated 37% increase in albumin passage across GEnC monolayers. Specific MMP9 knockdown by siRNA similarly blocked TNF-α effects. SDC4 is the predominant HS proteoglycan in the GEnC glycocalyx. TNF-α-induced MMP9-mediated shedding of SDC4 is likely to contribute to the endothelial glycocalyx disruption observed in diabetes and inflammatory states. © FASEB.

Effect of unfractionated heparin on endothelial glycocalyx in a septic shock model.

PubMed

Yini, S; Heng, Z; Xin, A; Xiaochun, M

2015-02-01

The constituents of vascular endothelial glycocalyx, such as syndecan-1 and heparan sulphate (HS), can be detected in the plasma of patients and animals with septic shock. However, the dynamics of glycocalyx degradation and its association with inflammation remains largely unknown. In this study, we investigated the association between the biomarkers of acute endothelial glycocalyx degradation and inflammatory factors. We also evaluated the effect of unfractionated heparin (UFH) on glycocalyx shedding in a canine septic shock model. Twenty adult beagle dogs were randomly allocated to one of the following four groups (n = 5): (1) a sham group; (2) a shock group [3.5 × 10(8) colony-forming unit (cfu) Escherichia coli (E. coli)/kg]; (3) a basic therapy group (sensitive antibiotics and 0.9% saline, 10 ml/kg/h); and (4) a heparin group (40 units/kg/h UFH plus basic therapy). After the onset of septic shock, systemic haemodynamic indices were measured. Endothelial glycocalyx degradation markers (i.e., syndecan-1, HS) and inflammatory factors [i.e., interleukin 6 (IL-6), tumour necrosis factor (TNF)-α], platelet count and activated partial thromboplastin time were measured at various time points. A lethal dose of E. coli induced a progressive septic shock model. We observed increased syndecan-1 and HS levels, which correlated with IL-6 and TNF-α in the septic shock model. The glycocalyx shedding was reduced by UFH, which might be regulated by the inhibition of inflammatory factors. A therapeutic dose of UFH can protect glycocalyx from shedding by inhibiting inflammation. Additional studies with larger sample sizes are needed to confirm our conclusions. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Alterations in Corneal Sensory Nerves During Homeostasis, Aging, and After Injury in Mice Lacking the Heparan Sulfate Proteoglycan Syndecan-1.

PubMed

Pal-Ghosh, Sonali; Tadvalkar, Gauri; Stepp, Mary Ann

2017-10-01

To determine the impact of the loss of syndecan 1 (SDC1) on intraepithelial corneal nerves (ICNs) during homeostasis, aging, and in response to 1.5-mm trephine and debridement injury. Whole-mount corneas are used to quantify ICN density and thickness over time after birth and in response to injury in SDC1-null and wild-type (WT) mice. High-resolution three-dimensional imaging is used to visualize intraepithelial nerve terminals (INTs), axon fragments, and lysosomes in corneal epithelial cells using antibodies against growth associated protein 43 (GAP43), βIII tubulin, and LAMP1. Quantitative PCR was performed to quantify expression of SDC1, SDC2, SDC3, and SDC4 in corneal epithelial mRNA. Phagocytosis was assessed by quantifying internalization of fluorescently labeled 1-μm latex beads. Intraepithelial corneal nerves innervate the corneas of SDC1-null mice more slowly. At 8 weeks, ICN density is less but thickness is greater. Apically projecting intraepithelial nerve terminals and lysosome-associated membrane glycoprotein 1 (LAMP1) are also reduced in unwounded SDC1-null corneas. Quantitative PCR and immunofluorescence studies show that SDC3 expression and localization are increased in SDC1-null ICNs. Wild-type and SDC1-null corneas lose ICN density and thickness as they age. Recovery of axon density and thickness after trephine but not debridement wounds is slower in SDC1-null corneas compared with WT. Experiments assessing phagocytosis show reduced bead internalization by SDC1-null epithelial cells. Syndecan-1 deficiency alters ICN morphology and homeostasis during aging, reduces epithelial phagocytosis, and impairs reinnervation after trephine but not debridement injury. These data provide insight into the mechanisms used by sensory nerves to reinnervate after injury.

Overexpression of syndecan-1, MUC-1, and putative stem cell markers in breast cancer leptomeningeal metastasis: a cerebrospinal fluid flow cytometry study.

PubMed

Cordone, Iole; Masi, Serena; Summa, Valentina; Carosi, Mariantonia; Vidiri, Antonello; Fabi, Alessandra; Pasquale, Alessia; Conti, Laura; Rosito, Immacolata; Carapella, Carmine Maria; Villani, Veronica; Pace, Andrea

2017-04-11

Cancer is a mosaic of tumor cell subpopulations, where only a minority is responsible for disease recurrence and cancer invasiveness. We focused on one of the most aggressive circulating tumor cells (CTCs) which, from the primitive tumor, spreads to the central nervous system (CNS), evaluating the expression of prognostic and putative cancer stem cell markers in breast cancer (BC) leptomeningeal metastasis (LM). Flow cytometry immunophenotypic analysis of cerebrospinal fluid (CSF) samples (4.5 ml) was performed in 13 consecutive cases of BCLM. Syndecan-1 (CD138), MUC-1 (CD227) CD45, CD34, and the putative cancer stem cell markers CD15, CD24, CD44, and CD133 surface expression were evaluated on CSF floating tumor cells. The tumor-associated leukocyte population was also characterized. Despite a low absolute cell number (8 cell/μl, range 1-86), the flow cytometry characterization was successfully conducted in all the samples. Syndecan-1 and MUC-1 overexpression was documented on BC cells in all the samples analyzed; CD44, CD24, CD15, and CD133 in 77%, 75%, 70%, and 45% of cases, respectively. A strong syndecan-1 and MUC-1 expression was also documented by immunohistochemistry on primary breast cancer tissues, performed in four patients. The CSF tumor population was flanked by T lymphocytes, with a different immunophenotype between the CSF and peripheral blood samples (P ≤ 0.02). Flow cytometry can be successfully employed for solid tumor LM characterization even in CSF samples with low cell count. This in vivo study documents that CSF floating BC cells overexpress prognostic and putative cancer stem cell biomarkers related to tumor invasiveness, potentially representing a molecular target for circulating tumor cell detection and LM treatment monitoring, as well as a primary target for innovative treatment strategies. The T lymphocyte infiltration, documented in all CSF samples, suggests a possible involvement of the CNS lymphatic system in both lymphoid and cancer cell migration into and out of the meninges, supporting the extension of a new form of cellular immunotherapy to LM. Due to the small number of cases, validation on large cohorts of patients are warranted to confirm these findings and to evaluate the impact and value of these results for diagnosis and management of LM.

Impact of Different Tidal Volume Levels at Low Mechanical Power on Ventilator-Induced Lung Injury in Rats.

PubMed

Moraes, Lillian; Silva, Pedro L; Thompson, Alessandra; Santos, Cintia L; Santos, Raquel S; Fernandes, Marcos V S; Morales, Marcelo M; Martins, Vanessa; Capelozzi, Vera L; de Abreu, Marcelo G; Pelosi, Paolo; Rocco, Patricia R M

2018-01-01

Tidal volume (V T ) has been considered the main determinant of ventilator-induced lung injury (VILI). Recently, experimental studies have suggested that mechanical power transferred from the ventilator to the lungs is the promoter of VILI. We hypothesized that, as long as mechanical power is kept below a safe threshold, high V T should not be injurious. The present study aimed to investigate the impact of different V T levels and respiratory rates (RR) on lung function, diffuse alveolar damage (DAD), alveolar ultrastructure, and expression of genes related to inflammation [interleukin (IL)-6], alveolar stretch (amphiregulin), epithelial [club cell secretory protein (CC)16] and endothelial [intercellular adhesion molecule (ICAM)-1] cell injury, and extracellular matrix damage [syndecan-1, decorin, and metalloproteinase (MMP)-9] in experimental acute respiratory distress syndrome (ARDS) under low-power mechanical ventilation. Twenty-eight Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 21 animals were randomly assigned to ventilation (2 h) with low mechanical power at three different V T levels ( n = 7/group): (1) V T = 6 mL/kg and RR adjusted to normocapnia; (2) V T = 13 mL/kg; and 3) V T = 22 mL/kg. In the second and third groups, RR was adjusted to yield low mechanical power comparable to that of the first group. Mechanical power was calculated as [(Δ[Formula: see text]/Est, L )/2]× RR (ΔP, L = transpulmonary driving pressure, Est, L = static lung elastance). Seven rats were not mechanically ventilated (NV) and were used for molecular biology analysis. Mechanical power was comparable among groups, while V T gradually increased. ΔP, L and mechanical energy were higher in V T = 22 mL/kg than V T = 6 mL/kg and V T = 13 mL/kg ( p < 0.001 for both). Accordingly, DAD score increased in V T = 22 mL/kg compared to V T = 6 mL/kg and V T = 13 mL/kg [23(18.5-24.75) vs. 16(12-17.75) and 16(13.25-18), p < 0.05, respectively]. V T = 22 mL/kg was associated with higher IL-6, amphiregulin, CC16, MMP-9, and syndecan-1 mRNA expression and lower decorin expression than V T = 6 mL/kg. Multiple linear regression analyses indicated that V T was able to predict changes in IL-6 and CC16, whereas ΔP, L predicted pHa, oxygenation, amphiregulin, and syndecan-1 expression. In the model of ARDS used herein, even at low mechanical power, high V T resulted in VILI. V T control seems to be more important than RR control to mitigate VILI.

ß3 integrin modulates transforming growth factor beta induced (TGFBI) function and paclitaxel response in ovarian cancer cells.

PubMed

Tumbarello, David A; Temple, Jillian; Brenton, James D

2012-05-28

The extracellular matrix (ECM) has a key role in facilitating the progression of ovarian cancer and we have shown recently that the secreted ECM protein TGFBI modulates the response of ovarian cancer to paclitaxel-induced cell death. We have determined TGFBI signaling from the extracellular environment is preferential for the cell surface αvß3 integrin heterodimer, in contrast to periostin, a TGFBI paralogue, which signals primarily via a ß1 integrin-mediated pathway. We demonstrate that suppression of ß1 integrin expression, in ß3 integrin-expressing ovarian cancer cells, increases adhesion to rTGFBI. In addition, Syndecan-1 and -4 expression is dispensable for adhesion to rTGFBI and loss of Syndecan-1 cooperates with the loss of ß1 integrin to further enhance adhesion to rTGFBI. The RGD motif present in the carboxy-terminus of TGFBI is necessary, but not sufficient, for SKOV3 cell adhesion and is dispensable for adhesion of ovarian cancer cells lacking ß3 integrin expression. In contrast to TGFBI, the carboxy-terminus of periostin, lacking a RGD motif, is unable to support adhesion of ovarian cancer cells. Suppression of ß3 integrin in SKOV3 cells increases resistance to paclitaxel-induced cell death while suppression of ß1 integrin has no effect. Furthermore, suppression of TGFBI expression stimulates a paclitaxel resistant phenotype while suppression of fibronectin expression, which primarily signals through a ß1 integrin-mediated pathway, increases paclitaxel sensitivity. Therefore, different ECM components use distinct signaling mechanisms in ovarian cancer cells and in particular, TGFBI preferentially interacts through a ß3 integrin receptor mediated mechanism to regulate the response of cells to paclitaxel-induced cell death.

Effect of 21-day head down bed rest on urine proteins related to endothelium: Correlations with changes in carbohydrate metabolism

NASA Astrophysics Data System (ADS)

Kashirina, D.; Pastushkova, L.; Custaud, M. A.; Dobrokhotov, I.; Brzhozovsky, A.; Navasiolava, N.; Nosovsky, A.; Kononikhin, A.; Nikolaev, E.; Larina, I.

2017-08-01

We performed liquid chromatography-mass spectrometric study of the urine proteome in 8 healthy volunteers aged between 20 and 44 y.o. who have completed 21-day head-down bed rest. ANDSystem software which builds associative networks was used to identify the urinary proteins functionally related to the endothelium. We identified 7 endothelium-related biological processes, directly linked to 13 urine proteins. We performed manual annotation of the proteins which were the most important in terms of endothelial functions. Analysis of the correlations with biochemical variables revealed a positive correlation between fasting blood glucose and the following urine proteins: albumin, CD44 antigen, endothelial protein C receptor, mucin-1, osteopontin, receptor tyrosine kinase. As well, we found a positive correlation between HOMA-insulin resistance index and the following urine proteins: endothelial protein C receptor and syndecan-4. These results might suggest the involvement of above-mentioned proteins in glucose metabolism and their participation in the response to changes in blood glucose level.

Syndecan-4 shedding impairs macrovascular angiogenesis in diabetes mellitus

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

Li, Ran; Xie, Jun; Wu, Han

Purpose: Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan cell surface receptor that modulates cell proliferation, migration, mechanotransduction, and endocytosis. The extracellular domain of synd4 sheds heavily in acute inflammation, but the shedding of synd4 in chronic inflammation, such as diabetes mellitus (DM), is still undefined. We investigated the alterations of synd4 endothelial expression in DM and the influence of impaired synd4 signaling on angiogenesis in human umbilical vein endothelial cells (HUVECs), diabetic rats, synd4 null mice, and db/db mice. Material and methods: HUVECs were incubated with advanced glycation end products (AGEs). Western blot analysis was used to determine synd4more » protein expression and ELISA was used to detect soluble synd4 fragments. The concentration of synd4 in the aortic endothelia of diabetic rats was detected by immunohistochemical staining. Aortic ring assays were performed to study the process of angiogenesis in the diabetic rats and in synd4 null and db/db mice. Recombinant adenoviruses containing the synd4 gene or null were constructed to enhance synd4 aortic expression in db/db mice. Results: Western blot analysis showed decreased expression of the synd4 extracellular domain in HUVECs, and ELISA detected increased soluble fragments of synd4 in the media. Synd4 endothelial expression in the aortas of diabetic rats was decreased. Aortic ring assay indicated impaired angiogenesis in synd4 null and db/db mice, which was partially reversed by synd4 overexpression in db/db mice. Conclusion: Synd4 shedding from vascular endothelial cells played an important role in the diabetes-related impairment of angiogenesis. -- Highlights: •Synd4 shedding from endothelial cells is accelerated under the stimulation of AGEs. •Extracellular domain of synd4 is diminished in the endothelium of DM rats. •Aortic rings of synd4 null mice showed impaired angiogenesis. •Overexpression of synd4 partly rescues macrovascular angiogenesis in db/db mice.« less

Effect of gonadectomy on AgRP-induced weight gain in rats.

PubMed

Goodin, Sean Z; Kiechler, Alicia R; Keichler, Alicia R; Smith, Marissa; Wendt, Donna; Strader, April D

2008-12-01

Agouti-related peptide (AgRP), the endogenous antagonist to the melanocortin 3 and 4 receptors, elicits robust hyperphagia and weight gain in rodents when administered directly into the central nervous system. The relative influence of AgRP to cause weight gain in rodents partially depends on the activity level of the melanocortin agonist-producing proopiomelanocortin neurons. Both proopiomelanocortin and AgRP neurons within the arcuate nucleus receive energy storage information from circulating peripheral signals such as leptin and insulin. Another modulator of AgRP activity includes the cell surface molecule syndecan-3. Because leptin and insulin affect food intake in a sexually dimorphic way in rodents and syndecan-3-deficient mice regulate adiposity levels through distinct physiological mechanisms, we hypothesized that AgRP-induced weight gain would also be sexually dimorphic in rats. In the present study, the behavioral and physiological effects of centrally-administered AgRP in male and female were investigated. In male rats, AgRP (1 nmol) induced 5 days (P < 0.0001) of significantly elevated feeding compared with vehicle-treated controls, while females displayed 3 days of hyperphagia (P < 0.05). However, 1 wk after the injection, both male and female rats gained the same percent body weight (6%). Interestingly, female rats exhibited a greater reduction in energy expenditure (Vo2) following AgRP compared with male rats (P < 0.05). Removal of the gonads did not alter cumulative food intake in male or female rats but did attenuate the dramatic reduction in Vo2 exhibited by females. Both intact and gonadectomized rats demonstrated significantly increased respiratory quotient supporting the anabolic action of AgRP (P < 0.01). These findings are novel in that they reveal sex-specific underlying physiology used to achieve weight gain following central AgRP in rats.

Enhanced anorexigenic signaling in lean obesity resistant syndecan-3 null mice

PubMed Central

Zheng, Qiao; Zhu, Jinling; Shanabrough, Marya; Borok, Erzsebet; Benoit, Stephen C.; Horvath, Tamas L.; Clegg, Deborah J.; Reizes, Ofer

2010-01-01

Obesity is associated with increased risk of diabetes, cardiovascular disease and several types of cancers. The hypothalamus is a region of the brain critical in the regulation of body weight. One of the critical and best studied hypothalamic circuits is comprised of the melanocortinergic orexigenic agouti -related protein (AgRP) and anorexigenic α-melanocyte stimulating hormone (α-MSH) neurons. These neurons project axons to the same hypothalamic target neurons and balance each other’s activity leading to body weight regulation. We previously showed that the brain proteoglycan syndecan-3 regulates feeding behavior and body weight, and syndecan-3 null (SDC-3−/−) mice are lean and obesity resistant. Here we show that the melanocortin agonist MTII potently suppresses food intake and activates the hypothalamic paraventricular nuclei (PVN) in SDC-3−/− mice based on c-fos immunoreactivity. Interestingly, we determined that the AgRP neuropeptide is reduced in the PVN of SDC-3−/− mice compared to wild type mice. In contrast, neuropeptide Y, coexpressed in the AgRP neuron, is not differentially expressed nor is the counteracting neuropeptide αMSH. These findings are unprecedented and indicate that AgRP protein localization can be selectively regulated within the hypothalamus resulting in altered neuropeptide response and tone. PMID:20923696

Combinatorial Roles of Heparan Sulfate Proteoglycans and Heparan Sulfates in Caenorhabditis elegans Neural Development

PubMed Central

Kinnunen, Tarja K.

2014-01-01

Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and adult physiology of all metazoan organisms. Most of the known molecular interactions of HSPGs are attributed to the structurally highly complex heparan sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan) contains HS modifications that differ from another HSPG (such as glypican) has remained largely unresolved. Here, a neural model in C. elegans is used to demonstrate for the first time the relationship between specific HSPGs and HS modifications in a defined biological process in vivo. HSPGs are critical for the migration of hermaphrodite specific neurons (HSNs) as genetic elimination of multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the migrating neuron and in the matrix, act in parallel to support neuron migration. Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6, function in a linear signaling pathway and glypican/lon-2 and HS 2-O-sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1 and hst-6. These results suggest core protein specific HS modifications that are critical for HSN migration. In C. elegans, the core protein specificity of distinct HS modifications may be in part regulated at the level of tissue specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic analysis reveals that there is a delicate balance of HS modifications and eliminating one HS modifying enzyme in a compromised genetic background leads to significant changes in the overall phenotype. These findings are of importance with the view of HS as a critical regulator of cell signaling in normal development and disease. PMID:25054285

Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

PubMed

Lehnert, Per; Johansson, Pär I; Ostrowski, Sisse R; Møller, Christian H; Bang, Lia E; Olsen, Peter Skov; Carlsen, Jørn

2017-02-01

Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

OPG/membranous--RANKL complex is internalized via the clathrin pathway before a lysosomal and a proteasomal degradation.

PubMed

Tat, Steeve Kwan; Padrines, Marc; Theoleyre, Sandrine; Couillaud-Battaglia, Severine; Heymann, Dominique; Redini, Françoise; Fortun, Yannick

2006-10-01

The members of the OPG/RANK/RANKL (osteoprotegerin/receptor activator of nuclear factor kappaB/RANK ligand) triad are involved in various osteolytic pathologies such as bone tumors. Although many studies described the use of OPG during the treatment of bone diseases, its bioavailability and the mechanism by which the cells control the extracellular OPG remains blurred. The present work uses a strongly RANKL expressing cellular model to assess the becoming and the bioavailability of exogenous OPG in the context of its interactions with RANKL. The human kidney cell line 293, which initially expresses neither OPG nor RANKL, was stably transfected by the full length of mouse transmembranous form of RANKL (293RL). When OPG is incubated with 293RL cells, the extracellular concentration of OPG was strongly decreased in a time-dependent manner. The OPG disappearance was not inhibited by the addition of several proteases inhibitors, thus excluding any extracellular protease degradation. Contrary to previous results obtained on myeloma cells, which strongly express syndecan-1, the OPG disappearance was unaffected by the use of an antibody against syndecan-1. However, this event was abolished by an antibody against RANKL. These results, not necessarily conflicting, could be in relation with the expression level of the receptors in the two cellular models. In this context, an internalization process was put forward. Confocal microscopy demonstrated via the clathrin pathway an internalization of OPG mediated by RANKL. After being internalized, OPG was then degraded by the proteasome and the lysosome. A similar internalization phenomenon was also observed in osteoblast cells expressing physiologically RANKL, thus validating our data observed on 293RL cells. Western blotting analysis revealed that the half-life of RANKL was greatly reduced in the presence of OPG, pointing out that OPG binding to RANKL induces an enhancement of the ligand internalization. By the light of these results, the inhibitory effect of OPG on bone resorption can be explained not only by a decoy receptor function, competitor inhibitor of the RANK/RANKL binding, but also by the modulation of the RANKL half-life induced by OPG. Reciprocally, this modulation contributes to reduce the bioavailability of OPG.

Genetic Variants in SDC3 Gene are Significantly Associated with Growth Traits in Two Chinese Beef Cattle Breeds.

PubMed

Huang, Yong-Zhen; Wang, Qin; Zhang, Chun-Lei; Fang, Xing-Tang; Song, En-Liang; Chen, Hong

2016-01-01

Identification of the genes and polymorphisms underlying quantitative traits, and understanding these genes and polymorphisms affect economic growth traits, are important for successful marker-assisted selection and more efficient management strategies in commercial cattle (Bos taurus) population. Syndecan-3 (SDC3), a member of the syndecan family of type I transmembrane heparan sulfate proteoglycans is a novel regulator of feeding behavior and body weight. The aim of this study is to examine the association of the SDC3 polymorphism with growth traits in Chinese Jiaxian and Qinchuan cattle breeds (). Four single nucleotide polymorphisms (SNPs: 1-4) were detected in 555 cows from three Chinese native cattle breeds by means of sequencing pooled DNA samples and polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) methods. We found one SNP (g.28362A > G) in intron and three SNPs (g.30742T > G, g.30821C > T and 33418 A > G) in exons. The statistical analyses indicated that these SNPs of SDC3 gene were associated with bovine body height, body length, chest circumference, and circumference of cannon bone (P < 0.05). The mutant-type variant was superior for growth traits; the heterozygote was associated with higher growth traits compared to wild-type homozygote. Our result confirms the polymorphisms in the SDC3 gene are associated with growth traits that may be used for marker-assisted selection in beef cattle breeding programs.

The Role of the Neurofibromin-Syndecan-CASK Complex in the Regulation of Synaptic Ras-MAPK Signaling and Dendritic Spine Plasticity

DTIC Science & Technology

2006-02-01

Morgan, K., Hasz, D. E., Mao, Z., and Largaespada, D. A. (2005). Nf1 gene inactivation in acute myeloid leukemia cells confers cytarabine resistance through MAPK and mTOR pathways. Leukemia. VII. Appendices: None

A Proteomic Approach to Characterize Protein Shedding

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

Ahram, Mamoun; Adkins, Joshua N.; Auberry, Deanna L.

2005-01-01

Shedding (i.e., proteolysis of ectodomains of membrane proteins) plays an important pathophysiological role. In order to study the feasibility of identifying shed proteins, we analyzed serum-free media of human mammary epithelial cells by mass spectrometry following induction of shedding by the phorbol ester, 4β-phorbol 12-myristate 13-acetate (PMA). Different means of sample preparation, including biotinylation of cell surface proteins, isolation of glycosylated proteins, and preparation of crude protein fraction, were carried out to develop the optimal method of sample processing. The collected proteins were digested with trypsin and analyzed by reversed-phase capillary liquid chromatography interfaced to an ion-trap mass spectrometer. Themore » resulting peptide spectra were interpreted using the program SEQUEST. Analyzing the sample containing the crude protein mixture without chemical modification or separation resulted in the greatest number of identifications, including putatively shed proteins. Overall, 93 membrane-associated proteins were identified including 57 that contain at least one transmembrane domain and 36 that indirectly associate with the extracellular surface of the plasma membrane. Of the 57 transmembrane proteins, 43 were identified by extracellular peptides providing strong evidence for them originating from regulated proteolysis or shedding processes. We combined results from the different experiments and used a peptide count method to estimate changes in protein abundance. Using this approach, we identified 2 proteins, syndecan-4 and hepatoma-derived growth factor, whose abundances increased in media of cells treated with PMA. We also detected proteins whose abundances decreased after PMA treatment such as 78-kDa glucose-regulated protein and calreticulin. Further analysis using immunoblotting validated the abundance changes for syndecan-4 and 78-kDa glucose-regulated protein as a result of PMA treatment. These results demonstrate that mass spectrometry can be used to identify low-abundance shed proteins and to estimate changes in protein abundances.« less

Binding of Y-P30 to Syndecan 2/3 Regulates the Nuclear Localization of CASK

PubMed Central

Landgraf, Peter; Mikhaylova, Marina; Macharadze, Tamar; Borutzki, Corinna; Zenclussen, Ana-Claudia; Wahle, Petra; Kreutz, Michael R.

2014-01-01

The survival promoting peptide Y-P30 has documented neuroprotective effects as well as cell survival and neurite outgrowth promoting activity in vitro and in vivo. Previous work has shown that multimerization of the peptide with pleiotrophin (PTN) and subsequent binding to syndecan (SDC) -2 and -3 is involved in its neuritogenic effects. In this study we show that Y-P30 application regulates the nuclear localization of the SDC binding partner Calcium/calmodulin-dependent serine kinase (CASK) in neuronal primary cultures during development. In early development at day in vitro (DIV) 8 when mainly SDC-3 is expressed supplementation of the culture medium with Y-P30 reduces nuclear CASK levels whereas it has the opposite effect at DIV 18 when SDC-2 is the dominant isoform. In the nucleus CASK regulates gene expression via its association with the T-box transcription factor T-brain-1 (Tbr-1) and we indeed found that gene expression of downstream targets of this complex, like the GluN2B NMDA-receptor, exhibits a corresponding down- or up-regulation at the mRNA level. The differential effect of Y-P30 on the nuclear localization of CASK correlates with its ability to induce shedding of the ectodomain of SDC-2 but not -3. shRNA knockdown of SDC-2 at DIV 18 and SDC-3 at DIV 8 completely abolished the effect of Y-P30 supplementation on nuclear CASK levels. During early development a protein knockdown of SDC-3 also attenuated the effect of Y-P30 on axon outgrowth. Taken together these data suggest that Y-P30 can control the nuclear localization of CASK in a SDC-dependent manner. PMID:24498267

Syndecan-1-Dependent Suppression of PDK1/Akt/Bad Signaling by Docosahexaenoic Acid Induces Apoptosis in Prostate Cancer1

PubMed Central

Hu, Yunping; Sun, Haiguo; Owens, Rick T; Gu, Zhennan; Wu, Jansheng; Chen, Yong Q; O'Flaherty, Joseph T; Edwards, Iris J

2010-01-01

Evidence indicates that diets enriched in n-3 polyunsaturated fatty acids (n-3 PUFAs) reduce the risk of prostate cancer, but biochemical mechanisms are unclear. Syndecan-1 (SDC-1), a transmembrane heparan sulfate proteoglycan, supports the integrity of the epithelial compartment. In tumor cells of epithelial lineage, SDC-1 is generally downregulated. This may result in perturbation of homeostasis and lead to progression of malignancy. Our studies have shown that the n-3 PUFA species, docosahexaenoic acid (DHA), increases SDC-1 expression in prostate tissues of Pten knockout (PtenP-/-) mice/cells and human prostate cancer cells. We have now determined that DHA-mediated up-regulation of SDC-1 induces apoptosis. Bovine serum albumin-bound DHA and exogenous human recombinant SDC-1 ecotodomain were delivered to PC3 and LNCaP cells in the presence or absence of SDC-1 small interfering (si)RNA. In the presence of control siRNA, both DHA and SDC-1 ectodomain induced apoptosis, whereas SDC-1 silencing blocked DHA-induced but not SDC-1 ectodomain-induced apoptosis. Downstream effectors of SDC-1 signaling linked to n-3 PUFA-induced apoptosis involved the 3′-phosphoinositide-dependent kinase 1 (PDK1)/Akt/Bad integrating network. A diet enriched in n-3 PUFA decreased phosphorylation of PDK1, Akt (T308), and Bad in prostates of PtenP-/- mice. Similar results were observed in human prostate cancer cells in response to DHA and SDC-1 ectodomain. The effect of DHA on PDK1/Akt/Bad signaling was abrogated by SDC-1 siRNA. These findings define a mechanism by which SDC-1-dependent suppression of phosphorylation of PDK1/Akt/Bad mediates n-3 PUFA-induced apoptosis in prostate cancer. PMID:20927321

A Simple PB/LIE Free Energy Function Accurately Predicts the Peptide Binding Specificity of the Tiam1 PDZ Domain.

PubMed

Panel, Nicolas; Sun, Young Joo; Fuentes, Ernesto J; Simonson, Thomas

2017-01-01

PDZ domains generally bind short amino acid sequences at the C-terminus of target proteins, and short peptides can be used as inhibitors or model ligands. Here, we used experimental binding assays and molecular dynamics simulations to characterize 51 complexes involving the Tiam1 PDZ domain and to test the performance of a semi-empirical free energy function. The free energy function combined a Poisson-Boltzmann (PB) continuum electrostatic term, a van der Waals interaction energy, and a surface area term. Each term was empirically weighted, giving a Linear Interaction Energy or "PB/LIE" free energy. The model yielded a mean unsigned deviation of 0.43 kcal/mol and a Pearson correlation of 0.64 between experimental and computed free energies, which was superior to a Null model that assumes all complexes have the same affinity. Analyses of the models support several experimental observations that indicate the orientation of the α 2 helix is a critical determinant for peptide specificity. The models were also used to predict binding free energies for nine new variants, corresponding to point mutants of the Syndecan1 and Caspr4 peptides. The predictions did not reveal improved binding; however, they suggest that an unnatural amino acid could be used to increase protease resistance and peptide lifetimes in vivo . The overall performance of the model should allow its use in the design of new PDZ ligands in the future.

A Simple PB/LIE Free Energy Function Accurately Predicts the Peptide Binding Specificity of the Tiam1 PDZ Domain

PubMed Central

Panel, Nicolas; Sun, Young Joo; Fuentes, Ernesto J.; Simonson, Thomas

2017-01-01

PDZ domains generally bind short amino acid sequences at the C-terminus of target proteins, and short peptides can be used as inhibitors or model ligands. Here, we used experimental binding assays and molecular dynamics simulations to characterize 51 complexes involving the Tiam1 PDZ domain and to test the performance of a semi-empirical free energy function. The free energy function combined a Poisson-Boltzmann (PB) continuum electrostatic term, a van der Waals interaction energy, and a surface area term. Each term was empirically weighted, giving a Linear Interaction Energy or “PB/LIE” free energy. The model yielded a mean unsigned deviation of 0.43 kcal/mol and a Pearson correlation of 0.64 between experimental and computed free energies, which was superior to a Null model that assumes all complexes have the same affinity. Analyses of the models support several experimental observations that indicate the orientation of the α2 helix is a critical determinant for peptide specificity. The models were also used to predict binding free energies for nine new variants, corresponding to point mutants of the Syndecan1 and Caspr4 peptides. The predictions did not reveal improved binding; however, they suggest that an unnatural amino acid could be used to increase protease resistance and peptide lifetimes in vivo. The overall performance of the model should allow its use in the design of new PDZ ligands in the future. PMID:29018806

Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway.

PubMed

Lee, Se-Jin; Huynh, Thanh V; Lee, Yun-Sil; Sebald, Suzanne M; Wilcox-Adelman, Sarah A; Iwamori, Naoki; Lepper, Christoph; Matzuk, Martin M; Fan, Chen-Ming

2012-08-28

Myostatin and activin A are structurally related secreted proteins that act to limit skeletal muscle growth. The cellular targets for myostatin and activin A in muscle and the role of satellite cells in mediating muscle hypertrophy induced by inhibition of this signaling pathway have not been fully elucidated. Here we show that myostatin/activin A inhibition can cause muscle hypertrophy in mice lacking either syndecan4 or Pax7, both of which are important for satellite cell function and development. Moreover, we show that muscle hypertrophy after pharmacological blockade of this pathway occurs without significant satellite cell proliferation and fusion to myofibers and without an increase in the number of myonuclei per myofiber. Finally, we show that genetic ablation of Acvr2b, which encodes a high-affinity receptor for myostatin and activin A specifically in myofibers is sufficient to induce muscle hypertrophy. All of these findings are consistent with satellite cells playing little or no role in myostatin/activin A signaling in vivo and render support that inhibition of this signaling pathway can be an effective therapeutic approach for increasing muscle growth even in disease settings characterized by satellite cell dysfunction.

The Multi-Biomarker Approach for Heart Failure in Patients with Hypertension

PubMed Central

Bielecka-Dabrowa, Agata; Gluba-Brzózka, Anna; Michalska-Kasiczak, Marta; Misztal, Małgorzata; Rysz, Jacek; Banach, Maciej

2015-01-01

We assessed the predictive ability of selected biomarkers using N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the incremental predictive value of the following biomarkers was investigated: Collagen III N-terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4, tumor necrosis factor-α (TNF-α), interleukin 1 receptor type I (IL1R1), galectin-3, cardiotrophin-1 (CT-1), transforming growth factor β (TGF-β) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest discriminative value for HF was observed for NT-proBNP (area under the receiver operating characteristic curve (AUC) = 0.873) and TGF-β (AUC = 0.878). On the basis of ROC curve analysis we found that CT-1 > 152 pg/mL, TGF-β < 7.7 ng/mL, syndecan > 2.3 ng/mL, NT-proBNP > 332.5 pg/mL, CysC > 1 mg/L and NGAL > 39.9 ng/mL were significant predictors of overt HF. There was only a small improvement in predictive ability of the multi-biomarker panel including the four biomarkers with the best performance in the detection of HF—NT-proBNP, TGF-β, CT-1, CysC—compared to the panel with NT-proBNP, TGF-β and CT-1 only. Biomarkers with different pathophysiological backgrounds (NT-proBNP, TGF-β, CT-1, CysC) give additive prognostic value for incident HF in hypertensive patients compared to NT-proBNP alone. PMID:25984599

Measurement of lipocalin-2 and syndecan-4 levels to differentiate bacterial from viral infection in children with community-acquired pneumonia.

PubMed

Esposito, Susanna; Bianchini, Sonia; Gambino, Monia; Madini, Barbara; Di Pietro, Giada; Umbrello, Giulia; Presicce, Maria Lory; Ruggiero, Luca; Terranova, Leonardo; Principi, Nicola

2016-07-20

In this study, we evaluated the lipocalin-2 (LIP2) and syndecan-4 (SYN4) levels in children who were hospitalized for radiologically confirmed CAP in order to differentiate bacterial from viral infection. The results regarding the LIP2 and SYN4 diagnostic outcomes were compared with the white blood cell (WBC) count and C reactive protein (CRP) levels. A total of 110 children <14 years old who were hospitalized for radiologically confirmed CAP were enrolled. Serum samples were obtained upon admission and on day 5 to measure the levels of LIP2, SYN4, and CRP as well as the WBC. Polymerase chain reaction of the respiratory secretions and tests on blood samples were performed to detect respiratory viruses, Streptococcus pneumoniae, and Mycoplasma pneumoniae. CAP was considered to be due to a probable bacterial infection in 74 children (67.3 %) and due to a probable viral infection in 16 children (14.5 %). Overall, 84 children (76.4 %) were diagnosed with severe CAP. The mean values of the WBC count and the LIP2 and SYN4 levels did not differ among the probable bacterial, probable viral, and undetermined cases. However, the CRP serum concentrations were significantly higher in children with probable bacterial CAP than in those with probable viral disease (32.2 ± 55.5 mg/L vs 9.4 ± 17.0 mg/L, p < 0.05). The WBC count was the best predictor of severe CAP, but the differences among the studied variables were marginal. The WBC count was significantly lower on day 5 in children with probable bacterial CAP (p < 0.01) and in those with an undetermined etiology (p < 0.01). The CRP and LIP2 levels were significantly lower 5 days after enrollment in all of the studied groups, independent of the supposed etiology of CAP (p < 0.01 for all comparisons). No statistically significant variation was observed for SYN4. Measuring the LIP2 and SYN4 levels does not appear to solve the problem of the poor reliability of routine laboratory tests in defining the etiology and severity of pediatric CAP. Currently, the CRP levels and WBC, when combined with evaluation of clinical data, can be used to limit the overuse of antibiotics as much as possible and to provide the best treatment to the patient.

Fibronectin regulates Wnt7a signaling and satellite cell expansion

PubMed Central

Bentzinger, C. Florian; Wang, Yu Xin; von Maltzahn, Julia; Soleimani, Vahab D.; Yin, Hang; Rudnicki, Michael A.

2012-01-01

SUMMARY The influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a co-receptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche by transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo over-expression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 co-receptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis. PMID:23290138

Regulation of cytokine signaling by B cell antigen receptor and CD40-controlled expression of heparan sulfate proteoglycans.

PubMed

van der Voort, R; Keehnen, R M; Beuling, E A; Spaargaren, M; Pals, S T

2000-10-16

Recently, biochemical, cell biological, and genetic studies have converged to reveal that integral membrane heparan sulfate proteoglycans (HSPGs) are critical regulators of growth and differentiation of epithelial and connective tissues. As a large number of cytokines involved in lymphoid tissue homeostasis or inflammation contain potential HS-binding domains, HSPGs presumably also play important roles in the regulation of the immune response. In this report, we explored the expression, regulation, and function of HSPGs on B lymphocytes. We demonstrate that activation of the B cell antigen receptor (BCR) and/or CD40 induces a strong transient expression of HSPGs on human tonsillar B cells. By means of these HSPGs, the activated B cells can bind hepatocyte growth factor (HGF), a cytokine that regulates integrin-mediated B cell adhesion and migration. This interaction with HGF is highly selective since the HSPGs did not bind the chemokine stromal cell-derived factor (SDF)-1 alpha, even though the affinities of HGF and SDF-1alpha for heparin are similar. On the activated B cells, we observed induction of a specific HSPG isoform of CD44 (CD44-HS), but not of other HSPGs such as syndecans or glypican-1. Interestingly, the expression of CD44-HS on B cells strongly promotes HGF-induced signaling, resulting in an HS-dependent enhanced phosphorylation of Met, the receptor tyrosine kinase for HGF, as well as downstream signaling molecules including Grb2-associated binder 1 (Gab1) and Akt/protein kinase B (PKB). Our results demonstrate that the BCR and CD40 control the expression of HSPGs, specifically CD44-HS. These HSPGs act as functional coreceptors that selectively promote cytokine signaling in B cells, suggesting a dynamic role for HSPGs in antigen-specific B cell differentiation.

Drosophila Neurexin IV Interacts with Roundabout and is Required for Repulsive Midline Axon Guidance

PubMed Central

Banerjee, Swati; Blauth, Kevin; Peters, Kimberly; Rogers, Stephen L.; Fanning, Alan S.; Bhat, Manzoor A.

2010-01-01

Slit/Roundabout (Robo) signaling controls midline repulsive axon guidance. However, proteins that interact with Slit/Robo at the cell surface remain largely uncharacterized. Here, we report that the Drosophila transmembrane septate junction-specific protein, Neurexin IV (Nrx IV), functions in midline repulsive axon guidance. Nrx IV is expressed in the neurons of the developing ventral nerve cord and nrx IV mutants show crossing and circling of ipsilateral axons and fused commissures. Interestingly, the axon guidance defects observed in nrx IV mutants seem independent of its other binding partners such as Contactin and Neuroglian and the midline glia protein Wrapper that interacts in trans with Nrx IV. nrx IV mutants show diffuse Robo localization and dose-dependent genetic interactions between nrx IV/robo and nrx IV/slit indicate that they function in a common pathway. In vivo biochemical studies reveal that Nrx IV associates with Robo, Slit and Syndecan, and interactions between Robo and Slit, or Nrx IV and Slit, are affected in nrx IV and robo mutants, respectively. Coexpression of Nrx IV and Robo in mammalian cells confirms that these proteins retain the ability to interact in a heterologous system. Furthermore, we demonstrate that the extracellular region of Nrx IV is sufficient to rescue Robo localization and axon guidance phenotypes in nrx IV mutants. Together our studies establish that Nrx IV is essential for proper Robo localization, and identify Nrx IV as a novel interacting partner of the Slit/Robo signaling pathway. PMID:20410118

Drosophila neurexin IV interacts with Roundabout and is required for repulsive midline axon guidance.

PubMed

Banerjee, Swati; Blauth, Kevin; Peters, Kimberly; Rogers, Stephen L; Fanning, Alan S; Bhat, Manzoor A

2010-04-21

Slit/Roundabout (Robo) signaling controls midline repulsive axon guidance. However, proteins that interact with Slit/Robo at the cell surface remain largely uncharacterized. Here, we report that the Drosophila transmembrane septate junction-specific protein Neurexin IV (Nrx IV) functions in midline repulsive axon guidance. Nrx IV is expressed in the neurons of the developing ventral nerve cord, and nrx IV mutants show crossing and circling of ipsilateral axons and fused commissures. Interestingly, the axon guidance defects observed in nrx IV mutants seem independent of its other binding partners, such as Contactin and Neuroglian and the midline glia protein Wrapper, which interacts in trans with Nrx IV. nrx IV mutants show diffuse Robo localization, and dose-dependent genetic interactions between nrx IV/robo and nrx IV/slit indicate that they function in a common pathway. In vivo biochemical studies reveal that Nrx IV associates with Robo, Slit, and Syndecan, and interactions between Robo and Slit, or Nrx IV and Slit, are affected in nrx IV and robo mutants, respectively. Coexpression of Nrx IV and Robo in mammalian cells confirms that these proteins retain the ability to interact in a heterologous system. Furthermore, we demonstrate that the extracellular region of Nrx IV is sufficient to rescue Robo localization and axon guidance phenotypes in nrx IV mutants. Together, our studies establish that Nrx IV is essential for proper Robo localization and identify Nrx IV as a novel interacting partner of the Slit/Robo signaling pathway.

Resuscitation with Pooled and Pathogen-Reduced Plasma Attenuates the Increase in Brain Water Content following Traumatic Brain Injury and Hemorrhagic Shock in Rats.

PubMed

Genét, Gustav Folmer; Bentzer, Peter; Ostrowski, Sisse Rye; Johansson, Pär Ingemar

2017-03-01

Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim of this study was to investigate whether pooled and pathogen-reduced plasma (OctaplasLG ® [OCTA]; Octapharma, Stockholm, Sweden) was comparable to FFP with regard to effects on brain water content, BBB permeability, and plasma biomarkers of endothelial glycocalyx shedding and cell damage. After fluid percussion brain injury, hemorrhage (20 mL/kg), and 90-min shock, 48 male Sprague-Dawley rats were randomized to resuscitation with OCTA, FFP, or NS (n = 16/group). Brain water content (wet/dry weight) and BBB permeability (transfer constant for 51 Cr-EDTA) were measured at 24 h. Plasma osmolality, oncotic pressure, and biomarkers of systemic glycocalyx shedding (syndecan-1) and cell damage (histone-complexed DNA) were measured at 0 and 23 h. At 24 h, brain water content was 80.44 ± 0.39%, 80.82 ± 0.82%, and 81.15 ± 0.86% in the OCTA, FFP, and NS groups (lower in OCTA vs. NS; p = 0.026), with no difference in BBB permeability. Plasma osmolality and oncotic pressures were highest in FFP and OCTA resuscitated, and osmolality was further highest in OCTA versus FFP (p = 0.027). In addition, syndecan-1 was highest in FFP and OCTA resuscitated (p = 0.010). These results suggest that pooled solvent-detergent (SD)-treated plasma attenuates the post-traumatic increase in brain water content, and that this effect may, in part, be explained by a high crystalloid and colloid osmotic pressure in SD-treated plasma.

Syndecan-1 knock-down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns

PubMed Central

2010-01-01

Background Successful embryonic implantation depends on a synchronized embryo-maternal dialogue. Chemokines, such as chemokine ligand 1 (CXCL1), play essential roles in the maternal reproductive tract leading to morphological changes during decidualization, mediating maternal acceptance towards the semi-allograft embryo and induction of angiogenesis. Chemokine binding to their classical G-protein coupled receptors is essentially supported by the syndecan (Sdc) family of heparan sulfate proteoglycans. The aim of this study was to identify the involvement of Sdc-1 at the embryo-maternal interface regarding changes of the chemokine and angiogenic profile of the decidua during the process of decidualization and implantation in human endometrium. Methods A stable Sdc-1 knock-down was generated in the immortalized human endometrial stromal cell line St-T1 and was named KdS1. The ability of KdS1 to decidualize was proven by Insulin-like growth factor binding 1 (IGFBP1) and prolactin (PRL) confirmation on mRNA level before further experiments were carried out. Dot blot protein analyses of decidualized knock-down cells vs non-transfected controls were performed. In order to imitate embryonic implantation, decidualized KdS1 were then incubated with IL-1beta, an embryo secretion product, vs controls. Statistical analyses were performed applying the Student's t-test with p < 0.05, p < 0.02 and p < 0.01 and one way post-hoc ANOVA test with p < 0.05 as cut-offs for statistical significance. Results The induction of the Sdc-1 knock-down revealed significant changes in cytokine and angiogenic factor expression profiles of dKdS1 vs decidualized controls. Incubation with embryonic IL-1beta altered the expression patterns of KdS1 chemokines and angiogenic factors towards inflammatory-associated molecules and factors involved in matrix regulation. Conclusions Sdc-1 knock-down in human endometrial stroma cells led to fulminant changes regarding cytokine and angiogenic factor expression profiles upon decidualization and imitation of embryonic contact. Sdc-1 appears to play an important role as a co-receptor and storage factor for many cytokines and angiogenic factors during decidualization and implantation period, supporting proper implantation and angiogenesis by regulation of chemokine and angiogenic factor secretion in favour of the implanting embryo. PMID:21044331

Xin, an actin binding protein, is expressed within muscle satellite cells and newly regenerated skeletal muscle fibers.

PubMed

Hawke, Thomas J; Atkinson, Daniel J; Kanatous, Shane B; Van der Ven, Peter F M; Goetsch, Sean C; Garry, Daniel J

2007-11-01

Xin is a muscle-specific actin binding protein of which its role and regulation within skeletal muscle is not well understood. Here we demonstrate that Xin mRNA is robustly upregulated (>16-fold) within 12 h of skeletal muscle injury and is localized to the muscle satellite cell population. RT-PCR confirmed the expression pattern of Xin during regeneration, as well as within primary muscle myoblast cultures, but not other known stem cell populations. Immunohistochemical staining of single myofibers demonstrate Xin expression colocalized with the satellite cell marker Syndecan-4 further supporting the mRNA expression of Xin in satellite cells. In situ hybridization of regenerating muscle 5-7 days postinjury illustrates Xin expression within newly regenerated myofibers. Promoter-reporter assays demonstrate that known myogenic transcription factors [myocyte enhancer factor-2 (MEF2), myogenic differentiation-1 (MyoD), and myogenic factor-5 (Myf-5)] transactivate Xin promoter constructs supporting the muscle-specific expression of Xin. To determine the role of Xin within muscle precursor cells, proliferation, migration, and differentiation analysis using Xin, short hairpin RNA (shRNA) were undertaken in C2C12 myoblasts. Reducing endogenous Xin expression resulted in a 26% increase (P < 0.05) in cell proliferation and a 20% increase (P < 0.05) in myoblast migratory capacity. Skeletal muscle myosin heavy chain protein levels were increased (P < 0.05) with Xin shRNA administration; however, this was not accompanied by changes in myoglobin protein (another marker of differentiation) nor overt morphological differences relative to differentiating control cells. Taken together, the present findings support the hypothesis that Xin is expressed within muscle satellite cells during skeletal muscle regeneration and is involved in the regulation of myoblast function.

Motoneurons secrete angiogenin to induce RNA cleavage in astroglia.

PubMed

Skorupa, Alexandra; King, Matthew A; Aparicio, Isabela M; Dussmann, Heiko; Coughlan, Karen; Breen, Bridget; Kieran, Dairin; Concannon, Caoimhin G; Marin, Philippe; Prehn, Jochen H M

2012-04-11

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder affecting motoneurons. Mutations in angiogenin, encoding a member of the pancreatic RNase A superfamily, segregate with ALS. We previously demonstrated that angiogenin administration shows promise as a neuroprotective therapeutic in studies using transgenic ALS mice and primary motoneuron cultures. Its mechanism of action and target cells in the spinal cord, however, are largely unknown. Using mixed motoneuron cultures, motoneuron-like NSC34 cells, and primary astroglia cultures as model systems, we here demonstrate that angiogenin is a neuronally secreted factor that is endocytosed by astroglia and mediates neuroprotection in paracrine. We show that wild-type angiogenin acts unidirectionally to induce RNA cleavage in astroglia, while the ALS-associated K40I mutant is also secreted and endocytosed, but fails to induce RNA cleavage. Angiogenin uptake into astroglia requires heparan sulfate proteoglycans, and engages clathrin-mediated endocytosis. We show that this uptake mechanism exists for mouse and human angiogenin, and delivers a functional RNase output. Moreover, we identify syndecan 4 as the angiogenin receptor mediating the selective uptake of angiogenin into astroglia. Our data provide new insights into the paracrine activities of angiogenin in the nervous system, and further highlight the critical role of non-neuronal cells in the pathogenesis of ALS.

Influence of chick hatch time and access to feed on broiler muscle development.

PubMed

Powell, D J; Velleman, S G; Cowieson, A J; Singh, M; Muir, W I

2016-06-01

The effect of hatch time and the timing of access to feed on growth rate and breast muscle development was assessed in Ross 308 broiler chickens. Chicks were removed from the incubator upon hatching, and classified as early (EH), midterm (MH), or late (LH) hatchers, based on the duration of their incubation. Feed and water were available either immediately at hatch, or 24 h after the conclusion of the hatch period. Hatchling body weight was uniform regardless of hatch time. Subsequently, bodyweight was increased in EH compared to LH birds following immediate access to feed, until 7 d in female, and 14 d in male birds. Relative breast weight was increased until 28 d in birds with immediate access to feed, and also EH and MH birds regardless of access to feed. Pectoralis major muscle morphology and expression of the myogenic regulatory factors myogenic determination factor 1 (MYOD1) and myogenin, and the proteoglycans syndecan-4, glypican-1, and decorin were measured. Myogenin and glypican-1 stimulate satellite cell (SC) differentiation. Glypican-1 expression was unaffected by treatment. A late increase in myogenin expression was observed in MH birds with delayed access to feed, and all LH birds. Syndecan-4 and MYOD1, expressed in proliferating SC, and decorin, which stimulates satellite cell proliferation and differentiation, were variably upregulated in the first wk posthatch in the same birds. These data suggest SC were activated and proliferating, but had reduced differentiation in later hatching and feed deprived birds. Conversely, EH birds with immediate access to feed had maximal myofiber width at 7 d, while fiber width was increased in birds with immediate access to feed compared to those with delayed access to feed through 40 d of age. These results demonstrate that delaying chick access to feed for 24 h upon removal from the incubator will impair muscle growth. Additionally, hatch time influences muscle development, with accelerated muscle growth in EH and MH, compared to LH birds, irrespective of access to feed. © 2016 Poultry Science Association Inc.

Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

PubMed

Fahlén, M; Zhang, H; Löfgren, L; Masironi, B; von Schoultz, E; von Schoultz, B; Sahlin, L

2017-05-01

Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

Syndecan-1 regulates adipogenesis: new insights in dedifferentiated liposarcoma tumorigenesis.

PubMed

Zaragosi, Laure-Emmanuelle; Dadone, Bérengère; Michiels, Jean-François; Marty, Marion; Pedeutour, Florence; Dani, Christian; Bianchini, Laurence

2015-01-01

Syndecan-1 (SDC1/CD138) is one of the main cell surface proteoglycans and is involved in crucial biological processes. Only a few studies have analyzed the role of SDC1 in mesenchymal tumor pathogenesis. In particular, its involvement in adipose tissue tumors has never been investigated. Dedifferentiated liposarcoma, one of the most frequent types of malignant adipose tumors, has a high potential of recurrence and metastastic evolution. Classical chemotherapy is inefficient in metastatic dedifferentiated liposarcoma and novel biological markers are needed for improving its treatment. In this study, we have analyzed the expression of SDC1 in well-differentiated/dedifferentiated liposarcomas and showed that SDC1 is highly overexpressed in dedifferentiated liposarcoma compared with normal adipose tissue and lipomas. Silencing of SDC1 in liposarcoma cells impaired cell viability and proliferation. Using the human multipotent adipose-derived stem cell model of human adipogenesis, we showed that SDC1 promotes proliferation of undifferentiated adipocyte progenitors and inhibits their adipogenic differentiation. Altogether, our results support the hypothesis that SDC1 might be involved in liposarcomagenesis. It might play a prominent role in the dedifferentiation process occurring when well-differentiated liposarcoma progress to dedifferentiated liposarcoma. Targeting SDC1 in these tumors might provide a novel therapeutic strategy. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

RKIP and HMGA2 regulate breast tumor survival and metastasis through lysyl oxidase and syndecan-2.

PubMed

Sun, M; Gomes, S; Chen, P; Frankenberger, C A; Sankarasharma, D; Chung, C H; Chada, K K; Rosner, M R

2014-07-03

Elucidating targets of physiological tumor metastasis suppressors can highlight key signaling pathways leading to invasion and metastasis. To identify downstream targets of the metastasis suppressor Raf-1 kinase inhibitory protein (RKIP/PEBP1), we utilized an integrated approach based upon statistical analysis of tumor gene expression data combined with experimental validation. Previous studies from our laboratory identified the architectural transcription factor and oncogene, high mobility group AT-hook 2 (HMGA2), as a target of inhibition by RKIP. Here we identify two signaling pathways that promote HMGA2-driven metastasis. Using both human breast tumor cells and an MMTV-Wnt mouse breast tumor model, we show that RKIP induces and HMGA2 inhibits expression of miR-200b; miR-200b directly inhibits expression of lysyl oxidase (LOX), leading to decreased invasion. RKIP also inhibits syndecan-2 (SDC2), which is aberrantly expressed in breast cancer, via downregulation of HMGA2; but this mechanism is independent of miR-200. Depletion of SDC2 induces apoptosis and suppresses breast tumor growth and metastasis in mouse xenografts. RKIP, LOX and SDC2 are coordinately regulated and collectively encompass a prognostic signature for metastasis-free survival in ER-negative breast cancer patients. Taken together, our findings reveal two novel signaling pathways targeted by the metastasis suppressor RKIP that regulate remodeling of the extracellular matrix and tumor survival.

ATP release due to Thy-1–integrin binding induces P2X7-mediated calcium entry required for focal adhesion formation

PubMed Central

Henríquez, Mauricio; Herrera-Molina, Rodrigo; Valdivia, Alejandra; Alvarez, Alvaro; Kong, Milene; Muñoz, Nicolás; Eisner, Verónica; Jaimovich, Enrique; Schneider, Pascal; Quest, Andrew F. G.; Leyton, Lisette

2011-01-01

Thy-1, an abundant mammalian glycoprotein, interacts with αvβ3 integrin and syndecan-4 in astrocytes and thus triggers signaling events that involve RhoA and its effector p160ROCK, thereby increasing astrocyte adhesion to the extracellular matrix. The signaling cascade includes calcium-dependent activation of protein kinase Cα upstream of Rho; however, what causes the intracellular calcium transients required to promote adhesion remains unclear. Purinergic P2X7 receptors are important for astrocyte function and form large non-selective cation pores upon binding to their ligand, ATP. Thus, we evaluated whether the intracellular calcium required for Thy-1-induced cell adhesion stems from influx mediated by ATP-activated P2X7 receptors. Results show that adhesion induced by the fusion protein Thy-1-Fc was preceded by both ATP release and sustained intracellular calcium elevation. Elimination of extracellular ATP with Apyrase, chelation of extracellular calcium with EGTA, or inhibition of P2X7 with oxidized ATP, all individually blocked intracellular calcium increase and Thy-1-stimulated adhesion. Moreover, Thy-1 mutated in the integrin-binding site did not trigger ATP release, and silencing of P2X7 with specific siRNA blocked Thy-1-induced adhesion. This study is the first to demonstrate a functional link between αvβ3 integrin and P2X7 receptors, and to reveal an important, hitherto unanticipated, role for P2X7 in calcium-dependent signaling required for Thy-1-stimulated astrocyte adhesion. PMID:21502139

Immunohistochemical sweat gland profiles.

PubMed

Noël, Fanchon; Piérard, Gérald E; Delvenne, Philippe; Quatresooz, Pascale; Humbert, Philippe; Piérard-Franchimont, Claudine

2013-09-01

Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands. © 2013 Wiley Periodicals, Inc.

Mucosal expression of basic fibroblastic growth factor, Syndecan 1 and tumor necrosis factor-alpha in diverticular disease of the colon: a case-control study.

PubMed

Tursi, A; Elisei, W; Brandimarte, G; Giorgetti, G M; Inchingolo, C D; Nenna, R; Picchio, M; Giorgio, F; Ierardi, E

2012-09-01

Inflammation may be detected in diverticular disease (DD), and fibrosis may also develop. We assessed the mucosal expression of bFGF, SD1, and TNF-α in DD according to the severity of the disease. Moreover, we assessed the response to therapy of these cytokines in acute uncomplicated diverticulitis (AUD). Fifteen patients affected by AUD and seven patients affected by symptomatic uncomplicated diverticular disease (SUDD) were enrolled. Patients with asymptomatic diverticulosis (AD), segmental colitis associated with diverticulosis (SCAD), ulcerative colitis (UC), and healthy subjects (HC) served as control groups. The expression of bFGF, SD1, and TNF-α was significantly higher in diverticulitis than in healthy controls, in diverticulosis, and in uncomplicated diverticular disease. Cytokines were significantly higher in uncomplicated diverticular disease than in healthy controls. Cytokine expression in diverticulitis did not differ significantly from that of ulcerative colitis. After treatment, TNF-α expression dropped significantly. Mucosal TNF-α is overexpressed only in symptomatic DD, while SD1 and bFGF are already overexpressed in AD. Finally, TNF-α but not SD1 or bFGF expression seems to be influenced by the treatment in AUD. © 2012 Blackwell Publishing Ltd.

CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia.

PubMed

Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Rugor, Julianna; Solano, Maria Emilia; Arck, Petra Clara; Gauster, Martin; Huppertz, Berthold; Emontzpohl, Christoph; Stoppe, Christian; Bernhagen, Jürgen; Leng, Lin; Bucala, Richard; Schulz, Herbert; Heuser, Arnd; Weedon-Fekjær, M Susanne; Johnsen, Guro M; Peetz, Dirk; Luft, Friedrich C; Staff, Anne Cathrine; Müller, Dominik N; Dechend, Ralf; Herse, Florian

2016-06-24

We hypothesized that cluster of differentiation 74 (CD74) downregulation on placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. Preeclamptic pregnancies feature hypertension, proteinuria, and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies. We performed whole-genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By reverse transcriptase-polymerase chain reaction, we confirmed this finding in early-onset (<34 gestational week, n=26) and late-onset (≥34 gestational week, n=24) samples from preeclamptic women, compared with healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry, and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared with controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM, ICAM4, and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naive and activated macrophages lacking CD74 showed a shift toward a proinflammatory signature with an increased secretion of tumor necrosis factor-α, chemokine (C-C motif) ligand 5, and monocyte chemotactic protein-1, when cocultured with trophoblasts compared with control macrophages. Trophoblasts stimulated by these factors express more CYP2J2, sFlt1, TNFα, and IL-8. CD74-knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas, and impaired spiral artery remodeling with fetal growth restriction. CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation toward a proinflammatory signature and a disturbed crosstalk with trophoblasts. © 2016 American Heart Association, Inc.

Relationship between tumour necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor in human multiple myeloma patients.

PubMed

Bolkun, Lukasz; Lemancewicz, Dorota; Piszcz, Jaroslaw; Moniuszko, Marcin; Bolkun-Skornicka, Urszula; Szkiladz, Malgorzata; Jablonska, Ewa; Kloczko, Janusz; Dzieciol, Janusz

2015-12-01

Tumour necrosis factor-alfa (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of proteins, plays a role in the regulation of vascular responses, but its effect on the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL concentrations in parallel with pro-angiogenic cytokines in serum and their expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of TRAIL and TNF-α, as well as of VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. Furthermore, we observed a significant decrease in all studied pro-angiogenic cytokines and significant increase of TRAIL concentration after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with progression during the induction treatment. It was also established that TRAIL correlated statistically and negatively with pro-angiogenic cytokines such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. In summary, our data indicate that in MM patients, both clinical course and treatment responsiveness are associated with dynamic yet corresponding changes of levels of TRAIL parallel pro-angiogenic mediators such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. Copyright © 2014 John Wiley & Sons, Ltd.

Endothelial Glycocalyx as a Shield Against Diabetic Vascular Complications: Involvement of Hyaluronan and Hyaluronidases.

PubMed

Dogné, Sophie; Flamion, Bruno; Caron, Nathalie

2018-07-01

The endothelial glycocalyx (EG), which covers the apical surface of the endothelial cells and floats into the lumen of the vessels, is a key player in vascular integrity and cardiovascular homeostasis. The EG is composed of PGs (proteoglycans), glycoproteins, glycolipids, and glycosaminoglycans, in particular hyaluronan (HA). HA seems to be implicated in most of the functions described for EG such as creating a space between blood and the endothelium, controlling vessel permeability, restricting leukocyte and platelet adhesion, and allowing an appropriate endothelial response to flow variation through mechanosensing. The amount of HA in the EG may be regulated by HYAL (hyaluronidase) 1, the most active somatic hyaluronidase. HYAL1 seems enriched in endothelial cells through endocytosis from the bloodstream. The role of the other main somatic hyaluronidase, HYAL2, in the EG is uncertain. Damage to the EG, accompanied by shedding of one or more of its components, is an early sign of various pathologies including diabetes mellitus. Shedding increases the blood or plasma concentration of several EG components, such as HA, heparan sulfate, and syndecan. The plasma levels of these molecules can then be used as sensitive markers of EG degradation. This has been shown in type 1 and type 2 diabetic patients. Recent experimental studies suggest that preserving the size and amount of EG HA in the face of diabetic insults could be a useful novel therapeutic strategy to slow diabetic complications. One way to achieve this goal, as suggested by a murine model of HYAL1 deficiency, may be to inhibit the function of HYAL1. The same approach may succeed in other pathological situations involving endothelial dysfunction and EG damage. © 2018 American Heart Association, Inc.

Protein profile of basal prostate epithelial progenitor cells--stage-specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo.

PubMed

Höfner, Thomas; Klein, Corinna; Eisen, Christian; Rigo-Watermeier, Teresa; Haferkamp, Axel; Sprick, Martin R

2016-04-01

The long-term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin(-)Sca-1(+) CD49f(+) Trop2(high)-phenotype) and human (Lin(-) CD49f(+) TROP2(high)) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti-human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single-cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f(+)/TROP2(high) phenotype of basal prostate progenitor cells and characterized by in vivo sandwich-transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9(+)/CD24(+)/CD29(+)/CD44(+)/CD47(+)/CD49f(+)/CD104(+)/CD147(+)/CD326(+)/Trop2(high) of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan-1 and stage-specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f(+) TROP2(+) basal prostate progenitor cells. Transplantation experiments suggest that CD49f(+) TROP2(high) SSEA-4(high) human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f(+) TROP2(high) or CD49f(+) TROP2(high) SSEA-4(low) cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA-4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Isolation, characterization, and molecular regulation of muscle stem cells

PubMed Central

Fukada, So-ichiro; Ma, Yuran; Ohtani, Takuji; Watanabe, Yoko; Murakami, Satoshi; Yamaguchi, Masahiko

2013-01-01

Skeletal muscle has great regenerative capacity which is dependent on muscle stem cells, also known as satellite cells. A loss of satellite cells and/or their function impairs skeletal muscle regeneration and leads to a loss of skeletal muscle power; therefore, the molecular mechanisms for maintaining satellite cells in a quiescent and undifferentiated state are of great interest in skeletal muscle biology. Many studies have demonstrated proteins expressed by satellite cells, including Pax7, M-cadherin, Cxcr4, syndecan3/4, and c-met. To further characterize satellite cells, we established a method to directly isolate satellite cells using a monoclonal antibody, SM/C-2.6. Using SM/C-2.6 and microarrays, we measured the genes expressed in quiescent satellite cells and demonstrated that Hesr3 may complement Hesr1 in generating quiescent satellite cells. Although Hesr1- or Hesr3-single knockout mice show a normal skeletal muscle phenotype, including satellite cells, Hesr1/Hesr3-double knockout mice show a gradual decrease in the number of satellite cells and increase in regenerative defects dependent on satellite cell numbers. We also observed that a mouse's genetic background affects the regenerative capacity of its skeletal muscle and have established a line of DBA/2-background mdx mice that has a much more severe phenotype than the frequently used C57BL/10-mdx mice. The phenotype of DBA/2-mdx mice also seems to depend on the function of satellite cells. In this review, we summarize the methodology of direct isolation, characterization, and molecular regulation of satellite cells based on our results. The relationship between the regenerative capacity of satellite cells and progression of muscular disorders is also summarized. In the last part, we discuss application of the accumulating scientific information on satellite cells to treatment of patients with muscular disorders. PMID:24273513

Cerebroglycan: an integral membrane heparan sulfate proteoglycan that is unique to the developing nervous system and expressed specifically during neuronal differentiation

PubMed Central

1994-01-01

Heparan sulfate proteoglycans (HSPGs) are found on the surface of all adherent cells and participate in the binding of growth factors, extracellular matrix glycoproteins, cell adhesion molecules, and proteases and antiproteases. We report here the cloning and pattern of expression of cerebroglycan, a glycosylphosphatidylinositol (GPI)- anchored HSPG that is found in the developing rat brain (previously referred to as HSPG M13; Herndon, M. E., and A. D. Lander. 1990. Neuron. 4:949-961). The cerebroglycan core protein has a predicted molecular mass of 58.6 kD and five potential heparan sulfate attachment sites. Together with glypican (David, G., V. Lories, B. Decock, P. Marynen, J.-J. Cassiman, and H. Van den Berghe. 1990. J. Cell Biol. 111:3165-3176), it defines a family of integral membrane HSPGs characterized by GPI linkage and conserved structural motifs, including a pattern of 14 cysteine residues that is absolutely conserved. Unlike other known integral membrane HSPGs, including glypican and members of the syndecan family of transmembrane proteoglycans, cerebroglycan is expressed in only one tissue: the nervous system. In situ hybridization experiments at several developmental stages strongly suggest that cerebroglycan message is widely and transiently expressed by immature neurons, appearing around the time of final mitosis and disappearing after cell migration and axon outgrowth have been completed. These results suggest that cerebroglycan may fulfill a function related to the motile behaviors of developing neurons. PMID:8294498

Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

PubMed

Jary, Marine; Lecomte, Thierry; Bouché, Olivier; Kim, Stefano; Dobi, Erion; Queiroz, Lise; Ghiringhelli, Francois; Etienne, Hélène; Léger, Julie; Godet, Yann; Balland, Jérémy; Lakkis, Zaher; Adotevi, Olivier; Bonnetain, Franck; Borg, Christophe; Vernerey, Dewi

2016-11-15

In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p < 0.0001). This score had a good discrimination ability (C-index = 0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values. © 2016 UICC.

Syndecan-2 Is a Novel Target of Insulin-Like Growth Factor Binding Protein-3 and Is Over-Expressed in Fibrosis

PubMed Central

Ruiz, Ximena D.; Mlakar, Logan R.; Yamaguchi, Yukie; Su, Yunyun; Larregina, Adriana T.; Pilewski, Joseph M.; Feghali-Bostwick, Carol A.

2012-01-01

Extracellular matrix deposition and tissue scarring characterize the process of fibrosis. Transforming growth factor beta (TGFβ) and Insulin-like growth factor binding protein-3 (IGFBP-3) have been implicated in the pathogenesis of fibrosis in various tissues by inducing mesenchymal cell proliferation and extracellular matrix deposition. We identified Syndecan-2 (SDC2) as a gene induced by TGFβ in an IGFBP-3-dependent manner. TGFβ induction of SDC2 mRNA and protein required IGFBP-3. IGFBP-3 independently induced production of SDC2 in primary fibroblasts. Using an ex-vivo model of human skin in organ culture expressing IGFBP-3, we demonstrate that IGFBP-3 induces SDC2 ex vivo in human tissue. We also identified Mitogen-activated protein kinase-interacting kinase (Mknk2) as a gene induced by IGFBP-3. IGFBP-3 triggered Mknk2 phosphorylation resulting in its activation. Mknk2 independently induced SDC2 in human skin. Since IGFBP-3 is over-expressed in fibrotic tissues, we examined SDC2 levels in skin and lung tissues of patients with systemic sclerosis (SSc) and lung tissues of patients with idiopathic pulmonary fibrosis (IPF). SDC2 levels were increased in fibrotic dermal and lung tissues of patients with SSc and in lung tissues of patients with IPF. This is the first report describing elevated levels of SDC2 in fibrosis. Increased SDC2 expression is due, at least in part, to the activity of two pro-fibrotic factors, TGFβ and IGFBP-3. PMID:22900087

Syndecan-2 is a novel target of insulin-like growth factor binding protein-3 and is over-expressed in fibrosis.

PubMed

Ruiz, Ximena D; Mlakar, Logan R; Yamaguchi, Yukie; Su, Yunyun; Larregina, Adriana T; Pilewski, Joseph M; Feghali-Bostwick, Carol A

2012-01-01

Extracellular matrix deposition and tissue scarring characterize the process of fibrosis. Transforming growth factor beta (TGFβ) and Insulin-like growth factor binding protein-3 (IGFBP-3) have been implicated in the pathogenesis of fibrosis in various tissues by inducing mesenchymal cell proliferation and extracellular matrix deposition. We identified Syndecan-2 (SDC2) as a gene induced by TGFβ in an IGFBP-3-dependent manner. TGFβ induction of SDC2 mRNA and protein required IGFBP-3. IGFBP-3 independently induced production of SDC2 in primary fibroblasts. Using an ex-vivo model of human skin in organ culture expressing IGFBP-3, we demonstrate that IGFBP-3 induces SDC2 ex vivo in human tissue. We also identified Mitogen-activated protein kinase-interacting kinase (Mknk2) as a gene induced by IGFBP-3. IGFBP-3 triggered Mknk2 phosphorylation resulting in its activation. Mknk2 independently induced SDC2 in human skin. Since IGFBP-3 is over-expressed in fibrotic tissues, we examined SDC2 levels in skin and lung tissues of patients with systemic sclerosis (SSc) and lung tissues of patients with idiopathic pulmonary fibrosis (IPF). SDC2 levels were increased in fibrotic dermal and lung tissues of patients with SSc and in lung tissues of patients with IPF. This is the first report describing elevated levels of SDC2 in fibrosis. Increased SDC2 expression is due, at least in part, to the activity of two pro-fibrotic factors, TGFβ and IGFBP-3.

A role for RNA post-transcriptional regulation in satellite cell activation

PubMed Central

2012-01-01

Background Satellite cells are resident skeletal muscle stem cells responsible for muscle maintenance and repair. In resting muscle, satellite cells are maintained in a quiescent state. Satellite cell activation induces the myogenic commitment factor, MyoD, and cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent satellite cell to a transit-amplifying myoblast is poorly understood. Methods Satellite cells isolated by FACS from uninjured skeletal muscle and 12 h post-muscle injury from wild type and Syndecan-4 null mice were probed using Affymetrix 430v2 gene chips and analyzed by Spotfiretm and Ingenuity Pathway analysis to identify gene expression changes and networks associated with satellite cell activation, respectively. Additional analyses of target genes identify miRNAs exhibiting dynamic changes in expression during satellite cell activation. The function of the miRNAs was assessed using miRIDIAN hairpin inhibitors. Results An unbiased gene expression screen identified over 4,000 genes differentially expressed in satellite cells in vivo within 12 h following muscle damage and more than 50% of these decrease dramatically. RNA binding proteins and genes involved in post-transcriptional regulation were significantly over-represented whereas splicing factors were preferentially downregulated and mRNA stability genes preferentially upregulated. Furthermore, six computationally identified miRNAs demonstrated novel expression through muscle regeneration and in satellite cells. Three of the six miRNAs were found to regulate satellite cell fate. Conclusions The quiescent satellite cell is actively maintained in a state poised to activate in response to external signals. Satellite cell activation appears to be regulated by post-transcriptional gene regulation. PMID:23046558

Proteoglycans and neuronal migration in the cerebral cortex during development and disease

PubMed Central

Maeda, Nobuaki

2015-01-01

Chondroitin sulfate proteoglycans and heparan sulfate proteoglycans are major constituents of the extracellular matrix and the cell surface in the brain. Proteoglycans bind with many proteins including growth factors, chemokines, axon guidance molecules, and cell adhesion molecules through both the glycosaminoglycan and the core protein portions. The functions of proteoglycans are flexibly regulated due to the structural variability of glycosaminoglycans, which are generated by multiple glycosaminoglycan synthesis and modifying enzymes. Neuronal cell surface proteoglycans such as PTPζ, neuroglycan C and syndecan-3 function as direct receptors for heparin-binding growth factors that induce neuronal migration. The lectican family, secreted chondroitin sulfate proteoglycans, forms large aggregates with hyaluronic acid and tenascins, in which many signaling molecules and enzymes including matrix proteases are preserved. In the developing cerebrum, secreted chondroitin sulfate proteoglycans such as neurocan, versican and phosphacan are richly expressed in the areas that are strategically important for neuronal migration such as the striatum, marginal zone, subplate and subventricular zone in the neocortex. These proteoglycans may anchor various attractive and/or repulsive cues, regulating the migration routes of inhibitory neurons. Recent studies demonstrated that the genes encoding proteoglycan core proteins and glycosaminoglycan synthesis and modifying enzymes are associated with various psychiatric and intellectual disorders, which may be related to the defects of neuronal migration. PMID:25852466

Quantification of a Non-conventional Protein Secretion: The Low-Molecular-Weight FGF-2 Example.

PubMed

Arcondéguy, Tania; Touriol, Christian; Lacazette, Eric

2016-01-01

Quantification of secreted factors is most often measured with enzyme-linked immunosorbent assay (ELISA), Western Blot, or more recently with antibody arrays. However, some of these, like low-molecular-weight fibroblast growth factor-2 (LMW FGF-2; the 18 kDa form), exemplify a set of secreted but almost non-diffusible molecular actors. It has been proposed that phosphorylated FGF-2 is secreted via a non-vesicular mechanism and that heparan sulfate proteoglycans function as extracellular reservoir but also as actors for its secretion. Heparan sulfate is a linear sulfated polysaccharide present on proteoglycans found in the extracellular matrix or anchored in the plasma membrane (syndecan). Moreover the LMW FGF-2 secretion appears to be activated upon FGF-1 treatment. In order to estimate quantification of such factor export across the plasma membrane, technical approaches are presented (evaluation of LMW FGF-2: (1) secretion, (2) extracellular matrix reservoir, and (3) secretion modulation by surrounding factors) and the importance of such procedures in the comprehension of the biology of these growth factors is underlined.

Peritoneum from Trypanosoma cruzi-infected mice is a homing site of Syndecan-1 neg plasma cells which mainly provide non-parasite-specific antibodies.

PubMed

Merino, Maria C; Montes, Carolina L; Acosta-Rodriguez, Eva V; Bermejo, Daniela A; Amezcua-Vesely, Maria C; Gruppi, Adriana

2010-05-01

Humoral immunity during experimental Chagas disease has been considered a double-edge sword, critical to control Trypanosoma cruzi spreading but also associated to tissue damage. Peritoneal B-1 cells have been linked to the pathogenesis of Chagas disease; however, they may also help to control the infection by providing a fast wave of antibodies. In the present work, we determined that peritoneal B-cell response to T. cruzi is characterized by a marked reduction of CD19(+) B cells due to plasma cell differentiation rather than to cell death. Both peritoneal B-2 and B-1 cells decrease after parasite infection, but with different kinetics. Thus, the reduction in B-2 cell number can be detected from day 4 postinfection while the number of B-1 cells decreases only after 15 days of infection. Differentiation of peritoneal B-1 and B-2 cells into IgM-secreting cells was triggered by parasites but not by cytokines produced by peritoneal cells. Electron microscopy studies showed that peritoneum of infected mice lodges plasma cells with typical morphology as well as atypical plasma cells named 'Mott-like cells' containing high number of cytoplasmatic Ig(+) granules. The plasma cells induced during the infection showed a phenotype that may allow their persistence in peritoneum and they may contribute to the high levels of antibodies exhibited at the chronic phase of infection. We also showed that the peritoneal B-cell response is scarcely specific for the invading pathogen and rather constitute an important source of non-parasite-specific IgM and IgG in the infected host.

TIM-1 signaling in B cells regulates antibody production

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

Ma, Juan; Usui, Yoshihiko; Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku-ku, Tokyo 160-0023

Highlights: {yields} TIM-1 is highly expressed on anti-IgM + anti-CD40-stimulated B cells. {yields} Anti-TIM-1 mAb enhanced proliferation and Ig production on activated B cell in vitro. {yields} TIM-1 signaling regulates Ab production by response to TI-2 and TD antigens in vivo. -- Abstract: Members of the T cell Ig and mucin (TIM) family have recently been implicated in the control of T cell-mediated immune responses. In this study, we found TIM-1 expression on anti-IgM- or anti-CD40-stimulated splenic B cells, which was further up-regulated by the combination of anti-IgM and anti-CD40 Abs. On the other hand, TIM-1 ligand was constitutively expressedmore » on B cells and inducible on anti-CD3{sup +} anti-CD28-stimulated CD4{sup +} T cells. In vitro stimulation of activated B cells by anti-TIM-1 mAb enhanced proliferation and expression of a plasma cell marker syndecan-1 (CD138). We further examined the effect of TIM-1 signaling on antibody production in vitro and in vivo. Higher levels of IgG2b and IgG3 secretion were detected in the culture supernatants of the anti-TIM-1-stimulated B cells as compared with the control IgG-stimulated B cells. When immunized with T-independent antigen TNP-Ficoll, TNP-specific IgG1, IgG2b, and IgG3 Abs were slightly increased in the anti-TIM-1-treated mice. When immunized with T-dependent antigen OVA, serum levels of OVA-specific IgG2b, IgG3, and IgE Abs were significantly increased in the anti-TIM-1-treated mice as compared with the control IgG-treated mice. These results suggest that TIM-1 signaling in B cells augments antibody production by enhancing B cell proliferation and differentiation.« less

Thermogenic profiling using magnetic resonance imaging of dermal and other adipose tissues

PubMed Central

Kasza, Ildiko; Hernando, Diego; Roldán-Alzate, Alejandro; Alexander, Caroline M.; Reeder, Scott B.

2016-01-01

Dermal white adipose tissue (dWAT) was recently recognized for its potential to modify whole body metabolism. Here, we show that dWAT can be quantified using a high-resolution, fat-specific magnetic resonance imaging (MRI) technique. Noninvasive MRI has been used to describe adipocyte depots for many years; the MRI technique we describe uses an advanced fat-specific method to measure the thickness of dWAT, together with the total volume of WAT and the relative activation/fat depletion of brown adipose tissues (BAT). Since skin-embedded adipocytes may provide natural insulation, they provide an important counterpoint to the activation of thermogenic brown and beige adipose tissues, whereby these distinct depots are functionally interrelated and require simultaneous assay. This method was validated using characterized mouse cohorts of a lipodystrophic, dWAT-deficient strain (syndecan-1 KO) and 2 obese models (diet-induced obese mice and genetically obese animals, ob/ob). Using a preliminary cohort of normal human subjects, we found the thickness of skin-associated fat varied 8-fold, from 0.13–1.10 cm; on average, this depot is calculated to weigh 8.8 kg. PMID:27668285

Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor KIR2DL4: heparan sulfate directly modulates KIR2DL4-mediated responses

PubMed Central

Brusilovsky, Michael; Cordoba, Moti; Rosental, Benyamin; Hershkovitz, Oren; Andrake, Mark D.; Pecherskaya, Anna; Einarson, Margret B.; Zhou, Yan; Braiman, Alex

2013-01-01

KIR2DL4 (CD158d) is a distinct member of the killer cell Ig-like receptor (KIR) family in human NK cells that can induce cytokine production and cytolytic activity in resting NK cells. Soluble HLA-G, normally expressed only by fetal-derived trophoblast cells, was reported to be a ligand for KIR2DL4; however, KIR2DL4 expression is not restricted to the placenta and can be found in CD56high subset of peripheral blood NK cells. We demonstrated that KIR2DL4 can interact with alternative ligand(s), expressed by cells of epithelial or fibroblast origin. A genome-wide high-throughput siRNA screen revealed that KIR2DL4 recognition of cells surface ligand(s) is directly regulated by heparan sulfate (HS) glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1). KIR2DL4 was found to directly interact with HS/heparin, and the D0-domain of KIR2DL4 was essential for this interaction. Accordingly, exogenous HS/heparin can regulate cytokine production by KIR2DL4-expressing NK cells and HEK293T cells (HEK293T-2DL4) and induces differential localization of KIR2DL4 to rab5+ and rab7+ endosomes, thus leading to down-regulation of cytokine production and degradation of the receptor. Furthermore, we showed that intimate interaction of syndecan-4 (SDC4) HS Proteo-Glycan (HSPG) and KIR2DL4 directly affects receptor endocytosis and membrane trafficking. PMID:24127555

Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link.

PubMed

Cicinelli, Ettore; Trojano, Giuseppe; Mastromauro, Marcella; Vimercati, Antonella; Marinaccio, Marco; Mitola, Paola Carmela; Resta, Leonardo; de Ziegler, Dominique

2017-08-01

To evaluate the association between endometriosis end chronic endometritis (CE) diagnosed by hysteroscopy, conventional histology, and immunohistochemistry. Case-control study. University hospital. Women with and without endometriosis who have undergone hysterectomy. Retrospective evaluation of 78 women who have undergone hysterectomy and were affected by endometriosis and 78 women without endometriosis. CE diagnosed based on conventional histology and immunohistochemistry with anti-syndecan-1 antibodies to identify CD138 cells. The prevalence of CE was statistically significantly higher in the women with endometriosis as compared with the women who did not have endometriosis (33 of 78, 42.3% vs. 12 of 78, 15.4% according to hysteroscopy; and 30 of 78, 38.5% vs. 11 of 78, 14.1% according to histology). The women were divided into two groups, 115 patients without CE and 41 patients with CE. With univariate analysis, parity was associated with a lower risk for CE, and endometriosis was associated with a statistically significantly elevated risk of CE. Using multivariate analysis, parity continued to be associated with a lower incidence of CE, whereas endometriosis was associated with a 2.7 fold higher risk. The diagnosis of CE is more frequent in women with endometriosis. Although no etiologic relationships between CE and endometriosis can be established, this study suggests that CE should be considered and if necessary ruled out in women with endometriosis, particularly if they have abnormal uterine bleeding. Identification and appropriate treatment of CE may avoid unnecessary surgery. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Dendritic space-filling requires a neuronal type-specific extracellular permissive signal in Drosophila.

PubMed

Poe, Amy R; Tang, Lingfeng; Wang, Bei; Li, Yun; Sapar, Maria L; Han, Chun

2017-09-19

Neurons sometimes completely fill available space in their receptive fields with evenly spaced dendrites to uniformly sample sensory or synaptic information. The mechanisms that enable neurons to sense and innervate all space in their target tissues are poorly understood. Using Drosophila somatosensory neurons as a model, we show that heparan sulfate proteoglycans (HSPGs) Dally and Syndecan on the surface of epidermal cells act as local permissive signals for the dendritic growth and maintenance of space-filling nociceptive C4da neurons, allowing them to innervate the entire skin. Using long-term time-lapse imaging with intact Drosophila larvae, we found that dendrites grow into HSPG-deficient areas but fail to stay there. HSPGs are necessary to stabilize microtubules in newly formed high-order dendrites. In contrast to C4da neurons, non-space-filling sensory neurons that develop in the same microenvironment do not rely on HSPGs for their dendritic growth. Furthermore, HSPGs do not act by transporting extracellular diffusible ligands or require leukocyte antigen-related (Lar), a receptor protein tyrosine phosphatase (RPTP) and the only known Drosophila HSPG receptor, for promoting dendritic growth of space-filling neurons. Interestingly, another RPTP, Ptp69D, promotes dendritic growth of C4da neurons in parallel to HSPGs. Together, our data reveal an HSPG-dependent pathway that specifically allows dendrites of space-filling neurons to innervate all target tissues in Drosophila .

Lacritin and other new proteins of the lacrimal functional unit.

PubMed

McKown, Robert L; Wang, Ningning; Raab, Ronald W; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B; Laurie, Gordon W

2009-05-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as 'an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them'. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over 200 new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin's low nanomolar mitogenic activity. The lacritin-binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction.

Mechanisms of triglyceride metabolism in patients with bile acid diarrhea

PubMed Central

Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

2016-01-01

Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment. PMID:27570415

PAR1 activation affects the neurotrophic properties of Schwann cells.

PubMed

Pompili, Elena; Fabrizi, Cinzia; Somma, Francesca; Correani, Virginia; Maras, Bruno; Schininà, Maria Eugenia; Ciraci, Viviana; Artico, Marco; Fornai, Francesco; Fumagalli, Lorenzo

2017-03-01

Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR. Copyright © 2017 Elsevier Inc. All rights reserved.

Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth.

PubMed

Iida, Joji; Dorchak, Jesse; Clancy, Rebecca; Slavik, Juliana; Ellsworth, Rachel; Katagiri, Yasuhiro; Pugacheva, Elena N; van Kuppevelt, Toin H; Mural, Richard J; Cutler, Mary Lou; Shriver, Craig D

2015-01-15

There are lines of evidence demonstrating that NEDD9 (Cas-L, HEF-1) plays a key role in the development, progression, and metastasis of breast cancer cells. We previously reported that NEDD9 plays a critical role for promoting migration and growth of MDA-MB-231. In order to further characterize the mechanisms of NEDD9-mediated cancer migration and growth, stable cells overexpressing NEDD9 were generated using HCC38 as a parental cell line which expresses low level of endogenous NEDD9. Microarray studies demonstrated that core proteins of CD44 and Serglycin were markedly upregulated in HCC38(NEDD9) cells compared to HCC38(Vector) cells, while those of Syndecan-1, Syndecan-2, and Versican were downregulated in HCC38(NEDD9). Importantly, enzymes generating chondroitin sulfate glycosaminoglycans (CS) such as CHST11, CHST15, and CSGALNACT1 were upregulated in HCC38(NEDD9) compared to HCC38(Vector). Immunofluorescence studies using specific antibody, GD3G7, confirmed the enhanced expression of CS-E subunit in HCC38(NEDD9). Immunoprecipitation and western blotting analysis demonstrated that CS-E was attached to CD44 core protein. We demonstrated that removing CS by chondroitinase ABC significantly inhibited anchorage-independent colony formation of HCC38(NEDD9) in methylcellulose. Importantly, the fact that GD3G7 significantly inhibited colony formation of HCC38(NEDD9) cells suggests that CS-E subunit plays a key role in this process. Furthermore, treatment of HCC38(NEDD9) cells with chondroitinase ABC or GD3G7 significantly inhibited mammosphere formation. Exogenous addition of CS-E enhanced colony formation and mammosphere formation of HCC38 parental and HCC38(Vector) cells. These results suggest that NEDD9 regulates the synthesis and expression of tumor associated glycocalyx structures including CS-E, which plays a key role in promoting and regulating breast cancer progression and metastasis and possibly stem cell phenotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

Proteoglycans in polarized epithelial Madin-Darby canine kidney cells.

PubMed Central

Svennevig, K; Prydz, K; Kolset, S O

1995-01-01

Madin-Darby canine kidney (MDCK) cells were cultured on polycarbonate filters to study the synthesis and sorting of proteoglycans in polarized epithelial cells. Two strains of MDCK cells were used. MDCK I cells resemble distal tubule epithelial cells, and MDCK II cells share some characteristics with proximal tubule cells. Both strains were grown to confluency and labelled with [35S]sulphate for 24 h. The apical and basolateral media and the cell fractions were harvested and analysed by DEAE ion-exchange chromatography. A large portion of the [35S]sulphate-labelled macromolecules bound strongly to the ion-exchange columns, and could be eluted in three distinct peaks. The latest eluting peak was demonstrated to contain almost exclusively chondroitin sulphate, whereas peak 2 contained mostly heparan sulphate, demonstrated by using chondroitinase ABC and nitrous acid (pH 1.5) respectively to depolymerize the [35S]glycosaminoglycan chains. Peak 1 contained negligible amounts of proteoglycans. Large differences could be observed in proteoglycan sorting in MDCK I and II cells. Strain I secreted approx. 67% of the proteoglycans to the apical side and 17% to the basolateral side. The cell fraction contained 17% of the proteoglycans after 24 h of labelling. In contrast, 19% of the proteoglycans were sorted to the apical side of MDCK II cells and 61% to the basolateral side, whereas the cell fraction contained 20%. Furthermore, the level of [35S]proteoglycan biosynthesis (apical and basolateral media and cell fraction total) was higher in MDCK I cells than in strain II. Based on the amount of material degraded by chondroitinase ABC and nitrous acid respectively, and the total amounts of [35S]proteoglycans recovered from the cells, it was calculated that the MDCK I strain synthesized approx. 56% chondroitin sulphate and 44% heparan sulphate. In contrast, the MDCK II strain synthesized 69% heparan sulphate and 31% chondroitin sulphate. To further identify the [35S]proteoglycans synthesized by MDCK I and II cells, antibodies against perlecan, versican and syndecan were used. The antibody against mouse syndecan did not cross-react with any of the proteoglycans produced in MDCK I or II cells. Both MDCK I and II cells expressed perlecan; 57-61% could be recovered from the basolateral fractions and 18-34% from the apical medium. Versican was also found in both MDCK I and II cells. Compared with perlecan, a larger percentage of versican (43-53%) was found in the cell fractions. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:7487945

Early expression of pregnancy-specific glycoprotein 22 (PSG22) by trophoblast cells modulates angiogenesis in mice.

PubMed

Blois, Sandra M; Tirado-González, Irene; Wu, Julie; Barrientos, Gabriela; Johnson, Briana; Warren, James; Freitag, Nancy; Klapp, Burghard F; Irmak, Ster; Ergun, Suleyman; Dveskler, Gabriela S

2012-06-01

Mouse and human pregnancy-specific glycoproteins (PSG) are known to exert immunomodulatory functions during pregnancy by inducing maternal leukocytes to secrete anti-inflammatory cytokines that promote a tolerogenic decidual microenvironment. Many such anti-inflammatory mediators also function as proangiogenic factors, which, along with the reported association of murine PSG with the uterine vasculature, suggest that PSG may contribute to the vascular adaptations necessary for successful implantation and placental development. We observed that PSG22 is strongly expressed around the embryonic crypt on Gestation Day 5.5, indicating that trophoblast giant cells are the main source of PSG22 during the early stages of pregnancy. PSG22 treatment up-regulated the secretion of transforming growth factor beta 1 and vascular endothelial growth factor A (VEGFA) in murine macrophages, uterine dendritic cells, and natural killer cells. A possible role of PSGs in uteroplacental angiogenesis is further supported by the finding that incubation of endothelial cells with PSG22 resulted in the formation of tubes in the presence and absence of VEGFA. We determined that PSG22, like human PSG1 and murine PSG17 and PSG23, binds to the heparan sulfate chains in syndecans. Therefore, our findings indicate that despite the independent evolution and expansion of human and rodent PSG, members in both families have conserved functions that include their ability to induce anti-inflammatory cytokines and proangiogenic factors as well as to induce the formation of capillary structures by endothelial cells. In summary, our results indicate that PSG22, the most abundant PSG expressed during mouse early pregnancy, is likely a major contributor to the establishment of a successful pregnancy.

MDA-9/Syntenin regulates protective autophagy in anoikis-resistant glioma stem cells.

PubMed

Talukdar, Sarmistha; Pradhan, Anjan K; Bhoopathi, Praveen; Shen, Xue-Ning; August, Laura A; Windle, Jolene J; Sarkar, Devanand; Furnari, Frank B; Cavenee, Webster K; Das, Swadesh K; Emdad, Luni; Fisher, Paul B

2018-05-14

Glioma stem cells (GSCs) comprise a small subpopulation of glioblastoma multiforme cells that contribute to therapy resistance, poor prognosis, and tumor recurrence. Protective autophagy promotes resistance of GSCs to anoikis, a form of programmed cell death occurring when anchorage-dependent cells detach from the extracellular matrix. In nonadherent conditions, GSCs display protective autophagy and anoikis-resistance, which correlates with expression of melanoma differentiation associated gene-9/Syntenin (MDA-9) (syndecan binding protein; SDCBP). When MDA-9 is suppressed, GSCs undergo autophagic death supporting the hypothesis that MDA-9 regulates protective autophagy in GSCs under anoikis conditions. MDA-9 maintains protective autophagy through phosphorylation of BCL2 and by suppressing high levels of autophagy through EGFR signaling. MDA-9 promotes these changes by modifying FAK and PKC signaling. Gain-of-function and loss-of-function genetic approaches demonstrate that MDA-9 regulates pEGFR and pBCL2 expression through FAK and pPKC. EGFR signaling inhibits autophagy markers (ATG5, Lamp1, LC3B), helping to maintain protective autophagy, and along with pBCL2 maintain survival of GSCs. In the absence of MDA-9, this protective mechanism is deregulated; EGFR no longer maintains protective autophagy, leading to highly elevated and sustained levels of autophagy and consequently decreased cell survival. In addition, pBCL2 is down-regulated in the absence of MDA-9, leading to cell death in GSCs under conditions of anoikis. Our studies confirm a functional link between MDA-9 expression and protective autophagy in GSCs and show that inhibition of MDA-9 reverses protective autophagy and induces anoikis and cell death in GSCs.

Fabrication of biomimetic nanomaterials and their effect on cell behavior

NASA Astrophysics Data System (ADS)

Porri, Teresa Jane

Cells in vivo respond to an intricate combination of chemical and mechanical signals. The corneal epithelium, a structure which prevents the admission of bacteria and undesirable molecules into the eye, grows on a basement membrane which presents both nanoscale topographic and adhesive chemical signals. An effective approach to biomaterials design takes advantage of the synergistic effects of the multiple cellular inputs which are available to engineer cell-substrate interactions. We have previously demonstrated the effects of nanoscale topography on a variety of corneal epithelial cell behaviors. To gain a better understanding of cell-level control in vivo, we employ a systems-level approach which looks at the effect of nanoscale topography in conjunction with a biomimetic surface chemistry. First, we discuss a novel method of fabricating nanoscale topography through templated electroless deposition of gold into PVP-coated polycarbonate membranes. This technique creates nanowires of gold with an uniform outer diameter that is dependent upon the size of the pores in the membrane used, and a nanowire length that is dependent upon the extent of etching into the polymer membrane. The gold nanowires can be modified with self-assembled monolayers (SAMs) of alkanethiols. Using these substrates, we study the effect of topographic length scale and surface chemistry on cells attached to a discontinuous nanoscale topography, and find a transition in cellular behavior at a length scale (between 600 and 2000 nm inter-wire spacing) that is commensurate with the transition length scale seen on surfaces presenting continuous grooves and ridges. Secondly, we study the effect of non-fouling peptide-modified SAMs on cellular behavior. We examine the effect of co-presented RGD and AG73 peptides and show that cell spreading is a function of the relative ratios of RGD and AG73 present on the surface. Finally, we explore the combinatorial effects of biologically relevant chemistry with anisotropic nanoscale topography with dimensions that vary from the micron to the nanoscale. We show that integrin binding, syndecan binding, and topographic length scale each independently influence epithelial cell response to nanoscale features, lending a high degree of control over cell morphologic responses.

Interleukin-5 regulates genes involved in B-cell terminal maturation.

PubMed

Horikawa, Keisuke; Takatsu, Kiyoshi

2006-08-01

Interleukin (IL)-5 induces CD38-activated splenic B cells to differentiate into immunoglobulin M-secreting cells and undergo micro to gamma 1 class switch recombination (CSR) at the DNA level, resulting in immunoglobulin G1 (IgG1) production. Interestingly, IL-4, a well-known IgG1-inducing factor does not induce immunoglobulin production or micro to gamma 1 CSR in CD38-activated B cells. In the present study, we implemented complementary DNA microarrays to investigate the contribution of IL-5-induced gene expression in CD38-stimulated B cells to immunoglobulin-secreting cell differentiation and micro to gamma 1 CSR. IL-5 and IL-4 stimulation of CD38-activated B cells induced the expression of 418 and 289 genes, respectively, that consisted of several clusters. Surprisingly, IL-5-inducible 78 genes were redundantly regulated by IL-4. IL-5 and IL-4 also suppressed the gene expression of 319 and 325 genes, respectively, 97 of which were overlapped. Genes critically regulated by IL-5 include immunoglobulin-related genes such as J chain and immunoglobulinkappa, and genes involved in B-cell maturation such as BCL6, activation-induced cytidine deaminase (Aid) and B lymphocyte-induced maturation protein-1 (Blimp-1) and tend to be induced slowly after IL-5 stimulation. Intriguingly, among genes, the retroviral induction of Blimp-1 and Aid in CD38-activated B cells could induce IL-4-dependent maturation to Syndecan-1+ antibody-secreting cells and micro to gamma 1 CSR, respectively, in CD38-activated B cells. Taken together, preferential Aid and Blimp-1 expression plays a critical role in IL-5-induced immunoglobulin-secreting cell differentiation and micro to gamma 1 CSR in CD38-activated B cells.

Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA): safety and efficacy of low-dose prostacyclin administration and blood pressure target in addition to standard therapy, as compared to standard therapy alone, in post-cardiac arrest syndrome patients: study protocol for a randomized controlled trial.

PubMed

Meyer, Anna Sina P; Ostrowski, Sisse R; Kjaergaard, Jesper; Johansson, Pär I; Hassager, Christian

2016-08-02

Morbidity and mortality following initial survival of cardiac arrest remain high despite great efforts to improve resuscitation techniques and post-resuscitation care, in part due to the ischemia-reperfusion injury secondary to the restoration of the blood circulation. Patients resuscitated from cardiac arrest display evidence of endothelial injury and coagulopathy (hypocoagulability, hyperfibrinolysis), which in associated with poor outcome. Recent randomized controlled trials have revealed that treatment with infusion of prostacyclin reduces endothelial damage after major surgery and AMI. Thus, a study is pertinent to investigate if prostacyclin infusion as a therapeutic intervention reduces endothelial damage without compromising, or even improving, the hemostatic competence in resuscitated cardiac arrest patients. Post-cardiac arrest patients frequently have a need for vasopressor therapy (catecholamines) to achieve the guideline-supported blood pressure goals. To evaluate a possible catecholamine interaction with the primary endpoints of this study, included patients will be randomized into two different blood pressure goals within guideline-recommended targets. A randomized, placebo-controlled, double-blind investigator-initiated pilot trial in 40 out-of-hospital-cardiac-arrest (OHCA) patients will be conducted. Patients will be randomly assigned to either the active treatment group (48 hours of active study drug (iloprost, 1 ng/kg/min) or to the control group [placebo (saline) infusion]. Target mean blood pressure levels will be allocated 1:1 to 65 mmHg or approximately 75 mmHg, which gives four different permutations, namely: (i) iloprost/65 mHg, (ii) iloprost/75 mmHg, (iii) placebo/65 mmHg, and (iv) placebo/75 mmHg. All randomized patients will be treated in accordance with state-of-the art therapy including targeted temperature management. The primary endpoint of this study is change in biomarkers indicative of endothelial activation and damage, [soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), nucleosomes] and sympathoadrenal over activation (epinephrine/norepinephrine) from baseline to 48 hours post-randomization. The secondary endpoints of this trial will include: (1) the hemostatic profile [change in functional hemostatic blood test (thrombelastography (TEG) and whole blood platelet aggregometry (multiplate)) blood cell and endothelial cell-derived microparticles]; (2) feasibility of blood pressure target intervention (target 90 %); (3) interaction of primary endpoints and blood pressure target; (4) levels of neuron-specific enolase at 48 hours post-inclusion according to blood pressure targets. The ENDO-RCA study is a pilot study trial that investigates safety and efficacy of low-dose infusion of prostacyclin administration as compared to standard therapy in post-cardiac arrest syndrome patients. Trial registration at ClinicalTrials.gov (identifier NCT02685618 ) on 18 February 2016.

Decreasing the metastatic potential in cancers--targeting the heparan sulfate proteoglycans.

PubMed

Fjeldstad, K; Kolset, S O

2005-09-01

The heterogeneity of proteoglycans (PG)s contributes to their functional diversity. Many functions depend on their ability to bind and modulate the activity of components of the extracellular matrix (ECM). The ability of PGs to interact with other molecules, such as growth factors, is largely determined by the fine structure of the glycosaminoglycan (GAG) chains. Tumorigenesis is associated with changes in the PG synthesis. Heparan sulfate (HS) PGs are involved in several aspects of cancer biology including tumor progression, angiogenesis, and metastasis. PGs can have both tumor promoting and tumor suppressing activities depending on the protein core, the GAG attached, molecules they associate with, localization, the tumor subtype, stages, and degree of tumor differentiation. Perlecan is an angiogenic factor involved in tumor invasiveness. The C-terminal domain V of perlecan, named endorepellin, has however been shown to inhibit angiogenesis. Another angiogenic factor is endostatin, the COOH-terminal domain of the part-time PG collagen XVIII. Glypicans and syndecans may promote local cancer cell growth in some cancer tissues, but inhibit tissue invasion and metastasis in others. The GAG hyaluronan (HA) promotes cancer growth by providing a loose matrix for migrating tumor cells and mediates adhesion of cancer cells. HSPG degrading enzymes like heparanase, heparitinase, and other enzymes such as hyaluronidase and MMP are also important in tumor metastasis. Several different treatment strategies that target PGs have been developed. They have the potential to be effective in reducing tumor growth and inhibit the formation of metastases. PGs are also valuable tumor markers in several cancers.

Dental Cell Sheet Biomimetic Tooth Bud Model

PubMed Central

Monteiro, Nelson; Smith, Elizabeth E.; Angstadt, Shantel; Zhang, Weibo; Khademhosseini, Ali

2016-01-01

Tissue engineering and regenerative medicine technologies offer promising therapies for both medicine and dentistry. Our long-term goal is to create functional biomimetic tooth buds for eventual tooth replacement in humans. Here, our objective was to create a biomimetic 3D tooth bud model consisting of dental epithelial (DE) – dental mesenchymal (DM) cell sheets (CSs) combined with biomimetic enamel organ and pulp organ layers created using GelMA hydrogels. Pig DE or DM cells seeded on temperature-responsive plates at various cell densities (0.02, 0.114 and 0.228 cells 106/cm2) and cultured for 7, 14 and 21 days were used to generate DE and DM cell sheets, respectively. Dental CSs were combined with GelMA encapsulated DE and DM cell layers to form bioengineered 3D tooth buds. Biomimetic 3D tooth bud constructs were cultured in vitro, or implanted in vivo for 3 weeks. Analyses were performed using micro-CT, H&E staining, polarized light (Pol) microscopy, immunofluorescent (IF) and immunohistochemical (IHC) analyses. H&E, IHC and IF analyses showed that in vitro cultured multilayered DE-DM CSs expressed appropriate tooth marker expression patterns including SHH, BMP2, RUNX2, tenascin and syndecan, which normally direct DE-DM interactions, DM cell condensation, and dental cell differentiation. In vivo implanted 3D tooth bud constructs exhibited mineralized tissue formation of specified size and shape, and SHH, BMP2 and RUNX2and dental cell differentiation marker expression. We propose our biomimetic 3D tooth buds as models to study optimized DE-DM cell interactions leading to functional biomimetic replacement tooth formation. PMID:27565550

Lacritin and Other New Proteins of the Lacrimal Functional Unit

PubMed Central

McKown, Robert L.; Wang, Ningning; Raab, Ronald W.; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B.; Laurie, Gordon W.

2009-01-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as ‘an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them’. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over two hundred new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin’s low nanomolar mitogenic activity. The lacritin binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction. PMID:18840430

Effect of ovarian steroids on gene expression related to synapse assembly in serotonin neurons of macaques.

PubMed

Bethea, Cynthia L; Reddy, Arubala P

2012-07-01

Dendritic spines are the elementary structural units of neural plasticity. In a model of hormone replacement therapy (HT), we sought to determine the effect of estradiol (E) and progesterone (P) on gene expression related to synapse assembly in a laser-captured preparation enriched for serotonin neurons from rhesus macaques. Microarray analysis was conducted (n = 2 animals/treatment), and the results were confirmed for pivotal genes with qRT-PCR on additional laser-captured material (n = 3 animals/treatment). Ovariectomized rhesus macaques were treated with placebo, E, or E + P via Silastic implants for 1 month. The midbrain was obtained, sectioned, and immunostained for tryptophan hydroxylase (TPH). TPH-positive neurons were laser captured using an arcturus laser dissection microscope (Pixel II). RNA from laser-captured serotonin neurons was hybridized to Rhesus Affymetrix GeneChips for screening purposes. There was a twofold or greater change in the expression of 63 probe sets in the cell adhesion molecule (CAM) category, and 31 probe sets in the synapse assembly category were similarly altered in E- and E + P-treated animals. qRT-PCR assays showed that E treatment induced a significant increase in ephrin receptor A4 (EPHA4) and in integrin A8 (ITGA8) but not in ephrin receptor B4 (EPHB4) or integrin B8 (ITGB8) expression. E also increased expression of cadherin 11 (CDH11), neuroligin 3 (NLGN3), neurexin 3 (NRXN3), syndecan 2 (SCD2), and neural cell adhesion molecule (NCAM) compared with placebo. Supplemental P treatment suppressed E-induced gene expression. In summary, ovarian steroids target gene expression of adhesion molecules in serotonin neurons that are important for synapse assembly. Copyright © 2012 Wiley Periodicals, Inc.

Glycosaminoglycan-Mediated Downstream Signaling of CXCL8 Binding to Endothelial Cells

PubMed Central

Derler, Rupert; Weber, Corinna; Strutzmann, Elisabeth; Miller, Ingrid; Kungl, Andreas

2017-01-01

The recruitment of leukocytes, mediated by endothelium bound chemokine gradients, is a vital process in inflammation. The highly negatively charged, unbranched polysaccharide family of glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate mediate chemokine immobilization. Specifically the binding of CXCL8 (interleukin 8) to GAGs on endothelial cell surfaces is known to regulate neutrophil recruitment. Currently, it is not clear if binding of CXCL8 to GAGs leads to endothelial downstream signaling in addition to the typical CXCR1/CXCR2 (C-X-C motif chemokine receptor 1 and 2)-mediated signaling which activates neutrophils. Here we have investigated the changes in protein expression of human microvascular endothelial cells induced by CXCL8. Tumor necrosis factor alpha (TNFα) stimulation was used to mimic an inflammatory state which allowed us to identify syndecan-4 (SDC4) as the potential proteoglycan co-receptor of CXCL8 by gene array, real-time PCR and flow cytometry experiments. Enzymatic GAG depolymerization via heparinase III and chondroitinase ABC was used to emulate the effect of glycocalyx remodeling on CXCL8-induced endothelial downstream signaling. Proteomic analyses showed changes in the expression pattern of a number of endothelial proteins such as Zyxin and Caldesmon involved in cytoskeletal organization, cell adhesion and cell mobility. These results demonstrate for the first time a potential role of GAG-mediated endothelial downstream signaling in addition to the well-known CXCL8-CXCR1/CXCR2 signaling pathways in neutrophils. PMID:29207576

Development, validation and application of a micro-liquid chromatography-tandem mass spectrometry based method for simultaneous quantification of selected protein biomarkers of endothelial dysfunction in murine plasma.

PubMed

Suraj, Joanna; Kurpińska, Anna; Olkowicz, Mariola; Niedzielska-Andres, Ewa; Smolik, Magdalena; Zakrzewska, Agnieszka; Jasztal, Agnieszka; Sitek, Barbara; Chlopicki, Stefan; Walczak, Maria

2018-02-05

The objective of this study was to develop and validate the method based on micro-liquid chromatography-tandem mass spectrometry (microLC/MS-MRM) for simultaneous determination of adiponectin (ADN), von Willebrand factor (vWF), soluble form of vascular cell adhesion molecule 1 (sVCAM-1), soluble form of intercellular adhesion molecule 1 (sICAM-1) and syndecan-1 (SDC-1) in mouse plasma. The calibration range was established from 2.5pmol/mL to 5000pmol/mL for ADN; 5pmol/mL to 5000pmol/mL for vWF; 0.375pmol/mL to 250pmol/mL for sVCAM-1 and sICAM-1; and 0.25pmol/mL to 250pmol/mL for SDC-1. The method was applied to measure the plasma concentration of selected proteins in mice fed high-fat diet (HFD), and revealed the pro-thrombotic status by increased concentration of vWF (1.31±0.17 nmol/mL (Control) vs 1.98±0.09 nmol/mL (HFD), p <0.05) and the dysregulation of adipose tissue metabolism by decreased concentration of ADN (0.62±0.08 nmol/mL (Control) vs 0.37±0.06 nmol/mL (HFD), p <0.05). In conclusion, the microLC/MS-MRM-based method allows for reliable measurements of selected protein biomarkers of endothelial dysfunction in mouse plasma. Copyright © 2017 Elsevier B.V. All rights reserved.

Breast cancer stem cells, EMT and therapeutic targets

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

Kotiyal, Srishti; Bhattacharya, Susinjan, E-mail: s.bhattacharya@jiit.ac.in

Highlights: • Therapeutic targeting or inhibition of the key molecules of signaling pathways can control growth of breast cancer stem cells (BCSCs). • Development of BCSCs also involves miRNA interactions. • Therapeutic achievement can be done by targeting identified targets in the BCSC pathways. - Abstract: A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo “epithelial to mesenchymal transition” (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they aremore » also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-β, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and syndecan which can be targeted for therapeutic achievements.« less

Loss of intra-islet heparan sulfate is a highly sensitive marker of type 1 diabetes progression in humans.

PubMed

Simeonovic, Charmaine J; Popp, Sarah K; Starrs, Lora M; Brown, Debra J; Ziolkowski, Andrew F; Ludwig, Barbara; Bornstein, Stefan R; Wilson, J Dennis; Pugliese, Alberto; Kay, Thomas W H; Thomas, Helen E; Loudovaris, Thomas; Choong, Fui Jiun; Freeman, Craig; Parish, Christopher R

2018-01-01

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells in pancreatic islets are progressively destroyed. Clinical trials of immunotherapies in recently diagnosed T1D patients have only transiently and partially impacted the disease course, suggesting that other approaches are required. Our previous studies have demonstrated that heparan sulfate (HS), a glycosaminoglycan conventionally expressed in extracellular matrix, is present at high levels inside normal mouse beta cells. Intracellular HS was shown to be critical for beta cell survival and protection from oxidative damage. T1D development in Non-Obese Diabetic (NOD) mice correlated with loss of islet HS and was prevented by inhibiting HS degradation by the endoglycosidase, heparanase. In this study we investigated the distribution of HS and heparan sulfate proteoglycan (HSPG) core proteins in normal human islets, a role for HS in human beta cell viability and the clinical relevance of intra-islet HS and HSPG levels, compared to insulin, in human T1D. In normal human islets, HS (identified by 10E4 mAb) co-localized with insulin but not glucagon and correlated with the HSPG core proteins for collagen type XVIII (Col18) and syndecan-1 (Sdc1). Insulin-positive islets of T1D pancreases showed significant loss of HS, Col18 and Sdc1 and heparanase was strongly expressed by islet-infiltrating leukocytes. Human beta cells cultured with HS mimetics showed significantly improved survival and protection against hydrogen peroxide-induced death, suggesting that loss of HS could contribute to beta cell death in T1D. We conclude that HS depletion in beta cells, possibly due to heparanase produced by insulitis leukocytes, may function as an important mechanism in the pathogenesis of human T1D. Our findings raise the possibility that intervention therapy with dual activity HS replacers/heparanase inhibitors could help to protect the residual beta cell mass in patients recently diagnosed with T1D.

Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis

PubMed Central

Audebert, Stéphane; Helmbacher, Françoise; Dono, Rosanna; Maina, Flavio

2015-01-01

The successive events that cells experience throughout development shape their intrinsic capacity to respond and integrate RTK inputs. Cellular responses to RTKs rely on different mechanisms of regulation that establish proper levels of RTK activation, define duration of RTK action, and exert quantitative/qualitative signalling outcomes. The extent to which cells are competent to deal with fluctuations in RTK signalling is incompletely understood. Here, we employ a genetic system to enhance RTK signalling in a tissue-specific manner. The chosen RTK is the hepatocyte growth factor (HGF) receptor Met, an appropriate model due to its pleiotropic requirement in distinct developmental events. Ubiquitously enhanced Met in Cre/loxP-based Rosa26 stopMet knock-in context (Del-R26 Met) reveals that most tissues are capable of buffering enhanced Met-RTK signalling thus avoiding perturbation of developmental programs. Nevertheless, this ubiquitous increase of Met does compromise selected programs such as myoblast migration. Using cell-type specific Cre drivers, we genetically showed that altered myoblast migration results from ectopic Met expression in limb mesenchyme rather than in migrating myoblasts themselves. qRT-PCR analyses show that ectopic Met in limbs causes molecular changes such as downregulation in the expression levels of Notum and Syndecan4, two known regulators of morphogen gradients. Molecular and functional studies revealed that ectopic Met expression in limb mesenchyme does not alter HGF expression patterns and levels, but impairs HGF bioavailability. Together, our findings show that myoblasts, in which Met is endogenously expressed, are capable of buffering increased RTK levels, and identify mesenchymal cells as a cell type vulnerable to ectopic Met-RTK signalling. These results illustrate that embryonic cells are sensitive to alterations in the spatial distribution of RTK action, yet resilient to fluctuations in signalling levels of an RTK when occurring in its endogenous domain of activity. PMID:26393505

MDA-MB-231 breast cancer cell viability, motility and matrix adhesion are regulated by a complex interplay of heparan sulfate, chondroitin-/dermatan sulfate and hyaluronan biosynthesis.

PubMed

Viola, Manuela; Brüggemann, Kathrin; Karousou, Evgenia; Caon, Ilaria; Caravà, Elena; Vigetti, Davide; Greve, Burkhard; Stock, Christian; De Luca, Giancarlo; Passi, Alberto; Götte, Martin

2017-06-01

Proteoglycans and glycosaminoglycans modulate numerous cellular processes relevant to tumour progression, including cell proliferation, cell-matrix interactions, cell motility and invasive growth. Among the glycosaminoglycans with a well-documented role in tumour progression are heparan sulphate, chondroitin/dermatan sulphate and hyaluronic acid/hyaluronan. While the mode of biosynthesis differs for sulphated glycosaminoglycans, which are synthesised in the ER and Golgi compartments, and hyaluronan, which is synthesized at the plasma membrane, these polysaccharides partially compete for common substrates. In this study, we employed a siRNA knockdown approach for heparan sulphate (EXT1) and heparan/chondroitin/dermatan sulphate-biosynthetic enzymes (β4GalT7) in the aggressive human breast cancer cell line MDA-MB-231 to study the impact on cell behaviour and hyaluronan biosynthesis. Knockdown of β4GalT7 expression resulted in a decrease in cell viability, motility and adhesion to fibronectin, while these parameters were unchanged in EXT1-silenced cells. Importantly, these changes were associated with a decreased expression of syndecan-1, decreased signalling response to HGF and an increase in the synthesis of hyaluronan, due to an upregulation of the hyaluronan synthases HAS2 and HAS3. Interestingly, EXT1-depleted cells showed a downregulation of the UDP-sugar transporter SLC35D1, whereas SLC35D2 was downregulated in β4GalT7-depleted cells, indicating an intricate regulatory network that connects all glycosaminoglycans synthesis. The results of our in vitro study suggest that a modulation of breast cancer cell behaviour via interference with heparan sulphate biosynthesis may result in a compensatory upregulation of hyaluronan biosynthesis. These findings have important implications for the development of glycosaminoglycan-targeted therapeutic approaches for malignant diseases.

Mechanisms of Heparanase Inhibitors in Cancer Therapy

PubMed Central

Heyman, Benjamin; Yang, Yiping

2016-01-01

Heparanase is an endo-β-D-glucuronidase capable of cleaving heparan sulfate (HS) side chains contributing to break down of the extracellular matrix. Increased expression of heparanase has been found in numerous malignancies, and is associated with a poor prognosis. It has generated significant interest as a potential anti-neoplastic target because of the multiple roles it plays in tumor growth and metastasis. The pro-tumorigenic effects of heparanase are enhanced by the release of HS side chains, with subsequent increase in bioactive fragments and increased cytokine levels; both promoting tumor invasion, angiogenesis and metastasis. Preclinical experiments have shown heparanase inhibitors to substantially reduce tumor growth and metastasis leading to clinical trials with heparan sulfate mimetics. In this review we will examine heparanase’s role in tumor biology, its interaction with heparan surface proteoglycans, specifically syndecan-1; as well as the mechanism of action for heparanase inhibitors developed as anti-neoplastic therapeutics. PMID:27576132

Chronic endometritis in women with recurrent pregnancy loss and recurrent implantation failure: prevalence and role of office hysteroscopy and immunohistochemistry in diagnosis.

PubMed

Bouet, Pierre-Emmanuel; El Hachem, Hady; Monceau, Elise; Gariépy, Gilles; Kadoch, Isaac-Jacques; Sylvestre, Camille

2016-01-01

To determine the prevalence of chronic endometritis (CE) in patients with recurrent implantation failure (RIF) after IVF and unexplained recurrent pregnancy loss (RPL). Prospective observational study between November 2012 and March 2015. University-affiliated private IVF clinic. Women with RIF after IVF (group 1) and unexplained RPL (group 2). Office hysteroscopy followed by an endometrial biopsy was performed as part of the workup for RIF and RPL. The diagnosis of CE was histologically confirmed using immunohistochemistry stains for syndecan-1 (CD138). The prevalence of CE in each group and the sensitivity/specificity of office hysteroscopy in the diagnosis of CE. Ninety-nine patients were included (46 in group 1 and 53 in group 2). The mean age was 36.3 ± 4.9 years in group 1 and 34.5 ± 4.9 years in group 2. Five biopsies were uninterpretable (three in group 1 and two in group 2) because of insufficient specimen. The prevalence of CE was 14% (6/43) in group 1 and 27% (14/51) in group 2. The sensitivity and specificity of office hysteroscopy in the diagnosis of CE were 40% (8/20) and 80% (59/74), respectively. We found a high prevalence of immunohistochemically confirmed CE in women with RIF and RPL. Office hysteroscopy is a useful diagnostic tool but should be complemented by an endometrial biopsy for the diagnosis of CE. NCT01762098. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Time-dependent changes in gene expression induced in vitro by interleukin-1β in equine articular cartilage.

PubMed

Löfgren, Maria; Svala, Emilia; Lindahl, Anders; Skiöldebrand, Eva; Ekman, Stina

2018-05-01

Osteoarthritis is an inflammatory and degenerative joint disease commonly affecting horses. To identify genes of relevance for cartilage pathology in osteoarthritis we studied the time-course effects of interleukin (IL)-1β on equine articular cartilage. Articular cartilage explants from the distal third metacarpal bone were collected postmortem from three horses without evidence of joint disease. The explants were stimulated with IL-1β for 27 days and global gene expression was measured by microarray. Gene expression was compared to that of unstimulated explants at days 3, 9, 15, 21 and 27. Release of inflammatory proteins was measured using Proximity Extension Assay. Stimulation with IL-1β led to time-dependent changes in gene expression related to inflammation, the extracellular matrix (ECM), and phenotypic alterations. Gene expression and protein release of cytokines, chemokines, and matrix-degrading enzymes increased in the stimulated explants. Collagen type II was downregulated from day 15, whereas other ECM molecules were downregulated earlier. In contrast molecules involved in ECM signaling (perlecan, chondroitin sulfate proteoglycan 4, and syndecan 4) were upregulated. At the late time points, genes related to a chondrogenic phenotype were downregulated, and genes related to a hypertrophic phenotype were upregulated, suggesting a transition towards hypertrophy later in the culturing period. The data suggest that this in vitro model mimics time course events of in vivo inflammation in OA and it may be valuable as an in vitro tool to test treatments and to study disease mechanisms. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of New Biomarkers in the Prediction of Malignant Mesothelioma in Subjects with Environmental Asbestos Exposure.

PubMed

Demir, Melike; Kaya, Halide; Taylan, Mahsuk; Ekinci, Aysun; Yılmaz, Sureyya; Teke, Fatma; Sezgi, Cengizhan; Tanrikulu, Abdullah Cetin; Meteroglu, Fatih; Senyigit, Abdurrahman

2016-06-01

The purpose of this study was to investigate the potential value of certain biomarkers in predicting the presence of malignant pleural mesothelioma (MPM) in individuals environmentally exposed to asbestos. This prospective study investigated three groups; a control group composed of 41 healthy subjects, an asbestos exposure group consisting of 48 individuals, and a MPM group consisting of 42 patients. Serum levels of soluble mesothelin-related peptide (SMRP), thioredoxin-1 (TRX), epidermal growth factor receptor (EGFR), fibulin-3, syndecan-1 (SDC-1), and mesothelin were determined. Benign pleural plaques were present in 27 (58.3 %) of the individuals in the asbestos exposure group. The asbestos exposure group had significantly higher mean TRX, SMRP, and mesothelin levels compared to the control group (p = 0.023, p = 0.011, and p < 0.001, respectively). Compared to the asbestos exposure group, the MPM group had significantly higher mean EGFR, TRX, SMRP, and fibulin-3 levels (p = 0.041, p = 0.023, p = 0.002, and p = 0.001, respectively), and significantly lower mean SDC-1 levels (p = 0.002). Unlike the other biomarkers, SMRP and TRX levels increased in a graded fashion among the control, asbestos exposure, and MPM groups, respectively. Area under the curve values for SMRP and TRX were 0.86 and 0.72, respectively (95 % CI 0.79-0.92 and p < 0.001 for SMRP, and 95 % CI 0.62-0.81 and p < 0.001 for TRX). The cut-off value for SMRP was 0.62 nmol/l (sensitivity: 97.6 %, specificity: 68.9 %, positive predictive value (PPV): 56.2 %, and negative predictive value (NPV): 98.3 %) and for TRX was 156.67 ng/ml (sensitivity: 92.9 %, specificity: 77.6 %, PPV: 41.4 %, and NPV: 92.1 %). The combination of the biomarkers reached a sensitivity of 100 %, but had lower specificity (as high as 27.7 %). Serum biomarkers may be helpful for early diagnosis of MPM in asbestos-exposed cases. SMRP and TRX increased in a graded fashion from the controls to asbestos exposure and MPM groups. These two seem to be the most valuable biomarkers for the diagnosis of MPM, both individually and in combination.

Alpha or beta human chorionic gonadotropin knockdown decrease BeWo cell fusion by down-regulating PKA and CREB activation

PubMed Central

Saryu Malhotra, Sudha; Suman, Pankaj; Kumar Gupta, Satish

2015-01-01

The aim of the present study is to delineate the role of human chorionic gonadotropin (hCG) in trophoblast fusion. In this direction, using shRNA lentiviral particles, α- and β-hCG silenced ‘BeWo’ cell lines were generated. Treatment of both α- and β-hCG silenced BeWo cells with either forskolin or exogenous hCG showed a significant reduction in cell fusion as compared with control shRNA treated cells. Studies by qRT-PCR, Western blotting and immunofluorescence revealed down-regulation of fusion-associated proteins such as syncytin-1 and syndecan-1 in the α- and β-hCG silenced cells. Delineation of downstream signaling pathways revealed that phosphorylation of PKA and CREB were compromised in the silenced cells whereas, no significant changes in p38MAPK and ERK1/2 phosphorylation were observed. Moreover, β-catenin activation was unaffected by either α- or β-hCG silencing. Further, inhibition of PKA by H89 inhibitor led to a significant decrease in BeWo cell fusion but had no effect on β-catenin activation suggesting the absence of non-canonical β-catenin stabilization via PKA. Interestingly, canonical activation of β-catenin was associated with the up-regulation of Wnt 10b expression. In summary, this study establishes the significance of hCG in the fusion of trophoblastic BeWo cells, but there may be additional factors involved in this process. PMID:26053549

CD138 Expression Is Observed in the Urothelial Epithelium and in Various Urothelial Carcinomas, and Cannot Be Evidence for Plasmacytoid Urothelial Carcinoma.

PubMed

Goto, Keisuke

2016-10-01

CD138 (syndecan-1) immunoexpression has been reported to be specific for the plasmacytoid variant of urothelial carcinomas (UCs). The aim of this study was to examine the utility of CD138 immunohistochemistry for diagnosing the plasmacytoid variant of UCs. The extent and intensity of CD138 immunostaining were evaluated in 22 infiltrating UCs, 2 other infiltrating carcinomas, 15 noninvasive urothelial lesions, 3 other benign lesions, and perilesional normal tissues. CD138 immunostaining of the normal urothelial epithelium was universally diffuse and strong. In addition, all 42 cases of urinary tract lesions exhibited positive CD138 immunostaining; however, 1 of 3 plasmacytoid variants exhibited focal CD138 expression. The frequency of CD138 positivity in plasmacytoid variants may be relatively low, compared with that observed in the conventional types and other variants; thus, it is not appropriate to assume that CD138 expression in UCs is specific for plasmacytoid variants. © The Author(s) 2016.

Patterns of mRNA and protein expression during minus-lens compensation and recovery in tree shrew sclera.

PubMed

Gao, Hong; Frost, Michael R; Siegwart, John T; Norton, Thomas T

2011-04-12

To increase our understanding of the mechanisms that remodel the sclera during the development of lens-induced myopia, when the sclera responds to putative "go" signals of retinal origin, and during recovery from lens-induced myopia, when the sclera responds to retinally-derived "stop" signals. Seven groups of tree shrews were used to examine mRNA levels during minus lens compensation and recovery. Starting 24 days after eye opening (days of visual experience [VE]) lens compensation animals wore a monocular -5D lens for 1, 4, or 11 days. Recovery animals wore the -5D lens for 11 days, which was then removed for 1 or 4 days. Normal animals were examined at 24 and 38 days of VE. All groups contained 8 animals. Scleral mRNA levels were examined in the treated and contralateral control eyes with quantitative real-time polymerase chain reaction (qPCR) for 27 genes divided into four categories: 1) signaling molecules, 2) matricellular proteins, 3) metalloproteinases (MPs) and tissue inhibitors of metalloproteinases (TIMPs), and 4) cell adhesion and other proteins. Four groups (n=5 per group) were used to examine protein levels. One group wore a -5D lens for 4 days. A second group recovered for 4 days after 11 days of -5D lens treatment. Two groups were used to examine age-matched normal protein levels at 28 and 39 days of VE. The levels of six scleral proteins that showed differential mRNA expression were examined with quantitative western blots. Nineteen of the genes showed differential (treated eye versus control eye) expression of mRNA levels in at least one group of animals. Which genes showed differential expression differed after 1 and 4 days of compensation and after 1 or 4 days of recovery. The mRNA level for one gene, a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), was upregulated in the treated eyes after 1 day of compensation. After 4 days, transforming growth factor beta receptor 3 (TGFBR3), transforming growth factor-beta-induced protein ig-h3 (TGFBI), and matrix metalloproteinase 14 (MMP14) mRNA levels were upregulated. Downregulated were mRNA levels for transforming growth factor beta-1 (TGFB1), transforming growth factor beta-2 (TGFB2), thrombospondin 1 (THBS1), tenascin (TNC), osteonectin (SPARC), osteopontin (SPP1), tissue inhibitor of metalloproteinases 3 (TIMP3), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). After 11 days of lens wear, there was no differential expression. During recovery, after 1 day, treated-eye mRNA downregulation was found for TGFB2, TGFBR1, TGFBR2, TGFBR3, SPARC, ADAMTS1, ADAMTS5, syndecan 4 (SDC4), and collagen type VI, alpha 1 (COL6A1). After 4 days, TGFB1, TGFB2, TGFB3, THBS2, and TIMP3 mRNA levels were upregulated in the recovering eye. Significant downregulation, relative to normal eyes, was found in both the control and treated eyes for most genes after 1 day of compensation; a similar decrease was found, compared to lens-compensated eyes, after one day of recovery. Protein levels for THBS1 showed positive correlation with the differential mRNA levels and TGFBR3 showed a negative correlation. No differential protein expression was found for TGFB2, TGFBI, MMP14, and TIMP3. The different patterns of differential mRNA expression during minus lens compensation (hyperopia) and recovery (myopia) show that scleral fibroblasts distinguish between "go" and "stop" conditions. There is evidence of binocular global downregulation of genes at the start of both lens wear and recovery. As additional information accumulates about changes in gene expression that occur during compensation and recovery the "signature" of differential changes may help us to understand in more detail how the sclera responds in "go" and "stop" conditions.

Fibroblast growth factor-2 (FGF2) and syndecan-1 (SDC1) are potential biomarkers for putative circulating CD15+/CD30+ cells in poor outcome Hodgkin lymphoma patients

PubMed Central

2013-01-01

Background High risk, unfavorable classical Hodgkin lymphoma (cHL) includes those patients with primary refractory or early relapse, and progressive disease. To improve the availability of biomarkers for this group of patients, we investigated both tumor biopsies and peripheral blood leukocytes (PBL) of untreated (chemo-naïve, CN) Nodular Sclerosis Classic Hodgkin Lymphoma (NS-cHL) patients for consistent biomarkers that can predict the outcome prior to frontline treatment. Methods and materials Bioinformatics data mining was used to generate 151 candidate biomarkers, which were screened against a library of 10 HL cell lines. Expression of FGF2 and SDC1 by CD30+ cells from HL patient samples representing good and poor outcomes were analyzed by qRT-PCR, immunohistochemical (IHC), and immunofluorescence analyses. Results To identify predictive HL-specific biomarkers, potential marker genes selected using bioinformatics approaches were screened against HL cell lines and HL patient samples. Fibroblast Growth Factor-2 (FGF2) and Syndecan-1 (SDC1) were overexpressed in all HL cell lines, and the overexpression was HL-specific when compared to 116 non-Hodgkin lymphoma tissues. In the analysis of stratified NS-cHL patient samples, expression of FGF2 and SDC1 were 245 fold and 91 fold higher, respectively, in the poor outcome (PO) group than in the good outcome (GO) group. The PO group exhibited higher expression of the HL marker CD30, the macrophage marker CD68, and metastatic markers TGFβ1 and MMP9 compared to the GO group. This expression signature was confirmed by qualitative immunohistochemical and immunofluorescent data. A Kaplan-Meier analysis indicated that samples in which the CD30+ cells carried an FGF2+/SDC1+ immunophenotype showed shortened survival. Analysis of chemo-naive HL blood samples suggested that in the PO group a subset of CD30+ HL cells had entered the circulation. These cells significantly overexpressed FGF2 and SDC1 compared to the GO group. The PO group showed significant down-regulation of markers for monocytes, T-cells, and B-cells. These expression signatures were eliminated in heavily pretreated patients. Conclusion The results suggest that small subsets of circulating CD30+/CD15+ cells expressing FGF2 and SDC1 represent biomarkers that identify NS-cHL patients who will experience a poor outcome (primary refractory and early relapsing). PMID:23988031

Proteoglycan-based diversification of disease outcome in head and neck cancer patients identifies NG2/CSPG4 and syndecan-2 as unique relapse and overall survival predicting factors.

PubMed

Farnedi, Anna; Rossi, Silvia; Bertani, Nicoletta; Gulli, Mariolina; Silini, Enrico Maria; Mucignat, Maria Teresa; Poli, Tito; Sesenna, Enrico; Lanfranco, Davide; Montebugnoli, Lucio; Leonardi, Elisa; Marchetti, Claudio; Cocchi, Renato; Ambrosini-Spaltro, Andrea; Foschini, Maria Pia; Perris, Roberto

2015-05-03

Tumour relapse is recognized to be the prime fatal burden in patients affected by head and neck squamous cell carcinoma (HNSCC), but no discrete molecular trait has yet been identified to make reliable early predictions of tumour recurrence. Expression of cell surface proteoglycans (PGs) is frequently altered in carcinomas and several of them are gradually emerging as key prognostic factors. A PG expression analysis at both mRNA and protein level, was pursued on primary lesions derived from 173 HNSCC patients from whom full clinical history and 2 years post-surgical follow-up was accessible. Gene and protein expression data were correlated with clinical traits and previously proposed tumour relapse markers to stratify high-risk patient subgroups. HNSCC lesions were indeed found to exhibit a widely aberrant PG expression pattern characterized by a variable expression of all PGs and a characteristic de novo transcription/translation of GPC2, GPC5 and NG2/CSPG4 respectively in 36%, 72% and 71% on 119 cases. Importantly, expression of NG2/CSPG4, on neoplastic cells and in the intralesional stroma (Hazard Ratio [HR], 6.76, p = 0.017) was strongly associated with loco-regional relapse, whereas stromal enrichment of SDC2 (HR, 7.652, p = 0.007) was independently tied to lymphnodal infiltration and disease-related death. Conversely, down-regulated SDC1 transcript (HR, 0.232, p = 0.013) uniquely correlated with formation of distant metastases. Altered expression of PGs significantly correlated with the above disease outcomes when either considered alone or in association with well-established predictors of poor prognosis (i.e. T classification, previous occurrence of precancerous lesions and lymphnodal metastasis). Combined alteration of all three PGs was found to be a reliable predictor of shorter survival. An unprecedented PG-based prognostic portrait is unveiled that incisively diversifies disease course in HNSCC patients beyond the currently known clinical and molecular biomarkers.

Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis†.

PubMed

Khan, Khaleque Newaz; Fujishita, Akira; Kitajima, Michio; Hiraki, Koichi; Nakashima, Masahiro; Masuzaki, Hideaki

2014-11-01

Is there any risk of intra-uterine bacterial colonization and concurrent occurrence of endometritis in women with endometriosis? An increase in intra-uterine microbial colonization and concurrent endometritis occurred in women with endometriosis that was further increased after GnRH agonist (GnRHa) treatment. Higher bacterial contamination of menstrual blood and increased endotoxin level in menstrual and peritoneal fluids have been found in women with endometriosis than in control women. However, information on intra-uterine microbial colonization across the phases of the menstrual cycle and possible occurrence of endometritis in women with endometriosis is still lacking. This is a case-controlled study with prospective collection of vaginal smears/endometrial samples from women with and without endometriosis and retrospective evaluation. Vaginal smears and endometrial smears were collected from 73 women with endometriosis and 55 control women. Twenty of the women with endometriosis and 19 controls had received GnRHa therapy for a period of 4-6 months. Vaginal pH was measured by intra-vaginal insertion of a pH paper strip. The bacterial vaginosis (BV) score was analyzed by Gram-staining of vaginal smears and based on a modified Nugent-BV scoring system. A panel of bacteria was analyzed by culture of endometrial samples from women treated with GnRHa or not treated. Immunohistochemcial analysis was performed using antibody against Syndecan-1 (CD138) and myeloperoxidase in endometrial biopsy specimens from women with and without endometriosis. A significant shifting of intra-vaginal pH to ≥4.5 was observed in women with endometriosis compared with control women (79.3 versus 58.4%, P < 0.03). Compared with untreated women, use of GnRHa therapy also shifted vaginal pH to ≥4.5 in both control women (P = 0.004) and in women with endometriosis (P = 0.03). A higher risk of increasing intermediate flora (total score, 4-6) (P = 0.05) was observed in women with endometriosis who had GnRHa treatment versus untreated women. The number of colony forming units (CFU/ml) of Gardnerella, α-Streptococcus, Enterococci and Escherichia coli was significantly higher in endometrial samples from women with endometriosis than control women (P < 0.05 for each bacteria). GnRHa-treated women also showed significantly higher colony formation for some of these bacteria in endometrial samples than in untreated women (Gardnerella and E. coli for controls; Gardnerella, Enterococci and E. coli for women with endometriosis, P < 0.05 for all). Although there was no significant difference in the occurrence of acute endometritis between women with and without endometriosis, both GnRHa-treated controls and women with endometriosis had a significantly higher occurrence of acute endometritis (P = 0.003 for controls, P = 0.001 for endometriosis versus untreated women). Multiple analysis of covariance analysis revealed that an intra-vaginal pH of ≥4.5 (P = 0.03) and use of GnRHa (P = 0.04) were potential factors that were significantly and independently associated with intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis. These findings indicated the occurrence of sub-clinical uterine infection and endometritis in women with endometriosis after GnRHa treatment. We cannot exclude the introduction of bias from unknown previous treatment with immunosuppressing or anti-microbial agents. We have studied a limited range of bacterial species and used only culture-based methods. More sensitive molecular approaches would further delineate the similarities/differences between the vaginal cavity and uterine environment. Our current findings may have epidemiological and biological implications and help in understanding the pathogenesis of endometriosis and related disease burden. The worsening of intra-uterine microbial colonization and higher occurrence of endometritis in women with endometriosis who were treated with GnRHa identifies some future therapeutic avenues for the management, as well as prevention of recurrence, of endometriosis. Further studies are needed to examine intra-uterine colonization of a broad range of common bacteria as well as different viruses and their role in the occurrence of endometritis. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study. Not applicable. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

RT-PCR analysis of RNA extracted from Bouin-fixed and paraffin-embedded lymphoid tissues.

PubMed

Gloghini, Annunziata; Canal, Barbara; Klein, Ulf; Dal Maso, Luigino; Perin, Tiziana; Dalla-Favera, Riccardo; Carbone, Antonino

2004-11-01

In the present study, we have investigated whether RNA can be efficiently isolated from Bouin-fixed or formalin-fixed, paraffin-embedded lymphoid tissue specimens. To this aim, we applied a new and simple method that includes the combination of proteinase K digestion and column purification. By this method, we demonstrated that the amplification of long fragments could be accomplished after a pre-heating step before cDNA synthesis associated with the use of enzymes that work at high temperature. By means of PCR using different primers for two examined genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]- and CD40), we amplified segments of cDNA obtained by reverse transcription of the isolated RNA extracted from Bouin-fixed or formalin-fixed paraffin-embedded tissues. Amplified fragments of the expected sizes were obtained for both genes tested indicating that this method is suitable for the isolation of high-quality RNA. To explore the possibility for giving accurate real time quantitative RT-PCR results, cDNA obtained from matched frozen, Bouin-fixed and formalin-fixed neoplastic samples (two diffuse large cell lymphomas, one plasmacytoma) was tested for the following target genes: CD40, Aquaporin-3, BLIMP1, IRF4, Syndecan-1. Delta threshold cycle (DeltaC(T)) values for Bouin-fixed and formalin-fixed paraffin-embedded tissues and their correlation with those for frozen samples showed an extremely high correlation (r > 0.90) for all of the tested genes. These results show that the method of RNA extraction we propose is suitable for giving accurate real time quantitative RT-PCR results.

What happens in the thymus does not stay in the thymus: how T cells recycle the CD4+-CD8+ lineage commitment transcriptional circuitry to control their function

PubMed Central

Vacchio, Melanie S.; Bosselut, Rémy

2016-01-01

MHC-restricted CD4+ and CD8+ T cell are at the core of most adaptive immune responses. Although these cells carry distinct functions, they arise from a common precursor during thymic differentiation, in a developmental sequence that matches CD4 and CD8 expression and functional potential with MHC restriction. While the transcriptional control of CD4+-CD8+ lineage choice in the thymus is now better understood, less was known about what maintains the CD4+- and CD8+-lineage integrity of mature T cells. In this review, we discuss the mechanisms that establish in the thymus, and maintain in post-thymic cells, the separation of these lineages. We focus on recent studies that address the mechanisms of epigenetic control of Cd4 expression and emphasize how maintaining a transcriptional circuitry nucleated around Thpok and Runx proteins, the key architects of CD4+-CD8+ lineage commitment in the thymus, is critical for CD4+ T cell helper functions. PMID:27260768

Production and characterization of monoclonal antibodies specific for canine CD138 (syndecan-1) for nuclear medicine preclinical trials on spontaneous tumours.

PubMed

Diab, M; Nguyen, F; Berthaud, M; Maurel, C; Gaschet, J; Verger, E; Ibisch, C; Rousseau, C; Chérel, M; Abadie, J; Davodeau, F

2017-09-01

We isolated 11 antibodies specific for canine CD138 (cCD138) to validate the interest of CD138 antigen targeting in dogs with spontaneous mammary carcinoma. The affinity of the monoclonal antibodies in the nanomolar range is suitable for immunohistochemistry and nuclear medicine applications. Four distinct epitopes were recognized on cCD138 by this panel of antibodies. CD138 expression in canine healthy tissues is comparable to that reported in humans. CD138 is frequently expressed in canine mammary carcinomas corresponding to the human triple negative breast cancer subtype, with cytoplasmic and membranous expression. In canine diffuse large B-cell lymphoma, CD138 expression is associated with the 'non-germinal center' phenotype corresponding to the most aggressive subtype in humans. This homology of CD138 expression between dogs and humans confirms the relevance of tumour-bearing dogs as spontaneous models for nuclear medicine applications, especially for the evaluation of new tumour targeting strategies for diagnosis by phenotypic imaging and radio-immunotherapy. © 2016 John Wiley & Sons Ltd.

Integrated Treatment to Achieve Functional Recovery for First-Episode Psychosis

PubMed Central

Valencia, Marcelo; Juarez, Francisco; Ortega, Hector

2012-01-01

This study describes an integrated treatment approach that was implemented to enhance functional recovery in first-episode psychotic patients. Patients were randomized to two treatment conditions: either to an integrated treatment approach: pharmacotherapy, psychosocial treatment, and psychoeducation (experimental group: N = 39) or to medication alone (control group: N = 34). Patients were evaluated at baseline and after one year of treatment. Functional recovery was assessed according to symptomatic and functional remission. At the end of treatment, experimental patients showed a 94.9% of symptomatic remission compared to 58.8% of the control group. Functional remission was 56.4% for the experimental group and 3.6% for the control group, while 56.4% of the experimental group met both symptomatic and functional remission criteria and were considered recovered compared to 2.9% of the control group. PMID:22970366

WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy

PubMed Central

Bakula, Daniela; Müller, Amelie J.; Zuleger, Theresia; Takacs, Zsuzsanna; Franz-Wachtel, Mirita; Thost, Ann-Katrin; Brigger, Daniel; Tschan, Mario P.; Frickey, Tancred; Robenek, Horst; Macek, Boris; Proikas-Cezanne, Tassula

2017-01-01

Autophagy is controlled by AMPK and mTOR, both of which associate with ULK1 and control the production of phosphatidylinositol 3-phosphate (PtdIns3P), a prerequisite for autophagosome formation. Here we report that WIPI3 and WIPI4 scaffold the signal control of autophagy upstream of PtdIns3P production and have a role in the PtdIns3P effector function of WIPI1-WIPI2 at nascent autophagosomes. In response to LKB1-mediated AMPK stimulation, WIPI4-ATG2 is released from a WIPI4-ATG2/AMPK-ULK1 complex and translocates to nascent autophagosomes, controlling their size, to which WIPI3, in complex with FIP200, also contributes. Upstream, WIPI3 associates with AMPK-activated TSC complex at lysosomes, regulating mTOR. Our WIPI interactome analysis reveals the scaffold functions of WIPI proteins interconnecting autophagy signal control and autophagosome formation. Our functional kinase screen uncovers a novel regulatory link between LKB1-mediated AMPK stimulation that produces a direct signal via WIPI4, and we show that the AMPK-related kinases NUAK2 and BRSK2 regulate autophagy through WIPI4. PMID:28561066

Paediatric Rome III Criteria-Related Abdominal Pain Is Associated With Helicobacter pylori and Not With Calprotectin.

PubMed

Sýkora, Josef; Huml, Michal; Siala, Konrad; Pomahačová, Renáta; Jehlička, Petr; Liška, Jiří; Kuntscherová, Jana; Schwarz, Jan

2016-10-01

Abdominal pain-related functional gastrointestinal disorders in children include functional dyspepsia, functional abdominal pain, irritable bowel syndrome, and abdominal migraine. We aimed to evaluate a possible association between functional abdominal pain disorders and Helicobacter pylori infection and faecal calprotectin level. Prospective observational study including consecutive children with functional gastrointestinal disorders fulfilling Rome III criteria (cases) and age/sex-matched healthy controls. H pylori has been detected by biopsy-based tests and stool-antigen detection, faecal calprotectin by enzyme-linked immunosorbent assay. A total of 56 cases (27 with functional dyspepsia) and 56 controls were enrolled. H pylori being detected in 17 of 56 cases (30.4%) and 4 of 56 controls (7.1%, odds ratio: 5.7; 95% confidence interval [CI]: 1.8-18.2, P = 0.003). H pylori was detected significantly more frequently in cases with functional dyspepsia (14/27, 51.9% odds ratio: 14.0; 95% CI: 3.9-49.7, P = 0.00001) than in controls and not in cases with other well-recognized functional gastrointestinal complaints (3/29, 10.3%). The median faecal calprotectin level was similar in cases (7.8 μg/g, 95% CI: 7.8-8.4) including those with gastritis, and controls (9.1 μg/g, 95% CI: 7.8-11.3). Gastritis features were more frequent in H pylori-infected and noninfected cases with functional dyspepsia (27/27, 100%) than in cases with other abdominal functional complaints (15/29, 51.7%, P = 0.007). H pylori gastritis and noninfectious gastritis were associated with functional dyspepsia in children referred for abdominal pain-related functional gastrointestinal disorders while faecal calprotectin is not a predictor of gastritis and is similar in children with functional abdominal pain symptoms and in controls.

A Positive Control for Detection of Functional CD4 T Cells in PBMC: The CPI Pool.

PubMed

Schiller, Annemarie; Zhang, Ting; Li, Ruliang; Duechting, Andrea; Sundararaman, Srividya; Przybyla, Anna; Kuerten, Stefanie; Lehmann, Paul V

2017-12-07

Testing of peripheral blood mononuclear cells (PBMC) for immune monitoring purposes requires verification of their functionality. This is of particular concern when the PBMC have been shipped or stored for prolonged periods of time. While the CEF (Cytomegalo-, Epstein-Barr and Flu-virus) peptide pool has become the gold standard for testing CD8 cell functionality, a positive control for CD4 cells is so far lacking. The latter ideally consists of proteins so as to control for the functionality of the antigen processing and presentation compartments, as well. Aiming to generate a positive control for CD4 cells, we first selected 12 protein antigens from infectious/environmental organisms that are ubiquitous: Varicella, Influenza, Parainfluenza, Mumps, Cytomegalovirus, Streptococcus , Mycoplasma , Lactobacillus , Neisseria , Candida , Rubella, and Measles. Of these antigens, three were found to elicited interferon (IFN)-γ-producing CD4 cells in the majority of human test subjects: inactivated cytomegalo-, parainfluenza-, and influenza virions (CPI). While individually none of these three antigens triggered a recall response in all donors, the pool of the three (the 'CPI pool'), did. One hundred percent of 245 human donors tested were found to be CPI positive, including Caucasians, Asians, and African-Americans. Therefore, the CPI pool appears to be suitable to serve as universal positive control for verifying the functionality of CD4 and of antigen presenting cells.

Soluble syndecan-1 (SDC1) serum level as an independent pre-operative predictor of cancer-specific survival in prostate cancer.

PubMed

Szarvas, Tibor; Reis, Henning; Vom Dorp, Frank; Tschirdewahn, Stephan; Niedworok, Christian; Nyirady, Peter; Schmid, Kurt W; Rübben, Herbert; Kovalszky, Ilona

2016-08-01

PSA-screening detects many cases of clinically non-aggressive prostate cancer (PC) leading to significant overtreatment. Therefore, pre-operatively available prognostic biomarkers are needed to help therapy decisions. Syndecan-1 (SDC1) is a promising prognostic tissue marker in several cancers including PC but serum levels of shedded SDC1-ectodomain (sSDC1) have not been assessed in PC. A total of 150 patients with PC were included in this study (n = 99 serum samples, n = 103 paraffin-embedded samples (FFPE), n = 52 overlap). SDC1 protein expression and cellular localization was evaluated by immunohistochemistry (IHC), while sSDC1 serum concentrations were measured by ELISA. Serum sSDC1 levels were compared to those of MMP7, which is known to be a protease involved in SDC1 ectodomain-shedding. Clinico-pathological and follow-up data were collected and correlated with SDC1 tissue and serum levels. Disease (PC)-specific (DSS) and overall-survival (OS) were primary endpoints. Median follow-up was 167 months in the serum- and 146 months in the FFPE-group. SDC1-reactivity was higher in non-neoplastic prostate glands compared to PC. In addition, cytoplasmatic, but not membranous SDC1 expression was enhanced in PC patients with higher Gleason-score >6 PC (P = 0.016). Soluble SDC1-levels were higher in patients with Gleason-score >6 (P = 0.043) and metastatic disease (P = 0.022) as well as in patients with progressed disease treated with palliative transurethral resection (P = 0.002). In addition, sSDC1 levels were associated with higher MMP7 serum concentration (P = 0.005). In univariable analyses, only sSDC1-levels exhibited a trend to unfavorable DSS (P = 0.077). In a multivariable pre-operative model, high pre-operative sSDC1-level (>123 ng/ml) proved to be an independent marker of adverse OS (P = 0.048) and DSS (P = 0.020). The present study does not confirm the prognostic relevance of SDC1-IHC. The significant higher sSDC1 serum levels in advanced cases of PC, suggest that SDC1 shedding might be involved in PC progression. Additionally, high sSDC1-level proved to be an independent factor of adverse OS and DSS in a multivariable pre-operative model, making evaluation of sSDC1-levels a promising tool for pre-operative risk-stratification and/or therapy monitoring. Prostate 76:977-985, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A Network of HSPG Core Proteins and HS Modifying Enzymes Regulates Netrin-Dependent Guidance of D-Type Motor Neurons in Caenorhabditis elegans

PubMed Central

Gysi, Stephan; Rhiner, Christa; Flibotte, Stephane; Moerman, Donald G.; Hengartner, Michael O.

2013-01-01

Heparan sulfate proteoglycans (HSPGs) are proteins with long covalently attached sugar side chains of the heparan sulfate (HS) type. Depending on the cellular context HS chains carry multiple structural modifications such as sulfate residues or epimerized sugars allowing them to bind to a wide range of molecules. HSPGs have been found to play extremely diverse roles in animal development and were shown to interact with certain axon guidance molecules. In this study we describe the role of the Caenorhabditis elegans HSPG core proteins Syndecan (SDN-1) and Glypican (LON-2) and the HS modifying enzymes in the dorsal guidance of D-type motor axons, a process controlled mainly by the conserved axon guidance molecule UNC-6/Netrin. Our genetic analysis established the specific HS code relevant for this axon guidance event. Using two sensitized genetic backgrounds, we isolated novel components influencing D-type motor axon guidance with a link to HSPGs, as well as new alleles of several previously characterized axon guidance genes. Interestingly, the dorsal axon guidance defects induced by mutations in zfp-1 or lin-35 depended on the transgene oxIs12 used to visualize the D-type motor neurons. oxIs12 is a large multi-copy transgene that enlarges the X chromosome by approximately 20%. In a search for genes with a comparable phenotype we found that a mutation in the known dosage compensation gene dpy-21 showed similar axon guidance defects as zfp-1 or lin-35 mutants. Thus, derepression of genes on X, where many genes relevant for HS dependent axon guidance are located, might also influence axon guidance of D-type motor neurons. PMID:24066155

Different Hippocampus Functional Connectivity Patterns in Healthy Young Adults with Mutations of APP/Presenilin-1/2 and APOEε4.

PubMed

Zheng, Li Juan; Su, Yun Yan; Wang, Yun Fei; Schoepf, U Joseph; Varga-Szemes, Akos; Pannell, Jonathan; Liang, Xue; Zheng, Gang; Lu, Guang Ming; Yang, Gui Fen; Zhang, Long Jiang

2018-04-01

This study aims to explore the hippocampus-based functional connectivity patterns in young, healthy APP and/or presenilin-1/2 mutation carriers and APOE ε4 subjects. Seventy-eight healthy young adults (33 male, mean age 24.0 ± 2.2 years; 18 APP and/or presenilin1/2 mutation carriers [APP/presenilin-1/2 group], 30 APOE ε4 subjects [APOE ε4 group], and 30 subjects without the above-mentioned genes [control group]) underwent resting-state functional MR imaging and neuropsychological assessments. Bilateral hippocampus functional connectivity patterns were compared among three groups. The brain regions with statistical differences were then extracted, and correlation analyses were performed between Z values of the brain regions and neuropsychological results. Compared with control group, both APOE ε4 group and APP/presenilin-1/2 group showed increased functional connectivity in medial prefrontal cortex and precuneus for the seeds of bilateral hippocampi. The APOE ε4 group displayed increased functional connectivity from bilateral hippocampi to the left middle temporal gyrus compared with the control group. Moreover, compared with the APP/presenilin-1/2 group, the APOE ε4 group also had markedly increased functional connectivity in right hippocampus-left middle temporal gyrus. The Z values of right hippocampus-left middle temporal gyrus correlated with various neuropsychological results across all the subjects, as well as in APOE ε4 group. Young healthy adults carrying APOE ε4 and APP/presenilin-1/2 displayed different hippocampus functional connectivity patterns, which may underlie the discrepant mechanisms of gene-modulated cognitive dysfunction in Alzheimer's disease.

The effects of visual control whole body vibration exercise on balance and gait function of stroke patients.

PubMed

Choi, Eon-Tak; Kim, Yong-Nam; Cho, Woon-Soo; Lee, Dong-Kyu

2016-11-01

[Purpose] This study aims to verify the effects of visual control whole body vibration exercise on balance and gait function of stroke patients. [Subjects and Methods] A total of 22 stroke patients were randomly assigned to two groups; 11 to the experimental group and 11 to the control group. Both groups received 30 minutes of Neuro-developmental treatment 5 times per week for 4 weeks. The experimental group additionally performed 10 minutes of visual control whole body vibration exercise 5 times per week during the 4 weeks. Balance was measured using the Functional Reach Test. Gait was measured using the Timed Up and Go Test. [Results] An in-group comparison in the experimental group showed significant differences in the Functional Reach Test and Timed Up and Go Test. In comparing the groups, the Functional Reach Test and Timed Up and Go Test of the experimental group were more significantly different compared to the control group. [Conclusion] These results suggest that visual control whole body vibration exercise has a positive effect on the balance and gait function of stroke patients.

Mindfulness Meditation Training and Executive Control Network Resting State Functional Connectivity: A Randomized Controlled Trial.

PubMed

Taren, Adrienne A; Gianaros, Peter J; Greco, Carol M; Lindsay, Emily K; Fairgrieve, April; Brown, Kirk Warren; Rosen, Rhonda K; Ferris, Jennifer L; Julson, Erica; Marsland, Anna L; Creswell, J David

Mindfulness meditation training has been previously shown to enhance behavioral measures of executive control (e.g., attention, working memory, cognitive control), but the neural mechanisms underlying these improvements are largely unknown. Here, we test whether mindfulness training interventions foster executive control by strengthening functional connections between dorsolateral prefrontal cortex (dlPFC)-a hub of the executive control network-and frontoparietal regions that coordinate executive function. Thirty-five adults with elevated levels of psychological distress participated in a 3-day randomized controlled trial of intensive mindfulness meditation or relaxation training. Participants completed a resting state functional magnetic resonance imaging scan before and after the intervention. We tested whether mindfulness meditation training increased resting state functional connectivity (rsFC) between dlPFC and frontoparietal control network regions. Left dlPFC showed increased connectivity to the right inferior frontal gyrus (T = 3.74), right middle frontal gyrus (MFG) (T = 3.98), right supplementary eye field (T = 4.29), right parietal cortex (T = 4.44), and left middle temporal gyrus (T = 3.97, all p < .05) after mindfulness training relative to the relaxation control. Right dlPFC showed increased connectivity to right MFG (T = 4.97, p < .05). We report that mindfulness training increases rsFC between dlPFC and dorsal network (superior parietal lobule, supplementary eye field, MFG) and ventral network (right IFG, middle temporal/angular gyrus) regions. These findings extend previous work showing increased functional connectivity among brain regions associated with executive function during active meditation by identifying specific neural circuits in which rsFC is enhanced by a mindfulness intervention in individuals with high levels of psychological distress. Clinicaltrials.gov,NCT01628809.

106-17 Telemetry Standards Recorder and Reproducer Command and Control Chapter 6

DTIC Science & Technology

2017-07-01

6-35 6.3 MIL-STD-1553 Remote Terminal Command and Control ..................................... 6-36 6.4 Discrete Command and...6-6 Figure 6-9. Required Discrete Control Functions...6-36 Figure 6-10. Discrete Control and Indicator Functional Diagram .......................................... 6-37 Telemetry Standards

Generic command interpreter for robot controllers

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

Werner, J.

1991-04-09

Generic command interpreter programs have been written for robot controllers at Sandia National Laboratories (SNL). Each interpreter program resides on a robot controller and interfaces the controller with a supervisory program on another (host) computer. We call these interpreter programs monitors because they wait, monitoring a communication line, for commands from the supervisory program. These monitors are designed to interface with the object-oriented software structure of the supervisory programs. The functions of the monitor programs are written in each robot controller's native language but reflect the object-oriented functions of the supervisory programs. These functions and other specifics of the monitormore » programs written for three different robots at SNL will be discussed. 4 refs., 4 figs.« less

The Not4 E3 Ligase and CCR4 Deadenylase Play Distinct Roles in Protein Quality Control

PubMed Central

Halter, David; Collart, Martine A.; Panasenko, Olesya O.

2014-01-01

Eukaryotic cells control their proteome by regulating protein production and protein clearance. Protein production is determined to a large extent by mRNA levels, whereas protein degradation depends mostly upon the proteasome. Dysfunction of the proteasome leads to the accumulation of non-functional proteins that can aggregate, be toxic for the cell, and, in extreme cases, lead to cell death. mRNA levels are controlled by their rates of synthesis and degradation. Recent evidence indicates that these rates have oppositely co-evolved to ensure appropriate mRNA levels. This opposite co-evolution has been correlated with the mutations in the Ccr4-Not complex. Consistently, the deadenylation enzymes responsible for the rate-limiting step in eukaryotic mRNA degradation, Caf1 and Ccr4, are subunits of the Ccr4-Not complex. Another subunit of this complex is a RING E3 ligase, Not4. It is essential for cellular protein solubility and has been proposed to be involved in co-translational quality control. An open question has been whether this role of Not4 resides strictly in the regulation of the deadenylation module of the Ccr4-Not complex. However, Not4 is important for proper assembly of the proteasome, and the Ccr4-Not complex may have multiple functional modules that participate in protein quality control in different ways. In this work we studied how the functions of the Caf1/Ccr4 and Not4 modules are connected. We concluded that Not4 plays a role in protein quality control independently of the Ccr4 deadenylase, and that it is involved in clearance of aberrant proteins at least in part via the proteasome. PMID:24465968

Effects of Exercise on Cognitive Function in Older People with Dementia: A Randomized Controlled Trial.

PubMed

Toots, Annika; Littbrand, Håkan; Boström, Gustaf; Hörnsten, Carl; Holmberg, Henrik; Lundin-Olsson, Lillemor; Lindelöf, Nina; Nordström, Peter; Gustafson, Yngve; Rosendahl, Erik

2017-01-01

Although physical exercise has been suggested to influence cognitive function, previous exercise studies show inconsistent results in people with dementia. To investigate effects of exercise on cognitive function in people with dementia. The Umeå Dementia and Exercise (UMDEX) study, a cluster-randomized controlled trial, was set in 16 nursing homes in Umeå, Sweden. One hundred-and-forty-one women and 45 men with dementia; mean age of 85 y and mean Mini-Mental State Examination (MMSE) score of 15, were randomized to a High-Intensity Functional Exercise program or a seated attention control activity. Blinded assessors measured global cognitive function using the MMSE and the Alzheimer's disease Assessment Scale - Cognitive subscale (ADAS-Cog), and executive function using Verbal fluency (VF) at baseline and 4 months (directly after intervention completion), and MMSE and VF at 7 months. Linear mixed models showed no between-group effects in mean difference from baseline (95% confidence intervals, CI) at 4 months in MMSE (-0.27; 95% CI -1.4 to 0.87, p = 0.644), ADAS-Cog (-1.04, 95% CI -4 to 1.92, p = 0.491), or VF (-0.53, 95% CI -1.42 to 0.35, p = 0.241) or at 7 months in MMSE (-1.15, 95% CI -2.32 to 0.03, p = 0.056) or VF (-0.18, 95% CI -1.09 to 0.74, p = 0.707). A 4-month, high-intensity functional exercise program had no superior effects on global cognition or executive function in people with dementia living in nursing homes when compared with an attention control activity.

Probe-Hole Field Emission Microscope System Controlled by Computer

NASA Astrophysics Data System (ADS)

Gong, Yunming; Zeng, Haishan

1991-09-01

A probe-hole field emission microscope system, controlled by an Apple II computer, has been developed and operated successfully for measuring the work function of a single crystal plane. The work functions on the clean W(100) and W(111) planes are measured to be 4.67 eV and 4.45 eV, respectively.

Cerebral Hemodynamics and Systemic Endothelial Function Are Already Impaired in Well-Controlled Type 2 Diabetic Patients, with Short-Term Disease

PubMed Central

Altavilla, Riccardo; Di Flaviani, Alessandra; Giordani, Ilaria; Malandrucco, Ilaria; Picconi, Fabiana; Passarelli, Francesco; Pasqualetti, Patrizio; Ercolani, Matilde; Vernieri, Fabrizio; Frontoni, Simona

2013-01-01

Objective Impaired cerebral vasomotor reactivity (VMR) and flow-mediated dilation (FMD) were found in selected subgroups of type 2 diabetes mellitus (T2DM) patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN). Research Design and Methods Twenty-six T2DM patients with short-term (4.40±4.80 years) and well-controlled (HbA1C = 6.71±1.29%) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also. Results FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively) compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p<.001 and p<.05). T2DM patients also displayed reduced VMR values than controls (39.4% SD 12.4 vs 51.7%, SD 15.5; p<.05). Sympatho-vagal balance was not different in T2DM patients compared to healthy subjects. FMD and shear rate FMD did not correlate with VMR in T2DM patients or in controls (p>.05). Conclusions In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved. PMID:24391751

F-16 Simulator for Man-in-the-Loop Testing of Aircraft Control Systems (SIMTACS).

DTIC Science & Technology

1987-12-01

Figures Figure Page 2.1. General Hardware Arrangement..................... 12 3.1. DFCS Longitudinal Control Block Diagram .... 21 3.2. DFCS Gain...Functions for Longitudinal Control 22 3.3. DFCS Lateral-Directional Control Block Diagram........................................... 23 3.4. DFCS Gain...Functions for Lateral-Directional Control........................................... 24 3.5. DFCS Control Surface Mixer....................... 25 3.6

KLF2 and KLF4 control endothelial identity and vascular integrity

PubMed Central

Sangwung, Panjamaporn; Zhou, Guangjin; Nayak, Lalitha; Chan, E. Ricky; Kang, Dong-Won; Zhang, Rongli; Lu, Yuan; Sugi, Keiki; Fujioka, Hisashi; Shi, Hong; Lapping, Stephanie D.; Ghosh, Chandra C.; Higgins, Sarah J.; Parikh, Samir M.; Jain, Mukesh K.

2017-01-01

Maintenance of vascular integrity in the adult animal is needed for survival, and it is critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here, we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome, thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke. EC-DKO animals exhibit profound compromise in vascular integrity and profound dysregulation of the coagulation system. Collectively, these studies establish an absolute requirement for KLF2/4 for maintenance of endothelial and vascular integrity in the adult animal. PMID:28239661

Control aspects of the Schuchuli Village stand-alone photovoltaic power system

NASA Astrophysics Data System (ADS)

Groumpos, P. P.; Culler, J. E.; Delombard, R.

1984-11-01

A photovoltaic power system in an Arizona Indian village was installed. The control subsystem of this photovoltaic power system was analyzed. The four major functions of the control subsystem are: (1) voltage regulation; (2) load management; (3) water pump control; and (4) system protection. The control subsystem functions flowcharts for the control subsystem operation, and a computer program that models the control subsystem are presented.

Control aspects of the Schuchuli Village stand-alone photovoltaic power system

NASA Technical Reports Server (NTRS)

Groumpos, P. P.; Culler, J. E.; Delombard, R.

1984-01-01

A photovoltaic power system in an Arizona Indian village was installed. The control subsystem of this photovoltaic power system was analyzed. The four major functions of the control subsystem are: (1) voltage regulation; (2) load management; (3) water pump control; and (4) system protection. The control subsystem functions flowcharts for the control subsystem operation, and a computer program that models the control subsystem are presented.

Regulation of Cell Diameter, For3p Localization, and Cell Symmetry by Fission Yeast Rho-GAP Rga4p

PubMed Central

Das, Maitreyi; Wiley, David J.; Medina, Saskia; Vincent, Helen A.; Larrea, Michelle; Oriolo, Andrea

2007-01-01

Control of cellular dimensions and cell symmetry are critical for development and differentiation. Here we provide evidence that the putative Rho-GAP Rga4p of Schizosaccharomyces pombe controls cellular dimensions. rga4Δ cells are wider in diameter and shorter in length, whereas Rga4p overexpression leads to reduced diameter of the growing cell tip. Consistent with a negative role in cell growth control, Rga4p protein localizes to the cell sides in a “corset” pattern, and to the nongrowing cell tips. Additionally, rga4Δ cells show an altered growth pattern similar to that observed in mutants of the formin homology protein For3p. Consistent with these observations, Rga4p is required for normal localization of For3p and for normal distribution of the actin cytoskeleton. We show that different domains of the Rga4p protein mediate diverse morphological functions. The C-terminal GAP domain mediates For3p localization to the cell tips and maintains cell diameter. Conversely, overexpression of the N-terminal LIM homology domain of Rga4p promotes actin cable formation in a For3p-dependent manner. Our studies indicate that Rga4p functionally interacts with For3p and has a novel function in the control of cell diameter and cell growth. PMID:17377067

Dark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trial.

PubMed

Hammer, Alexandra; Koppensteiner, Renate; Steiner, Sabine; Niessner, Alexander; Goliasch, Georg; Gschwandtner, Michael; Hoke, Matthias

2015-01-01

Flavonoid-rich dark chocolate has positive effects on vascular function in healthy subjects and in patients at risk of atherosclerosis. The impact of dark chocolate on endothelial and microvascular function in patients with symptomatic peripheral artery disease (PAD) has not been investigated so far. In an investigator blinded, randomized, controlled, cross-over trial we assessed the effect of flavonoid-rich dark chocolate and cocoa-free control chocolate on flow-mediated dilatation (FMD) of the brachial artery and on microvascular function (assessed by Laser Doppler fluxmetry) in 21 patients with symptomatic (Fontaine stage II) PAD. Measurements were done in each patient on 2 single days, with an interval of 7 days, at baseline and at 2 hours after ingestion of 50 g dark chocolate or 50 g white chocolate, respectively. FMD remained unchanged after intake of dark chocolate (baseline and 2 hours after ingestion, %: 5.1 [IQR 4.4 to 7.3] and 5.5 [IQR 3.9 to 10.4]; p = 0.57, and after intake of white chocolate (baseline and 2 hours after ingestion, %: 6.4 [IQR 4.5 to 11.4] and 4.4 [IQR 2.6 to 8.7]; p = 0.14. Similarly, microcirculatory parameters were not significantly altered after intake of any chocolate compared with the respective baseline values. In conclusion, a single consumption of 50 g dark chocolate has no effect on endothelial and microvascular function in patients with symptomatic PAD.

32 CFR 631.9 - Duties and functions of boards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ENFORCEMENT AND CRIMINAL INVESTIGATIONS ARMED FORCES DISCIPLINARY CONTROL BOARDS AND OFF-INSTALLATION LIAISON AND OPERATIONS Armed Forces Disciplinary Control Boards § 631.9 Duties and functions of boards. The... 32 National Defense 4 2011-07-01 2011-07-01 false Duties and functions of boards. 631.9 Section...

32 CFR 631.9 - Duties and functions of boards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENFORCEMENT AND CRIMINAL INVESTIGATIONS ARMED FORCES DISCIPLINARY CONTROL BOARDS AND OFF-INSTALLATION LIAISON AND OPERATIONS Armed Forces Disciplinary Control Boards § 631.9 Duties and functions of boards. The... 32 National Defense 4 2010-07-01 2010-07-01 true Duties and functions of boards. 631.9 Section 631...

A role for the melanocortin 4 receptor in sexual function.

PubMed

Van der Ploeg, Lex H T; Martin, William J; Howard, Andrew D; Nargund, Ravi P; Austin, Christopher P; Guan, Xiaoming; Drisko, Jennifer; Cashen, Doreen; Sebhat, Iyassu; Patchett, Arthur A; Figueroa, David J; DiLella, Anthony G; Connolly, Brett M; Weinberg, David H; Tan, Carina P; Palyha, Oksana C; Pong, Sheng-Shung; MacNeil, Tanya; Rosenblum, Charles; Vongs, Aurawan; Tang, Rui; Yu, Hong; Sailer, Andreas W; Fong, Tung Ming; Huang, Cathy; Tota, Michael R; Chang, Ray S; Stearns, Ralph; Tamvakopoulos, Constantin; Christ, George; Drazen, Deborah L; Spar, Brian D; Nelson, Randy J; MacIntyre, D Euan

2002-08-20

By using a combination of genetic, pharmacological, and anatomical approaches, we show that the melanocortin 4 receptor (MC4R), implicated in the control of food intake and energy expenditure, also modulates erectile function and sexual behavior. Evidence supporting this notion is based on several findings: (i) a highly selective non-peptide MC4R agonist augments erectile activity initiated by electrical stimulation of the cavernous nerve in wild-type but not Mc4r-null mice; (ii) copulatory behavior is enhanced by administration of a selective MC4R agonist and is diminished in mice lacking Mc4r; (iii) reverse transcription (RT)-PCR and non-PCR based methods demonstrate MC4R expression in rat and human penis, and rat spinal cord, hypothalamus, brainstem, pelvic ganglion (major autonomic relay center to the penis), but not in rat primary corpus smooth muscle cavernosum cells; and (iv) in situ hybridization of glans tissue from the human and rat penis reveal MC4R expression in nerve fibers and mechanoreceptors in the glans of the penis. Collectively, these data implicate the MC4R in the modulation of penile erectile function and provide evidence that MC4R-mediated proerectile responses may be activated through neuronal circuitry in spinal cord erectile centers and somatosensory afferent nerve terminals of the penis. Our results provide a basis for the existence of MC4R-controlled neuronal pathways that control sexual function.

Randomized controlled comparative study on effect of training to improve lower limb motor paralysis in convalescent patients with post-stroke hemiplegia

PubMed Central

Kawakami, Kenji; Miyasaka, Hiroyuki; Nonoyama, Sayaka; Hayashi, Kazuya; Tonogai, Yusuke; Tanino, Genichi; Wada, Yosuke; Narukawa, Akihisa; Okuyama, Yuko; Tomita, Yutaka; Sonoda, Shigeru

2015-01-01

[Purpose] The motor paralysis-improving effect on the hemiplegic lower limb was compared among mirror therapy, integrated volitional-control electrical stimulation, therapeutic electrical stimulation, repetitive facilitative exercises, and the standard training method in post-stroke hemiplegia patients. [Subjects and Methods] Eighty one stroke patients admitted to a convalescent rehabilitation ward were randomly allocated to the above 5 treatment groups. Each patient performed functional training of the paralytic lower limb for 20 minutes a day for 4 weeks, and changes in the lower limb function were investigated using the Stroke Impairment Assessment Set. [Results] The hip and knee joint functions did not significantly improve in the standard training control group, but significant improvements were observed after 4 weeks in the other intervention groups. Significant improvement was noted in the ankle joint function in all groups. [Conclusion] Although the results were influenced by spontaneous recovery and the standard training in the control group, the hip and knee joints were more markedly improved by the interventions in the other 4 groups of patients with moderate paralysis, compared to the control group. PMID:26504331

Different Use of Cell Surface Glycosaminoglycans As Adherence Receptors to Corneal Cells by Gram Positive and Gram Negative Pathogens

PubMed Central

García, Beatriz; Merayo-Lloves, Jesús; Rodríguez, David; Alcalde, Ignacio; García-Suárez, Olivia; Alfonso, José F.; Baamonde, Begoña; Fernández-Vega, Andrés; Vazquez, Fernando; Quirós, Luis M.

2016-01-01

The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive, and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies. PMID:27965938

Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project. ACT/Control/Guidance System study. Volume 2: Appendices

NASA Technical Reports Server (NTRS)

1982-01-01

The integrated application of active controls (IAAC) technology to an advanced subsonic transport is reported. Supplementary technical data on the following topics are included: (1) 1990's avionics technology assessment; (2) function criticality assessment; (3) flight deck system for total control and functional features list; (4) criticality and reliability assessment of units; (5) crew procedural function task analysis; and (6) recommendations for simulation mechanization.

Relationship between fatigue, perfectionism, and functional dysphonia.

PubMed

O'Hara, James; Miller, Tracey; Carding, Paul; Wilson, Janet; Deary, Vincent

2011-06-01

Increased levels of fatigue and perfectionism were noted during evaluation of cognitive behavioral therapy for the treatment of functional dysphonia. The investigators thus aimed to explore levels of general fatigue and perfectionism in patients with functional dysphonia and controls. Case-control study. Teaching hospital, United Kingdom. Patients recruited through speech therapy were asked to recruit a friend as a control, of the same sex and within 5 years of their age. An 11-point fatigue questionnaire, previously validated on a normal population, was analyzed using both Likert (0123) and bimodal (0011) systems, with a score greater than 4 on the bimodal system implying substantial fatigue. A 35-point perfectionism questionnaire was also completed and analyzed for "healthy" and "unhealthy" perfectionist traits. There were 75 cases and 62 controls. The mean fatigue score in patients with functional dysphonia was 17.0 and 14.4 for the controls (Likert, P = .009). Under the bimodal scoring system, the mean fatigue scores in functional dysphonia (5.10) and controls (3.01) were also significantly different (P = .003). The mean perfectionism scores were 98.9 for patients with functional dysphonia and 91.2 for controls (P = 0.043). To the investigators' knowledge, this is the first substantial report that fatigue and perfectionism scores are significantly elevated in functional dysphonia. Functional dysphonia is shown to be analogous to other medically unexplained physical symptoms that are also marked by generic somatopsychic distress and for which multiple factors are implicated in their onset and maintenance. This has implications for both research and treatment.

Association between melanocortin-4 receptor mutations and eating behaviors in obese patients: a case--control study.

PubMed

Valette, M; Poitou, C; Kesse-Guyot, E; Bellisle, F; Carette, C; Le Beyec, J; Hercberg, S; Clément, K; Czernichow, S

2014-06-01

Melanocortin-4 receptor (MC4R) gene mutations are involved in the leptin-melanocortin pathways that control food intake. The effect of these mutations on eating behavior phenotypes is still debated. To determine the association between functional MC4R mutations and eating behaviors, dietary intake and physical activity, we sequenced the MC4R gene in 4653 obese adults. Among them, 19 adults carriers of functional MC4R mutation were matched on age, sex and body mass index with two randomly-paired controls without MC4R mutation (n=57). We found that eating behaviors and physical activity did not differ between groups. In particular, cases were not at increased risk of binge eating disorders. Subjects carriers of MC4R mutation reported a higher proportion of dietary carbohydrates intakes (43.2±7.1 and 39.2±8.1% of total energy intake, respectively, P=0.048) and a lower proportion of dietary lipids (34.3±6.7 and 38.5±6.7% of total energy intake, respectively, P=0.018). In conclusion, mutation carriers differ from controls by a higher consumption of carbohydrates counterbalanced by a lower consumption of lipids expressed as percentage of total energy intake. However, functional MC4R mutations do not have a higher risk of compulsive eating contrary to what was previously suggested.

Sexual function and hormone profile in young adult men with idiopathic gynecomastia: Comparison with healthy controls.

PubMed

Sir, Emin; Üçer, Oktay; Aksoy, Alper; Güngör, Melike; Ceylan, Yasin

2016-01-22

To compare sexual function and hormone profile in male patients with gynecomastia with matched controls. Forty-seven male subjects with gynecomastia and thirty healthy controls were enrolled in this study. Serum free T3, free T4, TSH, FSH, prolactin, estradiol, total testosterone, free testosterone, DHEA-SO4, LH and total PSA were measured in the patients and controls. Sexual function of the patients and controls were evaluated using International Index of Erectile Function (IIEF). The hormone values and IIEF scores of the patients were statistically compared with the controls'. The mean of age, body mass index, right and left testicular volume in the patient and control group were similar. The mean FSH and free T3 values of the patients were significantly lower than the controls (p = 0.007 and p = 0.03, respectively). The mean of the other hormone values in the both groups were found to be statistically similar (p > 0.05). The mean ±SD of total IIEF scores in the patient and control group were 60.14 ± 8.78 and 65.24 ± 5.52, respectively (p = 0.007). Although the mean IIEF-erectile function, orgasmic function and intercourse satisfaction scores in the patient group were significantly lower than the control group (p < 0.001, p = 0.004 and p = 0.001, respectively), the mean IIEF-desire score of the patients was significantly higher than the controls (p = 0.002). We found that the hormone profiles (except FSH and free T3) of the patients with gynecomastia were similar with the controls. However, gynecomastia adversely affected male sexual function.

Thematic mapper flight model preshipment review data package. Volume 4: Appendix. Part E: Electronics module data

NASA Technical Reports Server (NTRS)

1982-01-01

Tests to verify the as-designed performance of all circuits within the thematic mapper electronics module unit are described. Specifically, the tests involved the evaluation of the scan line corrector driver, shutter drivers function, cal lamp controller function, post amplifier function, command decoder verification unit, and the temperature and actuator controllers function.

Air swallowing, belching, acid and non-acid reflux in patients with functional dyspepsia.

PubMed

Conchillo, J M; Selimah, M; Bredenoord, A J; Samsom, M; Smout, A J P M

2007-04-15

Frequent belching is a common symptom in patients with functional dyspepsia with a reported incidence up to 80%. We hypothesized that patients with functional dyspepsia possibly have a higher frequency of belching than healthy subjects secondary to frequent air swallowing. To assess air swallowing, belching, acid and non-acid reflux patterns of patients with functional dyspepsia. Combined 24-h oesophageal impedance and pH monitoring was performed in 10 functional dyspepsia patients and 10 controls. Analysis of the impedance-pH signals included incidence of air swallows, belching, acid and non-acid reflux. The incidence of air swallows in functional dyspepsia patients were significantly higher compared with controls (153 +/- 15 vs. 79 +/- 10, P < 0.001), while the incidence of liquid-only swallows were not significantly increased. The proportions of gas-containing reflux episodes (belches) and non-acid reflux episodes in functional dyspepsia patients were significantly higher when compared with controls (66.4 vs. 44.4%, P = 0.04 and 70.1 vs. 45.9%, P = 0.009, respectively). Patients with functional dyspepsia swallow air more frequently than controls and this is associated with an increased incidence of non-acid gaseous gastro-oesophageal reflux.

Stressful life events and maltreatment in conversion (functional neurological) disorder: systematic review and meta-analysis of case-control studies.

PubMed

Ludwig, Lea; Pasman, Joëlle A; Nicholson, Timothy; Aybek, Selma; David, Anthony S; Tuck, Sharon; Kanaan, Richard A; Roelofs, Karin; Carson, Alan; Stone, Jon

2018-04-01

Stressful life events and maltreatment have traditionally been considered crucial in the development of conversion (functional neurological) disorder, but the evidence underpinning this association is not clear. We aimed to assess the association between stressors and functional neurological disorder. We systematically reviewed controlled studies reporting stressors occurring in childhood or adulthood, such as stressful life events and maltreatment (including sexual, physical abuse, and emotional neglect) and functional neurological disorder. We did a meta-analysis, with assessments of methodology, sources of bias, and sensitivity analyses. 34 case-control studies, with 1405 patients, were eligible. Studies were of moderate-to-low quality. The frequency of childhood and adulthood stressors was increased in cases compared with controls. Odds ratios (OR) were higher for emotional neglect in childhood (49% for cases vs 20% for controls; OR 5·6, 95% CI 2·4-13·1) compared with sexual abuse (24% vs 10%; 3·3, 2·2-4·8) or physical abuse (30% vs 12%; 3·9, 2·2-7·2). An association with stressful life events preceding onset (OR 2·8, 95% CI 1·4-6·0) was stronger in studies with better methods (interviews; 4·3, 1·4-13·2). Heterogeneity was significant between studies (I 2 21·1-90·7%). 13 studies that specifically ascertained that the participants had not had either severe life events or any subtype of maltreatment all found a proportion of patients with functional neurological disorder reporting no stressor. Stressful life events and maltreatment are substantially more common in people with functional neurological disorder than in healthy controls and patient controls. Emotional neglect had a higher risk than traditionally emphasised sexual and physical abuse, but many cases report no stressors. This outcome supports changes to diagnostic criteria in DSM-5; stressors, although relevant to the cause in many patients, are not a core diagnostic feature. This result has implications for ICD-11. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

B.A.I.L.A. - A Latin dance randomized controlled trial for older Spanish-speaking Latinos: Rationale, design, and methods

PubMed Central

Marquez, David X.; Wilbur, JoEllen; Hughes, Susan; Berbaum, Michael L.; Wilson, Robert; Buchner, David M.; McAuley, Edward

2014-01-01

Physical activity (PA) has documented health benefits, but older Latinos are less likely to engage in leisure time PA than older non-Latino whites. Dance holds promise as a culturally appropriate form of PA that challenges individuals physically and cognitively. This paper describes a randomized controlled trial that will test the efficacy of BAILAMOS©, a 4-month Latin dance program followed by a 4-month maintenance program, for improving lifestyle PA and health outcomes. Older adults (n = 332), aged 55+, Latino/Hispanic, Spanish speaking, with low PA levels, and at risk for disability will be randomized to one of two programs, a dance program or health education control group. BAILAMOS© is a 4-month program that meets two times per week for one hour per session. Dance sessions focus on instruction, including four styles of dance, and couples dancing. Bi-monthly “Fiestas de Baile” (dance parties) are also included, in which participants dance and practice what they have learned.. Monthly 1-hour discussion sessions utilize a Social Cognitive framework and focus on knowledge, social support, and self-efficacy to increase lifestyle PA. The health education control group will meet one time per week for two hours per session. Primary outcomes including PA changes and secondary outcomes including self-efficacy, physical function, cognitive function, and disability will be assessed at baseline, 4, and 8 months. It is hypothesized that PA, self-efficacy, physical function, cognitive function, and functional limitations and disability scores will be significantly better in the BAILAMOS© group at 4 and 8 months compared to the control group. PMID:24969395

Postoperative Functional Recovery After Gastrectomy in Patients Undergoing Enhanced Recovery After Surgery

PubMed Central

Jeong, Oh; Ryu, Seong Yeob; Park, Young Kyu

2016-01-01

Abstract Enhanced recovery after surgery (ERAS) is increasingly used in several abdominal surgeries to accelerate postoperative recovery and reduce the length of stay. The aim of this study was to investigate the pattern of functional recovery after gastrectomy in patients undergoing ERAS and to analyze factors that affect postoperative recovery. In all, 168 gastric cancer patients enrolled in a clinical trial evaluating ERAS compliance after gastrectomy were prospectively assessed with respect to postoperative functional recovery using discharge criteria, evaluating 4 major functional outcomes: adequate pain control, ability to mobilize and self-care, tolerance of oral intake, and no abnormal physical findings or laboratory test. The mean completion time of overall discharge criteria was 5.1 ± 3.2 days. The mean completion time for each dimension were 4.4 ± 0.9 days for adequate pain control, 4.1 ± 0.8 days for ability to mobilize and self-care, 4.3 ± 1.1 days for no abnormal physical signs or laboratory test, and 4.6 ± 1.2 days for tolerance of oral intake. The mean length of stay was 7.2 ± 3.2 days, and readmission rate was 2.4% (n = 4). There was 9.5% (n = 16) of morbidity and no hospital mortality. Female sex (P < 0.001) and age (≥65 years; P = 0.049) were significantly associated with a slower recovery in tolerance of oral intake, and total gastrectomy was significantly associated with delayed completion of adequate pain control (P = 0.003). Functional recovery after gastrectomy can be achieved after about 5 days in patients undergoing ERAS. Female sex, old age, and total gastrectomy are factors that delay normal functional recovery after gastrectomy. PMID:27057836

The relationship between irritable bowel syndrome, functional dyspepsia, chronic fatigue and overactive bladder syndrome: a controlled study 6 years after acute gastrointestinal infection.

PubMed

Persson, Robert; Wensaas, Knut-Arne; Hanevik, Kurt; Eide, Geir Egil; Langeland, Nina; Rortveit, Guri

2015-06-10

To investigate in a cohort with previous gastrointestinal infection and a control group the prevalence of overactive bladder syndrome (OAB), and how it was associated with three other functional disorders; irritable bowel syndrome (IBS), functional dyspepsia (FD) and chronic fatigue (CF). Controlled historic cohort study including 724 individuals with laboratory confirmed giardiasis six years earlier, and 847 controls matched by gender and age. Prevalence and odds ratios (OR) with 95 % confidence intervals (CI) were calculated. The prevalence of OAB was 18.7 % (134/716) in the exposed group and 13.6 % (113/833) in the control group (p = 0.007). The association between OAB and IBS was strong in the control group (OR: 2.42; 95 % CI: 1.45 to 4.04), but insignificant in the Giardia exposed (OR: 1.29; 95 % CI: 0.88 to 1.88). The association between OAB and FD was weak in both groups. CF was strongly associated with OAB (OR: 2.73; 95 % CI: 1.85 to 4.02 in the exposed and OR: 2.79; 95 % CI: 1.69 to 4.62 in the controls), and this association remained when comorbid conditions were excluded. Sporadic IBS was associated with increased risk of OAB, whereas post-infectious IBS was not. An apparent association between OAB and previous Giardia infection can be ascribed to comorbid functional disorders.

Contextual Control by Function and Form of Transfer of Functions

ERIC Educational Resources Information Center

Perkins, David R.; Dougher, Michael J.; Greenway, David E.

2007-01-01

This study investigated conditions leading to contextual control by stimulus topography over transfer of functions. Three 4-member stimulus equivalence classes, each consisting of four (A, B, C, D) topographically distinct visual stimuli, were established for 5 college students. Across classes, designated A stimuli were open-ended linear figures,…

A PI4P-driven electrostatic field controls cell membrane identity and signaling in plants

PubMed Central

Simon, Mathilde Laetitia Audrey; Platre, Matthieu Pierre; Marquès-Bueno, Maria Mar; Armengot, Laia; Stanislas, Thomas; Bayle, Vincent; Caillaud, Marie-Cécile; Jaillais, Yvon

2016-01-01

Many signaling proteins permanently or transiently localize to specific organelles for function. It is well established that certain lipids act as biochemical landmarks to specify compartment identity. However, they also influence membrane biophysical properties, which emerge as important features in specifying cellular territories. Such parameters include the membrane inner surface potential, which varies according to the lipid composition of each organelle. Here, we found that the plant plasma membrane (PM) and the cell plate of dividing cells have a unique electrostatic signature controlled by phosphatidylinositol-4-phosphate (PI4P). Our results further reveal that, contrarily to other eukaryotes, PI4P massively accumulates at the PM, establishing it as a critical hallmark of this membrane in plants. Membrane surface charges control the PM localization and function of the polar auxin transport regulator PINOID, as well as proteins from the BRI1 KINASE INHIBITOR1 (BKI1)/MEMBRANE ASSOCIATED KINASE REGULATORs (MAKRs) family, which are involved in brassinosteroid and receptor-like kinase signaling. We anticipate that this PI4P-driven physical membrane property will control the localization and function of many proteins involved in development, reproduction, immunity and nutrition. PMID:27322096

Effects of a high‐intensity functional exercise program on depressive symptoms among people with dementia in residential care: a randomized controlled trial

PubMed Central

Conradsson, Mia; Hörnsten, Carl; Rosendahl, Erik; Lindelöf, Nina; Holmberg, Henrik; Nordström, Peter; Gustafson, Yngve; Littbrand, Håkan

2015-01-01

Objectives The aim of this study is to evaluate the effect of a high‐intensity functional exercise program on depressive symptoms among older care facility residents with dementia. Methods Residents (n = 186) with a diagnosis of dementia, age ≥ 65 years, Mini‐Mental State Examination score ≥ 10, and dependence in activities of daily living were included. Participants were randomized to a high‐intensity functional exercise program or a non‐exercise control activity conducted 45 min every other weekday for 4 months. The 15‐item Geriatric Depression Scale (GDS) and the Montgomery–Åsberg Depression Rating Scale (MADRS) were administered by blinded assessors at baseline, 4, and 7 months. Results No difference between the exercise and control activity was found in GDS or MADRS score at 4 or 7 months. Among participants with GDS scores ≥ 5, reductions in GDS score were observed in the exercise and control groups at 4 months (–1.58, P = 0.001 and –1.54, P = 0.004) and 7 months (–1.25, P = 0.01 and –1.45, P = 0.007). Among participants with MADRS scores ≥ 7, a reduction in MADRS score was observed at 4 months in the control group (–2.80, P = 0.009) and at 7 months in the exercise and control groups (–3.17, P = 0.003 and –3.34, P = 0.002). Conclusions A 4‐month high‐intensity functional exercise program has no superior effect on depressive symptoms relative to a control activity among older people with dementia living in residential care facilities. Exercise and non‐exercise group activities may reduce high levels of depressive symptoms. PMID:26644304

Effectiveness of myofascial release in the management of plantar heel pain: a randomized controlled trial.

PubMed

Ajimsha, M S; Binsu, D; Chithra, S

2014-06-01

Previous studies have reported that stretching of the calf musculature and the plantar fascia are effective management strategies for plantar heel pain (PHP). However, it is unclear whether myofascial release (MFR) can improve the outcomes in this population. To investigate whether myofascial release (MFR) reduces the pain and functional disability associated with plantar heel pain (PHP) in comparison with a control group receiving sham ultrasound therapy (SUST). Randomized, controlled, double blinded trial. Nonprofit research foundation clinic in India. Sixty-six patients, 17 men and 49 women with a clinical diagnosis of PHP were randomly assigned into MFR or a control group and given 12 sessions of treatment per client over 4 weeks. The Foot Function Index (FFI) scale was used to assess pain severity and functional disability. The primary outcome measure was the difference in FFI scale scores between week 1 (pretest score), week 4 (posttest score), and follow-up at week 12 after randomization. Additionally, pressure pain thresholds (PPT) were assessed over the affected gastrocnemii and soleus muscles, and over the calcaneus, by an assessor blinded to the treatment allocation. The simple main effects analysis showed that the MFR group performed better than the control group in weeks 4 and 12 (P<0.001). Patients in the MFR and control groups reported a 72.4% and 7.4% reduction, respectively, in their pain and functional disability in week 4 compared with that in week 1, which persisted as 60.6% in the follow-up at week 12 in the MFR group compared to the baseline. The mixed ANOVA also revealed significant group-by-time interactions for changes in PPT over the gastrocnemii and soleus muscles, and the calcaneus (P<0.05). This study provides evidence that MFR is more effective than a control intervention for PHP. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of 4-chlorophenol wastewater treatment on sludge acute toxicity, microbial diversity and functional genes expression in an activated sludge process.

PubMed

Zhao, Jianguo; Li, Yahe; Li, Yu; Yu, Zeya; Chen, Xiurong

2018-05-31

In this study, the effects of 4-chlorophenol (4-CP) wastewater treatment on sludge acute toxicity of luminescent bacteria, microbial diversity and functional genes expression of Pseudomonas were explored. Results showed that in the entire operational process, the sludge acute toxicity acclimated by 4-CP in a sequencing batch bioreactor (SBR) was significantly higher than the control SBR without 4-CP. The dominant phyla in acclimated SBR were Proteobacteria and Firmicutes, which also existed in control SBR. Some identified genera in acclimated SBR were responsible for 4-CP degradation. At the stable operational stages, the functional genes expression of Pseudomonas in acclimated SBR was down-regulated at the end of SBR cycle, and their expression mechanisms needed further research. This study provides a theoretical support to comprehensively understand the sludge performance in industrial wastewater treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Improved Function With Enhanced Protein Intake per Meal: A Pilot Study of Weight Reduction in Frail, Obese Older Adults.

PubMed

Porter Starr, Kathryn N; Pieper, Carl F; Orenduff, Melissa C; McDonald, Shelley R; McClure, Luisa B; Zhou, Run; Payne, Martha E; Bales, Connie W

2016-10-01

Obesity is a significant cause of functional limitations in older adults; yet, concerns that weight reduction could diminish muscle along with fat mass have impeded progress toward an intervention. Meal-based enhancement of protein intake could protect function and/or lean mass but has not been studied during geriatric obesity reduction. In this 6-month randomized controlled trial, 67 obese (body mass index ≥30kg/m(2)) older (≥60 years) adults with a Short Physical Performance Battery score of 4-10 were randomly assigned to a traditional (Control) weight loss regimen or one with higher protein intake (>30g) at each meal (Protein). All participants were prescribed a hypo-caloric diet, and weighed and provided dietary guidance weekly. Physical function (Short Physical Performance Battery) and lean mass (BOD POD), along with secondary measures, were assessed at 0, 3, and 6 months. At the 6-month endpoint, there was significant (p < .001) weight loss in both the Control (-7.5±6.2kg) and Protein (-8.7±7.4kg) groups. Both groups also improved function but the increase in the Protein (+2.4±1.7 units; p < .001) was greater than in the Control (+0.9±1.7 units; p < .01) group (p = .02). Obese, functionally limited older adults undergoing a 6-month weight loss intervention with a meal-based enhancement of protein quantity and quality lost similar amounts of weight but had greater functional improvements relative to the Control group. If confirmed, this dietary approach could have important implications for improving the functional status of this vulnerable population (ClinicalTrials.gov identifier: NCT01715753). © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

Improved Function With Enhanced Protein Intake per Meal: A Pilot Study of Weight Reduction in Frail, Obese Older Adults

PubMed Central

Pieper, Carl F.; Orenduff, Melissa C.; McDonald, Shelley R.; McClure, Luisa B.; Zhou, Run; Payne, Martha E.; Bales, Connie W.

2016-01-01

Abstract Background: Obesity is a significant cause of functional limitations in older adults; yet, concerns that weight reduction could diminish muscle along with fat mass have impeded progress toward an intervention. Meal-based enhancement of protein intake could protect function and/or lean mass but has not been studied during geriatric obesity reduction. Methods: In this 6-month randomized controlled trial, 67 obese (body mass index ≥30kg/m2) older (≥60 years) adults with a Short Physical Performance Battery score of 4–10 were randomly assigned to a traditional (Control) weight loss regimen or one with higher protein intake (>30g) at each meal (Protein). All participants were prescribed a hypo-caloric diet, and weighed and provided dietary guidance weekly. Physical function (Short Physical Performance Battery) and lean mass (BOD POD), along with secondary measures, were assessed at 0, 3, and 6 months. Results: At the 6-month endpoint, there was significant (p < .001) weight loss in both the Control (−7.5±6.2kg) and Protein (−8.7±7.4kg) groups. Both groups also improved function but the increase in the Protein (+2.4±1.7 units; p < .001) was greater than in the Control (+0.9±1.7 units; p < .01) group (p = .02). Conclusion: Obese, functionally limited older adults undergoing a 6-month weight loss intervention with a meal-based enhancement of protein quantity and quality lost similar amounts of weight but had greater functional improvements relative to the Control group. If confirmed, this dietary approach could have important implications for improving the functional status of this vulnerable population (ClinicalTrials.gov identifier: NCT01715753). PMID:26786203

Predicting Cognitive, Functional, and Diagnostic Change over 4 Years Using Baseline Subjective Cognitive Complaints in the Sydney Memory and Ageing Study.

PubMed

Slavin, Melissa J; Sachdev, Perminder S; Kochan, Nicole A; Woolf, Claudia; Crawford, John D; Giskes, Katrina; Reppermund, Simone; Trollor, Julian N; Draper, Brian; Delbaere, Kim; Brodaty, Henry

2015-09-01

There is limited understanding of the usefulness of subjective cognitive complaint(s) (SCC) in predicting longitudinal outcome because most studies focus solely on memory (as opposed to nonmemory cognitive) complaints, do not collect data from both participants and informants, do not control for relevant covariates, and have limited outcome measures. Therefore the authors investigate the usefulness of participant and informant SCCs in predicting change in cognition, functional abilities, and diagnostic classification of mild cognitive impairment or dementia in a community-dwelling sample over 4 years. Nondemented participants (N = 620) in the Sydney Memory and Ageing Study aged between 70 and 90 years completed 15 memory and 9 nonmemory SCC questions. An informant completed a baseline questionnaire that included 15 memory and 4 nonmemory SCC questions relating to the participant. Neuropsychological, functional, and diagnostic assessments were carried out at baseline and again at 4-year follow-up. Cross-sectional and longitudinal analyses were carried out to determine the association between SCC indices and neuropsychological, functional, and diagnostic data while controlling for psychological measures. Once participant characteristics were controlled for, participant complaints were generally not predictive of cognitive or functional decline, although participant memory-specific complaints were predictive of diagnostic conversion. Informant-related memory questions were associated with global cognitive and functional decline and with diagnostic conversion over 4 years. Informant memory complaint questions were better than participant complaints in predicting cognitive and functional decline as well as diagnoses over 4 years. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Meta-analysis of executive functioning in ecstasy/polydrug users.

PubMed

Roberts, C A; Jones, A; Montgomery, C

2016-06-01

Ecstasy/3,4-methylenedioxymethamphetamine (MDMA) use is proposed to cause damage to serotonergic (5-HT) axons in humans. Therefore, users should show deficits in cognitive processes that rely on serotonin-rich, prefrontal areas of the brain. However, there is inconsistency in findings to support this hypothesis. The aim of the current study was to examine deficits in executive functioning in ecstasy users compared with controls using meta-analysis. We identified k = 39 studies, contributing 89 effect sizes, investigating executive functioning in ecstasy users and polydrug-using controls. We compared function-specific task performance in 1221 current ecstasy users and 1242 drug-using controls, from tasks tapping the executive functions - updating, switching, inhibition and access to long-term memory. The significant main effect demonstrated overall executive dysfunction in ecstasy users [standardized mean difference (SMD) = -0.18, 95% confidence interval (CI) -0.26 to -0.11, Z = 5.05, p < 0.001, I 2 = 82%], with a significant subgroup effect (χ 2 = 22.06, degrees of freedom = 3, p < 0.001, I 2 = 86.4%) demonstrating differential effects across executive functions. Ecstasy users showed significant performance deficits in access (SMD = -0.33, 95% CI -0.46 to -0.19, Z = 4.72, p < 0.001, I 2 = 74%), switching (SMD = -0.19, 95% CI -0.36 to -0.02, Z = 2.16, p < 0.05, I 2 = 85%) and updating (SMD = -0.26, 95% CI -0.37 to -0.15, Z = 4.49, p < 0.001, I 2 = 82%). No differences were observed in inhibitory control. We conclude that this is the most comprehensive analysis of executive function in ecstasy users to date and provides a behavioural correlate of potential serotonergic neurotoxicity.

Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

PubMed

Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

2016-06-01

Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

[Study on the fund to ensure the implementation of public function of province-level, city-level and county-level center of disease prevention and control in China].

PubMed

Chang, Feng-shui; Wang, Ying; Luo, Li; Sun, Mei

2005-11-01

To calculate the fund to ensure the implementation of public function of province-level, city-level and county-level center of disease prevention and control in China. The principle was to fulfill public function, promote professional efficiency and give a comprehensive attention to employee depletion. Basic data were collected by sample CDC investigation. Value of some special indicators was demonstrated by specialist group. Results To ensure the implementation of public function, a total of 15.7 billion Yen per year should be allocated to all province-level, city-level and county-level center of disease prevention and control. The personnel expenses was 8.4 billion Yen and the daily expenses was 7.4 billion Yen per year.

New insights into potential functions for the protein 4.1superfamily of proteins in kidney epithelium

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

Calinisan, Venice; Gravem, Dana; Chen, Ray Ping-Hsu

2005-06-17

Members of the protein 4.1 family of adapter proteins are expressed in a broad panel of tissues including various epithelia where they likely play an important role in maintenance of cell architecture and polarity and in control of cell proliferation. We have recently characterized the structure and distribution of three members of the protein 4.1 family, 4.1B, 4.1R and 4.1N, in mouse kidney. We describe here binding partners for renal 4.1 proteins, identified through the screening of a rat kidney yeast two-hybrid system cDNA library. The identification of putative protein 4.1-based complexes enables us to envision potential functions for 4.1more » proteins in kidney: organization of signaling complexes, response to osmotic stress, protein trafficking, and control of cell proliferation. We discuss the relevance of these protein 4.1-based interactions in kidney physio-pathology in the context of their previously identified functions in other cells and tissues. Specifically, we will focus on renal 4.1 protein interactions with beta amyloid precursor protein (beta-APP), 14-3-3 proteins, and the cell swelling-activated chloride channel pICln. We also discuss the functional relevance of another member of the protein 4.1 superfamily, ezrin, in kidney physiopathology.« less

Knowing Minds, Controlling Actions: The Developmental Relations between Theory of Mind and Executive Function from 2 to 4 Years of Age

ERIC Educational Resources Information Center

Muller, Ulrich; Liebermann-Finestone, Dana P.; Carpendale, Jeremy I. M.; Hammond, Stuart I.; Bibok, Maximilian B.

2012-01-01

This longitudinal study examined the concurrent and predictive relations between executive function (EF) and theory of mind (ToM) in 82 preschoolers who were assessed when they were 2, 3, and 4 years old. The results showed that the concurrent relation between EF and ToM, after controlling for age, verbal ability, and sex, was significant at 3 and…

A Randomized Controlled Trial Examining the Effects of Reflexology on Children With Functional Constipation.

PubMed

Canbulat Sahiner, Nejla; Demirgoz Bal, Meltem

Functional constipation is a common problem in Turkey that affects up to 10% of children. Reflexologists claim that reflexology can be beneficial in the treatment of constipation. The aim of this randomized controlled study was to determine the effectiveness of reflexology in treating functional constipation in children. Thirty-seven children who were referred to a pediatrician with functional constipation as defined by the Rome III criteria were recruited to the study. After the physician's diagnosis, two groups (intervention/control) were created. The intervention and control groups comprised 17 and 20 children, respectively. Each child in the intervention group was given a foot massage for 10 minutes five times a week, and toilet/diet/motivation training was given to their parents. The test period lasted for 4 weeks. Toilet/diet/motivation training was undertaken for 30 minutes once per week (for a total of 4 weeks) in an interactive manner. The parents of children in the control group received equivalent toilet/diet/motivation training only. No significant differences in terms of feces frequency and feces consistency were noted between the intervention and control groups (p > .05). This study sample showed that only toilet/diet/motivation training had potential benefit for treating functional constipation in children. Further larger randomized trials are required to establish whether there are benefits to foot message in the treatment of functional constipation in children.

Mirror therapy improves hand function in subacute stroke: a randomized controlled trial.

PubMed

Yavuzer, Gunes; Selles, Ruud; Sezer, Nebahat; Sütbeyaz, Serap; Bussmann, Johannes B; Köseoğlu, Füsun; Atay, Mesut B; Stam, Henk J

2008-03-01

To evaluate the effects of mirror therapy on upper-extremity motor recovery, spasticity, and hand-related functioning of inpatients with subacute stroke. Randomized, controlled, assessor-blinded, 4-week trial, with follow-up at 6 months. Rehabilitation education and research hospital. A total of 40 inpatients with stroke (mean age, 63.2y), all within 12 months poststroke. Thirty minutes of mirror therapy program a day consisting of wrist and finger flexion and extension movements or sham therapy in addition to conventional stroke rehabilitation program, 5 days a week, 2 to 5 hours a day, for 4 weeks. The Brunnstrom stages of motor recovery, spasticity assessed by the Modified Ashworth Scale (MAS), and hand-related functioning (self-care items of the FIM instrument). The scores of the Brunnstrom stages for the hand and upper extremity and the FIM self-care score improved more in the mirror group than in the control group after 4 weeks of treatment (by 0.83, 0.89, and 4.10, respectively; all P<.01) and at the 6-month follow-up (by 0.16, 0.43, and 2.34, respectively; all P<.05). No significant differences were found between the groups for the MAS. In our group of subacute stroke patients, hand functioning improved more after mirror therapy in addition to a conventional rehabilitation program compared with a control treatment immediately after 4 weeks of treatment and at the 6-month follow-up, whereas mirror therapy did not affect spasticity.

Cardiovascular autonomic function in Cushing's syndrome.

PubMed

Fallo, F; Maffei, P; Dalla Pozza, A; Carli, M; Della Mea, P; Lupia, M; Rabbia, F; Sonino, N

2009-01-01

Cardiac autonomic dysfunction is associated with increased cardiovascular mortality. No data on sympathovagal balance are available in patients with Cushing's syndrome, in whom cardiovascular risk is high. We studied 10 patients with newly diagnosed Cushing's syndrome (1 male/9 females; age mean+/-SD, 47+/-10 yr) and 10 control subjects matched for age, sex, body mass index, and cardiovascular risk factors. In both groups there were 7 patients with arterial hypertension, 3 with diabetes mellitus, and 2 with obesity. Cardiac autonomic function was evaluated by analysis of short time heart rate variability (HRV) measures in frequency domain over 24-h, daytime, and nighttime. The 24-h ambulatory blood pressure monitoring and echocardiography were also performed. In comparison with controls, patients with Cushing's syndrome had lower 24-h (1.3+/-0.6 vs 3.7+/-1.5, mean+/-SD, p<0.01), daytime (2.0+/-1.4 vs 4.5+/-1.6, p<0.01), and night-time (1.0+/-0.4 vs 3.5+/-2.3, p<0.01) low-frequency/ high frequency (LF/HF) power ratio. In the presence of similar LF power, the difference was due to elevation in HF power in Cushing's syndrome compared to controls: 24-h, 12.7+/-6.7 vs 5.8+/-2.8, p<0.01; daytime, 10.2+/-7.3 vs 4.5+/-2.1, p<0.05; nighttime, 14.2+/-7.0 vs 7.8+/-4.7, p<0.05. Eight Cushing patients vs 4 controls had a non-dipping blood pressure profile. At echocardiography, Cushing patients had a greater left ventricular mass index and/or relative wall thickness, and impaired diastolic function, compared with controls. Compared to controls, patients with Cushing's syndrome showed a sympathovagal imbalance, characterized by a relatively increased parasympathetic activity. Whether this autonomic alteration is meant to counterbalance cortisol-induced effects on blood pressure and cardiac structure/function or has a different pathophysiological significance is still unknown.

Functional electrical stimulation enhancement of upper extremity functional recovery during stroke rehabilitation: a pilot study.

PubMed

Alon, Gad; Levitt, Alan F; McCarthy, Patricia A

2007-01-01

To test if functional electrical stimulation (FES) can enhance the recovery of upper extremity function during early stroke rehabilitation. Open-label block-randomized trial, begun during inpatient rehabilitation and continued at the patients' home. Patients were assigned to either FES combined with task-specific upper extremity rehabilitation (n = 7) or a control group that received task-specific therapy alone (n = 8) over 12 weeks. Outcome measures . Hand function (Box & Blocks, B & B; Jebsen-Taylor light object lift, J-T) and motor control (modified Fugl-Meyer, mF-M) were video-recorded for both upper extremities at baseline, 4, 8, and 12 weeks. B&B mean score at 12 weeks favored (P = .049) the FES group (42.3 +/- 16.6 blocks) over the control group (26.3 +/- 11.0 blocks). The FES group J-T task was 6.7 +/- 2.9 seconds and faster (P = .049) than the 11.8 +/- 5.4 seconds of the control group. Mean mF-M score of the FES group at 12 weeks was 49.3 +/- 5.1 points out of 54, compared to the control group that scored 40.6 +/- 8.2 points (P = .042). All patients regained hand function. Upper extremity task-oriented training that begins soon after stroke that incorporates FES may improve upper extremity functional use in patients with mild/moderate paresis more than task-oriented training without FES.

[Reference interval in preliminary investigation of maternal thyroid function during pregnancy in Shenzhen China].

PubMed

Yu, Lian; Yue, Huakui; Lin, Haoyun; Wu, Wenyuan

2014-11-04

To explore the thyroid function distribution of different trimesters among normal pregnant women and establish the reference interval for maternal thyroid function during pregnancy in Shenzhen, China. A prospective study was conducted for healthy pregnant women in first trimester (n = 334), second trimester (n = 272), third trimester (n = 271) and non-pregnant controls (n = 77) from December 2012 to June 2013 at our hospital. Free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), triiodothyronine (TT3) and thyroxine (T4) of four groups were measured and analyzed. And the reference intervals for different trimesters were established. TSH declined in the first trimester and then rose in the second trimester. The reference ranges of TSH for early, middle and late pregnancy were 0.08-4.39, 0.41-4.16 and 0.30-5.46 mIU/L respectively. FT4 and healthy control groups showed no significant difference in the first trimester. But it declined in the second trimester. The reference ranges of FT4 for early, middle and late pregnancy were 7.74-14.58, 6.81-12.00 and 6.36-10.99 pmol/L respectively. FT3 rose slightly in the first trimester and then gradually decreased. The reference ranges of FT3 for early, middle and late pregnancy were 3.59-5.59, 3.34-4.91 and 3.09-4.58 pmol/L respectively. As compared with healthy control women in Shenzhen, thyroid function indicators of pregnant women show statistically significant differences. And the establishment of indicators of women's thyroid function reference intervals for different trimesters has important clinical significance in Shenzhen.

Cognitive function and army rejection rate in young adult male offspring of women with diabetes: a Danish population-based cohort study.

PubMed

Nielsen, Gunnar Lauge; Dethlefsen, Claus; Sørensen, Henrik Toft; Pedersen, Jan Fog; Molsted-Pedersen, Lars

2007-11-01

While maternal diabetes is a known risk factor for perinatal complications, there is little data on long-term intellectual outcome in offspring. We compare the rejection rate and cognitive functioning of military conscripts according to maternal diabetes status during pregnancy. We identified a cohort of Danish male offspring of diabetic mothers born between 1976 and 1984 and followed this cohort together with population-based control subjects to military conscription. The main outcome was army rejection rate and cognitive function measured with a validated intelligence test. The army rejection rate was 52.5% among 282 men whose mothers had diabetes during pregnancy and 45.4% among 870 control subjects (risk difference 7.3 [95% CI 0.6-14.0]). Mean cognitive scores were 41.4 units (95% CI 40.2-42.6) in diabetes-exposed conscripts and 42.7 units (42.0-43.4) in control subjects. Stratification by gestational age, Apgar score, and White's class (A-F) did not change the associations. In a subgroup analysis using available data on A1C levels during pregnancy, this variable was inversely associated with cognitive functioning. In men with maternal A1C <7%, cognitive scores were identical to those in control subjects. The slightly higher army rejection rate in men with maternal diabetes indicates higher morbidity. The identical cognitive functioning in cases of well-controlled maternal diabetes compared with that in control subjects is reassuring, but the negative association between A1C and cognitive score highlights the importance of striving for optimal metabolic control in diabetic women who are or plan to become pregnant.

Effects of Oral L-Carnitine on Liver Functions after Transarterial Chemoembolization in Intermediate-Stage HCC Patients.

PubMed

Hassan, Abeer; Tsuda, Yasuhiro; Asai, Akira; Yokohama, Keisuke; Nakamura, Ken; Sujishi, Tetsuya; Ohama, Hideko; Tsuchimoto, Yusuke; Fukunishi, Shinya; Abdelaal, Usama M; Arafa, Usama A; Hassan, Ali T; Kassem, Ali M; Higuchi, Kazuhide

2015-01-01

Transarterial chemoembolization (TACE) is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP) score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P < 0.01). Conversely, the control group reported a significant CP score deterioration at 1 week (P < 0.05) and 12 weeks after TACE (P < 0.05). L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P < 0.05) and 4 weeks after TACE (P < 0.05). L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P < 0.05), and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P < 0.05). The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination. Conclusion. L-carnitine maintained and improved liver functions after TACE.

Integrated command, control, communications and computation system functional architecture

NASA Technical Reports Server (NTRS)

Cooley, C. G.; Gilbert, L. E.

1981-01-01

The functional architecture for an integrated command, control, communications, and computation system applicable to the command and control portion of the NASA End-to-End Data. System is described including the downlink data processing and analysis functions required to support the uplink processes. The functional architecture is composed of four elements: (1) the functional hierarchy which provides the decomposition and allocation of the command and control functions to the system elements; (2) the key system features which summarize the major system capabilities; (3) the operational activity threads which illustrate the interrelationahip between the system elements; and (4) the interfaces which illustrate those elements that originate or generate data and those elements that use the data. The interfaces also provide a description of the data and the data utilization and access techniques.

Individual Differences in Executive Functioning and Theory of Mind: An Investigation of Inhibitory Control and Planning Ability

ERIC Educational Resources Information Center

Carlson, Stephanie M.; Moses, Louis J.; Claxton, Laura J.

2004-01-01

This research examined the relative contributions of two aspects of executive function--inhibitory control and planning ability--to theory of mind in 49 3- and 4-year-olds. Children were given two standard theory of mind measures (Appearance-Reality and False Belief), three inhibitory control tasks (Bear/Dragon, Whisper, and Gift Delay), three…

A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib

PubMed Central

Yang, Lida; Kaur, Harmandeep; Pestel, Jenny; Looso, Mario; Nolte, Hendrik; Krishnan, Ramesh K.; Bünemann, Moritz; Offermanns, Stefan; Swiercz, Jakub M.

2017-01-01

Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A. We further show that binding of Plexin-B1 to Sema4A promotes the interaction of Sema4A with Scrib, thereby removing Scrib from its complex with the Rac/Cdc42 exchange factor βPIX and decreasing the activity of the small guanosine triphosphatase Rac1 and Cdc42. Our data unravel a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A, which controls cell migration. PMID:28007914

Early self-managed focal sensorimotor rehabilitative training enhances functional mobility and sensorimotor function in patients following total knee replacement: a controlled clinical trial.

PubMed

Moutzouri, Maria; Gleeson, Nigel; Coutts, Fiona; Tsepis, Elias; John, Gliatis

2018-02-01

To assess the effects of early self-managed focal sensorimotor training compared to functional exercise training after total knee replacement on functional mobility and sensorimotor function. A single-blind controlled clinical trial. University Hospital of Rion, Greece. A total of 52 participants following total knee replacement. The primary outcome was the Timed Up and Go Test and the secondary outcomes were balance, joint position error, the Knee Outcome Survey Activities of Daily Living Scale, and pain. Patients were assessed on three separate occasions (presurgery, 8 weeks post surgery, and 14 weeks post surgery). Participants were randomized to either focal sensorimotor exercise training (experimental group) or functional exercise training (control group). Both groups received a 12-week home-based programme prescribed for 3-5 sessions/week (35-45 minutes). Consistently greater improvements ( F 2,98  = 4.3 to 24.8; P < 0.05) in group mean scores favour the experimental group compared to the control group: Timed Up and Go (7.8 ± 2.9 seconds vs. 4.6 ± 2.6 seconds); balance (2.1 ± 0.9° vs. 0.7 ± 1.2°); joint position error (13.8 ± 7.3° vs. 6.2 ± 9.1°); Knee Outcome Survey Activities of Daily Living Scale (44.2 ± 11.3 vs. 26.1 ± 11.4); and pain (5.9 ± 1.3 cm vs. 4.6 ± 1.1 cm). Patterns of improvement for the experimental group over time were represented by a relative effect size range of 1.3-6.5. Overall, the magnitude of improvements in functional mobility and sensorimotor function endorses using focal sensorimotor training as an effective mode of rehabilitation following knee replacement.

Effects of different seating equipment on postural control and upper extremity function in children with cerebral palsy.

PubMed

Sahinoğlu, Dilek; Coskun, Gürsoy; Bek, Nilgün

2017-02-01

Adaptive seating supports for cerebral palsy are recommended to develop and maintain optimum posture, and functional use of upper extremities. To compare the effectiveness of different seating adaptations regarding postural alignment and related functions and to investigate the effects of these seating adaptations on different motor levels. Prospective study. A total of 20 children with spastic cerebral palsy (Gross Motor Function Classification System 3-5) were included. Postural control and function (Seated Postural Control Measure, Sitting Assessment Scale) were measured in three different systems: standard chair, adjustable seating system and custom-made orthosis. In results of all participants ungrouped, there was a significant difference in most parameters of both measurement tools in favor of custom-made orthosis and adjustable seating system when compared to standard chair ( p < 0.0017). There was a difference among interventions in most of the Seated Postural Control Measure results in Level 4 when subjects were grouped according to Gross Motor Function Classification System levels. A difference was observed between standard chair and adjustable seating system in foot control, arm control, and total Sitting Assessment Scale scores; and between standard chair and custom-made orthosis in trunk control, arm control, and total Sitting Assessment Scale score in Level 4. There was no difference in adjustable seating system and custom-made orthosis in Sitting Assessment Scale in this group of children ( p < 0.017). Although custom-made orthosis fabrication is time consuming, it is still recommended since it is custom made, easy to use, and low-cost. On the other hand, the adjustable seating system can be modified according to a patient's height and weight. Clinical relevance It was found that Gross Motor Function Classification System Level 4 children benefitted most from the seating support systems. It was presented that standard chair is sufficient in providing postural alignment. Both custom-made orthosis and adjustable seating system have pros and cons and the best solution for each will be dependent on a number of factors.

Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

PubMed

Zhu, Zheng-Feng; Meng, Kai; Zhong, Yu-Cheng; Qi, Liang; Mao, Xiao-Bo; Yu, Kun-Wu; Zhang, Wei; Zhu, Peng-Fei; Ren, Ze-Peng; Wu, Bang-Wei; Ji, Qin-Wei; Wang, Xiang; Zeng, Qiu-Tang

2014-01-01

CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS. One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction. We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

Effect of hypoxia on the expression of genes encoding insulin-like growth factors and some related proteins in U87 glioma cells without IRE1 function.

PubMed

Minchenko, Dmytro O; Kharkova, A P; Halkin, O V; Karbovskyi, L L; Minchenko, O H

2016-04-01

The aim of the present study was to investigate the effect of hypoxia on the expression of genes encoding insulin-like growth factors (IGF1 and IGF2), their receptor (IGF1R), binding protein-4 (IGFBP4), and stanniocalcin 2 (STC2) in U87 glioma cells in relation to inhibition of endoplasmic reticulum stress signaling mediated by IRE1 (inositol requiring enzyme 1) for evaluation of their possible significance in the control of tumor growth. The expression of IGF1, IGF2, IGF1R, IGFBP4, and STC2 genes in U87 glioma cells transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia was studied by qPCR. The expression of IGF1 and IGF2 genes is down-regulated in glioma cells without IRE1 signaling enzyme function in comparison with the control cells. At the same time, the expression of IGF1R, IGFBP4, and STC2 genes was up-regulated in glioma cells upon inhibition of IRE1, with more significant changes for IGFBP4 and STC2 genes. We also showed that hypoxia does not change significantly the expression of IGF1, IGF2, and IGF1R genes but up-regulated IGFBP4 and STC2 genes expression in control glioma cells. Moreover, the inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 in glioma cells does not change significantly the effect of hypoxia on the expression of IGF1, IGF1R, and IGFBP4 genes but introduces sensitivity of IGF2 gene to hypoxic condition. Thus, the expression of IGF2 gene is resistant to hypoxia only in control glioma cells and significantly down-regulated in cells without functional activity of IRE1 signaling enzyme, which is central mediator of the unfolded protein response and an important component of the tumor growth as well as metabolic diseases. Results of this study demonstrate that the expression of IGF1 and IGF1R genes is resistant to hypoxic condition both in control U87 glioma cells and cells without IRE1 signaling enzyme function. However, hypoxia significantly up-regulates the expression of IGFBP4 gene independently on the inhibition of IRE1 enzyme. These data show that proteins encoded by these genes are resistant to hypoxia except IGFBP4 and participate in the regulation of metabolic and proliferative processes through IRE1 signaling.

A ground based phase control system for the solar power satellite, volume 4

NASA Technical Reports Server (NTRS)

Chie, C. M.

1980-01-01

A ground phase control system is studied as an alternative approach to the current reference retrodirective phase control system in order to simplify the spaceborne hardware requirement. Based on waveform selections, functional subsystems to implement the ground-based phase control concept are identified and functionally represented. It was concluded that the feasibility of the concept becomes unclear if the conditions of the ionosphere and satellite motion are not met.

Impact of Attention Training on Academic Achievement, Executive Functioning, and Behavior: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Kirk, Hannah; Gray, Kylie; Ellis, Kirsten; Taffe, John; Cornish, Kim

2017-01-01

Children with intellectual and developmental disabilities (IDD) experience significant difficulties in attention, learning, executive functions, and behavioral regulation. Emerging evidence suggests that computerized cognitive training may remediate these impairments. In a double blind controlled trial, 76 children with IDD (4-11 years) were…

Pathways from maternal effortful control to child self-regulation: The role of maternal emotional support.

PubMed

Zeytinoglu, Selin; Calkins, Susan D; Swingler, Margaret M; Leerkes, Esther M

2017-03-01

This study examined the direct and indirect pathways from maternal effortful control to 2 aspects of children's self-regulation-executive functioning and behavioral regulation-via maternal emotional support. Two hundred seventy-eight children and their primary caregivers (96% mothers) participated in laboratory visits when children were 4 and 5 years, and teachers reported on children's behavior at kindergarten. At the 4-year assessment, maternal effortful control was measured using the Adult Temperament Questionnaire (Evans & Rothbart, 2007) and maternal emotional support was observed during a semistructured mother-child problem-solving task. At the 5-year assessment, children's executive functioning was measured using laboratory tasks designed to assess updating/working memory, inhibitory control, and cognitive flexibility, whereas behavioral regulation was assessed via teacher-report questionnaires on children's attention control, discipline and persistence, and work habits. Results from structural equation modeling indicated that, after controlling for child gender and minority status, and maternal education, maternal effortful control was indirectly associated with both child executive functioning and behavioral regulation through maternal emotional support. Maternal effortful control had a direct association with children's teacher-reported behavioral regulation but not observed executive functioning. These findings suggest that maternal effortful control may be a key contributing factor to the development of children's self-regulatory competencies through its impact on maternal emotional support. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Pathways from Maternal Effortful Control to Child Self-Regulation: The Role of Maternal Emotional Support

PubMed Central

Zeytinoglu, Selin; Calkins, Susan D.; Swingler, Margaret M.; Leerkes, Esther M.

2016-01-01

This study examined the direct and indirect pathways from maternal effortful control to two aspects of children’s self-regulation – executive functioning and behavioral regulation – via maternal emotional support. Two hundred and seventy eight children and their primary caregivers (96% mothers) participated in laboratory visits when children were 4 and 5 years, and teachers reported on children’s behavior at kindergarten. At the 4-year assessment, maternal effortful control was measured using the Adult Temperament Questionnaire (ATQ; Evans & Rothbart, 2007) and maternal emotional support was observed during a semi-structured mother-child problem-solving task. At the 5-year assessment, children’s executive functioning was measured using laboratory tasks designed to assess updating/working memory, inhibitory control, and cognitive flexibility, whereas behavioral regulation was assessed via teacher-report questionnaires on children’s attention control, discipline and persistence, and work habits. Results from structural equation modeling indicated that, after controlling for child gender and minority status, and maternal education, maternal effortful control was indirectly associated with both child executive functioning and behavioral regulation through maternal emotional support. Maternal effortful control had a direct association with children’s teacher-reported behavioral regulation but not observed executive functioning. These findings suggest that maternal effortful control may be a key contributing factor to the development of children’s self-regulatory competencies through its impact on maternal emotional support. PMID:27929315

Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease

PubMed Central

McLane, Laura M.; Steblyanko, Maria; Anikeeva, Nadia; Ablanedo-Terrazas, Yuria; Demers, Korey; Eller, Michael A.; Streeck, Hendrik; Jansson, Marianne; Sönnerborg, Anders; Canaday, David H.; Naji, Ali; Wherry, E. John; Robb, Merlin L.; Reyes-Teran, Gustavo; Sykulev, Yuri; Betts, Michael R.

2018-01-01

CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues. PMID:29652923

The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

PubMed

Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

2018-01-29

Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

Heterogeneous Concurrent Modeling and Design in Java (Volume 2: Ptolemy II Software Architecture)

DTIC Science & Technology

2008-04-01

file (EPS) suitable for inclusion in word processors. The image in figure 7.3 is such an EPS file imported into FrameMaker . At this time, the EPS...can be imported into word processors. This figure was imported into FrameMaker . 152 Ptolemy II Plot Package 7.2.4 Modifying the format You can control...FixToken class 57 FrameMaker 149 full name 4 function closures 59 function dependency 48 FunctionDependency class 48 FunctionToken 122 FunctionToken

Systematic review of physiotherapy interventions to improve gross motor capacity and performance in children and adolescents with an acquired brain injury.

PubMed

Baque, Emmah; Sakzewski, Leanne; Barber, Lee; Boyd, Roslyn N

2016-01-01

To systematically review the efficacy of physiotherapy interventions to improve gross motor capacity, performance and societal participation in children aged 5-17 years with an acquired brain injury (ABI). Randomized and non-randomized controlled trials, cohort, case series, case-control and case studies were included and classified according to grades of evidence. Methodological quality of studies was assessed using the Downs and Black (D&B) scale and quantitative data was analysed using effect sizes. Two home-based studies investigated functional strength training (one randomized controlled trial, n = 20, level 2b, D&B = 16/32 and one non-randomized self-control study, n = 19, level 4, D&B = 15/32). Four studies evaluated virtual reality including: one pilot study, n = 50, level 4, D&B = 22/32; one single-subject, non-concurrent, randomized multiple baseline study, n = 3, level 4, D&B = 15/32; one case series study, n = 2, level 4, D&B = 15/32; one case study, n = 1, level 4, D&B = 15/32. Effect sizes for the randomized controlled trial ranged between 0.30-1.29 for the Functional Reach and Timed Up and Go outcome measures. There is preliminary evidence to support the efficacy of physiotherapy interventions to improve gross motor outcomes in children with an ABI. Both functional strength training and virtual-reality based therapy are potential treatment options for clinicians to prescribe in either home or clinical settings.

Functional training reduces body fat and improves functional fitness and cholesterol levels in postmenopausal women: a randomized clinical trial.

PubMed

Neves, Lucas M; Fortaleza, Ana C; Rossi, Fabrício E; Diniz, Tiego A; Codogno, Jamile S; Gobbo, Luis A; Gobbi, Sebastião; Freitas, Ismael F

2017-04-01

This randomized clinical trial with concealed allocations, and blinding of the assessors and the data analyst, was aimed at determining the effects of 16 weeks of functional training on the body composition, functional fitness and lipid profiles in postmenopausal women. The study began with 64 subjects (N.=32 functional training and N.=32 control group) and ended with 50 subjects (N.=28 functional training and N.=22 control group). The exercise was conducted in circuit training format with 8 stations related to the development of muscular strength (using elastic bands for resistance) plus 3 stations focused on balance, coordination, and agility. The training session also incorporated an 18 to 30 minute walk. The control group did not participate in the exercise programs during the period of study. The participants were evaluated before and after the training period as regards their body composition (fat and lean mass), functional fitness, abdominal strength and blood chemistry variables. Significant reductions were observed in all body composition variables related to fat (FM= -3.4 and Android FM= -7.7%) (P<0.05). The functional fitness components had significant improvements in coordination (-33.3%), strength (66.5%), agility (-19.5%) and aerobic capacity (-7%), and significant improvement in abdominal strength (188.2%). We observed significant improvements in total cholesterol (-4.4%) and HDL (-9.9%). The observed data lead us to conclude that functional training utilizing with elastic bands and unstable bases causes significantly improved in body composition, functional fitness and lipid profiles.

Triglycerides are negatively correlated with cognitive function in nondemented aging adults.

PubMed

Parthasarathy, Vishnu; Frazier, Darvis T; Bettcher, Brianne M; Jastrzab, Laura; Chao, Linda; Reed, Bruce; Mungas, Dan; Weiner, Michael; DeCarli, Charles; Chui, Helena; Kramer, Joel H

2017-09-01

Vascular risk factors like hyperlipidemia may adversely affect brain function. We hypothesized that increased serum triglycerides are associated with decreased executive function and memory in nondemented elderly subjects. We also researched possible vascular mediators and white matter microstructure as assessed with diffusion tensor imaging (DTI). Participants were 251 nondemented elderly adults (54% male) with a mean age of 78 (SD = 6.4; range: 62-94) years and a mean education of 15.6 (SD = 2.9; range: 8-23) years. Fasting blood samples were used to detect serum triglyceride and low-density lipoprotein (LDL) levels along with ApoE4 status. DTI was used to determine whole brain fractional anisotropy (FA). Composite executive and memory scores were derived from item response theory. Clinical Dementia Rating (CDR) scores provided informant-based measures of daily functioning. Triglyceride levels were inversely correlated with executive function, but there was no relationship with memory. Controlling for age, gender, and education did not affect this correlation. This relationship persisted after controlling for vascular risk factors like LDL, total cholesterol, CDR and ApoE4 status. Lastly, adding whole-brain FA to the model did not affect the correlation between triglycerides and executive function. Triglyceride levels are inversely correlated with executive function in nondemented elderly adults after controlling for age, education, gender, total cholesterol, LDL, ApoE4 status, CDR, and white-matter microstructure. The fact that the effect of triglycerides on cognition was not clearly mediated by vascular risks or cerebrovascular injury raises questions about widely held assumptions of how triglycerides might impact cognition function. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Melanopsin Phototransduction Contributes to Light-Evoked Choroidal Expansion and Rod L-Type Calcium Channel Function In Vivo.

PubMed

Berkowitz, Bruce A; Schmidt, Tiffany; Podolsky, Robert H; Roberts, Robin

2016-10-01

In humans, rodents, and pigeons, the dark → light transition signals nonretinal brain tissue to increase choroidal thickness, a major control element of choroidal blood flow, and thus of photoreceptor and retinal pigment epithelium function. However, it is unclear which photopigments in the retina relay the light signal to the brain. Here, we test the hypothesis that melanopsin (Opn4)-regulated phototransduction modulates light-evoked choroidal thickness expansion in mice. Two-month-old C57Bl/6 wild-type (B6), 4- to 5-month-old C57Bl/6/129S6 wild-type (B6 + S6), and 2-month-old melanopsin knockout (Opn4-/-) on a B6 + S6 background were studied. Retinal anatomy was evaluated in vivo by optical coherence tomography and MRI. Choroidal thickness in dark and light were measured by diffusion-weighted MRI. Rod cell L-type calcium channel (LTCC) function in dark and light (manganese-enhanced MRI [MEMRI]) was also measured. Opn4-/- mice did not show the light-evoked expansion of choroidal thickness observed in B6 and B6 + S6 controls. Additionally, Opn4-/- mice had lower than normal rod cell and inner retinal LTCC function in the dark but not in the light. These deficits were not due to structural abnormalities because retinal laminar architecture and thickness, and choroidal thickness in the Opn4-/- mice were similar to controls. First time evidence is provided that melanopsin phototransduction contributes to dark → light control of murine choroidal thickness. The data also highlight a contribution in vivo of melanopsin phototransduction to rod cell and inner retinal depolarization in the dark.

Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients

PubMed Central

McDonald, Georgia; Deepak, Shantal; Miguel, Laura; Hall, Cleo J.; Isenberg, David A.; Magee, Anthony I.; Butters, Terry; Jury, Elizabeth C.

2014-01-01

Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE) have multiple defects in lymphocyte signaling and function that contribute to disease pathogenesis. Such defects could be attributed to alterations in metabolic processes, including abnormal control of lipid biosynthesis pathways. Here, we reveal that CD4+ T cells from SLE patients displayed an altered profile of lipid raft–associated glycosphingolipids (GSLs) compared with that of healthy controls. In particular, lactosylceramide, globotriaosylceramide (Gb3), and monosialotetrahexosylganglioside (GM1) levels were markedly increased. Elevated GSLs in SLE patients were associated with increased expression of liver X receptor β (LXRβ), a nuclear receptor that controls cellular lipid metabolism and trafficking and influences acquired immune responses. Stimulation of CD4+ T cells isolated from healthy donors with synthetic and endogenous LXR agonists promoted GSL expression, which was blocked by an LXR antagonist. Increased GSL expression in CD4+ T cells was associated with intracellular accumulation and accelerated trafficking of GSL, reminiscent of cells from patients with glycolipid storage diseases. Inhibition of GSL biosynthesis in vitro with a clinically approved inhibitor (N-butyldeoxynojirimycin) normalized GSL metabolism, corrected CD4+ T cell signaling and functional defects, and decreased anti-dsDNA antibody production by autologous B cells in SLE patients. Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis and suggest that targeting GSL biosynthesis restores T cell function in SLE. PMID:24463447

Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients.

PubMed

McDonald, Georgia; Deepak, Shantal; Miguel, Laura; Hall, Cleo J; Isenberg, David A; Magee, Anthony I; Butters, Terry; Jury, Elizabeth C

2014-02-01

Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE) have multiple defects in lymphocyte signaling and function that contribute to disease pathogenesis. Such defects could be attributed to alterations in metabolic processes, including abnormal control of lipid biosynthesis pathways. Here, we reveal that CD4+ T cells from SLE patients displayed an altered profile of lipid raft-associated glycosphingolipids (GSLs) compared with that of healthy controls. In particular, lactosylceramide, globotriaosylceramide (Gb3), and monosialotetrahexosylganglioside (GM1) levels were markedly increased. Elevated GSLs in SLE patients were associated with increased expression of liver X receptor β (LXRβ), a nuclear receptor that controls cellular lipid metabolism and trafficking and influences acquired immune responses. Stimulation of CD4+ T cells isolated from healthy donors with synthetic and endogenous LXR agonists promoted GSL expression, which was blocked by an LXR antagonist. Increased GSL expression in CD4+ T cells was associated with intracellular accumulation and accelerated trafficking of GSL, reminiscent of cells from patients with glycolipid storage diseases. Inhibition of GSL biosynthesis in vitro with a clinically approved inhibitor (N-butyldeoxynojirimycin) normalized GSL metabolism, corrected CD4+ T cell signaling and functional defects, and decreased anti-dsDNA antibody production by autologous B cells in SLE patients. Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis and suggest that targeting GSL biosynthesis restores T cell function in SLE.

Effects of the FITKids randomized controlled trial on executive control and brain function.

PubMed

Hillman, Charles H; Pontifex, Matthew B; Castelli, Darla M; Khan, Naiman A; Raine, Lauren B; Scudder, Mark R; Drollette, Eric S; Moore, Robert D; Wu, Chien-Ting; Kamijo, Keita

2014-10-01

To assess the effect of a physical activity (PA) intervention on brain and behavioral indices of executive control in preadolescent children. Two hundred twenty-one children (7-9 years) were randomly assigned to a 9-month afterschool PA program or a wait-list control. In addition to changes in fitness (maximal oxygen consumption), electrical activity in the brain (P3-ERP) and behavioral measures (accuracy, reaction time) of executive control were collected by using tasks that modulated attentional inhibition and cognitive flexibility. Fitness improved more among intervention participants from pretest to posttest compared with the wait-list control (1.3 mL/kg per minute, 95% confidence interval [CI]: 0.3 to 2.4; d = 0.34 for group difference in pre-to-post change score). Intervention participants exhibited greater improvements from pretest to posttest in inhibition (3.2%, 95% CI: 0.0 to 6.5; d = 0.27) and cognitive flexibility (4.8%, 95% CI: 1.1 to 8.4; d = 0.35 for group difference in pre-to-post change score) compared with control. Only the intervention group increased attentional resources from pretest to posttest during tasks requiring increased inhibition (1.4 µV, 95% CI: 0.3 to 2.6; d = 0.34) and cognitive flexibility (1.5 µV, 95% CI: 0.6 to 2.5; d = 0.43). Finally, improvements in brain function on the inhibition task (r = 0.22) and performance on the flexibility task correlated with intervention attendance (r = 0.24). The intervention enhanced cognitive performance and brain function during tasks requiring greater executive control. These findings demonstrate a causal effect of a PA program on executive control, and provide support for PA for improving childhood cognition and brain health. Copyright © 2014 by the American Academy of Pediatrics.

Cognitive function in patients with primary adrenal insufficiency (Addison's disease).

PubMed

Schultebraucks, Katharina; Wingenfeld, Katja; Heimes, Jana; Quinkler, Marcus; Otte, Christian

2015-05-01

Patients with primary adrenal insufficiency (AI) need to replace glucocorticoids and mineralocorticoids that act on glucocorticoid (GR) and mineralocorticoid receptors (MR). Both receptors are highly expressed in the hippocampus and are closely associated with cognitive function, which might be impaired by insufficient or increased GR and MR stimulation. However, little is known about cognitive function in patients with AI. It was examined whether patients with AI exhibit worse cognitive function compared to sex-, age-, and education-matched controls. Cognitive function (executive function, concentration, verbal memory, visual memory, working memory, and autobiographical memory) was assessed in 30 patients with AI (mean age 52.4 yrs. ±14.4, n=21 women, mean duration of illness 18.2 yrs. ±11.1) and 30 matched controls. We also measured depressive symptoms, body mass index (BMI), and blood pressure. Patients with AI showed more depressive symptoms, had a greater BMI and lower systolic blood pressure compared to controls. Adjusted analyses controlling for these variables revealed that patients with AI performed significantly worse in verbal learning (F=7.8, p=.007). Executive function, concentration, working memory, verbal memory, visuospatial memory, and autobiographical memory did not differ between groups. No clinically relevant cognitive impairment was found in patients with AI compared to matched controls. Even long-term glucocorticoid and mineralocorticoid substitution over almost two decades appears to have only subtle effects on cognition in patients with AI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Current and advanced act control system definition study

NASA Technical Reports Server (NTRS)

1982-01-01

The Current and Advanced Technology ACT control system definition tasks of the Integrated Application of Active Controls (IAAC) Technology project within the Energy Efficient Transport Program are summarized. The systems mechanize six active control functions: (1) pitch augmented stability; (2) angle of attack limiting; (3) lateral/directional augmented stability; (4) gust load alleviation; (5) maneuver load control; and (6) flutter mode control. The redundant digital control systems meet all function requirements with required reliability and declining weight and cost as advanced technology is introduced.

Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study.

PubMed

Männikkö, Roope; Wong, Leonie; Tester, David J; Thor, Michael G; Sud, Richa; Kullmann, Dimitri M; Sweeney, Mary G; Leu, Costin; Sisodiya, Sanjay M; FitzPatrick, David R; Evans, Margaret J; Jeffrey, Iona J M; Tfelt-Hansen, Jacob; Cohen, Marta C; Fleming, Peter J; Jaye, Amie; Simpson, Michael A; Ackerman, Michael J; Hanna, Michael G; Behr, Elijah R; Matthews, Emma

2018-04-14

Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant death in high-income countries. Central respiratory system dysfunction seems to contribute to these deaths. Excitation that drives contraction of skeletal respiratory muscles is controlled by the sodium channel NaV1.4, which is encoded by the gene SCN4A. Variants in NaV1.4 that directly alter skeletal muscle excitability can cause myotonia, periodic paralysis, congenital myopathy, and myasthenic syndrome. SCN4A variants have also been found in infants with life-threatening apnoea and laryngospasm. We therefore hypothesised that rare, functionally disruptive SCN4A variants might be over-represented in infants who died from SIDS. We did a case-control study, including two consecutive cohorts that included 278 SIDS cases of European ancestry and 729 ethnically matched controls without a history of cardiovascular, respiratory, or neurological disease. We compared the frequency of rare variants in SCN4A between groups (minor allele frequency <0·00005 in the Exome Aggregation Consortium). We assessed biophysical characterisation of the variant channels using a heterologous expression system. Four (1·4%) of the 278 infants in the SIDS cohort had a rare functionally disruptive SCN4A variant compared with none (0%) of 729 ethnically matched controls (p=0·0057). Rare SCN4A variants that directly alter NaV1.4 function occur in infants who had died from SIDS. These variants are predicted to significantly alter muscle membrane excitability and compromise respiratory and laryngeal function. These findings indicate that dysfunction of muscle sodium channels is a potentially modifiable risk factor in a subset of infant sudden deaths. UK Medical Research Council, the Wellcome Trust, National Institute for Health Research, the British Heart Foundation, Biotronik, Cardiac Risk in the Young, Higher Education Funding Council for England, Dravet Syndrome UK, the Epilepsy Society, the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, and the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Targeting Behavioral Symptoms and Functional Decline in Dementia: A Randomized Clinical Trial.

PubMed

Gitlin, Laura N; Arthur, Paul; Piersol, Catherine; Hessels, Virginia; Wu, Samuel S; Dai, Yunfeng; Mann, William C

2018-02-01

Dementia-related behavioral symptoms and functional dependence result in poor quality of life for persons with dementia and their caregivers. The goal was to determine whether a home-based activity program (Tailored Activity Program; TAP-VA) would reduce behavioral symptoms and functional dependence of veterans with dementia and caregiver burden. Single-blind (interviewer), parallel, randomized, controlled trial (Clinicaltrials.gov: NCT01357564). Veteran's homes. Veterans with dementia and their family caregivers (N = 160 dyads). Dyads in TAP-VA underwent 8 sessions with occupational therapists to customize activities to the interests and abilities of the veterans and educate their caregivers about dementia and use of customized activity. Caregivers assigned to attention control received up to 8 telephone-based dementia education sessions with a research team member. Primary outcomes included number of behaviors and frequency of their occurrence multiplied by severity of occurrence; secondary outcomes were functional dependence, pain, emotional well-being, caregiver burden (time spent caregiving, upset with behaviors) and affect at 4 (primary endpoint) and 8 months. Of 160 dyads (n = 76 TAP-VA; n = 84 control), 111 completed 4-month interviews (n = 51 TAP-VA; n = 60 control), and 103 completed 8-month interviews (n = 50 TAP-VA; n = 53 control). At 4 months, compared to controls, the TAP-VA group showed reductions in number (difference in mean change from baseline = -0.68, 95% CI = -1.23 to -0.13) and frequency by severity (-24.3, 95% CI = -45.6 to -3.1) of behavioral symptoms, number of activities needing assistance with (-0.80, 95% CI = -1.41 to -0.20), functional dependence level (4.09, 95% CI = 1.06, 7.13), and pain (-1.18, 95% CI = -2.10 to -0.26). Caregivers of veterans in TAP-VA reported less behavior-related distress. Benefits did not extend to 8 months. TAP-VA had positive immediate effects and no adverse events. Because TAP-VA reduces behavioral symptoms, slows functional dependence, and alleviates pain and caregiver distress, it is a viable treatment option for families. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Motions and functional performance after supervised physical therapy program versus home-based program after arthroscopic anterior shoulder stabilization: a randomized clinical trial.

PubMed

Ismail, M M; El Shorbagy, K M

2014-01-01

To compare the effects of a standardized supervised physical therapy versus a controlled home-based programs on the rate of shoulder motion and functional recovery after arthroscopic anterior shoulder stabilization. Twenty-seven patients (18-35years) underwent arthroscopic anterior shoulder stabilization. Patients were randomized into two groups. A supervised group (n=14) received a rehabilitation program, 3 sessions/week for 24 weeks and a controlled home treated group (n=13) who followed a home-based program for same period. Range of motion (ROM) of the shoulder was assessed 4 times after each phase of rehabilitation and function was assessed after the 3rd and 4th phase of rehabilitation. Both groups achieved a significant progressive increase in all shoulder motions throughout the study period. Patients in the supervised group achieved 92.6% and 94.2% of the contralateral side in abduction and forward elevation respectively. The controlled home-based group achieved 87.1% and 94.7% of abduction and forward elevation respectively. For external rotation, the percentage ROM achieved was 81.1% for the supervised group and 76.4% for the controlled home-based group. For function assessment, the two groups showed a significant improvement. However, the two groups were not significantly different from each other in all measured variables. A controlled home-based physical therapy program is as effective as a supervised program in increasing shoulder range of motion and function after arthroscopic anterior shoulder stabilization. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pulsatile dry cupping in chronic low back pain - a randomized three-armed controlled clinical trial.

PubMed

Teut, M; Ullmann, A; Ortiz, M; Rotter, G; Binting, S; Cree, M; Lotz, F; Roll, S; Brinkhaus, B

2018-04-02

We aimed to investigate the effectiveness of two different forms of dry pulsatile cupping in patients with chronic low back pain (cLBP) compared to medication on demand only in a three-armed randomized trial. 110 cLBP patients were randomized to regular pulsatile cupping with 8 treatments plus paracetamol on demand (n = 37), minimal cupping with 8 treatments plus paracetamol on demand (n = 36) or the control group with paracetamol on demand only (n = 37). Primary outcome was the pain intensity on a visual analogue scale (VAS, 0-100 mm) after 4 weeks, secondary outcome parameter included VAS pain intensity after 12 weeks, back function as measured with the 'Funktionsfragebogen Hannover Rücken' (FFbH-R) and health related quality of life questionnaire Short form 36 (SF-36) after 4 and 12 weeks. The mean baseline-adjusted VAS after 4 weeks was 34.9 mm (95% CI: 28.7; 41.2) for pulsatile cupping, 40.4 (34.2; 46.7) for minimal cupping and 56.1 (49.8; 62.4) for control group, resulting in statistically significant differences between pulsatile cupping vs. control (21.2 (12.2; 30.1); p < 0.001) and minimal cupping vs. control (15.7 (6.9; 24.4); p = 0.001). After 12 weeks, mean adjusted VAS difference between pulsatile cupping vs. control was 15.1 ((3.1; 27.1); p = 0.014), and between minimal cupping vs. control 11.5 ((- 0.44; 23.4); p = 0.059). Differences of VAS between pulsatile cupping and minimal cupping showed no significant differences after 4 or 12 weeks. Pulsatile cupping was also better (- 5.8 (- 11.5;-0.1); p = 0.045) compared to control for back function after 4 weeks, but not after 12 weeks (- 5.4 (- 11.7;0.8); p = 0.088), pulsatile cupping also showed better improvements on SF-36 physical component scale compared to control at 4 and 12 weeks (- 5.6 (- 9.3;-2.0); p = 0.003; - 6.1 (- 9.9;-2.4); p = 0.002). For back function and quality of life minimal cupping group was not statistically different to control after 4 and 12 weeks. Paracetamol intake did not differ between the groups (cupping vs. control (7.3 (- 0.4;15.0); p = 0.063); minimal cupping vs. control (6.3 (- 2.0;14.5); p = 0.133). Both forms of cupping were effective in cLBP without showing significant differences in direct comparison after four weeks, only pulsatile cupping showed effects compared to control after 12 weeks. The study was registered at ClinicalTrials.gov (identifier: NCT02090686 ).

Erectile dysfunction in older male stroke patients: correlation between side of hemiplegia and erectile function.

PubMed

Sikiru, Lamina; Shmaila, Hanif; Yusuf, Gagarawa Saidu

2009-06-01

This study was conducted to determine the effects of hemiplegia on erectile function in stroke patients. One hundred and five stroke patients grouped into left (61.78 +/- 7.79 years) and 55 right hemiplegic (62.11 +/- 9.32 years) and 40 age-matched controls (64.00 +/- 8.53 years). The International Index of Erectile Function questionnaire was used for data collection. One way analysis of variance and Spearman correlation tests were used in data analysis. Erectile function was significantly decreased in the both right (IIEF-5, 7.55 +/- 4.07) and left hemiplegic groups (IIEF-5, 10.40 +/- 5.70) compared with the control group (IIEF-5, 20.50 +/- 4.2 7) p < 0.05. Side of hemiplegia significantly correlated with erectile dysfunction at p < 0.01. Conclusively, stroke mostly affects erectile function of right hemiplegia.

Ethnic differences in macrovascular and microvascular function in systolic heart failure.

PubMed

Shantsila, Eduard; Wrigley, Benjamin; Shantsila, Alena; Tapp, Luke D; Blann, Andrew D; Gill, Paramjit S; Lip, Gregory Y H

2011-11-01

Endothelial dysfunction is implicated in the pathophysiological features of heart failure (HF), and ethnic differences in the presentation of cardiovascular disease are evident, with an excess seen among South Asians (SAs). However, data on ethnic differences in endothelial function in HF are limited. In a cross-sectional study, we recruited 128 subjects with systolic HF: 50 SAs, 50 whites, and 28 African Caribbeans (ACs). In addition, SAs with systolic HF were compared with 40 SAs with coronary artery disease without HF ("disease controls") and 40 SA healthy controls. Macrovascular endothelial function was assessed by measurement of flow-mediated dilation (FMD) in response to hyperemia, arterial stiffness was assessed by the pulse-wave velocity, and microvascular endothelial function was assessed by forearm laser Doppler flowmetry. CD144-expressing endothelial microparticles were measured by flow cytometry. When compared with disease controls and healthy controls, SAs with HF had an impaired microvascular response to acetylcholine (P=0.001) and reduced FMD (P<0.001). In comparing ethnic groups, SAs with HF had an impaired response to acetylcholine (123±95.5%) compared with whites (258±156%) and ACs (286±173%, P<0.001 for both). Whites had a higher FMD (8.49±4.63%) than SAs (4.76±4.78%, P<0.001) and ACs (4.55±3.56%, P=0.01). No difference in endothelial-independent response was observed between study groups or in pulse-wave velocity. Ethnicity remained associated with microvascular endothelial function even after adjustment for age, presence of hypertension and diabetes mellitus, blood pressure, and glucose levels (P=0.003). There were no differences in numbers of endothelial microparticles. The SAs with HF have impaired microvascular and macrovascular endothelial function but preserved arterial elastic properties. Significant ethnic differences in endothelial function are evident in subjects with HF, with ethnicity being associated with microvascular endothelial dysfunction in this disorder.

Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health.

PubMed

Deming, Janise D; Pak, Joseph S; Brown, Bruce M; Kim, Moon K; Aung, Moe H; Eom, Yun Sung; Shin, Jung-A; Lee, Eun-Jin; Pardue, Machelle T; Craft, Cheryl Mae

2015-08-01

Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions. A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4-/-) compared with age-matched control, wild-type mice. When 2-month-old Arr4-/- mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4-/- mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4-/- mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged. Our study demonstrates that Arr4-/- mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy.

Supervisory Control Information Management Research (SCIMR) Studies: Determination of Efficiency for a Variety of Input Control Equipment (DEVICE)

DTIC Science & Technology

2010-08-01

Belkin n52te, the Saitek Cyborg Command Unit, the Wacom Bamboo Fun with stylus, the Wacom Bamboo Fun with touch, and the Xbox 360 controller...4 4 Saitek Cyborg Command Unit function mapping ....................................... 4 iv 5 Wacom Bamboo Fun with stylus and touch...versus Belkin n52te by task . 30 B-2 Participants’ preferences for standard mouse versus Saitek Cyborg Command Unit by task

Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

PubMed Central

Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian

2017-01-01

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands—nonstimulated and stimulated salivary flow, α-amylase, total protein—and salivary exoglycosidase activities—N-acetyl-β-hexosaminidase (HEX, HEX A, and HEX B), β-glucuronidase, α-fucosidase, β-galactosidase, and α-mannosidase—was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α-amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands. PMID:29464184

Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes.

PubMed

Maciejczyk, Mateusz; Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian; Zalewska, Anna

2017-01-01

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands-nonstimulated and stimulated salivary flow, α -amylase, total protein-and salivary exoglycosidase activities-N-acetyl- β -hexosaminidase (HEX, HEX A, and HEX B), β -glucuronidase, α -fucosidase, β -galactosidase, and α -mannosidase-was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α -amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

12 CFR 561.4 - Affiliate.

Code of Federal Regulations, 2010 CFR

2010-01-01

... other persons exercising similar functions at the preceding election, or controls in any manner the election of a majority of its directors, trustees, or other persons exercising similar functions; or (b) Of... exercising similar functions are directors of any one savings association. ...

The Change of Left Ventricular Function in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement.

PubMed

Chen, Xuedi; Gao, Cuixia; Gong, Ningning; Wang, Yu; Tian, Limin

2018-01-01

The main purpose of this study was to explore the relationships between serca2a, Ryr2, adipokines, and the left ventricular function in the subclinical hypothyroidism with different TSH levels and to determine the impact of L-T4 treatment on these indexes. Sixty-five male Wistar rats were randomly divided into five groups: control group; sHT A, B, and C group; and sHT + T4 group. The sHT rats were induced by methimazole (MMI), and the sHT + T4 rats were administered with L-T4 treatment after 8 weeks of MMI administration. Serum TT4, TSH, APN, chemerin, and TNF- α were detected by radioimmunoassay kits and ELISA kits; left ventricular function was measured by PowerLab system via subclavian artery catheter. The expression of Serca2a, Ryr2, APN, chemerin, and TNF- α were detected by RT-PCR, Western blot, and immunohistochemistry. The sHT groups had significantly higher TSH, chemerin, and TNF- α and lower Serca2a, Ryr2, and APN. The left ventricular pressure and heart rate in sHT groups were significantly lower in control and sHT + T4 group. Histopathological examination revealed the pathological changes in the sHT rats' heart. L-T4 administration reduced TSH level and improved left ventricular function. TSH can impair left ventricular function by regulating several factors, and L-T4 treatment ameliorates it in sHT rats.

Randomised controlled trial of colostrum to improve intestinal function in patients with short bowel syndrome.

PubMed

Lund, P; Sangild, P T; Aunsholt, L; Hartmann, B; Holst, J J; Mortensen, J; Mortensen, P B; Jeppesen, P B

2012-09-01

Colostrum is rich in immunoregulatory, antimicrobial and trophic components supporting intestinal development and function in newborns. We assessed whether bovine colostrum could enhance intestinal adaptation and function in adult short bowel syndrome (SBS) patients. Twelve SBS patients in this randomised cross-over study received 4 weeks oral supplement of bovine colostrum or an iso-energetic and iso-proteinaceous control (2.4 MJ/d, 500 ml/day) separated by a 4-week washout period. Patients were admitted four times for 72-h periods of fluid, electrolyte and nutrient balance studies. Meals, faeces and urine were weighed, and energy, macronutrient and electrolyte contents were analysed to calculate net nutrient uptake. Body composition was measured by dual-energy X-ray absorptiometry scans, and functional tests of handgrip strength and lung functions were performed. Eight patients completed the study and were included in the analysis. Both supplements (colostrum and control) not only increased protein (0.96 ± 0.42 MJ/d, P=0.004 1.03 ± 0.44 MJ/d, P=0.003) and energy (1.46 ± 1.02 MJ/d, P=0.005, 1.76 ± 1.46 MJ/d, P=0.01) absorption but also absolute faecal wet weight excretions (231 ± 248 g/d, P=0.002, 319 ± 299 g/d, P=0.03), compared with baseline measurements. Both supplements improved handgrip strength (P=0.03) while only the control supplement increased lean body mass (1.12 ± 1.33 kg, P<0.049). Colostrum was not found to be superior to the control. Intake of high-protein milk supplements increased net nutrient absorption for adult SBS patients, but at the expense of increased diarrhoea. Despite high contents of bioactive factors, colostrum did not significantly improve intestinal absorption, body composition or functional tests compared with the control.

A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib.

PubMed

Sun, Tianliang; Yang, Lida; Kaur, Harmandeep; Pestel, Jenny; Looso, Mario; Nolte, Hendrik; Krasel, Cornelius; Heil, Daniel; Krishnan, Ramesh K; Santoni, Marie-Josée; Borg, Jean-Paul; Bünemann, Moritz; Offermanns, Stefan; Swiercz, Jakub M; Worzfeld, Thomas

2017-01-02

Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A. We further show that binding of Plexin-B1 to Sema4A promotes the interaction of Sema4A with Scrib, thereby removing Scrib from its complex with the Rac/Cdc42 exchange factor βPIX and decreasing the activity of the small guanosine triphosphatase Rac1 and Cdc42. Our data unravel a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A, which controls cell migration. © 2017 Sun et al.

49 CFR 236.771 - Machine, control.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Machine, control. 236.771 Section 236.771..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.771 Machine, control. An assemblage of manually operated devices for controlling the functions of a traffic...

49 CFR 236.771 - Machine, control.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Machine, control. 236.771 Section 236.771..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.771 Machine, control. An assemblage of manually operated devices for controlling the functions of a traffic...

49 CFR 236.771 - Machine, control.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Machine, control. 236.771 Section 236.771..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.771 Machine, control. An assemblage of manually operated devices for controlling the functions of a traffic...

49 CFR 236.771 - Machine, control.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Machine, control. 236.771 Section 236.771..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.771 Machine, control. An assemblage of manually operated devices for controlling the functions of a traffic...

Effects of Rosiglitazone, Glyburide, and Metformin on β-Cell Function and Insulin Sensitivity in ADOPT

PubMed Central

Kahn, Steven E.; Lachin, John M.; Zinman, Bernard; Haffner, Steven M.; Aftring, R. Paul; Paul, Gitanjali; Kravitz, Barbara G.; Herman, William H.; Viberti, Giancarlo; Holman, Rury R.

2011-01-01

OBJECTIVE ADOPT (A Diabetes Outcome Progression Trial) demonstrated that initial monotherapy with rosiglitazone provided superior durability of glycemic control compared with metformin and glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine measures of β-cell function and insulin sensitivity from an oral glucose tolerance test (OGTT) over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS Recently diagnosed, drug-naïve patients with type 2 diabetes (4,360 total) were treated for a median of 4.0 years with rosiglitazone, metformin, or glyburide and were examined with periodic metabolic testing using an OGTT. RESULTS Measures of β-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide. Persistent improvements were seen in those who completed 4 years of monotherapy and marked deterioration of β-cell function in those who failed to maintain adequate glucose control with initial monotherapy. CONCLUSIONS The favorable combined changes in β-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes. PMID:21415383

Effects of rosiglitazone, glyburide, and metformin on β-cell function and insulin sensitivity in ADOPT.

PubMed

Kahn, Steven E; Lachin, John M; Zinman, Bernard; Haffner, Steven M; Aftring, R Paul; Paul, Gitanjali; Kravitz, Barbara G; Herman, William H; Viberti, Giancarlo; Holman, Rury R

2011-05-01

ADOPT (A Diabetes Outcome Progression Trial) demonstrated that initial monotherapy with rosiglitazone provided superior durability of glycemic control compared with metformin and glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine measures of β-cell function and insulin sensitivity from an oral glucose tolerance test (OGTT) over a 4-year period among the three treatments. Recently diagnosed, drug-naïve patients with type 2 diabetes (4,360 total) were treated for a median of 4.0 years with rosiglitazone, metformin, or glyburide and were examined with periodic metabolic testing using an OGTT. Measures of β-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide. Persistent improvements were seen in those who completed 4 years of monotherapy and marked deterioration of β-cell function in those who failed to maintain adequate glucose control with initial monotherapy. The favorable combined changes in β-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes.

Reducing Short-Wavelength Blue Light in Dry Eye Patients with Unstable Tear Film Improves Performance on Tests of Visual Acuity.

PubMed

Kaido, Minako; Toda, Ikuko; Oobayashi, Tomoo; Kawashima, Motoko; Katada, Yusaku; Tsubota, Kazuo

2016-01-01

To investigate whether suppression of blue light can improve visual function in patients with short tear break up time (BUT) dry eye (DE). Twenty-two patients with short BUT DE (10 men, 12 women; mean age, 32.4 ± 6.4 years; age range, 23-43 years) and 18 healthy controls (10 men, 8 women; mean age, 30.1 ± 7.4 years; age range, 20-49 years) underwent functional visual acuity (VA) examinations with and without wearing eyeglasses with 50% blue light blocked lenses. The functional VA parameters were starting VA, functional VA, and visual maintenance ratio. The baseline mean values (logarithm of the minimum angle of resolution, logMAR) of functional VA and the visual maintenance ratio were significantly worse in the DE patients than in the controls (P < 0.05), while no significant difference was observed in the baseline starting VA (P > 0.05). The DE patients had significant improvement in mean functional VA and visual maintenance ratio while wearing the glasses (P < 0.05), while there were no significant changes with and without the glasses in the control group (P > 0.05). Protecting the eyes from short-wavelength blue light may help to ameliorate visual impairment associated with tear instability in patients with DE. This finding represents a new concept, which is that the blue light exposure might be harmful to visual function in patients with short BUT DE.

Reducing Short-Wavelength Blue Light in Dry Eye Patients with Unstable Tear Film Improves Performance on Tests of Visual Acuity

PubMed Central

Kaido, Minako

2016-01-01

Purpose To investigate whether suppression of blue light can improve visual function in patients with short tear break up time (BUT) dry eye (DE). Methods Twenty-two patients with short BUT DE (10 men, 12 women; mean age, 32.4 ± 6.4 years; age range, 23–43 years) and 18 healthy controls (10 men, 8 women; mean age, 30.1 ± 7.4 years; age range, 20–49 years) underwent functional visual acuity (VA) examinations with and without wearing eyeglasses with 50% blue light blocked lenses. The functional VA parameters were starting VA, functional VA, and visual maintenance ratio. Results The baseline mean values (logarithm of the minimum angle of resolution, logMAR) of functional VA and the visual maintenance ratio were significantly worse in the DE patients than in the controls (P < 0.05), while no significant difference was observed in the baseline starting VA (P > 0.05). The DE patients had significant improvement in mean functional VA and visual maintenance ratio while wearing the glasses (P < 0.05), while there were no significant changes with and without the glasses in the control group (P > 0.05), Conclusions Protecting the eyes from short-wavelength blue light may help to ameliorate visual impairment associated with tear instability in patients with DE. This finding represents a new concept, which is that the blue light exposure might be harmful to visual function in patients with short BUT DE. PMID:27045760

Sim1 Neurons Are Sufficient for MC4R-Mediated Sexual Function in Male Mice.

PubMed

Semple, Erin; Hill, Jennifer W

2018-01-01

Sexual dysfunction is a poorly understood condition that affects up to one-third of men around the world. Existing treatments that target the periphery do not work for all men. Previous studies have shown that central melanocortins, which are released by pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus, can lead to male erection and increased libido. Several studies specifically implicate the melanocortin 4 receptor (MC4R) in the central control of sexual function, but the specific neural circuitry involved is unknown. We hypothesized that single-minded homolog 1 (Sim1) neurons play an important role in the melanocortin-mediated regulation of male sexual behavior. To test this hypothesis, we examined the sexual behavior of mice expressing MC4R only on Sim1-positive neurons (tbMC4Rsim1 mice) in comparison with tbMC4R null mice and wild-type controls. In tbMC4Rsim1 mice, MC4R reexpression was found in the medial amygdala and paraventricular nucleus of the hypothalamus. These mice were paired with sexually experienced females, and their sexual function and behavior was scored based on mounting, intromission, and ejaculation. tbMC4R null mice showed a longer latency to mount, a reduced intromission efficiency, and an inability to reach ejaculation. Expression of MC4R only on Sim1 neurons reversed the sexual deficits seen in tbMC4R null mice. This study implicates melanocortin signaling via the MC4R on Sim1 neurons in the central control of male sexual behavior. Copyright © 2018 Endocrine Society.

Thrombolysis based on magnetically-controlled surface-functionalized Fe3O4 nanoparticle

PubMed Central

Chang, Ming; Lin, Yu-Hao; Gabayno, Jacque Lynn; Li, Qian; Liu, Xiaojun

2017-01-01

ABSTRACT In this study, the control of magnetic fields to manipulate surface-functionalized Fe3O4 nanoparticles by urokinase coating is investigated for thrombolysis in a microfluidic channel. The urokinase-coated Fe3O4 nanoparticles are characterized using particle size distribution, zeta potential measurement and spectroscopic data. Thrombolytic ratio tests reveal that the efficiency for thrombus cleaning is significantly improved when using magnetically-controlled urokinase-coated Fe3O4 nanoparticles than pure urokinase solution. The average increase in the rate of thrombolysis with the use of urokinase-coated Fe3O4 nanoparticles is about 50%. In vitro thrombolysis test in a microfluidic channel using the coated nanoparticles shows nearly complete removal of thrombus, a result that can be attributed to the clot busting effect of the urokinase as it inhibits the possible formation of blood bolus during the magnetically-activated microablation process. The experiment further demonstrates that a thrombus mass of 10.32 mg in the microchannel is fully removed in about 180 s. PMID:27689864

Slower nerve conduction velocity in individuals with functional ankle instability.

PubMed

Simon, J; Docherty, C

2014-08-01

The purpose of this study is to quantify nerve conduction velocity differences in individuals with functional ankle instability compared to a "healthy" population. 38 participants ages 18-30 were recruited from a large university with approximately 43,000 students. 19 subjects (9 men and 10 women; age=21.0±1.4 years; height=172.0±9.3 cm; mass=74.4±1 2.4 kg) with symptoms of functional ankle instability were in the functional ankle instability group. 19 subjects (10 men, 9 women; age=22.0±2.6 years; height=169.8±9.1 cm; mass=69.0±14.8 kg) with "healthy" ankles were in the control group. Nerve conduction velocity was conducted using one trial at 2 different sites: posterior to the fibular head (fibular), and 10 cm superior/posterior of the first site (popliteal). Nerve conduction velocity (m/sec) was assessed using a SierraWave II system (Cadwell Laboratories; Kennewick, WA). A MANCOVA was performed on the two dependent variables (fibular and popliteal). Covariates included surface temperature of the leg, body mass index, and age. The independent variable was group (functional ankle instability and control). The effect of group was significantly related to nerve conduction velocity at the fibular site (F(1, 27) =16.49, p=0.01) and popliteal site (F(1, 27)=4.51, p=0.01), with responses significantly faster for individuals in the control group than the functional ankle instability group. These results indicate that patients with functional ankle instability might have damage to the peroneal nerve which results in slower peroneal nerve conduction velocity. © Georg Thieme Verlag KG Stuttgart · New York.

Functional Visual Improvement After Cataract Surgery in Eyes With Age-Related Macular Degeneration: Results of the Ophthalmic Surgical Outcomes Data Project.

PubMed

Stock, Michael V; Vollman, David E; Baze, Elizabeth F; Chomsky, Amy S; Daly, Mary K; Lawrence, Mary G

2015-04-01

To determine if cataract surgery on eyes with AMD confers as much functional visual improvement as surgery on eyes without retinal pathology. This is a retrospective analysis of 4924 cataract surgeries from the Veterans Healthcare Administration Ophthalmic Surgical Outcomes Data Project (OSOD). We included cases of eyes with AMD that had both preoperative and postoperative NEI-VFQ-25 questionnaires submitted and compared their outcomes with controls without retinal pathology. We excluded patients with other retinal pathologies (740 patients). The analyses compared changes in visual acuity and overall functional visual improvement and its subscales using t-tests, multivariate logistic regressions, and linear regression modeling. Preoperative and postoperative questionnaires were submitted by 58.3% of AMD and 63.8% of no retinal pathology cases (controls). Analysis of overall score showed that cataract surgery on eyes with AMD led to increased visual function (13.8 ± 2.4 NEI-VFQ units, P < 0.0001); however, increases were significantly less when compared with controls (-6.4 ± 2.9 NEI-VFQ units, P < 0.0001). Preoperative best-corrected visual acuity (preBCVA) in AMD was predictive of postoperative visual function (r = -0.38, P < 0.0001). In controls, postoperative visual function was only weakly associated with preBCVA (r = -0.075, P = 0.0002). Patients with AMD with vision of 20/40 or better had overall outcomes similar to controls (-2.2 ± 4.7 NEI-VFQ units, P = 0.37). Cataract surgery on eyes with AMD offers an increase in functional visual improvement; however, the amount of benefit is associated with the eye's preBCVA. For eyes with preBCVA of 20/40 or greater, the improvement is similar to that of patients without retinal pathology. However, if preBCVA is less than 20/40, the amount of improvement was shown to be significantly less and decreased with decreasing preBCVA.

Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function

PubMed Central

Mackroth, Maria Sophia; Abel, Annemieke; Steeg, Christiane; Schulze zur Wiesch, Julian; Jacobs, Thomas

2016-01-01

In acute Plasmodium falciparum (P. falciparum) malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P. falciparum malaria treated in Germany. Flow cytometric analysis showed a more frequent expression of CTLA4 and PD1 on CD4+ T cells of malaria patients than of healthy control subjects. In vitro stimulation with P. falciparum-infected red blood cells revealed a distinct population of PD1+CTLA4+CD4+ T cells that simultaneously produced IFNγ and IL10. This antigen-specific cytokine production was enhanced by blocking PD1/PDL1 and CTLA4. PD1+CTLA4+CD4+ T cells were further isolated based on surface expression of PD1 and their inhibitory function investigated in-vitro. Isolated PD1+CTLA4+CD4+ T cells suppressed the proliferation of the total CD4+ population in response to anti-CD3/28 and plasmodial antigens in a cell-extrinsic manner. The response to other specific antigens was not suppressed. Thus, acute P. falciparum malaria induces P. falciparum-specific PD1+CTLA4+CD4+ Teffector cells that coproduce IFNγ and IL10, and inhibit other CD4+ T cells. Transient induction of regulatory Teffector cells may be an important mechanism that controls T cell responses and might prevent severe inflammation in patients with malaria and potentially other acute infections. PMID:27802341

Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model.

PubMed

Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Kawaguchi, Naomasa; Nakatani, Satoshi; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

2016-02-01

Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart. We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5). Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P < 0.001; tau, 47 [6.0] vs 36 [4.4] ms: P = 0.005. Ejection fraction, 22 (6.0) versus 46 (7.5) %, P < 0.001; end-systolic elastance, 2.5 (0.4) versus 8.2 (3.5) mm Hg/ml, P = 0.001). Histological examination revealed that the volume of collagen I and the collagen I/III ratio in the myocardium were significantly higher in the control than that in the SMCST group (collagen I, 6.0 [0.8] vs 2.6 [1.3]; P = 0.006; collagen I/III ratio, 4.8 [1.7] vs 1.2 [0.4]; P = 0.010). The potential of SMCST to ameliorate both systolic and diastolic performance was proven. The SMCST may be an alternative therapy of conventional medical treatment in the dilated cardiomyopathy heart.

Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model

PubMed Central

Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Kawaguchi, Naomasa; Nakatani, Satoshi; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

2016-01-01

Background Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart. Methods We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5). Results Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P < 0.001; tau, 47 [6.0] vs 36 [4.4] ms: P = 0.005. Ejection fraction, 22 (6.0) versus 46 (7.5) %, P < 0.001; end-systolic elastance, 2.5 (0.4) versus 8.2 (3.5) mm Hg/ml, P = 0.001). Histological examination revealed that the volume of collagen I and the collagen I/III ratio in the myocardium were significantly higher in the control than that in the SMCST group (collagen I, 6.0 [0.8] vs 2.6 [1.3]; P = 0.006; collagen I/III ratio, 4.8 [1.7] vs 1.2 [0.4]; P = 0.010). Conclusions The potential of SMCST to ameliorate both systolic and diastolic performance was proven. The SMCST may be an alternative therapy of conventional medical treatment in the dilated cardiomyopathy heart. PMID:26636739

Right Atrial Deformation in Predicting Outcomes in Pediatric Pulmonary Hypertension.

PubMed

Jone, Pei-Ni; Schäfer, Michal; Li, Ling; Craft, Mary; Ivy, D Dunbar; Kutty, Shelby

2017-12-01

Elevated right atrial (RA) pressure is a risk factor for mortality, and RA size is prognostic of adverse outcomes in pulmonary hypertension (PH). There is limited data on phasic RA function (reservoir, conduit, and pump) in pediatric PH. We sought to evaluate (1) the RA function in pediatric PH patients compared with controls, (2) compare the RA deformation indices with Doppler indices of diastolic dysfunction, functional capacity, biomarkers, invasive hemodynamics, and right ventricular functional indices, and (3) evaluate the potential of RA deformation indices to predict clinical outcomes. Sixty-six PH patients (mean age 7.9±4.7 years) were compared with 36 controls (7.7±4.4 years). RA and right ventricular deformation indices were obtained using 2-dimensional speckle tracking (2DCPA; TomTec, Germany). RA strain, strain rates, emptying fraction, and right ventricular longitudinal strain were measured. RA function was impaired in PH patients versus controls ( P <0.001). There were significant associations between RA function with invasive hemodynamics ( P <0.01). RA reservoir, pump function, the rate of RA filling, and atrial minimum volume predicted adverse clinical outcomes (hazard ratio [HR], 0.15; confidence interval [CI], 0.03-0.73; P <0.01; HR, 0.05; CI, 0.003-0.43; P <0.004; HR, 0.04; CI, 0.006-0.56; P <0.01; and HR, 8.6; CI, 1.6-37.2; P <0.01, respectively). RA deformation properties are significantly altered in pediatric PH patients. Progressive worsening of RA reservoir and conduit functions is related to changes in right ventricular diastolic dysfunction. RA reservoir function, pump function, the rate of atrial filling, and atrial minimum volume emerged as outcome predictors in pediatric PH. © 2017 American Heart Association, Inc.

Elevated ATF4 Expression, in the Absence of Other Signals, Is Sufficient for Transcriptional Induction via CCAAT Enhancer-binding Protein-activating Transcription Factor Response Elements*

PubMed Central

Shan, Jixiu; Örd, Daima; Örd, Tõnis; Kilberg, Michael S.

2009-01-01

Protein limitation in vivo or amino acid deprivation of cells in culture causes a signal transduction cascade consisting of activation of the kinase GCN2 (general control nonderepressible 2), phosphorylation of eukaryotic initiation factor 2, and increased synthesis of activating transcription factor (ATF) 4 by a translational control mechanism. In a self-limiting transcriptional program, ATF4 transiently activates a wide range of downstream target genes involved in transport, cellular metabolism, and other cell functions. Simultaneous activation of other signal transduction pathways by amino acid deprivation led to the question of whether or not the increased abundance of ATF4 alone was sufficient to trigger the transcriptional control mechanisms. Using 293 cells that ectopically express ATF4 in a tetracycline-inducible manner showed that ATF4 target genes were activated in the absence of amino acid deprivation. Ectopic expression of ATF4 alone resulted in effective recruitment of the general transcription machinery, but some reduction in histone modification was observed. These data document that ATF4 alone is sufficient to trigger the amino acid-responsive transcriptional control program. However, the absolute amount of ectopic ATF4 required to achieve the same degree of transcriptional activation observed after amino acid limitation was greater, suggesting that other factors may serve to enhance ATF4 function. PMID:19509279

Volitional regulation of brain responses to food stimuli in overweight and obese subjects: A real-time fMRI feedback study.

PubMed

Spetter, Maartje S; Malekshahi, Rahim; Birbaumer, Niels; Lührs, Michael; van der Veer, Albert H; Scheffler, Klaus; Spuckti, Sophia; Preissl, Hubert; Veit, Ralf; Hallschmid, Manfred

2017-05-01

Obese subjects who achieve weight loss show increased functional connectivity between dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC), key areas of executive control and reward processing. We investigated the potential of real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback training to achieve healthier food choices by enhancing self-control of the interplay between these brain areas. We trained eight male individuals with overweight or obesity (age: 31.8 ± 4.4 years, BMI: 29.4 ± 1.4 kg/m 2 ) to up-regulate functional connectivity between the dlPFC and the vmPFC by means of a four-day rt-fMRI neurofeedback protocol including, on each day, three training runs comprised of six up-regulation and six passive viewing trials. During the up-regulation runs of the four training days, participants successfully learned to increase functional connectivity between dlPFC and vmPFC. In addition, a trend towards less high-calorie food choices emerged from before to after training, which however was associated with a trend towards increased covertly assessed snack intake. Findings of this proof-of-concept study indicate that overweight and obese participants can increase functional connectivity between brain areas that orchestrate the top-down control of appetite for high-calorie foods. Neurofeedback training might therefore be a useful tool in achieving and maintaining weight loss. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pediatric aquatic therapy on motor function and enjoyment in children diagnosed with cerebral palsy of various motor severities.

PubMed

Lai, Chih-Jou; Liu, Wen-Yu; Yang, Tsui-Fen; Chen, Chia-Ling; Wu, Ching-Yi; Chan, Rai-Chi

2015-02-01

This study investigates the effects of pediatric aquatic therapy on motor function, enjoyment, activities of daily living, and health-related quality of life for children with spastic cerebral palsy of various motor severities. Children with spastic cerebral palsy were assigned to a pediatric aquatic therapy group (n = 11; mean age = 85.0 ± 33.1 months; male : female = 4 : 7) or a control group (n = 13; mean age = 87.6 ± 34.0 months; male : female = 9 : 4). The statistic results indicate that the pediatric aquatic therapy group had greater average 66-item Gross Motor Function Measure following intervention than the control group (η(2) = 0.308, P = .007), even for children with Gross Motor Function Classification System level IV (5.0 vs 1.3). The pediatric aquatic therapy group had higher Physical Activity Enjoyment Scale scores than the control group at post-treatment (P = .015). These findings demonstrate that pediatric aquatic therapy can be an effective and alternative therapy for children with cerebral palsy even with poor Gross Motor Function Classification System level. © The Author(s) 2014.

Cardiac strain findings in children with latent rheumatic heart disease detected by echocardiographic screening.

PubMed

Beaton, Andrea; Richards, Hedda; Ploutz, Michelle; Gaur, Lasya; Aliku, Twalib; Lwabi, Peter; Ensing, Greg; Sable, Craig

2017-08-01

Identification of patients with latent rheumatic heart disease by echocardiography presents a unique opportunity to prevent disease progression. Myocardial strain is a more sensitive indicator of cardiac performance than traditional measures of systolic function. The objective of this study was to test the hypothesis that abnormalities in myocardial strain may be present in children with latent rheumatic heart disease. Standard echocardiography images with electrocardiogram gating were obtained from Ugandan children found to have latent rheumatic heart disease as well as control subjects. Traditional echocardiography measures of systolic function were obtained, and offline global longitudinal strain analysis was performed. Comparison between groups was performed using strain as a continuous (Mann-Whitney U-test) and categorical (cut-off 5th percentile for age) variable. Our study included 14 subjects with definite rheumatic heart disease, 13 with borderline rheumatic heart disease, and 112 control subjects. None of the subjects had abnormal left ventricular size or ejection fraction. Global longitudinal strain was lower than the 5th percentile in 44% of the subjects with any rheumatic heart disease (p=0.002 versus controls) and 57% of the subjects with definite rheumatic heart disease (p=0.03). The mean absolute strain values were significantly lower when comparing subjects with any rheumatic heart disease with controls (20.4±3.95 versus 22.4±4.35, p=0.025) and subjects with definite rheumatic heart disease with controls (19.9±4.25 versus 22.4±4.35, p=0.033). Global longitudinal strain is decreased in subjects with rheumatic heart disease in the absence of abnormal systolic function. Larger studies with longer-term follow-up are required to determine whether there is a role for strain to help better understand the pathophysiology of latent rheumatic heart disease.

Kinematics and constraints associated with swashplate blade pitch control

NASA Technical Reports Server (NTRS)

Leyland, Jane A.

1993-01-01

An important class of techniques to reduce helicopter vibration is based on using a Higher Harmonic controller to optimally define the Higher Harmonic blade pitch. These techniques typically require solution of a general optimization problem requiring the determination of a control vector which minimizes a performance index where functions of the control vector are subject to inequality constraints. Six possible constraint functions associated with swashplate blade pitch control were identified and defined. These functions constrain: (1) blade pitch Fourier Coefficients expressed in the Rotating System, (2) blade pitch Fourier Coefficients expressed in the Nonrotating System, (3) stroke of the individual actuators expressed in the Nonrotating System, (4) blade pitch expressed as a function of blade azimuth and actuator stroke, (5) time rate-of-change of the aforementioned parameters, and (6) required actuator power. The aforementioned constraints and the associated kinematics of swashplate blade pitch control by means of the strokes of the individual actuators are documented.

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

PubMed Central

Johnson, Susan; Eller, Michael; Teigler, Jeffrey E.; Maloveste, Sebastien M.; Schultz, Bruce T.; Soghoian, Damien Z.; Lu, Richard; Oster, Alexander F.; Chenine, Agnès-Laurence; Alter, Galit; Dittmer, Ulf; Marovich, Mary; Robb, Merlin L.; Michael, Nelson L.; Bolton, Diane

2015-01-01

ABSTRACT CD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection. IMPORTANCE The ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology. PMID:25972560

Unilateral versus bilateral robot-assisted rehabilitation on arm-trunk control and functions post stroke: a randomized controlled trial.

PubMed

Wu, Ching-Yi; Yang, Chieh-Ling; Chen, Ming-de; Lin, Keh-Chung; Wu, Li-Ling

2013-04-12

Although the effects of robot-assisted arm training after stroke are promising, the relative effects of unilateral (URT) vs. bilateral (BRT) robot-assisted arm training remain uncertain. This study compared the effects of URT vs. BRT on upper extremity (UE) control, trunk compensation, and function in patients with chronic stroke. This was a single-blinded, randomized controlled trial. The intervention was implemented at 4 hospitals. Fifty-three patients with stroke were randomly assigned to URT, BRT, or control treatment (CT). Each group received UE training for 90 to 105 min/day, 5 days/week, for 4 weeks. The kinematic variables for arm motor control and trunk compensation included normalized movement time, normalized movement units, and the arm-trunk contribution slope in unilateral and bilateral tasks. Motor function and daily function were measured by the Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and ABILHAND Questionnaire. The BRT and CT groups elicited significantly larger slope values (i.e., less trunk compensation) at the start of bilateral reaching than the URT group. URT led to significantly better effects on WMFT-Time than BRT. Differences in arm control kinematics and performance on the MAL and ABILHAND among the 3 groups were not significant. BRT and URT resulted in differential improvements in specific UE/trunk performance in patients with stroke. BRT elicited larger benefits than URT on reducing compensatory trunk movements at the beginning of reaching. In contrast, URT produced better improvements in UE temporal efficiency. These relative effects on movement kinematics, however, did not translate into differential benefits in daily functions. ClinicalTrials.gov: NCT00917605.

Association of HLA-DRB1 alleles and neuropsychological function in autism.

PubMed

Chien, Yi-Ling; Wu, Yu-Yu; Chen, Chia-Hsiang; Gau, Susan Shur-Fen; Huang, Yu-Shu; Chien, Wei-Hsien; Hu, Fu-Chang; Chao, Yu-Lin

2012-02-01

Evidence suggests an association between autism and immune dysfunction. The associations between human lymphocyte antigen (HLA)-A2, B44, DRβ1*04 (DR4), C4B, and haplotype B44-SC30-DR4 and autism have been reported in western countries but there is a lack of such information in Asian population. This study aimed to assess the association between HLA-DRB1 allele frequencies and the clinical phenomenology of autism. The sample included 141 participants (male, 87.2%), who were diagnosed with autistic disorder based on clinical assessments and structured interviews using the Chinese version of the Autism Diagnostic Interview-Revised, and 156 healthy controls (male, 38.6%). The HLA-DRB1 alleles were determined by sequencing-based typing method. A subsample of patients (n=39) were assessed for intelligence and neuropsychological functions. The results showed that the pattern of DRB1 allele frequencies was significantly different between patients with autism and the controls (P=0.047). After adjusting for sex by haplotype regression, the frequencies of DR4, DR11, and DR14 were significantly different between patients with autism and healthy controls. In addition, patients with autism and DR4, DR11, or DR14 had different performance on intelligence and neuropsychology tests. Despite a relatively small sample size and a case-control association design, the findings suggest HLA-DRB1 gene might be associated with autism in Han Chinese. The true functional variants associated with autism in our samples remain to be further clarified. It warrants a replication study of a larger family sample and to validate the HLA genetic association with autism and its influence on neuropsychological function.

Functional Assessment and Intervention by Nursing Assistants in Hospice and Palliative Care Inpatient Care Settings: A Quality Improvement Pilot Study.

PubMed

Mueller, Karen; Hamilton, Gillian; Rodden, Betheny; DeHeer, Hendrick D

2016-03-01

This study assessed the impact of a nursing assistant-led functional intervention in an urban hospice. Thirty-three patients participated. A physical therapist trained 4 nursing assistants to assess 4 basic functional activities at admission and discharge and to provide daily activity training to intervention group participants. Control group participants were assessed at admission and discharge and received the usual standard of care. Both groups improved. The intervention group participants demonstrated significant improvement in the Timed up and Go test as well as their self-reported ability to achieve goals on the Patient-Specific Functional Scale. Control group participants made significant improvements in the ability to move from supine to sit in bed. These findings suggest that nursing assistants can provide activity-based assessment and intervention leading to improved function among patients in hospice. © The Author(s) 2014.

[The research of establishing discriminant function for patients with angina pectoris by stepwise analysis based on serum inflammatory factors].

PubMed

Chen, Zhi-bin; Liang, Yan-bing; Tang, Hao; Wang, Zhong-hua; Zeng, Li-jin; Wu, Jing-guo; Li, Zhen-yu; Ma, Zhong-fu

2012-12-01

To improve cost-efficiency, discriminant functions in stepwise method was founded for the differential diagnosis of angina pectoris by detecting the serum level of high-sensitivity C-reactive protein (hs-CRP), macrophage migration inhibitory factor (MIF), interleukin-4 (IL-4) and interleukin-10 (IL-10) in patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP). Thirty-nine SAP patients and 47 UAP patients were enrolled into the study, while 39 healthy volunteers were enrolled into the controlled group forming the entire set of training samples. The serum levels of hs-CRP, MIF, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Data was analyzed by software to define discriminant functions in the ways of "entering" and "stepwise". Both functions were evaluated by the results of validation. By the way of "enter independent together", the following discriminant functions were defined based on the data of training samples' age, hs-CRP, MIF, IL-4, IL-10: healthy control group =-129.858 + 2.869×age -2.451×hs-CRP + 1.393×MIF + 6.001×IL-4 + 4.848×IL-10; SAP group=-161.037 + 2.896×age-2.022×hs-CRP + 1.662×MIF + 6.703×IL-4 + 6.287×IL-10; UAP group=-199.087 + 2.468×age-1.440×hs-CRP + 3.404×MIF-13.875×IL-4 + 7.752×IL-10. Retrospective validation showed 4.8% of total miss-grouping, while cross-validation showed 5.6% of total miss-grouping. By the way of "stepwise", the above data was screened by software and training samples' age, MIF and IL-10 were suggested to define the following functions: healthy control group = - 125.218 + 2.659 × age + 0.599×MIF + 5.040 × IL-10; SAP group=-157.864 + 2.721×age + 1.008×MIF + 6.468×IL-10; UAP group=- 197.327 + 2.360×age + 2.932×MIF + 7.640×IL-10. Both retrospective and cross validation showed 6.4% of total miss-grouping. Both sets of discriminant functions had the same efficiency (100%) for differential diagnosis of SAP and UAP. The discriminant functions based on samples' age, MIF and IL-10, which were screened and suggested by stepwise method, may contribute to the differential diagnosis of atypical SAP and UAP, and therefore demonstrate better cost-efficiency.

Effect of female genital mutilation/cutting; types I and II on sexual function: case-controlled study.

PubMed

Ismail, Sahar A; Abbas, Ahmad M; Habib, Dina; Morsy, Hanan; Saleh, Medhat A; Bahloul, Mustafa

2017-08-30

The existing literature is contradictory regarding effects of female genital mutilation/cutting (FGM/C) on sexual functions. The aim of this study was to explore the impact of type I and II FGM/C on sexual function of Egyptian women. We recruited 197 cut women and 197 control women from those visiting Assiut University hospitals for different reasons. We asked each woman to fill the Arabic female sexual function index (FSFI) (a self reported 19-item questionnaire assessing the main domains of female sexual function). Genital Examination was done to confirm the type of FGM. Female sexual dysfunction (FSD) was found in 83.8% of FGM/C cases in contrast to 64.5% of the control. The total FSFI score in the FGM/C group (19.82 ± 7.1) was significantly lower than in the control group (23.34 ± 8.1). Concerning the types of FGM/C, type 73.6% of cases had type I and 26.4% had type II. Type I FGM/C was performed mainly by physicians (62.1%) while type II was performed mainly by midwives (44.4%). FSD was found in 83.4% of FGM/C I cases and in 84.6% of FGM/C II cases. There was no statistically significant difference between the two types of FGM/C as regards total and individual domain scores except for the pain domain. There were significantly lower total and individual domain scores in both FGM/C types except for the desire domain compared to control. In this study, FGM/C was associated with reduced scores of FSFI on all domains scores, and among both types I and II, both were associated with sexual dysfunction.

Concerted activities of Mcm4, Sld3, and Dbf4 in control of origin activation and DNA replication fork progression

PubMed Central

Sheu, Yi-Jun; Kinney, Justin B.; Stillman, Bruce

2016-01-01

Eukaryotic chromosomes initiate DNA synthesis from multiple replication origins in a temporally specific manner during S phase. The replicative helicase Mcm2-7 functions in both initiation and fork progression and thus is an important target of regulation. Mcm4, a helicase subunit, possesses an unstructured regulatory domain that mediates control from multiple kinase signaling pathways, including the Dbf4-dependent Cdc7 kinase (DDK). Following replication stress in S phase, Dbf4 and Sld3, an initiation factor and essential target of Cyclin-Dependent Kinase (CDK), are targets of the checkpoint kinase Rad53 for inhibition of initiation from origins that have yet to be activated, so-called late origins. Here, whole-genome DNA replication profile analysis is used to access under various conditions the effect of mutations that alter the Mcm4 regulatory domain and the Rad53 targets, Sld3 and Dbf4. Late origin firing occurs under genotoxic stress when the controls on Mcm4, Sld3, and Dbf4 are simultaneously eliminated. The regulatory domain of Mcm4 plays an important role in the timing of late origin firing, both in an unperturbed S phase and in dNTP limitation. Furthermore, checkpoint control of Sld3 impacts fork progression under replication stress. This effect is parallel to the role of the Mcm4 regulatory domain in monitoring fork progression. Hypomorph mutations in sld3 are suppressed by a mcm4 regulatory domain mutation. Thus, in response to cellular conditions, the functions executed by Sld3, Dbf4, and the regulatory domain of Mcm4 intersect to control origin firing and replication fork progression, thereby ensuring genome stability. PMID:26733669

Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity.

PubMed

Klawonn, Anna M; Wilhelms, Daniel B; Lindström, Sarah H; Singh, Anand Kumar; Jaarola, Maarit; Wess, Jürgen; Fritz, Michael; Engblom, David

2018-01-01

The neurotransmitter acetylcholine has been implicated in reward learning and drug addiction. However, the roles of the various cholinergic receptor subtypes on different neuron populations remain elusive. Here we study the function of muscarinic M4 receptors (M4Rs) in dopamine D1 receptor (D1R) expressing neurons and cholinergic neurons (expressing choline acetyltransferase; ChAT), during various reward-enforced behaviors and in a "waiting"-impulsivity test. We applied cell-type-specific gene deletions targeting M4Rs in D1RCre or ChATCre mice. Mice lacking M4Rs in D1R-neurons displayed greater cocaine seeking and drug-primed reinstatement than their littermate controls in a Pavlovian conditioned place preference (CPP) paradigm. Furthermore, the M4R-D1RCre mice initiated significantly more premature responses (PRs) in the 5-choice-serial-reaction-time-task (5CSRTT) than their littermate controls, indicating impaired waiting impulse control. In contrast, mice lacking M4Rs in cholinergic neurons did not acquire cocaine Pavlovian conditioning. The M4R-ChATCre mice were also unable to learn positive reinforcement to either natural reward or cocaine in an operant runway paradigm. Immediate early gene (IEG) expression ( cFos and FosB ) induced by repeated cocaine injections was significantly increased in the forebrain of M4R-D1RCre mice, whereas it remained normal in the M4R-ChATCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality. Furthermore, we found that neurons expressing both M4Rs and D1Rs are important for signaling impulse control.

A critical role for transcription factor Smad4 in T cell function independent of transforming growth factor beta receptor signaling

PubMed Central

Gu, Ai-Di; Zhang, Song; Wang, Yunqi; Xiong, Hui; Curtis, Thomas A.; Wan, Yisong Y.

2014-01-01

Summary Transforming growth factor-beta (TGF-β) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-β signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-βR) deletion and compromised T-cell-mediated tumor rejection. While Smad4 was dispensable for T cell generation, homeostasis and effector function, it was essential for T cell proliferation following activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-βR-independent role for Smad4 in promoting T cell function, autoimmunity and anti-tumor immunity. PMID:25577439

A critical role for transcription factor Smad4 in T cell function that is independent of transforming growth factor β receptor signaling.

PubMed

Gu, Ai-Di; Zhang, Song; Wang, Yunqi; Xiong, Hui; Curtis, Thomas A; Wan, Yisong Y

2015-01-20

Transforming growth factor-beta (TGF-β) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-β signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-βR) deletion and compromised T-cell-mediated tumor rejection. Although Smad4 was dispensable for T cell generation, homeostasis, and effector function, it was essential for T cell proliferation after activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-βR-independent role for Smad4 in promoting T cell function, autoimmunity, and anti-tumor immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health

PubMed Central

Deming, Janise D.; Pak, Joseph S.; Brown, Bruce M.; Kim, Moon K.; Aung, Moe H.; Eom, Yun Sung; Shin, Jung-a; Lee, Eun-Jin; Pardue, Machelle T.; Craft, Cheryl Mae

2015-01-01

Purpose Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions. Methods A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4−/−) compared with age-matched control, wild-type mice. Results When 2-month-old Arr4−/− mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4−/− mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4−/− mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged. Conclusions Our study demonstrates that Arr4−/− mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy. PMID:26284544

Th17 cells and CD4(+) multifunctional T cells in patients with systemic lupus erythematosus.

PubMed

Araújo, Júlio Antônio Pereira; Mesquita, Danilo; de Melo Cruvinel, Wilson; Salmazi, Karina Inácio; Kallás, Esper Georges; Andrade, Luis Eduardo Coelho

2016-01-01

Recent evidence suggests that abnormalities involving Th17 lymphocytes are associated with the pathophysiology of systemic lupus erythematosus (SLE). In addition, multifunctional T cells (MFT), i.e., those producing multiple cytokines simultaneously, are present in the inflammatory milieu and may be implicated in the autoimmune process observed in SLE. In the present study, we aimed to characterize the functional status of CD4(+) T cells in SLE by simultaneously determining the concentration of IL-2, IFN-γ and IL-17 in lymphocyte cultures under exogenous and self-antigenic stimuli. Eighteen patients with active disease, 18 with inactive disease, and 14 healthy controls had functional status of CD4(+) T cells analyzed. We found that SLE patients presented a decreased number of total CD4(+) cells, an increased number of activated T cells, and an increased frequency of Th17 cells compared to healthy controls (HC). MFT cells had increased frequency in SLE patients and there was an increased frequency of tri-functional MFT in patients with active SLE compared with those with inactive SLE. Interestingly, MTF cells produced larger amounts of IFNγ than mono-functional T cells in patients and controls. Taken together these data indicate the participation of recently activated Th17 cells and MTF cells in the SLE pathophysiology. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Mice null for Frizzled4 (Fzd4-/-) are infertile and exhibit impaired corpora lutea formation and function.

PubMed

Hsieh, Minnie; Boerboom, Derek; Shimada, Masayuki; Lo, Yuet; Parlow, Albert F; Luhmann, Ulrich F O; Berger, Wolfgang; Richards, JoAnne S

2005-12-01

Previous studies showed that transcripts encoding specific Wnt ligands and Frizzled receptors including Wnt4, Frizzled1 (Fzd1), and Frizzled4 (Fzd4) were expressed in a cell-specific manner in the adult mouse ovary. Overlapping expression of Wnt4 and Fzd4 mRNA in small follicles and corpora lutea led us to hypothesize that the infertility of mice null for Fzd4 (Fzd4-/-) might involve impaired follicular growth or corpus luteum formation. Analyses at defined stages of reproductive function indicate that immature Fzd4-/- mouse ovaries contain follicles at many stages of development and respond to exogenous hormone treatments in a manner similar to their wild-type littermates, indicating that the processes controlling follicular development and follicular cell responses to gonadotropins are intact. Adult Fzd4-/- mice also exhibit normal mating behavior and ovulate, indicating that endocrine events controlling these processes occur. However, Fzd4-/- mice fail to become pregnant and do not produce offspring. Histological and functional analyses of ovaries from timed mating pairs at Days 1.5-7.5 postcoitus (p.c.) indicate that the corpora lutea of the Fzd4-/- mice do not develop normally. Expression of luteal cell-specific mRNAs (Lhcgr, Prlr, Cyp11a1 and Sfrp4) is reduced, luteal cell morphology is altered, and markers of angiogenesis and vascular formation (Efnb1, Efnb2, Ephb4, Vegfa, Vegfc) are low in the Fzd4-/- mice. Although a recently identified, high-affinity FZD4 ligand Norrin (Norrie disease pseudoglioma homolog) is expressed in the ovary, adult Ndph-/- mice contain functional corpora lutea and do not phenocopy Fzd4-/- mice. Thus, Fzd4 appears to impact the formation of the corpus luteum by mechanisms that more closely phenocopy Prlr null mice.

Dynamic characteristics of heart rate control by the autonomic nervous system in rats.

PubMed

Mizuno, Masaki; Kawada, Toru; Kamiya, Atsunori; Miyamoto, Tadayoshi; Shimizu, Shuji; Shishido, Toshiaki; Smith, Scott A; Sugimachi, Masaru

2010-09-01

We estimated the transfer function of autonomic heart rate (HR) control by using random binary sympathetic or vagal nerve stimulation in anaesthetized rats. The transfer function from sympathetic stimulation to HR response approximated a second-order, low-pass filter with a lag time (gain, 4.29 +/- 1.55 beats min(1) Hz(1); natural frequency, 0.07 +/- 0.03 Hz; damping coefficient, 1.96 +/- 0.64; and lag time, 0.73 +/- 0.12 s). The transfer function from vagal stimulation to HR response approximated a first-order, low-pass filter with a lag time (gain, 8.84 +/- 4.51 beats min(1) Hz(1); corner frequency, 0.12 +/- 0.06 Hz; and lag time, 0.12 +/- 0.08 s). These results suggest that the dynamic characteristics of HR control by the autonomic nervous system in rats are similar to those of larger mammals.

Modeling transport kinetics in clinoptilolite-phosphate rock systems

NASA Technical Reports Server (NTRS)

Allen, E. R.; Ming, D. W.; Hossner, L. R.; Henninger, D. L.

1995-01-01

Nutrient release in clinoptilolite-phosphate rock (Cp-PR) systems occurs through dissolution and cation-exchange reactions. Investigating the kinetics of these reactions expands our understanding of nutrient release processes. Research was conducted to model transport kinetics of nutrient release in Cp-PR systems. The objectives were to identify empirical models that best describe NH4, K, and P release and define diffusion-controlling processes. Materials included a Texas clinoptilolite (Cp) and North Carolina phosphate rock (PR). A continuous-flow thin-disk technique was used. Models evaluated included zero order, first order, second order, parabolic diffusion, simplified Elovich, Elovich, and power function. The power-function, Elovich, and parabolic-diffusion models adequately described NH4, K, and P release. The power-function model was preferred because of its simplicity. Models indicated nutrient release was diffusion controlled. Primary transport processes controlling nutrient release for the time span observed were probably the result of a combination of several interacting transport mechanisms.

Health-related quality of life among children with Turner syndrome: controlled cross-sectional study.

PubMed

Amedro, Pascal; Tahhan, Nabil; Bertet, Helena; Jeandel, Claire; Guillaumont, Sophie; Mura, Thibault; Picot, Marie-Christine

2017-08-28

The aim of the study was to assess health-related quality of life (HR-QoL) in children with Turner syndrome in comparison with controls. We prospectively recruited 16 female girls with Turner syndrome (mean age 15.2±2.6 years) and 78 female controls (mean age 12.7±2.8 years) in randomly selected schools. We used the PedsQL, a generic HR-QoL questionnaire (self and parents' versions). Global HR-QoL scores in Turner syndrome were lower than controls for self-reports (respectively, 74.3±3.0 vs. 82.8±1.3, p=0.01) and parents' reports (62.7±3.8 vs. 80.1±1.7, p<0.0001). In Turner syndrome, self-reported HR-QoL was impaired in school functioning (70.6±4.0 vs. 80.71±1.7, p=0.02), social functioning (78.2±4.0 vs. 90.4±1.8, p<0.01) and physical functioning (78.5±3.2 vs. 87.1±1.4, p=0.02), but not in emotional functioning. Parents' reported HR-QoL was impaired in all four dimensions. HR-QoL was impaired in this cohort of young females with Turner syndrome, as in previously reported adult studies. In addition to medical treatment and routine clinical follow-up, female girls and teenagers with Turner syndrome should also be supported psychologically by social, educational and psychotherapeutic interventions that aim to address their self-esteem and emotional difficulties.

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection

PubMed Central

Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D.; Ndung'u, Thumbi

2017-01-01

ABSTRACT Immune control of viral infections is heavily dependent on helper CD4+ T cell function. However, the understanding of the contribution of HIV-specific CD4+ T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4+ T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4+ T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4+ T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4+ T cells in HIV controllers than progressors (P = 0.0001), and these expanded Gag-specific CD4+ T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control (r = −0.5, P = 0.02). These data identify an association between HIV-specific CD4+ T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4+ T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4+ T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4+ T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4+ T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4+ T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4+ T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections. PMID:28077659

A PtdIns(4)P-driven electrostatic field controls cell membrane identity and signalling in plants.

PubMed

Simon, Mathilde Laetitia Audrey; Platre, Matthieu Pierre; Marquès-Bueno, Maria Mar; Armengot, Laia; Stanislas, Thomas; Bayle, Vincent; Caillaud, Marie-Cécile; Jaillais, Yvon

2016-06-20

Many signalling proteins permanently or transiently localize to specific organelles. It is well established that certain lipids act as biochemical landmarks to specify compartment identity. However, they also influence membrane biophysical properties, which emerge as important features in specifying cellular territories. Such parameters include the membrane inner surface potential, which varies according to the lipid composition of each organelle. Here, we found that the plant plasma membrane (PM) and the cell plate of dividing cells have a unique electrostatic signature controlled by phosphatidylinositol-4-phosphate (PtdIns(4)P). Our results further reveal that, contrarily to other eukaryotes, PtdIns(4)P massively accumulates at the PM, establishing it as a critical hallmark of this membrane in plants. Membrane surface charges control the PM localization and function of the polar auxin transport regulator PINOID as well as proteins from the BRI1 KINASE INHIBITOR1 (BKI1)/MEMBRANE ASSOCIATED KINASE REGULATOR (MAKR) family, which are involved in brassinosteroid and receptor-like kinase signalling. We anticipate that this PtdIns(4)P-driven physical membrane property will control the localization and function of many proteins involved in development, reproduction, immunity and nutrition.

Beyond the known functions of the CCR4-NOT complex in gene expression regulatory mechanisms: New structural insights to unravel CCR4-NOT mRNA processing machinery.

PubMed

Ukleja, Marta; Valpuesta, José María; Dziembowski, Andrzej; Cuellar, Jorge

2016-10-01

Large protein assemblies are usually the effectors of major cellular processes. The intricate cell homeostasis network is divided into numerous interconnected pathways, each controlled by a set of protein machines. One of these master regulators is the CCR4-NOT complex, which ultimately controls protein expression levels. This multisubunit complex assembles around a scaffold platform, which enables a wide variety of well-studied functions from mRNA synthesis to transcript decay, as well as other tasks still being identified. Solving the structure of the entire CCR4-NOT complex will help to define the distribution of its functions. The recently published three-dimensional reconstruction of the complex, in combination with the known crystal structures of some of the components, has begun to address this. Methodological improvements in structural biology, especially in cryoelectron microscopy, encourage further structural and protein-protein interaction studies, which will advance our comprehension of the gene expression machinery. © 2016 WILEY Periodicals, Inc.

Fundus Autofluorescence in the Abca4−/− Mouse Model of Stargardt Disease—Correlation With Accumulation of A2E, Retinal Function, and Histology

PubMed Central

Charbel Issa, Peter; Barnard, Alun R.; Singh, Mandeep S.; Carter, Emma; Jiang, Zhichun; Radu, Roxana A.; Schraermeyer, Ulrich; MacLaren, Robert E.

2013-01-01

Purpose. To investigate fundus autofluorescence (AF) characteristics in the Abca4−/− mouse, an animal model for AMD and Stargardt disease, and to correlate findings with functional, structural, and biochemical assessments. Methods. Blue (488 nm) and near-infrared (790 nm) fundus AF images were quantitatively and qualitatively analyzed in pigmented Abca4−/− mice and wild type (WT) controls in vivo. Functional, structural, and biochemical assessments included electroretinography (ERG), light and electron microscopic analysis, and A2E quantification. All assessments were performed across age groups. Results. In Abca4−/− mice, lipofuscin-related 488 nm AF increased early in life with a ceiling effect after 6 months. This increase was first paralleled by an accumulation of typical lipofuscin granules in the retinal pigment epithelium (RPE). Later, lipofuscin and melanin granules decreased in number, whereas melanolipofuscin granules increased. This increase in melanolipofuscin granules paralleled an increase in melanin-related 790 nm AF. Old Abca4−/− mice revealed a flecked fundus AF pattern at both excitation wavelengths. The amount of A2E, a major lipofuscin component, increased 10- to 12-fold in 6- to 9-month-old Abca4−/− mice compared with controls, while 488 nm AF intensity only increased 2-fold. Despite pronounced lipofuscin accumulation in the RPE of Abca4−/− mice, ERG and histology showed a slow age-related thinning of the photoreceptor layer similar to WT controls up to 12 months. Conclusions. Fundus AF can be used to monitor lipofuscin accumulation and melanin-related changes in vivo in mouse models of retinal disease. High RPE lipofuscin may not adversely affect retinal structure or function over prolonged time intervals, and melanin-related changes (melanolipofuscin formation) may occur before the decline in retinal function. PMID:23761084

Functional MUC4 suppress epithelial-mesenchymal transition in lung adenocarcinoma metastasis.

PubMed

Gao, Liuwei; Liu, Jun; Zhang, Bin; Zhang, Hua; Wang, Daowei; Zhang, Tiemei; Liu, Yang; Wang, Changli

2014-02-01

The mucin MUC4 is a high molecular weight membrane-bound transmembrane glycoprotein that is frequently detected in invasive and metastatic cancer. The overexpression of MUC4 is associated with increased risks for several types of cancer. However, the functional role of MUC4 is poorly understood in lung adenocarcinoma. Using antisense-MUC4-RNA transfected adenocarcinoma cells, we discovered that the loss of MUC4 expression results in epithelial-mesenchymal transition (EMT). We found morphological alterations and the repression of the epithelial marker E-cadherin in transfected cells. Additionally, the loss of MUC4 caused the upregulation of the mesenchymal marker vimentin compared to control cells. Using a MUC4-knockdown versus control LTEP xenograft mice model (129/sv mice), we also found that EMT happened in lung tissues of MUC4-knockdown-LTEP xenograft mice. Moreover, antisense-MUC4-RNA transfected cells had a significantly increased cellular migration ability in vitro. The loss of MUC4 also occurred in lung adenocarcinoma patients with lymph node metastases. We further investigated MUC4 and found that it plays a critical role in regulating EMT by modulating β-catenin. Taken together, our study reveals a novel role for MUC4 in suppressing EMT and suggests that the assessment of MUC4 may function as a prognostic biomarker and could be a potential therapeutic target for lung adenocarcinoma metastasis.

Testosterone regulates erectile function and Vcsa1 expression in the corpora of rats.

PubMed

Chua, Rowena G; Calenda, Giulia; Zhang, Xinhua; Siragusa, Joseph; Tong, Yuehong; Tar, Moses; Aydin, Memduh; DiSanto, Michael E; Melman, Arnold; Davies, Kelvin P

2009-05-06

Vcsa1 plays an important role in the erectile physiology of the rat. We conducted experiments to determine if erectile function, testosterone levels and Vcsa1 expression were correlated. In orchiectomized rats, total testosterone in blood fell from an average of 4 ng/ml to <0.04 ng/ml. Erectile function was significantly lower compared to controls and Vcsa1 expression was significantly (>6-fold) decreased. Injection of orchiectomized animals with testosterone (2 mg in 100ml sesame oil every 4 days for 2 weeks) restored average levels of testosterone to 2 ng/ml, increased erectile function and significantly increased Vcsa1 expression. In isolated corporal cells there was testosterone dependent Vcsa1 expression. However, intracorporal injection of orchiectomized animals with a plasmid expressing Vcsa1 or its gene product Sialorphin (previously demonstrated to improve erectile function in old animals) gave no significant improvement in erectile function. Also, the ability of Sialorphin to reduce tension in corporal smooth muscle strips isolated from orchiectomized animals was impaired compared to controls.

CARDIAC STRUCTURAL AND FUNCTIONAL ABNORMALITIES IN FEMALES WITH UNTREATED HYPOPITUITARISM DUE TO SHEEHAN SYNDROME: RESPONSE TO HORMONE REPLACEMENT THERAPY.

PubMed

Laway, Bashir Ahmad; Ramzan, Mahroosa; Allai, Mohd Sultan; Wani, Arshad Iqbal; Misgar, Raiz Ahmad

2016-09-01

Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment. Twenty-three females with treatment-naïve hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state. Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 ± 3.5 mm in cases vs. 47.6 ± 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 ± 18.0 mL versus 106.5 ± 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 ± 19.2 g in cases and 108.0 ± 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 ± 12.0 mL in cases and 74.4 ± 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 ± 6.2 % in cases against 69.9 ± 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 ± 4.7% versus 40.1 ± 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state. Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism. ACTH = adrenocorticotrophic hormone BMI = body mass index DT = deceleration time EDV = end-diastolic volume EF = ejection fraction FS = fractional shortening GH = growth hormone IGF-1 = insulin growth factor-1 ITT = insulin tolerance test IVSd = interventricular septal diameter LH = luteinizing hormone LV = left ventricular LVEDD = LV end diastolic dimension LVEDV = LV end diastolic volume LVM = LV mass MRI = magnetic resonance imaging MVP = mitral value prolapse PPH = postpartum hemorrhage PWd = posterior wall diameter SS = Sheehan syndrome SV = stroke volume T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone.

Power Extension Package (PEP) system definition extension, orbital service module systems analysis study. Volume 4: PEP functional specification

NASA Technical Reports Server (NTRS)

1979-01-01

The functional, performance, design, and test requirements for the Orbiter power extension package and its associated ground support equipment are defined. Both government and nongovernment standards and specifications are cited for the following subsystems: electrical power, structural/mechanical, avionics, and thermal control. Quality control assurance provisions and preparation for delivery are also discussed.

Comparative Evaluation of Flow Quantification across the Atrioventricular Valve in Patients with Functional Univentricular Heart after Fontan's Surgery and Healthy Controls: Measurement by 4D Flow Magnetic Resonance Imaging and Streamline Visualization.

PubMed

She, Hoi Lam; Roest, Arno A W; Calkoen, Emmeline E; van den Boogaard, Pieter J; van der Geest, Rob J; Hazekamp, Mark G; de Roos, Albert; Westenberg, Jos J M

2017-01-01

To evaluate the inflow pattern and flow quantification in patients with functional univentricular heart after Fontan's operation using 4D flow magnetic resonance imaging (MRI) with streamline visualization when compared with the conventional 2D flow approach. Seven patients with functional univentricular heart after Fontan's operation and twenty-three healthy controls underwent 4D flow MRI. In two orthogonal two-chamber planes, streamline visualization was applied, and inflow angles with peak inflow velocity (PIV) were measured. Transatrioventricular flow quantification was assessed using conventional 2D multiplanar reformation (MPR) and 4D MPR tracking the annulus and perpendicular to the streamline inflow at PIV, and they were validated with net forward aortic flow. Inflow angles at PIV in the patient group demonstrated wide variation of angles and directions when compared with the control group (P < .01). The use of 4D flow MRI with streamlines visualization in quantification of the transatrioventricular flow had smaller limits of agreement (2.2 ± 4.1 mL; 95% limit of agreement -5.9-10.3 mL) when compared with the static plane assessment from 2DFlow MRI (-2.2 ± 18.5 mL; 95% limit of agreement agreement -38.5-34.1 mL). Stronger correlation was present in the 4D flow between the aortic and trans-atrioventricular flow (R 2 correlation in 4D flow: 0.893; in 2D flow: 0.786). Streamline visualization in 4D flow MRI confirmed variable atrioventricular inflow directions in patients with functional univentricular heart with previous Fontan's procedure. 4D flow aided generation of measurement planes according to the blood flood dynamics and has proven to be more accurate than the fixed plane 2D flow measurements when calculating flow quantifications. © 2016 Wiley Periodicals, Inc.

Effects of exercise training with traditional dancing on functional capacity and quality of life in patients with schizophrenia: a randomized controlled study.

PubMed

Kaltsatou, A; Kouidi, E; Fountoulakis, K; Sipka, C; Theochari, V; Kandylis, D; Deligiannis, A

2015-09-01

To examine the effects of an eight-month exercise training programme with Greek traditional dancing on functional capacity and quality of life in patients with schizophrenia. Randomized controlled trial. Sports Medicine Laboratory. A total of 31 patients, aged 59.9 ± 14.1 years. They were randomly assigned either to a Greek traditional dancing programme (Group A) or to a sedentary control group (Group B). A functional capacity assessment was performed at baseline and the end of the study. Global Assessment of Functioning Scale and Positive and Negative Syndrome Scale were also used. Quality of life was examined using the Quality of Life and Satisfaction questionnaire. After the eight months, Group A increased walking distance in the 6-minute walk test (328.4 ± 35.9 vs. 238.0 ± 47.6 m), sit-to-stand test (19.1 ± 1.8 vs. 25.1 ± 1.4 seconds), Berg Balance Scale score (53.1 ± 2.1 vs. 43.2 ± 6.7), lower limbs maximal isometric force (77.7 ± 25.7 vs. 51.0 ± 29.8 lb), Positive and Negative Syndrome Scale total score (77.0 ± 23.1 vs. 82.0 ± 24.4), Global Assessment of Functioning Scale total score (51.3 ± 15.5 vs. 47.7 ± 13.3) and Quality of Life total score (34.9 ± 5.2 vs. 28 ± 4.5), compared with Group B. Our results demonstrate that Greek traditional dances improve functional capacity and quality of life in patients with schizophrenia. © The Author(s) 2014.

A case control study of association between cognition and functional capacity in schizophrenia.

PubMed

Narayanan, Sreelatha S; Bhatia, Triptish; Velligan, Dawn I; Nimgaonkar, Vishwajit L; Deshpande, Smita N

2015-12-01

Cognitive functions are important prognostic factors for schizophrenia (SZ), while ability to perform activities of daily living are important measures of functional capacity. The relationship between cognition and functional capacity has not been tested extensively in India. To compare persons with SZ with controls on measures of cognition and functional capacity, and evaluate correlations between cognitive performance and functional capacity. Schizophrenia outpatients and controls without psychiatric illness (DSM IV) who completed the MATRICS Consensus Cognitive Battery and Functional Assessment Battery comprised of two tests from University of California San Diego (UCSD) Performance Based Skill Assessment (UPSA), one Test of Adaptive Behavior in Schizophrenia (TABS) and one test from University of California San Diego Performance Based Skill Assessment Brief edition (UPSA-B). Cognitive and functional domains were examined using regression analyses, with relevant covariates. Cases (N=51) though younger, were more educated than controls (N=41). Adjusting for education, controls performed better than cases in 3/7 cognitive and 4/5 domains of functional capacity but similarly in 'household management'. Among both cases and controls, cognitive measures of verbal learning and speed of processing overlapped with functional capacity (3 domains). Working memory was associated with one functional domain. Consistent with other studies, Indian patients with schizophrenia performed worse than controls on several domains of cognition and functional capacity; these domains were correlated. Speed of processing and verbal learning are most frequently associated with functional capacity indices and should be targeted to improve skills of daily living among persons with SZ. Copyright © 2015. Published by Elsevier B.V.

Standardized Solution for Management Controller for MTCA.4

NASA Astrophysics Data System (ADS)

Makowski, D.; Fenner, M.; Ludwig, F.; Mavrič, U.; Mielczarek, A.; Napieralski, A.; Perek, P.; Schlarb, H.

2015-06-01

The Micro Telecommunications Computing Architecture (MTCA) standard is a modern platform that is gaining popularity in the area of High Energy Physics (HEP) experiments. The standard provides extensive management, monitoring and diagnostics functionalities. The hardware control and monitoring is based on the Intelligent Platform Management Interface (IPMI), that was initially developed for supervision of complex computers operation. The original IPMI specification was extended to support functions required by the MTCA specification. The Module Management Controller (MMC) is required on each Advanced Mezzanine Card (AMC) installed in MTCA chassis. The Rear Transition Modules (RTMs) have to be equipped with RTM Management Controllers (RMCs) which is required by the MTCA.4 subsidiary specification. The commercially available implementations of MMC and RMC are expensive and do not provide the complete functionality that is required by specific HEP applications. Therefore, many research centers and commercial companies work on their own implementation of AMC and RTM controllers. The available implementations suffer because of lack of common approach and interoperability problems. Since both Lodz University of Technology (TUL) and Deutsches Elektronen-Synchrotron (DESY) have long-term experience in developing ATCA and MTCA hardware, the authors decided to develop a unified solution of management controller fully compliant with AMC and MTCA.4 standards. The MMC v1.00 solution is dedicated for management of AMC and RTM modules. The MMC v1.00 is based on Atmel ATxmega MCUs and can be fully customized by the user or used as a drop-in-module without any modifications. The paper discusses the functionality of the MMC v1.00 solution. The implementation was verified with developed evaluation kits for AMC and RTM cards.

A 4-week neuromuscular training program and gait patterns at the ankle joint.

PubMed

Coughlan, Garrett; Caulfield, Brian

2007-01-01

Previous research into the rehabilitation of ankle sprains has primarily focused on outcome measures that do not replicate functional activities, thus making it difficult to extrapolate the results relative to the weight-bearing conditions under which most ankle sprains occur. To measure the effects of a training program on gait during walking and running in an active athletic population. Matched-pairs, controlled trial. University motion analysis laboratory. Ten subjects from an athletic population (7 healthy, 3 with functional ankle instability: age = 25.8 +/- 3.9 years, height = 177.6 +/- 6.1 cm, mass = 66.8 +/- 7.4 kg) and 10 controls matched for age, sex, activity, and ankle instability (7 healthy, 3 with functional ankle instability: age = 27.4 +/- 5.8 years, height = 178.7 +/- 10.8 cm, mass = 71.6 +/- 10.0 kg). A 4-week neuromuscular training program undertaken by the treatment group. We measured ankle position and velocity in the frontal (x) and sagittal (y) planes in all subjects during treadmill walking and running for the periods 100 milliseconds before heel strike, at heel strike, and 100 milliseconds after heel strike. A 4-week neuromuscular training program resulted in no significant changes in ankle position or velocity during treadmill walking and running. The mechanisms by which neuromuscular training improves function in normal subjects and those with functional ankle instability do not appear to result in measurable changes in gait kinematics. Our findings raise issues regarding methods of ankle sprain rehabilitation and the measurement of their effectiveness in improving functional activities. Further research in a larger population with functional ankle instability is necessary.

Human Impairment from Living near Confined Animal (Hog) Feeding Operations

PubMed Central

Kilburn, Kaye H.

2012-01-01

Problem. To determine whether neighbors around manure lagoons and massive hog confinement buildings who complained of offensive odors and symptoms had impaired brain and lung functions. Method. We compared near hog manure neighbors of lagoons to people living beyond 3 kilometers in Ohio and to unexposed people controls in a nearby state for neurophysiological, cognitive, recall and memory functions, and pulmonary performance. Results. The 25 exposed subjects averaged 4.3 neurobehavioral abnormalities, significantly different from 2.5 for local controls and 2.3 for Tennessee controls. Exposed subjects mean forced vital capacity and expiratory volume in 1 sec were reduced significantly compared to local and regional controls. Conclusions. Near neighbors of hog enclosures and manure lagoon gases had impaired neurobehavioral functions and pulmonary functions and these effects extended to nearby people thought to be controls. Hydrogen sulfide must be abated because people living near lagoons cannot avoid rotten egg gas. PMID:22496706

Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in human endothelial cells.

PubMed

Lopes da Silva, Mafalda; O'Connor, Marie N; Kriston-Vizi, Janos; White, Ian J; Al-Shawi, Raya; Simons, J Paul; Mössinger, Julia; Haucke, Volker; Cutler, Daniel F

2016-05-15

Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-Golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIβ in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. When stimulated with histamine, these cells release normal levels of VWF yet, under flow, form very few platelet-catching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls. This is the first demonstration that lipid kinases can control the biosynthesis of VWF and the formation of WPBs that are capable of full haemostatic function. © 2016. Published by The Company of Biologists Ltd.

Py4Syn: Python for synchrotrons.

PubMed

Slepicka, H H; Canova, H F; Beniz, D B; Piton, J R

2015-09-01

In this report, Py4Syn, an open-source Python-based library for data acquisition, device manipulation, scan routines and other helper functions, is presented. Driven by easy-to-use and scalability ideals, Py4Syn offers control system agnostic solution and high customization level for scans and data output, covering distinct techniques and facilities. Here, most of the library functionalities are described, examples of use are shown and ideas for future implementations are presented.

Upper airway sensory function in children with obstructive sleep apnea syndrome.

PubMed

Tapia, Ignacio E; Bandla, Preetam; Traylor, Joel; Karamessinis, Laurie; Huang, Jingtao; Marcus, Carole L

2010-07-01

Children with the obstructive sleep apnea syndrome (OSAS) have impaired responses to hypercapnia, subatmospheric pressure, and inspiratory resistive loading during sleep. This may be due, in part, to an impairment in the afferent limb of the upper airway sensory pathway. Therefore, we hypothesized that children with OSAS had diminished upper airway sensation compared to controls. Case-control. Academic hospital. Subjects with OSAS aged 6-16 years, and age- and BMI-matched controls. Two-point discrimination (TPD) was measured during wakefulness with modified calipers in the anterior tongue, right interior cheek, and hard palate. Thirteen children with OSAS and 9 controls were tested. The age (mean +/- SD) for OSAS and controls was 11 +/- 4 vs. 13 +/- 2 years (NS); OSAS BMI Z score 2.4 +/- 0.5, controls 2.2 +/- 0.5 (NS); OSAS apnea hypopnea index 31 +/- 48, controls 0.4 +/- 0.5 events/hour (P < 0.001). Children with OSAS had impaired TPD in the anterior tongue (median [range]) = 9 [3-14] mm, controls 3 [1-7], P = 0.002) and hard palate (OSAS 6 [3-9] mm, controls 3 [1-4], P < 0.001). TPD in the cheek was similar between the groups (P = 0.12). TPD in the anterior tongue and hard palate was impaired in children with OSAS during wakefulness. We speculate that this impairment might be due to a primary sensory function abnormality or secondary to nerve damage and/or hypoxemia caused by OSAS. Further studies after treatment of OSAS are needed.

Effects of short-term resistance training and pulsed electromagnetic fields on bone metabolism and joint function in severe haemophilia A patients with osteoporosis: a randomized controlled trial.

PubMed

Parhampour, Behrouz; Torkaman, Giti; Hoorfar, Hamid; Hedayati, Mehdi; Ravanbod, Roya

2014-05-01

To assess the effects of short-term resistance training and pulsed electromagnetic fields on bone metabolism and joint function in patients with haemophilia with osteoporosis. A randomized, controlled, patient and blood sample assessor-blinded, six-week trial, three times weekly. Hospital outpatients with severe haemophilia A and osteoporosis. Forty-eight patients were randomly assigned to resistance training (RT, n = 13), combined resistance training with pulsed electromagnetic fields (RTPEMF, n = 12), pulsed electromagnetic fields (PEMF, n = 11) and control (n = 12) groups. The RT group received 30-40 minutes of resistance exercises and placebo pulsed electromagnetic fields. The RTPEMF group received the same exercises with lower repetition and 30 minutes of pulsed electromagnetic fields. The PEMF group was exposed to 60 minutes of pulsed electromagnetic fields (30 Hz and 40 Gauss). Bone-specific alkaline phosphatase, N-terminal telopeptide of type 1 collagen, and joint function, using the modified Colorado Questionnaire, were measured before and after the programme. The absolute change of bone-specific alkaline phosphatase was significant in the RT and RTPEMF groups compared with the control group (25.41 ± 14.40, 15.09 ± 5.51, and -4.73 ± 2.93 U/L, respectively). The absolute changes in the total score for joint function were significant for knees, ankles, and elbows in the RT group (9.2 ± 1.38, 5.1 ± 0.5, and 3.2 ± 0.8, respectively) and the RTPEMF group (7.7 ± 1.0, 3.3 ± 0.6, and 2.5 ± 0.7, respectively) compared to the PEMF and control groups. This value was significant for knee joints in the PEMF group compared to the control group (3.4 ± 0.5 and 0.66 ± 0.4, respectively). Resistance training is effective for improving bone formation and joint function in severe haemophilia A patients with osteoporosis.

[Study of the effect of occupational exposure to glyphosate on hepatorenal function].

PubMed

Zhang, F; Pan, L P; Ding, E M; Ge, Q J; Zhang, Z H; Xu, J N; Zhang, L; Zhu, B L

2017-07-06

Objective: To explore the effect of occupational exposure to glyphosate on hepatorenal function. Methods: 526 workers who were occupationally exposed to glyphosate from 5 glyphosate-producing factories were selected as cases; and another 442 administrative staffs who were not exposed to glyphosate were selected as controls from April to November, 2014. All the subjects accepted occupational health examination. The concentration level of glyphosate in the air of workshop was detected and the time weighted average concentration (TWA) was calculated. And analyze the difference of hepatorenal fuction between case group and control group. Result: The age of the subjects in the case and control groups were separately (35.6±10.3), (34.3±9.7) years old, with the length of working for (6.5±5.7), (7.7±6.8) years. The TWA of glyphosate in the case group was between <0.03-48.91 mg/m(3), with the geometric mean at 3.78 mg/m(3). The overall rates of abnormal hepatic and renal function in the case group were 14.4% (76 cases) and 16.2% (85 cases), respectively; while those were 5.0% (22 cases) and 4.8% (21 cases), respectively in control group, and the difference showed statistical significance ( P <0.05). When TWA reached <0.03-6.00 mg/m(3), the difference of hepatorenal fuction between case group and control group showed statistical significance, and the rates of abnormal hepatic and renal function was 8.0% (36/447) and 9.8% (44/447) respectively in case group. When cumulative exposure level reached <1.56-68.64 g, the difference of hepatorenal fuction between case group and control group showed statistical significance, and the rates increased to 9.2% (37/404) and 10.4% (42/404) respectively in group of cases. Conclusion: Glyphosate can affect the hepatic and renal function among occupational exposure population, and there was an association between the effect and the exposure dose.

Army Science Board 1993 Summer Study on Innovative Acquisition Strategies for the 90s

DTIC Science & Technology

1994-07-01

temporay "patch," but the sooner standards are established and enforced, the sooner the "seamless" Command, Control, Communications, and Intelligence ...opportunities are present to upgrade Close Combat Heavy systems’ abilities to perform the functions of intelligence and control and the counter-fire function of...35 $000 210 20 302 BUSSI 411RI .DWIB in VIIE YS PRhIIS 5 Is 6000 120 20 145 PIO0IIO0M/1 12I VI14 SYS PRJMH AVC4OM SEC 3 as 500 165 is it VO4TROL [a

Gold nanoparticles on titanium and interaction with prototype protein.

PubMed

Padmos, J Daniel; Duchesne, Paul; Dunbar, Michael; Zhang, Peng

2010-10-01

Modifying titanium (Ti) implant surfaces with functional proteins can strengthen the interface between prosthesis and bone. A prototype system was developed using gold nanoparticles (AuNPs) to immobilize proteins onto Ti. An electroless (galvanic displacement) deposition method was first used to form AuNPs of controlled size and coverage on commercial Ti foil (giving Ti-AuNPs). Parameters were then modified to create two groups of discs (n = 26) with different average AuNP diameters. Scanning electron microscopy and X-ray photoelectron spectroscopy were used to characterize the morphology and surface structure of Ti-AuNPs. To study the interaction of Ti-AuNPs with proteins, Ti discs (n = 8) modified with plain AuNPs and discs (n = 8) modified with thiol (HS--R--COOH)-functionalized AuNPs were treated with lysozyme solution. The amount and activity of the lysozyme on the discs were examined with Micro-BCA and enzymatic assays. Lysozyme was immobilized onto the discs, and the assays showed that the discs with thiol-functionalized AuNPs, discs with bare AuNPs, and Ti controls had average lysozyme adsorptions of 23 x 10(4), 2.3 x 10(4), and 5.7 x 10(4) microg/m2, respectively. The activity assays showed that 21.5, 18.4, and 12.5% of the adsorbed lysozyme was active on the discs with thiol-functionalized AuNPs, discs with bare AuNPs, and Ti controls, respectively. This technique holds promise for binding functional biomolecules to surgical implants, hence possibly creating implant surfaces that react to their local environment. Copyright 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

β2‑adrenergic receptor functionality and genotype in two different models of chronic inflammatory disease: Liver cirrhosis and osteoarthritis.

PubMed

Roca, Reyes; Esteban, Pablo; Zapater, Pedro; Inda, María-Del-Mar; Conte, Anna Lucia; Gómez-Escolar, Laura; Martínez, Helena; Horga, José F; Palazon, José M; Peiró, Ana M

2018-06-01

The present study was designed to investigate the functional status of β2 adrenoceptors (β2AR) in two models of chronic inflammatory disease: liver cirrhosis (LC) and osteoarthritis (OA). The β2AR gene contains three single nucleotide polymorphisms at amino acid positions 16, 27 and 164. The aim of the present study was to investigate the potential influence of lymphocyte β2AR receptor functionality and genotype in LC and OA patients. Blood samples from cirrhotic patients (n=52, hepatic venous pressure gradient 13±4 mmHg, CHILD 7±2 and MELD 11±4 scores), OA patients (n=30, 84% Kellgren‑Lawrence severity 4 grade, 14% knee replacement joint) and healthy volunteers as control group (n=26) were analyzed. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and basal and isoproterenol induced adenylate cyclase activity (isoproterenol stimulus from 10‑9 to 10‑4 mM), and β2AR allelic variants (rs1042713, rs1042714, rs1800888) were determined. β2AR functionality was decreased in the two different models of chronic inflammatory disease studied, OA (50% vs. control) and LC (85% vs. control). In these patients, the strength of the β2AR response to adrenergic stimulation was very limited. Adrenergic modulation of PBMC function through the β2AR stimulus is decreased in chronic inflammatory processes including LC and OA, suggesting that the adrenergic system may be important in the development of these processes.

Acute and chronic hypothyroidism are associated with similar left ventricular diastolic dysfunction relative to the euthyroid state: results of doppler echocardiographic comparisons.

PubMed

Gauna, A; Messuti, H; Papadopulos, G; Benchuga, G; Viale, F; Marlowe, R J; Silva Croome, M C

2011-10-01

How the duration of hypothyroidism affects left ventricular diastolic function is not well-characterized. We sought to compare left ventricular diastolic function in acutely vs chronically hypothyroid patients vs euthyroid controls, and within individuals while on vs off T4. We prospectively performed such comparisons measuring pulsed-wave and color M-mode Doppler echocardiographic variables: early or late mitral peak velocities (E wave or A wave, respectively), E wave/A wave ratio, E wave deceleration time, isovolumic relaxation time (IVRT), mitral flow propagation velocity (Vp), E wave/Vp ratio. Subjects comprised the acute HYPO group, 10 patients undergoing T4 withdrawal ≥ 6 months post-primary treatment for differentiated thyroid cancer (DTC); the chronic HYPO group, 23 treatment-naïve Hashimoto thyroiditis patients; and 21 healthy euthyroid controls. Subjects were adults aged ≤ 60 yr, predominantly female, with sinus rhythm; exclusion criteria were cardiovascular or thyroid disorder besides DTC (Hashimoto thyroiditis) in acute (chronic) HYPO patients or medication (besides thyroid hormone) affecting cardiac or thyroid function. Mean IVRT was significantly delayed and mean Vp, significantly slowed in both HYPO groups vs controls (p<0.0005), but did not differ between HYPO groups. These variables also were significantly impaired (p<0.05) within individuals when off vs on T4 (no.=8 acute, 10 chronic HYPO patients). Both HYPO groups had elevated mean E wave/Vp ratios vs controls, but the elevation reached significance (p<0.05) only in the larger chronic HYPO group. Left ventricular diastolic dysfunction is largely similar in acutely or chronically hypothyroid patients off T4 vs healthy controls or the same patients on T4.

Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized controlled trial

PubMed Central

Michopoulos, Vasiliki; Mancini, Fulvia; Loucks, Tammy L.; Berga, Sarah L.

2013-01-01

Objective To determine whether cognitive behavior therapy (CBT), which we previously showed restored ovarian function in women with functional hypothalamic amenorrhea (FHA), also ameliorated hypercortisolemia and improved other neuroendocrine and metabolic concomitants of in FHA. Design Randomized controlled trial. Intervention CBT vs. observation. Setting Clinical research center at an academic medical university. Patient(s) Seventeen women with FHA were randomized either to CBT or observation. Main Outcome Measure(s) Circulatory concentrations of cortisol, leptin, TSH, total and free thyronine (T3), and total and free thyroxine (T4) before and immediately after completion of CBT or observation. Each woman served as her own control. Results CBT but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T3, or T4 levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, while levels of T3 and T4 remained unchanged. Conclusions CBT ameliorated hypercortisolism and improved neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacological approach aimed at alleviating problematic attitudes not only restored ovarian activity but also improved neuroendocrine and metabolic function in women with FHA. PMID:23507474

Effects of oral iron(III) hydroxide polymaltose complex supplementation on hemoglobin increase, cognitive function, affective behavior and scholastic performance of adolescents with varying iron status: a single centre prospective placebo controlled study.

PubMed

Devaki, Pallaki Baby; Chandra, Ranjit K; Geisser, Peter

2009-01-01

To assess the effects of iron supplementation on iron status, cognitive function, affective behavior and scholastic performance in adolescents with varying iron status. Adolescents of both sexes with varying iron status were allocated to four treatment groups by using inclusion criteria. Three of the four groups (iron deficient anemic, iron deficient and control supplement) received iron(III) hydroxide polymaltose complex (IPC, Maltofer) containing 100 mg of elemental iron 6 days a week for 8 months, while the fourth group (control placebo) was given a placebo. Hematological parameters, cognitive function, affective behavior and scholastic performance were assessed at baseline, 4 months and 8 months of supplementation. Cognitive and scholastic performance test scores for the three supplemented groups increased from baseline to 4 months and from 4 months to 8 months (with concomitant increases in hematological parameters), whereas no increase was observed in the placebo group. No increase was seen in affective behavior scores for any of the groups during or after supplementation. IPC supplementation for eight months yielded significant improvements in cognitive function and scholastic performance in Indian adolescents with and without iron deficiency and anemia.

Active Noise and Vibration Control Literature Survey: Controller Technologies

DTIC Science & Technology

1999-11-01

5.4 Schematic Flowchart of System Identification [Soderstrom, 1989] ................. 5. 7 Measurement System (open-loop...approaches: measurement systems and transfer functions identification [Norton, 1986]. The following figure illustrates the general flowchart ...data SCI Figure 5.3. Schematic flowchart of system identification [Soderstrom, 1989] 5.7 The first type of identification {see Figure 5.4) uses open

[Clinical Trials for Treatment of Stroke Patients with Dysphagia by Vitalstim Electroacupuncture Combined with Swallowing Rehabilitation Training].

PubMed

Zhang, Sheng-Yu; Liu, Shao-Bing; Wu, Wei; Chen, Yi-Min; Liao, Kang-Lin; Xiang, Yong; Pan, Dun

2017-04-25

To observe the clinical effect of vitalstim electroacupuncture (EA) combined with swallowing rehabilitation training in the treatment of stroke patients with dysphagia. A total of 80 stroke patients with dysphagia were randomized into treatment and control groups ( n =40 in each group). Patients of the control group were treated by regular medication for anti-platelet aggregation and anti-coagulation, lipid-lowering, neuroprotection, blood glucose control and blood pressure control, etc. and swallowing function rehabilitation training, and those of the treatment group treated by EA stimulation of Fengchi (GB 20), Jinjin (EX-HN 12) and Yuye (EX-HN 13) with a Vitalstim Electrostimulator and manual acupuncture stimulation of Lianquan (CV 23), Tiantu (CV 22) in combination with regular medication plus swallowing function training as those mentioned in the control group. The EA and manual acupuncture stimulation treatment was conducted once daily, 6 times a week and 4 weeks altogether. The therapeutic effect was assessed by using Kubota swallowing ability test (6 levels), dysphagia subscale (0-6 scores) of the neurological deficit degrees, videofluorography (VFG) assessment (markedly effective, effective and invalid, for evaluating the function and symmetry state of the swallowing movements), and the MOS Item Short Form Health Survey (SF-36, 8 minor items of two major aspects in physiological function, mental health, emotional function, social function and overall health) for assessing the patients' daily-life quality. After the treatment, the dysphagia score of the treatment group was signi-ficantly lower than that of the control group ( P <0.05). VFG outcomes showed that, of the two 40 patients in the control and treatment groups, 16 and 23 experienced a marked improvement, 20 and 15 were effective, 4 and 2 were ineffective, with the markedly effective rate being 40.0% and 57.5%, respectively. The daily-life quality scores for physiological function, mental health, emotional function, social function and overall health were all notably increased after the treatment in both groups, particularly in the treatment group ( P <0.05). The therapeutic effects of the treatment group were remarkably superior to those of the control group in improving dysphagia (showed by dysphagia score and VFG outcomes) and life quality. EA treatment combined with swallowing function rehabilitation training is effective in improving swallowing ability and daily-life quality in stroke patients with dysphagia.

Postural sensorimotor training versus sham exercise in physiotherapy of patients with chronic non-specific low back pain: An exploratory randomised controlled trial

PubMed Central

Wirth, Brigitte

2018-01-01

Sensorimotor training (SMT) is popularly applied as exercise in rehabilitation settings, particularly for musculoskeletal pain. With insufficient evidence on its effect on pain and function, this exploratory randomised controlled trial investigated the potential effects of SMT in rehabilitation of chronic non-specific low back pain. Two arms received 9x30 minutes physiotherapy with added interventions: The experimental arm received 15 minutes of postural SMT while the comparator arm performed 15 minutes of added sub-effective low-intensity training. A treatment blinded tester assessed outcomes at baseline 2–4 days prior to intervention, pre- and post-intervention, and at 4-week follow-up. Main outcomes were pain and functional status assessed with a 0–100mm visual analogue scale and the Oswestry Disability Questionnaire. Additionally, postural control was analysed using a video-based tracking system and a pressure plate during perturbed stance. Robust, nonparametric multivariate hypothesis testing was performed. 22 patients (11 females, aged 32 to 75 years) with mild to moderate chronic pain and functional limitations were included for analysis (11 per arm). At post-intervention, average values of primary outcomes improved slightly, but not to a clinically relevant or statistically significant extent. At 4-week follow-up, there was a significant improvement by 12 percentage points (pp) on the functional status questionnaire in the SMT-group (95% confidence intervall (CI) = 5.3pp to 17.7pp, p < 0.001) but not in the control group (4 pp improvement, CI = 11.8pp to 19.2pp). However, group-by-time interaction effects for functional status (Q = 3.3, 19 p = 0.07) and pain (Q = 0.84, p = 0.51) were non-significant. Secondary kinematic outcomes did not change over time in either of the groups. Despite significant improvement of functional status after SMT, overall findings of this exploratory study suggest that SMT provides no added benefit for pain reduction or functional improvement in patients with moderate chronic non-specific low back pain. Trial registration: ClinicalTrials.gov NCT02304120 and related study protocol, DOI: 10.1186/1471-2474-15-382. PMID:29522571

The effects of treatment with liraglutide on atherothrombotic risk in obese young women with polycystic ovary syndrome and controls.

PubMed

Kahal, Hassan; Aburima, Ahmed; Ungvari, Tamas; Rigby, Alan S; Coady, Anne M; Vince, Rebecca V; Ajjan, Ramzi A; Kilpatrick, Eric S; Naseem, Khalid M; Atkin, Stephen L

2015-04-02

Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular (CV) risk markers. In this study our aim was to assess the effects of six months treatment with liraglutide 1.8 mg od on obesity, and CV risk markers, particularly platelet function, in young obese women with PCOS compared to controls of similar age and weight. Carotid intima-media wall thickness (cIMT) was measured by B-mode ultrasonography, platelet function by flow cytometry, clot structure/lysis by turbidimetric assays and endothelial function by ELISA and post-ischaemic reactive hyperemia (RHI). Data presented as mean change (6-month - baseline) ± standard deviation. Nineteen obese women with PCOS and 17 controls, of similar age and weight, were recruited; baseline atherothrombotic risk markers did not differ between the two groups. Twenty five (69.4%) participants completed the study (13 PCOS, 12 controls). At six months, weight was significantly reduced by 3.0 ± 4.2 and 3.8 ± 3.4 kg in the PCOS and control groups, respectively; with no significant difference between the two groups, P = 0.56. Similarly, HOMA-IR, triglyceride, hsCRP, urinary isoprostanes, serum endothelial adhesion markers (sP-selectin, sICAM and sVCAM), and clot lysis area were equally significantly reduced in both groups compared to baseline. Basal platelet P-selectin expression was significantly reduced at six months in controls -0.17 ± 0.26 but not PCOS -0.12 ± 0.28; between groups difference, 95% confidence interval = -0.14 - 0.26, P = 0.41. No significant changes were noted in cIMT or RHI. Six months treatment with liraglutide (1.8 mg od) equally affected young obese women with PCOS and controls. In both groups, liraglutide treatment was associated with 3-4% weight loss and significant reduction in atherothrombosis markers including inflammation, endothelial function and clotting. Our data support the use of liraglutide as weight loss medication in simple obesity and suggest a potential beneficial effect on platelet function and atherothrombotic risk at 6 months of treatment. Clinical trial reg. no. ISRCTN48560305. Date of registration 22/05/2012.

Influence of gene dosage and autoregulation of the regulatory genes INO2 and INO4 on inositol/choline-repressible gene transcription in the yeast Saccharomyces cerevisiae.

PubMed

Schwank, S; Hoffmann, B; Sch-uller, H J

1997-06-01

Expression of structural genes of phospholipid biosynthesis in yeast is mediated by the inositol/choline-responsive element (ICRE). ICRE-dependent gene activation, requiring the regulatory genes INO2 and INO4, is repressed in the presence of the phospholipid precursors inositol and choline. INO2 and, to a less extent, INO4 are positively autoregulated by functional ICRE sequences in the respective upstream regions. However, an INO2 allele devoid of its ICRE functionally complemented an ino2 mutation and completely restored inositol/choline regulation of Ino2p-dependent reporter genes. Low-level expression of INO2 and INO4 genes, each under control of the heterologous MET25 promoter, did not alter the regulatory pattern of target genes. Thus, upstream regions of INO2 and INO4 are not crucial for transcriptional control of ICRE-dependent genes by inositol and choline. Interestingly, over-expression of INO2, but not of INO4, counteracted repression by phospholipid precursors. Possibly, a functional antagonism between INO2 and a negative regulator is the key event responsible for repression or de-repression.

T-cell help permits memory CD8(+) T-cell inflation during cytomegalovirus latency.

PubMed

Walton, Senta M; Torti, Nicole; Mandaric, Sanja; Oxenius, Annette

2011-08-01

CD4(+) T cells are implied to sustain CD8(+) T-cell responses during persistent infections. As CD4(+) T cells are often themselves antiviral effectors, they might shape CD8(+) T-cell responses via help or via controlling antigen load. We used persistent murine CMV (MCMV) infection to dissect the impact of CD4(+) T cells on virus-specific CD8(+) T cells, distinguishing between increased viral load in the absence of CD4(+) T cells and CD4(+) T-cell-mediated helper mechanisms. Absence of T-helper cells was associated with sustained lytic MCMV replication and led to a slow and gradual reduction of the size and function of the MCMV-specific CD8(+) T-cell pool. However, when virus replication was controlled in the absence of CD4(+) T cells, CD8(+) T-cell function was comparably impaired, but in addition CD8(+) T-cell inflation, a hallmark of CMV infection, was completely abolished. Thus, CD8(+) T-cell inflation during latent CMV infection is strongly dependent on CD4(+) T-cell helper functions, which can partially be compensated by ongoing lytic viral replication in the absence of CD4(+) T cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Elite control of HIV: is this the right model for a functional cure?

PubMed

Cockerham, Leslie R; Hatano, Hiroyu

2015-02-01

A cure for HIV is still greatly needed and has become a global research priority. A unique subset of HIV-infected individuals who spontaneously control HIV exists, and these are known as 'elite controllers'. They may represent a natural model for a 'functional cure' in which there is long term control of viral replication and remission from symptoms of HIV infection in the absence of antiretroviral therapy. However, controllers have evidence of ongoing inflammation, CD4(+) T cell depletion, and perhaps even inflammation-associated cardiovascular disease, suggesting that this natural long term virologic control may be coming at an immunologic and clinical cost. These individuals may continue to provide continued insights into mechanisms of host control; however, they may not represent the best model of a functional cure, if we believe that a cure should require a disease-free (and not just a treatment-free) state. Copyright © 2014 Elsevier Ltd. All rights reserved.

47 CFR 74.434 - Remote control operation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Remote control operation. 74.434 Section 74.434 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES EXPERIMENTAL RADIO... functions to permit proper operation of the station. (b) A remote control system must be designed, installed...

47 CFR 74.434 - Remote control operation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 4 2012-10-01 2012-10-01 false Remote control operation. 74.434 Section 74.434 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES EXPERIMENTAL RADIO... functions to permit proper operation of the station. (b) A remote control system must be designed, installed...

47 CFR 74.434 - Remote control operation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 4 2014-10-01 2014-10-01 false Remote control operation. 74.434 Section 74.434 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES EXPERIMENTAL RADIO... functions to permit proper operation of the station. (b) A remote control system must be designed, installed...

47 CFR 74.434 - Remote control operation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Remote control operation. 74.434 Section 74.434 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES EXPERIMENTAL RADIO... functions to permit proper operation of the station. (b) A remote control system must be designed, installed...

47 CFR 74.434 - Remote control operation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 4 2013-10-01 2013-10-01 false Remote control operation. 74.434 Section 74.434 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES EXPERIMENTAL RADIO... functions to permit proper operation of the station. (b) A remote control system must be designed, installed...

Association of TRPV4 gene polymorphisms with chronic obstructive pulmonary disease.

PubMed

Zhu, Guohua; Gulsvik, Amund; Bakke, Per; Ghatta, Srinivas; Anderson, Wayne; Lomas, David A; Silverman, Edwin K; Pillai, Sreekumar G

2009-06-01

Chronic obstructive pulmonary disease (COPD) is characterized by airway epithelial damage, bronchoconstriction, parenchymal destruction and mucus hypersecretion. Upon activation by a broad range of stimuli, transient receptor potential vanilloid 4 (TRPV4) functions to control airway epithelial cell volume and epithelial and endothelial permeability; it also triggers bronchial smooth muscle contraction and participates in autoregulation of mucociliary transport. These functions of TRPV4 may be important for the regulation of COPD pathogenesis, so TRPV4 is a candidate gene for COPD. We genotyped 20 single nucleotide polymorphisms (SNPs) in TRPV4, and tested qualitative COPD and quantitative FEV(1) and FEV(1)/(F)VC phenotypes in two independent large populations. The family population had 606 pedigrees including 1891 individuals, and the case-control sample included 953 COPD cases and 956 controls. Family-based association tests were performed in the family data. Logistic regression and linear models were used in the case-control data to replicate the association results. In the family data, seven out of 20 SNPs tested were associated with COPD (2.5 x 10(-4) < or = P < or = 0.04) and six SNPs were associated with FEV(1)/VC (0.02 < or = P < or = 0.03) from family-based association tests (PBAT) analysis. Four out of the seven SNPs associated with COPD demonstrated replicated associations with the same effect directions in the case-control population (0.02 < or = P < or = 0.03). Significant haplotype associations supported the results of single SNP analyses. Thus, polymorphisms in the TRPV4 gene are associated with COPD.

Sleep and Cardiometabolic Function in Obese Adolescent Girls with Polycystic Ovary Syndrome

PubMed Central

Nandalike, Kiran; Agarwal, Chhavi; Strauss, Temima; Coupey, Susan M.; Isasi, Carmen R.; Sin, Sanghun; Arens, Raanan

2012-01-01

Objective To compare the polysomnography findings and cardiometabolic function among adolescent girls with PCOS and matched female and male controls. Method Retrospective chart review of electronic medical records of 28 girls with PCOS (age: 16.8±1.9 yrs, BMI Z-score 2.4±0.4), 28 control females (age: 17.1±1.8, BMI Z-score 2.4±0.3) and 28 control males (age: 16.6±1.6, BMI Z-score 2.5±0.5) in a tertiary care center. Results The prevalence of obstructive sleep apnea (OSA) was higher in girls with PCOS compared to control females (16/28 (57%) vs. 4/28(14.3%), p<0.01), however, was comparable to that of the control males (16/28(57%) vs. 21/28(75%), p=0.4). Girls with PCOS had a significantly higher prevalence of insulin resistance compared to control females and control males (20/28 (71.4%) vs. 9/22 (41.0%) (p=0.04) vs. 8/23 (34.8%) (p=0.01). Among girls with PCOS, those with OSA had significantly higher proportions of metabolic syndrome (9/16 (56.3% ) vs. 1/12 (8.3%) p=0.03), higher insulin resistance (13/16 (81.3%) vs. 5/12 (41.6%), p=0.03), elevated daytime systolic blood pressure (128.4±12.8 vs. 115.6±11.4, p<0.01), lower HDL (38.6±8.7 vs. 49±10.9, p=0.01) and elevated triglycerides (149.7±87.7 vs. 93.3±25.8, p=0.03) compared to those without OSA. Conclusions We report a higher prevalence of OSA and metabolic dysfunction in a selected group of obese girls with PCOS referred with sleep related complaints compared to BMI matched control girls without PCOS. We also report higher prevalence of cardiometabolic dysfunction in girls with PCOS and OSA compared to girls with PCOS without OSA. PMID:22921588

MIL-STD-1760 Application Guidelines

DTIC Science & Technology

1991-09-01

64 6.9 Video Switch Functional Diagram ......................................................... 67 6.10 F-16... Video Control .............................................................................. 68 6.11 F-16 Video System...76 6.17 Second Video Line to STAs 4, 5, and 6 1760 ASIs ................................ 77 6.18 Functional

The mirror therapy program enhances upper-limb motor recovery and motor function in acute stroke patients.

PubMed

Lee, Myung Mo; Cho, Hwi-Young; Song, Chang Ho

2012-08-01

The purpose of this study was to evaluate the effects of the mirror therapy program on upper-limb motor recovery and motor function in patients with acute stroke. Twenty-six patients who had an acute stroke within 6 mos of study commencement were assigned to the experimental group (n = 13) or the control group (n = 13). Both experimental and control group members participated in a standard rehabilitation program, but only the experimental group members additionally participated in mirror therapy program, for 25 mins twice a day, five times a week, for 4 wks. The Fugl-Meyer Assessment, Brunnstrom motor recovery stage, and Manual Function Test were used to assess changes in upper-limb motor recovery and motor function after intervention. In upper-limb motor recovery, the scores of Fugl-Meyer Assessment (by shoulder/elbow/forearm items, 9.54 vs. 4.61; wrist items, 2.76 vs. 1.07; hand items, 4.43 vs. 1.46, respectively) and Brunnstrom stages for upper limb and hand (by 1.77 vs. 0.69 and 1.92 vs. 0.50, respectively) were improved more in the experimental group than in the control group (P < 0.05). In upper-limb motor function, the Manual Function Test score (by shoulder item, 5.00 vs. 2.23; hand item, 5.07 vs. 0.46, respectively) was significantly increased in the experimental group compared with the control group (P < 0.01). No significant differences were found between the groups for the coordination items in Fugl-Meyer Assessment. This study confirms that mirror therapy program is an effective intervention for upper-limb motor recovery and motor function improvement in acute stroke patients. Additional research on mirror therapy program components, intensity, application time, and duration could result in it being used as a standardized form of hand rehabilitation in clinics and homes.

Effect of hemicellulose from rice bran on low fat meatballs chemical and functional properties.

PubMed

Hu, Guohua; Yu, Wenjian

2015-11-01

The paper study the functional properties of hemicellulose B (RBHB) and rice bran insoluble dietary fibre (RBDF) to develop an acceptable low fat meat product enriched with high content fibre from defatted rice bran. Meatballs were produced with three different formulations including 2%, 4% and 6% RBHB or RBDF addition. The total trans fatty acids were lower and the ratio of total unsaturated fatty acids to total saturated fatty acids was higher in the samples with added RBHB than in the control meatballs. Meatballs containing RBHB had lower concentrations of total fat and total trans fatty acids than the control samples. Sensory evaluations revealed that meatballs with 2%, 4% and 6% RBHB were overall acceptable. This confirms that the RBHB preparation from defatted rice bran has great potential in food applications, especially in development of functional foods including functional meat products. Copyright © 2014 Elsevier Ltd. All rights reserved.

Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System.

PubMed

Barbieri, Federica; Thellung, Stefano; Würth, Roberto; Gatto, Federico; Corsaro, Alessandro; Villa, Valentina; Nizzari, Mario; Albertelli, Manuela; Ferone, Diego; Florio, Tullio

2014-01-01

Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioning via autocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas.

Over ground walking and body weight supported walking improve mobility equally in cerebral palsy: a randomised controlled trial.

PubMed

Swe, Ni Ni; Sendhilnnathan, Sunitha; van Den Berg, Maayken; Barr, Christopher

2015-11-01

To assess partial body weight supported treadmill training versus over ground training for walking ability in children with mild to moderate cerebral palsy. Randomised controlled trial. A Special Needs school in Singapore. Thirty children with cerebral palsy, aged 6-18, with a Gross Motor Function Classification System score of II-III. Two times 30 minute sessions of walking training per week for 8 weeks, progressed as tolerated, either over ground (control) or using partial body weight supported treadmill training (intervention). The 10 metre walk test, and the 6 minute walk test. Secondary measures were sub-sections D and E on the Gross Motor Function Measure. Outcomes were assessed at baseline, and after 4 and 8 weeks of training. There was no effect of group allocation on any outcome measure, while time was a significant factor for all outcomes. Walking speed improved significantly more in the intervention group by week 4 (0.109 (0.067)m/s vs 0.048 (0.071)m/s, P=0.024) however by week 8 the change from baseline was similar (intervention 0.0160 (0.069)m/s vs control 0.173 (0.109)m/s, P=0.697). All gains made by week 4 were significantly improved on by week 8 for the 10 metre walk test, 6 minute walk test, and the gross motor function measure. Partial body weight supported treadmill training is no more effective than over ground walking at improving aspects of walking and function in children with mild to moderate cerebral palsy. Gains seen in 4 weeks can be furthered by 8 weeks. © The Author(s) 2015.

Non-suppressive regulatory T cell subset expansion in pulmonary arterial hypertension.

PubMed

Sada, Yoshiharu; Dohi, Yoshihiro; Uga, Sayuri; Higashi, Akifumi; Kinoshita, Hiroki; Kihara, Yasuki

2016-08-01

Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4(+)CD45RA(+)FoxP3(low) resting Tregs (rTregs), CD4(+)CD45RA(-)FoxP3(high) activated Tregs (aTregs), and CD4(+)CD45RA(-)FoxP3(low) non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4(+) T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p < 0.05). Of the three subsets, the proportion of non-Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p < 0.01), whereas those of rTregs and aTregs were not different between the two groups. Moreover, the expression levels of cytotoxic T lymphocyte antigen 4, a functional cell surface molecule, in aTregs (p < 0.05) and non-Tregs (p < 0.05) were significantly higher in PAH patients compared with controls. These results suggested the non-Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH.

Response to Congressional Recommendations Regarding the FAA’s En Route Air Traffic Control Computer System.

DTIC Science & Technology

1982-01-01

demand, aviation system changes, and higner levels of ATC automition in the far term 1990-2DOJ). .--.. . . . . . . . . . . . . . .". . L...functions are nearing completion of their development cycle and will be ready for implementation in the 1980’s: 1) Conflict Alert for VFR Intruders (CA...next Section 11.4.2. S0 2- Ilo 11.4.2 Description of the Functional Improvements 1. Conflict Alert for VFR Intruders (CA/VFR) The CA/VFR functional

Stinger Post Hybrid Simulation: Design Description and Users’ Manual

DTIC Science & Technology

1983-04-01

function of three variables. Table 4 MVFG Modes £ ?*" Mode Function Number Argument Number Trunking Station Address Output Hole Argument...between JA and J7. This permits the signal to control a normally-open, single-throw minature relay. It closes the remote operate line when a logic...logic functions are also performed on the card. A normally- open, single-throw minature relay (U5) and an AND gate (1/4 of Ul) are used to perform the

Spatial Control of Functional Response in 4D-Printed Active Metallic Structures

NASA Astrophysics Data System (ADS)

Ma, Ji; Franco, Brian; Tapia, Gustavo; Karayagiz, Kubra; Johnson, Luke; Liu, Jun; Arroyave, Raymundo; Karaman, Ibrahim; Elwany, Alaa

2017-04-01

We demonstrate a method to achieve local control of 3-dimensional thermal history in a metallic alloy, which resulted in designed spatial variations in its functional response. A nickel-titanium shape memory alloy part was created with multiple shape-recovery stages activated at different temperatures using the selective laser melting technique. The multi-stage transformation originates from differences in thermal history, and thus the precipitate structure, at various locations created from controlled variations in the hatch distance within the same part. This is a first example of precision location-dependent control of thermal history in alloys beyond the surface, and utilizes additive manufacturing techniques as a tool to create materials with novel functional response that is difficult to achieve through conventional methods.

Inhibition of Oct 3/4 mitigates the cardiac progenitor-derived myocardial repair in infarcted myocardium.

PubMed

Zhao, Yu Tina; Du, Jianfeng; Chen, Youfang; Tang, Yaoliang; Qin, Gangjian; Lv, Guorong; Zhuang, Shougang; Zhao, Ting C

2015-12-24

Recent evidence has demonstrated that cardiac progenitor cells play an essential role in the induction of angiomyogenesis in infarcted myocardium. We and others have shown that engraftment of c-kit(+) cardiac stem cells (CSCs) into infarcted hearts led to myocardium regeneration and neovascularization, which was associated with an improvement of ventricular function. The purpose of this study is aimed at investigating the functional role of transcription factor (TF) Oct3/4 in facilitating CSCs to promote myocardium regeneration and preserve cardiac performance in the post-MI heart. c-kit(+) CSCs were isolated from adult hearts and re-introduced into the infarcted myocardium in which the mouse MI model was created by permanent ligation of the left anterior descending artery (LAD). The Oct3/4 of CSCs was inhibited by transfection of Oct3/4 siRNA, and transfection of CSCs with control siRNA serves as control groups. Myocardial functions were evaluated by echocardiographic measurement. Histological analysis was employed to assess newly formed cardiogenesis, neovascularization, and cell proliferations. Terminal deoxynucleotidyltransferase (TdT) nick-end labeling (TUNEL) was carried out to assess apoptotic cardiomyocytes. Real time polymerase chain reaction and Western blot were carried out to evaluate the level of Oct 3/4 in CSCs. Two weeks after engraftment, CSCs increased ventricular functional recovery as shown by a serial echocardiographic measurement, which is concomitant with the suppression of cardiac hypertrophy and attenuation of myocardial interstitial fibrosis. Suppression of Oct 3/4 of CSCs abrogated functional improvements and mitigated the hypertrophic response and cardiac remodeling. Transplantation of c-kit(+) CSCs into MI hearts promoted cardiac regeneration and neovascularization, which were abolished with the knockdown of Oct3/4. Additionally, suppression of Oct3/4 abrogated myocyte proliferation in the CSC-engrafted myocardium. Our results indicate that CSCs-derived cardiac regeneration improves the restoration of cardiac function and is mediated through Oct 3/4.

Cognitive Training and Transcranial Direct Current Stimulation for Mild Cognitive Impairment in Parkinson's Disease: A Randomized Controlled Trial

PubMed Central

Gasson, Natalie; Johnson, Andrew R.; Booth, Leon; Loftus, Andrea M.

2018-01-01

This study examined whether standard cognitive training, tailored cognitive training, transcranial direct current stimulation (tDCS), standard cognitive training + tDCS, or tailored cognitive training + tDCS improved cognitive function and functional outcomes in participants with PD and mild cognitive impairment (PD-MCI). Forty-two participants with PD-MCI were randomized to one of six groups: (1) standard cognitive training, (2) tailored cognitive training, (3) tDCS, (4) standard cognitive training + tDCS, (5) tailored cognitive training + tDCS, or (6) a control group. Interventions lasted 4 weeks, with cognitive and functional outcomes measured at baseline, post-intervention, and follow-up. The trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12614001039673). While controlling for moderator variables, Generalized Linear Mixed Models (GLMMs) showed that when compared to the control group, the intervention groups demonstrated variable statistically significant improvements across executive function, attention/working memory, memory, language, activities of daily living (ADL), and quality of life (QOL; Hedge's g range = 0.01 to 1.75). More outcomes improved for the groups that received standard or tailored cognitive training combined with tDCS. Participants with PD-MCI receiving cognitive training (standard or tailored) or tDCS demonstrated significant improvements on cognitive and functional outcomes, and combining these interventions provided greater therapeutic effects. PMID:29780572

The influence of joint hypermobility on functional movement control in an elite netball population: A preliminary cohort study.

PubMed

Soper, Kessie; Simmonds, Jane V; Kaz Kaz, Hanadi; Ninis, Nelly

2015-05-01

To ascertain the prevalence of General Joint Hypermobility (GJH) and Joint Hypermobility Syndrome (JHS) in elite level netballers. To investigate whether GJH influences functional movement control and explore whether symptoms of dysautonomia are reported in this population. Observational within-subject cross-sectional design. Field based study. 27 elite level netballers (14-26 years). GJH and JHS were assessed using the Beighton scale, 5 point questionnaire and the Brighton Criteria. Functional movement control was measured using posturography on a force platform and the Star Excursion Balance Test (SEBT). The prevalence of GJH was 63% (n = 17) (Beighton score ≥4/9) and JHS was 15% (n = 4). Symptoms of dysautonomia were minimally prevalent. A trend was observed in which participants with GJH demonstrated increased postural instability on the functional tests. Following Bonferroni adjustment, this was statistically significant only when comparing posturographic data between the distinctly hypermobile participants and the rest of the group for path area (p = 0.002) and velocity (p = 0.002) on the left side. A high prevalence of GJH was observed. A trend towards impairment of functional movement control was observed in the netballers with GJH. This observation did not reach statistical significance except for posturographic path area and velocity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain heparan sulphate proteoglycans are altered in developing foetus when exposed to in-utero hyperglycaemia.

PubMed

Sandeep, M S; Nandini, C D

2017-08-01

In-utero exposure of foetus to hyperglycaemic condition affects the growth and development of the organism. The brain is one of the first organs that start to develop during embryonic period and glycosaminoglycans (GAGs) and proteoglycans (PGs) are one of the key molecules involved in its development. But studies on the effect of hyperglycaemic conditions on brain GAGs/PGs are few and far between. We, therefore, looked into the changes in brain GAGs and PGs at various developmental stages of pre- and post-natal rats from non-diabetic and diabetic mothers as well as in adult rats induced with diabetes using a diabetogenic agent, Streptozotocin. Increased expression of GAGs especially that of heparan sulphate class in various developmental stages were observed in the brain as a result of in-utero hyperglycaemic condition but not in that of adult rats. Changes in disaccharides of heparan sulphate (HS) were observed in various developmental stages. Furthermore, various HSPGs namely, syndecans-1 and -3 and glypican-1 were overexpressed in offspring from diabetic mother. However, in adult diabetic rats, only glypican-1 was overexpressed. The offsprings from diabetic mothers became hyperphagic at the end of 8 weeks after birth which can have implications in the long run. Our results highlight the likely impact of the in-utero exposure of foetus to hyperglycaemic condition on brain GAGs/PGs compared to diabetic adult rats.

A Cleavage-potentiated Fragment of Tear Lacritin Is Bactericidal*

PubMed Central

McKown, Robert L.; Coleman Frazier, Erin V.; Zadrozny, Kaneil K.; Deleault, Andrea M.; Raab, Ronald W.; Ryan, Denise S.; Sia, Rose K.; Lee, Jae K.; Laurie, Gordon W.

2014-01-01

Antimicrobial peptides are important as the first line of innate defense, through their tendency to disrupt bacterial membranes or intracellular pathways and potentially as the next generation of antibiotics. How they protect wet epithelia is not entirely clear, with most individually inactive under physiological conditions and many preferentially targeting Gram-positive bacteria. Tears covering the surface of the eye are bactericidal for Gram-positive and -negative bacteria. Here we narrow much of the bactericidal activity to a latent C-terminal fragment in the prosecretory mitogen lacritin and report that the mechanism combines membrane permeabilization with rapid metabolic changes, including reduced levels of dephosphocoenzyme A, spermidine, putrescine, and phosphatidylethanolamines and elevated alanine, leucine, phenylalanine, tryptophan, proline, glycine, lysine, serine, glutamate, cadaverine, and pyrophosphate. Thus, death by metabolic stress parallels cellular attempts to survive. Cleavage-dependent appearance of the C-terminal cationic amphipathic α-helix is inducible within hours by Staphylococcus epidermidis and slowly by another mechanism, in a chymotrypsin- or leupeptin protease-inhibitable manner. Although bactericidal at low micromolar levels, within a biphasic 1–10 nm dose optimum, the same domain is mitogenic and cytoprotective for epithelia via a syndecan-1 targeting mechanism dependent on heparanase. Thus, the C terminus of lacritin is multifunctional by dose and proteolytic processing and appears to play a key role in the innate protection of the eye, with wider potential benefit elsewhere as lacritin flows from exocrine secretory cells. PMID:24942736

Early alterations in soleus GLUT-4, glucose transport, and glycogen in voluntary running rats

NASA Technical Reports Server (NTRS)

Henriksen, Erik J.; Halseth, Amy E.

1994-01-01

Voluntary wheel running (WR) by juvenile female rats was used as a noninterventional model of soleus muscle functional overload to study the regulation of insulin-stimulated glucose transport activity by the glucose transporter (GLUT-4 isoform) protein level and glycogen concentration. Soleus total protein content was significantly greater (+18%;P greater than 0.05) than in age-matched controls after 1 wk of WR, and this hypertrophic response continued in weeks 2-4 (+24-32%). GLUT-4 protein was 39% greater than in controls in 1-wk WR soleus, and this adaptation was accompanied by a similar increase in in vitro insulin-stimulated glucose transport activity(+29%). After 2 and 4 wk of WR, however, insulin-stimulated glucose transport activity had returned to control levels, despite a continued elevation (+25-28%) of GLUT-4 protein. At these two time points, glycogen concentration was significantly enhanced in WR soleus (+21-42%), which coincided with significant reductions in glycogen synthase activity ratios (-23 to-41%). These results indicate that, in this model of soleus muscle functional overload, the GLUT-4 protein level may initially regulate insulin-stimulated glucose transport activity in the absence of changes in other modifying factors. However,this regulation of glucose transport activity by GLUT-4 protein may be subsequently overridden by elevated glycogen concentration.

Sexual function of women suffering from anorexia nervosa and bulimia nervosa.

PubMed

Gonidakis, Fragiskos; Kravvariti, Vasilliki; Varsou, Eleftheria

2015-01-01

The cross-sectional study aimed at examining the sexual function of young adult women suffering from eating disorders. The authors interviewed 53 women (26 with anorexia nervosa and 27 with bulimia nervosa) and 58 female students. Each participant was administered the Female Sexual Function Index, the Eating Attitudes Test, the Body Shape Questionnaire, and the Beck Depression Inventory. Comparisons among the 3 groups showed that patients with anorexia nervosa scored lower in each Female Sexual Function Index subscale than did healthy controls. There was no significant difference between bulimia nervosa and healthy controls. Sexual functionality of patients with anorexia nervosa was correlated only with body mass index (r = 0.5, p =.01). Sexual functionality of patients with bulimia nervosa was correlated only with the Beck Depression Inventory (r = -0.4, p =.03) Patients with anorexia nervosa had more disturbed sexual function than did controls. Sexual function can be related to the level of starvation and symptoms of depression.

Virtual Reality Training with Cognitive Load Improves Walking Function in Chronic Stroke Patients.

PubMed

Cho, Ki Hun; Kim, Min Kyu; Lee, Hwang-Jae; Lee, Wan Hee

2015-08-01

Virtual reality training is considered as an effective intervention method of stroke patients, and the virtual reality system for therapeutic rehabilitation has emphasized the cognitive factors to improve walking function. The purpose of current study was to investigate the effect of virtual reality training with cognitive load (VRTCL) on walking function of chronic stroke. Chronic stroke patients were randomly assigned to the VRTCL group (11 patients, including 5 men; mean age, 60.0 years; post-stroke duration, 273.9 days) or control group (11 patients, including 2 men; mean age, 58.6 years; post-stroke duration, 263.9 days). All subjects participated in the standard rehabilitation program that consisted of physical and occupational therapies. In addition, VRTCL group participated in the VRTCL for 4 weeks (30 min per day and five times a week), while those in the control group participated in virtual reality treadmill training. Walking function under single (walking alone) and dual task (walking with cognitive tasks) conditions was assessed using an electrical walkway system. After the 4-week intervention, under both single and dual task conditions, significant improvement on walking function was observed in VRTCL and control groups (P < 0.05). In addition, in the dual task condition, greater improvement on walking function was observed in the VRTCL group, compared with the control group (P < 0.05). These findings demonstrated the efficacy of VRTCL on the walking function under the dual task condition. Therefore, we suggest that VRTCL may be an effective method for the achievement of independent walking in chronic stroke patients.

Effect of granulocyte colony stimulating EPC on cardiac function and myocardial energy expenditure in patients with heart failure after myocardial infarction.

PubMed

Zhao, Zilin; Luo, Jianchun; Ma, Lixian; Luo, Xia; Huang, Liangyan

2015-01-01

To study the changes of cardiac function and myocardial energy expenditure following treatment with granulocyte colony stimulating factor (G-CSF) in patients with heart failure after myocardial infarction. Thirty-eight patients with heart failure after myocardial infarction were randomized into G-CSF treatment group and control group. All the patients received conventional treatment (medication and interventional therapy), and the patients in treatment group were given additional G-CSF (600 μg/day) for 7 consecutive days. The plasma level of brain-type natriuretic peptide (BNP) and the number of endothelial progenitor cells (EPC) in the peripheral blood were detected before and at 7 days and 4 months after the treatment. The cardiac functions (LVEF, FS, LVIDs, PWTs, EDV, SV, ET) was evaluated by ultrasonic imaging before and at 2 weeks and 4 months after the treatment. The MEE and circumferential end-systolic wall stress (cESS) were calculated by correlation formula. The number of EPC was significantly higher in the treatment group than in the control group after the treatment especially at 7 days (P<0.01). In both groups, BNP level was lowered significantly after the treatment to recover the normal level (P<0.01). The cardiac functions and myocardial energy expenditure were improved in all the patients at 2 weeks and 4 months after the treatment, and the improvement was more obvious in the treatment group (P<0.05), especially in terms of the MEE and cESS was significantly lowered in the treatment group than in the control group after the treatment at 2 weeks (P<0.01), the LVEF and FS was significantly increased in the treatment group than in the control group after the treatment at 4 months (P<0.01). EPC mobilization by G-CSF can effectively improve the cardiac functions, lessen ventricular remodeling and reduce myocardial energy expenditure in patients with heart failure after myocardial infarction.

The effect of preoperative training on functional recovery in patients undergoing total knee arthroplasty: A systematic review and meta-analysis.

PubMed

Ma, Jian-Xiong; Zhang, Lu-Kai; Kuang, Ming-Jie; Zhao, Jie; Wang, Ying; Lu, Bin; Sun, Lei; Ma, Xin-Long

2018-03-01

A meta-analysis to evaluate the efficacy of preoperative training on functional recovery in patients undergoing total knee arthroplasty. Randomized controlled trials (RCTs) about relevant studies were searched from PubMed (1996-2017.4), Embase (1980-2017.4), and the Cochrane Library (CENTRAL 2017.4). Nine studies which evaluated the effect of preoperative training on functional recovery in patients undergoing TKA were included in our meta-analysis. Meta-analysis results were collected and analyzed by Review Manager 5.3 (Copenhagen: The Nordic Cochrane Center the Collaboration 2014). Nine studies containing 777 patients meet the inclusion criteria. Our pooled data analysis indicated that preoperative training was as effective as the control group in terms of visual analogue scale(VAS) score at ascend stairs (P = 0.41) and descend stars (P = 0.80), rang of motion (ROM) of flexion (P = 0.86) and extension (P = 0.60), short form 36 (SF-36) of physical function score (P = 0.07) and bodily pain score (P = 0.39), western Ontario and Macmaster universities osteoarthritis index (WOMAC) function score (P = 0.10), and time up and go (P = 0.28). While differences were found in length of stay (P < 0.05). Our meta-analysis demonstrated that preoperative training have the similar efficacy on functional recovery in patients following total knee arthroplasty compared with control group. However, high quality studies with more patients were needed in future. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

A quantitative approach to measure women's sexual function using electromyography: a preliminary study of the Kegel exercise.

PubMed

Mohktar, Mas Sahidayana; Ibrahim, Fatimah; Mohd Rozi, Nur Farahana; Mohd Yusof, Juhaida; Ahmad, Siti Anom; Su Yen, Khong; Omar, Siti Zawiah

2013-12-13

Currently, the reference standard used to clinically assess sexual function among women is a qualitative questionnaire. Hence, a generalised and quantitative measurement tool needs to be available as an alternative. This study investigated whether an electromyography (EMG) measurement technique could be used to help quantify women's sexual function. A preliminary intervention study was conducted on 12 female subjects, who were randomised into a control (n=6) and an intervention (n=6) group. Intervention involved a set regimen of pelvic floor muscle exercises (Kegel) and the control group did not have any treatment. All subjects were asked to answer a validated, self-rated Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ). EMG measurements of the pelvic floor muscles (PFM) and the abdominal muscles were taken from all women at recruitment and 8 weeks after study commencement. After 8 weeks, most of the subjects in the control group did not display any noted positive difference in either PISQ score (4/6) or in their muscle strength (4/6). However, a noted progressive difference were observed in subjects who were placed in the Kegel group; PISQ score (5/6) and muscles strength (4/6). The noted difference in the Kegel group subjects was that if progress is observed in the sexual function, improvement is also observed in the strength of at least 2 types of muscles (either abdominal or PFM muscles). Thus, EMG measurement is a potential technique to quantify the changes in female sexual function. Further work will be conducted to validate this assumption.

Integrating Planning and Control for Constrained Dynamical Systems

DTIC Science & Technology

2007-12-01

38 4.2 Mapping from polygonal cell to disk . . . . . . . . . . . . . . . . . . . . . . . . . 39 4.3 Convergent potential ...some idealized potential function. The feedback control policies defined in this thesis are specifically designed to satisfy the low-level constraints...problem into different parts, only focusing on one part, and leaving the rest to others. Some techniques work only in ideal conditions; while others solve

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection.

PubMed

Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D; Ndung'u, Thumbi; Ndhlovu, Zaza M

2017-04-01

Immune control of viral infections is heavily dependent on helper CD4 + T cell function. However, the understanding of the contribution of HIV-specific CD4 + T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4 + T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4 + T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4 + T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4 + T cells in HIV controllers than progressors ( P = 0.0001), and these expanded Gag-specific CD4 + T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control ( r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4 + T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4 + T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4 + T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4 + T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4 + T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4 + T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4 + T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections. Copyright © 2017 American Society for Microbiology.

Dark chocolate improves coronary vasomotion and reduces platelet reactivity.

PubMed

Flammer, Andreas J; Hermann, Frank; Sudano, Isabella; Spieker, Lukas; Hermann, Matthias; Cooper, Karen A; Serafini, Mauro; Lüscher, Thomas F; Ruschitzka, Frank; Noll, Georg; Corti, Roberto

2007-11-20

Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis. We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36+/-0.51 to 2.51+/-0.59 mm, P<0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5+/-11.4% versus -4.3+/-11.7% in the placebo group, P=0.01). Platelet adhesion decreased from 4.9+/-1.1% to 3.8+/-0.8% (P=0.04) in the dark chocolate group but remained unchanged in the control group. Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.

Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles

NASA Astrophysics Data System (ADS)

Lavado, Andrea S.; Chauhan, Veeren M.; Alhaj Zen, Amer; Giuntini, Francesca; Jones, D. Rhodri E.; Boyle, Ross W.; Beeby, Andrew; Chan, Weng C.; Aylott, Jonathan W.

2015-08-01

Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(ii) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(ii) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(ii) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures.Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(ii) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(ii) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(ii) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures. Electronic supplementary information (ESI) available: Materials and experimental methods for the synthesis of (1) positively charged alkyne functionalized nanoparticles (2) Zn(ii) and Cu(ii) centred porphyrin (3); conjugating porphyrins to alkyne-functionalized nanoparticles via click chemistry (4) nanoparticle characterisation (size charge and fluorescence), (5) synthesis of BPTFMC (6) hMSC collection, storage and preparation (7) delivery of porphyrin functionalized nanoparticles (8) staining mitochondria, cumulative ROS production and determination of nanoparticles subcellular localisation (9) fluorescence microscopy and controlled irradiation of hMSCs (10) flow cytometry and controlled irradiation using a custom built irradiator. In addition, results highlighting: (1) nanoparticles emission spectra, size and charge, (2) BPTFMC fluorescence response and (3) hMSCs following light irradiation using flow cytometry. See DOI: 10.1039/c5nr00795j

Functional hypothalamic amenorrhea is associated with elevated ghrelin and disordered eating.

PubMed

Schneider, Lisa F; Warren, Michelle P

2006-12-01

To determine whether ghrelin, an orexigen released by the stomach, is elevated in women with hypothalamic amenorrhea who are of normal weight and whether this is associated with abnormal eating behaviors. Controlled clinical study. Healthy volunteers in an academic research environment. Twenty-seven women with functional hypothalamic amenorrhea (FHA) and 42 normally menstruating women. None. Ghrelin and eating behavior. Ghrelin was significantly elevated in FHA (648.4 +/- 92.0 pg/mL vs. controls 596.7 +/- 79.0 pg/mL), while leptin, although lower, was not significantly so (FHA 5.4 +/- 2.8 ng/mL vs. controls 6.4 +/- 3 ng/mL). Eating Attitudes Test (EAT) scores were also significantly elevated in FHA (15.3 +/- 10.6 vs. controls 10.3 +/- 8.4), particularly on the subscale that measured bulimic behaviors. However, FHA patients consumed significantly more kilocalories (1,930 kcal/day vs. 1,588 kcal/day). High ghrelin in women with FHA may be linked to abnormal dietary behaviors, as reflected in high EAT scores yet characterized by normal caloric intake. Ghrelin may act as a restraining metabolic signal preventing a return to cyclicity in women with both disordered eating and FHA, prolonging amenorrhea when leptin has returned to normal.

Predictors of Stress Fracture Susceptibility in Young Female Recruits

DTIC Science & Technology

2004-09-02

fracture as women who ran 4 or more times a week (OR = 2.17; 95% CI, 1.0-4.5). Among measures of reproductive history and birth control pill use, only...the analyses on menstrual function. No significant associations were found for birth control pill use. After adjusting for age and other potential...and Odds Ratios by Measures of Self-Reported Reproductive History, and Birth Control Use, Female Marine Corps Recruits, Parris Island, March 1995 to

Adding motor control training to muscle strengthening did not substantially improve the effects on clinical or kinematic outcomes in women with patellofemoral pain: A randomised controlled trial.

PubMed

Rabelo, Nayra Deise Dos Anjos; Costa, Leonardo Oliveira Pena; Lima, Bruna Maria de; Dos Reis, Amir Curcio; Bley, André Serra; Fukuda, Thiago Yukio; Lucareli, Paulo Roberto Garcia

2017-10-01

Randomized controlled trial. Patients with Patellofemoral pain (PFP) usually present muscular weakness, pain and impaired motor control. Muscle strengthening is an effective treatment strategy for PFP, but the additional benefits of movement control training remain unknown. Therefore, the aim of this study was to compare the effects of movement control training associated with muscle strengthening, with a conventional program of strengthening alone in women with PFP. Thirty-four women were randomly assigned to two groups. The Strengthening group (S group) performed 12 sessions to strengthen the knee and hip muscles. The Movement Control & Strengthening group (MC&S group) performed the same exercises and movement control training of the trunk and lower limbs. Effects of the treatment (i.e., between-group differences) were calculated using linear mixed models. Primary outcomes were function and pain intensity after completion of the treatment protocol. Secondary outcomes were; muscle strength and kinematic outcomes during the step down task after 4 weeks of treatment; and function and pain intensity 3 and 6 months after randomization. The MC&S group did not present significantly better function (MD -2.5 points, 95% CI;-10.7-5.5) or pain (MD -0.3 points, 95% CI;-1.7-1.0) at 4 weeks. There was a small difference in favour of the MC&S group for AKPS scores at 3 months (MD -8.5 points; 95% CI;-16.8 to -0.3). No significant between-group differences were observed for the other outcomes. Movement control training was no more effective than the isolated strengthening protocol, in terms of pain, function, muscle strength, or kinematics. Copyright © 2017 Elsevier B.V. All rights reserved.

Skin autofluorescence is associated with arterial stiffness and insulin level in endurance runners and healthy controls - Effects of aging and endurance exercise.

PubMed

Couppé, Christian; Dall, Christian Have; Svensson, Rene Brüggebusch; Olsen, Rasmus Huan; Karlsen, Anders; Praet, Stephan; Prescott, Eva; Magnusson, S Peter

2017-05-01

Life-long regular endurance exercise yields positive effects on cardiovascular and metabolic function, disease and mortality rate. Glycation may be a major mechanism behind age-related diseases. However, it remains unknown if skin autofluorescence (SAF), which reflects glycation, is related to arterial and metabolic function in life-long endurance runners and sedentary controls. Healthy elderly men: 15 life-long endurance runners (OT) (64±4years) and 12 old untrained (OU) (66±4years), and healthy young men; ten young athletes (YT) (26±4years) matched to OT for running distance, and 12 young untrained (YU) (24±3years) were recruited. Endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI@75 and AI) were measured by an operator-independent PAT 2000. SAF was non-invasively determined using an autofluorescence spectrometer. For AI@75 there was an effect of age (p<0.0001), but not training (p=0.71). There was an interaction for endothelial function (p<0.05): YT had higher RHI than YU (p<0.05) and OU (p<0.01). SAF was associated with arterial stiffness (r 2 =0.57, p<0.001), insulin and HOMA-index levels after age correction (both r 2 =0.19, p<0.05). To our knowledge, these are the first data to show that skin autofluorescence (SAF) is linked to human arterial stiffness and insulin resistance in well-trained elderly and young men as well as sedentary controls. SAF may in the future be a helpful tool to predict vascular and metabolic dysfunction (early signs of aging and pathology). Surprisingly, endurance running only had modest effects on cardiovascular function compared to lean healthy controls. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of special exercise programs on functional movement screen scores and injury prevention in preprofessional young football players.

PubMed

Dinc, Engin; Kilinc, Bekir Eray; Bulat, Muge; Erten, Yunus Turgay; Bayraktar, Bülent

2017-10-01

To increase movement capacity and to reduce injury risk in young soccer players by implementing a special functional exercise program based on functional movement screen (FMS) and correctives. 67 young male athletes 14-19 years of age from a Super League Football Club Academy participated in the study. Functional movement patterns were evaluated with FMS assessment protocol. Deep squat, hurdle step, inline lunge, shoulder mobility, active straight leg raise, trunk stability push-up, and rotatory stability were examined in FMS. Considering the FMS scores the number of intervention and control groups were defined as 24 and 43, respectively. Intervention program was composed of 1 hr twice a week sessions in total of 12 weeks with 4 weeks of mobility, 4 weeks of stability, and 4 weeks of integration exercises. At the end of 12-week intervention and control groups were re-evaluated with FMS protocol. Contact and noncontact sports injuries recorded during one season. In intervention group there was statistically significant difference in increase in total FMS scores ( P <0.01), deep squat ( P ≤0.001), hurdle step ( P <0.05), inline lunge ( P <0.01), and trunk stability push-up ( P <0.01). In control group total FMS, deep squat, and trunk stability push-up scores increased with a statistical difference ( P <0.01, P <0.05, P ≤0.01, respectively). The incidence of noncontact injury in control group was higher than intervention group ( P <0.05). Periodic movement screening and proper corrections with functional training is valuable in order to create better movement capacity to build better physical performance and more effective injury prevention.

Injectable Microsphere Gel Progressively Improves Global Ventricular Function, Regional Contractile Strain, and Mitral Regurgitation after Myocardial Infarction

PubMed Central

McGarvey, Jeremy R; Kondo, Norihiro; Witschey, Walter RT; Takebe, Manabu; Aoki, Chikashi; Burdick, Jason A.; Spinale, Francis G; Gorman, Joseph H; Pilla, James J; Gorman, Robert C

2014-01-01

Background There is continued need for therapies which reverse or abate the remodeling process following myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. Methods Twenty five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into four groups: one week treatment, one week control, four week treatment, and four week control. Following infarction, animals received either twenty 150μl calcium hydroxyapatite gel or saline injections within the infarct. At their respective timepoints, echocardiograms, cardiac MRI, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. Results Global and regional LV function were depressed in all infarcted subjects at one week compared to healthy controls. By four weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared to infarcted controls (EF 48.5±1.9% vs. 38.0±1.7%, p<0.01). Similarly, regional borderzone radial contractile strain (16.3±1.5% vs. 11.2±1.5%, p=0.04), MR grade (0.4±0.2 vs. 1.2±0.2, p=0.04), and infarct thickness (7.8±0.5mm vs. 4.5±0.2mm, p<0.01) were improved at this timepoint in the treatment group compared to infarct controls. Conclusions Calcium hydroxyapatite injection following MI progressively improves global LV function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is viable alternative in the current management of heart failure. PMID:25524397

Extension of suboptimal control theory for flow around a square cylinder

NASA Astrophysics Data System (ADS)

Fujita, Yosuke; Fukagata, Koji

2017-11-01

We extend the suboptimal control theory to control of flow around a square cylinder, which has no point symmetry on the impulse response from the wall in contrast to circular cylinders and spheres previously studied. The cost functions examined are the pressure drag (J1), the friction drag (J2), the squared difference between target pressure and wall pressure (J3) and the time-averaged dissipation (J4). The control input is assumed to be continuous blowing and suction on the cylinder wall and the feedback sensors are assumued on the entire wall surface. The control law is derived so as to minimize the cost function under the constraint of linearized Navier-Stokes equation, and the impulse response field to be convolved with the instantaneous flow quanties are numerically obtained. The amplitide of control input is fixed so that the maximum blowing/suction velocity is 40% of the freestream velocity. When J2 is used as the cost function, the friction drag is reduced as expected but the mean drag is found to increase. In constast, when J1, J3, and J4 were used, the mean drag was found to decrease by 21%, 12%, and 22%, respectively; in addition, vortex shedding is suppressed, which leads to reduction of lift fluctuations.

Effect of dolutegravir functional monotherapy on HIV-1 virological response in integrase strand transfer inhibitor resistant patients.

PubMed

Naeger, Lisa K; Harrington, Patrick; Komatsu, Takashi; Deming, Damon

2016-01-01

VIKING-4 assessed the safety and efficacy of dolutegravir in heavily antiretroviral treatment-experienced patients who had documented integrase strand transfer inhibitor (INSTI) resistance-associated substitutions in their HIV. VIKING-4 had a placebo-controlled 7-day dolutegravir functional monotherapy phase followed by dolutegravir plus an optimized background regimen for 48 weeks. Independent resistance analyses evaluated week 48 virological responses in the VIKING-4 trial based on the presence of baseline INSTI resistance-associated substitutions and baseline dolutegravir phenotypic susceptibility. Response rates at week 48 based on baseline dolutegravir resistance subgroups were compared for the 7-day dolutegravir functional monotherapy arm and placebo-control arm. Additionally, genotypic and phenotypic resistance at day 8 and time of failure was analysed for the virological failures from both arms. Week 48 response rates for VIKING-4 were 23% (3/13) in the 7-day dolutegravir functional monotherapy arm compared with 60% (9/15) in the 7-day placebo arm. Response rates were consistently lower in the dolutegravir functional monotherapy arm across baseline INSTI genotypic and phenotypic subgroups. There was a higher proportion of virological failures in the 7-day dolutegravir functional monotherapy arm (n=6/13; 46%) compared with the 7-day placebo arm (n=3/15; 20%). Additionally, five virological failures in the dolutegravir arm had virus expressing emergent INSTI resistance-associated substitutions compared with two in the placebo arm. Analysis of response rates and resistance emergence in VIKING-4 suggests careful consideration should be given to the duration of functional monotherapy in future studies of highly treatment-experienced patients to reduce the risk of resistance and virological failure.

A 4-Week Neuromuscular Training Program and Gait Patterns at the Ankle Joint

PubMed Central

Coughlan, Garrett; Caulfield, Brian

2007-01-01

Context: Previous research into the rehabilitation of ankle sprains has primarily focused on outcome measures that do not replicate functional activities, thus making it difficult to extrapolate the results relative to the weight-bearing conditions under which most ankle sprains occur. Objective: To measure the effects of a training program on gait during walking and running in an active athletic population. Design: Matched-pairs, controlled trial. Setting: University motion analysis laboratory. Patients or Other Participants: Ten subjects from an athletic population (7 healthy, 3 with functional ankle instability: age = 25.8 ± 3.9 years, height = 177.6 ± 6.1 cm, mass = 66.8 ± 7.4 kg) and 10 controls matched for age, sex, activity, and ankle instability (7 healthy, 3 with functional ankle instability: age = 27.4 ± 5.8 years, height = 178.7 ± 10.8 cm, mass = 71.6 ± 10.0 kg). Intervention(s): A 4-week neuromuscular training program undertaken by the treatment group. Main Outcome Measure(s): We measured ankle position and velocity in the frontal (x) and sagittal (y) planes in all subjects during treadmill walking and running for the periods 100 milliseconds before heel strike, at heel strike, and 100 milliseconds after heel strike. Results: A 4-week neuromuscular training program resulted in no significant changes in ankle position or velocity during treadmill walking and running. Conclusions: The mechanisms by which neuromuscular training improves function in normal subjects and those with functional ankle instability do not appear to result in measurable changes in gait kinematics. Our findings raise issues regarding methods of ankle sprain rehabilitation and the measurement of their effectiveness in improving functional activities. Further research in a larger population with functional ankle instability is necessary. PMID:17597944

Reducing robotic guidance during robot-assisted gait training improves gait function: a case report on a stroke survivor.

PubMed

Krishnan, Chandramouli; Kotsapouikis, Despina; Dhaher, Yasin Y; Rymer, William Z

2013-06-01

To test the feasibility of patient-cooperative robotic gait training for improving locomotor function of a chronic stroke survivor with severe lower-extremity motor impairments. Single-subject crossover design. Performed in a controlled laboratory setting. A 62-year-old man with right temporal lobe ischemic stroke was recruited for this study. The baseline lower-extremity Fugl-Meyer score of the subject was 10 on a scale of 34, which represented severe impairment in the paretic leg. However, the subject had a good ambulation level (community walker with the aid of a stick cane and ankle-foot orthosis) and showed no signs of sensory or cognitive impairments. The subject underwent 12 sessions (3 times per week for 4wk) of conventional robotic training with the Lokomat, where the robot provided full assistance to leg movements while walking, followed by 12 sessions (3 times per week for 4wk) of patient-cooperative robotic control training, where the robot provided minimal guidance to leg movements during walking. Clinical outcomes were evaluated before the start of the intervention, immediately after 4 weeks of conventional robotic training, and immediately after 4 weeks of cooperative control robotic training. These included: (1) self-selected and fast walking speed, (2) 6-minute walk test, (3) Timed Up & Go test, and (4) lower-extremity Fugl-Meyer score. Results showed that clinical outcomes changed minimally after full guidance robotic training, but improved considerably after 4 weeks of reduced guidance robotic training. The findings from this case study suggest that cooperative control robotic training is superior to conventional robotic training and is a feasible option to restoring locomotor function in ambulatory stroke survivors with severe motor impairments. A larger trial is needed to verify the efficacy of this advanced robotic control strategy in facilitating gait recovery after stroke. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The Contribution of Executive Functions to Participation in School Activities of Children with High Functioning Autism Spectrum Disorder

ERIC Educational Resources Information Center

Zingerevich, Chaya; Patricia D., LaVesser

2009-01-01

This study describes the contribution of executive functions to participation in school activities of children diagnosed with ASD ages 6-9 years while controlling for sensory processing. Twenty-four children, ages 73-112 months (S.D. = 11.4), diagnosed with high functioning ASD were assessed with the Wisconsin Card Sorting Test. Their teachers…

Effect of functional electrical stimulation with mirror therapy on upper extremity motor function in poststroke patients.

PubMed

Kim, HyunJin; Lee, GyuChang; Song, ChangHo

2014-04-01

Motor recovery of the upper extremity in stroke patients is an important goal of rehabilitation. In particular, motor recovery can be accelerated when physical and cognitive interventions are combined. Thus, the aim of this study was to investigate the effects of functional electrical stimulation (FES) with mirror therapy (MT) on motor function of upper extremity in stroke patients. Twenty-seven stroke patients were recruited, and the 23 subjects who met the inclusion criteria were randomly allocated into 2 groups: the experimental group (n = 12) and the control group (n = 11). Both groups received conventional rehabilitation training for 60 minutes/day and 5 days/week for 4 weeks. In addition, members of the experimental group received FES with MT and members of the control group received FES without MT for 30 minutes/day and 5 days/week for 4 weeks. Immediately before and after intervention, motor recovery was measured using the Fugl-Meyer (FM) assessment, Brunnstrom's motor recovery stage (BMRS), the Manual Function Test (MFT), and the Box and Block Test (BBT). Significant upper extremity motor improvements were observed in the experimental and control groups according to the FM, BMRS, MFT, and BBT (P < .05). In particular, FM subscores for wrist, hand, and co-ordination and MFT subscores for hand function were more significantly improved in the experimental group (P < .05). Motor functions of the upper extremity were improved by FES with MT versus controls. The study shows that FES with MT during poststroke rehabilitation may effectively improve motor functions of the upper extremity. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Superoxide dismutase analog (TEMPOL: 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) treatment restores erectile function in diabetes-induced impotence

PubMed Central

Kawakami, Toshifumi; Urakami, Shinji; Hirata, Hiroshi; Tanaka, Yuichiro; Nakajima, Koichi; Enokida, Hideki; Shiina, Hiroaki; Ogishima, Tatsuya; Tokizane, Takashi; Kawamoto, Ken; Miura, Kazukiyo; Ishii, Nobuhisa; Dahiya, Rajvir

2014-01-01

We hypothesized that administration of the superoxide dismutase (SOD) mimetic Tempol (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) may reverse diabetes induced ED(erectile dysfunction). To test this hypothesis, ROS related genes (SOD1, SOD2, GPx1, CAT, NOS2, NOS3), erectile functional studies, and immunohistochemical analysis were performed in diabetic rats treated with or without Tempol. Thirty Sprague-Dawley (3–4 months old) rats were divided into 3 groups (n=10 each), 20 with diabetes (diabetic control and Tempol treatment) and 10 healthy controls. Twelve weeks after induction of diabetes by streptozotocin and Tempol treatment, all groups underwent in vivo cavernous nerve stimulation. Rat crura were harvested and expression of antioxidative defense enzymes examined by semi-quantitative RT-PCR. To confirm the RT-PCR results, we performed immunohistochemistry (IHC) for catalase (CAT) and iNOS (NOS2). Nitration of tyrosine groups in proteins was also examined by IHC. Mean intracavernous pressure in the diabetic group was significantly lower than in healthy controls (p<0.001) and was reversed by Tempol treatment (p<0.0108). NOS2 protein expression was significantly increased in diabetic animals compared to healthy controls and Tempol restored NOS2 protein level. Nitrotyrosine was also higher in diabetic animals and though Tempol treatment decreased its formation, it remained higher than that found in healthy controls. This study suggests that Tempol treatment increased erectile function through modulating oxidative stress related genes in diabetic rats. This is the first report about the relationship between diabetes induced erectile dysfunction and oxidative stress, and anti-oxidative therapy using the superoxide dismutase mimetic, Tempol to restore erectile function. PMID:19554009

Are the women with Sjögren's Syndrome satisfied with their sexual activity?

PubMed

Isik, Hatice; Isik, Metin; Aynioglu, Oner; Karcaaltincaba, Deniz; Sahbaz, Ahmet; Beyazcicek, Tugba; Harma, Mehmet Ibrahim; Demircan, Nejat

Females with Sjögren's Syndrome (SS) often experience vaginal dryness and dyspareunia, along with glandular and extraglandular symptoms. We aimed to evaluate sexual function and life quality in women with SS. Forty-six premenopausal women with SS and 47 age-matched controls were studied. Age, duration of the disease, medications, and comorbid diseases were noted. Participants completed 36-Item Short Form Health Survey (SF-36) and Female Sexual Function Index (FSFI). Patients were asked about vaginal discharge and itching in the last month, and if they informed their rheumatologists about any sexual problems. Gynecologic examinations were performed and vaginal smears were taken on each participant. The median total scores of FSFI were significantly lower in the SS group than the controls [17.12 (2.4-27.8) and 27.4 (16.9-36.0), respectively, p<0.001]. In the SS group, 37 (80.4%) and in the control group 18 (38.3%) of patients were sexually dissatisfied (p<0.001). Vaginal dryness and lubricant use were significantly increased in patients with SS compared to controls (p<0.001). Life quality scores were significantly lower in patients with SS than the controls (p<0.001). Vaginal dryness was negatively correlated with FSFI total (r=-0.312, p=0.035) and subscores except desire and arousal. Physical functioning, role physical and role emotional scores were positively correlated with total FSFI scores (r=0.449, p=0.002, r=0.371, p=0.011, r=0.299, p=0.043, respectively). Women with SS experience less satisfaction with sexual activity, which can be affected by age, vaginal dryness, physical pain, and impaired function due to the disease. Therefore, rheumatologists should pay attention to these symptoms and management. Copyright © 2017 Elsevier Editora Ltda. All rights reserved.

Antrodia Cinnamomea Reduces Carbon Tetrachloride-induced Hepatotoxicity In Male Wister Rats.

PubMed

Shih, Yung-Luen; Wu, Ming-Fang; Lee, Ching-Hsiao; Yeh, Ming-Yang; Chou, Jason; Liu, Jia-You; Lu, Hsu-Feng; Huang, Yi-Ping; Liao, Nien-Chieh; Chung, Jing-Gung

2017-01-01

Antrodia cinnamomea is found with polysaccharides, lipids, vitamins, fibers and ash (minerals) and is well known in Taiwan as a traditional Chinese medicine. Its biological activities have been reported to have anti-inflammatory, anti-fatigue, anti-tumor and immunomodulatory effects, but its protective effects on liver function are still unclear. We determined if Antrodia cinnamomea was hepatoprotective against carbon tetrachloride (CCl 4 ) toxicity in Wistar rats. Six groups were used in the study: 1) control (no induction by CCl 4 ); 2) negative control (CCl 4 -induction and no treatment); 3) positive control (silymarin treatment); 4) groups 4-6 were treated with CC1 4 and different concentrations (350 mg/kg, 1,400 mg/kg, 3,150 mg/kg) of Antrodia cinnamomea. Blood and liver samples of rats were harvested and then detected by biochemical and tissue histochemical analysis. Activity of the antioxidative enzymes glutathione peroxidase, superoxide dismutase and catalase in the liver were also monitored. Only the high-dose treatment was able to decrease serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels and improve liver function. High and medium doses increased total liver protein and reduced hydroxyproline. It was also observed that the high dose treatment reduced lipid peroxidation. Liver sections of CC1 4 treated animals receiving Antrodia cinnamomea showed less fibrosis compared to the CCl 4 control group. This finding suggested that Antrodia cinnamomea can either enhance liver recovering from CCl 4 damage or attenuate CCl 4 toxicity in rats. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Work and Rest Patterns and Psychomotor Vigilance Performance of Crewmemebers of the USS Jason Dunham: A Comparison of the 3/9 and 6/6 Watchstanding Schedules

DTIC Science & Technology

2014-12-31

collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1...24 3. Posttest Questionnaires .................................................................................. 26 4. Work...abnormal behavior for humans. Many human physiological functions are controlled by the circadian clock; for example, sleep and its associated functions

A Randomized Controlled Trial of the Impact of Therapeutic Horse Riding on the Quality of Life, Health, and Function of Children with Cerebral Palsy

ERIC Educational Resources Information Center

Davis, E.; Davies, B.; Wolfe, R.; Raadsveld, R.; Heine, B.; Thomason, P.; Dobson, Fiona; Graham, H. K.

2009-01-01

This randomized controlled trial examined whether therapeutic horse riding has a clinically significant impact on the physical function, health and quality of life (QoL) of children with cerebral palsy (CP). Ninety-nine children aged 4 to 12 years with no prior horse riding experience and various levels of impairment (Gross Motor Function…

Function of Serum Complement in Drinking Water Arsenic Toxicity

PubMed Central

Islam, Laila N.; Zahid, M. Shamim Hasan; Nabi, A. H. M. Nurun; Hossain, Mahmud

2012-01-01

Serum complement function was evaluated in 125 affected subjects suffering from drinking water arsenic toxicity. Their mean duration of exposure was 7.4 ± 5.3 yrs, and the levels of arsenic in drinking water and urine samples were 216 ± 211 and 223 ± 302 μg/L, respectively. The mean bactericidal activity of complement from the arsenic patients was 92% and that in the unexposed controls was 99% (P < 0.01), but heat-inactivated serum showed slightly elevated activity than in controls. In patients, the mean complement C3 was 1.56 g/L, and C4 was 0.29 g/L compared to 1.68 g/L and 0.25 g/L, respectively, in the controls. The mean IgG in the arsenic patients was 24.3 g/L that was highly significantly elevated (P < 0.001). Arsenic patients showed a significant direct correlation between C3 and bactericidal activity (P = 0.014). Elevated levels of C4 indicated underutilization and possibly impaired activity of the classical complement pathway. We conclude reduced function of serum complement in drinking water arsenic toxicity. PMID:22545044

Social-cognitive functioning and social skills in patients with early treated phenylketonuria: a PKU-COBESO study.

PubMed

Jahja, Rianne; van Spronsen, Francjan J; de Sonneville, Leo M J; van der Meere, Jaap J; Bosch, Annet M; Hollak, Carla E M; Rubio-Gozalbo, M Estela; Brouwers, Martijn C G J; Hofstede, Floris C; de Vries, Maaike C; Janssen, Mirian C H; van der Ploeg, Ans T; Langendonk, Janneke G; Huijbregts, Stephan C J

2016-05-01

Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and social skills. Ninety five PKU-patients (mean age 21.6 ± 10.2 years) and 95 healthy controls (mean age 19.6 ± 8.7 years) were compared on performance of computerized and paper-and-pencil tasks measuring social-cognitive abilities and on parent- and self-reported social skills, using multivariate analyses of variance, and controlling for general cognitive ability (IQ-estimate). Further comparisons were made between patients using tetrahydrobiopterin (BH4, N = 30) and patients not using BH4. Associations with Phe-levels on the day of testing, during childhood, during adolescence and throughout life were examined. PKU-patients showed poorer social-cognitive functioning and reportedly had poorer social skills than controls (regardless of general cognitive abilities). Quality of social-cognitive functioning was negatively related to recent Phe-levels and Phe-levels between 8 and 12 years for adolescents with PKU. Quality of social skills was negatively related to lifetime phenylalanine levels in adult patients, and specifically to Phe-levels between 0 and 7, and between 8 and 12 years. There were no differences with respect to social outcome measures between the BH4 and non-BH4 groups. PKU-patients have Phe-related difficulties with social-cognitive functioning and social skills. Problems seem to be more evident among adolescents and adults with PKU. High Phe-levels during childhood and early adolescence seem to be of greater influence than current and recent Phe-levels for these patients.

Mirror therapy enhances lower-extremity motor recovery and motor functioning after stroke: a randomized controlled trial.

PubMed

Sütbeyaz, Serap; Yavuzer, Gunes; Sezer, Nebahat; Koseoglu, B Füsun

2007-05-01

To evaluate the effects of mirror therapy, using motor imagery training, on lower-extremity motor recovery and motor functioning of patients with subacute stroke. Randomized, controlled, assessor-blinded, 4-week trial, with follow-up at 6 months. Rehabilitation education and research hospital. A total of 40 inpatients with stroke (mean age, 63.5 y), all within 12 months poststroke and without volitional ankle dorsiflexion. Thirty minutes per day of the mirror therapy program, consisting of nonparetic ankle dorsiflexion movements or sham therapy, in addition to a conventional stroke rehabilitation program, 5 days a week, 2 to 5 hours a day, for 4 weeks. The Brunnstrom stages of motor recovery, spasticity assessed by the Modified Ashworth Scale (MAS), walking ability (Functional Ambulation Categories [FAC]), and motor functioning (motor items of the FIM instrument). The mean change score and 95% confidence interval (CI) of the Brunnstrom stages (mean, 1.7; 95% CI, 1.2-2.1; vs mean, 0.8; 95% CI, 0.5-1.2; P=.002), as well as the FIM motor score (mean, 21.4; 95% CI, 18.2-24.7; vs mean, 12.5; 95% CI, 9.6-14.8; P=.001) showed significantly more improvement at follow-up in the mirror group compared with the control group. Neither MAS (mean, 0.8; 95% CI, 0.4-1.2; vs mean, 0.3; 95% CI, 0.1-0.7; P=.102) nor FAC (mean, 1.7; 95% CI, 1.2-2.1; vs mean, 1.5; 95% CI, 1.1-1.9; P=.610) showed a significant difference between the groups. Mirror therapy combined with a conventional stroke rehabilitation program enhances lower-extremity motor recovery and motor functioning in subacute stroke patients.

Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan.

PubMed

Miwa, Hiroto; Osada, Taro; Nagahara, Akihito; Ohkusa, Toshifumi; Hojo, Mariko; Tomita, Toshihiko; Hori, Kazutoshi; Matsumoto, Takayuki; Sato, Nobuhiro

2006-12-01

Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis, there has been no well-controlled study of functional dyspepsia. The aim of this study was to assess the efficacy of a 4-week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia. In a double-blinded, randomized, placebo-controlled, single-center study, 81 patients with functional dyspepsia were recruited and treated with rebamipide (100 mg, t.i.d.) or placebo for 4 weeks. Symptoms were assessed at baseline and at the end of the study period by a symptom questionnaire. Quality of life was evaluated by the QPD 32. Data was analyzed for symptoms from 38 patients who received rebamipide and 33 patients who received placebo treatment. Overall symptoms were significantly improved in both the rebamipide and placebo treatment groups from the untreated baseline after 4 weeks of treatment, and the mean changes in overall symptoms were not significantly different between the groups. However, the improvement in symptom score was significantly greater in the treatment arm than in the placebo arm for three items, which were bloating, belching, and pain or discomfort that was relieved after a meal. Regarding quality of life, social restriction and pain intensity were significantly improved in the rebamipide treatment group in per-protocol analysis (P = 0.048 and P = 0.031, respectively). Although rebamipide was not significantly better than placebo in reducing overall symptoms by 4 weeks' treatment, it may partially improve the symptoms. It may also be beneficial in improvement of quality of life in Japanese patients with functional dyspepsia.

The positive regulatory function of the 5'-proximal open reading frames in GCN4 mRNA can be mimicked by heterologous, short coding sequences.

PubMed Central

Williams, N P; Mueller, P P; Hinnebusch, A G

1988-01-01

Translational control of GCN4 expression in the yeast Saccharomyces cerevisiae is mediated by multiple AUG codons present in the leader of GCN4 mRNA, each of which initiates a short open reading frame of only two or three codons. Upstream AUG codons 3 and 4 are required to repress GCN4 expression in normal growth conditions; AUG codons 1 and 2 are needed to overcome this repression in amino acid starvation conditions. We show that the regulatory function of AUG codons 1 and 2 can be qualitatively mimicked by the AUG codons of two heterologous upstream open reading frames (URFs) containing the initiation regions of the yeast genes PGK and TRP1. These AUG codons inhibit GCN4 expression when present singly in the mRNA leader; however, they stimulate GCN4 expression in derepressing conditions when inserted upstream from AUG codons 3 and 4. This finding supports the idea that AUG codons 1 and 2 function in the control mechanism as translation initiation sites and further suggests that suppression of the inhibitory effects of AUG codons 3 and 4 is a general consequence of the translation of URF 1 and 2 sequences upstream. Several observations suggest that AUG codons 3 and 4 are efficient initiation sites; however, these sequences do not act as positive regulatory elements when placed upstream from URF 1. This result suggests that efficient translation is only one of the important properties of the 5' proximal URFs in GCN4 mRNA. We propose that a second property is the ability to permit reinitiation following termination of translation and that URF 1 is optimized for this regulatory function. Images PMID:3065626

49 CFR 214.505 - Required environmental control and protection systems for new on-track roadway maintenance...

Code of Federal Regulations, 2010 CFR

2010-10-01

... brooms; (4) Rotary scarifiers; (5) Undercutters; and (6) Functional equivalents of any of the machines... types identified in paragraphs (a)(1) through (a)(5) of this section, or functionally equivalent thereto...) of this section, or functionally equivalent thereto. The list shall be kept current and made...

49 CFR 214.505 - Required environmental control and protection systems for new on-track roadway maintenance...

Code of Federal Regulations, 2013 CFR

2013-10-01

... brooms; (4) Rotary scarifiers; (5) Undercutters; and (6) Functional equivalents of any of the machines... types identified in paragraphs (a)(1) through (a)(5) of this section, or functionally equivalent thereto...) of this section, or functionally equivalent thereto. The list shall be kept current and made...

49 CFR 214.505 - Required environmental control and protection systems for new on-track roadway maintenance...

Code of Federal Regulations, 2011 CFR

2011-10-01

... brooms; (4) Rotary scarifiers; (5) Undercutters; and (6) Functional equivalents of any of the machines... types identified in paragraphs (a)(1) through (a)(5) of this section, or functionally equivalent thereto...) of this section, or functionally equivalent thereto. The list shall be kept current and made...

49 CFR 214.505 - Required environmental control and protection systems for new on-track roadway maintenance...

Code of Federal Regulations, 2012 CFR

2012-10-01

... brooms; (4) Rotary scarifiers; (5) Undercutters; and (6) Functional equivalents of any of the machines... types identified in paragraphs (a)(1) through (a)(5) of this section, or functionally equivalent thereto...) of this section, or functionally equivalent thereto. The list shall be kept current and made...

49 CFR 214.505 - Required environmental control and protection systems for new on-track roadway maintenance...

Code of Federal Regulations, 2014 CFR

2014-10-01

... brooms; (4) Rotary scarifiers; (5) Undercutters; and (6) Functional equivalents of any of the machines... types identified in paragraphs (a)(1) through (a)(5) of this section, or functionally equivalent thereto...) of this section, or functionally equivalent thereto. The list shall be kept current and made...

Neuropsychologic predictors of competency in Alzheimer's disease using a rational reasons legal standard.

PubMed

Marson, D C; Cody, H A; Ingram, K K; Harrell, L E

1995-10-01

To identify neuropsychologic predictors of competency performance and status in Alzheimer's disease (AD) using a specific legal standard (LS). This study is a follow-up to the competency assessment research reported in this issue of the archives. Univariate and multivariate analyses of independent neuropsychologic test measures with a dependent measure of competency to consent to treatment. University medical center. Fifteen normal older control subjects and 29 patients with probable AD. Subjects were administered a battery of neuropsychologic measures theoretically linked to competency function, as well as two clinical vignettes testing their capacity to consent to medical treatment under five different LSs. The present study focused on one specific LS: the capacity to provide "rational reasons" for a treatment choice (LS4). Neuropsychologic test scores were correlated with scores on LS4 for the normal control group and the AD group. The resulting univariate predictors were then analyzed using stepwise regression and discriminant function to identify the key multivariate predictors of competency performance and status under LS4. Measures of word fluency predicted the LS4 scores of controls (R2 = .33) and the AD group (R2 = .36). A word fluency measure also emerged as the best single predictor of competency status for the full subject sample (n = 44), correctly classifying 82% of cases. Dementia severity (Mini-Mental State Examination score) did not emerge as a multivariate predictor of competency performance or status. Interestingly, measures of verbal reasoning and memory were not strongly associated with LS4. Word fluency measures predicted the normative performance and intact competency status of older control subjects and the declining performance and compromised competency status of patients with AD on a "rational reasons" standard of competency to consent to treatment. Cognitive capacities related to frontal lobe function appear to underlie the capacity to formulate rational reasons for a treatment choice. Neuropsychologic studies of competency function have important theoretical and clinical value.

Striatal functional connectivity changes following specific balance training in elderly people: MRI results of a randomized controlled pilot study.

PubMed

Magon, Stefano; Donath, Lars; Gaetano, Laura; Thoeni, Alain; Radue, Ernst-Wilhelm; Faude, Oliver; Sprenger, Till

2016-09-01

Practice-induced effects of specific balance training on brain structure and activity in elderly people are largely unknown. In the present study, we investigated morphological and functional brain changes following slacking training (balancing over nylon ribbons) in a group of elderly people. Twenty-eight healthy volunteers were recruited and randomly assigned to the intervention (mean age: 62.3±5.4years) or control group (mean age: 61.8±5.3years). The intervention group completed six-weeks of slackline training. Brain morphological changes were investigated using voxel-based morphometry and functional connectivity changes were computed via independent component analysis and seed-based analyses. All analyses were applied to the whole sample and to a subgroup of participants who improved in slackline performance. The repeated measures analysis of variance showed a significant interaction effect between groups and sessions. Specifically, the Tukey post-hoc analysis revealed a significantly improved slackline standing performance after training for the left leg stance time (pre: 4.5±3.6s vs. 26.0±30.0s, p<0.038) as well as for tandem stance time (pre: 1.4±0.6s vs. post: 4.5±4.0s, p=0.003) in the intervention group. No significant changes in balance performance were observed in the control group. The MRI analysis did not reveal morphological or functional connectivity differences before or after the training between the intervention and control groups (whole sample). However, subsequent analysis in subjects with improved slackline performance showed a decrease of connectivity between the striatum and other brain areas during the training period. These preliminary results suggest that improved balance performance with slackline training goes along with an increased efficiency of the striatal network. Copyright © 2016 Elsevier B.V. All rights reserved.

Aortic valve function after bicuspidization of the unicuspid aortic valve.

PubMed

Aicher, Diana; Bewarder, Moritz; Kindermann, Michael; Abdul-Khalique, Hashim; Schäfers, Hans-Joachim

2013-05-01

Unicuspid aortic valve (UAV) anatomy leads to dysfunction of the valve in young individuals. We introduced a reconstructive technique of bicuspidizing the UAV. Initially we copied the typical asymmetry of a normal bicuspid aortic valve (BAV) (I), later we created a symmetric BAV (II). This study compared the hemodynamic function of the two designs of a bicuspidized UAV. Aortic valve function was studied at rest and during exercise in 28 patients after repair of UAV (group I, n = 8; group II, n = 20). There were no differences among the groups I and II with respect to gender, age, body size, or weight. All patients were in New York Heart Association class I. Six healthy adults served as control individuals. All patients were studied with transthoracic echocardiography between 4 and 65 months postoperatively. Systolic gradients were assessed by continuous wave Doppler while patients were at rest and exercising on a bicycle ergometer. Aortic regurgitation was grade I or less in all patients. Resting gradients were significantly elevated in group I compared with group II and control individuals (group I, peak 33.8 ± 7.8 mm Hg; mean 19.1 ± 5.4 mm Hg; group II, peak 15.8 ± 5.4, mean 8.2 ± 2.8 mm Hg; control individuals, peak 6.0 ± 1.6, mean 3.2 ± 0.8 mm Hg; p < 0.001). At 100 W peak gradients were highest in group I (group I, 62.7 ± 16.7 mm Hg; group II, 28.1 ± 7.6 mm Hg; control individuals, 15.4 ± 4.6 mm Hg; p < 0.001). Converting a UAV into a symmetric bicuspid design results in adequate valve competence. A symmetric repair design leads to improved systolic aortic valve function at rest and during exercise. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Characterization of Microbiota in Children with Chronic Functional Constipation.

PubMed

de Meij, Tim G J; de Groot, Evelien F J; Eck, Anat; Budding, Andries E; Kneepkens, C M Frank; Benninga, Marc A; van Bodegraven, Adriaan A; Savelkoul, Paul H M

2016-01-01

Disruption of the intestinal microbiota is considered an etiological factor in pediatric functional constipation. Scientifically based selection of potential beneficial probiotic strains in functional constipation therapy is not feasible due to insufficient knowledge of microbiota composition in affected subjects. The aim of this study was to describe microbial composition and diversity in children with functional constipation, compared to healthy controls. Fecal samples from 76 children diagnosed with functional constipation according to the Rome III criteria (median age 8.0 years; range 4.2-17.8) were analyzed by IS-pro, a PCR-based microbiota profiling method. Outcome was compared with intestinal microbiota profiles of 61 healthy children (median 8.6 years; range 4.1-17.9). Microbiota dissimilarity was depicted by principal coordinate analysis (PCoA), diversity was calculated by Shannon diversity index. To determine the most discriminative species, cross validated logistic ridge regression was performed. Applying total microbiota profiles (all phyla together) or per phylum analysis, no disease-specific separation was observed by PCoA and by calculation of diversity indices. By ridge regression, however, functional constipation and controls could be discriminated with 82% accuracy. Most discriminative species were Bacteroides fragilis, Bacteroides ovatus, Bifidobacterium longum, Parabacteroides species (increased in functional constipation) and Alistipes finegoldii (decreased in functional constipation). None of the commonly used unsupervised statistical methods allowed for microbiota-based discrimination of children with functional constipation and controls. By ridge regression, however, both groups could be discriminated with 82% accuracy. Optimization of microbiota-based interventions in constipated children warrants further characterization of microbial signatures linked to clinical subgroups of functional constipation.

Testosterone Regulates Erectile Function and Vcsa1 Expression in the Corpora of Rats

PubMed Central

Chua, Rowena G.; Calenda, Giulia; Zhang, Xinhua; Siragusa, Joseph; Tong, Yuehong; Tar, Moses; Aydin, Memduh; DiSanto, Michael E.; Melman, Arnold; Davies, Kelvin P.

2009-01-01

Summary Vcsa1 plays an important role in the erectile physiology of the rat. We conducted experiments to determine if erectile function, testosterone levels and Vcsa1 expression were correlated. In orchiectomized rats, total testosterone in blood fell from an average of 4ng/ml to <0.04ng/ml. Erectile function was significantly lower compared to controls and Vcsa1 expression was significantly (>6-fold) decreased. Injection of orchiectomized animals with testosterone (2mg in 100ml sesame oil every 4 days for two weeks) restored average levels of testosterone to 2ng/ml, increased erectile function and significantly increased Vcsa1 expression. In isolated corporal cells there was testosterone dependent Vcsa1 expression. However, intracorporal injection of orchiectomized animals with a plasmid expressing Vcsa1 or its gene product Sialorphin (previously demonstrated to improve erectile function in old animals) gave no significant improvement in erectile function. Also, the ability of Sialorphin to reduce tension in corporal smooth muscle strips isolated from orchiectomized animals was impaired compared to controls. PMID:19428993

Evaluation of olfactory function in adults with primary hypothyroidism.

PubMed

Günbey, Emre; Karlı, Rıfat; Gökosmanoğlu, Feyzi; Düzgün, Berkan; Ayhan, Emre; Atmaca, Hulusi; Ünal, Recep

2015-10-01

Sufficient clinical data are not available on the effect of hypothyroidism on olfactory function in adults. In this study, we aimed to evaluate the olfactory function of adult patients diagnosed with primary hypothyroidism. Forty-five patients aged between 18 and 60 years who were diagnosed with clinical primary hypothyroidism and 45 healthy controls who had normal thyroid function tests were included in the study. Sniffin' Sticks olfactory test results of the 2 groups were compared. The relationships between thyroid function tests and olfactory parameters were evaluated. Odor threshold, identification, and discrimination scores of the hypothyroid group were significantly lower than those of the control group (p < 0.001). A significant positive correlation was detected between free triiodothyronine (FT3) levels and odor threshold, identification, and discrimination scores (p < 0.001). There was no significant relationship between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) levels and olfactory parameters. Our study revealed diminished olfactory function in adults with hypothyroidism. FT3 levels were found to have a more significant relationship with olfactory parameters than TSH or FT4 levels. © 2015 ARS-AAOA, LLC.

User’s Guide for COMBIMAN Programs (COMputerized BIomechanical MAN-Model). Version 4.

DTIC Science & Technology

1981-01-01

103 2.2.23 STATE SWITCH Function (PFK29) 105 2.2.24 RESTART PROGRAM Function (PFK30) 110 2.2.25 END PROGRAM Function (PFK31) il 2.3 EXECUTING THE JOB...108 40 Transformation Equation Developed for Positioning Stomach Link (Set State Switch 72 ON) 109 41 JOB CONTROL CARDS to Execute CBM04. 114 42...154 50b Program CBMAM Survey Member Dimension Definition Cards. 154 51 Example of Survey, or Type 1, Member. 155 52 Job Control Cards to Execute CBMAM

Upper limb training using Wii Sports Resort for children with hemiplegic cerebral palsy: a randomized, single-blind trial.

PubMed

Chiu, Hsiu-Ching; Ada, Louise; Lee, Hsin-Min

2014-10-01

To investigate whether Wii Sports Resort training is effective and if any benefits are maintained. Randomized, single-blind trial. Sixty-two hemiplegic children with cerebral palsy (6-13 years). Experimental group undertook six weeks of home-based Wii Sports Resort training plus usual therapy, while the control group received usual therapy. Outcomes were coordination, strength, hand function, and carers' perception of hand function, measured at baseline, six, and 12 weeks by a blinded assessor. There was a trend of mean difference (MD) for the experimental group to have more grip strength by six (MD 4.0 N, 95% confidence interval (CI) -0.8 to 8.8, p = 0.10) and 12 (MD 4.1 N, 95% CI -2.1 to 10.3, p = 0.19) weeks, and to have a higher quantity of hand function according to carers' perception by six (MD 4.5 N, 95% CI -0.7 to 9.7, p = 0.09) and strengthened by 12 (MD 6.4, 95% CI 0.6 to 12.3, p = 0.03) weeks than the control group. There was no difference between groups in coordination and hand function by six or 12 weeks. Wii training did not improve coordination, strength, or hand function. Beyond the intervention, carers perceived that the children used their hands more. © The Author(s) 2014.

Regular physical exercise improves endothelial function in heart transplant recipients.

PubMed

Schmidt, Alice; Pleiner, Johannes; Bayerle-Eder, Michaela; Wiesinger, Günther F; Rödler, Suzanne; Quittan, Michael; Mayer, Gert; Wolzt, Michael

2002-04-01

Impaired endothelial function is detectable in heart transplant (HTX) recipients and regarded as risk factor for coronary artery disease. We have studied whether endothelial function can be improved in HTX patients participating in a regular physical training program as demonstrated in patients with chronic heart failure, hypertension and coronary artery disease. Male HTX patients and healthy, age-matched controls were studied. Seven HTX patients (age: 60 +/- 6 yr; 6 +/- 2 yr of HTX) participated in an outpatient training program, six HTX patients (age: 63 +/- 8 yr; 7 +/- 1 yr of HTX) maintained a sedentary lifestyle without regular physical exercise since transplantation. A healthy control group comprised six subjects (age: 62 +/- 6 yr). Vascular function was assessed by flow-mediated dilation of the brachial artery (FMD). Systemic haemodynamic responses to intravenous infusion of the endothelium independent vasodilator sodium nitroprusside (SNP) and to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of constitutive nitric oxide synthase, were also measured. Resting heart rate was significantly lower (p < 0.05) in healthy controls (66 +/- 13) than in the HTX training group (83 +/- 11) and in non-training HTX patients (91 +/- 9), baseline blood pressure also tended to be lower in healthy subjects and in the training HTX patients. FMD was significantly higher (p < 0.05) in the control group (8.4 +/- 2.2%) and in the training group (7.1 +/- 2.4%), compared with non-training HTX patients (1.4 +/- 0.8%). The response of systolic blood pressure (p = 0.08) and heart rate (p < 0.05) to L-NMMA was reduced in sedentary HTX patients compared with healthy controls and heart rate response to SNP was also impaired in sedentary HTX patients. Regular aerobic physical training restores vascular function in HTX patients, who are at considerable risk for developing vascular complications. This effect is demonstrable in conduit and systemic resistance arteries.

Polymer-entanglement-driven coassembly of hybrid superparamagnetic nanoparticles: Tunable structures and flexible functionalization.

PubMed

Zhan, Xiaohui; Yi, Qiangying; Cai, Shuang; Zhou, Xiaoxi; Ma, Shaohua; Lan, Fang; Gu, Zhongwei; Wu, Yao

2017-12-15

In this study, we report a facile and versatile strategy for preparing a type of pH-responsive superparamagnetic hybrid coassemblies featuring a series of controls over the morphology and multi-functionalization simultaneously and efficiently. Via the entanglement interactions, the combine of fixed PEG-b-P4VP modified Fe 3 O 4 NPs (D-Fe 3 O 4 @mPEG-b-P4VP) and different well-designed free PEG-b-P4VP, which are analogous to two amphiphiles, contributes these hybrid superstructures with multiple, well-defined morphologies and targeted fluorescent properties. In contrast to other studies, our work overcame several defects (e.g., interior NPs' randomness, cumbersome assembly parameter adjustment and functionalization) of the conventional assembly of modified inorganic NPs and demonstrated that this coassembly strategy can be used as a versatile tool for the controllable assembly of other NPs or polymers. Finally, taking the coassembly C1 as a desirable drug delivery carrier, good biocompatibility and pH-triggered drug release were successfully verified. The current study indicated that these magnetic coassemblies are promising as multifunctional and multipurpose carriers in biological, medical, catalytic, and coating applications. Copyright © 2017. Published by Elsevier Inc.

Codimension-Two Bifurcation, Chaos and Control in a Discrete-Time Information Diffusion Model

NASA Astrophysics Data System (ADS)

Ren, Jingli; Yu, Liping

2016-12-01

In this paper, we present a discrete model to illustrate how two pieces of information interact with online social networks and investigate the dynamics of discrete-time information diffusion model in three types: reverse type, intervention type and mutualistic type. It is found that the model has orbits with period 2, 4, 6, 8, 12, 16, 20, 30, quasiperiodic orbit, and undergoes heteroclinic bifurcation near 1:2 point, a homoclinic structure near 1:3 resonance point and an invariant cycle bifurcated by period 4 orbit near 1:4 resonance point. Moreover, in order to regulate information diffusion process and information security, we give two control strategies, the hybrid control method and the feedback controller of polynomial functions, to control chaos, flip bifurcation, 1:2, 1:3 and 1:4 resonances, respectively, in the two-dimensional discrete system.

Effect of Mindfulness Training on Asthma Quality of Life and Lung Function: A Randomized Controlled Trial

PubMed Central

Pbert, Lori; Madison, J. Mark; Druker, Susan; Olendzki, Nicholas; Magner, Robert; Reed, George; Carmody, James

2014-01-01

Background Improving asthma patients’ quality of life is an important clinical outcome. This study evaluated the efficacy of mindfulness-based stress reduction (MBSR) in improving quality of life and lung function in patients with asthma. Methods A randomized controlled trial compared an 8 week MBSR group-based program (n = 42) to an educational control program (n = 41) in adults with mild, moderate or severe persistent asthma recruited at a university hospital outpatient primary care and pulmonary care clinic. Primary outcomes were quality of life assessed by the Asthma Quality of Life Questionnaire (AQOL), and lung function assessed by change from baseline in two-week average morning peak expiratory flow (PEF). Secondary outcomes were asthma control assessed by 2007 NIH/NHLBI guidelines, and stress assessed by Perceived Stress Scale. Follow-up assessments were conducted at 10 weeks, 6 and 12 months. Results At 12 months MBSR resulted in clinically significant improvements in quality of life (intervention effect 0.55 (95% CI 0.21, 0.89, p=0.001)) and perceived stress (intervention effect −4.5 (95% CI −7.1, −1.9; p= 0.001)). No significant effect was found on lung function (morning PEF, PEF variability, and FEV1). At 12 months the percentage of patients in MBSR with well-controlled asthma showed a non-statistically significant increase (7.3% at baseline to 19.4%) compared to the control condition (7.5% and 7.9%, respectively) (p=0.30). Conclusions MBSR produced lasting clinically significant improvements in asthma-related quality of life and stress in patients with persistent asthma, even in the absence of improvements in lung function. PMID:22544892

The Variability of Sesquiterpenes Emitted from Two Zea mays Cultivars Is Controlled by Allelic Variation of Two Terpene Synthase Genes Encoding Stereoselective Multiple Product Enzymes

PubMed Central

Köllner, Tobias G.; Schnee, Christiane; Gershenzon, Jonathan; Degenhardt, Jörg

2004-01-01

The mature leaves and husks of Zea mays release a complex blend of terpene volatiles after anthesis consisting predominantly of bisabolane-, sesquithujane-, and bergamotane-type sesquiterpenes. The varieties B73 and Delprim release the same volatile constituents but in significantly different proportions. To study the molecular genetic and biochemical mechanisms controlling terpene diversity and distribution in these varieties, we isolated the closely related terpene synthase genes terpene synthase4 (tps4) and tps5 from both varieties. The encoded enzymes, TPS4 and TPS5, each formed the same complex mixture of sesquiterpenes from the precursor farnesyl diphosphate but with different proportions of products. These mixtures correspond to the sesquiterpene blends observed in the varieties B73 and Delprim, respectively. The differences in the stereoselectivity of TPS4 and TPS5 are determined by four amino acid substitutions with the most important being a Gly instead of an Ala residue at position 409 at the catalytic site of the enzyme. Although both varieties contain tps4 and tps5 alleles, their differences in terpene composition result from the fact that B73 has only a single functional allele of tps4 and no functional alleles of tps5, whereas Delprim has only a functional allele of tps5 and no functional alleles of tps4. Lack of functionality was shown to be attributable to frame-shift mutations or amino acid substitutions that greatly reduce the activity of their encoded proteins. Therefore, the diversity of sesquiterpenes in these two maize cultivars is strongly influenced by single nucleotide changes in the alleles of two terpene synthase genes. PMID:15075399

The variability of sesquiterpenes emitted from two Zea mays cultivars is controlled by allelic variation of two terpene synthase genes encoding stereoselective multiple product enzymes.

PubMed

Köllner, Tobias G; Schnee, Christiane; Gershenzon, Jonathan; Degenhardt, Jörg

2004-05-01

The mature leaves and husks of Zea mays release a complex blend of terpene volatiles after anthesis consisting predominantly of bisabolane-, sesquithujane-, and bergamotane-type sesquiterpenes. The varieties B73 and Delprim release the same volatile constituents but in significantly different proportions. To study the molecular genetic and biochemical mechanisms controlling terpene diversity and distribution in these varieties, we isolated the closely related terpene synthase genes terpene synthase4 (tps4) and tps5 from both varieties. The encoded enzymes, TPS4 and TPS5, each formed the same complex mixture of sesquiterpenes from the precursor farnesyl diphosphate but with different proportions of products. These mixtures correspond to the sesquiterpene blends observed in the varieties B73 and Delprim, respectively. The differences in the stereoselectivity of TPS4 and TPS5 are determined by four amino acid substitutions with the most important being a Gly instead of an Ala residue at position 409 at the catalytic site of the enzyme. Although both varieties contain tps4 and tps5 alleles, their differences in terpene composition result from the fact that B73 has only a single functional allele of tps4 and no functional alleles of tps5, whereas Delprim has only a functional allele of tps5 and no functional alleles of tps4. Lack of functionality was shown to be attributable to frame-shift mutations or amino acid substitutions that greatly reduce the activity of their encoded proteins. Therefore, the diversity of sesquiterpenes in these two maize cultivars is strongly influenced by single nucleotide changes in the alleles of two terpene synthase genes.

Functional capacity improves in-line with neuromuscular performance after 12 weeks of non-linear periodization strength training in the elderly.

PubMed

Moura, Bruno Monteiro de; Sakugawa, Raphael Luiz; Orssatto, Lucas Bet da Rosa; de Lima, Luis Antonio Pereira; Pinto, Ronei Silveira; Walker, Simon; Diefenthaeler, Fernando

2017-12-06

While it is accepted that resistance training can improve functional capacity in older individuals, the neuromuscular source of this improvement has yet to be identified. This study investigated the link between improved neuromuscular performance and functional capacity after a 12-week resistance training period in untrained healthy older individuals. Fifteen older men and women (60-71 years) adhered to a 4-week control period, followed by 12 weeks of non-linear resistance training for the lower limbs. Maximum dynamic leg press strength (1-RM), maximum isometric knee extension torque and rate of torque development (RTD) were evaluated at - 4, 0, 4, 8, and 12 weeks, and muscle activity was assessed at 0, 4, 8, and 12 weeks. Functional capacity tests (chair rise, stair ascent and descent, and timed up and go) were performed at - 4, 0, and 12 weeks. No changes occurred during the control period, but the group increased their 1-RM strength (from 142 ± 53 to 198 ± 43 kg, p = 0.001), which was accompanied by an increase in vastus lateralis activation (p = 0.008) during the intervention. Increase was observed at all RTD time intervals at week 8 (p < 0.05). Significant improvements in all the functional capacity tests were observed at week 12 (p < 0.05). Despite the expected increase in strength, RTD, muscle activity, and functional capacity, there was no significant relationship between the changes in neuromuscular performance and functional capacity. While resistance training elicits various positive improvements in healthy older individuals, actual strength gain did not influence the gain in functional capacity. The present study highlights the exact cause that improved the functional capabilities during resistance training are currently unknown.

Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized, controlled trial.

PubMed

Michopoulos, Vasiliki; Mancini, Fulvia; Loucks, Tammy L; Berga, Sarah L

2013-06-01

To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA. Randomized controlled trial. Clinical research center at an academic medical university. Seventeen women with FHA were randomized either to CBT or observation. CBT versus observation. Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T(3)), and total and free thyroxine (T(4)) before and immediately after completion of CBT or observation. (Each woman served as her own control.) Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T(3), or T(4) levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T(3) and T(4) remained unchanged. In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA. NCT01674426. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Modulation of Endoplasmic Reticulum Stress Controls CD4+ T-cell Activation and Antitumor Function.

PubMed

Thaxton, Jessica E; Wallace, Caroline; Riesenberg, Brian; Zhang, Yongliang; Paulos, Chrystal M; Beeson, Craig C; Liu, Bei; Li, Zihai

2017-08-01

The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca 2+ stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined. Gp96 is an ER protein with functions as a molecular chaperone and Ca 2+ buffering protein. We hypothesized that the ER stress response may be important for CD4 + T-cell activation and that gp96 may be integral to this process. To test our hypothesis, we utilized genetic deletion of the gp96 gene Hsp90b1 in a CD4 + T cell-specific manner. We show that gp96-deficient CD4 + T cells cannot undergo activation-induced glycolysis due to defective Ca 2+ mobilization upon TCR engagement. We found that activating naïve CD4 + T cells while inhibiting ER Ca 2+ exchange, through pharmacological blockade of the ER Ca 2+ channel inositol trisphosphate receptor (IP 3 R), led to a reduction in cytosolic Ca 2+ content and generated a pool of CD62L high /CD44 low CD4 + T cells compared with wild-type (WT) matched controls. In vivo IP 3 R-inhibited CD4 + T cells exhibited elevated tumor control above WT T cells. Together, these data show that ER-modulated cytosolic Ca 2+ plays a role in defining CD4 + T-cell phenotype and function. Factors associated with the ER stress response are suitable targets for T cell-based immunotherapies. Cancer Immunol Res; 5(8); 666-75. ©2017 AACR . ©2017 American Association for Cancer Research.

Assessment of cognitive function in patients with essential hypertension treated with lercanidipine

PubMed Central

Tisaire-Sánchez, J; Roma, J; CamachoAzcargorta, Ignacio; Bueno-Gómez, J; Mora-Maciá, J; Navarro, Angel

2006-01-01

Objectives The aim of this longitudinal, open-label, comparative, multicenter study was to assess cognitive function in hypertensive patients receiving mid-term treatment with lercanidipine. Methods Hypertensive patients aged 40 years or older were treated with lercanidipine (10mg daily) after 7–10 days washout period. The duration of the study was 6 months. Blood pressure (BP) was measured every 4 weeks (JNC 6th report). In patients with inadequate BP control, doxazosin was added and up-titrated. At baseline and after 6 months of treatment, cognitive function was evaluated using the Spanish validated version of the Mini-Mental State Examination (MMSE) and the Trail Making Test (TMT). Results In the study population of 467 patients, BP decreased from 154.4/95.3 mmHg at baseline to 134.8/80.7 mmHg at 6 months. At the end of the study, 98% of patients were receiving lercanidipine, 20% an angiotensin-converting enzyme inhibitor, and 6% doxazosin. Adequate BP control was obtained in 68% of patients. The mean (standard deviation) MMSE scores improved from 32.35 (2.59) to 33.25 (2.36) (p<0.0001). Patients with good BP control scored significantly better than those with inadequate BP control (p<0.05), which was already observed at the first month. Conclusions The third-generation calcium channel antagonist, lercanidipine, improved cognitive function after 6 months of treatment especially in patients with good BP control, suggesting that improvements in cognitive function may be associated with a decrease in BP. PMID:17323604

Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

PubMed Central

Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

2008-01-01

Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

40 CFR 610.21 - Device functional category and vehicle system effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... device's category will be based on: (1) Engineering principles governing operation of the device; (2... mechanical) All. Vapor Injectors All. Choke controls 1, 2, and 4. Air filters 1, 2, and 4. Fuel-air...

40 CFR 610.21 - Device functional category and vehicle system effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... device's category will be based on: (1) Engineering principles governing operation of the device; (2... mechanical) All. Vapor Injectors All. Choke controls 1, 2, and 4. Air filters 1, 2, and 4. Fuel-air...

40 CFR 610.21 - Device functional category and vehicle system effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... device's category will be based on: (1) Engineering principles governing operation of the device; (2... mechanical) All. Vapor Injectors All. Choke controls 1, 2, and 4. Air filters 1, 2, and 4. Fuel-air...

Effect of intensive glycaemic control on endothelial progenitor cells in patients with long-standing uncontrolled type 2 diabetes.

PubMed

Lev, Eli I; Singer, Joel; Leshem-Lev, Dorit; Rigler, Merav; Dadush, Oshrat; Vaduganathan, Muthiah; Battler, Alexander; Kornowski, Ran

2014-09-01

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. However, in patients with diabetes, EPC number and function are markedly reduced. It is unclear whether intensive glycaemic control can modify EPC properties in diabetic patients. We aimed to examine whether glycaemic control can improve EPC number and function in patients with long-standing uncontrolled type 2 diabetes. Thirty-five patients with treated type 2 diabetes and HgA1c ≥ 8.5% were included. Patients were tested at baseline and after 3-4 months of an intensive glycaemic control programme, with the aim of achieving HgA1c of 7%. The diabetes group was compared to 20 patients without diabetes (control). Circulating EPC levels were assessed by flow cytometry for expression of VEGFR2, CD133, and CD34. The capacity of the cells to form colony-forming units (CFUs), and their migration and viability were quantified after 1 week of culture. Patients with diabetes (mean age 61.1 ± 7 years, 28.6% women, disease duration of 19.2 ± 8 years) had a baseline HgA1c of 9.4 ± 0.8%. After the glycaemic control period, HgA1c decreased to 8 ± 0.8%. Circulating EPC levels increased significantly after the intensive control period and reached a level similar to the control group. The number of EPC CFUs also increased significantly after glycaemic control but remained lower than the control group. All EPC functional assays improved following the glycaemic control. In patients with uncontrolled long-standing type 2 diabetes, intensive glycaemic control was associated with an increase in the levels of circulating EPCs, and improvement in their functional properties. © The European Society of Cardiology 2013 Reprints and permissions:sagepub.co.uk/journalsPermissions.nav.

Sodium sulfate - Deposition and dissolution of silica

NASA Technical Reports Server (NTRS)

Jacobson, Nathan S.

1989-01-01

The hot-corrosion process for SiO2-protected materials involves deposition of Na2SO4 and dissolution of the protective SiO2 scale. Dew points for Na2SO4 deposition are calculated as a function of pressure, sodium content, and sulfur content. Expected dissolution regimes for SiO2 are calculated as a function of Na2SO4 basicity. Controlled-condition burner-rig tests on quartz verify some of these predicted dissolution regimes. The basicity of Na2SO4 is not always a simple function of P(SO3). Electrochemical measurements of an (Na2O) show that carbon creates basic conditions in Na2SO4, which explains the extensive corrosion of SiO2-protected materials containing carbon, such as SiC.

Health status in women with Turner syndrome: a questionnaire study on health status, education, work participation and aspects of sexual functioning.

PubMed

Naess, Eva Elisabeth; Bahr, David; Gravholt, Claus H

2010-05-01

Turner syndrome (TS) is a complex medical condition with specific cognitive and psychosocial characteristics and frequent medical morbidity. Few studies have investigated the influence this has on health status, education and ability to work. To explore health status, level of education, work participation, medical conditions, physical activity, satisfaction with life and aspects of sexual functioning in adult TS women and compare with a matched control group. A questionnaire was sent to 168 adult women with TS >18 years registered in a database of Frambu Resource Centre for Rare Disorders and The TS Association in Norway. We assessed health status with Short Form 36, education with Norwegian Standard Classification of Education, and employment with The General Nordic Questionnaire. Life satisfaction was measured with LiSat-9, and questions on psychological strain during life phases were included. Eighty women with TS (34.0 +/- 11.7 years) and 214 controls (32.9 +/- 10.6) responded. The TS group reported significantly more health problems and impaired health status in the two subscales "physical functioning" and "general health" (P < 0.001). Level of education and work participation was similar among TS and controls. TS moved away from their parents' home later than controls (20.4 +/- 4.0 vs. 18.7 +/- 2.1, P = 0.001). Age at sexual debut differed significantly (21.2 +/- 4.3 vs. 17.3 +/- 2.4 years, P < 0.001). TS attains the same level of education and level of employment as controls, they report more frequent occurrence of medical conditions, but scored lower on only two subscales in the SF-36. Despite considerable medical morbidity, TS seem to cope well with life.

Assessment and protection of esophageal mucosal integrity in patients with heartburn without esophagitis.

PubMed

Woodland, Philip; Lee, Chung; Duraisamy, Yasotha; Duraysami, Yasotha; Farré, Ricard; Dettmar, Peter; Sifrim, Daniel

2013-04-01

Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection. Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions. Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), P<0.05; acidic -22.8% (-31.4 to 14.1) vs. -9.4% (-17.2 to -1.6), P<0.01). Topical pretreatment with alginate but not with control solutions prevented the acid-induced decrease in TER (-1% (-5.9 to 3.9) vs. -13.5 (-24.1 to -3.0) vs. -13.2 (-21.7 to -4.8), P<0.05). Esophageal mucosa in patients with heartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.

Spatial Control of Functional Response in 4D-Printed Active Metallic Structures

PubMed Central

Ma, Ji; Franco, Brian; Tapia, Gustavo; Karayagiz, Kubra; Johnson, Luke; Liu, Jun; Arroyave, Raymundo; Karaman, Ibrahim; Elwany, Alaa

2017-01-01

We demonstrate a method to achieve local control of 3-dimensional thermal history in a metallic alloy, which resulted in designed spatial variations in its functional response. A nickel-titanium shape memory alloy part was created with multiple shape-recovery stages activated at different temperatures using the selective laser melting technique. The multi-stage transformation originates from differences in thermal history, and thus the precipitate structure, at various locations created from controlled variations in the hatch distance within the same part. This is a first example of precision location-dependent control of thermal history in alloys beyond the surface, and utilizes additive manufacturing techniques as a tool to create materials with novel functional response that is difficult to achieve through conventional methods. PMID:28429796

Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium

PubMed Central

Monaghan, Kevin; McNaughten, Jennifer; McGahon, Mary K.; Kelly, Catriona; Kyle, Daniel; Yong, Phaik Har

2015-01-01

Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the retinal microcirculation and that both channel expression and activity is downregulated by hyperglycaemia. Quantitative PCR and immunostaining demonstrated molecular expression of TRPV4 in cultured bovine retinal microvascular endothelial cells (RMECs). Functional TRPV4 activity was assessed in cultured RMECs from endothelial Ca2+-responses recorded using fura-2 microfluorimetry and electrophysiological recordings of membrane currents. The TRPV4 agonist 4α-phorbol 12,13-didecanoate (4-αPDD) increased [Ca2+]i in RMECs and this response was largely abolished using siRNA targeted against TRPV4. These Ca2+-signals were completely inhibited by removal of extracellular Ca2+, confirming their dependence on influx of extracellular Ca2+. The 4-αPDD Ca2+-response recorded in the presence of cyclopiazonic acid (CPA), which depletes the intracellular stores preventing any signal amplification through store release, was used as a measure of Ca2+-influx across the cell membrane. This response was blocked by HC067047, a TRPV4 antagonist. Under voltage clamp conditions, the TRPV4 agonist GSK1016790A stimulated a membrane current, which was again inhibited by HC067047. Following incubation with 25mM D-glucose TRPV4 expression was reduced in comparison with RMECs cultured under control conditions, as were 4αPDD-induced Ca2+-responses in the presence of CPA and ion currents evoked by GSK1016790A. Molecular expression of TRPV4 in the retinal vascular endothelium of 3 months’ streptozotocin-induced diabetic rats was also reduced in comparison with that in age-matched controls. We conclude that hyperglycaemia and diabetes reduce the molecular and functional expression of TRPV4 channels in retinal microvascular endothelial cells. These changes may contribute to diabetes induced endothelial dysfunction and retinopathy. PMID:26047504

Yoga respiratory training improves respiratory function and cardiac sympathovagal balance in elderly subjects: a randomised controlled trial

PubMed Central

Santaella, Danilo F; Devesa, Cesar R S; Rojo, Marcos R; Amato, Marcelo B P; Drager, Luciano F; Casali, Karina R; Montano, Nicola

2011-01-01

Objectives Since ageing is associated with a decline in pulmonary function, heart rate variability and spontaneous baroreflex, and recent studies suggest that yoga respiratory exercises may improve respiratory and cardiovascular function, we hypothesised that yoga respiratory training may improve respiratory function and cardiac autonomic modulation in healthy elderly subjects. Design 76 healthy elderly subjects were enrolled in a randomised control trial in Brazil and 29 completed the study (age 68±6 years, 34% males, body mass index 25±3 kg/m2). Subjects were randomised into a 4-month training program (2 classes/week plus home exercises) of either stretching (control, n=14) or respiratory exercises (yoga, n=15). Yoga respiratory exercises (Bhastrika) consisted of rapid forced expirations followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril. Pulmonary function, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate variability and blood pressure variability for spontaneous baroreflex determination were determined at baseline and after 4 months. Results Subjects in both groups had similar demographic parameters. Physiological variables did not change after 4 months in the control group. However, in the yoga group, there were significant increases in PEmax (34%, p<0.0001) and PImax (26%, p<0.0001) and a significant decrease in the low frequency component (a marker of cardiac sympathetic modulation) and low frequency/high frequency ratio (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex did not change, and quality of life only marginally increased in the yoga group. Conclusion Respiratory yoga training may be beneficial for the elderly healthy population by improving respiratory function and sympathovagal balance. Trial Registration CinicalTrials.gov identifier: NCT00969345; trial registry name: Effects of respiratory yoga training (Bhastrika) on heart rate variability and baroreflex, and quality of life of healthy elderly subjects. PMID:22021757

JPRS Report, Science & Technology, Japan.

DTIC Science & Technology

1988-08-03

SHIMBUN, 4 Feb 88] 72 Advanced Reactor Design System To Be Developed [GENSHIRYOKU SANGYO SHIMBUN, 4 Feb 88] 73 Functional Testing on " Mutsu ...new types of reactors. 13008 74 NUCLEAR ENGINEERING FUNCTIONAL TESTING ON " MUTSU " SCHEDULED 43062060c Tokyo GENSHIRYOKU SANGYO SHIMBUN in Japanese...and to rebuild the power supply rectifiers used in the instrumentation controls on the nuclear powered ship, the " Mutsu ," which was launched on 27

ACOSS Eleven (Active Control of Space Structures). Volume 1

DTIC Science & Technology

1983-12-01

Influence Function ................. 19 3.4 Mirror Deformations. ........................... o............. 23 3.5 Selection of Point Objects...to simulate errors in the knowledge of influence function . 5) The influence function for edge actuators may be different from that for interior... Influence Function Each of the three mirrors has 37 actuators distributed on an equi- lateral triangular lattice as shown in Figure 3-3. In consultation with

Characterization of Radar Signals Using Neural Networks

DTIC Science & Technology

1990-12-01

e***e*e*eeeeeeeeeeeesseeeeeese*eee*e*e************s /* Function Name: load.input.ptterns Number: 4.1 /* Description: This function determines wether ...XSE.last.layer Number: 8.5 */ /* Description: The function determines wether to backpropate the *f /* parameter by the sigmoidal or linear update...Sigmoidal Function," Mathematics of Control, Signals and Systems, 2:303-314 (March 1989). 6. Dayhoff, Judith E. Neural Network Architectures. New York: Van

Function of GATA Factors in the Adult Mouse Liver

PubMed Central

Zheng, Rena; Rebolledo-Jaramillo, Boris; Zong, Yiwei; Wang, Liqing; Russo, Pierre; Hancock, Wayne; Stanger, Ben Z.; Hardison, Ross C.; Blobel, Gerd A.

2013-01-01

GATA transcription factors and their Friend of Gata (FOG) cofactors control the development of diverse tissues. GATA4 and GATA6 are essential for the expansion of the embryonic liver bud, but their expression patterns and functions in the adult liver are unclear. We characterized the expression of GATA and FOG factors in whole mouse liver and purified hepatocytes. GATA4, GATA6, and FOG1 are the most prominently expressed family members in whole liver and hepatocytes. GATA4 chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) identified 4409 occupied sites, associated with genes enriched in ontologies related to liver function, including lipid and glucose metabolism. However, hepatocyte-specific excision of Gata4 had little impact on gross liver architecture and function, even under conditions of regenerative stress, and, despite the large number of GATA4 occupied genes, resulted in relatively few changes in gene expression. To address possible redundancy between GATA4 and GATA6, both factors were conditionally excised. Surprisingly, combined Gata4,6 loss did not exacerbate the phenotype resulting from Gata4 loss alone. This points to the presence of an unusually robust transcriptional network in adult hepatocytes that ensures the maintenance of liver function. PMID:24367609

Doping Level of Boron-Doped Diamond Electrodes Controls the Grafting Density of Functional Groups for DNA Assays.

PubMed

Švorc, Ĺubomír; Jambrec, Daliborka; Vojs, Marian; Barwe, Stefan; Clausmeyer, Jan; Michniak, Pavol; Marton, Marián; Schuhmann, Wolfgang

2015-09-02

The impact of different doping levels of boron-doped diamond on the surface functionalization was investigated by means of electrochemical reduction of aryldiazonium salts. The grafting efficiency of 4-nitrophenyl groups increased with the boron levels (B/C ratio from 0 to 20,000 ppm). Controlled grafting of nitrophenyldiazonium was used to adjust the amount of immobilized single-stranded DNA strands at the surface and further on the hybridization yield in dependence on the boron doping level. The grafted nitro functions were electrochemically reduced to the amine moieties. Subsequent functionalization with a succinic acid introduced carboxyl groups for subsequent binding of an amino-terminated DNA probe. DNA hybridization significantly depends on the probe density which is in turn dependent on the boron doping level. The proposed approach opens new insights for the design and control of doped diamond surface functionalization for the construction of DNA hybridization assays.

Investigation of the effects of the level of glycemic control on erectile function and pathophysiological mechanisms in diabetic rats.

PubMed

Cho, Sung Yong; Chai, Ji Sun; Lee, Sun Hee; Park, Kwanjin; Paick, Jae-Seung; Kim, Soo Woong

2012-06-01

Poor glycemic control is associated with erectile dysfunction (ED); however, differences in ED according to the level of glycemic control have been poorly investigated. The aim of this paper is to investigate the change in erectile function according to the level of glycemic control and to clarify the pathophysiological mechanism of diabetes-associated ED. Streptozotocin was injected into 55 male Sprague-Dawley rats classified into four groups: control (group 1), diabetes with multiple insulin injections (group 2), diabetes with a single injection (group 3), and untreated diabetes (group 4). Daily insulin injections in groups 2 and 3 were administered for 4 weeks after 10 weeks of diabetic induction. The main outcome measures are the anova or Kruskal-Wallis tests to evaluate glycosylated hemoglobin (HbA1c), testosterone levels, the ratios of intracavernosal pressure to mean arterial pressure (ICP/MAP), area under the ICP curve to MAP (AUC/MAP), and changes in cavernous tissue and protein expression related to Rho kinase and nitric oxide pathways. HbA1c levels were different between pairs of groups. Group 4 showed the lowest erectile parameters and group 2 showed near normal level. No differences in erectile parameters were found between groups 1 and 2 or between groups 3 and 4, except the ratio of AUC to MAP for group 1 was significantly higher than that of group 2 (20 Hz stimulation). Decrease in erectile function of group 2 was related to decreased expression of nitrergic nitric oxide synthase or decreased testosterone level compared with group 1. Groups 2 and 3 showed significant differences in erectile parameters, which were associated with difference in apoptotic index. Groups 3 and 4 showed no differences in erectile parameters, although these groups had significant differences in apoptotic index, smooth muscle component, and protein expression ratios of phosphorylated to total myosin phosphatase target subunit 1, endothelial nitric oxide synthase, and Akt. Improvement in glycemic control assists recovery from diabetes-associated ED; however, only tight glycemic control can provide recovery from ED to a near normal status. © 2012 International Society for Sexual Medicine.

Post-stroke aphasia recovery assessed with fMRI and a picture identification task

PubMed Central

Szaflarski, Jerzy P.; Eaton, Kenneth; Ball, Angel L.; Banks, Christi; Vannest, Jennifer; Allendorfer, Jane B.; Page, Stephen; Holland, Scott K.

2010-01-01

Background Stroke patients often display deficits in language function such as correctly naming objects. Our aim was to evaluate the reliability and the patterns of post-stroke language recovery using a picture identification task during fMRI at 4T. Material and Methods 4 healthy and 4 left MCA stroke subjects with chronic (>1 year) aphasia. Ten fMRI scans were performed for each subject over a 10-week period using a picture identification task. Active condition involved presenting subjects with a panel of 4 figures (e.g., drawings of 4 animals) every 6 seconds; subjects indicated which figure matched the written name in the center. Control condition was same/different judgment task of pairs of geometric figures (squares, octagons or combination) presented every 6 seconds. Thirty-second active/control blocks were repeated 5 times each; responses were recorded. Results Patients and controls exhibited similar demographic characteristics: age (46 vs. 53 years), personal handedness (EHI; 89 vs. 95), familial handedness (93 vs. 95) or years of education (14.3 vs. 14.8). For the active condition, controls performed better than patients (97.7% vs. 89.1%, p<0.001); performance was similar for the control condition (99.5% vs. 98.8%, p=0.23). During fMRI, controls exhibited bilateral, L>R positive blood oxygenation-level dependent (BOLD) activations in frontal and temporal language areas and symmetric retro-splenial and posterior cingulate areas and symmetric negative BOLD activations in bilateral fronto-temporal language networks. However, the patient group showed positive BOLD activations predominantly in peri-stroke areas and negative BOLD activations in the unaffected (right) hemisphere. Both the control and patient groups displayed high activation reliability (as measured by the ICC) in left frontal and temporal language areas, although the ICC in frontal regions of the patients was spread over a much larger peri-stroke area. Conclusion This study documents the utility of the picture identification task for post-stroke language recovery evaluation. Study data suggest that adult stroke patients utilize functional peri-stroke areas to perform language functions. PMID:20719532

Facile fabrication of BiVO4 nanofilms with controlled pore size and their photoelectrochemical performances

NASA Astrophysics Data System (ADS)

Feng, Chenchen; Jiao, Zhengbo; Li, Shaopeng; Zhang, Yan; Bi, Yingpu

2015-12-01

We demonstrate a facile method for the rational fabrication of pore-size controlled nanoporous BiVO4 photoanodes, and confirmed that the optimum pore-size distributions could effectively absorb visible light through light diffraction and confinement functions. Furthermore, in situ X-ray photoelectron spectroscopy (XPS) reveals more efficient photoexcited electron-hole separation than conventional particle films, induced by light confinement and rapid charge transfer in the inter-crossed worm-like structures.We demonstrate a facile method for the rational fabrication of pore-size controlled nanoporous BiVO4 photoanodes, and confirmed that the optimum pore-size distributions could effectively absorb visible light through light diffraction and confinement functions. Furthermore, in situ X-ray photoelectron spectroscopy (XPS) reveals more efficient photoexcited electron-hole separation than conventional particle films, induced by light confinement and rapid charge transfer in the inter-crossed worm-like structures. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06584d

Relationship between the body image and level of pain, functional status, severity of depression, and quality of life in patients with fibromyalgia syndrome.

PubMed

Akkaya, Nuray; Akkaya, Semih; Atalay, Nilgun Simsir; Balci, Ceyhan Sengul; Sahin, Fusun

2012-06-01

The aims were to investigate how the body image is affected in fibromyalgia syndrome (FMS) in comparison to healthy people, as well as to explore the relationship of the body image with the level of pain, functional status, severity of depression, and quality of life (QoL). Demographic variables, symptoms of fibromyalgia, and number of fibromyalgia tender points for 51 patients with FMS and 41 control subjects were recorded. All patients were asked to mark the level of pain on visual analogue scale (VAS). Six-minute walking test was recorded for functional assessment. The impact of the disease was evaluated by fibromyalgia impact questionnaire (FIQ). All patients were asked to complete body image scale (BIS), Beck depression inventory (BDI), and short form-36 (SF-36). There were no differences between groups with regard to demographic variables (p>0.05). Mean VAS was 7.5±1.4 for the patients with FMS and 0.3±0.4 for control subjects (p<0.05). Mean FIQ was 70.8±13.2 and 8.2±9.6 for the FMS and control groups, respectively (p<0.05). Mean BIS and BDI were 106.5±24.0 and 20.2±11.2 for FMS group and 66.3±23.4 and 3.4±4.0 for control group, respectively (p<0.05). SF-36 subscores were found to be significantly lower in patients with FMS than control subjects (p<0.05), except for the social function subscore. BIS score had significant relationships both with VAS (r=0.843) and FIQ (r=0.290) in patients with FMS (p<0.05). There were significant relationships between BIS scores and SF-36 pain (r= -0.288), energy/vitality (r= -0.519), mental health (r= -0.442), and general health (r= -0,492) subscores (p<0.05). Body image was associated with VAS in the multivariate linear regression analysis. The results of the present study indicate that body image is disturbed in patients with FMS compared to control subjects. For the evaluation of the level of pain, impact of the disease, and QoL in patients with FMS, it would be useful to consider the relationship of the body image disturbance with these parameters.

The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision.

PubMed

Vinberg, Frans; Wang, Tian; De Maria, Alicia; Zhao, Haiqing; Bassnett, Steven; Chen, Jeannie; Kefalov, Vladimir J

2017-06-26

Calcium (Ca 2+ ) plays an important role in the function and health of neurons. In vertebrate cone photoreceptors, Ca 2+ controls photoresponse sensitivity, kinetics, and light adaptation. Despite the critical role of Ca 2+ in supporting the function and survival of cones, the mechanism for its extrusion from cone outer segments is not well understood. Here, we show that the Na + /Ca 2+ , K + exchanger NCKX4 is expressed in zebrafish, mouse, and primate cones. Functional analysis of NCKX4-deficient mouse cones revealed that this exchanger is essential for the wide operating range and high temporal resolution of cone-mediated vision. We show that NCKX4 shapes the cone photoresponse together with the cone-specific NCKX2: NCKX4 acts early to limit response amplitude, while NCKX2 acts late to further accelerate response recovery. The regulation of Ca 2+ by NCKX4 in cones is a novel mechanism that supports their ability to function as daytime photoreceptors and promotes their survival.

Exercising body and mind: an integrated approach to functional independence in hospitalized older people.

PubMed

Mudge, Alison M; Giebel, Andrea J; Cutler, Alison J

2008-04-01

To evaluate the effect of a structured, multi-component, early rehabilitation program on functional status, delirium, and discharge outcomes of older acute medical inpatients. Prospective controlled trial with blinded outcome evaluation. Internal medicine service of a metropolitan tertiary teaching hospital in Brisbane, Australia. One hundred twenty-four consecutive inpatients aged 65 and older admitted from the emergency department to control or intervention medical ward. Exclusions included patients completely dependent before admission or admitted from a nursing home, patients too ill to participate or terminally ill, and patients with length of stay less than 72 hours. Early physiotherapy review with provision of an individualized graduated exercise program and activity diary, progressive encouragement of functional independence by nursing staff and other members of the multidisciplinary team, and cognitive stimulation sessions. Modified Barthel Index (MBI) at admission and discharge, timed up-and-go at admission and discharge, incidence of delirium and falls, measured activity, length of hospital stay, discharge destination, 30-day readmission rate. Intervention and control participants were well matched in terms of age, sex, diagnosis, and functional status. The intervention group had greater improvement in functional status than the control group, with a median MBI improvement of 8.5 versus 3.5 points (P=.03). In the intervention group, there was a reduction in delirium (19.4% vs 35.5%, P=.04) and a trend to reduced falls (4.8% vs 11.3%, P=.19). Length of stay, timed up-and-go, discharge destination, and readmissions did not differ between the groups. This intervention was effective in improving function in a vulnerable patient group.

Association of five genetic variants with chronic obstructive pulmonary disease susceptibility and spirometric phenotypes in a Chinese Han population.

PubMed

Yang, Jing; Zhou, Haixia; Liang, Binmiao; Xiao, Jun; Su, Zhiguang; Chen, Hong; Ma, Chunlan; Li, Dengxue; Feng, Yulin; Ou, Xuemei

2014-02-01

Recent genome-wide association studies have shown associations between variants at five loci (TNS1, GSTCD, HTR4, AGER and THSD4) and chronic obstructive pulmonary disease (COPD) or lung function. However, their association with COPD has not been proven in Chinese Han population, nor have COPD-related phenotypes been studied. The objective of this study was to look for associations between five single nucleotide polymorphisms (SNP) in these novel candidate genes and COPD susceptibility or lung function in a Chinese Han population. Allele and genotype data on 680 COPD patients and 687 healthy controls for sentinel SNP in these five loci were investigated. Allele frequencies and genotype distributions were compared between cases and controls, and odds ratios were calculated. Potential relationships between these SNP and COPD-related lung function were assessed. No significant associations were found between any of the SNP and COPD in cases and controls. The SNP (rs3995090) in HTR4 was associated with COPD (adjusted P = 0.022) in never-smokers, and the SNP (rs2070600) in AGER was associated with forced expiratory volume in 1 s (FEV1 %) predicted (β = -0.066, adjusted P = 0.016) and FEV1 /forced vital capacity (β = -0.071, adjusted P = 0.009) in all subjects. The variant at HTR4 was associated with COPD in never-smokers, and the SNP in AGER was associated with pulmonary function in a Chinese Han population. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

CD4+  CD25+  GARP+ regulatory T cells display a compromised suppressive function in patients with dilated cardiomyopathy.

PubMed

Wei, Yuzhen; Yu, Kunwu; Wei, Hui; Su, Xin; Zhu, Ruirui; Shi, Huairui; Sun, Haitao; Luo, Quan; Xu, Wenbin; Xiao, Junhui; Zhong, Yucheng; Zeng, Qiutang

2017-07-01

Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein A repetitions predominant (GARP) expressed on activated CD4 + T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4 +  CD25 +  GARP + regulatory T (Treg) cells in DCM. Forty-five DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral T helper type 1 (Th1) and Th17 number and their related cytokines [interferon-γ (IFN-γ), interleukin (IL-17)], and an obvious decrease in Treg number, transforming growth factor-β 1 (TGF-β 1 ) levels and the expression of forkhead box P3 (FOXP3) and GARP in patients with DCM compared with controls. In addition, the suppressive function of CD4 +  CD25 +  GARP + Treg cells was impaired in DCM patients upon T-cell receptor stimulation detected using CFSE dye. Lower level of TGF-β 1 and higher levels of IFN-γ and IL-17 detected using ELISA were found in supernatants of the cultured CD4 +  CD25 +  GARP + Treg cells in DCM patients compared with controls. Together, our results indicate that CD4 +  CD25 +  GARP + Treg cells are defective in DCM patients and GARP seems to be a better molecular definition of the regulatory phenotype. Therefore, it might be an attractive stategy to pay more attention to GARP in DCM patients. © 2017 John Wiley & Sons Ltd.

Levels and interactions of plasma xanthine oxidase, catalase and liver function parameters in Nigerian children with Plasmodium falciparum infection.

PubMed

Iwalokun, B A; Bamiro, S B; Ogunledun, A

2006-12-01

Elevated plasma levels of xanthine oxidase and liver function parameters have been associated with inflammatory events in several human diseases. While xanthine oxidase provides in vitro protection against malaria, its pathophysiological functions in vivo and interactions with liver function parameters remain unclear. This study examined the interactions and plasma levels of xanthine oxidase (XO) and uric acid (UA), catalase (CAT) and liver function parameters GOT, GPT and bilirubin in asymptomatic (n=20), uncomplicated (n=32), and severe (n=18) falciparum malaria children aged 3-13 years. Compared to age-matched control (n=16), significant (p<0.05) elevation in xanthine oxidase by 100-550%, uric acid by 15.4-153.8%, GOT and GPT by 22.1-102.2%, and total bilirubin by 2.3-86% according to parasitaemia (geometric mean parasite density (GMPD)=850-87100 parasites/microL) was observed in the malarial children. Further comparison with control revealed higher CAT level (16.2+/-0.5 vs 14.6+/-0.4 U/L; p<0.05) lacking significant (p>0.05) correlation with XO, but lower CAT level (13.4-5.4 U/L) with improved correlations (r=-0.53 to -0.91; p<0.05) with XO among the asymptomatic and symptomatic malaria children studied. 75% of control, 45% of asymptomatic, 21.9% of uncomplicated, and none of severe malaria children had Hb level>11.0 g/dL. Multivariate analyses further revealed significant (p<0.05) correlations between liver function parameters and xanthine oxidase (r=0.57-0.64) only in the severe malaria group. We conclude that elevated levels of XO and liver enzymes are biochemical features of Plasmodium falciparum parasitaemia in Nigerian children, with both parameters interacting differently to modulate the catalase response in asymptomatic and symptomatic falciparum malaria.

Effects of a 6-month multimodal training intervention on retention of functional fitness in older adults: a randomized-controlled cross-over design.

PubMed

Gudlaugsson, Janus; Gudnason, Vilmundur; Aspelund, Thor; Siggeirsdottir, Kristin; Olafsdottir, Anna S; Jonsson, Palmi V; Arngrimsson, Sigurbjorn A; Harris, Tamara B; Johannsson, Erlingur

2012-09-10

Older adults have the highest rates of disability, functional dependence and use of healthcare resources. Training interventions for older individuals are of special interest where regular physical activity (PA) has many health benefits. The main purpose of this study was to assess the immediate and long-term effects of a 6-month multimodal training intervention (MTI) on functional fitness in old adults. For this study, 117 participants, 71 to 90 years old, were randomized in immediate intervention group and a control group (delayed intervention group). The intervention consisted of daily endurance and twice-a-week strength training. The method was based on a randomized-controlled cross-over design. Short Physical Performance Battery (SPPB), 8 foot up-and-go test, strength performance, six min walking test (6 MW), physical activity, BMI and quality of life were obtained at baseline, after a 6-month intervention- and control phase, again after 6-month crossover- and delayed intervention phase, and after anadditional 6-month follow-up. After 6 months of MTI, the intervention group improved in physical performance compared with the control group via Short Physical Performance Battery (SPPB) score (mean diff = 0.6, 95 % CI: 0.1, 1.0) and 8-foot up-and-go test (mean diff = -1.0 s, 95 % CI: -1.5, -0.6), and in endurance performance via 6-minute walking test (6 MW) (mean diff = 44.2 meters, 95 % CI: 17.1, 71.2). In strength performance via knee extension the intervention group improved while control group declined (mean diff = 55.0 Newton, 95 % CI: 28.4, 81.7), and also in PA (mean diff = 125.9 cpm, 95 % CI: 96.0, 155.8). Long-term effects of MTI on the particpants was assesed by estimating the mean difference in the variables measured between time-point 1 and 4: SPPB (1.1 points, 95 % CI: 0.8, 1.4); 8-foot up-and-go (-0.9 s, 95 % CI: -1.2, -0.6); 6 MW (18.7 m, 95 % CI: 6.5, 31.0); knee extension (4.2 Newton, 95 % CI: -10.0, 18.3); hand grip (6.7 Newton, 95 % CI: -4.4, 17.8); PA (-4.0 cpm, 95 % CI: -33.9, 26.0); BMI (-0.6 kg/m2, 95 % CI: -0.9, -0.3) and Icelandic quality of life (0.3 points, 95 % CI: -0.7, 1.4). Our results suggest that regular MTI can improve and prevent decline in functional fitness in older individuals, influence their lifestyle and positively affect their ability to stay independent, thus reducing the need for institutional care. This study was approved by the National Bioethics Committee in Iceland, VSNb20080300114/03-1.

A Calmodulin C-Lobe Ca2+-Dependent Switch Governs Kv7 Channel Function.

PubMed

Chang, Aram; Abderemane-Ali, Fayal; Hura, Greg L; Rossen, Nathan D; Gate, Rachel E; Minor, Daniel L

2018-02-21

Kv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation. This C-lobe switch inhibits voltage-dependent activation of Kv7.4 and Kv7.5 but facilitates Kv7.1, demonstrating that mechanism is shared by Kv7 isoforms despite the different directions of CaM modulation. Our findings provide a unified framework for understanding how CaM controls different Kv7 isoforms and highlight the role of membrane proximal domains for controlling voltage-gated channel function. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

Design of a Linear Gaussian Control Law for an Adaptive Optics System

DTIC Science & Technology

1990-12-01

3-7 3.4. X-Axis Slice of Actuator :#49 Influence Function .. .. .... ...... ...... 3-9 3.5. Approximate Influence Function for Actuator #49... influence function is a mathematical representation of the effect of a single ac- tuator voltage on the local mirror shape. Usually, the influence ... function is nonzero only in the vicinity of the actuator: the influence function of an actualor has a limited spa- tial domain. Several factors affect the

Neuropsychological Profile Related with Executive Function of Chinese Preschoolers with Attention-Deficit/Hyperactivity Disorder: Neuropsychological Measures and Behavior Rating Scale of Executive Function-Preschool Version.

PubMed

Zhang, Hui-Feng; Shuai, Lan; Zhang, Jin-Song; Wang, Yu-Feng; Lu, Teng-Fei; Tan, Xin; Pan, Jing-Xue; Shen, Li-Xiao

2018-03-20

Previous studies have found that schoolchildren with attention-deficit/hyperactivity disorder (ADHD) showed difficulties in neuropsychological function. This study aimed to assess neuropsychological function in Chinese preschoolers with ADHD using broad neuropsychological measures and rating scales and to test whether the pattern and severity of neuropsychological weakness differed among ADHD presentations in preschool children. The 226 preschoolers (163 with ADHD and 63 controls) with the age of 4-5 years were included and assessed using the Behavior Rating Scale of Executive Function-Preschool Version (BRIEF-P) and a series of tests to investigate neuropsychological function. Preschoolers with ADHD showed higher scores in all domains of the BRIEF-P (inhibition: 30.64 ± 5.78 vs.20.69 ± 3.86, P < 0.001; shift: 13.40 ± 3.03 vs.12.41 ± 2.79, P = 0.039; emotional control:15.10 ± 3.53 vs.12.20 ± 2.46, P < 0.001; working memory: 28.41 ± 4.99 vs.20.95 ± 4.60, P < 0.001; plan/organize: 17.04 ± 3.30 vs.13.29 ± 2.40, P < 0.001) and lower scores of Statue (23.18 ± 7.84 vs.28.27 ± 3.18, P = 0.001), Word Generation (15.22 ± 6.52 vs.19.53 ± 7.69, P = 0.025), Comprehension of Instructions (14.00 ± 4.44 vs.17.02 ± 3.39, P = 0.016), Visuomotor Precision (P < 0.050), Toy delay (P = 0.048), and Matrices tasks (P = 0.011), compared with normal control. In terms of the differences among ADHD subtypes, all ADHD presentations had higher scores in several domains of the BRIEF-P (P < 0.001), and the ADHD-combined symptoms (ADHD-C) group had the poorest ratings on inhibition and the ability to Plan/Organize. For neuropsychological measures, the results suggested that the ADHD-C group had poorer performances than the ADHD-predominantly inattentive symptoms (ADHD-I) group on Statue tasks (F = 7.34, η 2 = 0.12, P < 0.001). Furthermore, the ADHD-hyperactive/impulsive symptoms group had significantly poorer performances compared to the ADHD-C group in the Block Construction task (F = 4.89, η 2 = 0.067, P = 0.003). However, no significant group differences were found between the ADHD-I group and normal control. Based on the combined evaluation of performance-based neuropsychological tests and the BRIEF-P, preschoolers with ADHD show difficulties of neuropsychological function in many aspects.

Quantifying subtle changes in cardiovascular mechanics in acromegaly: a Doppler myocardial imaging study.

PubMed

Jurcut, R; Găloiu, S; Florian, A; Vlădaia, A; Ioniţă, O R; Amzulescu, M S; Baciu, I; Popescu, B A; Coculescu, M; Ginghina, C

2014-11-01

To describe morphological and functional cardiovascular changes in acromegaly (ACM) patients, as well as to investigate the ability of Doppler-based myocardial deformation imaging (DMI) to characterize subtle dysfunction in ACM. 69 patients (pts) with ACM (mean age 47 ± 10 years, 27 men) and 31 controls (mean age 43 ± 16 years, matched for age and gender) were recruited. Standard echocardiography and DMI data were obtained for all patients. Peak systolic longitudinal strain values (S) were determined for the left and right ventricles. Radial S was measured at the level of the mid inferolateral segment. Using a high-resolution echo-tracking system, the main indices of arterial stiffness were measured. Of the ACM subjects, 57 had active disease (group A), and 12 controlled ACM (group B). All pts with ACM presented structural changes: a higher LV indexed mass (112 ± 36, 118 ± 23 vs 74 ± 18 g/m(2), p < 0.001) and a higher relative wall thickness (0.45 ± 0.09, 0.50 ± 0.07 vs 0.40 ± 0.07, p = 0.003) compared to controls. Also, ACM pts had functional changes: reduced LV ejection fraction (57 ± 5, 55 ± 5 vs 64 ± 4%, p < 0.001) and altered diastolic function (E/A 1.0 ± 0.4, 1.1 ± 0.1 vs 1.3 ± 0.3, p = 0.005) compared to controls. Both longitudinal and radial LV S values were lower in ACM compared to controls: -16.5 ± 3.5, -16.8 ± 4.3 vs -21.5 ± 3.8%, p < 0.001 for longitudinal and 38.3 ± 12.3, 35.6 ± 11.8 vs 52.2 ± 11.7%, p = 0.002 for radial strain. ACM pts present LV concentric hypertrophy and LV systolic and diastolic dysfunction, even in controlled disease. Altered global LV systolic function appears to be due both to longitudinal and radial dysfunction.

Heparin for prolonging peripheral intravenous catheter use in neonates: a randomized controlled trial.

PubMed

Upadhyay, A; Verma, K K; Lal, P; Chawla, D; Sreenivas, V

2015-04-01

To determine the efficacy of heparinized saline administered as intermittent flush on functional duration of the peripheral intravenous catheter (PIVC) in neonates. Randomized, double-blind and placebo-controlled trial. Neonatal intensive care unit of a teaching hospital. Term and preterm neonates born at >32 weeks of gestation who required PIVC only for intermittent administration of antibiotics. Eligible neonates were randomized to receive 1 ml of either heparinized saline (10 U ml(-1)) (n=60) or normal saline (n=60) every 12 h before and after intravenous antibiotics. Functional duration of first peripheral intravenous catheter. A total of 120 neonates were randomized to two groups of 60 neonates each. The mean (s.d.) of age of babies in case and control group was 5.7 (2.5) days and 4.6 (3.1) days, respectively. The average weight of babies in both the groups was 2.1 kg. Mean functional duration of first catheter was more in heparinized saline group, mean (s.d.) of 71.68 h  (27.3) as compared with 57.7 h (23.6) in normal saline group (P<0.005). The mean (95% confidence interval) difference in functional duration in the two groups was 13.9 h (4.7-23.15). Mean duration of patency for any catheter was also significantly more in heparinized saline group than control group. Heparinized saline flush increases the functional duration of peripheral intravenous catheter.

49 CFR 236.311 - Signal control circuits, selection through track relays or devices functioning as track relays...

Code of Federal Regulations, 2010 CFR

2010-10-01

... automatic interlocking. (a) The control circuits for aspects with indications more favorable than “proceed... 49 Transportation 4 2010-10-01 2010-10-01 false Signal control circuits, selection through track... automatic interlocking. 236.311 Section 236.311 Transportation Other Regulations Relating to Transportation...

The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p.

PubMed

Czimmerer, Zsolt; Varga, Tamas; Kiss, Mate; Vázquez, Cesaré Ovando; Doan-Xuan, Quang Minh; Rückerl, Dominik; Tattikota, Sudhir Gopal; Yan, Xin; Nagy, Zsuzsanna S; Daniel, Bence; Poliska, Szilard; Horvath, Attila; Nagy, Gergely; Varallyay, Eva; Poy, Matthew N; Allen, Judith E; Bacso, Zsolt; Abreu-Goodger, Cei; Nagy, Laszlo

2016-05-31

IL-4-driven alternative macrophage activation and proliferation are characteristic features of both antihelminthic immune responses and wound healing in contrast to classical macrophage activation, which primarily occurs during inflammatory responses. The signaling pathways defining the genome-wide microRNA expression profile as well as the cellular functions controlled by microRNAs during alternative macrophage activation are largely unknown. Hence, in the current work we examined the regulation and function of IL-4-regulated microRNAs in human and mouse alternative macrophage activation. We utilized microarray-based microRNA profiling to detect the dynamic expression changes during human monocyte-macrophage differentiation and IL-4-mediated alternative macrophage activation. The expression changes and upstream regulatory pathways of selected microRNAs were further investigated in human and mouse in vitro and in vivo models of alternative macrophage activation by integrating small RNA-seq, ChIP-seq, ChIP-quantitative PCR, and gene expression data. MicroRNA-controlled gene networks and corresponding functions were identified using a combination of transcriptomic, bioinformatic, and functional approaches. The IL-4-controlled microRNA expression pattern was identified in models of human and mouse alternative macrophage activation. IL-4-dependent induction of miR-342-3p and repression of miR-99b along with miR-125a-5p occurred in both human and murine macrophages in vitro. In addition, a similar expression pattern was observed in peritoneal macrophages of Brugia malayi nematode-implanted mice in vivo. By using IL4Rα- and STAT6-deficient macrophages, we were able to show that IL-4-dependent regulation of miR-342-3p, miR-99b, and miR-125a-5p is mediated by the IL-4Rα-STAT6 signaling pathway. The combination of gene expression studies and chromatin immunoprecipitation experiments demonstrated that both miR-342-3p and its host gene, EVL, are coregulated directly by STAT6. Finally, we found that miR-342-3p is capable of controlling macrophage survival through targeting an anti-apoptotic gene network including Bcl2l1. Our findings identify a conserved IL-4/STAT6-regulated microRNA signature in alternatively activated human and mouse macrophages. Moreover, our study indicates that miR-342-3p likely plays a pro-apoptotic role in such cells, thereby providing a negative feedback arm to IL-4-dependent macrophage proliferation.

Effects of anodal transcranial direct current stimulation combined with virtual reality for improving gait in children with spastic diparetic cerebral palsy: a pilot, randomized, controlled, double-blind, clinical trial.

PubMed

Collange Grecco, Luanda André; de Almeida Carvalho Duarte, Natália; Mendonça, Mariana E; Galli, Manuela; Fregni, Felipe; Oliveira, Claudia Santos

2015-12-01

To compare the effects of anodal vs. sham transcranial direct current stimulation combined with virtual reality training for improving gait in children with cerebral palsy. A pilot, randomized, controlled, double-blind, clinical trial. Rehabilitation clinics. A total of 20 children with diparesis owing to cerebral palsy. The experimental group received anodal stimulation and the control group received sham stimulation over the primary motor cortex during virtual reality training. All patients underwent the same training programme involving a virtual reality (10 sessions). Evaluations were performed before and after the intervention as well as at the one-month follow-up and involved gait analysis, the Gross Motor Function Measure, the Pediatric Evaluation Disability Inventory and the determination of motor evoked potentials. The experimental group had a better performance regarding gait velocity (experimental group: 0.63 ±0.17 to 0.85 ±0.11 m/s; control group: 0.73 ±0.15 to 0.61 ±0.15 m/s), cadence (experimental group: 97.4 ±14.1 to 116.8 ±8.7 steps/minute; control group: 92.6 ±10.4 to 99.7 ±9.7 steps/minute), gross motor function (dimension D experimental group: 59.7 ±12.8 to 74.9 ±13.8; control group: 58.9 ±10.4 to 69.4 ±9.3; dimension E experimental group: 59.0 ±10.9 to 79.1 ±8.5; control group: 60.3 ±10.1 to 67.4 ±11.4) and independent mobility (experimental group: 34.3 ±5.9 to 43.8 ±75.3; control group: 34.4 ±8.3 to 37.7 ±7.7). Moreover, transcranial direct current stimulation led to a significant increase in motor evoked potential (experimental group: 1.4 ±0.7 to 2.6 ±0.4; control group: 1.3 ±0.6 to 1.6 ±0.4). These preliminary findings support the hypothesis that anodal transcranial direct current stimulation combined with virtual reality training could be a useful tool for improving gait in children with cerebral palsy. © The Author(s) 2015.

Longitudinal Antecedents of Ego-Control and Ego-Resiliency in Late Adolescence.

ERIC Educational Resources Information Center

Block, Jack

Ego-control and ego-resiliency were evaluated in seven assessments conducted when subjects were 3, 4, 5, 7, 11, 14, and 18 years old. Ego-control refers to an individual's tendency to express or contain impulses, feelings, and desires. Ego-resiliency refers to the capacity to modify one's modal level of ego-control as a function of environmental…

[Quantity and function of T follicular helper cells in the bone marrow of patients with immune thrombocytopenia].

PubMed

Zhang, Yang; Qu, Wen; Ruan, Er-Bao; Fu, Rong; Wang, Guo-Jin; Liu, Hong; Wang, Xiao-Ming; Wu, Yu-Hong; Song, Jia; Xing, Li-Min; Guan, Jing; Li, Li-Juan; Wang, Hua-Quan; Shao, Zong-Hong

2014-06-01

This study was purposed to detect the quantity and function of bone marrow (BM) T follicular helper (Tfh) cells of patients with immune thrombocytopenia, and to explore the role of Tfh cells in the pathogenesis of ITP. Twenty-one newly diagnosed ITP patients, twenty ITP patients in recovery stage and eighteen normal controls were enrolled in this study. The percentages of Tfh cells, Tfh-related molecules ICOS, CD40L, IL-21 in BM were detected by flow cytometry (FCM), and the mRNA expression of BCL-6 in BMMNC was determined by semi-quantitive RT-PCR. Correlation of Tfh cell level with the disease severity of ITP patients was analysed. The results showed that the ratio of CD4(+)CXCR5(+)/CD4(+) cells in newly diagnosed ITP patients [(5.532 ± 2.599)%] was significantly higher than that in ITP patients with recovery stage [(4.064 ± 2.026)%] and controls [(4.048 ± 1.413)%] (P < 0.05). The ratio of CD4(+)CXCR5(+)ICOS(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(14.586 ± 8.561)%] was higher than that in recovery stage ITP patients [(12.884 ± 10.161)%] and controls [(7.487 ± 5.176)%]. The differences be-tween newly diagnosed ITP patients and controls were statistically significant (P < 0.05). The ratio of CD4(+)CXCR5(+) CD40L(+)/CD4(+) CXCR5(+) cells in newly diagnosed ITP patients [(15.309 ± 10.756)%] and in ITP patients with recovery stage [(18.242 ± 12.243)%] were significantly higher than that in controls [(8.618 ± 5.719) %] (P < 0.05). The ratio of intracytoplasm CD4(+) CXCR5(+) IL-21(+)/CD4(+)CXCR5(+) cells in newly diagnosed ITP patients [(58.560 ± 26.285)%] and in ITP patients with recovery stage [(57.035 ± 30.936)%] were significantly higher than that in controls [(36.289 ± 24.868)%] (P < 0.05). The relative expression levels of BCL-6 mRNA in BMMNC of three groups were (1.407 ± 0.264), (1.149 ± 0.217) and (0.846 ± 0.157), respectively. The differences between 3 groups were significant(P < 0.05). It is concluded that the quantity and function of Tfh cells in ITP patients increase, which may play an important role in the pathogenesis of ITP.

Energy-band engineering for tunable memory characteristics through controlled doping of reduced graphene oxide.

PubMed

Han, Su-Ting; Zhou, Ye; Yang, Qing Dan; Zhou, Li; Huang, Long-Biao; Yan, Yan; Lee, Chun-Sing; Roy, Vellaisamy A L

2014-02-25

Tunable memory characteristics are used in multioperational mode circuits where memory cells with various functionalities are needed in one combined device. It is always a challenge to obtain control over threshold voltage for multimode operation. On this regard, we use a strategy of shifting the work function of reduced graphene oxide (rGO) in a controlled manner through doping gold chloride (AuCl3) and obtained a gradient increase of rGO work function. By inserting doped rGO as floating gate, a controlled threshold voltage (Vth) shift has been achieved in both p- and n-type low voltage flexible memory devices with large memory window (up to 4 times for p-type and 8 times for n-type memory devices) in comparison with pristine rGO floating gate memory devices. By proper energy band engineering, we demonstrated a flexible floating gate memory device with larger memory window and controlled threshold voltage shifts.

Improving social functioning and reducing social isolation and loneliness among people with enduring mental illness: Report of a randomised controlled trial of supported socialisation.

PubMed

Sheridan, Ann J; Drennan, Jonathan; Coughlan, Barbara; O'Keeffe, Donal; Frazer, Kate; Kemple, Mary; Alexander, Denise; Howlin, Frances; Fahy, Anne; Kow, Veronica; O'Callaghan, Eadbhard

2015-05-01

This randomised controlled trial examined if for people with enduring mental illness, being supported to socialise leads to improved social functioning, increased self-esteem and extended social networks; a reduction in social isolation, social, emotional and family loneliness and a reduction in illness symptoms, namely depression. A prospective randomised controlled trial was undertaken from November 2007 to September 2011. Service users with a diagnosis of enduring mental illness (>18 years) were invited to participate. Participants were randomly allocated to intervention or control group conditions in a 1:1 ratio. Intervention group participants were matched with a volunteer partner, asked to engage in social/leisure activities for 2 hours weekly over a 9-month period, and received a €20 stipend monthly. Control group participants received a €20 monthly stipend and were asked to engage in a weekly social/leisure activity. Social functioning, the primary outcome, was measured using the Social Functioning Scale (SFS) at three time points (baseline, midpoint and endpoint). In all, 107 people completed this study. There were no significant differences between control and intervention groups at the commencement of the intervention on demographic characteristics or the main outcome measures of interest. Overall social functioning positively changed throughout the three time points from a mean of 99·7 (standard deviation (SD) = 15.1) at baseline, to a mean of 106.0 (SD = 27.0) at the endpoint for the control group, and from a mean of 100·4 (SD = 15.0) at Time 1 for the intervention group, to a mean of 104.1 (SD = 23.4) at the endpoint for the intervention group. The intervention showed no statistical differences between the control and intervention groups on primary or secondary outcome measures. The stipend and the stipend plus volunteer partner led to an increase in recreational social functioning; a decrease in levels of social loneliness, in depression and in the proportion living within a vulnerable social network. © The Author(s) 2014.

A microbial biogeochemistry network for soil carbon and nitrogen cycling and methane flux: model structure and application to Asia

NASA Astrophysics Data System (ADS)

Xu, X.; Song, C.; Wang, Y.; Ricciuto, D. M.; Lipson, D.; Shi, X.; Zona, D.; Song, X.; Yuan, F.; Oechel, W. C.; Thornton, P. E.

2017-12-01

A microbial model is introduced for simulating microbial mechanisms controlling soil carbon and nitrogen biogeochemical cycling and methane fluxes. The model is built within the CN (carbon-nitrogen) framework of Community Land Model 4.5, named as CLM-Microbe to emphasize its explicit representation of microbial mechanisms to biogeochemistry. Based on the CLM4.5, three new pools were added: bacteria, fungi, and dissolved organic matter. It has 11 pools and 34 transitional processes, compared with 8 pools and 9 transitional flow in the CLM4.5. The dissolve organic carbon was linked with a new microbial functional group based methane module to explicitly simulate methane production, oxidation, transport and their microbial controls. Comparing with CLM4.5-CN, the CLM-Microbe model has a number of new features, (1) microbial control on carbon and nitrogen flows between soil carbon/nitrogen pools; (2) an implicit representation of microbial community structure as bacteria and fungi; (3) a microbial functional-group based methane module. The model sensitivity analysis suggests the importance of microbial carbon allocation parameters on soil biogeochemistry and microbial controls on methane dynamics. Preliminary simulations validate the model's capability for simulating carbon and nitrogen dynamics and methane at a number of sites across the globe. The regional application to Asia has verified the model in simulating microbial mechanisms in controlling methane dynamics at multiple scales.

Circadian Regulation of Pineal Gland Rhythmicity

PubMed Central

Borjigin, Jimo; Zhang, L. Samantha; Calinescu, Anda-Alexandra

2011-01-01

The pineal gland is a neuroendocrine organ of the brain. Its main task is to synthesize and secrete melatonin, a nocturnal hormone with diverse physiological functions. This review will focus on the central and pineal mechanisms in generation of mammalian pineal rhythmicity including melatonin production. In particular, this review covers the following topics: (1) local control of serotonin and melatonin rhythms; (2) neurotransmitters involved in central control of melatonin; (3) plasticity of the neural circuit controlling melatonin production; (4) role of clock genes in melatonin formation; (5) phase control of pineal rhythmicity; (6) impact of light at night on pineal rhythms; and (7) physiological function of the pineal rhythmicity. PMID:21782887

Diversity in TAF proteomics: consequences for cellular differentiation and migration.

PubMed

Kazantseva, Jekaterina; Palm, Kaia

2014-09-19

Development is a highly controlled process of cell proliferation and differentiation driven by mechanisms of dynamic gene regulation. Specific DNA binding factors for establishing cell- and tissue-specific transcriptional programs have been characterised in different cell and animal models. However, much less is known about the role of "core transcription machinery" during cell differentiation, given that general transcription factors and their spatiotemporally patterned activity govern different aspects of cell function. In this review, we focus on the role of TATA-box associated factor 4 (TAF4) and its functional isoforms generated by alternative splicing in controlling lineage-specific differentiation of normal mesenchymal stem cells and cancer stem cells. In the light of our recent findings, induction, control and maintenance of cell differentiation status implies diversification of the transcription initiation apparatus orchestrated by alternative splicing.

Neural regulation of the kidney function in rats with cisplatin induced renal failure

PubMed Central

Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

Baroreflex buffering and susceptibility to vasoactive drugs

NASA Technical Reports Server (NTRS)

Jordan, Jens; Tank, Jens; Shannon, John R.; Diedrich, Andre; Lipp, Axel; Schroder, Christoph; Arnold, Guy; Sharma, Arya M.; Biaggioni, Italo; Robertson, David;

Childhood Obstructive Sleep Apnea Associates with Neuropsychological Deficits and Neuronal Brain Injury

PubMed Central

Halbower, Ann C; Degaonkar, Mahaveer; Barker, Peter B; Earley, Christopher J; Marcus, Carole L; Smith, Philip L; Prahme, M. Cristine; Mahone, E. Mark

2006-01-01

Background Childhood obstructive sleep apnea (OSA) is associated with neuropsychological deficits of memory, learning, and executive function. There is no evidence of neuronal brain injury in children with OSA. We hypothesized that childhood OSA is associated with neuropsychological performance dysfunction, and with neuronal metabolite alterations in the brain, indicative of neuronal injury in areas corresponding to neuropsychological function. Methods and Findings We conducted a cross-sectional study of 31 children (19 with OSA and 12 healthy controls, aged 6–16 y) group-matched by age, ethnicity, gender, and socioeconomic status. Participants underwent polysomnography and neuropsychological assessments. Proton magnetic resonance spectroscopic imaging was performed on a subset of children with OSA and on matched controls. Neuropsychological test scores and mean neuronal metabolite ratios of target brain areas were compared. Relative to controls, children with severe OSA had significant deficits in IQ and executive functions (verbal working memory and verbal fluency). Children with OSA demonstrated decreases of the mean neuronal metabolite ratio N-acetyl aspartate/choline in the left hippocampus (controls: 1.29, standard deviation [SD] 0.21; OSA: 0.91, SD 0.05; p = 0.001) and right frontal cortex (controls: 2.2, SD 0.4; OSA: 1.6, SD 0.4; p = 0.03). Conclusions Childhood OSA is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex. We speculate that untreated childhood OSA could permanently alter a developing child's cognitive potential. PMID:16933960

Endothelial and kidney function in women with a history of preeclampsia and healthy parous controls: A case control study.

PubMed

Lopes van Balen, Veronica A; Spaan, Julia J; Cornelis, Tom; Heidema, Wieteke M; Scholten, Ralph R; Spaanderman, Marc E A

2018-03-01

Preeclampsia (PE) is a pregnancy related endothelial disease characterized by hypertension and albuminuria. Postpartum endothelial dysfunction often persists in these women. We postulate that in women with a history of PE reduced endothelial dependent vasodilation coincides with attenuated kidney function, as both reflect endothelial dysfunction. We assessed endothelial and kidney function in women with a history of PE (n=79) and uncomplicated pregnancies (n=49) at least 4years postpartum. Women with hypertension, diabetes or kidney disease prior to pregnancy were excluded. Brachial artery flow mediated dilatation (FMD) was measured and analysed by a custom designed edge-detection and wall-tracking software. We measured albumin and creatinine levels in a 24-h urine sample and calculated glomerular filtration rate (GFR) by CKD-EPI. Women with a history of PE had lower FMD but comparable GFR and albumin creatinine ratio (ACR) compared with controls. Independent of obstetric history, in both controls and women with a history of PE respectively, GFR (r=0.19, p=0.17 and r=0.12, p=0.29) and albumin creatinine ratio (r=0.07, p=0.62 and r=0.06 p=0.57) did not correlate with FMD. At least 4years after pregnancy, women with a history of PE demonstrated decreased flow mediated dilatation when compared to healthy parous controls. In this study, decreased flow mediated dilation however did not coincide with decreased kidney function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study.

PubMed

Weir, Matthew A; Gomes, Tara; Mamdani, Muhammad; Juurlink, David N; Hackam, Daniel G; Mahon, Jeffrey L; Jain, Arsh K; Garg, Amit X

2011-06-01

Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide. We conducted a nested case-control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations. From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m(2) (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m(2) (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9-16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8-9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5-33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0-12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk. In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use.

Effects of a High-Intensity Functional Exercise Program on Dependence in Activities of Daily Living and Balance in Older Adults with Dementia

PubMed Central

Toots, Annika; Littbrand, Håkan; Lindelöf, Nina; Wiklund, Robert; Holmberg, Henrik; Nordström, Peter; Lundin-Olsson, Lillemor; Gustafson, Yngve; Rosendahl, Erik

2016-01-01

Objectives To investigate the effects of a high-intensity functional exercise program on independence in activities of  daily living (ADLs) and balance in older people with dementia and whether exercise effects differed between dementia types. Design Cluster-randomized controlled trial: Umeå Dementia and Exercise (UMDEX) study. Setting Residential care facilities, Umeå, Sweden. Participants Individuals aged 65 and older with a dementia diagnosis, a Mini-Mental State Examination score of 10 or greater, and dependence in ADLs (N = 186). Intervention Ninety-three participants each were allocated to the high-intensity functional exercise program, comprising lower limb strength and balance exercises, and 93 to a seated control activity. Measurements Blinded assessors measured ADL independence using the Functional Independence Measure (FIM) and Barthel Index (BI) and balance using the Berg Balance Scale (BBS) at baseline and 4 (directly after intervention completion) and 7 months. Results Linear mixed models showed no between-group effect on ADL independence at 4 (FIM=1.3, 95% confidence interval (CI)=−1.6–4.3; BI=0.6, 95% CI=−0.2–1.4) or 7 (FIM=0.8, 95% CI=−2.2–3.8; BI=0.6, 95% CI=−0.3–1.4) months. A significant between-group effect on balance favoring exercise was observed at 4 months (BBS=4.2, 95% CI=1.8–6.6). In interaction analyses, exercise effects differed significantly between dementia types. Positive between-group exercise effects were found in participants with non-Alzheimer's dementia according to the FIM at 7 months and BI and BBS at 4 and 7 months. Conclusion In older people with mild to moderate dementia living in residential care facilities, a 4-month high-intensity functional exercise program appears to slow decline in ADL independence and improve balance, albeit only in participants with non-Alzheimer's dementia. PMID:26782852

Effects of a High-Intensity Functional Exercise Program on Dependence in Activities of Daily Living and Balance in Older Adults with Dementia.

PubMed

Toots, Annika; Littbrand, Håkan; Lindelöf, Nina; Wiklund, Robert; Holmberg, Henrik; Nordström, Peter; Lundin-Olsson, Lillemor; Gustafson, Yngve; Rosendahl, Erik

2016-01-01

To investigate the effects of a high-intensity functional exercise program on independence in activities of daily living (ADLs) and balance in older people with dementia and whether exercise effects differed between dementia types. Cluster-randomized controlled trial: Umeå Dementia and Exercise (UMDEX) study. Residential care facilities, Umeå, Sweden. Individuals aged 65 and older with a dementia diagnosis, a Mini-Mental State Examination score of 10 or greater, and dependence in ADLs (N=186). Ninety-three participants each were allocated to the high-intensity functional exercise program, comprising lower limb strength and balance exercises, and 93 to a seated control activity. Blinded assessors measured ADL independence using the Functional Independence Measure (FIM) and Barthel Index (BI) and balance using the Berg Balance Scale (BBS) at baseline and 4 (directly after intervention completion) and 7 months. Linear mixed models showed no between-group effect on ADL independence at 4 (FIM=1.3, 95% confidence interval (CI)=-1.6-4.3; BI=0.6, 95% CI=-0.2-1.4) or 7 (FIM=0.8, 95% CI=-2.2-3.8; BI=0.6, 95% CI=-0.3-1.4) months. A significant between-group effect on balance favoring exercise was observed at 4 months (BBS=4.2, 95% CI=1.8-6.6). In interaction analyses, exercise effects differed significantly between dementia types. Positive between-group exercise effects were found in participants with non-Alzheimer's dementia according to the FIM at 7 months and BI and BBS at 4 and 7 months. In older people with mild to moderate dementia living in residential care facilities, a 4-month high-intensity functional exercise program appears to slow decline in ADL independence and improve balance, albeit only in participants with non-Alzheimer's dementia. © 2016 The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India.

PubMed

Elango, Nithya; Kasi, Vallikkannu; Vembhu, Bhuvaneswari; Poornima, Jeyanthi Govindasamy

2013-09-11

We assessed indoor air quality in photocopier centers and investigated whether occupational exposure to emissions from photocopiers is associated with decline in lung function or changes in haematological parameters, oxidative stress and inflammatory status. Indoor air quality was monitored in five photocopier centers. Pulmonary function was assessed by spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy control (31 male and 12 female) subjects. Hematological status, serum thio-barbituric acid reactive substances (TBARS), total ferric reducing antioxidant capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP), interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule 1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships between cumulative exposure, lung function and inflammatory markers were assessed. PM10 and PM2.5 were above the permissible levels in all the photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides, ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and benzo(a)pyrene were within Indian ambient air quality standards. Lung function was similar in the photocopier operators and control subjects. Serum TBARS was significantly higher and FRAC was lower among photocopier operators when compared to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher in the photocopier exposed group. Photocopiers emit high levels of particulate matter. Long term exposure to emissions from photocopiers was not associated with decreased lung function, but resulted in high oxidative stress and systemic inflammation leading to high risk of cardiovascular diseases.

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India

PubMed Central

2013-01-01

Background We assessed indoor air quality in photocopier centers and investigated whether occupational exposure to emissions from photocopiers is associated with decline in lung function or changes in haematological parameters, oxidative stress and inflammatory status. Methods Indoor air quality was monitored in five photocopier centers. Pulmonary function was assessed by spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy control (31 male and 12 female) subjects. Hematological status, serum thio-barbituric acid reactive substances (TBARS), total ferric reducing antioxidant capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP), interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule 1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships between cumulative exposure, lung function and inflammatory markers were assessed. Results PM10 and PM2.5 were above the permissible levels in all the photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides, ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and benzo(a)pyrene were within Indian ambient air quality standards. Lung function was similar in the photocopier operators and control subjects. Serum TBARS was significantly higher and FRAC was lower among photocopier operators when compared to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher in the photocopier exposed group. Conclusions Photocopiers emit high levels of particulate matter. Long term exposure to emissions from photocopiers was not associated with decreased lung function, but resulted in high oxidative stress and systemic inflammation leading to high risk of cardiovascular diseases. PMID:24025094

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic)

PubMed Central

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R.; Matloub, Hani S.; Pritchard, Kirkwood A.; Jaradeh, Safwan S.; Havlik, Robert

2017-01-01

Background Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. Methods A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Results Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. Conclusions The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. PMID:26433438

Aquaporin 4 in Astrocytes is a Target for Therapy in Alzheimer's Disease.

PubMed

Lan, Yu-Long; Chen, Jian-Jiao; Hu, Gang; Xu, Jun; Xiao, Ming; Li, Shao

2017-01-01

Current experimental evidence points to the conclusion that aquaporin 4 (AQP4), which is an important water-channel membrane protein found in the brain, could play major roles in various brain conditions pathologically including pathogenesis of Alzheimer's disease (AD). In this paper, we review how AQP4 and altered astrocyte functions interact in AD, and provide experimental evidence highlighting the importance of this topic for the future investigations. The interactions of AQP4 are as follows: (i) AQP4 could influence astrocytic calcium signaling and potassium homeostasis. (ii) AQP4 is linked with the removal of interstitial β-amyloid and glutamate transmission. (iii) Furthermore, AQP4 modulates the reactive astrogliosis and neuroinflammation mechanisms. (iv) To add to this, AQP4 could participate in the AD pathogenesis through affecting neurotrophic factor production. It is therefore possible to identify certain functional molecules that regulate astrocyte make-up and functions. However, making crucial efforts to develop specific agents or drugs that target AQP4 function and test their therapeutic efficiency will be a breakthrough for addressing AD in that AQP4 controls the various physiological as well as pathophysiological features of astrocytes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Neural systemic impairment from whole-body vibration.

PubMed

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; LoGiudice, John; Sanger, James R; Matloub, Hani S; Havlik, Robert

2015-05-01

Insidious brain microinjury from motor vehicle-induced whole-body vibration (WBV) has not yet been investigated. For a long time we have believed that WBV would cause cumulative brain microinjury and impair cerebral function, which suggests an important risk factor for motor vehicle accidents and secondary cerebral vascular diseases. Fifty-six Sprague-Dawley rats were divided into seven groups (n = 8): 1) 2-week normal control group, 2) 2-week sham control group (restrained in the tube without vibration), 3) 2-week vibration group (exposed to whole-body vibration at 30 Hz and 0.5g acceleration for 4 hr/day, 5 days/week, for 2 weeks), 4) 4-week sham control group, 5) 4-week vibration group, 6) 8-week sham control group, and 7) 8-week vibration group. At the end point, all rats were evaluated in behavior, physiological, and brain histopathological studies. The cerebral injury from WBV is a cumulative process starting with vasospasm squeezing of the endothelial cells, followed by constriction of the cerebral arteries. After the 4-week vibration, brain neuron apoptosis started. After the 8-week vibration, vacuoles increased further in the brain arteries. Brain capillary walls thickened, mean neuron size was obviously reduced, neuron necrosis became prominent, and wide-ranging chronic cerebral edema was seen. These pathological findings are strongly correlated with neural functional impairments. © 2014 Wiley Periodicals, Inc.

Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on blood pressure and renal function.

PubMed

Nygård, Peder; Jansman, Frank G A; Kruik-Kollöffel, Willemien J; Barnaart, Alex F W; Brouwers, Jacobus R B J

2012-06-01

The combined post-operative use of diuretics and/or renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti-inflammatory drug (NSAID) associated renal failure because of a drug-drug interaction. The aim of this study was to investigate the effect of the short-term (<4 days) post-operative combined use of NSAIDs with diuretics and/or RAAS inhibitors on renal function and blood pressure. One teaching hospital in the Netherlands. The study-design was a prospective, observational cohort-study. Based on postoperative treatment with NSAIDs, the intervention-group was compared to a control-group (no NSAIDs treatment). Systolic blood pressure and renal function expressed by the estimated glomular filtration rate (eGFR) calculated with the modification of renal desease formula. 97 patients were included in the intervention-group, 53 patients in the control-group. Patient characteristics were comparable except for one variable: 'combined use of a diuretic with a RAAS inhibitor' which was higher in the control-group (62 vs. 43 %, p = 0.046). Odds ratio for clinically relevant increase in systolic blood pressure was 0.66 (CI95 % 0.3-1.5). Odds ratio for clinical relevant decrease in renal function was 2.44 (CI95 % 1.1-5.2). On day 4 eGFR of 3 patients in the intervention- and 1 in the control-group was <50 ml/min/1.73 m(2). Odds ratios showed no significant difference of a clinically relevant increase in systolic blood pressure but showed a higher risk for a clinically relevant decrease in renal function in the intervention group. However this decrease resulted in a relevant impaired renal function (<50 ml/min/1.73 m(2)) in only 3 patients in the interventiongroup and 1 patient in the control-group. In the post-operative patient, without preexisting impaired renal function, concurrent diuretics and/or renin-angiotensinaldosterone system inhibitor therapy can be combined with short-term NSAID treatment.

Characterization of Microbiota in Children with Chronic Functional Constipation

PubMed Central

de Meij, Tim G. J.; de Groot, Evelien F. J.; Eck, Anat; Budding, Andries E.; Kneepkens, C. M. Frank; Benninga, Marc A.; van Bodegraven, Adriaan A.; Savelkoul, Paul H. M.

2016-01-01

Objectives Disruption of the intestinal microbiota is considered an etiological factor in pediatric functional constipation. Scientifically based selection of potential beneficial probiotic strains in functional constipation therapy is not feasible due to insufficient knowledge of microbiota composition in affected subjects. The aim of this study was to describe microbial composition and diversity in children with functional constipation, compared to healthy controls. Study Design Fecal samples from 76 children diagnosed with functional constipation according to the Rome III criteria (median age 8.0 years; range 4.2–17.8) were analyzed by IS-pro, a PCR-based microbiota profiling method. Outcome was compared with intestinal microbiota profiles of 61 healthy children (median 8.6 years; range 4.1–17.9). Microbiota dissimilarity was depicted by principal coordinate analysis (PCoA), diversity was calculated by Shannon diversity index. To determine the most discriminative species, cross validated logistic ridge regression was performed. Results Applying total microbiota profiles (all phyla together) or per phylum analysis, no disease-specific separation was observed by PCoA and by calculation of diversity indices. By ridge regression, however, functional constipation and controls could be discriminated with 82% accuracy. Most discriminative species were Bacteroides fragilis, Bacteroides ovatus, Bifidobacterium longum, Parabacteroides species (increased in functional constipation) and Alistipes finegoldii (decreased in functional constipation). Conclusions None of the commonly used unsupervised statistical methods allowed for microbiota-based discrimination of children with functional constipation and controls. By ridge regression, however, both groups could be discriminated with 82% accuracy. Optimization of microbiota-based interventions in constipated children warrants further characterization of microbial signatures linked to clinical subgroups of functional constipation. PMID:27760208

Vitamin B12 intake and status and cognitive function in elderly people.

PubMed

Doets, Esmée L; van Wijngaarden, Janneke P; Szczecińska, Anna; Dullemeijer, Carla; Souverein, Olga W; Dhonukshe-Rutten, Rosalie A M; Cavelaars, Adrienne E J M; van 't Veer, Pieter; Brzozowska, Anna; de Groot, Lisette C P G M

2013-01-01

Current recommendations on vitamin B12 intake vary from 1.4 to 3.0 μg per day and are based on the amount needed for maintenance of hematologic status or on the amount needed to compensate obligatory losses. This systematic review evaluates whether the relation between vitamin B12 intake and cognitive function should be considered for underpinning vitamin B12 recommendations in the future. The authors summarized dose-response evidence from randomized controlled trials and prospective cohort studies on the relation of vitamin B12 intake and status with cognitive function in adults and elderly people. Two randomized controlled trials and 6 cohort studies showed no association or inconsistent associations between vitamin B12 intake and cognitive function. Random-effects meta-analysis showed that serum/plasma vitamin B12 (50 pmol/L) was not associated with risk of dementia (4 cohort studies), global cognition z scores (4 cohort studies), or memory z scores (4 cohort studies). Although dose-response evidence on sensitive markers of vitamin B12 status (methylmalonic acid and holotranscobalamin) was scarce, 4 of 5 cohort studies reported significant associations with risk of dementia, Alzheimer's disease, or global cognition. Current evidence on the relation between vitamin B12 intake or status and cognitive function is not sufficient for consideration in the development of vitamin B12 recommendations. Further studies should consider the selection of sensitive markers of vitamin B12 status. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Bilateral improvements in lower extremity function after unilateral balance training in individuals with chronic ankle instability.

PubMed

Hale, Sheri A; Fergus, Andrea; Axmacher, Rachel; Kiser, Kimberly

2014-01-01

Bilateral improvements in postural control have been reported among individuals with acute lateral ankle sprains and individuals with chronic ankle instability (CAI) when only the unstable ankle is rehabilitated. We do not know if training the stable ankle will improve function on the unstable side. To explore the effects of a unilateral balance-training program on bilateral lower extremity balance and function in individuals with CAI when only the stable limb is trained. Cohort study. University clinical research laboratory. A total of 34 volunteers (8 men, 26 women; age = 24.32 ± 4.95 years, height = 167.01 ± 9.45 cm, mass = 77.54 ± 23.76 kg) with CAI were assigned to the rehabilitation (n = 17) or control (n = 17) group. Of those, 27 (13 rehabilitation group, 14 control group) completed the study. Balance training twice weekly for 4 weeks. Foot and Ankle Disability Index (FADI), FADI Sport (FADI-S), Star Excursion Balance Test, and Balance Error Scoring System. The rehabilitation and control groups differed in changes in FADI-S and Star Excursion Balance Test scores over time. Only the rehabilitation group improved in the FADI-S and in the posteromedial and anterior reaches of the Star Excursion Balance Test. Both groups demonstrated improvements in posterolateral reach; however, the rehabilitation group demonstrated greater improvement than the control group. When the groups were combined, participants reported improvements in FADI and FADI-S scores for the unstable ankle but not the stable ankle. Our data suggest training the stable ankle may result in improvements in balance and lower extremity function in the unstable ankle. This further supports the existence of a centrally mediated mechanism in the development of postural-control deficits after injury, as well as improved postural control after rehabilitation.

Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis

PubMed Central

Hawkins, Charlene; Shaginurova, Guzel; Shelton, D. Auriel; Herazo-Maya, Jose D.; Oswald-Richter, Kyra A.; Young, Anjuli; Celada, Lindsay J.; Kaminski, Naftali; Sevin, Carla

2017-01-01

Investigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results from chronic antigenic stimulation. T cell exhaustion is defined by decreased cytokine production upon TCR activation, decreased proliferation, increased expression of inhibitory cell surface receptors, and increased susceptibility to apoptosis. We characterized sarcoidosis CD4+ T cell immune function in systemic and local environments among subjects undergoing disease progression compared to those experiencing disease resolution. Spontaneous and TCR-stimulated Th1 cytokine expression and proliferation assays were performed in 53 sarcoidosis subjects and 30 healthy controls. PD-1 expression and apoptosis were assessed by flow cytometry. Compared to healthy controls, sarcoidosis CD4+ T cells demonstrated reductions in Th1 cytokine expression, proliferative capacity (p < 0.05), enhanced apoptosis (p < 0.01), and increased PD-1 expression (p < 0.001). BAL-derived CD4+ T cells also demonstrated multiple facets of T cell exhaustion (p < 0.05). Reversal of CD4+ T cell exhaustion was observed in subjects undergoing spontaneous resolution (p < 0.05). Sarcoidosis CD4+ T cells exhibit loss of cellular function during progressive disease that follows the archetype of T cell exhaustion. PMID:29234685

Selective CD28 blockade attenuates CTLA-4–dependent CD8+ memory T cell effector function and prolongs graft survival

PubMed Central

Liu, Danya; Badell, I. Raul; Ford, Mandy L.

2018-01-01

Memory T cells pose a significant problem to successful therapeutic control of unwanted immune responses during autoimmunity and transplantation, as they are differentially controlled by cosignaling receptors such as CD28 and CTLA-4. Treatment with abatacept and belatacept impede CD28 signaling by binding to CD80 and CD86, but they also have the unintended consequence of blocking the ligands for CTLA-4, a process that may inadvertently boost effector responses. Here, we show that a potentially novel anti-CD28 domain antibody (dAb) that selectively blocks CD28 but preserves CTLA-4 coinhibition confers improved allograft survival in sensitized recipients as compared with CTLA-4 Ig. However, both CTLA-4 Ig and anti-CD28 dAb similarly and significantly reduced the accumulation of donor-reactive CD8+ memory T cells, demonstrating that regulation of the expansion of CD8+ memory T cell populations is controlled in part by CD28 signals and is not significantly impacted by CTLA-4. In contrast, selective CD28 blockade was superior to CTLA-4 Ig in inhibiting IFN-γ, TNF, and IL-2 production by CD8+ memory T cells, which in turn resulted in reduced recruitment of innate CD11b+ monocytes into allografts. Importantly, this superiority was CTLA-4 dependent, demonstrating that effector function of CD8+ memory T cells is regulated by the balance of CD28 and CTLA-4 signaling. PMID:29321374

The primacy of primary control is a human universal: a reply to Gould's (1999) critique of the life-span theory of control.

PubMed

Heckhausen, J; Schulz, R

1999-07-01

This reply to S. J. Gould's (1999) critique of J. Heckhausen and R. Schulz's (1995) life-span theory of control addresses four issues: (1) the universal claim that primary control holds functional primacy over secondary control, (2) the status of secondary control as a confederate to primary control, (3) empirical evidence and paradigms for investigating universality and cultural variations, and (4) the capacity of the human control system to manage both gains and losses in control throughout the life span and aging-related decline in particular. Theoretical perspectives and empirical evidence from evolutionary, comparative, developmental, and cultural psychology are presented to support the authors' view that primary control striving holds functional primacy throughout the life span and across cultural and historical settings. Recommendations for empirically investigating the variations in the way primary control striving is expressed in different cultures are outlined.

[Effect of long-term use of albendazole on mice liver].

PubMed

Zheng, Qi; Liu, Cong-Shan; Jiang, Bin; Xu, Li-Li; Zhang, Hao-Bing

2013-06-01

To observe the change in serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), direct bilirubin (DBL), indirect bilirubin (IBIL), albumin (ALB) and globulin (GLB), and mouse liver ultrastructure during 1-16 weeks of albendazole treatment. 180 female Kunming mice were divided randomly into albendazole treatment group and negative control group. Each mouse of albendazole treatment group was treated with 136.3 mg/(kg x d) albendazole. The mice in control group were given same amount of physiological saline. After 1, 2, 4, 6, 8, 10, 12, 14 and 16 weeks of treatment, 10 mice from each group were randomly selected, serum samples were collected and analyzed for the above seven liver function indices. Pathological changes of liver were observed by transmission electron microscopy. Linear regression analysis was conducted for the relationship between liver function indices(dependent variable) and pathological scores (independent variable). During 1-16 weeks of albendazole treatment, there was no significant difference in serum levels of DBL, IBIL, ALB and GLB between albendazole treatment group and control group. Compared with other treatment period, after 12 weeks of treatment the serum levels of ALT (55.2 +/- 23.7), AST(176.4 +/- 49.2) and ALP(141.1 +/- 19.4) in albendazole treatment group were higher than that of the control (35.5 +/- 8.6, 108.2 +/- 21.9, 84.0 +/- 24.8) (P < 0.05). After 2, 8, 10, 12 and 14 weeks of treatment, the pathological score of albendazole treatment group was 11.8 +/- 4.8, 10.6 +/- 4.8, 13.6 +/- 3.5, 29.8 +/- 10.7, and 5.6 +/- 2.5, respectively, which was higher than that of the control (0.8 +/- 0.4, 1.2 +/- 0.8, 2.4 +/- 2.0, 1.2 +/- 0.4, 1.4 +/- 1.1) (P < 0.05). Among the three liver function indices AST, ALT and ALP, AST was the best fit index for linear regression. The regression formula was Y = -17.616 + 0.188X. Long-term treatment with albendazole at a dosage of 136.3 mg/(kg x d) for mice can cause significant elevation of serum levels of ALT, AST and ALP, and result in mild pathological changes in the liver.

A CMOS current-mode log(x) and log(1/x) functions generator

NASA Astrophysics Data System (ADS)

Al-Absi, Munir A.; Al-Tamimi, Karama M.

2014-08-01

A novel Complementary Metal Oxide Semiconductor (CMOS) current-mode low-voltage and low-power controllable logarithmic function circuit is presented. The proposed design utilises one Operational Transconductance Amplifier (OTA) and two PMOS transistors biased in weak inversion region. The proposed design provides high dynamic range, controllable amplitude, high accuracy and is insensitive to temperature variations. The circuit operates on a ±0.6 V power supply and consumes 0.3 μW. The functionality of the proposed circuit was verified using HSPICE with 0.35 μm 2P4M CMOS process technology.

Comprehensive approach to study complement C4 in systemic lupus erythematosus: Gene polymorphisms, protein levels and functional activity.

PubMed

Tsang-A-Sjoe, M W P; Bultink, I E M; Korswagen, L A; van der Horst, A; Rensink, I; de Boer, M; Hamann, D; Voskuyl, A E; Wouters, D

2017-12-01

Genetic variation of the genes encoding complement component C4 is strongly associated with systemic lupus erythematosus (SLE), a chronic multi-organ auto-immune disease. This study examined C4 and its isotypes on a genetic, protein, and functional level in 140 SLE patients and 104 healthy controls. Gene copy number (GCN) variation, silencing CT-insertion, and the retroviral HERV-K(C4) insertion) were analyzed with multiplex ligation-dependent probe amplification. Increased susceptibility to SLE was found for low GCN (≪2) of C4A. Serositis was the only clinical manifestation associated with low C4A GCN. One additional novel silencing mutation in the C4A gene was found by Sanger sequencing. This mutation causes a premature stop codon in exon 11. Protein concentrations of C4 isoforms C4A and C4B were determined with ELISA and were significantly lower in SLE patients compared to healthy controls. To study C4 isotypes on a functional level, a new C4 assay was developed, which distinguishes C4A from C4B by its binding capacity to amino or hydroxyl groups, respectively. This assay showed high correlation with ELISA and detected crossing over of Rodgers and Chido antigens in 3.2% (8/244) of individuals. The binding capacity of available C4 to its substrates was unaffected in SLE. Our study provides, for the first time, a complete overview of C4 in SLE from genetic variation to binding capacity using a novel test. As this test detects crossing over of Rodgers and Chido antigens, it will allow for more accurate measurement of C4 in future studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Opioid maintenance therapy restores CD4+ T cell function by normalizing CD4+CD25(high) regulatory T cell frequencies in heroin user.

PubMed

Riss, Gina-Lucia; Chang, Dae-In; Wevers, Carolin; Westendorf, Astrid M; Buer, Jan; Scherbaum, Norbert; Hansen, Wiebke

2012-08-01

There is an increasing body of evidence that heroin addiction is associated with severe alterations in immune function, which might contribute to an increased risk to contract infectious diseases like hepatitis B and C or HIV. However, the impact of heroin consumption on the CD4(+) T cell compartment is not well understood. Therefore, we analyzed the frequency and functional phenotype of CD4(+) T cells as well as immune-suppressive CD4(+)CD25(high) regulatory T cells (Tregs) isolated from the peripheral blood of opiate addicts currently abusing heroin (n=27) in comparison to healthy controls (n=25) and opiate addicts currently in opioid maintenance treatment (OMT; n=27). Interestingly, we detected a significant increase in the percentage of CD4(+)CD25(high) Tregs in the peripheral blood of heroin addicted patients in contrast to patients in OMT. The proliferative response of CD4(+) T cells upon stimulation with anti-CD3 and anti-CD28 antibodies was significantly decreased in heroin users, but could be restored by depletion of CD25(high) regulatory T cells from CD4(+) T cells to similar values as observed from healthy controls and patients in OMT. These results suggest that impaired immune responses observed in heroin users are related to the expansion of CD4(+)CD25(high) Tregs and more importantly, can be restored by OMT. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of subclinical infantile thiamine deficiency on motor function in preschool children.

PubMed

Harel, Yael; Zuk, Luba; Guindy, Michal; Nakar, Orly; Lotan, Dafna; Fattal-Valevski, Aviva

2017-10-01

We investigated the long-term implications of infantile thiamine (vitamin B1) deficiency on motor function in preschoolers who had been fed during the first 2 years of life with a faulty milk substitute. In this retrospective cohort study, 39 children aged 5-6 years who had been exposed to a thiamine-deficient formula during infancy were compared with 30 age-matched healthy children with unremarkable infant nutritional history. The motor function of the participants was evaluated with The Movement Assessment Battery for Children (M-ABC) and the Zuk Assessment. Both evaluation tools revealed statistically significant differences between the exposed and unexposed groups for gross and fine motor development (p < .001, ball skills p = .01) and grapho-motor development (p = .004). The differences were especially noteworthy on M-ABC testing for balance control functioning (p < .001, OR 5.4; 95% CI 3.4-7.4) and fine motor skills (p < .001, OR 3.2; 95% CI 1.8-4.6). In the exposed group, both assessments concurred on the high rate of children exhibiting motor function difficulties in comparison to unexposed group (M-ABC: 56% vs. 10%, Zuk Assessment: 59% vs. 3%, p < .001). Thiamine deficiency in infancy has long-term implications on gross and fine motor function and balance skills in childhood, thiamine having a crucial role in normal motor development. The study emphasizes the importance of proper infant feeding and regulatory control of breast milk substitutes. © 2017 John Wiley & Sons Ltd.

Long-term myocardial preservation: effects of hyperkalemia, sodium channel, and Na/K/2Cl cotransport inhibition on extracellular potassium accumulation during hypothermic storage.

PubMed

Snabaitis, A K; Shattock, M J; Chambers, D J

1999-07-01

We previously demonstrated improved myocardial preservation with polarized (tetrodotoxin-induced), compared with depolarized (hyperkalemia-induced), arrest and hypothermic storage. This study was undertaken to determine whether polarized arrest reduced ionic imbalance during ischemic storage and whether this was influenced by Na+/K +/2Cl- cotransport inhibition. We used the isolated crystalloid perfused working rat heart preparation (1) to measure extracellular K+ accumulation (using a K+-sensitive intramyocardial electrode) during ischemic (control), depolarized (K+ 16 mmol/L), and polarized (tetrodotoxin, 22 micromol/L) arrest and hypothermic (7.5 degrees C) storage (5 hours), (2) to determine dose-dependent (0.1, 1.0, 10 and 100 micromol/L) effects of the Na +/K+/2Cl- cotransport inhibitor, furosemide, on extracellular K+ accumulation during polarized arrest and 7.5 degrees C storage, and (3) to correlate extracellular K+ accumulation to postischemic recovery of cardiac function. Characteristic triphasic profiles of extracellular K+ accumulation were observed in control and depolarized arrested hearts; a significantly attenuated profile with polarized arrested hearts demonstrated reduced extracellular K+ accumulation, correlating with higher postischemic function (recovery of aortic flow was 54% +/-4% [P =.01] compared with 39% +/-3% and 32% +/-3% in depolarized and control hearts, respectively). Furosemide (0.1, 1.0, 10, and 100 micromol/L) modified extracellular K+ accumulation by -18%, -38%, -0.2%, and +9%, respectively, after 30 minutes and by -4%, -27%, +31%, and +42%, respectively, after 5 hours of polarized storage. Recovery of aortic flow was 53% +/-4% (polarized arrest alone), 56% +/-8%, 70% +/-2% (P =.04 vs control), 69% +/-4% (P =.04 vs control), and 65% +/-3% ( P =. 04 vs control), respectively. Polarized arrest was associated with a reduced ionic imbalance (demonstrated by reduced extracellular K+ accumulation) and improved recovery of cardiac function. Further attenuation of extracellular K + accumulation (by furosemide) resulted in additional recovery.

Thalamic Functional Connectivity in Mild Traumatic Brain Injury: Longitudinal Associations With Patient-Reported Outcomes and Neuropsychological Tests.

PubMed

Banks, Sarah D; Coronado, Rogelio A; Clemons, Lori R; Abraham, Christine M; Pruthi, Sumit; Conrad, Benjamin N; Morgan, Victoria L; Guillamondegui, Oscar D; Archer, Kristin R

2016-08-01

(1) To examine differences in patient-reported outcomes, neuropsychological tests, and thalamic functional connectivity (FC) between patients with mild traumatic brain injury (mTBI) and individuals without mTBI and (2) to determine longitudinal associations between changes in these measures. Prospective observational case-control study. Academic medical center. A sample (N=24) of 13 patients with mTBI (mean age, 39.3±14.0y; 4 women [31%]) and 11 age- and sex-matched controls without mTBI (mean age, 37.6±13.3y; 4 women [36%]). Not applicable. Resting state FC (3T magnetic resonance imaging scanner) was examined between the thalamus and the default mode network, dorsal attention network, and frontoparietal control network. Patient-reported outcomes included pain (Brief Pain Inventory), depressive symptoms (Patient Health Questionnaire-9), posttraumatic stress disorder ([PTSD] Checklist - Civilian Version), and postconcussive symptoms (Rivermead Post-Concussion Symptoms Questionnaire). Neuropsychological tests included the Delis-Kaplan Executive Function System Tower test, Trails B, and Hotel Task. Assessments occurred at 6 weeks and 4 months after hospitalization in patients with mTBI and at a single visit for controls. Student t tests found increased pain, depressive symptoms, PTSD symptoms, and postconcussive symptoms; decreased performance on Trails B; increased FC between the thalamus and the default mode network; and decreased FC between the thalamus and the dorsal attention network and between the thalamus and the frontoparietal control network in patients with mTBI as compared with controls. The Spearman correlation coefficient indicated that increased FC between the thalamus and the dorsal attention network from baseline to 4 months was associated with decreased pain and postconcussive symptoms (corrected P<.05). Findings suggest that alterations in thalamic FC occur after mTBI, and improvements in pain and postconcussive symptoms are correlated with normalization of thalamic FC over time. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Immune functions of the garment workers.

PubMed

Sultana, R; Ferdous, K J; Hossain, M; Zahid, M S H; Islam, L N

2012-10-01

Occupational exposure to cotton dust, fibers, metal fumes and different chemicals used in the aparrel manufacturing industries cause a wide range of physical and psychological health problems in the garment workers that may also affect their immune function. To assess the immune system function in garment workers. A total of 45 workers of a garment factory, and 41 control subjects, not exposed to the garment working environment were enrolled in this study. In the study subjects, the complement system function was assessed as bactericidal activity on Escherichia coli DH5α cells using the standard plate count method. Serum complement components C3 and C4 were measured by immunoprecipitation, and IgG was measured by immunonephelometry. The bactericidal activity of serum complement in the garment workers (range: 93.5%-99.9%) was significantly (p<0.01) lower than that in the controls (range: 98.6%-100%). The heat-inactivated serum of the workers showed a significantly enhanced bactericidal activity. In the garment workers, the mean levels of complement C3, and C4 were 1.75 and 0.26 g/L, respectively that were close to those of the controls. The mean IgG level in the garment workers was 13.5 g/L that was significantly (p<0.001) higher than that in the controls. Working in a garment factory may affect the immune system.

The protocol and design of a randomised controlled study on training of attention within the first year after acquired brain injury.

PubMed

Bartfai, Aniko; Markovic, Gabriela; Sargenius Landahl, Kristina; Schult, Marie-Louise

2014-05-08

To describe the design of the study aiming to examine intensive targeted cognitive rehabilitation of attention in the acute (<4 months) and subacute rehabilitation phases (4-12 months) after acquired brain injury and to evaluate the effects on function, activity and participation (return to work). Within a prospective, randomised, controlled study 120 consecutive patients with stroke or traumatic brain injury were randomised to 20 hours of intensive attention training by Attention Process Training or by standard, activity based training. Progress was evaluated by Statistical Process Control and by pre and post measurement of functional and activity levels. Return to work was also evaluated in the post-acute phase. Primary endpoints were the changes in the attention measure, Paced Auditory Serial Addition Test and changes in work ability. Secondary endpoints included measurement of cognitive functions, activity and work return. There were 3, 6 and 12-month follow ups focussing on health economics. The study will provide information on rehabilitation of attention in the early phases after ABI; effects on function, activity and return to work. Further, the application of Statistical Process Control might enable closer investigation of the cognitive changes after acquired brain injury and demonstrate the usefulness of process measures in rehabilitation. The study was registered at ClinicalTrials.gov Protocol. NCT02091453, registered: 19 March 2014.

Contractile properties of rat skeletal muscles following storage at 4 degrees C.

PubMed

van der Heijden, E P; Kroese, A B; Stremel, R W; Bär, P R; Kon, M; Werker, P M

1999-07-01

The purpose of this study was to assess the potential of preservation solutions for protecting skeletal muscle function during storage at 4 degrees C. The soleus and the cutaneus trunci (CT) from the rat were stored for 2, 8 or 16 h at 4 degrees C in University of Wisconsin solution (UW), HTK-Bretschneider solution (HTK) or Krebs-Henseleit solution (KH). After storage, muscles were stimulated electrically to analyse the isometric contractile properties, such as the maximum tetanic tension (P(0)). Histological analysis was also performed. In separate experiments, the effect of the diffusion distance on muscle preservation was studied by bisecting the soleus. After 8 h of storage in UW or HTK, the contractile properties of the CT were similar to those of the control, whereas those of the soleus were reduced (P(0) values of 16% and 69% of control in UW and HTK respectively). At 16 h, the contractile properties of the CT (P(O) 28%) were again better preserved than those of the soleus (P(0) 9%). Muscle function deteriorated most after storage in KH (P(0) at 16 h: soleus, 3%; CT, 17%). The bisected soleus was equally well preserved as the CT (P(O) of bisected soleus at 8 h in UW and HTK: 86%). The functional data corresponded well with the histological data, which showed increasing muscle fibre derangement with increasing storage time. For both muscles and all solutions, the threshold stimulus current increased with increasing storage time (control, 0.1 mA; 16 h, 1.2 mA) and was strongly correlated with the deterioration in contractile properties. It is concluded that, at 4 degrees C, muscle is preserved better in UW and HTK (intracellular-like solutions) than in KH (extracellular-like solution). The soleus and CT were best protected in HTK. The diffusion distance is a critical factor for successful preservation of muscle function at 4 degrees C. The reduced function after 16 h of storage at 4 degrees C was caused by hypercontraction and necrosis of about 25% of the muscle fibres, and by deterioration of the electrical component of excitation-contraction coupling of the remaining fibres.

Impact of HIV Infection on Diastolic Function and Left Ventricular Mass

PubMed Central

Hsue, Priscilla Y.; Hunt, Peter W.; Ho, Jennifer E.; Farah, Husam H.; Schnell, Amanda; Hoh, Rebecca; Martin, Jeffrey N.; Deeks, Steven G.; Bolger, Ann F.

2010-01-01

Background HIV patients have increased risk for cardiovascular disease, but the underlying mechanisms remain unknown. The purpose of this study was to determine the prevalence of echocardiographic abnormalities among asymptomatic HIV-infected individuals compared to HIV-uninfected individuals. Methods/Results We performed echocardiography in 196 HIV-infected adults and 52 controls. Left ventricular ejection fraction (LVEF), left ventricular mass indexed to the body surface area (LVMI), and diastolic function were assessed according to American Society of Echocardiography standards. LVMI was higher in HIV-infected patients (77.2g/m2 in HIV patients vs. 66.5g/m2 in controls, p<0.0001). LVEF was similar in both groups. Eight(4%) of the HIV patients had evidence of LV systolic dysfunction (defined as an EF<50%) versus none of the controls; 97(50%) had mild diastolic dysfunction compared to 29% of the HIV-uninfected subjects (p=0.008). After adjustment for hypertension and race, HIV-infected participants had a mean 8g/m2 larger LVMI compared to controls (p=0.001). Higher LVMI was independently associated with lower nadir CD4 T cell count, suggesting that immunodeficiency may play a role in this process. After adjustment for age and traditional risk factors, HIV patients had a 2.4 greater odds of having diastolic dysfunction as compared to controls (p=0.019). Conclusions HIV-infected patients had a higher prevalence of diastolic dysfunction and higher LVMI compared to controls. These differences were not readily explained by differences in traditional risk factors and were independently associated with HIV infection. These results suggest that contemporary asymptomatic HIV patients manifest mild functional and morphological cardiac abnormalities which are independently associated with HIV infection. PMID:19933410

Impact of early postoperative enteral nutrition on clinical outcomes in patients with gastric cancer.

PubMed

Li, B; Liu, H Y; Guo, S H; Sun, P; Gong, F M; Jia, B Q

2015-06-29

The impact of early enteral nutrition (EEN) on clinical outcomes of gastric cancer patients was investigated. Three hundred pa-tients undergoing gastric cancer surgery from July 2010 to May 2014 were randomly divided into experimental and control groups (n = 150/group). Experimental group patients received enteral nutrition in water during the early postoperative period. Control group patients received conventional perioperative treatment. Patients' clinical outcomes, post-operative immune function, and nutritional statuses were compared, which revealed that the postoperative fever duration (80.2 ± 6.0 vs 88.1 ± 8.1 h, P < 0.05), anal exhaust time (78.8 ± 9.3 vs 85.3 ± 8.4 h, P < 0.05), and length of hospitalization (7.73 ± 2.13 vs 9.77 ± 1.76 days, P < 0.01) differed significantly. Treatment costs in thousands of dol-lars were 31.24 ± 3.21 for the experimental group and 35.61 ± 2.32 for the control group; this difference was statistically significant (P < 0.01). The incidence of postoperative complications did not significantly differ between the experimental and control groups [14.0% (21/150) vs 17.3% (26/150), P > 0.05]. At postoperative days 3 and 7, the CD3(+), CD4(+), natural killer cell, albumin, and prealbumin levels and CD4(+)/CD8(+) ra-tio were significantly higher in the experimental group than the control group (all P < 0.05). CD8(+) cell counts were significantly lower in the experimental group than the control group (P < 0.05). Postsurgical oral EEN can improve nutritional status and immune function and promote early recovery of intestinal function in patients with gastric cancer.

The prevalence of affective disorder and in particular of a rapid cycling of bipolar disorder in patients with abnormal thyroid function tests.

PubMed

Oomen, H A; Schipperijn, A J; Drexhage, H A

1996-08-01

Cognitive and affective functioning is sensitive to changes in thyroid hormones. We have sought to determine: (1) the prevalence of thyroid function abnormalities in a psychiatric population on admission (as compared to the prevalence in a normal population), and (2) whether such thyroid function abnormalities are associated with the occurrence or development of cognitive and affective disorders. Serum was collected 2-3 weeks after hospitalization in 3 major clinics from 3756 psychiatric patients in 1987-1990, stored, and assayed in 1993 for the presence of antibodies against the TSH-receptor and thyroperoxidase (TPO-Ab) and for TSH levels. The psychiatric cohort was matched with a control population of healthy individuals living in the same area (n = 1877). The prevalence study was followed by a case-control study involving patients from one clinic that had routinely assigned a DSM-IIIR classification to its patients. Cases were those admissions with thyroid abnormalities and three subgroups of cases were randomly formed demonstrating either TSH less than 0.4 mU/l (n = 44) or over 4.0 mU/l (n = 44), or TPO-Ab positivity (n = 50). Cases were compared to random controls from the same psychiatric population, viz patients without thyroid abnormalities (n = 83). Comparison was with respect to their psychiatric follow-up diagnosis (the investigator was blinded to the thyroid test results). Prevalence study. The percentage of patients positive for TSH-receptor-Ab was 0.26 (9/3504), for TPO-Ab was 10.0 (331/3316) and outside the TSH range of 0.4-4.0 mU/l was 10.0 ((332/3316): 5.9% (198/3316) > 4.0 mU/l and 4.1% (134/3316) < 0.4 mU/l). Abnormal total thyroxine levels were found in only 9.8% of subjects with abnormal TSH, indicating the predominantly subclinical character of the thyroid alteration. In comparison, the healthy area controls over 55 years of age showed the same prevalence of positive TPO-antibodies and TSH under 0.4 mU/l, but a higher prevalence of TSH over 4.0 mU/l. CASE-CONTROL STUDY: In the case control analysis differences could not be noticed with regard to prevalences of dementia, schizophrenia or other psychiatric illnesses apart from the prevalence of affective disorders which were more prevalent in TPO-Ab positive patients and patients with a low serum TSH. Since prior use of lithium, carbamezapine, carbimazole and/or thyroxine could be a factor of importance in this association, analyses were also carried out excluding patients with such prior drug use. In these analyses affective disorders were still more prevalent in patients with a low serum TSH (particularly in males, 40% in cases vs 9% in controls, P < 0.05). The most significant association was however between TPO-antibody positivity (and in particular with high titre and/or with TSH > 4.0 mU/l) and a subgroup of the affective disorders, viz with a rapid cycling of bipolar disorder (18% in cases vs 0% in controls, P < 0.001). Though causal relations cannot be determined from this cross-sectional study, this admission survey found early forms of autoimmune thyroid disease, sometimes characterized only by TPO-Abs, highly significantly associated with rapid cycles of a bipolar disorder. It also found a weak association between subclinical hyperthyroidism (low serum TSH without TPO-Ab positivity) and affective disorder.

Gastric secretory function in coeliac disease.

PubMed

Marcello, U; Deganello, A; Consolaro, G; Zoppi, G

1979-01-18

Volume, total titrable acidity, total proteolytic activity and pepsin activity have been determined in 14 coeliac patients and in 8 controls of comparable ages and body weights. Basal secretion (B.O.), total outputs (T. O.) and peak outputs (P.O.) after pentagastrin injection have been determined. Peak outputs (values 60 min/kg) of these parameters are as follows: volume 5.0+/-1.7 ml in coeliacs, 4.3+/-1.2 ml in controls; total titrable acidity 406.1+/-155.0 mEq in patients, 296.1+/-182.4 in conttrols; total proteolytic activity 962.1+/-501.1 micronEq in coeliacs, 569.6+/-272.2 in controls; pepsin activity 789.1+/-521.8 micronEq in patients, 447.6+/-150.4 in controls.

Percentage and function of CD4+CD25+ regulatory T cells in patients with hyperthyroidism

PubMed Central

Jiang, Ting-Jun; Cao, Xue-Liang; Luan, Sha; Cui, Wan-Hui; Qiu, Si-Huang; Wang, Yi-Chao; Zhao, Chang-Jiu; Fu, Peng

2018-01-01

The current study observed the percentage of peripheral blood (PB) CD4+CD25+ regulatory T cells (Tregs) and the influence of CD4+CD25+ Tregs on the proliferation of naïve CD4 T cells in patients with hyperthyroidism. Furthermore, preliminary discussions are presented on the action mechanism of CD4+CD25+ Tregs on hyperthyroidism attacks. The present study identified that compared with the percentage of PB CD4+CD25+ Tregs in healthy control subjects, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism (P>0.05). For patients with hyperthyroidism, CD4+CD25+ Tregs exhibited significantly reduced inhibition of the proliferation of naïve CD4 T cells and decreased secretion capacity on the cytokines of CD4 T cells, compared with those of healthy control subjects (P<0.05). In addition, it was demonstrated that thyroid function of patients with hyperthyroidism was significantly improved (P<0.05) subsequent to receiving medication. Compared with the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism before treatment, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in hyperthyroidism patients following treatment (P>0.05). In the patients with hyperthyroidism, following treatment, CD4+CD25+ Tregs exhibited significantly increased inhibition of the proliferation of naïve CD4 T cells and increased secretion capacity of CD4 T cell cytokines, compared with those of the patients with hyperthyroidism prior to treatment (P<0.05). PB CD4+CD25+ Tregs function was decreased in patients with hyperthyroidism, and its non-proportional decrease may be closely associated with the occurrence and progression of hyperthyroidism. PMID:29207121

Arabidopsis HD-Zip II transcription factors control apical embryo development and meristem function.

PubMed

Turchi, Luana; Carabelli, Monica; Ruzza, Valentino; Possenti, Marco; Sassi, Massimiliano; Peñalosa, Andrés; Sessa, Giovanna; Salvi, Sergio; Forte, Valentina; Morelli, Giorgio; Ruberti, Ida

2013-05-01

The Arabidopsis genome encodes ten Homeodomain-Leucine zipper (HD-Zip) II proteins. ARABIDOPSIS THALIANA HOMEOBOX 2 (ATHB2), HOMEOBOX ARABIDOPSIS THALIANA 1 (HAT1), HAT2, HAT3 and ATHB4 are regulated by changes in the red/far red light ratio that induce shade avoidance in most of the angiosperms. Here, we show that progressive loss of HAT3, ATHB4 and ATHB2 activity causes developmental defects from embryogenesis onwards in white light. Cotyledon development and number are altered in hat3 athb4 embryos, and these defects correlate with changes in auxin distribution and response. athb2 gain-of-function mutation and ATHB2 expression driven by its promoter in hat3 athb4 result in significant attenuation of phenotypes, thus demonstrating that ATHB2 is functionally redundant to HAT3 and ATHB4. In analogy to loss-of-function mutations in HD-Zip III genes, loss of HAT3 and ATHB4 results in organ polarity defects, whereas triple hat3 athb4 athb2 mutants develop one or two radialized cotyledons and lack an active shoot apical meristem (SAM). Consistent with overlapping expression pattern of HD-Zip II and HD-Zip III gene family members, bilateral symmetry and SAM defects are enhanced when hat3 athb4 is combined with mutations in PHABULOSA (PHB), PHAVOLUTA (PHV) or REVOLUTA (REV). Finally, we show that ATHB2 is part of a complex regulatory circuit directly involving both HD-Zip II and HD-Zip III proteins. Taken together, our study provides evidence that a genetic system consisting of HD-Zip II and HD-Zip III genes cooperates in establishing bilateral symmetry and patterning along the adaxial-abaxial axis in the embryo as well as in controlling SAM activity.

[The randomized controlled trial of the treatment for clavicular fracture by rotatory manual reduction with forceps holder and retrograde percutaneous pinning transfixation].

PubMed

Bi, Hong-zheng; Yang, Mao-qing; Tan, Yuan-chao; Fu, Song

2008-07-01

To study the curative effect and safety of rotatory manual reduction with forceps holder and retrograde percutaneous pinning transfixation in treating clavicular fracture. All 201 cases of clavicular fractures were randomly divided into treatment group (101 cases) and control group (100 cases). The treatment group was treated by rotatory manual reduction with forceps holder and retrograde percutaneous pinning transfixation. The control group was treated by open reduction and internal fixation with Kirschner pin. All cases were followed up for 4 to 21 months (mean 10.6 months). SPSS was used to analyze clinic healing time of fracture and shoulder-joint function in both two groups. After operation, 101 cases of treatment group achieved union of fracture and the clinical healing time was 28 to 49 days (mean 34.5+/-2.7 days). In control group,there were 4 cases with nonunion of fracture,the other 96 cases were union,the clinical healing time was 36 to 92 days (mean 55.3+/-4.8 days). The excellent and good rate of shoulder-joint function was 100% in treatment group and 83% in control group. By t-test and chi2-test, there was significant difference between the two groups in curative effect (P<0.05). Rotatory manual reduction with forceps holder and retrograde pinning transfixation can be used in various kinds of clavicular shaft fracture, with many virtues such as easy operation, reliable fixation, short union time of fracture, good functional recovery of shoulder-joint and no incision scar affecting appearance.

Role of SDF‐1:CXCR4 in Impaired Post‐Myocardial Infarction Cardiac Repair in Diabetes

PubMed Central

Mayorga, Maritza E.; Kiedrowski, Matthew; McCallinhart, Patricia; Forudi, Farhad; Ockunzzi, Jeremiah; Weber, Kristal; Chilian, William; Penn, Marc S.

2017-01-01

Abstract Diabetes is a risk factor for worse outcomes following acute myocardial infarction (AMI). In this study, we tested the hypothesis that SDF‐1:CXCR4 expression is compromised in post‐AMI in diabetes, and that reversal of this defect can reverse the adverse effects of diabetes. Mesenchymal stem cells (MSC) isolated from green fluorescent protein (GFP) transgenic mice (control MSC) were induced to overexpress stromal cell‐derived factor‐1 (SDF‐1). SDF‐1 expression in control MSC and SDF‐1‐overexpressing MSC (SDF‐1:MSC) were quantified using enzyme‐linked immunosorbent assay (ELISA). AMI was induced on db/db and control mice. Mice were randomly selected to receive infusion of control MSC, SDF‐1:MSC, or saline into the border zone after AMI. Serial echocardiography was used to assess cardiac function. SDF‐1 and CXCR4 mRNA expression in the infarct zone of db/db mice and control mice were quantified. Compared to control mice, SDF‐1 levels were decreased 82%, 91%, and 45% at baseline, 1 day and 3 days post‐AMI in db/db mice, respectively. CXCR4 levels are increased 233% at baseline and 54% 5 days post‐AMI in db/db mice. Administration of control MSC led to a significant improvement in ejection fraction (EF) in control mice but not in db/db mice 21 days after AMI. In contrast, administration of SDF‐1:MSC produced a significant improvement in EF in both control mice and db/db mice 21 days after AMI. The SDF‐1:CXCR4 axis is compromised in diabetes, which appears to augment the deleterious consequences of AMI. Over‐express of SDF‐1 expression in diabetes rescues cardiac function post AMI. Our results suggest that modulation of SDF‐1 may improve post‐AMI cardiac repair in diabetes. stem cells translational medicine 2018;7:115–124 PMID:29119710

Muscle, functional and cognitive adaptations after flywheel resistance training in stroke patients: a pilot randomized controlled trial.

PubMed

Fernandez-Gonzalo, Rodrigo; Fernandez-Gonzalo, Sol; Turon, Marc; Prieto, Cristina; Tesch, Per A; García-Carreira, Maria del Carmen

2016-04-06

Resistance exercise (RE) improves neuromuscular function and physical performance after stroke. Yet, the effects of RE emphasizing eccentric (ECC; lengthening) actions on muscle hypertrophy and cognitive function in stroke patients are currently unknown. Thus, this study explored the effects of ECC-overload RE training on skeletal muscle size and function, and cognitive performance in individuals with stroke. Thirty-two individuals with chronic stroke (≥6 months post-stroke) were randomly assigned into a training group (TG; n = 16) performing ECC-overload flywheel RE of the more-affected lower limb (12 weeks, 2 times/week; 4 sets of 7 maximal closed-chain knee extensions; <2 min of contractile activity per session) or a control group (CG; n = 16), maintaining daily routines. Before and after the intervention, quadriceps femoris volume, maximal force and power for each leg were assessed, and functional and dual task performance, and cognitive functions were measured. Quadriceps femoris volume of the more-affected leg increased by 9.4 % in TG. Muscle power of the more-affected, trained (48.2 %), and the less-affected, untrained limb (28.1 %) increased after training. TG showed enhanced balance (8.9 %), gait performance (10.6 %), dual-task performance, executive functions (working memory, verbal fluency tasks), attention, and speed of information processing. CG showed no changes. ECC-overload flywheel resistance exercise comprising 4 min of contractile activity per week offers a powerful aid to regain muscle mass and function, and functional performance in individuals with stroke. While the current intervention improved cognitive functions, the cause-effect relationship, if any, with the concomitant neuromuscular adaptations remains to be explored. Clinical Trials NCT02120846.

A randomized, controlled trial of aerobic exercise for treatment-related fatigue in men receiving radical external beam radiotherapy for localized prostate carcinoma.

PubMed

Windsor, Phyllis M; Nicol, Kathleen F; Potter, Joan

2004-08-01

Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental. Aerobic walking improves physical functioning and has been an intervention for chemotherapy-related fatigue. A prospective, randomized, controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma. Sixty-six men were randomized before they received radical radiotherapy for localized prostate carcinoma, with 33 men randomized to an exercise group and 33 men randomized to a control group. Outcome measures were fatigue and distance walked in a modified shuttle test before and after radiotherapy. There were no significant between group differences noted with regard to fatigue scores at baseline (P = 0.55) or after 4 weeks of radiotherapy (P = 0.18). Men in the control group had significant increases in fatigue scores from baseline to the end of radiotherapy (P = 0.013), with no significant increases observed in the exercise group (P = 0.203). A nonsignificant reduction (2.4%) in shuttle test distance at the end of radiotherapy was observed in the control group; however, in the exercise group, there was a significant increase (13.2%) in distance walked (P = 0.0003). Men who followed advice to rest and take things easy if they became fatigued demonstrated a slight deterioration in physical functioning and a significant increase in fatigue at the end of radiotherapy. Home-based, moderate-intensity walking produced a significant improvement in physical functioning with no significant increase in fatigue. Improved physical functioning may be necessary to combat radiation fatigue.

Effects of Trypanocidal Drugs on the Function of Trypanosomes.

DTIC Science & Technology

1978-09-01

trtod) -Odr__primary results during this past year are: a. 7 tbihdtosriso rpnooabue T rciETO10 n T. brucel 427) in vitro as cultured infective...A 174 .I A -V. A, A’ ~ ~ hA 4 T. brucel 0--a BERENIL TRE:ATEO, 5 mg/kg 0-4 CONTROL 20.0- 10.0: 8.0- 4 .0- 0 I- 1.0 - HOURS Figure 22 t7 d **VI Figure...URIDINE INCORPORATION 14- 12- CONTROL 0 E I- I- ETHIDIUM O BROMIDE 4 6 ANTRYCIDE 2 BERENIL SURAMIN 0 10 20 30 40 50 60 MINUTES Figure 29 T. brucel

Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: a study of the effects of zinc deficiency during lactation.

PubMed

Hashimoto, Ayako; Nakagawa, Miki; Tsujimura, Natsuki; Miyazaki, Shiho; Kizu, Kumiko; Goto, Tomoko; Komatsu, Yusuke; Matsunaga, Ayu; Shirakawa, Hitoshi; Narita, Hiroshi; Kambe, Taiho; Komai, Michio

2016-03-01

Systemic and cellular zinc homeostasis is elaborately controlled by ZIP and ZnT zinc transporters. Therefore, detailed characterization of their expression properties is of importance. Of these transporter proteins, Zip4 functions as the primarily important transporter to control systemic zinc homeostasis because of its indispensable function of zinc absorption in the small intestine. In this study, we closely investigated Zip4 protein accumulation in the rat small intestine in response to zinc status using an anti-Zip4 monoclonal antibody that we generated and contrasted this with the zinc-responsive activity of the membrane-bound alkaline phosphatase (ALP). We found that Zip4 accumulation is more rapid in response to zinc deficiency than previously thought. Accumulation increased in the jejunum as early as 1 day following a zinc-deficient diet. In the small intestine, Zip4 protein expression was higher in the jejunum than in the duodenum and was accompanied by reduction of ALP activity, suggesting that the jejunum can become zinc deficient more easily. Furthermore, by monitoring Zip4 accumulation levels and ALP activity in the duodenum and jejunum, we reasserted that zinc deficiency during lactation may transiently alter plasma glucose levels in the offspring in a sex-specific manner, without affecting homeostatic control of zinc metabolism. This confirms that zinc nutrition during lactation is extremely important for the health of the offspring. These results reveal that rapid Zip4 accumulation provides a significant conceptual advance in understanding the molecular basis of systemic zinc homeostatic control, and that properties of Zip4 protein accumulation are useful to evaluate zinc status closely. Copyright © 2016 the American Physiological Society.

Palmitoylation of the β4-Subunit Regulates Surface Expression of Large Conductance Calcium-activated Potassium Channel Splice Variants*

PubMed Central

Chen, Lie; Bi, Danlei; Tian, Lijun; McClafferty, Heather; Steeb, Franziska; Ruth, Peter; Knaus, Hans Guenther; Shipston, Michael J.

2013-01-01

Regulatory β-subunits of large conductance calcium- and voltage-activated potassium (BK) channels play an important role in generating functional diversity and control of cell surface expression of the pore forming α-subunits. However, in contrast to α-subunits, the role of reversible post-translational modification of intracellular residues on β-subunit function is largely unknown. Here we demonstrate that the human β4-subunit is S-acylated (palmitoylated) on a juxtamembrane cysteine residue (Cys-193) in the intracellular C terminus of the regulatory β-subunit. β4-Subunit palmitoylation is important for cell surface expression and endoplasmic reticulum (ER) exit of the β4-subunit alone. Importantly, palmitoylated β4-subunits promote the ER exit and surface expression of the pore-forming α-subunit, whereas β4-subunits that cannot be palmitoylated do not increase ER exit or surface expression of α-subunits. Strikingly, however, this palmitoylation- and β4-dependent enhancement of α-subunit surface expression was only observed in α-subunits that contain a putative trafficking motif (… REVEDEC) at the very C terminus of the α-subunit. Engineering this trafficking motif to other C-terminal α-subunit splice variants results in α-subunits with reduced surface expression that can be rescued by palmitoylated, but not depalmitoylated, β4-subunits. Our data reveal a novel mechanism by which palmitoylated β4-subunit controls surface expression of BK channels through masking of a trafficking motif in the C terminus of the α-subunit. As palmitoylation is dynamic, this mechanism would allow precise control of specific splice variants to the cell surface. Our data provide new insights into how complex interplay between the repertoire of post-transcriptional and post-translational mechanisms controls cell surface expression of BK channels. PMID:23504458

Change in Pulmonary Function after Incentive Spirometer Exercise in Children with Spastic Cerebral Palsy: A Randomized Controlled Study.

PubMed

Choi, Ja Young; Rha, Dong-wook; Park, Eun Sook

2016-05-01

The aim of this study was to investigate the effect of incentive spirometer exercise (ISE) on pulmonary function and maximal phonation time (MPT) in children with spastic cerebral palsy (CP). Fifty children with CP were randomly assigned to two groups: the experimental group and the control group. Both groups underwent comprehensive rehabilitation therapy. The experimental group underwent additional ISE. The forced vital capacity (FVC), forced expiratory volume at one second (FEV₁), FEV₁/FVC ratio, peak expiratory flow (PEF), and MPT were assessed as outcome measures before and after 4 weeks of training. There were significant improvements in FVC, FEV₁, PEF, and MPT in the experimental group, but not in the control group. In addition, the improvements in FVC, FEV₁, and MPT were significantly greater in the experimental group than in the control group. The results of this randomized controlled study support the use of ISE for enhancing pulmonary function and breath control for speech production in children with CP.

[The risk factors for worsening renal function in patients with chronic heart failure].

PubMed

Yang, Xiao-hong; Sun, Zhi-jun; Zheng, Li-qiang; Jia, Yuan-chun; Dong, Ling-ling

2011-07-01

To investigate the risk factors of worsening renal function (WRF) in patients with chronic heart failure (CHF) and WRF influence on prognosis. A case-control study were undertaken to analyze independent risk factor statistically related to incidence of WRF, and to assess the influence of WRF on prognosis. The independent predictors of WRF were creatinine level at admission (OR 2.248, 95%CI 1.088 - 4.647, P = 0.029) and NYHA class on admission (OR 2.485, 95%CI 1.385 - 4.459, P = 0.002). The mortality of patient with WRF was obviously higher than that of control group during hospitalization (OR 3.824, 95%CI 2.452 - 5.637, P < 0.015). WRF is a common complication among patients hospitalized for CHF, and is obviously associated with mortality during hospitalization. Higher creatinine level and weak heart function are independent risk factors for incidence of WRF of patients with CHF.

A design procedure and handling quality criteria for lateral directional flight control systems

NASA Technical Reports Server (NTRS)

Stein, G.; Henke, A. H.

1972-01-01

A practical design procedure for aircraft augmentation systems is described based on quadratic optimal control technology and handling-quality-oriented cost functionals. The procedure is applied to the design of a lateral-directional control system for the F4C aircraft. The design criteria, design procedure, and final control system are validated with a program of formal pilot evaluation experiments.

Longitudinal Trajectories of Metabolic Control across Adolescence: Associations with Parental Involvement, Adolescents’ Psychosocial Maturity, and Health Care Utilization

PubMed Central

King, Pamela S.; Berg, Cynthia A.; Butner, Jonathan; Drew, Linda M.; Foster, Carol; Donaldson, David; Murray, Mary; Swinyard, Michael; Wiebe, Deborah J.

2012-01-01

Purpose To predict trajectories of metabolic control across adolescence from parental involvement and adolescent psychosocial maturity, and to link metabolic control trajectories to health care utilization. Methods 252 adolescents (M age at study initiation = 12.5, SD=1.5, range 10–14 years) with type 1 diabetes (54.4% female, 92.8% Caucasian, length of diagnosis M=4.7 years, SD=3.0, range 1–12) participated in a 2-year longitudinal study. Metabolic control was gathered from medical records every three months. Adolescents completed measures of self-reliance (functional autonomy and extreme peer orientation), self-control (self-control and externalizing behavior), and parental involvement in diabetes care (acceptance, monitoring, and frequency of help). At the end of the study, mothers reported health care utilization (diabetes-related emergency room visits and hospitalizations) over the past six months. Results Latent class growth analyses indicated two distinct trajectories of metabolic control across adolescence: moderate control with slight deterioration (92% of the sample; average HbA1c = 8.18%) and poor control with rapid deterioration (8% of the sample; average HbA1c of 12.09%). Adolescents with poor and rapidly deteriorating metabolic control reported lower paternal monitoring and frequency of help with diabetes management, lower functional autonomy, and lower self-control than others. Those with poor and rapidly deteriorating metabolic control were 6.4 times more likely to report diabetes-related emergency room visits, and 9.3 times more likely to report diabetes-related hospitalizations near the end of the study. Conclusions Parental involvement and adolescents’ psychosocial maturity predict patterns of deteriorating metabolic control across adolescence and could be targeted for intervention. PMID:22525113

''Playstation eyetoy games'' improve upper extremity-related motor functioning in subacute stroke: a randomized controlled clinical trial.

PubMed

Yavuzer, G; Senel, A; Atay, M B; Stam, H J

2008-09-01

To evaluate the effects of ''Playstation EyeToy Games'' on upper extremity motor recovery and upper extremity-related motor functioning of patients with subacute stroke. The authors designed a randomized, controlled, assessor-blinded, 4-week trial, with follow-up at 3 months. A total of 20 hemiparetic inpatients (mean age 61.1 years), all within 12 months post-stroke, received 30 minutes of treatment with ''Playstation EyeToy Games'' per day, consisting of flexion and extension of the paretic shoulder, elbow and wrist as well as abduction of the paretic shoulder or placebo therapy (watching the games for the same duration without physical involvement into the games) in addition to conventional program, 5 days a week, 2-5 hours/day for 4 weeks. Brunnstrom's staging and self-care sub-items of the functional independence measure (FIM) were performed at 0 month (baseline), 4 weeks (post-treatment), and 3 months (follow-up) after the treatment. The mean change score (95% confidence interval) of the FIM self-care score (5.5 [2.9-8.0] vs 1.8 [0.1-3.7], P=0.018) showed significantly more improvement in the EyeToy group compared to the control group. No significant differences were found between the groups for the Brunnstrom stages for hand and upper extremity. ''Playstation EyeToy Games'' combined with a conventional stroke rehabilitation program have a potential to enhance upper extremity-related motor functioning in subacute stroke patients.

Flavonoid-Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomized Controlled Clinical Trial.

PubMed

Bondonno, Nicola P; Bondonno, Catherine P; Blekkenhorst, Lauren C; Considine, Michael J; Maghzal, Ghassan; Stocker, Roland; Woodman, Richard J; Ward, Natalie C; Hodgson, Jonathan M; Croft, Kevin D

2018-02-01

The cardioprotective effects of apples are primarily attributed to flavonoids, found predominantly in the skin. This study aimed to determine if acute and/or chronic (4 weeks) ingestion of flavonoid-rich apples improves endothelial function, blood pressure (BP), and arterial stiffness in individuals at risk for cardiovascular diseases (CVD). In this randomized, controlled cross-over trial, acute and 4 week intake of apple with skin (high flavonoid apple, HFA) is compared to intake of apple flesh only (low flavonoid apple, LFA) in 30 participants. The primary outcome is endothelial function assessed using flow-mediated dilation (FMD) of the brachial artery, while main secondary outcomes are 24 h ambulatory BP and arterial stiffness. Other outcomes include fasting serum glucose and lipoprotein profile, plasma heme oxygenase-1 (Hmox-1), F 2 -isoprostanes, flavonoid metabolites, and plasma and salivary nitrate (NO 3 - ) and nitrite (NO 2 - ) concentrations. Compared to LFA control, the HFA results in a significant increase in FMD acutely (0.8%, p < 0.001) and after 4 weeks chronic intake (0.5%, p < 0.001), and in plasma flavonoid metabolites (p < 0.0001). Other outcomes are not altered significantly. A lower risk of CVD with higher apple consumption could be mediated by the beneficial effect of apple skin on endothelial function, both acutely and chronically. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exercise training reduces the frequency of menopausal hot flushes by improving thermoregulatory control.

PubMed

Bailey, Tom G; Cable, N Timothy; Aziz, Nabil; Dobson, Rebecca; Sprung, Victoria S; Low, David A; Jones, Helen

2016-07-01

Postmenopausal hot flushes occur due to a reduction in estrogen production causing thermoregulatory and vascular dysfunction. Exercise training enhances thermoregulatory control of sweating, skin and brain blood flow. We aimed to determine if improving thermoregulatory control and vascular function with exercise training alleviated hot flushes. Twenty-one symptomatic women completed a 7-day hot flush questionnaire and underwent brachial artery flow-mediated dilation and a cardiorespiratory fitness test. Sweat rate and skin blood flow temperature thresholds and sensitivities, and middle cerebral artery velocity (MCAv) were measured during passive heating. Women performed 16 weeks of supervised exercise training or control, and measurements were repeated. There was a greater improvement in cardiorespiratory fitness (4.45 mL/kg/min [95% CI: 1.87, 8.16]; P = 0.04) and reduced hot flush frequency (48 hot flushes/wk [39, 56]; P < 0.001) after exercise compared with control. Exercise reduced basal core temperature (0.14°C [0.01, 0.27]; P = 0.03) and increased basal MCAv (2.8 cm/s [1.0, 5.2]; P = 0.04) compared with control. Sweat rate and skin blood flow thresholds occurred approximately 0.19°C and 0.17°C earlier, alongside improved sweating sensitivity with exercise. MCAv decreased during heating (P < 0.005), but was maintained 4.5 cm/s (3.6, 5.5; P < 0.005) higher during heating after exercise compared with control (0.6 cm/s [-0.4, 1.4]). Exercise training that improves cardiorespiratory fitness reduces self-reported hot flushes. Improvements are likely mediated through greater thermoregulatory control in response to increases in core temperature and enhanced vascular function in the cutaneous and cerebral circulations.