Endothelial cells promote the proliferation of lymphocytes partly through the Wnt pathway via LEF-1

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

Wang, Shu-Hong; Nan, Ke-Jun, E-mail: nankj@163.com; Wang, Yao-Chun

The function of T cells and B cells is to recognize specific 'non-self' antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells. Endothelial cells (ECs) can trigger the activation of T cells through their class I and class II MHC molecules. In this study, we examined the effect of ECs on the proliferation of lymphocytes. We report that the proliferation of T and B cells can be improved by interaction with ECs. LEF-1 is one of the main molecularmore » mediators in this process, and the inhibition of LEF-1 induces apoptosis. These results suggest that LEF-1 modulates positively the proliferation of lymphocytes induced by their interaction with ECs.« less

Lef1 regulates Dusp6 to influence neuromast formation and spacing in the zebrafish posterior lateral line primordium.

PubMed

Matsuda, Miho; Nogare, Damian Dalle; Somers, Katherine; Martin, Kathleen; Wang, Chongmin; Chitnis, Ajay B

2013-06-01

The posterior lateral line primordium (PLLp) migrates caudally and periodically deposits neuromasts. Coupled, but mutually inhibitory, Wnt-FGF signaling systems regulate proto-neuromast formation in the PLLp: FGF ligands expressed in response to Wnt signaling activate FGF receptors and initiate proto-neuromast formation. FGF receptor signaling, in turn, inhibits Wnt signaling. However, mechanisms that determine periodic neuromast formation and deposition in the PLLp remain poorly understood. Previous studies showed that neuromasts are deposited closer together and the PLLp terminates prematurely in lef1-deficient zebrafish embryos. It was suggested that this results from reduced proliferation in the leading domain of the PLLp and/or premature incorporation of progenitors into proto-neuromasts. We found that rspo3 knockdown reduces proliferation in a manner similar to that seen in lef1 morphants. However, it does not cause closer neuromast deposition or premature termination of the PLLp, suggesting that such changes in lef1-deficient embryos are not linked to changes in proliferation. Instead, we suggest that they are related to the role of Lef1 in regulating the balance of Wnt and FGF functions in the PLLp. Lef1 determines expression of the FGF signaling inhibitor Dusp6 in leading cells and regulates incorporation of cells into neuromasts; reduction of Dusp6 in leading cells in lef1-deficient embryos allows new proto-neuromasts to form closer to the leading edge. This is associated with progressively slower PLLp migration, reduced spacing between deposited neuromasts and premature termination of the PLLp system.

Lef1 regulates Dusp6 to influence neuromast formation and spacing in the zebrafish posterior lateral line primordium

PubMed Central

Matsuda, Miho; Nogare, Damian Dalle; Somers, Katherine; Martin, Kathleen; Wang, Chongmin; Chitnis, Ajay B.

2013-01-01

The posterior lateral line primordium (PLLp) migrates caudally and periodically deposits neuromasts. Coupled, but mutually inhibitory, Wnt-FGF signaling systems regulate proto-neuromast formation in the PLLp: FGF ligands expressed in response to Wnt signaling activate FGF receptors and initiate proto-neuromast formation. FGF receptor signaling, in turn, inhibits Wnt signaling. However, mechanisms that determine periodic neuromast formation and deposition in the PLLp remain poorly understood. Previous studies showed that neuromasts are deposited closer together and the PLLp terminates prematurely in lef1-deficient zebrafish embryos. It was suggested that this results from reduced proliferation in the leading domain of the PLLp and/or premature incorporation of progenitors into proto-neuromasts. We found that rspo3 knockdown reduces proliferation in a manner similar to that seen in lef1 morphants. However, it does not cause closer neuromast deposition or premature termination of the PLLp, suggesting that such changes in lef1-deficient embryos are not linked to changes in proliferation. Instead, we suggest that they are related to the role of Lef1 in regulating the balance of Wnt and FGF functions in the PLLp. Lef1 determines expression of the FGF signaling inhibitor Dusp6 in leading cells and regulates incorporation of cells into neuromasts; reduction of Dusp6 in leading cells in lef1-deficient embryos allows new proto-neuromasts to form closer to the leading edge. This is associated with progressively slower PLLp migration, reduced spacing between deposited neuromasts and premature termination of the PLLp system. PMID:23637337

Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties.

PubMed Central

Van de Wetering, M; Castrop, J; Korinek, V; Clevers, H

1996-01-01

Previously, we reported the isolation of cDNA clones representing four alternative splice forms of TCF-1, a T-cell-specific transcription factor. In the present study, Western blotting (immunoblotting) yielded a multitude of TCF-1 proteins ranging from 25-55 kDa, a pattern not simply explained from the known splice alternatives. Subsequent cDNA cloning, PCR amplification, and analysis by rapid amplification of 5' cDNA ends revealed (i) the presence of an alternative upstream promoter, which extended the known N terminus by 116 amino acids, (ii) the presence of four alternative exons, and (iii) the existence of a second reading frame in the last exon encoding an extended C terminus. Inclusion of the extended N terminus into the originally reported protein resulted in a striking similarity to the lymphoid factor Lef-1. Several of the TCF-1 isoforms, although less potent, mimicked Lef-1 in transactivating transcription through the T-cell receptor alpha-chain (TCR-alpha) enhancer. These data provide a molecular basis for the complexity of the expressed TCF-1 proteins and establish the existence of functional differences between these isoforms. Furthermore, the functional redundancy between Tcf-1 and Lef-1 explains the apparently normal TCR-alpha expression in single Tcf-1 or Lef-1 knockout mice despite the firm in vitro evidence for the importance of the Tcf/Lef site in the TCR-alpha enhancer. PMID:8622675

MiR-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor LEF1.

PubMed

Liu, Yanwei; Yan, Wei; Zhang, Wei; Chen, Lingchao; You, Gan; Bao, Zhaoshi; Wang, Yongzhi; Wang, Hongjun; Kang, Chunsheng; Jiang, Tao

2012-09-01

The invasive behavior of glioblastoma multiforme (GBM) cells is one of the most important reasons for the poor prognosis of this cancer. For invasion, tumor cells must acquire an ability to digest the extracellular matrix and infiltrate the normal tissue bordering the tumor. Preventing this by altering effector molecules can significantly improve a patient's prognosis. Accumulating evidence suggests that miRNAs are involved in multiple biological functions, including cell invasion, by altering the expression of multiple target genes. The expression levels of miR-218 correlate with the invasive potential of GBM cells. In this study, we found that miR-218 expression was low in glioma tissues, especially in GBM. The data showed an inverse correlation in 60 GBM tissues between the levels of miR-218 and MMP mRNAs (MMP-2, -7 and -9). Additionally, ectopic expression of miR-218 suppressed the invasion of GBM cells whereas inhibition of miR-218 expression enhanced the invasive ability. Numerous members of the MMP family are downstream effectors of the Wnt/LEF1 pathway. Target prediction databases and luciferase data showed that LEF1 is a new direct target of miR-218. Importantly, western blot assays demonstrated that miR-218 can reduce protein levels of LEF1 and MMP-9. We, therefore, hypothesize that miR-218 directly targets LEF1, resulting in reduced synthesis of MMP-9. Results suggest that miR-218 is involved in the invasive behavior of GBM cells and by targeting LEF1 and blocking the invasive axis, miR-218-LEF1-MMPs, it may be useful for developing potential clinical strategies.

Activation of EVI1 transcription by the LEF1/β-catenin complex with p53-alteration in myeloid blast crisis of chronic myeloid leukemia

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

Manachai, Nawin; Saito, Yusuke; Nakahata, Shingo

The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to progression of CML to blast crisis (BC). Aberrant high expression of ecotropic viral integration site 1 (EVI1) is frequently observed in CML during myeloid-BC as a potent driver with a CML stem cell signature; however, the precise molecular mechanism of EVI1 transcriptional regulation during CML progression is poorly defined. Here, we demonstrate the transcriptional activity of EVI1more » is dependent on activation of lymphoid enhancer-binding factor 1 (LEF1)/β-catenin complex by BCR-ABL with loss of p53 function during CML-BC. The activation of β-catenin is partly dependent on BCR-ABL expression through enhanced GSK3β phosphorylation, and EVI1 expression is directly enhanced by the LEF1/β-catenin complex bound to the EVI1 promoter region. Moreover, the loss of p53 expression is inversely correlated with high expression of EVI1 in CML leukemia cells with an aggressive phase of CML, and a portion of the activation mechanism of EVI1 expression is dependent on β-catenin activation through GSK3β phosphorylation by loss of p53. Therefore, we found that the EVI1 activation in CML-BC is dependent on LEF1/β-catenin activation by BCR-ABL expression with loss of p53 function, representing a novel selective therapeutic approach targeting myeloid blast crisis progression. - Highlights: • Transcriptional regulation of EVI1 in CML-BC is proposed. • EVI1 transcription is directly regulated by LEF1/β-catenin complex in CML-BC. • Loss of p53 function as a key regulator for β-catenin-EVI1 in CML myeloid-BC. • The LEF1/β-catenin binding site on the EVI1 promoter is a new target for CML-BC.« less

Operative management of partial-thickness tears of the proximal hamstring muscles in athletes.

PubMed

Bowman, Karl F; Cohen, Steven B; Bradley, James P

2013-06-01

Partial tears of the hamstring muscle origin represent a challenging clinical problem to the patient and orthopaedic surgeon. Although nonoperative treatment is frequently met with limited success, there is a paucity of data on the efficacy of surgical management for partial proximal hamstring tears in the active and athletic population. To evaluate the results of an anatomic repair for partial tears of the hamstring muscle origin in athletes. Case series; Level of evidence, 4. The records of 17 patients with partial tears of the proximal hamstring origin were reviewed after institutional review board approval was obtained. All patients were treated with open debridement and primary tendon repair after failure of at least 6 months of nonoperative therapy. Clinical and operative records, radiographs, and magnetic resonance images were reviewed for all patients. A patient-reported outcomes survey was completed by 14 patients that included the Lower Extremity Functional Score (LEFS), Marx activity rating scale, custom LEFS and Marx scales, and subjective patient satisfaction scores. Early and late postoperative complications were recorded. There were 3 male and 14 female patients; their average age was 43 years (range, 19-64 years) and average follow-up was 32 months (range, 12-51 months). There were 2 collegiate athletes (field hockey, track), 14 amateur athletes (distance running, waterskiing, tennis), and a professional bodybuilder. Postoperative LEFS was 73.3 ± 9.9 (range, 50-80) and custom LEFS was 66.7 ± 17.0 (range, 37-80) of a maximum 80 points. The most commonly reported difficulty was with prolonged sitting and explosive direction change while running. The average Marx score was 6.5 ± 5.3 (range, 0-16) of a maximum 16, correlating with a greater return to recreational running activities in this patient cohort than regular participation in pivoting or cutting sports. Marx custom scores were 20 of a maximum 20 in all patients, demonstrating no disability in the operative extremity with activities of daily living. No patient underwent a subsequent surgery. One patient was not satisfied with the result and reported persistent symptoms during competitive distance running. All patients were able to return to their preoperative level of activity after surgery. Anatomic surgical treatment of partial proximal hamstring avulsions can lead to satisfactory functional outcomes, a high rate of return to athletic activity, and low complication rate. This procedure should be reserved for patients who have failed an extended course of nonoperative treatment, and the proximity of the sciatic nerve mandates a careful assessment of the risk-benefit ratio before surgery is undertaken.

Prospective study of recovery from copperhead snake envenomation: an observational study.

PubMed

Lavonas, Eric J; Gerardo, Charles J

2015-05-15

Although much is known about signs, symptoms, and management in the acute phase of crotaline snake envenomation, little is known about signs, symptoms, function, and quality of life during the recovery phase. The purpose of this observational pilot investigation is to evaluate the utility of several clinical outcome instruments in the setting of copperhead snakebite, and to characterize the clinical course of recovery. This is a multi-center prospective, open-label, observational study of patients envenomated by copperhead snakes. We administered the Disabilities of the Arm, Shoulder, and Hand (DASH), Lower Extremity Functional Scale (LEFS), Patient-Specific Functional Scale (PSFS), Work Productivity and Ability Impairment: Special Health Problem (WPAI: SHP), Patients' Global Impression of Change (PGIC), Patient's Global Assessment of Recovery (PGAR), and SF-36 instruments, obtained numeric pain rating scales, and measured grip strength, walking speed, and swelling prior to hospital discharge and 3, 7, 14, 21, and 28 days after envenomation. 20 subjects were enrolled; none were lost to follow-up. Most (80%) had moderate severity swelling, and most (75%) received antivenom. Across the broad range of measures, abnormalities of pain, swelling, impairments of physical and role function, and quality of life persisted for 7-14 days in most subjects. Validated self-reported outcome measures, such as the DASH, LEFS, PSFS, PGIC, SF-36, and the daily activities impairment portion of the WPAI: SHP were more responsive than measurements of swelling or walking speed. Data quality issues limited the utility of the work impairment portion of the WPAI: SHP. Residual signs, symptoms, and impairment in some subjects lasted through the 28-day study period. The study design precluded any assessment of the effectiveness of antivenom. Signs, symptoms, impaired function, and decreased quality of life typically last 7 - 14 days after copperhead envenomation. Several tools appear responsive and useful in studying recovery from pit viper envenomation. ClinicalTrials.gov NCT01651299.

Dominance of free wall radial motion in global right ventricular function of heart transplant recipients.

PubMed

Lakatos, Bálint Károly; Tokodi, Márton; Assabiny, Alexandra; Tősér, Zoltán; Kosztin, Annamária; Doronina, Alexandra; Rácz, Kristóf; Koritsánszky, Kinga Bianka; Berzsenyi, Viktor; Németh, Endre; Sax, Balázs; Kovács, Attila; Merkely, Béla

2018-03-01

Assessment of right ventricular (RV) function using conventional echocardiography might be inadequate as the radial motion of the RV free wall is often neglected. Our aim was to quantify the longitudinal and the radial components of RV function using three-dimensional (3D) echocardiography in heart transplant (HTX) recipients. Fifty-one HTX patients in stable cardiovascular condition without history of relevant rejection episode or chronic allograft vasculopathy and 30 healthy volunteers were enrolled. RV end-diastolic (EDV) volume and total ejection fraction (TEF) were measured by 3D echocardiography. Furthermore, we quantified longitudinal (LEF) and radial ejection fraction (REF) by decomposing the motion of the RV using the ReVISION method. RV EDV did not differ between groups (HTX vs control; 96 ± 27 vs 97 ± 2 mL). In HTX patients, TEF was lower, however, tricuspid annular plane systolic excursion (TAPSE) decreased to a greater extent (TEF: 47 ± 7 vs 54 ± 4% [-13%], TAPSE: 11 ± 5 vs 21 ± 4 mm [-48%], P < .0001). In HTX patients, REF/TEF ratio was significantly higher compared to LEF/TEF (REF/TEF vs LEF/TEF: 0.58 ± 0.10 vs 0.27 ± 0.08, P < .0001), while in controls the REF/TEF and LEF/TEF ratio was similar (0.45 ± 0.07 vs 0.47 ± 0.07). Current results confirm the superiority of radial motion in determining RV function in HTX patients. Parameters incorporating the radial motion are recommended to assess RV function in HTX recipients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

NF-{kappa}B regulates Lef1 gene expression in chondrocytes

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

Yun, Kangsun; Choi, Yoo Duk; Nam, Jong Hee

The relation of Wnt/{beta}-catenin signaling to osteoarthritis progression has been revealed with little information on the underlying molecular mechanism. In this study we found overexpression of Lef1 in cartilage tissue of osteoarthritic patients and elucidated molecular mechanism of NF-{kappa}B-mediated Lef1 gene regulation in chondrocytes. Treatment of IL-1{beta} augmented Lef1 upregulation and nuclear translocation of NF-{kappa}B in chondrocytes. Under IL-1{beta} signaling, treatment of NF-{kappa}B nuclear translocation inhibitor SN-50 reduced Lef1 expression. A conserved NF-{kappa}B-binding site between mouse and human was selected through bioinformatic analysis and mapped at the 14 kb upstream of Lef1 transcription initiation site. NF-{kappa}B binding to the sitemore » was confirmed by chromatin immunoprecipitation assay. Lef1 expression was synergistically upregulated by interactions of NF-{kappa}B with Lef1/{beta}-catenin in chondrocytes. Our results suggest a pivotal role of NF-{kappa}B in Lef1 expression in arthritic chondrocytes or cartilage degeneration.« less

Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis.

PubMed

Kuwabara, Tomoko; Hsieh, Jenny; Muotri, Alysson; Yeo, Gene; Warashina, Masaki; Lie, Dieter Chichung; Moore, Lynne; Nakashima, Kinichi; Asashima, Makoto; Gage, Fred H

2009-09-01

In adult hippocampus, new neurons are continuously generated from neural stem cells (NSCs), but the molecular mechanisms regulating adult neurogenesis remain elusive. We found that Wnt signaling, together with the removal of Sox2, triggered the expression of NeuroD1 in mice. This transcriptional regulatory mechanism was dependent on a DNA element containing overlapping Sox2 and T-cell factor/lymphoid enhancer factor (TCF/LEF)-binding sites (Sox/LEF) in the promoter. Notably, Sox/LEF sites were also found in long interspersed nuclear element 1 (LINE-1) elements, consistent with their critical roles in the transition of NSCs to proliferating neuronal progenitors. Our results describe a previously unknown Wnt-mediated regulatory mechanism that simultaneously coordinates activation of NeuroD1 and LINE-1, which is important for adult neurogenesis and survival of neuronal progenitors. Moreover, the discovery that LINE-1 retro-elements embedded in the mammalian genome can function as bi-directional promoters suggests that Sox/LEF regulatory sites may represent a general mechanism, at least in part, for relaying environmental signals to other nearby loci to promote adult hippocampal neurogenesis.

Baculovirus LEF-11 nuclear localization signal is important for viral DNA replication.

PubMed

Chen, Tingting; Dong, Zhanqi; Hu, Nan; Hu, Zhigang; Dong, Feifan; Jiang, Yaming; Li, Jun; Chen, Peng; Lu, Cheng; Pan, Minhui

2017-06-15

Baculovirus LEF-11 is a small nuclear protein that is involved in viral late gene transcription and DNA replication. However, the characteristics of its nuclear localization signal and its impact on viral DNA replication are unknown. In the present study, systemic bioinformatics analysis showed that the baculovirus LEF-11 contains monopartite and bipartite classical nuclear localization signal sequences (cNLSs), which were also detected in a few alphabaculovirus species. Localization of representative LEF-11 proteins of four baculovirus genera indicated that the nuclear localization characteristics of baculovirus LEF-11 coincided with the predicted results. Moreover, Bombyx mori nucleopolyhedrovirus (BmNPV) LEF-11 could be transported into the nucleus during viral infection in the absence of a cNLSs. Further investigations demonstrated that the NLS of BmNPV LEF-11 is important for viral DNA replication. The findings of the present study indicate that the characteristics of the baculovirus LEF-11 protein and the NLS is essential to virus DNA replication and nuclear transport mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of reliability and responsiveness of patient-reported clinical outcome measures in knee osteoarthritis rehabilitation.

PubMed

Williams, Valerie J; Piva, Sara R; Irrgang, James J; Crossley, Chad; Fitzgerald, G Kelley

2012-08-01

Secondary analysis, pretreatment-posttreatment observational study. To compare the reliability and responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Outcome Survey activities of daily living subscale (KOS-ADL), and the Lower Extremity Functional Scale (LEFS) in individuals with knee osteoarthritis (OA). The WOMAC is the current standard in patient-reported measures of function in patients with knee OA. The KOS-ADL and LEFS were designed for potential use in patients with knee OA. If the KOS-ADL and LEFS are to be considered viable alternatives to the WOMAC for measuring patient-reported function in individuals with knee OA, they should have measurement properties comparable to the WOMAC. It would also be important to determine whether either of these instruments may be superior to the WOMAC in terms of reliability or responsiveness in this population. Data from 168 subjects with knee OA, who participated in a rehabilitation program, were used in the analyses. Reliability and responsiveness of each outcome measure were estimated at follow-ups of 2, 6, and 12 months. Reliability was estimated by calculating the intraclass correlation coefficient (ICC2,1) for subjects who were unchanged in status from baseline at each follow-up time, based on a global rating of change score. To examine responsiveness, the standard error of the measurement, minimal detectable change, minimal clinically important difference, and the Guyatt responsiveness index were calculated for each outcome measure at each follow-up time. All 3 outcome measures demonstrated reasonable reliability and responsiveness to change. Reliability and responsiveness tended to decrease somewhat with increasing follow-up time. There were no substantial differences between outcome measures for reliability or any of the 3 measures of responsiveness at any follow-up time. The results do not indicate that one outcome measure is more reliable or responsive than another when applied to subjects with knee OA. We believe that all 3 instruments are appropriate outcome measures to examine change in functional status of patients with knee OA.

Synthesis of Gold Mediated Biocompatible Nanocomposite of Lactone Enriched Fraction from Sahadevi (Vernonia cinerea Lees): An Assessment of Antimalarial Potential.

PubMed

Jyotshna; Shanker, Karuna; Khare, Puja; Tiwari, Nimisha; Mohanty, Shilpa; Bawankule, Dnyaneshwar U; Pal, Anirban

2016-01-01

Metals reduction into submicro/nano size through bhasma preparations for therapeutic use is well established in ancient traditional system of Indian medicines i.e. Ayurveda. Recently, nanotechnology has drawn the attention of researchers to develeope various size and shape nanoparicles / composite for number of applications.In this article, we report the enrichment of lactone enriched fraction (LEF) by liquid-liquid portioning of Vernonia cinerea metabolic extract and sysnthesis of mediated nano-gold composite (LEF-AuNPs) in single step process. The morphological characteristic based on transmission electron microscope (TEM) image analysis showed that LEF-AuNPs were predominantly nanopolygons and nanobots in shapes ranging from 50-200 nm in size. Abundance of phytochemicals in both LEF and LEF-AuNPs was dissimilar. In LEF, montanol- a diterpenoid, while in LEF-AuNPs, neophytadiene- a phytanes was the major compound. HPLC profile of relatively polar compounds also varied drastically. In-vitro biocompatibility, cytotoxicity [MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) based assay] and storage stabilitiy of LEF-AuNPs were evaluated. The moderate ability of LEF-AuNPs to restrict parasitaemia, extended mean survival time of mice infected with Plasmodium berghei and lack of any evident toxicity provides new opportunities for the safe delivery and applications of such nanocomposites in malaria therapy.

Impact of mitral regurgitation on clinical outcomes of patients with low-ejection fraction, low-gradient severe aortic stenosis undergoing transcatheter aortic valve implantation.

PubMed

O'Sullivan, Crochan J; Stortecky, Stefan; Bütikofer, Anne; Heg, Dik; Zanchin, Thomas; Huber, Christoph; Pilgrim, Thomas; Praz, Fabien; Buellesfeld, Lutz; Khattab, Ahmed A; Blöchlinger, Stefan; Carrel, Thierry; Meier, Bernhard; Zbinden, Stephan; Wenaweser, Peter; Windecker, Stephan

2015-02-01

Up to 1 in 6 patients undergoing transcatheter aortic valve implantation (TAVI) present with low-ejection fraction, low-gradient (LEF-LG) severe aortic stenosis and concomitant relevant mitral regurgitation (MR) is present in 30% to 55% of these patients. The effect of MR on clinical outcomes of LEF-LG patients undergoing TAVI is unknown. Of 606 consecutive patients undergoing TAVI, 113 (18.7%) patients with LEF-LG severe aortic stenosis (mean gradient ≤40 mm Hg, aortic valve area <1.0 cm(2), left ventricular ejection fraction <50%) were analyzed. LEF-LG patients were dichotomized into ≤mild MR (n=52) and ≥moderate MR (n=61). Primary end point was all-cause mortality at 1 year. No differences in mortality were observed at 30 days (P=0.76). At 1 year, LEF-LG patients with ≥moderate MR had an adjusted 3-fold higher rate of all-cause mortality (11.5% versus 38.1%; adjusted hazard ratio, 3.27 [95% confidence interval, 1.31-8.15]; P=0.011), as compared with LEF-LG patients with ≤mild MR. Mortality was mainly driven by cardiac death (adjusted hazard ratio, 4.62; P=0.005). As compared with LEF-LG patients with ≥moderate MR assigned to medical therapy, LEF-LG patients with ≥moderate MR undergoing TAVI had significantly lower all-cause mortality (hazard ratio, 0.38; 95% confidence interval, 0.019-0.75) at 1 year. Moderate or severe MR is a strong independent predictor of late mortality in LEF-LG patients undergoing TAVI. However, LEF-LG patients assigned to medical therapy have a dismal prognosis independent of MR severity suggesting that TAVI should not be withheld from symptomatic patients with LEF-LG severe aortic stenosis even in the presence of moderate or severe MR. © 2015 American Heart Association, Inc.

Detection of anthrax lef with DNA-based photonic crystal sensors

NASA Astrophysics Data System (ADS)

Zhang, Bailin; Dallo, Shatha; Peterson, Ralph; Hussain, Syed; Weitao, Tao; Ye, Jing Yong

2011-12-01

Bacillus anthracis has posed a threat of becoming biological weapons of mass destruction due to its virulence factors encoded by the plasmid-borne genes, such as lef for lethal factor. We report the development of a fast and sensitive anthrax DNA biosensor based on a photonic crystal structure used in a total-internal-reflection configuration. For the detection of the lef gene, a single-stranded DNA lef probe was biotinylated and immobilized onto the sensor via biotin-streptavidin interactions. A positive control, lef-com, was the complementary strand of the probe, while a negative control was an unrelated single-stranded DNA fragment from the 16S rRNA gene of Acinetobacter baumannii. After addition of the biotinylated lef probe onto the sensor, significant changes in the resonance wavelength of the sensor were observed, resulting from binding of the probe to streptavidin on the sensor. The addition of lef-com led to another significant increase as a result of hybridization between the two DNA strands. The detection sensitivity for the target DNA reached as low as 0.1 nM. In contrast, adding the unrelated DNAs did not cause an obvious shift in the resonant wavelength. These results demonstrate that detection of the anthrax lef by the photonic crystal structure in a total-internal-reflection sensor is highly specific and sensitive.

LEF1 is preferentially expressed in the tubal-peritoneal junctions and is a reliable marker of tubal intraepithelial lesions

PubMed Central

Schmoeckel, Elisa; Odai-Afotey, Ashley A.; Schleiβheimer, Michael; Rottmann, Miriam; Flesken-Nikitin, Andrea; Ellenson, Lora H.; Kirchner, Thomas; Mayr, Doris; Nikitin, Alexander Yu.

2017-01-01

Recently it has been reported that serous tubal intraepithelial carcinoma (STIC), the likely precursor of ovarian/extra-uterine high-grade serous carcinoma, are frequently located in the vicinity of tubal-peritoneal junctions, consistent with the cancer-prone features of many epithelial transitional regions. To test if p53 (aka TP53)-signatures and secretory cell outgrowths (SCOUTs) also localize to tubal-peritoneal junctions, we examined these lesions in the fallopian tubes of patients undergoing salpingo-oophorectomy for sporadic high-grade serous carcinomas or as a prophylactic procedure for carriers of familial BRCA1 or 2 mutations. STICs were located closest to the tubal-peritoneal junctions with an average distance of 1.31 mm, while SCOUTs were not detected in the fimbriated end of the fallopian tube. Since many epithelial transitional regions contain stem cells, we also determined the expression of stem cell markers in the normal fallopian tube, tubal intraepithelial lesions and high-grade serous carcinomas. Of those, LEF1 was consistently expressed in the tubal-peritoneal junctions and all lesions, independent of p53 status. All SCOUTs demonstrated strong nuclear expression of β-catenin consistent with the LEF1 participation in the canonical WNT pathway. However, β-catenin was preferentially located in the cytoplasm of cells comprising STICs and p53 signatures, suggesting WNT-independent function of LEF1 in those lesions. Both frequency of LEF1 expression and β-catenin nuclear expression correlated with the worst 5 year patient survival, supporting important role of both proteins in high-grade serous carcinoma. Taken together, our findings suggest the existence of stem cell niche within the tubal-peritoneal junctions. Furthermore, they support the notion that the pathogenesis of SCOUTs is distinct from that of STICs and p53 signatures. The location and discrete patterns of LEF1 and β-catenin expression may serve as highly sensitive and reliable ancillary markers for the detection and differential diagnosis of tubal intraepithelial lesions. PMID:28664938

Functional outcome of tibial fracture with acute compartment syndrome and correlation to deep posterior compartment pressure.

PubMed

Goyal, Saumitra; Naik, Monappa A; Tripathy, Sujit Kumar; Rao, Sharath K

2017-05-18

To measure single baseline deep posterior compartment pressure in tibial fracture complicated by acute compartment syndrome (ACS) and to correlate it with functional outcome. Thirty-two tibial fractures with ACS were evaluated clinically and the deep posterior compartment pressure was measured. Urgent fasciotomy was needed in 30 patients. Definite surgical fixation was performed either primarily or once fasciotomy wound was healthy. The patients were followed up at 3 mo, 6 mo and one year. At one year, the functional outcome [lower extremity functional scale (LEFS)] and complications were assessed. Three limbs were amputated. In remaining 29 patients, the average times for clinical and radiological union were 25.2 ± 10.9 wk (10 to 54 wk) and 23.8 ± 9.2 wk (12 to 52 wk) respectively. Nine patients had delayed union and 2 had nonunion who needed bone grafting to augment healing. Most common complaint at follow up was ankle stiffness (76%) that caused difficulty in walking, running and squatting. Of 21 patients who had paralysis at diagnosis, 13 (62%) did not recover and additional five patients developed paralysis at follow-up. On LEFS evaluation, there were 14 patients (48.3%) with severe disability, 10 patients (34.5%) with moderate disability and 5 patients (17.2%) with minimal disability. The mean pressures in patients with minimal disability, moderate disability and severe disability were 37.8, 48.4 and 58.79 mmHg respectively ( P < 0.001). ACS in tibial fractures causes severe functional disability in majority of patients. These patients are prone for delayed union and nonunion; however, long term disability is mainly because of severe soft tissue contracture. Intra-compartmental pressure (ICP) correlates with functional disability; patients with relatively high ICP are prone for poor functional outcome.

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

Asally, Munehiro; Yoneda, Yoshihiro

Nuclear accumulation of {beta}-catenin plays an important role in the Wnt signaling pathway. In the nucleus, {beta}-catenin acts as a transcriptional co-activator for TCF/LEF family of transcription factors. It has been shown that lef-1 contains a typical basic type nuclear localization signal (NLS) and is transported into the nucleus by the conventional import pathway. In this study, we found that a mutant lef-1 lacking the classical NLS accumulated in the nucleus of living cells, when {beta}-catenin was co-expressed. In addition, in a cell-free import assay, lef-1 migrated into the nucleus in the presence of {beta}-catenin alone without any other solublemore » factors. In contrast, another mutant lef-1 lacking the {beta}-catenin binding domain failed to migrate into the nucleus, even in the presence of {beta}-catenin. These findings indicate that {beta}-catenin alone can mediate the nuclear import of lef-1 through the direct binding. Collectively, we propose that there are two distinct pathways for the nuclear import of lef-1: importin {alpha}/{beta}-mediated and {beta}-catenin-mediated one, which provides a novel paradigm for Wnt signaling pathway.« less

Short-term effects of hip abductors and lateral rotators strengthening in females with patellofemoral pain syndrome: a randomized controlled clinical trial.

PubMed

Fukuda, Thiago Yukio; Rossetto, Flavio Marcondes; Magalhães, Eduardo; Bryk, Flavio Fernandes; Lucareli, Paulo Roberto Garcia; de Almeida Aparecida Carvalho, Nilza

2010-11-01

Randomized clinical trial. To investigate the influence of strengthening the hip abductor and lateral rotator musculature on pain and function of females with patellofemoral pain syndrome (PFPS). Hip muscle weakness in women athletes has been the focus of many recent studies and is suggested as an important impairment to address in the conservative treatment of women with PFPS. However, it is still not well established if strengthening these muscles is associated with clinical improvement in pain and function in sedentary females with PFPS. Seventy females (average±SD age, 25±07 years), with a diagnosis of unilateral PFPS, were distributed randomly into 3 groups: 22 females in the knee exercise group, who received a conventional treatment that emphasized stretching and strengthening of the knee musculature; 23 females in the knee and hip exercise group, who performed exercises to strengthen the hip abductors and external rotators in addition to the same exercises performed by those in the knee exercise group; and of the 25 females who did not receive any treatment. The females of the nontreatment group (control) were instructed to maintain their normal daily activities. An 11-point numerical pain rating scale (NPRS) was used to assess pain during stair ascent and descent. The lower extremity functional scale (LEFS) and the anterior knee pain scale (AKPS) were used to assess function. The single-limb single hop test was also used as a functional outcome to measure preintervention and 4-week postintervention function. The 3 groups were homogeneous prior to treatment in respect to demographic, pain, and functional scales data. Both the knee exercise and the knee and hip exercise groups showed significant improvement in the LEFS, the AKPS, and the NPRS, when compared to the control group (P<.05 and P<.001, respectively). But, when we considered minimal clinically important differences, only the knee and hip exercise group demonstrated mean improvements in AKPS and pain scores that were large enough to be clinically meaningful. For the single-limb single hop test, both groups receiving an intervention showed greater improvement than the control group, but there was no difference between the 2 interventions (P>.05). Rehabilitation programs focusing on knee strengthening exercises and knee strengthening exercises supplemented by hip strengthening exercises were both effective in improving function and reducing pain in sedentary women with PFPS. Improvements of pain and function were greater for the group that performed the hip strengthening exercises, but the difference was significant only for pain rating while descending stairs. Therapy, level 1b-.

Leflunomide is associated with a higher flare rate compared to methotrexate in the treatment of chronic uveitis in juvenile idiopathic arthritis.

PubMed

Bichler, J; Benseler, S M; Krumrey-Langkammerer, M; Haas, J-P; Hügle, B

2015-01-01

Chronic anterior uveitis is a serious complication of juvenile idiopathic arthritis (JIA); disease flares are highly associated with loss of vision. Leflunomide (LEF) is used successfully for JIA joint disease but its effectiveness in uveitis has not been determined. The aim of this study was to determine whether LEF improves flare rates of uveitis in JIA patients compared to preceding methotrexate (MTX) therapy. A single-centre retrospective study of consecutive children with JIA and chronic anterior uveitis was performed. All children initially received MTX and were then switched to LEF. Demographic, clinical, and laboratory data, dose and duration of MTX and LEF therapy, concomitant medications and rate of anterior uveitis flares, as determined by an expert ophthalmologist, were obtained. Flare rates were compared using a generalized linear mixed model with a negative binomial distribution. A total of 15 children were included (80% females, all antinuclear antibody positive). The median duration of MTX therapy was 51 (range 26-167) months; LEF was given for a median of 12 (range 4-47) months. Anti-tumour necrosis factor (anti-TNF-α) co-medication was given to four children while on MTX. By contrast, LEF was combined with anti-TNF-α treatment in six children. On MTX, JIA patients showed a uveitis flare rate of 0.0247 flares/month, while LEF treatment was associated with a significantly higher flare rate of 0.0607 flares/month (p = 0.008). Children with JIA had significantly more uveitis flares on LEF compared to MTX despite receiving anti-TNF-α co-medication more frequently. Therefore, LEF may need to be considered less effective in controlling chronic anterior uveitis.

Lef1-dependent hypothalamic neurogenesis inhibits anxiety

PubMed Central

Xie, Yuanyuan; Panahi, Samin; Gaynes, John A.; Watters, Harrison N.; Zhou, Dingxi; Xue, Hai-Hui; Fung, Camille M.; Levine, Edward M.; Letsou, Anthea; Brennan, K. C.

2017-01-01

While innate behaviors are conserved throughout the animal kingdom, it is unknown whether common signaling pathways regulate the development of neuronal populations mediating these behaviors in diverse organisms. Here, we demonstrate that the Wnt/ß-catenin effector Lef1 is required for the differentiation of anxiolytic hypothalamic neurons in zebrafish and mice, although the identity of Lef1-dependent genes and neurons differ between these 2 species. We further show that zebrafish and Drosophila have common Lef1-dependent gene expression in their respective neuroendocrine organs, consistent with a conserved pathway that has diverged in the mouse. Finally, orthologs of Lef1-dependent genes from both zebrafish and mouse show highly correlated hypothalamic expression in marmosets and humans, suggesting co-regulation of 2 parallel anxiolytic pathways in primates. These findings demonstrate that during evolution, a transcription factor can act through multiple mechanisms to generate a common behavioral output, and that Lef1 regulates circuit development that is fundamentally important for mediating anxiety in a wide variety of animal species. PMID:28837622

Leflunomide use during the first 33 months after food and drug administration approval: experience with a national cohort of 3,325 patients.

PubMed

Siva, Chokkalingam; Eisen, Seth A; Shepherd, Rebecca; Cunningham, Francesca; Fang, Meika A; Finch, William; Salisbury, Don; Singh, Jasvinder A; Stern, Richard; Zarabadi, S Alireza

2003-12-15

To describe leflunomide (LEF) use in a national cohort of 3,325 veterans. Prescriptions for LEF and 9 disease-modifying antirheumatic drugs written between October 1998 and June 2001 at all Veterans Affairs (VA) medical centers were obtained from VA national databases. LEF was initiated with a loading dose of 100 mg daily for 3 days in 61% of patients, and 42% of patients discontinued LEF. LEF was more likely to be discontinued if a 3-day 100-mg loading dose was prescribed, patients were younger than 44 years or older than 75 years, or reported an annual family income <$60,000. Review of medical records of 291 discontinuers revealed that the most common reasons for discontinuation were inefficacy (30%), gastrointestinal symptoms (29%), medication noncompliance or lost to followup (14%), and elevated liver enzymes (5%). LEF is relatively safe in clinical practice. The VA's national databases provide an excellent, inexpensive resource for postmarketing evaluation of rheumatologic medications.

Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/β-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage.

PubMed

Feng, Xiao-Yu; Wu, Xiao-Shan; Wang, Jin-Song; Zhang, Chun-Mei; Wang, Song-Lin

2018-02-01

Homeobox protein MSX-1 (hereafter referred to as MSX-1) is essential for early tooth-germ development. Tooth-germ development is arrested at bud stage in Msx1 knockout mice, which prompted us to study the functions of MSX-1 beyond this stage. Here, we investigated the roles of MSX-1 during late bell stage. Mesenchymal cells of the mandibular first molar were isolated from mice at embryonic day (E)17.5 and cultured in vitro. We determined the expression levels of β-catenin, bone morphogenetic protein 2 (Bmp2), Bmp4, and lymphoid enhancer-binding factor 1 (Lef1) after knockdown or overexpression of Msx1. Our findings suggest that knockdown of Msx1 promoted expression of Bmp2, Bmp4, and Lef1, resulting in elevated differentiation of odontoblasts, which was rescued by blocking the expression of these genes. In contrast, overexpression of Msx1 decreased the expression of Bmp2, Bmp4, and Lef1, leading to a reduction in odontoblast differentiation. The regulation of Bmp2, Bmp4, and Lef1 by Msx1 was mediated by the Wnt/β-catenin signaling pathway. Additionally, knockdown of Msx1 impaired cell proliferation and slowed S-phase progression, while overexpression of Msx1 also impaired cell proliferation and prolonged G1-phase progression. We therefore conclude that MSX-1 maintains cell proliferation by regulating transition of cells from G1-phase to S-phase and prevents odontoblast differentiation by inhibiting expression of Bmp2, Bmp4, and Lef1 at the late bell stage via the Wnt/β-catenin signaling pathway. © 2017 Eur J Oral Sci.

Activation of EVI1 transcription by the LEF1/β-catenin complex with p53-alteration in myeloid blast crisis of chronic myeloid leukemia.

PubMed

Manachai, Nawin; Saito, Yusuke; Nakahata, Shingo; Bahirvani, Avinash Govind; Osato, Motomi; Morishita, Kazuhiro

2017-01-22

The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to progression of CML to blast crisis (BC). Aberrant high expression of ecotropic viral integration site 1 (EVI1) is frequently observed in CML during myeloid-BC as a potent driver with a CML stem cell signature; however, the precise molecular mechanism of EVI1 transcriptional regulation during CML progression is poorly defined. Here, we demonstrate the transcriptional activity of EVI1 is dependent on activation of lymphoid enhancer-binding factor 1 (LEF1)/β-catenin complex by BCR-ABL with loss of p53 function during CML-BC. The activation of β-catenin is partly dependent on BCR-ABL expression through enhanced GSK3β phosphorylation, and EVI1 expression is directly enhanced by the LEF1/β-catenin complex bound to the EVI1 promoter region. Moreover, the loss of p53 expression is inversely correlated with high expression of EVI1 in CML leukemia cells with an aggressive phase of CML, and a portion of the activation mechanism of EVI1 expression is dependent on β-catenin activation through GSK3β phosphorylation by loss of p53. Therefore, we found that the EVI1 activation in CML-BC is dependent on LEF1/β-catenin activation by BCR-ABL expression with loss of p53 function, representing a novel selective therapeutic approach targeting myeloid blast crisis progression. Copyright © 2016 Elsevier Inc. All rights reserved.

Anterior cruciate ligament tears treated with percutaneous injection of autologous bone marrow nucleated cells: a case series

PubMed Central

Centeno, Christopher J; Pitts, John; Al-Sayegh, Hasan; Freeman, Michael D

2015-01-01

Introduction This was a prospective case series designed to investigate treatment for anterior cruciate ligament (ACL) tears using an injection of autologous bone marrow concentrate. Methods Consecutive adult patients presenting to a private outpatient interventional musculoskeletal and pain practice with knee pain, ACL laxity on exam, and magnetic resonance imaging (MRI) evidence of a grade 1, 2, or 3 ACL tears with less than 1 cm retraction were eligible for this study. Eligible patients were treated with an intraligamentous injection of autologous bone marrow concentrate, using fluoroscopic guidance. Pre- and postprocedural sagittal MRI images of the ACLs were analyzed using ImageJ software to objectively quantify changes between pre- and posttreatment scans. Five different types of measurement of ACL pixel intensity were examined as a proxy for ligament integrity. In addition pain visual analog scale (VAS) and Lower Extremity Functional Scale (LEFS) values were recorded at baseline and at 1 month, 3 months, 6 months, and annually postinjection. Objective outcomes measured were pre- to post-MRI measurement changes, as analyzed by the ImageJ software. Subjective outcomes measured were changes in the VAS and LEFS, and a self-rated percentage improvement. Results Seven of ten patients showed improvement in at least four of five objective measures of ACL integrity in their postprocedure MRIs. In the entire study group, the mean gray value, median, raw integrated density, and modal gray value all decreased toward low-signal ACLs (P=0.01, P=0.02, P=0.002, and P=0.08), indications of improved ligament integrity. Seven of ten patients responded to the self-rated metrics follow up. The mean VAS change was a decrease of 1.7 (P=0.25), the mean LEFS change was an increase of 23.3 (P=0.03), and mean reported improvement was 86.7%. Conclusion Based on this small case series, autologous bone marrow concentrate shows promise in the treatment of grade 1, 2, and possibly grade 3 ACL tears without retraction. Further investigation using a controlled study design is warranted. PMID:26261424

Orthosis-Shaped Sandals Are as Efficacious as In-Shoe Orthoses and Better than Flat Sandals for Plantar Heel Pain: A Randomized Control Trial.

PubMed

Vicenzino, Bill; McPoil, Thomas G; Stephenson, Aoife; Paul, Sanjoy K

2015-01-01

To investigate efficacy of a contoured sandal being marketed for plantar heel pain with comparison to a flat flip-flop and contoured in-shoe insert/orthosis. 150 volunteers aged 50 (SD: 12) years with plantar heel pain (>4 weeks) were enrolled after responding to advertisements and eligibility determined by telephone and at first visit. Participants were randomly allocated to receive commercially available contoured sandals (n = 49), flat flip-flops (n = 50) or over the counter, pre-fabricated full-length foot orthotics (n = 51). Primary outcomes were a 15-point Global Rating of Change scale (GROC: 1 = a very great deal worse, 15 = a very great deal better), 13 to 15 representing an improvement and the 20-item Lower Extremity Function Scale (LEFS) on which participants rate 20 common weight bearing activities and activities of daily living on a 5-point scale (0 = extreme difficulty, 4 = no difficulty). Secondary outcomes were worst level of heel pain in the preceding week, and the foot and ankle ability measure. Outcomes were collected blind to allocation. Analyses were done on an intention to treat basis with 12 weeks being the primary outcome time of interest. The contoured sandal was 68% more likely to report improvement in terms of GROC compared to flat flip-flop. On the LEFS the contoured sandal was 61% more likely than flat flip-flop to report improvement. The secondary outcomes in the main reflected the primary outcomes, and there were no differences between contoured sandal and shoe insert. Physicians can have confidence in supporting a patient's decision to wear contoured sandals or in-shoe orthoses as one of the first and simple strategies to manage their heel pain. The Australian New Zealand Clinical Trials Registry ACTRN12612000463875.

Utilization of manual therapy to the lumbar spine in conjunction with traditional conservative care for individuals with bilateral lower extremity complex regional pain syndrome: A case series.

PubMed

Walston, Zachary; Hernandez, Luis; Yake, Dale

2018-06-06

Conservative therapies for complex regional pain syndrome (CRPS) have traditionally focused on exercise and desensitization techniques targeted at the involved extremity. The primary purpose of this case series is to report on the potential benefit of utilizing manual therapy to the lumbar spine in conjunction with traditional conservative care when treating patients with lower extremity CRPS. Two patients with the diagnosis of lower extremity CRPS were treated with manual therapy to the lumbar spine in conjunction with education, exercise, desensitization, and soft tissue techniques for the extremity. Patient 1 received 13 sessions over 6 weeks resulting in a 34-point improvement in oswestry disability index (ODI) and 35-point improvement in lower extremity functional scale (LEFS). Patient 2 received 21 sessions over 12 weeks resulting in a 28-point improvement in ODI and a 41-point improvement in LEFS. Both patients exhibited reductions in pain and clinically meaningful improvements in function. Manual therapies when applied to the lumbar spine in these patients as part of a comprehensive treatment plan resulted in improved spinal mobility, decreased pain, and reduction is distal referred symptoms. Although one cannot infer a cause and effect relationship from a case series, this report identifies meaningful clinical outcomes potentially associated with manual physical therapy to the lumbar spine for two patients with complex regional pain syndrome type 1.

The planarian TCF/LEF factor Smed-tcf1 is required for the regeneration of dorsal-lateral neuronal subtypes.

PubMed

Brown, David D R; Molinaro, Alyssa M; Pearson, Bret J

2018-01-15

The adult brain of the planarian Schmidtea mediterranea (a freshwater flatworm) is a dynamic structure with constant cell turnover as well as the ability to completely regenerate de novo. Despite this, function and pattern is achieved in a reproducible manner from individual to individual in terms of the correct spatial and temporal production of specific neuronal subtypes. Although several signaling molecules have been found to be key to scaling and cell turnover, the mechanisms by which specific neural subtypes are specified remain largely unknown. Here we performed a 6 day RNAseq time course on planarians that were regenerating either 0, 1, or 2 heads in order to identify novel regulators of brain regeneration. Focusing on transcription factors, we identified a TCF/LEF factor, Smed-tcf1, which was required to correctly pattern the dorsal-lateral cell types of the regenerating brain. The most severely affected neurons in Smed-tcf1(RNAi) animals were the dorsal GABAergic neurons, which failed to regenerate, leading to an inability of the animals to phototaxis away from light. Together, Smed-tcf1 is a critical regulator, required to pattern the dorsal-lateral region of the regenerating planarian brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Stage-specific control of connective tissue growth factor (CTGF/CCN2) expression in chondrocytes by Sox9 and beta-catenin.

PubMed

Huang, Bau-Lin; Brugger, Sean M; Lyons, Karen M

2010-09-03

CCN2/connective tissue growth factor is highly expressed in hypertrophic chondrocytes and is required for chondrogenesis. However, the transcriptional mechanisms controlling its expression in cartilage are largely unknown. The activity of the Ccn2 promoter was, therefore, investigated in osteochondro-progenitor cells and hypertrophic chondrocytes to ascertain these mechanisms. Sox9 and T-cell factor (TCF) x lymphoid enhancer factor (LEF) factors contain HMG domains and bind to related consensus sites. TCF x LEF factors are normally repressive but when bound to DNA in a complex with beta-catenin become activators of gene expression. In silico analysis of the Ccn2 proximal promoter identified multiple consensus TCF x LEF elements, one of which was also a consensus binding site for Sox9. Using luciferase reporter constructs, the TCF x LEF x Sox9 site was found to be involved in stage-specific expression of Ccn2. Luciferase, electrophoretic mobility shift assay (EMSA), and ChIP analysis revealed that Sox9 represses Ccn2 expression by binding to the consensus TCF x LEF x Sox9 site. On the other hand, the same assays showed that in hypertrophic chondrocytes, TCF x LEF x beta-catenin complexes occupy the consensus TCF x LEF x Sox9 site and activate Ccn2 expression. Furthermore, transgenic mice in which lacZ expression is driven under the control of the proximal Ccn2 promoter revealed that the proximal Ccn2 promoter responded to Wnt signaling in cartilage. Hence, we propose that differential occupancy of the TCF x LEF x Sox9 site by Sox9 versus beta-catenin restricts high levels of Ccn2 expression to hypertrophic chondrocytes.

Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer.

PubMed

Chu, Maolin; Zhang, Chunying

2018-01-24

Angiogenesis plays an important role in bladder cancer (BCa). The immunosuppressive drug leflunomide has attracted worldwide attention. However, the effects of leflunomide on angiogenesis in cancer remain unclear. Here, we report the increased expression of soluble ephrin-A1 (sEphrin-A1) in supernatants of BCa cell lines (RT4, T24, and TCCSUP) co-cultured with human umbilical vein endothelial cells (HUVECs) compared with that in immortalized uroepithelial cells (SV-HUC-1) co-cultured with HUVECs. sEphrin-A1 is released from BCa cells as a monomeric protein that is a functional form of the ligand. The co-culture supernatants containing sEphrin-A1 caused the internalization and down-regulation of EphA2 on endothelial cells and dramatic functional activation of HUVECs. This sEphrin-A1/EphA2 system is mainly functional in regulating angiogenesis in BCa tissue. We showed that leflunomide (LEF) inhibited angiogenesis in a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder carcinogenesis model and a tumor xenograft model, as well as in BCa cell and HUVEC co-culture systems, via significant inhibition of the sEphrin-A1/EphA2 system. Ephrin-A1 overexpression could partially reverse LEF-induced suppression of angiogenesis and subsequent tumor growth inhibition. Thus, LEF has a significant anti-angiogenesis effect on BCa cells and BCa tissue via its inhibition of the functional angiogenic sEphrin-A1/EphA2 system and may have potential for treating BCa beyond immunosuppressive therapy.

Project 2000-3 Leading Edge Enterprise: Insights into Employment and Training Practices. Working Paper.

ERIC Educational Resources Information Center

Long, Michael; Fischer, John

Leading-edge firms (LEFs)--at the forefront of their industry in terms of growth or market share--may influence skill development through diffusion of technology, products, or practices and use of market power to set standards or change customer businesses. Study of LEFs can identify the type and mix of skills needed in the industry. LEFs are…

Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the β-Catenin/TCF/LEF-1 pathway in gastric cancer cells.

PubMed

Tang, Xiaoli; Zheng, Dong; Hu, Ping; Zeng, Zongyue; Li, Ming; Tucker, Lynne; Monahan, Renee; Resnick, Murray B; Liu, Manran; Ramratnam, Bharat

2014-03-01

Glycogen synthase kinase 3 beta (GSK3β) is a critical protein kinase that phosphorylates numerous proteins in cells and thereby impacts multiple pathways including the β-Catenin/TCF/LEF-1 pathway. MicroRNAs (miRs) are a class of noncoding small RNAs of ∼22 nucleotides in length. Both GSK3β and miR play myriad roles in cell functions including stem cell development, apoptosis, embryogenesis and tumorigenesis. Here we show that GSK3β inhibits the expression of miR-96, miR-182 and miR-183 through the β-Catenin/TCF/LEF-1 pathway. Knockout of GSK3β in mouse embryonic fibroblast cells increases expression of miR-96, miR-182 and miR-183, coinciding with increases in the protein level and nuclear translocation of β-Catenin. In addition, overexpression of β-Catenin enhances the expression of miR-96, miR-182 and miR-183 in human gastric cancer AGS cells. GSK3β protein levels are decreased in human gastric cancer tissue compared with surrounding normal gastric tissue, coinciding with increases of β-Catenin protein, miR-96, miR-182, miR-183 and primary miR-183-96-182 cluster (pri-miR-183). Furthermore, suppression of miR-183-96-182 cluster with miRCURY LNA miR inhibitors decreases the proliferation and migration of AGS cells. Knockdown of GSK3β with siRNA increases the proliferation of AGS cells. Mechanistically, we show that β-Catenin/TCF/LEF-1 binds to the promoter of miR-183-96-182 cluster gene and thereby activates the transcription of the cluster. In summary, our findings identify a novel role for GSK3β in the regulation of miR-183-96-182 biogenesis through β-Catenin/TCF/LEF-1 pathway in gastric cancer cells.

Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2.

PubMed

Wang, Ying; Dong, Jie; Li, Dali; Lai, Li; Siwko, Stefan; Li, Yi; Liu, Mingyao

2013-09-01

The key signaling networks regulating mammary stem cells are poorly defined. The leucine-rich repeat containing G protein-coupled receptor (Lgr) family has been implicated in intestinal, gastric, and epidermal stem cell functions. We investigated whether Lgr4 functions in mammary gland development and mammary stem cells. We found that Lgr4(-/-) mice had delayed ductal development, fewer terminal end buds, and decreased side-branching. Crucially, the mammary stem cell repopulation capacity was severely impaired. Mammospheres from Lgr4(-/-) mice showed decreased Wnt signaling. Wnt3a treatment prevented the adverse effects of Lgr4 loss on organoid formation. Chromatin immunoprecipitation analysis indicated that Sox2 expression was controlled by the Lgr4/Wnt/β-catenin/Lef1 pathway. Importantly, Sox2 overexpression restored the in vivo mammary regeneration potential of Lgr4(-/-) mammary stem cells. Therefore, Lgr4 activates Sox2 to regulate mammary development and stem cell functions via Wnt/β-catenin/Lef1. © AlphaMed Press.

Expression of the lef5 gene from Spodoptera exigua multiple nucleopolyhedrovirus contributes to the baculovirus stability in cell culture.

PubMed

Martínez-Solís, María; Jakubowska, Agata K; Herrero, Salvador

2017-10-01

Baculoviruses are a broad group of viruses infecting insects, predominately of the order Lepidoptera. They are used worldwide as biological insecticides and as expression vectors to produce recombinant proteins. Baculoviruses replicate in their host, although several cell lines have been developed for in vitro replication. Nevertheless, replication of baculoviruses in cell culture involves the generation of defective viruses with a decrease in productivity and virulence. Transcriptional studies of the Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) and the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infective process revealed differences in the expression patterns when the virus replicated under in vitro (Se301 cells) or in vivo (S. exigua larvae) conditions. The late expression factor 5 (lef5) gene was found to be highly overexpressed when the virus replicates in larvae. To test the possible role of lef5 expression in viral stability, recombinant AcMNPV expressing the lef5 gene from SeMNPV (Se-lef5) was generated and its stability was monitored during successive infection passages in Sf21 cells by evaluating the loss of several essential and non-essential genes. The gfp transgene was more stable in those viruses expressing the Se-LEF5 protein and the GFP-defective viruses were accumulated at a lower level when compared to its control viruses, confirming the positive influence of lef5 in viral stability during the multiplication process. This work describes for the first time a viral factor involved in transgene stability when baculoviruses replicate in cell culture, opening new ways to facilitate the in vitro production of recombinant proteins using baculovirus.

Photosystem II-cyclic electron flow powers exceptional photoprotection and record growth in the microalga Chlorella ohadii.

PubMed

Ananyev, Gennady; Gates, Colin; Kaplan, Aaron; Dismukes, G Charles

2017-11-01

The desert microalga Chlorella ohadii was reported to grow at extreme light intensities with minimal photoinhibition, tolerate frequent de/re-hydrations, yet minimally employs antenna-based non-photochemical quenching for photoprotection. Here we investigate the molecular mechanisms by measuring Photosystem II charge separation yield (chlorophyll variable fluorescence, Fv/Fm) and flash-induced O 2 yield to measure the contributions from both linear (PSII-LEF) and cyclic (PSII-CEF) electron flow within PSII. Cells grow increasingly faster at higher light intensities (μE/m 2 /s) from low (20) to high (200) to extreme (2000) by escalating photoprotection via shifting from PSII-LEF to PSII-CEF. This shifts PSII charge separation from plastoquinone reduction (PSII-LEF) to plastoquinol oxidation (PSII-CEF), here postulated to enable proton gradient and ATP generation that powers photoprotection. Low light-grown cells have unusually small antennae (332 Chl/PSII), use mainly PSII-LEF (95%) and convert 40% of PSII charge separations into O 2 (a high O 2 quantum yield of 0.06mol/mol PSII/flash). High light-grown cells have smaller antenna and lower PSII-LEF (63%). Extreme light-grown cells have only 42 Chl/PSII (no LHCII antenna), minimal PSII-LEF (10%), and grow faster than any known phototroph (doubling time 1.3h). Adding a synthetic quinone in excess to supplement the PQ pool fully uncouples PSII-CEF from its natural regulation and produces maximum PSII-LEF. Upon dark adaptation PSII-LEF rapidly reverts to PSII-CEF, a transient protection mechanism to conserve water and minimize the cost of antenna biosynthesis. The capacity of the electron acceptor pool (plastoquinone pool), and the characteristic times for exchange of (PQH 2 ) B with PQ pool and reoxidation of (PQH 2 ) pool were determined. Copyright © 2017. Published by Elsevier B.V.

Time Burden of Standardized Hip Questionnaires.

PubMed

Chughtai, Morad; Khlopas, Anton; Mistry, Jaydev B; Gwam, Chukwuweike U; Elmallah, Randa K; Mont, Michael A

2016-04-01

Many standardized scales and questionnaires have been developed to assess outcomes of patients undergoing total hip arthroplasty (THA). However, these surveys can be a burden to both patients and orthopaedists as some are time-inefficient. In addition, there is a paucity of reports assessing the time it takes to complete them. In this study we aimed to: (1) assess how long it takes to complete the most common standardized hip questionnaires; (2) determine the presence of variation in completion time; and (3) evaluate the effects of age, gender, and level of education on completion time. Based on a previous study, we selected the seven most commonly used hip scoring systems-Western Ontario and McMaster Universities Hip Outcome Assessment (WOMAC), Harris Hip Score (HHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), Larson Score, Short-form 36 (SF-36), modified Merle d'Aubigne and Postel Score (MDA), and Lower Extremity Functional Scale (LEFS). The standardized scales and questionnaires were randomly administered to 70 subjects. The subjects were unaware that they were being timed during completion of the questionnaire. We obtained the coefficients of variation of time for each questionnaire. The mean time to complete the questionnaire was then stratified and compared based on age, gender, and level of education. The mean time to complete each of the systems is listed in ascending order: Modified Merle d'Aubigne and Postel Score (MDA), Lower Extremity Functional Scale (LEFS), Western Ontario and McMaster Universities Hip Outcome Assessment (WOMAC), Harris Hip Score (HHS), Larson Score, Hip Disability and Osteoarthritis Outcome Score (HOOS), and Short-form 36 (SF-36). The WOMAC and Larson Score coefficients of variation were the largest, and the HOOS and MDA were the smallest. There was a significantly higher mean time to completion in those who were above or equal to the age of 55 years as compared to those who were below the age of 55 (227 vs. 166 seconds). There was no significant association found in time of completion between gender or education level. Standardized scales and questionnaire which assess THA patients can be burdensome and time-inefficient, which may lead to task-induced fatigue. This may result in inaccurate THA patient assessments, which do not reflect the patient's true state. Future studies should aim to create an encompassing questionnaire that is time efficient and can replace all currently used validated systems.

Pilot study: whole body manual subcutaneous adipose tissue (SAT) therapy improved pain and SAT structure in women with lipedema.

PubMed

Herbst, Karen L; Ussery, Christopher; Eekema, Alyna

2017-09-20

Background Lipedema is a common painful subcutaneous adipose tissue (SAT) disorder in women affecting the limbs. SAT therapy is a manual therapy to improve soft tissue quality. Objective Determine if SAT therapy improves pain and structure of lipedema SAT. Design Single arm prospective pilot study. Setting Academic medical center. Patients Seven women, 46 ± 5 years, weight 90 ± 19 kg, with lipedema. Intervention Twelve 90-min SAT therapy sessions over 4 weeks. Outcomes Dual X-ray absorptiometry (DXA) scans, SAT ultrasound (Vevo 2100), leg volumetrics, skin caliper assessment, tissue exam, weight, resting metabolic rate, pain assessment, lower extremity functional scale (LEFS) and body shape questionnaire (BSQ) at baseline and end of study. Results Weight, resting metabolic rate and BSQ did not change significantly. Limb fat over total body fat mass (p = 0.08) and trunk fat over total body mass trended down from baseline (p = 0.08) by DXA. Leg volume and caliper assessments in eight of nine areas (p < 0.007), LEFS (p = 0.002) and average pain (p = 0.007) significantly decreased from baseline. Fibrosis significantly decreased in the nodules, hips and groin. Ultrasound showed improved SAT structure in some subjects. Side effects included pain, bruising, itching, swelling and gastroesophageal reflux disease. All women said they would recommend SAT therapy to other women with lipedema. Limitations Small number of subjects. Conclusion SAT therapy in 4 weeks improved tissue structure, perceived leg function, and volume although shape was not affected. While side effects of SAT therapy were common, all women felt the therapy was beneficial.

Comparative Profiling of Primary Colorectal Carcinomas and Liver Metastases Identifies LEF1 as a Prognostic Biomarker

PubMed Central

Lin, Albert Y.; Chua, Mei-Sze; Choi, Yoon-La; Yeh, William; Kim, Young H.; Azzi, Raymond; Adams, Gregg A.; Sainani, Kristin; van de Rijn, Matt; So, Samuel K.; Pollack, Jonathan R.

2011-01-01

Purpose We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). Patients and Methods We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Results Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1. Conclusion Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. PMID:21383983

Dry cupping for plantar fasciitis: a randomized controlled trial.

PubMed

Ge, Weiqing; Leson, Chelsea; Vukovic, Corey

2017-05-01

[Purpose] The purpose of this study was to determine the effects of dry cupping on pain and function of patients with plantar fasciitis. [Subjects and Methods] Twenty-nine subjects (age 15 to 59 years old, 20 females and 9 males), randomly assigned into the two groups (dry cupping therapy and electrical stimulation therapy groups), participated in this study. The research design was a randomized controlled trial (RCT). Treatments were provided to the subjects twice a week for 4 weeks. Outcome measurements included the Visual Analogue Pain Scale (VAS) (at rest, first in the morning, and with activities), the Foot and Ankle Ability Measure (FAAM), the Lower Extremity Functional Scale (LEFS), as well as the pressure pain threshold. [Results]The data indicated that both dry cupping therapy and electrical stimulation therapy could reduce pain and increase function significantly in the population tested, as all the 95% Confidence Intervals (CIs) did not include 0 except for the pressure pain threshold. There was no significant difference between the dry cupping therapy and electrical stimulation groups in all the outcome measurements. [Conclusion] These results support that both dry cupping therapy and electrical stimulation therapy could reduce pain and increase function in the population tested.

Dry cupping for plantar fasciitis: a randomized controlled trial

PubMed Central

Ge, Weiqing; Leson, Chelsea; Vukovic, Corey

2017-01-01

[Purpose] The purpose of this study was to determine the effects of dry cupping on pain and function of patients with plantar fasciitis. [Subjects and Methods] Twenty-nine subjects (age 15 to 59 years old, 20 females and 9 males), randomly assigned into the two groups (dry cupping therapy and electrical stimulation therapy groups), participated in this study. The research design was a randomized controlled trial (RCT). Treatments were provided to the subjects twice a week for 4 weeks. Outcome measurements included the Visual Analogue Pain Scale (VAS) (at rest, first in the morning, and with activities), the Foot and Ankle Ability Measure (FAAM), the Lower Extremity Functional Scale (LEFS), as well as the pressure pain threshold. [Results]The data indicated that both dry cupping therapy and electrical stimulation therapy could reduce pain and increase function significantly in the population tested, as all the 95% Confidence Intervals (CIs) did not include 0 except for the pressure pain threshold. There was no significant difference between the dry cupping therapy and electrical stimulation groups in all the outcome measurements. [Conclusion] These results support that both dry cupping therapy and electrical stimulation therapy could reduce pain and increase function in the population tested. PMID:28603360

Orthosis-Shaped Sandals Are as Efficacious as In-Shoe Orthoses and Better than Flat Sandals for Plantar Heel Pain: A Randomized Control Trial

PubMed Central

Vicenzino, Bill; McPoil, Thomas G.; Stephenson, Aoife; Paul, Sanjoy K.

2015-01-01

Objective To investigate efficacy of a contoured sandal being marketed for plantar heel pain with comparison to a flat flip-flop and contoured in-shoe insert/orthosis. Method 150 volunteers aged 50 (SD: 12) years with plantar heel pain (>4 weeks) were enrolled after responding to advertisements and eligibility determined by telephone and at first visit. Participants were randomly allocated to receive commercially available contoured sandals (n = 49), flat flip-flops (n = 50) or over the counter, pre-fabricated full-length foot orthotics (n = 51). Primary outcomes were a 15-point Global Rating of Change scale (GROC: 1 = a very great deal worse, 15 = a very great deal better), 13 to 15 representing an improvement and the 20-item Lower Extremity Function Scale (LEFS) on which participants rate 20 common weight bearing activities and activities of daily living on a 5-point scale (0 = extreme difficulty, 4 = no difficulty). Secondary outcomes were worst level of heel pain in the preceding week, and the foot and ankle ability measure. Outcomes were collected blind to allocation. Analyses were done on an intention to treat basis with 12 weeks being the primary outcome time of interest. Results The contoured sandal was 68% more likely to report improvement in terms of GROC compared to flat flip-flop. On the LEFS the contoured sandal was 61% more likely than flat flip-flop to report improvement. The secondary outcomes in the main reflected the primary outcomes, and there were no differences between contoured sandal and shoe insert. Conclusions and Relevance Physicians can have confidence in supporting a patient's decision to wear contoured sandals or in-shoe orthoses as one of the first and simple strategies to manage their heel pain. Trial Registration The Australian New Zealand Clinical Trials Registry ACTRN12612000463875 PMID:26669302

Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal.

PubMed

Sun, Zhao; Yu, Wenjie; Sanz Navarro, Maria; Sweat, Mason; Eliason, Steven; Sharp, Thad; Liu, Huan; Seidel, Kerstin; Zhang, Li; Moreno, Myriam; Lynch, Thomas; Holton, Nathan E; Rogers, Laura; Neff, Traci; Goodheart, Michael J; Michon, Frederic; Klein, Ophir D; Chai, Yang; Dupuy, Adam; Engelhardt, John F; Chen, Zhi; Amendt, Brad A

2016-11-15

Sox2 marks dental epithelial stem cells (DESCs) in both mammals and reptiles, and in this article we demonstrate several Sox2 transcriptional mechanisms that regulate dental stem cell fate and incisor growth. Conditional Sox2 deletion in the oral and dental epithelium results in severe craniofacial defects, including impaired dental stem cell proliferation, arrested incisor development and abnormal molar development. The murine incisor develops initially but is absorbed independently of apoptosis owing to a lack of progenitor cell proliferation and differentiation. Tamoxifen-induced inactivation of Sox2 demonstrates the requirement of Sox2 for maintenance of the DESCs in adult mice. Conditional overexpression of Lef-1 in mice increases DESC proliferation and creates a new labial cervical loop stem cell compartment, which produces rapidly growing long tusk-like incisors, and Lef-1 epithelial overexpression partially rescues the tooth arrest in Sox2 conditional knockout mice. Mechanistically, Pitx2 and Sox2 interact physically and regulate Lef-1, Pitx2 and Sox2 expression during development. Thus, we have uncovered a Pitx2-Sox2-Lef-1 transcriptional mechanism that regulates DESC homeostasis and dental development. © 2016. Published by The Company of Biologists Ltd.

Molecular characterization of nucleopolyhedrovirus of three lepidopteran pests using late expression factor-8 gene.

PubMed

Jose, Jency; Jalali, S K; Shivalingaswamy, T M; Kumar, N K Krishna; Bhatnagar, R; Bandyopadhyay, A

2013-06-01

A PCR based method for detection of viral DNA in nucleopolyhedrovirus of three lepidopterans, Spodoptera litura, Amsacta albistriga and Helicoverpa armigera, was developed by employing the late expression factor-8 (lef-8) gene of three NPV using specific primers. The amplicons of 689, 699 and 665 bp were amplified, respectively, and the nucleotide sequences were submitted to GenBank and the accession numbers were obtained. The sequences of lef-8 gene of S. litura NPV and H. armigera NPV matched with those of their respective references in the GenBank database, thereby confirming their identity, however, the sequence of A. albistriga NPV was the first sequence submitted to the GenBank database. The sequence similarity analysis between the three lef-8 gene of NPV sequenced in the present study revealed that there was no significant similarity between them, however A. albistriga NPV and S. litura NPV were found to be closely related. CLUSTAL alignment of the sequences generated revealed general relatedness among NPVs lef-8 gene. The study confirmed that lef-8 gene can be used for quick and correct discriminatory identification of insect viruses.

Use of the gait profile score for the evaluation of patients with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type.

PubMed

Celletti, Claudia; Galli, Manuela; Cimolin, Veronica; Castori, Marco; Tenore, Nunzio; Albertini, Giorgio; Camerota, Filippo

2013-11-01

Gait analysis (GA) is widely used for clinical evaluations in various pathological states, both in children and in adults, such as in patients with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT). Otherwise, GA produces a large volume of data and there is the clinical need to provide also a quantitative measure of the patient's overall gait. Starting from this aim some global indexes were proposed by literature as a summary measure of the patient's gait, such as the Gait Profile Score (GPS). While validity of the GPS was demonstrated for the evaluation of the functional limitation of children with Cerebral Palsy, no studies have been conducted in patients JHS/EDS-HT. The aim of our study was therefore to investigate the effectiveness of the GPS in the quantification of functional limitation of patients with JHS/EDS-HT. Twenty-one adult (age: 36.1 ± 12.7 years) individuals with JHS/EDS-HT were evaluated using GA and from GA data the GPS was computed. The results evidenced that the GPS value of patients was 8.9 ± 2.6, statistically different from 4.6 ± 0.9 displayed by the control group. In particular, all values of Gait Variable Scores (GVS) which compose the GPS were higher if compared to controls, with the exception of Pelvic Tilt and Foot Progression. The correlations between GPS/GVS and Lower Extremity Functional Scale (LEFS) showed significant relationship between GPS and the item 11 ("Walking 2 blocks") (ρ=-0.56; p<0.05) and 12 ("Walking a mile") of LEFS (ρ=-0.76; p<0.05). Our results showed that GPS and GVS seem to be appropriate outcome measures for the evaluation of the functional limitation during gait of patients with JHS/EDS-HT. Copyright © 2013 Elsevier Ltd. All rights reserved.

Controlled morphology and optical properties of n-type porous silicon: effect of magnetic field and electrode-assisted LEF.

PubMed

Antunez, Edgar E; Campos, Jose; Basurto, Miguel A; Agarwal, Vivechana

2014-01-01

Fabrication of photoluminescent n-type porous silicon (nPS), using electrode-assisted lateral electric field accompanied with a perpendicular magnetic field, is reported. The results have been compared with the porous structures fabricated by means of conventional anodization and electrode-assisted lateral electric field without magnetic field. The lateral electric field (LEF) applied across the silicon substrate leads to the formation of structural gradient in terms of density, dimension, and depth of the etched pores. Apart from the pore shape tunability, the simultaneous application of LEF and magnetic field (MF) contributes to a reduction of the dimension of the pores and promotes relatively more defined pore tips as well as a decreased side-branching in the pore walls of the macroporous structure. Additionally, when using magnetic field-assisted etching, within a certain range of LEF, an enhancement of the photoluminescence (PL) response was obtained.

Controlled morphology and optical properties of n-type porous silicon: effect of magnetic field and electrode-assisted LEF

PubMed Central

2014-01-01

Fabrication of photoluminescent n-type porous silicon (nPS), using electrode-assisted lateral electric field accompanied with a perpendicular magnetic field, is reported. The results have been compared with the porous structures fabricated by means of conventional anodization and electrode-assisted lateral electric field without magnetic field. The lateral electric field (LEF) applied across the silicon substrate leads to the formation of structural gradient in terms of density, dimension, and depth of the etched pores. Apart from the pore shape tunability, the simultaneous application of LEF and magnetic field (MF) contributes to a reduction of the dimension of the pores and promotes relatively more defined pore tips as well as a decreased side-branching in the pore walls of the macroporous structure. Additionally, when using magnetic field-assisted etching, within a certain range of LEF, an enhancement of the photoluminescence (PL) response was obtained. PMID:25313298

Smad4 suppresses the tumorigenesis and aggressiveness of neuroblastoma through repressing the expression of heparanase.

PubMed

Qu, Hongxia; Zheng, Liduan; Jiao, Wanju; Mei, Hong; Li, Dan; Song, Huajie; Fang, Erhu; Wang, Xiaojing; Li, Shiwang; Huang, Kai; Tong, Qiangsong

2016-09-06

Heparanase (HPSE) is the only endo-β-D-glucuronidase that is correlated with the progression of neuroblastoma (NB), the most common extracranial malignancy in childhood. However, the mechanisms underlying HPSE expression in NB still remain largely unknown. Herein, through analyzing cis-regulatory elements and mining public microarray datasets, we identified SMAD family member 4 (Smad4) as a crucial transcription regulator of HPSE in NB. We demonstrated that Smad4 repressed the HPSE expression at the transcriptional levels in NB cells. Mechanistically, Smad4 suppressed the HPSE expression through directly binding to its promoter and repressing the lymphoid enhancer binding factor 1 (LEF1)-facilitated transcription of HPSE via physical interaction. Gain- and loss-of-function studies demonstrated that Smad4 inhibited the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. Restoration of HPSE expression prevented the NB cells from changes in these biological features induced by Smad4. In clinical NB specimens, Smad4 was under-expressed and inversely correlated with HPSE levels, while LEF1 was highly expressed and positively correlated with HPSE expression. Patients with high Smad4 expression, low LEF1 or HPSE levels had greater survival probability. These results demonstrate that Smad4 suppresses the tumorigenesis and aggressiveness of NB through repressing the HPSE expression.

Characterization of a baculovirus lacking the DBP (DNA-binding protein) gene

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

Vanarsdall, Adam L.; Mikhailov, Victor S.; N.K. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow 117808

2007-08-01

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) encodes two proteins that possess properties typical of single-stranded DNA-binding proteins (SSBs), late expression factor-3 (LEF-3), and a protein referred to as DNA-binding protein (DBP). Whereas LEF-3 is a multi-functional protein essential for viral DNA replication, transporting helicase into the nucleus, and forms a stable complex with the baculovirus alkaline nuclease, the role for DBP in baculovirus replication remains unclear. Therefore, to better understand the functional role of DBP in viral replication, a DBP knockout virus was generated from an AcMNPV bacmid and analyzed. The results of a growth curve analysis indicated that the dbpmore » knockout construct was unable to produce budded virus indicating that dbp is essential. The lack of DBP does not cause a general shutdown of the expression of viral genes, as was revealed by accumulation of early (LEF-3), late (VP39), and very late (P10) proteins in cells transfected with the dbp knockout construct. To investigate the role of DBP in DNA replication, a real-time PCR-based assay was employed and showed that, although viral DNA synthesis occurred in cells transfected with the dbp knockout, the levels were less than that of the control virus suggesting that DBP is required for normal levels of DNA synthesis or for stability of nascent viral DNA. In addition, analysis of the viral DNA replicated by the dbp knockout by using field inversion gel electrophoresis failed to detect the presence of genome-length DNA. Furthermore, analysis of DBP from infected cells indicated that similar to LEF-3, DBP was tightly bound to viral chromatin. Assessment of the cellular localization of DBP relative to replicated viral DNA by immunoelectron microscopy indicated that, at 24 h post-infection, DBP co-localized with nascent DNA at distinct electron-dense regions within the nucleus. Finally, immunoelectron microscopic analysis of cells transfected with the dbp knockout revealed that DBP is required for the production of normal-appearing nucleocapsids and for the generation of the virogenic stroma.« less

The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis.

PubMed

Ruiz-Padilla, A J; Gamez-Nava, J I; Saldaña-Cruz, A M; Murillo-Vazquez, J D; Vazquez-Villegas, M L; Zavaleta-Muñiz, S A; Martín-Márquez, B T; Ponce-Guarneros, J M; Rodriguez Jimenez, N A; Flores-Chavez, A; Sandoval-Garcia, F; Vasquez-Jimenez, J C; Cardona-Muñoz, E G; Totsuka-Sutto, S E; Gonzalez-Lopez, L

2016-01-01

Objective . To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results . Patients with MTX or LEF had significant decrement in DAS-28 ( p < 0.001); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07-1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05-2.3; p = 0.003), or CC (RR = 1.83; 95% CI = 1.07-3.14; p = 0.001). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03-1.72; p = 0.02). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that IL-6 -174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF.

Proton gradient regulation 5 supports linear electron flow to oxidize photosystem I.

PubMed

Takagi, Daisuke; Miyake, Chikahiro

2018-03-31

In higher plants, light drives the linear photosynthetic electron transport reaction from H 2 O to electron sinks, which is called as linear electron flow (LEF). LEF activity should be regulated depending on electron sinks; otherwise excess electrons accumulate in the thylakoid membranes and stimulate reactive oxygen species (ROS) production in photosystem I (PSI), which causes oxidative damage to PSI. To prevent ROS production in PSI, PSI should be oxidized during photosynthesis, and PROTON GRADIENT REGULATION 5 (PGR5) and PGR like 1 (PGRL1) are important to oxidized PSI. PGR5 and PGRL1 are recognized as a component of ferredoxin-dependent cyclic electron flow around PSI (Fd-CEF-PSI), however there is no direct evidence for the significant operation of Fd-CEF-PSI during photosynthesis in wild-type (WT) plants. Thus, electron distribution by PGR5 and PGRL1 between Fd-CEF-PSI and LEF is still elusive. Here, we show direct evidence that Fd-CEF-PSI activity is minor during steady state photosynthesis by measuring the Fd redox state in vivo in Arabidopsis thaliana. We found that Fd oxidation rate is determined by LEF activity during steady state photosynthesis in WT. On the other hand, pgr5 and pgrl1 showed lower electron transport efficiency from PSI to electron sinks through Fd during steady state photosynthesis. These results demonstrate that electrons are exclusively consumed in electron sinks through Fd, and the phenotypes of pgr5 and pgrl1 are likely caused by the disturbance of the LEF between PSI and electron sinks. We suggest that PGR5 and PGRL1 modulate the LEF according to electron sink activities around PSI. This article is protected by copyright. All rights reserved.

Whole-Genome Sequences of Variants of Bacillus anthracis Sterne and Their Toxin Gene Deletion Mutants

PubMed Central

Staab, A.; Plaut, R. D.; Pratt, C.; Lovett, S. P.; Wiley, M. R.; Biggs, T. D.; Bernhards, R. C.; Beck, L. C.; Palacios, G. F.; Stibitz, S.; Jones, K. L.; Goodwin, B. G.; Smith, M. A.

2017-01-01

ABSTRACT Here, we report the draft genome sequences of three laboratory variants of Bacillus anthracis Sterne and their double (Δlef Δcya) and triple (Δpag Δlef Δcya) toxin gene deletion derivatives. PMID:29122874

Light emitting fabric for photodynamic treatment of actinic keratosis

NASA Astrophysics Data System (ADS)

Thecua, E.; Vicentini, C.; Vignion, A.-S.; Lecomte, F.; Deleporte, P.; Mortier, L.; Szeimies, R.-M.; Mordon, S.

2017-02-01

The integration of optical fibers into flexible textile structures, by using knitting or weaving processes can allow the development of flexible light sources. The paper aims to present a new technology: Light Emitting Fabrics (LEF), which can be used for example for PDT of Actinic Keratosis in Dermatology. The predetermined macro-bending of optical fibers, led to a homogeneous side emission of light over the entire surface of the fabric. Tests showed that additional curvatures when applying the LEF on non-planar surfaces had no impact on light delivery and proved that LEF can adapt to the human morphology. The ability of the LEF, coupled with a 635nm LASER source, to deliver a homogeneous light to lesions is currently assessed in a clinical trial for the treatment of AK of the scalp by PDT. The low irradiance and progressive activation of the photosensitizer ensure a pain reduction, compared to discomfort levels experienced by patients during a conventional PDT session.

Combination of alcohol and fructose exacerbates metabolic imbalance in terms of hepatic damage, dyslipidemia, and insulin resistance in rats.

PubMed

Alwahsh, Salamah Mohammad; Xu, Min; Schultze, Frank Christian; Wilting, Jörg; Mihm, Sabine; Raddatz, Dirk; Ramadori, Giuliano

2014-01-01

Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (≤3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial β-oxidation of fatty acids (Cpt1α and Ppar-α expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage.

Alpha-glucosidase Inhibitory and Antioxidant Potential of Antidiabetic Herb Alternanthera sessilis: Comparative Analyses of Leaf and Callus Solvent Fractions.

PubMed

Chai, Tsun-Thai; Khoo, Chee-Siong; Tee, Chong-Siang; Wong, Fai-Chu

2016-01-01

Alternanthera sessilis is a medicinal herb which is consumed as vegetable and used as traditional remedies of various ailments in Asia and Africa. This study aimed to investigate the antiglucosidase and antioxidant activity of solvent fractions of A. sessilis leaf and callus. Leaf and callus methanol extracts were fractionated to produce hexane, chloroform, ethyl acetate, butanol, and water fractions. Antiglucosidase and 1,1-diphenyl-2-picrylhydrazyl scavenging activities as well as total phenolic (TP), total flavonoid (TF), and total coumarin (TC) contents were evaluated. Lineweaver-Burk plot analysis was performed on leaf and callus fractions with the strongest antiglucosidase activity. Leaf ethyl acetate fraction (LEF) had the strongest antiglucosidase (EC 50 0.55 mg/mL) and radical scavenging (EC 50 10.81 μg/mL) activity among leaf fractions. Callus ethyl acetate fraction (CEF) and chloroform fraction had the highest antiglucosidase (EC 50 0.25 mg/mL) and radical scavenging (EC 50 34.12 μg/mL) activity, respectively, among callus fractions. LEF and CEF were identified as noncompetitive and competitive α-glucosidase inhibitors, respectively. LEF and CEF had greater antiglucosidase activity than acarbose. Leaf fractions had higher phytochemical contents than callus fractions. LEF had the highest TP, TF, and TC contents. Antiglucosidase and antioxidant activities of leaf fractions correlated with phytochemical contents. LEF had potent antiglucosidase activity and concurrent antioxidant activity. CEF had the highest antiglucosidase activity among all fractions. Callus culture is a promising tool for enhancing production of potent α-glucosidase inhibitors. Leaf ethyl acetate fraction (LEF) had the strongest antiglucosidase (EC 50 0.55 mg/mL) and radical scavenging (EC 50 10.81 μg/mL) activity among leaf fractionsCallus ethyl acetate fraction (CEF) and chloroform fraction had the highest antiglucosidase (EC 50 0.25 mg/mL) and radical scavenging (EC 50 34.12 μg/mL) activity, respectively, among callus fractionsLEF and CEF were identified as noncompetitive and competitive á-glucosidase inhibitors, respectivelyAntiglucosidase and antioxidant activities of leaf fractions correlated with phytochemical contents. Abbreviations used: LHF: Leaf hexane fraction, LCF: Leaf chloroform fraction, LEF: Leaf ethyl acetate fraction, LBF: Leaf butanol fraction, LWF: Leaf water fraction, CHF: Callus hexane fraction, CCF: Callus chloroform fraction, CEF: Callus ethyl acetate fraction, CBF: Callus butanol fraction, CWF: Callus water fraction, TP: Total phenolic, TF: Total flavonoid, TC: Total coumarin.

Behavioral health in young adults with epilepsy: Implications for transition of care.

PubMed

Wagner, Janelle L; Wilson, Dulaney A; Kellermann, Tanja; Smith, Gigi; Malek, Angela M; Wannamaker, Braxton; Selassie, Anbesaw W

2016-12-01

Neurodevelopmental and behavioral health disorders commonly occur with epilepsy, yet risk for young adults is unknown. The aim of this study was to determine the distribution and risk characteristics of neurodevelopmental and behavior health comorbidities among young adults with epilepsy compared with those among young adults with migraine and healthy controls. A case-control study examining hospital admission, outpatient, and emergency department (ED) visits for young adults with an ICD-9-CM diagnosis of epilepsy, migraine, or lower extremity fracture (LEF) was conducted. The association of epilepsy, migraine, or LEF with comorbidities was evaluated with univariate and multivariate polytomous logistic regression. From 2000 to 2013, 29,139 young adults ages 19 to 25years were seen in hospitals and EDs for epilepsy (5666), migraine (17,507), or LEF (5966). Young adults with epilepsy had higher proportions of behavioral health comorbidities (51.8%) compared with controls with migraine (37.6%) or LEF (21.6%). In young adults with epilepsy compared with migraine, the increased risk of having any behavioral health comorbidity was 76%, and neurodevelopmental comorbidity was 297%. After adjustment, young adults with epilepsy showed significantly higher odds of each behavioral health comorbidity compared with controls with migraine and LEF. Young adults with epilepsy are particularly susceptible to behavioral health and neurodevelopmental disorders. Results are discussed within the context of transition to adult care. Copyright © 2016 Elsevier Inc. All rights reserved.

Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis.

PubMed

Conacci-Sorrell, Maralice E; Ben-Yedidia, Tamar; Shtutman, Michael; Feinstein, Elena; Einat, Paz; Ben-Ze'ev, Avri

2002-08-15

beta-catenin and plakoglobin (gamma-catenin) are homologous molecules involved in cell adhesion, linking cadherin receptors to the cytoskeleton. beta-catenin is also a key component of the Wnt pathway by being a coactivator of LEF/TCF transcription factors. To identify novel target genes induced by beta-catenin and/or plakoglobin, DNA microarray analysis was carried out with RNA from cells overexpressing either protein. This analysis revealed that Nr-CAM is the gene most extensively induced by both catenins. Overexpression of either beta-catenin or plakoglobin induced Nr-CAM in a variety of cell types and the LEF/TCF binding sites in the Nr-CAM promoter were required for its activation by catenins. Retroviral transduction of Nr-CAM into NIH3T3 cells stimulated cell growth, enhanced motility, induced transformation, and produced rapidly growing tumors in nude mice. Nr-CAM and LEF-1 expression was elevated in human colon cancer tissue and cell lines and in human malignant melanoma cell lines but not in melanocytes or normal colon tissue. Dominant negative LEF-1 decreased Nr-CAM expression and antibodies to Nr-CAM inhibited the motility of B16 melanoma cells. The results indicate that induction of Nr-CAM transcription by beta-catenin or plakoglobin plays a role in melanoma and colon cancer tumorigenesis, probably by promoting cell growth and motility.

Smad4 suppresses the tumorigenesis and aggressiveness of neuroblastoma through repressing the expression of heparanase

PubMed Central

Qu, Hongxia; Zheng, Liduan; Jiao, Wanju; Mei, Hong; Li, Dan; Song, Huajie; Fang, Erhu; Wang, Xiaojing; Li, Shiwang; Huang, Kai; Tong, Qiangsong

2016-01-01

Heparanase (HPSE) is the only endo-β-D-glucuronidase that is correlated with the progression of neuroblastoma (NB), the most common extracranial malignancy in childhood. However, the mechanisms underlying HPSE expression in NB still remain largely unknown. Herein, through analyzing cis-regulatory elements and mining public microarray datasets, we identified SMAD family member 4 (Smad4) as a crucial transcription regulator of HPSE in NB. We demonstrated that Smad4 repressed the HPSE expression at the transcriptional levels in NB cells. Mechanistically, Smad4 suppressed the HPSE expression through directly binding to its promoter and repressing the lymphoid enhancer binding factor 1 (LEF1)-facilitated transcription of HPSE via physical interaction. Gain- and loss-of-function studies demonstrated that Smad4 inhibited the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. Restoration of HPSE expression prevented the NB cells from changes in these biological features induced by Smad4. In clinical NB specimens, Smad4 was under-expressed and inversely correlated with HPSE levels, while LEF1 was highly expressed and positively correlated with HPSE expression. Patients with high Smad4 expression, low LEF1 or HPSE levels had greater survival probability. These results demonstrate that Smad4 suppresses the tumorigenesis and aggressiveness of NB through repressing the HPSE expression. PMID:27595937

Principle of radial transport in low temperature annular plasmas

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

Zhang, Yunchao, E-mail: yunchao.zhang@anu.edu.au; Charles, Christine; Boswell, Rod

2015-07-15

Radial transport in low temperature annular plasmas is investigated theoretically in this paper. The electrons are assumed to be in quasi-equilibrium due to their high temperature and light inertial mass. The ions are not in equilibrium and their transport is analyzed in three different situations: a low electric field (LEF) model, an intermediate electric field (IEF) model, and a high electric field (HEF) model. The universal IEF model smoothly connects the LEF and HEF models at their respective electric field strength limits and gives more accurate results of the ion mobility coefficient and effective ion temperature over the entire electricmore » field strength range. Annular modelling is applied to an argon plasma and numerical results of the density peak position, the annular boundary loss coefficient and the electron temperature are given as functions of the annular geometry ratio and Paschen number.« less

Bmp7 and Lef1 are the downstream effectors of androgen signaling in androgen-induced sex characteristics development in medaka.

PubMed

Ogino, Yukiko; Hirakawa, Ikumi; Inohaya, Keiji; Sumiya, Eri; Miyagawa, Shinichi; Denslow, Nancy; Yamada, Gen; Tatarazako, Norihisa; Iguchi, Taisen

2014-02-01

Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgen-dependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.

Luquillo Experimental Forest: Research History and Opportunities

Treesearch

Nancy L. Harris; Ariel E. Lugo; Sandra Brown; Tamara Heartsill-Scalley

2012-01-01

The goals of this Luquillo Experimental Forest: Research History and Opportunities are to synthesize the new research that has emerged from the LEF since the publication of Brown et al. (1983) into a concise summary of key research findings and to highlight opportunities for future research that will contribute to a greater understanding of the structure and function...

A systematic review of self-administered questionnaires for the functional assessment of patients with knee disabilities adapted into Spanish.

PubMed

Gómez-Valero, S; García-Pérez, F; Flórez-García, M T; Miangolarra-Page, J C

The aim of this study was to conduct a systematic review of self-administered knee-disability functional assessment questionnaires adapted to Spanish, analysing the quality of the transcultural adaptation procedure and the psychometric properties of the new version. A search was conducted in the main biomedical databases to find knee-function assessment scales adapted into Spanish, in order to assess their questionnaire adaptation process as well as their psychometric properties. Ten scales were identified; 3 for lower limb: 2 for any type of pathologies (Lower Limb Functional Index [LLFI]; Lower Extremity Functional Scale [LEFS]) and 1 specific for arthrosis (Arthrosis des Membres Inférieurs et Qualité de vie [AMICAL]); Other 3 for knee and hip pathologies (Western Ontario and McMaster Universities Osteoarthritis [WOMAC] index; Osteoarthritis Knee and Hip Quality of Life [OAKHQOL] questionnaire; Hip and Knee Questionnaire [HKQ]), and other 4 for knee: 2 general scales (Knee Injury and Osteoarthritis Outcome Score [KOOS]; Knee Society Clinical Rating System [KSS]) and 2 specifics (Victorian Institute of Sport Assessment [VISA-P] questionnaire for patients with patellar tendinopathy and Kujala Score for patellofemoral pain). The transcultural adaptation procedure was satisfactory, albeit somewhat less rigorous for HKQ and LLFI. In no study were all psychometric properties assessed. Reliability was analyzed in all cases, except in KSS. Validity was measured in all questionnaires. The transcultural adaptation procedure was satisfactory and the psychometric properties analysed were similar to both the original version and other versions adapted to other languages. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Local Education Funds: The Community Connection to Education Reform. A Report on a Consultation (Atlanta, Georgia, November 17, 1992).

ERIC Educational Resources Information Center

BellSouth Foundation, Inc. Atlanta, GA.

This booklet highlights consultation on the community link to educational reform. Participants included 25 representatives from local education funds (LEFs) in the southeastern United States and 9 representatives of statewide and regional organizations. This booklet describes the role of LEFs, which are independent, nonprofit, community-based…

Water Withdrawn From the Luquillo Experimental Forest, 2004

Treesearch

Kelly E. Crook; Fred N. Scatena; Catherine M. Pringle

2007-01-01

This study quantifies the amount of water withdrawn from the Luqillo Experimental Forest (LEF) in 2004. Spatially averaged mean monthly water budgets were generated for watersheds draining the LEF by combining long-term data from various government agencies with estimated extraction data. Results suggest that, on a typical day, 70 percent of water generated within the...

Variation in nutrient characteristics of surface soils from the Luquillo Experimental Forest of Puerto Rico: A multivariate perspective.

Treesearch

S. B. Cox; M. R. Willig; F. N. Scatena

2002-01-01

We assessed the effects of landscape features (vegetation type and topography), season, and spatial hierarchy on the nutrient content of surface soils in the Luquillo Experimental Forest (LEF) of Puerto Rico. Considerable spatial variation characterized the soils of the LEF, and differences between replicate sites within each combination of vegetation type (tabonuco vs...

Severe Bone Marrow Suppression Accompanying Pulmonary Infection and Hemorrhage of the Digestive Tract Associated with Leflunomide and Low-dose Methotrexate Combination Therapy

PubMed Central

Qu, Caihong; Lu, Ying; Liu, Weimin

2017-01-01

A 60-year-old male patient developed hyperpyrexia, cough, expectoration with blood-stained sputum, mouth ulcers, and suppurative tonsillitis after receiving 35 days of combination treatment with leflunomide (LEF) and low-dose methotrexate (MTX) for active rheumatoid arthritis. On admission, routine blood tests showed severe thrombocytopenia, agranulocytosis, and decreased hemoglobin concentration compared with the relatively normal results of 1 month previously during the first hospitalization. Chest radiography revealed inflammation in both lungs, and a fecal occult blood test was positive. Given this presentation, severe bone marrow suppression accompanying pulmonary infection and hemorrhage of the digestive tract associated with LEF and MTX combination therapy was diagnosed. After 28 days of symptomatic treatment, the patient's complications subsided gradually. This case highlighted that bone marrow suppression associated with MTX and LEF combination therapy could be very serious, even at a normal dose or especially at the beginning of treatment. MTX and LEF combination therapy should be used with caution or be limited in those with a history of pulmonary disease, hemorrhage of the digestive tract, or other relevant diseases. PMID:28405135

Research in the Luquillo Experimental Forest has advanced understanding of tropical forests and resolved management issues

Treesearch

A.E. Lugo; T. Heartsill Scalley

2014-01-01

Long-term research on the response of wet forests in the Luquillo Experimental Forest (LEF) to natural and anthropogenic disturbances yielded information useful for the management of these forests and to a better understanding of the functioning of tropical forests and how species composition changes under different distrubance regimes. We summarize studies on basal...

Survivin expression promotes VEGF-induced tumor angiogenesis via PI3K/Akt enhanced β-catenin/Tcf-Lef dependent transcription.

PubMed

Fernández, Jaime G; Rodríguez, Diego A; Valenzuela, Manuel; Calderon, Claudia; Urzúa, Ulises; Munroe, David; Rosas, Carlos; Lemus, David; Díaz, Natalia; Wright, Mathew C; Leyton, Lisette; Tapia, Julio C; Quest, Andrew Fg

2014-09-09

Early in cancer development, tumour cells express vascular endothelial growth factor (VEGF), a secreted molecule that is important in all stages of angiogenesis, an essential process that provides nutrients and oxygen to the nascent tumor and thereby enhances tumor-cell survival and facilitates growth. Survivin, another protein involved in angiogenesis, is strongly expressed in most human cancers, where it promotes tumor survival by reducing apoptosis as well as favoring endothelial cell proliferation and migration. The mechanisms by which cancer cells induce VEGF expression and angiogenesis upon survivin up-regulation remain to be fully established. Since the PI3K/Akt signalling and β-catenin-Tcf/Lef dependent transcription have been implicated in the expression of many cancer-related genes, including survivin and VEGF, we evaluated whether survivin may favor VEGF expression, release from tumor cells and induction of angiogenesis in a PI3K/Akt-β-catenin-Tcf/Lef-dependent manner. Here, we provide evidence linking survivin expression in tumor cells to increased β-catenin protein levels, β-catenin-Tcf/Lef transcriptional activity and expression of several target genes of this pathway, including survivin and VEGF, which accumulates in the culture medium. Alternatively, survivin downregulation reduced β-catenin protein levels and β-catenin-Tcf/Lef transcriptional activity. Also, using inhibitors of PI3K and the expression of dominant negative Akt, we show that survivin acts upstream in an amplification loop to promote VEGF expression. Moreover, survivin knock-down in B16F10 murine melanoma cells diminished the number of blood vessels and reduced VEGF expression in tumors formed in C57BL/6 mice. Finally, in the chick chorioallantoid membrane assay, survivin expression in tumor cells enhanced VEGF liberation and blood vessel formation. Importantly, the presence of neutralizing anti-VEGF antibodies precluded survivin-enhanced angiogenesis in this assay. These findings provide evidence for the existance of a posititve feedback loop connecting survivin expression in tumor cells to PI3K/Akt enhanced β-catenin-Tcf/Lef-dependent transcription followed by secretion of VEGF and angiogenesis.

The Genome of Gryllus bimaculatus Nudivirus Indicates an Ancient Diversification of Baculovirus-Related Nonoccluded Nudiviruses of Insects▿

PubMed Central

Wang, Yongjie; Kleespies, Regina G.; Huger, Alois M.; Jehle, Johannes A.

2007-01-01

The Gryllus bimaculatus nudivirus (GbNV) infects nymphs and adults of the cricket Gryllus bimaculatus (Orthoptera: Gryllidae). GbNV and other nudiviruses such as Heliothis zea nudivirus 1 (HzNV-1) and Oryctes rhinoceros nudivirus (OrNV) were previously called “nonoccluded baculoviruses” as they share some similar structural, genomic, and replication aspects with members of the family Baculoviridae. Their relationships to each other and to baculoviruses are elucidated by the sequence of the complete genome of GbNV, which is 96,944 bp, has an AT content of 72%, and potentially contains 98 predicted protein-coding open reading frames (ORFs). Forty-one ORFs of GbNV share sequence similarities with ORFs found in OrNV, HzNV-1, baculoviruses, and bacteria. Most notably, 15 GbNV ORFs are homologous to the baculovirus core genes, which are associated with transcription (lef-8, lef-9, lef-4, vlf-1, and lef-5), replication (dnapol), structural proteins (p74, pif-1, pif-2, pif-3, vp91, and odv-e56), and proteins of unknown function (38K, ac81, and 19kda). Homologues to these baculovirus core genes have been predicted in HzNV-1 as well. Six GbNV ORFs are homologous to nonconserved baculovirus genes dnaligase, helicase 2, rr1, rr2, iap-3, and desmoplakin. However, the remaining 57 ORFs revealed no homology or poor similarities to the current gene databases. No homologous repeat (hr) sequences but fourteen short direct repeat (dr) regions were detected in the GbNV genome. Gene content and sequence similarity suggest that the nudiviruses GbNV, HzNV-1, and OrNV form a monophyletic group of nonoccluded double-stranded DNA viruses, which separated from the baculovirus lineage before this radiated into dipteran-, hymenopteran-, and lepidopteran-specific clades of occluded nucleopolyhedroviruses and granuloviruses. The accumulated information on the GbNV genome suggests that nudiviruses form a highly diverse and phylogenetically ancient sister group of the baculoviruses, which have evolved in a variety of highly divergent host orders. PMID:17360757

Spatial and seasonal dynamics of surface soil carbon in the Luquillo Experimental Forest, Puerto Rico.

Treesearch

Hongqing Wang; Joseph D. Cornell; Charles A.S. Hall; David P. Marley

2002-01-01

We developed a spatially-explicit version of the CENTURY soil model to characterize the storage and flux of soil organic carbon (SOC, 0–30 cm depth) in the Luquillo Experimental Forest (LEF), Puerto Rico as a function of climate, vegetation, and soils. The model was driven by monthly estimates of average air temperature, precipitation, and potential evapotranspiration...

The course of health status and (health-related) quality of life following fracture of the lower extremity: a 6-month follow-up study.

PubMed

Van Son, M A C; De Vries, J; Roukema, J A; Gosens, T; Verhofstad, M H J; Den Oudsten, B L

2016-05-01

The aim of this prospective study was to describe the course of health status (HS), health-related quality of life, and quality of life (QOL) in patients with lower extremity fractures (LEF) up to 6 months post-fracture. Patients (n = 171; age range 18-100 years) completed the World Health Organization Quality of Life assessment instrument-Bref (WHOQOL-Bref) and the Short Musculoskeletal Function Assessment questionnaire (SMFA) at time of diagnosis (i.e., pre-injury status), 1 week, and 6 months post-fracture. Linear mixed modeling was performed. Interaction effects of time with treatment were detected for the WHOQOL-Bref facet Overall QOL and General health (p = .002) and Physical health (p = .003). Patients did not return to their pre-injury Physical health, Psychological health, and Environment 6 months post-fracture (p < .05). No effects were found for Social relationships. The SMFA subscale Lower extremity dysfunction showed main effects for time and treatment (p < .0001) with full recovery at 6 months (p = .998). An interaction effect of time with treatment was found for Daily life consequences (p < .0001) with nonoperatively treated patients showing full recovery (p = 1.00), whereas surgically treated patients did not (p = .002). Six months after LEF, patients still experienced impaired physical and psychological health on the WHOQOL-Bref compared to their pre-injury status. However, patients showed full recovery on SMFA Lower extremity dysfunction, indicating that the choice of the questionnaire influences the derived conclusions. LEF did not affect satisfaction with social relationships.

Identification of LMO2 transcriptome and interactome in diffuse large B-cell lymphoma

PubMed Central

Cubedo, Elena; Gentles, Andrew J.; Huang, Chuanxin; Natkunam, Yasodha; Bhatt, Shruti; Lu, Xiaoqing; Jiang, Xiaoyu; Romero-Camarero, Isabel; Freud, Aharon; Zhao, Shuchun; Bacchi, Carlos E.; Martínez-Climent, Jose A.; Sánchez-García, Isidro; Melnick, Ari

2012-01-01

LMO2 regulates gene expression by facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the germinal center (GC) and is expressed in GC-derived non-Hodgkin lymphomas. LMO2 is one of the most powerful prognostic indicators in diffuse large B-cell (DLBCL) patients. However, its function in GC B cells and DLBCL is currently unknown. In this study, we characterized the LMO2 transcriptome and transcriptional complex in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly, and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners, such as LDB1, E2A, HEB, Lyl1, ETO2, and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, nuclear factor of activated T-cells (NFATc1), and lymphoid enhancer-binding factor1 (LEF1) proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provides a platform for future elucidation of LMO2 function in GC B cells and DLBCL pathogenesis. PMID:22517897

Avian studies and research opportunities in the Luquillo Experimental Forest: a tropical rain forest in Puerto Rico

Treesearch

Joseph Wunderle, Jr; Wayne J. Arendt

2011-01-01

The Luquillo Experimental Forest (LEF) located on the Caribbean island of Puerto Rico has a rich history of ecological research, including a variety of avian studies, and is one of the most active ecological research sites in the Neotropics. The LEF spans an elevational range from 100 to 1075mover which five life zones and four forest types are found in a warm, humid...

Development of an Encompassing Questionnaire for Evaluating the Outcomes Following Total Knee Arthroplasty.

PubMed

Chughtai, Morad; Khlopas, Anton; Thomas, Melbin; Gwam, Chukwuweike U; Jauregui, Julio J; Elmallah, Randa K; Roche, Martin; Delanois, Ronald E

2017-01-10

There are many standardized scales and questionnaires used to evaluate TKA patients; however, individually they do not always assess patients adequately. Consequently, many are used in combinations to provide a thorough evaluation. However, this leads to redundancy, confusion, and an excessive patient time-burden. Therefore, the purpose of this study was to develop a usable combined knee questionnaire that combines questions in a non-redundant manner. Specifically, we aimed to: 1) create a combined knee questionnaire that encompasses questions from multiple systems, while eliminating redundancy; 2) correlate the new system with the existing validated questionnaires; and 3) determine the length of time it takes to administer this new questionnaire. In a previous study, it was determined that the six most commonly cited validated systems to assess the knee were the: Knee Society Score (KSS), The Western Ontario and McMaster Universities Arthritis Index (WOMAC), Knee injury and Osteoarthritis Outcome Score (KOOS), Lower Extremity Functional Scale (LEFS), Activity Rating Scale (ARS), and Short-Form-36 (SF-36). Therefore, we ensured that the new questionnaire encompassed all elements of these systems. After development of the combined questionnaire, we co-administered it to 20 subjects alongside the above validated questionnaires. We then transposed the corresponding answers from the combined questionnaire to each selected validated system to perform an intra-class correlation analysis. In addition, we recorded the length of time it took to administer the new questionnaire and compared it to the time it took to administer the individual validated questionnaires. Intra-class correlation analysis demonstrated statistically significant positive correlations between the KSS, WOMAC, KOOS, LEFS, ARS, SF-36, and the corresponding questions in the combined questionnaire. The mean length of time it took to administer the combined questionnaire (mean, 10.1 minutes, range, 6.6 to 12.6 minutes) was significantly shorter than the time it took to administer the selected validated questionnaires (mean, 21.3 minutes, range, 17.3 to 24.1 minutes). We have proposed an all-encompassing combined knee questionnaire that eliminates redundancy and inefficiency during the evaluation of TKA patients. It is a reliable, time-efficient system that can be utilized to fill out the most commonly used questionnaires for assessing TKA. Standardization and uniform use of this questionnaire may simplify future patient assessment following TKA.

Physical aspects of Hurricane Hugo in Puerto Rico

USGS Publications Warehouse

Scatena, F.N.; Larsen, Matthew C.

1991-01-01

On 18 September 1989 the western part ofHurricane Hugo crossed eastern Puerto Rico and the Luquillo Experimental Forest (LEF). Storm-facing slopes on the northeastern part of the island that were within 15 km of the eye and received greater than 200 mm of rain were most affected by the storm. In the LEF and nearby area, recurrence intervals associated with Hurricane Hugo were 50 yr for wind velocity, 10 to 31 yr for stream discharge, and 5 yr for rainfall intensity. To compare the magnitudes of the six hurricanes to pass over PuertoRico since 1899, 3 indices were developed using the standardized values of the product of: the maximum sustained wind speed at San Juan squared and storm duration; the square of the product of the maximum sustained wind velocity at San Juan and the ratio of the distance between the hurricane eye and San Juan to the distance between the eye and percentage of average annual rainfall delivered by the storm. Based on these indices, HurricaneHugo was of moderate intensity. However, because of the path of Hurricane Hugo, only one of these six storms (the 1932 storm) caused more damage to the LEF than Hurricane Hugo. Hurricanes of Hugo's magnitude are estimated to pass over the LEF once every 50-60 yr, on average. 

Bidirectional reporter assay using HAL promoter and TOPFLASH improves specificity in high-throughput screening of Wnt inhibitors.

PubMed

Yamaguchi, Kiyoshi; Zhu, Chi; Ohsugi, Tomoyuki; Yamaguchi, Yuko; Ikenoue, Tsuneo; Furukawa, Yoichi

2017-12-01

Constitutive activation of Wnt signaling plays an important role in colorectal and liver tumorigenesis. Cell-based assays using synthetic TCF/LEF (T-cell factor/lymphoid enhancer factor) reporters, as readouts of β-catenin/TCF-dependent transcriptional activity, have contributed greatly to the discovery of small molecules that modulate Wnt signaling. In the present study, we report a novel screening method, called a bidirectional dual reporter assay. Integrated transcriptome analysis identified a histidine ammonia-lyase gene (HAL) that was negatively regulated by β-catenin/TCF-dependent transcriptional activity. We leveraged a promoter region of the HAL gene as another transcriptional readout of Wnt signaling. Cells stably expressing both an optimized HAL reporter and the TCF/LEF reporter enabled bidirectional reporter activities in response to Wnt signaling. Increased HAL reporter activity and decreased TCF/LEF reporter activity were observed simultaneously in the cells when β-catenin/TCF7L2 was inhibited. Notably, this method could decrease the number of false positives observed when screening an inhibitor library compared with the conventional TCF/LEF assay. We found that Brefeldin A, a disruptor of the Golgi apparatus, inhibited the Wnt/β-catenin signaling pathway. The utility of our system could be expanded to examine other disease-associated pathways beyond the Wnt/β-catenin signaling pathway. © 2017 Wiley Periodicals, Inc.

A novel live attenuated anthrax spore vaccine based on an acapsular Bacillus anthracis Sterne strain with mutations in the htrA, lef and cya genes.

PubMed

Chitlaru, Theodor; Israeli, Ma'ayan; Rotem, Shahar; Elia, Uri; Bar-Haim, Erez; Ehrlich, Sharon; Cohen, Ofer; Shafferman, Avigdor

2017-10-20

We recently reported the development of a novel, next-generation, live attenuated anthrax spore vaccine based on disruption of the htrA (High Temperature Requirement A) gene in the Bacillus anthracis Sterne veterinary vaccine strain. This vaccine exhibited a highly significant decrease in virulence in murine, guinea pig and rabbit animal models yet preserved the protective value of the parental Sterne strain. Here, we report the evaluation of additional mutations in the lef and cya genes, encoding for the toxin components lethal factor (LF) and edema factor (EF), to further attenuate the SterneΔhtrA strain and improve its compatibility for human use. Accordingly, we constructed seven B. anthracis Sterne-derived strains exhibiting different combinations of mutations in the htrA, cya and lef genes. The various strains were indistinguishable in growth in vitro and in their ability to synthesise the protective antigen (PA, necessary for the elicitation of protection). In the sensitive murine model, we observed a gradual increase (ΔhtrA<ΔhtrAΔcya<ΔhtrAΔlef<ΔhtrAΔlefΔcya) in attenuation - up to 10 8 -fold relative to the parental Sterne vaccine strain. Most importantly, all various SterneΔhtrA derivative strains did not differ in their ability to elicit protective immunity in guinea pigs. Immunisation of guinea pigs with a single dose (10 9 spores) or double doses (>10 7 spores) of the most attenuated triple mutant strain SterneΔhtrAlef MUT Δcya induced a robust immune response, providing complete protection against a subsequent respiratory lethal challenge. Partial protection was observed in animals vaccinated with a double dose of as few as 10 5 spores. Furthermore, protective immune status was maintained in all vaccinated guinea pigs and rabbits for at least 40 and 30weeks, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

CrossTalk: The Journal of Defense Software Engineering. Volume 22, Number 5, July/August 2009

DTIC Science & Technology

2009-08-01

Office (GAO) and NASA studies of space systems [1, 2, 3, 4] document notorious major budget and schedule overruns, some exceeding 100 percent. Most...Handbook,” ISO 15288, and similar NASA , DoD, or company manu- als—and do not repeat the practices made therein, which are regarded as sound. The LEfSE...with the recent programmatic recommen- dations by GAO and NASA [1, 2, 3, 4]. The surveys indicated that LEfSE are regarded as important for program suc

Novel β-catenin target genes identified in thalamic neurons encode modulators of neuronal excitability

PubMed Central

2012-01-01

Background LEF1/TCF transcription factors and their activator β-catenin are effectors of the canonical Wnt pathway. Although Wnt/β-catenin signaling has been implicated in neurodegenerative and psychiatric disorders, its possible role in the adult brain remains enigmatic. To address this issue, we sought to identify the genetic program activated by β-catenin in neurons. We recently showed that β-catenin accumulates specifically in thalamic neurons where it activates Cacna1g gene expression. In the present study, we combined bioinformatics and experimental approaches to find new β-catenin targets in the adult thalamus. Results We first selected the genes with at least two conserved LEF/TCF motifs within the regulatory elements. The resulting list of 428 putative LEF1/TCF targets was significantly enriched in known Wnt targets, validating our approach. Functional annotation of the presumed targets also revealed a group of 41 genes, heretofore not associated with Wnt pathway activity, that encode proteins involved in neuronal signal transmission. Using custom polymerase chain reaction arrays, we profiled the expression of these genes in the rat forebrain. We found that nine of the analyzed genes were highly expressed in the thalamus compared with the cortex and hippocampus. Removal of nuclear β-catenin from thalamic neurons in vitro by introducing its negative regulator Axin2 reduced the expression of six of the nine genes. Immunoprecipitation of chromatin from the brain tissues confirmed the interaction between β-catenin and some of the predicted LEF1/TCF motifs. The results of these experiments validated four genes as authentic and direct targets of β-catenin: Gabra3 for the receptor of GABA neurotransmitter, Calb2 for the Ca2+-binding protein calretinin, and the Cacna1g and Kcna6 genes for voltage-gated ion channels. Two other genes from the latter cluster, Cacna2d2 and Kcnh8, appeared to be regulated by β-catenin, although the binding of β-catenin to the regulatory sequences of these genes could not be confirmed. Conclusions In the thalamus, β-catenin regulates the expression of a novel group of genes that encode proteins involved in neuronal excitation. This implies that the transcriptional activity of β-catenin is necessary for the proper excitability of thalamic neurons, may influence activity in the thalamocortical circuit, and may contribute to thalamic pathologies. PMID:23157480

Surgical Management of Rectus Femoris Avulsion Among Professional Soccer Players

PubMed Central

Sonnery-Cottet, Bertrand; Barbosa, Nuno Camelo; Tuteja, Sanesh; Gardon, Roland; Daggett, Matt; Monnot, Damien; Kajetanek, Charles; Thaunat, Mathieu

2017-01-01

Background: Rectus femoris injuries are common among athletes, especially in kicking sports such as soccer; however, proximal rectus femoris avulsions in athletes are a relatively rare entity. Purpose/Hypothesis: The purpose of this study was to describe and report the results of an original technique of surgical excision of the proximal tendon remnant followed by a muscular suture repair. Our hypothesis was that this technique limits the risk of recurrence in high-level athletes and allows for rapid recovery without loss of quadriceps strength. Study Design: Case series; Level of evidence, 4. Methods: Our retrospective series included 5 players aged 31.8 ± 3.9 years with acute proximal rectus femoris avulsion injuries who underwent a surgical resection of the proximal tendon between March 2012 and June 2014. Four of these players had recurrent rectus femoris injuries in the 9 months before surgery, while 1 player had surgery after a first injury. Mean follow-up was 18.2 ± 12.6 months, and minimum follow-up was 9 months. We analyzed the age, sex distribution, physical examination outcomes, type and mechanism of injury, diagnosis, treatment and complications during surgery, postoperative follow-up, and time to return to play. The Lower Extremity Functional Scale (LEFS) and Marx scores were obtained at 3-month follow-up, and isokinetic tests were performed before return to sports. A telephone interview was completed to determine the presence of recurrence at an average follow-up of 18.2 months. Results: At 3-month follow-up, all patients had Marx activity scores of 16 and LEFS scores of 80. Return to the previous level of play occurred at a mean of 15.8 ± 2.6 weeks after surgery, and none of the athletes suffered a recurrence. Isokinetic test results were comparable between both sides. Conclusion: The surgical treatment of proximal rectus femoris avulsions, consisting of resection of the tendinous part of the muscle, is a reliable and safe technique allowing a fast recovery in professional athletes. PMID:28203599

Predicting the temporal and spatial probability of orographic cloud cover in the Luquillo Experimental Forest in Puerto Rico using generalized linear (mixed) models.

Treesearch

Wei Wu; Charlesb Hall; Lianjun Zhang

2006-01-01

We predicted the spatial pattern of hourly probability of cloud cover in the Luquillo Experimental Forest (LEF) in North-Eastern Puerto Rico using four different models. The probability of cloud cover (defined as “the percentage of the area covered by clouds in each pixel on the map” in this paper) at any hour and any place is a function of three topographic variables...

EphB4 localises to the nucleus of prostate cancer cells

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

Mertens-Walker, Inga, E-mail: inga.mertenswalker@qut.edu.au; Australian Prostate Cancer Research Centre—Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba 4102, QLD; Lisle, Jessica E.

2015-04-10

The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of bothmore » NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor. - Highlights: • The EphB4 protein can be found in the nucleus of prostate cancer cell lines. • EphB4 contains two functional nuclear localisation signals. • Chromatin immunoprecipitation has identified potential genome sequences to which EphB4 binds. • Lef1 is a confirmed target for EphB4-mediated gene regulation.« less

β-Catenin-Dependent and -Independent Effects of ΔN-Plakoglobin on Epidermal Growth and Differentiation

PubMed Central

Teulière, J.; Faraldo, M. M.; Shtutman, M.; Birchmeier, W.; Huelsken, J.; Thiery, J. P.; Glukhova, M. A.

2004-01-01

Both β-catenin and plakoglobin can stimulate the expression of Lef/Tcf target genes in vitro. β-Catenin is known to associate with Lef/Tcf factors and to participate directly in transactivation in vivo, whereas the role of plakoglobin in transcriptional regulation has been less studied. To analyze the functions of plakoglobin in vivo, we generated transgenic mice expressing in the epidermis N-terminally truncated plakoglobin (ΔN122-PG) lacking the glycogen synthase kinase 3β phosphorylation sites and therefore protected against degradation (transgenic line K5-ΔN122-PG). The expression of ΔN122-PG led to the formation of additional hair germs, hyperplastic hair follicles, and noninvasive hair follicle tumors, a phenotype reminiscent of that induced by expression of N-terminally truncated β-catenin. However, if expressed in β-catenin-null epidermis, ΔN122-PG did not induce new hair follicle germs and follicular tumors. Thus, ΔN122-PG cannot substitute for β-catenin in its signaling functions in vivo and the phenotype observed in K5-ΔN122-PG mouse skin must be due to the aberrant activation of β-catenin signaling. On the other hand, the expression of ΔN122-PG in β-catenin-null skin significantly increased the survival rate of mutant mice, rescued differentiation, and limited excessive proliferation in the interfollicular epidermis, suggesting that plakoglobin may be involved in the intracellular signaling events essential for epidermal differentiation. PMID:15367683

Combinatorial expression of Lef1, Lhx2, Lhx5, Lhx9, Lmo3, Lmo4, and Prox1 helps to identify comparable subdivisions in the developing hippocampal formation of mouse and chicken

PubMed Central

Abellán, Antonio; Desfilis, Ester; Medina, Loreta

2014-01-01

We carried out a study of the expression patterns of seven developmental regulatory genes (Lef1, Lhx2, Lhx9, Lhx5, Lmo3, Lmo4, and Prox1), in combination with topological position, to identify the medial pallial derivatives, define its major subdivisions, and compare them between mouse and chicken. In both species, the medial pallium is defined as a pallial sector adjacent to the cortical hem and roof plate/choroid tela, showing moderate to strong ventricular zone expression of Lef1, Lhx2, and Lhx9, but not Lhx5. Based on this, the hippocampal formation (indusium griseum, dentate gyrus, Ammon's horn fields, and subiculum), the medial entorhinal cortex, and part of the amygdalo-hippocampal transition area of mouse appeared to derive from the medial pallium. In the chicken, based on the same position and gene expression profile, we propose that the hippocampus (including the V-shaped area), the parahippocampal area (including its caudolateral part), the entorhinal cortex, and the amygdalo-hippocampal transition area are medial pallial derivatives. Moreover, the combinatorial expression of Lef1, Prox1, Lmo4, and Lmo3 allowed the identification of dentate gyrus/CA3-like, CA1/subicular-like, and medial entorhinal-like comparable sectors in mouse and chicken, and point to the existence of mostly conserved molecular networks involved in hippocampal complex development. Notably, while the mouse medial entorhinal cortex derives from the medial pallium (similarly to the hippocampal formation, both being involved in spatial navigation and spatial memory), the lateral entorhinal cortex (involved in processing non-spatial, contextual information) appears to derive from a distinct dorsolateral caudal pallial sector. PMID:25071464

Wnt signaling pathway involvement in genotypic and phenotypic variations in Waardenburg syndrome type 2 with MITF mutations.

PubMed

Wang, Xue-Ping; Liu, Ya-Lan; Mei, Ling-Yun; He, Chu-Feng; Niu, Zhi-Jie; Sun, Jie; Zhao, Yu-Lin; Feng, Yong; Zhang, Hua

2018-05-01

Mutation in the gene encoding microphthalmia-associated transcription factor (MITF) lead to Waardenburg syndrome 2 (WS2), an autosomal dominantly inherited syndrome with auditory-pigmentary abnormalities, which is clinically and genetically heterogeneous. Haploinsufficiency may be the underlying mechanism for WS2. However, the mechanisms explaining the genotypic and phenotypic variations in WS2 caused by MITF mutations are unclear. A previous study revealed that MITF interacts with LEF-1, an important factor in the Wnt signaling pathway, to regulate its own transcription through LEF-1-binding sites on the MITF promoter. In this study, four different WS2-associated MITF mutations (p.R217I, p.R217G, p.R255X, p.R217del) that are associated with highly variable clinical features were chosen. According to the results, LEF-1 can activate the expression of MITF on its own, but MITF proteins inhibited the activation. This inhibition weakens when the dosage of MITF is reduced. Except for p.R217I, p.R255X, p.R217G, and p.R217del lose the ability to activate TYR completely and do not inhibit the LEF-1-mediated activation of the MITF-M promoter, and the haploinsufficiency created by mutant MITF can be overcome; correspondingly, the mutants' associated phenotypes are less severe than that of p.R217I. The dominant negative of p.R217del made it have a second-most severe phenotype. This study's data imply that MITF has a negative feedback loop of regulation to stabilize MITF gene dosage that involves the Wnt signaling pathway and that the interaction of MITF mutants with this pathway drives the genotypic and phenotypic differences observed in Waardenburg syndrome type 2 associated with MITF mutations.

Neurodevelopmental and mental health comorbidities in children and adolescents with epilepsy and migraine: a response to identified research gaps.

PubMed

Wagner, Janelle L; Wilson, Dulaney A; Smith, Gigi; Malek, Angela; Selassie, Anbesaw W

2015-01-01

To determine the distribution and risk characteristics of comorbid neurodevelopmental and mental health comorbidities among children and adolescents (6-18y) with epilepsy or migraine (i.e. a neurological condition with shared features and potential etiology) compared with lower extremity fracture (LEF). This case-control study involved a subset analysis of surveillance data in South Carolina, USA. Hospital admission, outpatient, and emergency department visits for individuals with an International Classification of Disease, 9th revision Clinical Modification diagnosis of epilepsy (n=6730; 54.5% females, 45.5% males; mean age [SD] 14y 2mo [4y 5mo]); migraine (n=10 495; 74.5% females, 25.5% males; 15y 6mo [2y 6mo]), or LEF (n=15 305; 40.3% females, 59.7% males; 13y 11mo [2y 11mo]) from January 1 2000 to December 31 2011 were identified. The association of epilepsy, migraine, or LEF with any mental health comorbidity was evaluated with univariate and multivariate polytomous logistic regression. Comorbidities were highly prevalent in children and adolescents, with epilepsy with a rate of 29.7% (95% confidence interval [CI]: 28.6-30.8) for mental health comorbidities and 30.8% (95% CI: 29.7-31.9) for neurodevelopmental comorbidities. The odds of mental health comorbidity was 2.20 (95% CI: 2.02-2.39) for children and adolescents with epilepsy and 1.60 (95% CI: 1.48-1.73) for migraine, in reference to children and adolescents with LEF after adjusting for potential confounders. Prevalence and risk for specific comorbidities are presented. Neuropathophysiological and psychosocial factors specific to epilepsy may provide more risk for adolescents with epilepsy compared to migraine. © 2014 Mac Keith Press.

Identification of the Transformational Properties and Transcriptional Targets of the Oncogenic SRY Transcription Factor SOX4

DTIC Science & Technology

2010-01-01

using linker -mediated PCR as described previously (25). Amplified DNA was labeled and hybridized in triplicate by NimbleGen Systems, Inc., to their human...leading edge analysis (37) of these gene sets identified TGFb–induced SMAD3 direct target genes (Supplementary Table S5) as enriched in SOX4 target...3.06E11 PAX5 Paired box 2.07E10 WHN Forkhead 2.94E10 SMAD3 SMAD 1.82E09 SMAD4 SMAD 3.33E09 MYC MYC 6.25E09 NFKAPPAB NF-nB 2.95E08 LEF1/TCF1 LEF

Insects of the Luquillo Mountains, Puerto Rico. Forest Service general technical report

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

Torres, J.A.

1994-07-01

In this review of the literature on forest entomology in Puerto Rico, emphasis is given to research conducted in the Luquillo Experimental Forest (LEF). This review should serve as an introduction to the insects inhabiting the LEF for researchers and as a guide for the identification of possible insect pests. There are three sections to this review. The first deals with basic insect ecology; the second, forest insect pests; and the third, insect attacks on dry wood and during wood seasoning. The reference section and appendices contain information on the systematics and taxonomy of different insect orders found in Puertomore » Rico.« less

Doehlert experimental design applied to optimization of light emitting textile structures

NASA Astrophysics Data System (ADS)

Oguz, Yesim; Cochrane, Cedric; Koncar, Vladan; Mordon, Serge R.

2016-07-01

A light emitting fabric (LEF) has been developed for photodynamic therapy (PDT) for the treatment of dermatologic diseases such as Actinic Keratosis (AK). A successful PDT requires homogenous and reproducible light with controlled power and wavelength on the treated skin area. Due to the shape of the human body, traditional PDT with external light sources is unable to deliver homogenous light everywhere on the skin (head vertex, hand, etc.). For better light delivery homogeneity, plastic optical fibers (POFs) have been woven in textile in order to emit laterally the injected light. The previous studies confirmed that the light power could be locally controlled by modifying the radius of POF macro-bendings within the textile structure. The objective of this study is to optimize the distribution of macro-bendings over the LEF surface in order to increase the light intensity (mW/cm2), and to guarantee the best possible light deliver homogeneity over the LEF which are often contradictory. Fifteen experiments have been carried out with Doehlert experimental design involving Response Surface Methodology (RSM). The proposed models are fitted to the experimental data to enable the optimal set up of the warp yarns tensions.

Deep sequencing reveals microbiota dysbiosis of tongue coat in patients with liver carcinoma.

PubMed

Lu, Haifeng; Ren, Zhigang; Li, Ang; Zhang, Hua; Jiang, Jianwen; Xu, Shaoyan; Luo, Qixia; Zhou, Kai; Sun, Xiaoli; Zheng, Shusen; Li, Lanjuan

2016-09-08

Liver carcinoma (LC) is a common malignancy worldwide, associated with high morbidity and mortality. Characterizing microbiome profiles of tongue coat may provide useful insights and potential diagnostic marker for LC patients. Herein, we are the first time to investigate tongue coat microbiome of LC patients with cirrhosis based on 16S ribosomal RNA (rRNA) gene sequencing. After strict inclusion and exclusion criteria, 35 early LC patients with cirrhosis and 25 matched healthy subjects were enrolled. Microbiome diversity of tongue coat in LC patients was significantly increased shown by Shannon, Simpson and Chao 1 indexes. Microbiome on tongue coat was significantly distinguished LC patients from healthy subjects by principal component analysis. Tongue coat microbial profiles represented 38 operational taxonomic units assigned to 23 different genera, distinguishing LC patients. Linear discriminant analysis (LDA) effect size (LEfSe) reveals significant microbial dysbiosis of tongue coats in LC patients. Strikingly, Oribacterium and Fusobacterium could distinguish LC patients from healthy subjects. LEfSe outputs show microbial gene functions related to categories of nickel/iron_transport, amino_acid_transport, energy produced system and metabolism between LC patients and healthy subjects. These findings firstly identify microbiota dysbiosis of tongue coat in LC patients, may providing novel and non-invasive potential diagnostic biomarker of LC.

Deep sequencing reveals microbiota dysbiosis of tongue coat in patients with liver carcinoma

NASA Astrophysics Data System (ADS)

Lu, Haifeng; Ren, Zhigang; Li, Ang; Zhang, Hua; Jiang, Jianwen; Xu, Shaoyan; Luo, Qixia; Zhou, Kai; Sun, Xiaoli; Zheng, Shusen; Li, Lanjuan

2016-09-01

Liver carcinoma (LC) is a common malignancy worldwide, associated with high morbidity and mortality. Characterizing microbiome profiles of tongue coat may provide useful insights and potential diagnostic marker for LC patients. Herein, we are the first time to investigate tongue coat microbiome of LC patients with cirrhosis based on 16S ribosomal RNA (rRNA) gene sequencing. After strict inclusion and exclusion criteria, 35 early LC patients with cirrhosis and 25 matched healthy subjects were enrolled. Microbiome diversity of tongue coat in LC patients was significantly increased shown by Shannon, Simpson and Chao 1 indexes. Microbiome on tongue coat was significantly distinguished LC patients from healthy subjects by principal component analysis. Tongue coat microbial profiles represented 38 operational taxonomic units assigned to 23 different genera, distinguishing LC patients. Linear discriminant analysis (LDA) effect size (LEfSe) reveals significant microbial dysbiosis of tongue coats in LC patients. Strikingly, Oribacterium and Fusobacterium could distinguish LC patients from healthy subjects. LEfSe outputs show microbial gene functions related to categories of nickel/iron_transport, amino_acid_transport, energy produced system and metabolism between LC patients and healthy subjects. These findings firstly identify microbiota dysbiosis of tongue coat in LC patients, may providing novel and non-invasive potential diagnostic biomarker of LC.

Papillon-Lefèvre syndrome: a successful outcome.

PubMed

Ahuja, Vanita; Shin, Richard Hochul; Mudgil, Adarsh; Nanda, Veena; Schoor, Robert

2005-11-01

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive condition manifested clinically by hyperkeratosis of the palms and soles and rapidly progressive periodontitis resulting in loss of deciduous and permanent teeth. This case report describes the clinical periodontal findings and treatment of a 10-year-old male patient with PLS. The patient provided informed consent, and the study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2000. Upon initial presentation, a full periodontal examination was completed. Conventional probing depths, clinical attachment levels (CAL), gingival index (GI), and plaque index (PI) were measured prior to initial therapy, which involved oral hygiene instruction and scaling and root planing. At reevaluation, initial treatment proved unsuccessful, and a surgical approach with concomitant systemic antibiotic therapy was implemented. In addition, the patient's dermatologist treated his palmoplantar keratoderma with systemic retinoids. Subsequently, the patient was placed on a strict 3-month maintenance protocol and was evaluated over a period of 1 year. Initial treatment with mechanical therapy, oral hygiene instruction, frequent recalls, and systemic antibiotics did not yield efficacious results. However, with the addition of surgical treatment, a favorable clinical outcome was obtained. Numerous treatment regimens for the periodontal disease seen in PLS can be found in the literature. We demonstrate successful treatment of the periodontal disease seen in this condition using mechanical therapy, systemic antibiotics, and surgical modalities; over a period of 1 year, we were able to achieve significant reductions in gingival inflammation and erythema.

Statistics, gymnastics and the origins of sport science in Belgium (and Europe).

PubMed

Delheye, Pascal

2014-01-01

This paper analyses the introduction of statistics in the field of gymnastics and its effect on the institutionalisation of physical education as a fully fledged academic discipline. Soon after Belgian independence, Adolphe Quetelet's research already resulted in large-scale anthropometric statistics - indeed, he developed an index that is still being used and is better known under the name of the body mass index. His insights were applied by promoters of gymnastics who wanted to make physical education more scientific. Thus, Clément Lefébure, director of the Ecole Normale de Gymnastique et d'Escrime in Brussels, set up a comparative experiment (with pre- and post-test measurements) by which he intended to show that the 'rational' method of Swedish gymnastics produced much better results than the 'empirical' method of Belgian/German Turnen. Lefébure's experiment, which was cited internationally but which was also strongly contested by opponents, was one of the factors that led to Swedish gymnastics being officially institutionalised in 1908 at the newly founded Higher Institute of Physical Education of the State University of Ghent, the first institute in the world where students could obtain a doctoral degree in physical education. Although it rested actually on very weak scientific foundations, the bastion of Swedish gymnastics built in Belgium in that pre-war period collapsed only in the 1960s. From then on, sport science could develop fully within the institutes for physical education.

Casein kinase 2 (CK2) increases survivin expression via enhanced β-catenin–T cell factor/lymphoid enhancer binding factor-dependent transcription

PubMed Central

Tapia, J. C.; Torres, V. A.; Rodriguez, D. A.; Leyton, L.; Quest, A. F. G.

2006-01-01

Increased expression of casein kinase 2 (CK2) is associated with hyperproliferation and suppression of apoptosis in cancer. Mutations in the tumor suppressor APC (adenomatous polyposis coli) are frequent in colon cancer and often augment β-catenin–T cell factor (Tcf)/lymphoid enhancer binding factor (Lef)-dependent transcription of genes such as c-myc and cyclin-D1. CK2 has also been implicated recently in the regulation of β-catenin stability. To identify mechanisms by which CK2 promotes survival, effects of the specific CK2 inhibitors 4,5,6,7-tetrabromobenzotriazole (TBB) and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole were assessed. TBB and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole significantly decreased proliferation and increased apoptosis of HT29(US) colon cancer cells. RT-PCR and immunoblot analysis revealed that both inhibitors decreased survivin mRNA and protein levels in HT29(US) cells. Similar effects were observed with TBB in human DLD-1 and SW-480 colorectal cells as well as ZR-75 breast cancer cells and HEK-293T embryonic kidney cells. Expression of GFP–CK2α in HEK-293T cells resulted in β-catenin–Tcf/Lef-dependent up-regulation of survivin and increased resistance to anticancer drugs. Augmented β-catenin–Tcf/Lef-dependent transcription and resistance to apoptosis observed upon GFP–CK2α expression were abolished by TBB. Alternatively, HEK-293T cells expressing GFP–survivin were resistant to TBB-induced apoptosis. Finally, siRNA-mediated down-regulation of CK2α in HEK-293T cells coincided with reduced β-catenin and survivin levels. Taken together, these results suggest that CK2 kinase activity promotes survival by increasing survivin expression via β-catenin–Tcf/Lef-mediated transcription. Hence, selective CK2 inhibition or down-regulation in tumors may provide an attractive opportunity for the development of novel cancer therapies. PMID:17005722

Surgical Management of Recurrent Musculotendinous Hamstring Injury in Professional Athletes

PubMed Central

Sonnery-Cottet, Bertrand; Daggett, Matt; Gardon, Roland; Pupim, Barbara; Clechet, Julien; Thaunat, Mathieu

2015-01-01

Background: Hamstring injury is the most common muscular lesion in athletes. The conservative treatment is well described, and surgical management is often indicated for proximal tendinous avulsions. To our knowledge, no surgical treatment has been proposed for failure of conservative treatment in musculotendinous hamstring lesions. Purpose: To describe the surgical management of proximal and distal hamstring musculotendinous junction lesions in professional athletes after failure of conservative treatment. Study Design: Case series; Level of evidence, 4. Methods: A consecutive series of 10 professional athletes, including 4 soccer players, 4 rugby players, and 2 handball players, underwent surgical intervention between October 2010 and June 2014 for the treatment of recurrent musculotendinous hamstring injuries. All athletes had failed at least 3 months of conservative treatment for a recurrent musculotendinous hamstring injury. Surgical resection of the musculotendinous scar tissue was performed using a longitudinal muscular suture. Lower Extremity Functional Scale (LEFS) and Marx scores were obtained at the 3-month follow-up, and a final phone interview was completed to determine recurrence of hamstring injury and return to previous level of play. Results: The mean age at surgery was 25.2 years (range, 19-35 years). The musculotendinous hamstring lesions involved 8 semitendinosus and 2 biceps femoris, with 6 injuries located proximally and 4 distally. Conservative treatment lasted a mean 5.1 months (range, 3-9 months) after last recurrence, and the patients had an average of 2.7 (range, 2-5) separate incidents of injury recurrence before surgical intervention was decided upon. At the 3-month follow-up, all patients had Marx activity scores of 16 and LEFS scores of 80. All 10 patients returned to the same level of play at a mean 3.4 months (range, 2-5 months). At a mean follow-up of 28.7 months, none of the athletes had suffered a recurrence. No surgical complication was encountered. Conclusion: In cases of failed conservative treatment of musculotendinous hamstring lesions, surgical intervention may be a viable treatment option in professional athletes and allows the patient to return to the same level of play. PMID:26535376

Manual physical therapy combined with high-intensity functional rehabilitation for severe lower extremity musculoskeletal injuries: a case series*

PubMed Central

Crowell, Michael S.; Deyle, Gail D.; Owens, Johnny; Gill, Norman W.

2016-01-01

Objectives Severe lower extremity trauma accounts for large healthcare costs and often results in elective amputation and poor long-term outcomes. The purpose of this case series is to describe an orthopedic manual physical therapy (OMPT) approach combined with a return to run (RTR) clinical pathway consisting of high-intensity functional rehabilitation with a custom energy-storing orthosis. Methods Three consecutive male patients, aged 21–23 years, with severe lower extremity musculoskeletal injuries were treated with a combined intervention that included a mean (SD) of 12 (2·1) OMPT sessions and 24 (8·7) functional rehabilitation sessions over a mean of 6 weeks (1·0). Additional training with a custom energy-storing orthosis consisted of a mean of 15 (1·2) additional sessions over 4 weeks. Patient self-report outcome measures and a variety of physical performance tests captured change in function. Results Baseline lower extremity functional scale (LEFS) and foot and ankle ability measure activities of daily living subscale (FAAM-ADL) scores indicated severe disability. All patients exceeded the minimal clinically important difference (MCID) in at least one self-report outcome or physical performance test without a brace. Two of three patients exceeded the MCID for at least two physical performance tests after training with and utilizing a custom energy-storing orthosis. Discussion Clinically meaningful changes in self-reported function or physical performance were observed in all patients. A multi-modal approach, including manual therapy and functional exercise, may address the entire spectrum of impairments in patients with severe lower extremity trauma, resulting in improvements in both braced and un-braced function. PMID:27252581

How relevant is heterogeneous chemistry on Mars? Strong tests via global mapping of water and ozone (sampled via O2 dayglow)

NASA Astrophysics Data System (ADS)

Villanueva, Geronimo Luis; Mumma, Michael J.; Novak, Robert E.

2015-11-01

Ozone and water are powerful tracers of photochemical processes on Mars. Considering that water is a condensable with a multifaceted hydrological cycle and ozone is continuously being produced / destroyed on short-time scales, their maps can test the validity of current 3D photochemical and dynamical models. Comparisons of modern GCM models (e.g., Lefèvre et al. 2004) with certain datasets (e.g., Clancy et al. 2012; Bertaux et al. 2012) point to significant disagreement, which in some cases have been related to heterogeneous (gas-dust) chemistry beyond the classical gas-gas homogeneous reactions.We address these concerns by acquiring full 2D maps of water and ozone (via O2 dayglow) on Mars, employing high spectral infrared spectrometers at ground-based telescopes (CRIRES/VLT and CSHELL/NASA-IRTF). By performing a rotational analysis on the O2 lines, we derive molecular temperature maps that we use to derive the vertical level of the emission (e.g., Novak et al. 2002). Our maps sample the full observable disk of Mars on March/25/2008 (Ls=50°, northern winter) and on Jan/29/2014 (Ls=83°, northern spring). The maps reveal a strong dependence of the O2 emission and water burden on local orography, while the temperature maps are in strong disagreement with current models. Could this be the signature of heterogeneous chemistry? We will present the global maps and will discuss possible scenarios to explain the observations.This work was partially funded by grants from NASA's Planetary Astronomy Program (344-32-51-96), NASA’s Mars Fundamental Research Program (203959.02.02.20.29), NASA’s Astrobiology Program (344-53-51), and the NSF-RUI Program (AST-805540). We thank the administration and staff of the European Southern Observatory/VLT and NASA-IRTF for awarding observing time and coordinating our observations.Bertaux, J.-L., Gondet, B., Lefèvre, F., et al. 2012. J. Geophys. Res. Pl. 117. pp. 1-9.Clancy, R.T., Sandor, B.J., Wolff, M.J., et al. 2012. J. Geophys. Res. Pl. 117. p. E00J10.Lefèvre, F., Lebonnois, S., Montmessin, F. & Forget, F. 2004. J. Geophys. Res. Pl. 109. pp. 1-20.Novak, R.E., Mumma, M.J., Disanti, M.A., et al. 2002. Icarus. 158 (1). pp. 14-23.

Reliability, Concurrent Validity, and Minimal Detectable Change for iPhone Goniometer App in Assessing Knee Range of Motion.

PubMed

Mehta, Saurabh P; Barker, Katherine; Bowman, Brett; Galloway, Heather; Oliashirazi, Nicole; Oliashirazi, Ali

2017-07-01

Much of the published works assessing the reliability of smartphone goniometer apps (SG) have poor generalizability since the reliability was assessed in healthy subjects. No research has established the values for standard error of measurement (SEM) or minimal detectable change (MDC) which have greater clinical utility to contextualize the range of motion (ROM) assessed using the SG. This research examined the test-retest reproducibility, concurrent validity, SEM, and MDC values for the iPhone goniometer app (i-Goni; June Software Inc., v.1.1, San Francisco, CA) in assessing knee ROM in patients with knee osteoarthritis or those after total knee replacement. A total of 60 participants underwent data collection which included the assessment of active knee ROM using the i-Goni and the universal goniometer (UG; EZ Read Jamar Goniometer, Patterson Medical, Warrenville, IL), knee muscle strength, and assessment of pain and lower extremity disability using quadruple numeric pain rating scale (Q-NPRS) and lower extremity functional scale (LEFS), respectively. Intraclass correlation coefficients (ICCs) were calculated to assess the reproducibility of the knee ROM assessed using the i-Goni and UG. Bland and Altman technique examined the agreement between these knee ROM. The SEM and MDC values were calculated for i-Goni assessed knee ROM to characterize the error in a single score and the index of true change, respectively. Pearson correlation coefficient examined concurrent relationships between the i-Goni and other measures. The ICC values for the knee flexion/extension ROM were superior for i-Goni (0.97/0.94) compared with the UG (0.95/0.87). The SEM values were smaller for i-Goni assessed knee flexion/extension (2.72/1.18 degrees) compared with UG assessed knee flexion/extension (3.41/1.62 degrees). Similarly, the MDC values were smaller for both these ROM for the i-Goni (6.3 and 2.72 degrees) suggesting smaller change required to infer true change in knee ROM. The i-Goni assessed knee ROM showed expected concurrent relationships with UG, knee muscle strength, Q-NPRS, and the LEFS. In conclusion, the i-Goni demonstrated superior reproducibility with smaller measurement error compared with UG in assessing knee ROM in the recruited cohort. Future research can expand the inquiry for assessing the reliability of the i-Goni to other joints. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Leading-Edge Flow Sensing for Aerodynamic Parameter Estimation

NASA Astrophysics Data System (ADS)

Saini, Aditya

The identification of inflow air data quantities such as airspeed, angle of attack, and local lift coefficient on various sections of a wing or rotor blade provides the capability for load monitoring, aerodynamic diagnostics, and control on devices ranging from air vehicles to wind turbines. Real-time measurement of aerodynamic parameters during flight provides the ability to enhance aircraft operating capabilities while preventing dangerous stall situations. This thesis presents a novel Leading-Edge Flow Sensing (LEFS) algorithm for the determination of the air -data parameters using discrete surface pressures measured at a few ports in the vicinity of the leading edge of a wing or blade section. The approach approximates the leading-edge region of the airfoil as a parabola and uses pressure distribution from the exact potential-ow solution for the parabola to _t the pressures measured from the ports. Pressures sensed at five discrete locations near the leading edge of an airfoil are given as input to the algorithm to solve the model using a simple nonlinear regression. The algorithm directly computes the inflow velocity, the stagnation-point location, section angle of attack and lift coefficient. The performance of the algorithm is assessed using computational and experimental data in the literature for airfoils under different ow conditions. The results show good correlation between the actual and predicted aerodynamic quantities within the pre-stall regime, even for a rotating blade section. Sensing the deviation of the aerodynamic behavior from the linear regime requires additional information on the location of ow separation on the airfoil surface. Bio-inspired artificial hair sensors were explored as a part of the current research for stall detection. The response of such artificial micro-structures can identify critical ow characteristics, which relate directly to the stall behavior. The response of the microfences was recorded via an optical microscope for ow over a at plate at different freestream velocities in the NCSU subsonic wind tunnel. Experiments were also conducted to characterize the directional sensitivity of the microstructures by creating ow reversal at the sensor location to assess the sensor response. The results show that the direction of microfence deflection correctly reflects the local ow behavior as the ow direction is reversed at the sensor location and the magnitude of deflection correlates qualitatively to an increase in the freestream velocity. The knowledge of the ow-separation location integrated with the LEFS algorithm allows the possibility of extending the LEFS analysis to post-stall flight regimes, which is explored in the current work. Finally, the application of the LEFS algorithm to unsteady aerodynamics is investigated to identify the critical sequence of events associated with the formation of leading-edge vortices. Signatures of vortex formation on the airfoil surface can be captured in the surface-pressure measurements. Real-time knowledge of the unsteady ow phenomena holds significant potential for exploiting the enhanced-lift characteristics related to vortex formation and inhibiting the detrimental effects of dynamic stall in engineering applications such as helicopters, wind turbines, bio-inspired flight, and energy harvesting devices. Computational data was used to assess the capability of the LEFS outputs to identity the signatures associated with vortex formation, i.e. onset of vortex shedding, detachment, and termination. The results demonstrate useful correlation between the LEFS outputs and the LEV signatures.

Identification of BSAP (Pax-5) target genes in early B-cell development by loss- and gain-of-function experiments.

PubMed Central

Nutt, S L; Morrison, A M; Dörfler, P; Rolink, A; Busslinger, M

1998-01-01

The Pax-5 gene codes for the transcription factor BSAP which is essential for the progression of adult B lymphopoiesis beyond an early progenitor (pre-BI) cell stage. Although several genes have been proposed to be regulated by BSAP, CD19 is to date the only target gene which has been genetically confirmed to depend on this transcription factor for its expression. We have now taken advantage of cultured pre-BI cells of wild-type and Pax-5 mutant bone marrow to screen a large panel of B lymphoid genes for additional BSAP target genes. Four differentially expressed genes were shown to be under the direct control of BSAP, as their expression was rapidly regulated in Pax-5-deficient pre-BI cells by a hormone-inducible BSAP-estrogen receptor fusion protein. The genes coding for the B-cell receptor component Ig-alpha (mb-1) and the transcription factors N-myc and LEF-1 are positively regulated by BSAP, while the gene coding for the cell surface protein PD-1 is efficiently repressed. Distinct regulatory mechanisms of BSAP were revealed by reconstituting Pax-5-deficient pre-BI cells with full-length BSAP or a truncated form containing only the paired domain. IL-7 signalling was able to efficiently induce the N-myc gene only in the presence of full-length BSAP, while complete restoration of CD19 synthesis was critically dependent on the BSAP protein concentration. In contrast, the expression of the mb-1 and LEF-1 genes was already reconstituted by the paired domain polypeptide lacking any transactivation function, suggesting that the DNA-binding domain of BSAP is sufficient to recruit other transcription factors to the regulatory regions of these two genes. In conclusion, these loss- and gain-of-function experiments demonstrate that BSAP regulates four newly identified target genes as a transcriptional activator, repressor or docking protein depending on the specific regulatory sequence context. PMID:9545244

The Urinary Microbiome Differs Significantly Between Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls as Well as Between Patients With Different Clinical Phenotypes.

PubMed

Shoskes, Daniel A; Altemus, Jessica; Polackwich, Alan S; Tucky, Barbara; Wang, Hannah; Eng, Charis

2016-06-01

To study the urinary microbiome of patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) compared with controls. We identified 25 patients with CP/CPPS and 25 men who were either asymptomatic or only had urinary symptoms. Midstream urine was collected. Symptom severity was measured with the National Institutes of Health Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the urine pellet and bacterial-specific 16Sr-DNA-capture identified by MiSeq sequencing. Taxonomic and functional bioinformatic analyses used principal coordinate analysis (PCoA)/MacQIIME, LEfSe, and PiCRUSt algorithms. Patients and controls were similar ages (52.3 vs 57.0 years, P = .27). For patients, median duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0, and mean UPOINT domains was 3.6. Weighted 3D UniFrac PCoA revealed tighter clustering of controls distinct from the wider clustering of cases (P = .001; α-diversity P = .005). Seventeen clades were overrepresented in patients, for example, Clostridia, and 5 were underrepresented, eg, Bacilli, resulting in predicted perturbations in functional pathways. PiCRUSt inferred differentially regulated pathways between cases and controls that may be of relevance including sporulation, chemotaxis, and pyruvate metabolism. PCoA-derived microbiomic differences were noted for neurologic/systemic domains (P = .06), whereas LEfSe identified differences associated with each of the 6 clinical features. Urinary microbiomes from patients with CP/CPPS have significantly higher alpha(phylogenetic) diversity which cluster differently from controls, and higher counts of Clostridia compared with controls, resulting in predicted perturbations of functional pathways which could suggest metabolite-specific targeted treatment. Several measures of severity and clinical phenotype have significant microbiome differences. Copyright © 2016 Elsevier Inc. All rights reserved.

MicroRNA-mediated Th2 bias in methimazole-induced acute liver injury in mice

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

Uematsu, Yasuaki, E-mail: yasuaki-uematsu@ds-pharm

MicroRNA (miRNA) is a class of small non-coding RNAs containing approximately 20 nucleotides that negatively regulate target gene expression. Little is known about the role of individual miRNAs and their targets in immune- and inflammation-related responses in drug-induced liver injury. In the present study, involvement of miRNAs in the T helper (Th) 2-type immune response was investigated using a methimazole (MTZ)-induced liver injury mouse model. Co-administration of L-buthionine-S,R-sulfoximine and MTZ induced acute hepatocellular necrosis and elevated plasma levels of alanine aminotransferase (ALT) from 4 h onward in female Balb/c mice. The hepatic mRNA expression of Th2 promotive factors was significantlymore » increased concomitantly with plasma ALT levels. In contrast, the hepatic mRNA expression of Th2 suppressive factors was significantly decreased during the early phase of liver injury. Comprehensive profiling of hepatic miRNA expression was analyzed before the onset of MTZ-induced liver injury. Using in silico prediction of miRNAs that possibly regulate Th2-related genes and subsequent quantification, we identified up-regulation of expression of miR-29b-1-5p and miR-449a-5p. Among targets of these miRNAs, down-regulation of Th2 suppressive transcription factors, such as SRY-related HMG-box 4 (SOX4) and lymphoid enhancer factor-1 (LEF1), were observed from the early phase of liver injury. In conclusion, negative regulation of the expression of SOX4 by miR-29b-1-5p and that of LEF1 by miR-449a-5p is suggested to play an important role in the development of Th2 bias in MTZ-induced liver injury. - Highlights: • Methimazole induced hepatic Th2 bias in the pathogenesis of liver injury in mice. • Rapid down-regulation of SOX4 and LEF1 may initiate and/or maintain hepatic Th2 bias. • Negative regulation of SOX4 by miR-29b-1-5p and LEF1 by miR-449a-5p was suggested.« less

Population-based comparative analysis of risk of death in children and adolescents with epilepsy and migraine.

PubMed

Selassie, Anbesaw W; Wilson, Dulaney A; Wagner, Janelle L; Smith, Gigi; Wannamaker, Braxton B

2015-12-01

Follow-up studies of children and adolescents with epilepsy (CAW-E) have revealed higher risk of mortality than children in the general population. The mortality experience of CAW-E relative to patients with other common neurologic disorders in the pediatric age group is yet undetermined. The objectives of this study are the following: (1) to compare the causes and the adjusted risk of death in CAW-E with that of children and adolescents with migraine (CAW-M) in reference to children and adolescents with lower extremity fracture (CAW-LEF), and children and adolescents in the general population; (2) to evaluate if disparate mortality risks exist by demographic characteristics. This retrospective cohort study included 56,781 children and adolescents 0-18 years of age hospitalized or treated in an emergency or outpatient department from 2000 to 2011 for epilepsy, migraine, or lower extremity fracture from all nonfederal health care facilities. Data on deaths were acquired from linked multiple causes of death data file using person-specific unique identifiers. Time of follow-up was from initial clinical encounter to time of death or censoring date of December 31, 2011. The association of risk characteristics with mortality was examined with Cox proportional hazard model after adjusting for potential confounders. Four hundred forty-seven CAW-E and 125 CAW-M died yielding mortality rates of 8.71 and 1.36 per 1,000 person-years, respectively. The 5-year risk of death was 4.38% for CAW-E, 0.68% for CAW-M, and 0.71% for CAW-LEF. Adjusted hazard ratios (HRs) were 3.81 (95% confidence interval [CI] 3.08-3.72) in CAW-E and 1.14 (95% CI 0.94-1.34) in CAW-M relative to CAW-LEF. Risk of death from neurodevelopmental comorbidities was 5.86 (95% CI 4.24-8.08) times greater than those without in the model that compared epilepsy with LEF. There is an elevated risk of death in CAW-E with neurodevelopmental comorbidities that remains to be proven. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Long-term change of disease behavior in Papillon-Lefèvre syndrome: seven years follow-up.

PubMed

Wang, Xinwen; Liu, Yang; Liu, Yuan; Dong, Guangying; Kenney, E Barrie; Liu, Qing; Ma, Zhiwei; Wang, Qingtao

2015-03-01

Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disease, characterized by severe periodontitis and palmoplantar hyperkeratosis. Mutations in the cathepsin C (CTSC) gene are the causative genetic factor. PLS starts at very early age, however, the age associated change of PLS has never been characterized. In this report, four PLS patients with CTSC mutations were followed up for seven years, periodontal condition and serum immunoglobulins (Igs) were recorded. Results showed that periodontal inflammation of PLS peaked at teenage years, but declined with time. At the same time the serum IgE change was consistent with the change, suggesting the possibility of using IgE as a monitoring index for PLS inflammation level, or to develop new target for therapy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A novel lymphoid enhancer-binding factor 1-cytoglobin axis promotes extravasation of osteosarcoma cells into the lungs.

PubMed

Pongsuchart, Mongkol; Kuchimaru, Takahiro; Yonezawa, Sakiko; Tran, Diem Thi Phuong; Kha, Nguyen The; Hoang, Ngoc Thi Hong; Kadonosono, Tetsuya; Kizaka-Kondoh, Shinae

2018-06-21

Lung metastasis is a major cause of mortality in patients with osteosarcoma (OS). A better understanding of the molecular mechanism of OS lung metastasis may facilitate development of new therapeutic strategies to prevent the metastasis. We have established high- and low-metastatic sublines (LM8-H and LM8-L respectively) from Dunn OS cell line LM8 by using in vivo image-guided screening. Among the genes whose expression was significantly increased in LM8-H compared to LM8-L, the transcription factor lymphoid enhancer-binding factor 1 (LEF1) was identified as a factor that promotes LM8-H cell extravasation into the lungs. To identify downstream effectors of LEF1 that are involved in OS lung metastasis, 13 genes were selected based on the LM8 microarray data and genome-wide meta-analysis of a public database for OS patients. Among them, the cytoglobin (Cygb) gene was identified as a key effector in promoting OS extravasation into the lungs. CYGB overexpression increased the extravasation ability of LM8-L cells, whereas knocking out the Cygb gene in LM8-H cells reduced this ability. Our results uncovered a novel LEF1-CYGB axis in OS lung metastasis and may open a new avenue for developing therapeutic strategies to prevent OS lung metastasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Postnatal ablation of osteoblast Smad4 enhances proliferative responses to canonical Wnt signaling through interactions with β-catenin

PubMed Central

Salazar, Valerie S.; Zarkadis, Nicholas; Huang, Lisa; Watkins, Marcus; Kading, Jacqueline; Bonar, Sheri; Norris, Jin; Mbalaviele, Gabriel; Civitelli, Roberto

2013-01-01

Summary Canonical Wnt (cWnt) signaling through β-catenin regulates osteoblast proliferation and differentiation to enhance bone formation. We previously reported that osteogenic action of β-catenin is dependent on BMP signaling. Here, we further examined interactions between cWnt and BMP in bone. In osteoprogenitors stimulated with BMP2, β-catenin localizes to the nucleus, physically interacts with Smad4, and is recruited to DNA-binding transcription complexes containing Smad4, R-Smad1/5 and TCF4. Furthermore, Tcf/Lef-dependent transcription, Ccnd1 expression and proliferation all increase when Smad4, 1 or 5 levels are low, whereas TCF/Lef activities decrease when Smad4 expression is high. The ability of Smad4 to antagonize transcription of Ccnd1 is dependent on DNA-binding activity but Smad4-dependent transcription is not required. In mice, conditional deletion of Smad4 in osterix+ cells increases mitosis of cells on trabecular bone surfaces as well as in primary osteoblast cultures from adult bone marrow and neonatal calvaria. By contrast, ablation of Smad4 delays differentiation and matrix mineralization by primary osteoblasts in response to Wnt3a, indicating that loss of Smad4 perturbs the balance between proliferation and differentiation in osteoprogenitors. We propose that Smad4 and Tcf/Lef transcription complexes compete for β-catenin, thus restraining cWnt-dependent proliferative signals while favoring the matrix synthesizing activity of osteoblasts. PMID:24101723

Combined orthodontic and periodontic treatment in a child with Papillon Lefèvre syndrome.

PubMed

AlSarheed, Maha A; Al-Sehaibany, Fares S

2015-08-01

A 9-year-old girl with Papillon-Lefèvre syndrome (PLS) was treated orthodontically 24 months after the start of mechanical and antibiotic therapy in adjunct with periodontal treatment every 6 weeks. After achieving stable periodontal conditions, orthodontic treatment was commenced to correct the teeth position, facial profile, and maxillary protraction. Following the combination therapy and a failure to detect Actinobacillus actinomycetemcomitans from any site in the oral cavity, orthodontic treatment with a fixed appliance was performed aside from creating space for eruption of permanent teeth. We found that combined periodontal and orthodontic treatment of PLS may be successful with a complex interdisciplinary regimen and close follow up. This is a 2-year follow-up case report of a girl with PLS. Orthodontic and periodontic therapy were offered using combined treatments of orthodontic and periodontal with the benefit of prosthodontic consultation, resulting in a treatment plan.

Combined orthodontic and periodontic treatment in a child with Papillon Lefèvre syndrome

PubMed Central

AlSarheed, Maha A.; Al-Sehaibany, Fares S.

2015-01-01

A 9-year-old girl with Papillon-Lefèvre syndrome (PLS) was treated orthodontically 24 months after the start of mechanical and antibiotic therapy in adjunct with periodontal treatment every 6 weeks. After achieving stable periodontal conditions, orthodontic treatment was commenced to correct the teeth position, facial profile, and maxillary protraction. Following the combination therapy and a failure to detect Actinobacillus actinomycetemcomitans from any site in the oral cavity, orthodontic treatment with a fixed appliance was performed aside from creating space for eruption of permanent teeth. We found that combined periodontal and orthodontic treatment of PLS may be successful with a complex interdisciplinary regimen and close follow up. This is a 2-year follow-up case report of a girl with PLS. Orthodontic and periodontic therapy were offered using combined treatments of orthodontic and periodontal with the benefit of prosthodontic consultation, resulting in a treatment plan. PMID:26219452

Functional outcome of knee arthrodesis with a monorail external fixator.

PubMed

Roy, Alfred Cyril; Albert, Sandeep; Gouse, Mohamad; Inja, Dan Barnabas

2016-04-01

Several methods for obtaining knee arthrodesis have been described in the literature and world; over, the commonest cause for arthrodesis is a failed arthroplasty. Less commonly, as in this series, post-infective or traumatic causes may also require a knee fusion wherein arthroplasty may not be indicated. We present salient advantages along with the radiological and functional outcome of twenty four patients treated with a single monorail external fixator. All patients went on develop fusion at an average of 5.4 months with an average limb length discrepancy of 3 cm (1.5-6 cm). Improvements in functional outcome as assessed by the lower extremity functional score (LEFS), and the SF-36 was significant (p = 0.000). Knee arthrodesis with a single monorail external fixator is a reasonable single-staged salvage option in patients wherein arthroplasty may not be the ideal choice. The outcome, though far from ideal, is definitely positive and predictable.

Lethal factor is not required for Bacillus anthracis virulence in guinea pigs and rabbits.

PubMed

Levy, Haim; Weiss, Shay; Altboum, Zeev; Schlomovitz, Josef; Rothschild, Nili; Blachinsky, Eran; Kobiler, David

2011-11-01

The major virulence factor of Bacillus anthracis is the tripartite anthrax toxin, comprising the protective antigen (PA), lethal factor (LF) and edema factor (EF). The LF of B. anthracis is a metalloprotease that has been shown to play an important role in pathogenicity. Deletion of this gene (lef) in the Sterne strain was reported to dramatically reduce the pathogenicity of this strain in mice, and was reported to be as dramatic as the deletion of PA. We evaluated the effect on pathogenicity of the lef deletion in the fully virulent Vollum strain in guinea pigs and NZW rabbits by either subcutaneous injection or intranasal instillation. In guinea pigs, no major differences between the mutant strain and the wild type could be detected in the LD(50) or mean time to death values. On the other hand, the lef deletion caused death of 50-70% of all rabbits infected with the mutant spores at doses equivalent or higher than the wild type LD(50). The surviving rabbits, which were infected with spore doses higher than the wild type LD(50), developed a protective immune response that conferred resistance to challenge with the wild type strain. These findings may indicate that the mutant lacking the LF is capable of host colonization which causes death in 50-70% of the animals and a protective immune response in the others. These results indicate that unlike the data obtained in mice, the LF mutation does not abolish B. anthracis pathogenicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identification and molecular characterization of the Choristoneura fumiferana multicapsid nucleopolyhedrovirus genomic region encoding the regulatory genes pkip, p47, lef-12, and gta.

PubMed

Lapointe, R; Back, D W; Ding, Q; Carstens, E B

2000-05-25

Choristoneura fumiferana multicapsid nucleopolyhedrovirus (CfMNPV) is a baculovirus pathogenic to spruce budworm, the most damaging insect pest in Canadian forestry. CfMNPV is less virulent to its host insect and its replication cycle is slower than the baculovirus type species Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) but the basis of these characteristics is not known. We have now identified, localized, and determined the sequence of the region of CfMNPV carrying potentially important regulatory genes including p47, lef-12, gta, and pkip. DNA database searches revealed that this region of CfMNPV is most closely related to the homologous OpMNPV genes. Transcription analysis demonstrated that CfMNPV P47 is encoded by a 1.6-kb transcript, LEF-12 is encoded by a 2.6-kb transcript, and GTA is encoded by a 2.1-kb transcript. Transcripts for these genes were detectable at 6 h postinfection but all of them showed a burst in expression levels between 12 and 24 h postinfection corresponding to the time of initiation of CfMNPV DNA replication. A polyclonal antibody, raised against CfMNPV P47, detected a nuclear 43-kDa polypeptide from 12 to 72 h postinfection, demonstrating that the CfMNPV p47 gene product is first expressed at a time corresponding to the burst of transcriptional activity between the early and the late phases. Both AcMNPV and CfMNPV P47 translocate to the nucleus of infected cells. Copyright 2000 Academic Press.

The End of the Line: Can Ferredoxin and Ferredoxin NADP(H) Oxidoreductase Determine the Fate of Photosynthetic Electrons?

PubMed Central

Goss, Tatjana; Hanke, Guy

2014-01-01

At the end of the linear photosynthetic electron transfer (PET) chain, the small soluble protein ferredoxin (Fd) transfers electrons to Fd:NADP(H) oxidoreductase (FNR), which can then reduce NADP+ to support C assimilation. In addition to this linear electron flow (LEF), Fd is also thought to mediate electron flow back to the membrane complexes by different cyclic electron flow (CEF) pathways: either antimycin A sensitive, NAD(P)H complex dependent, or through FNR located at the cytochrome b6f complex. Both Fd and FNR are present in higher plant genomes as multiple gene copies, and it is now known that specific Fd iso-proteins can promote CEF. In addition, FNR iso-proteins vary in their ability to dynamically interact with thylakoid membrane complexes, and it has been suggested that this may also play a role in CEF. We will highlight work on the different Fd-isoproteins and FNR-membrane association found in the bundle sheath (BSC) and mesophyll (MC) cell chloroplasts of the C4 plant maize. These two cell types perform predominantly CEF and LEF, and the properties and activities of Fd and FNR in the BSC and MC are therefore specialized for CEF and LEF respectively. A diversity of Fd isoproteins and dynamic FNR location has also been recorded in C3 plants, algae and cyanobacteria. This indicates that the principles learned from the extreme electron transport situations in the BSC and MC of maize might be usefully applied to understanding the dynamic transition between these states in other systems. PMID:24678667

Advanced quantitative methods in correlating sarcopenic muscle degeneration with lower extremity function biometrics and comorbidities

PubMed Central

Gíslason, Magnús; Sigurðsson, Sigurður; Guðnason, Vilmundur; Harris, Tamara; Carraro, Ugo; Gargiulo, Paolo

2018-01-01

Sarcopenic muscular degeneration has been consistently identified as an independent risk factor for mortality in aging populations. Recent investigations have realized the quantitative potential of computed tomography (CT) image analysis to describe skeletal muscle volume and composition; however, the optimum approach to assessing these data remains debated. Current literature reports average Hounsfield unit (HU) values and/or segmented soft tissue cross-sectional areas to investigate muscle quality. However, standardized methods for CT analyses and their utility as a comorbidity index remain undefined, and no existing studies compare these methods to the assessment of entire radiodensitometric distributions. The primary aim of this study was to present a comparison of nonlinear trimodal regression analysis (NTRA) parameters of entire radiodensitometric muscle distributions against extant CT metrics and their correlation with lower extremity function (LEF) biometrics (normal/fast gait speed, timed up-and-go, and isometric leg strength) and biochemical and nutritional parameters, such as total solubilized cholesterol (SCHOL) and body mass index (BMI). Data were obtained from 3,162 subjects, aged 66–96 years, from the population-based AGES-Reykjavik Study. 1-D k-means clustering was employed to discretize each biometric and comorbidity dataset into twelve subpopulations, in accordance with Sturges’ Formula for Class Selection. Dataset linear regressions were performed against eleven NTRA distribution parameters and standard CT analyses (fat/muscle cross-sectional area and average HU value). Parameters from NTRA and CT standards were analogously assembled by age and sex. Analysis of specific NTRA parameters with standard CT results showed linear correlation coefficients greater than 0.85, but multiple regression analysis of correlative NTRA parameters yielded a correlation coefficient of 0.99 (P<0.005). These results highlight the specificities of each muscle quality metric to LEF biometrics, SCHOL, and BMI, and particularly highlight the value of the connective tissue regime in this regard. PMID:29513690

Advanced quantitative methods in correlating sarcopenic muscle degeneration with lower extremity function biometrics and comorbidities.

PubMed

Edmunds, Kyle; Gíslason, Magnús; Sigurðsson, Sigurður; Guðnason, Vilmundur; Harris, Tamara; Carraro, Ugo; Gargiulo, Paolo

2018-01-01

Sarcopenic muscular degeneration has been consistently identified as an independent risk factor for mortality in aging populations. Recent investigations have realized the quantitative potential of computed tomography (CT) image analysis to describe skeletal muscle volume and composition; however, the optimum approach to assessing these data remains debated. Current literature reports average Hounsfield unit (HU) values and/or segmented soft tissue cross-sectional areas to investigate muscle quality. However, standardized methods for CT analyses and their utility as a comorbidity index remain undefined, and no existing studies compare these methods to the assessment of entire radiodensitometric distributions. The primary aim of this study was to present a comparison of nonlinear trimodal regression analysis (NTRA) parameters of entire radiodensitometric muscle distributions against extant CT metrics and their correlation with lower extremity function (LEF) biometrics (normal/fast gait speed, timed up-and-go, and isometric leg strength) and biochemical and nutritional parameters, such as total solubilized cholesterol (SCHOL) and body mass index (BMI). Data were obtained from 3,162 subjects, aged 66-96 years, from the population-based AGES-Reykjavik Study. 1-D k-means clustering was employed to discretize each biometric and comorbidity dataset into twelve subpopulations, in accordance with Sturges' Formula for Class Selection. Dataset linear regressions were performed against eleven NTRA distribution parameters and standard CT analyses (fat/muscle cross-sectional area and average HU value). Parameters from NTRA and CT standards were analogously assembled by age and sex. Analysis of specific NTRA parameters with standard CT results showed linear correlation coefficients greater than 0.85, but multiple regression analysis of correlative NTRA parameters yielded a correlation coefficient of 0.99 (P<0.005). These results highlight the specificities of each muscle quality metric to LEF biometrics, SCHOL, and BMI, and particularly highlight the value of the connective tissue regime in this regard.

Tumor Progression Is Mediated by Thymosin-β4 through a TGFβ/MRTF Signaling Axis.

PubMed

Morita, Tsuyoshi; Hayashi, Ken'ichiro

2018-05-01

Although enhanced thymosin β4 (TMSB4X/Tβ4) expression is associated with tumor progression and metastasis, its tumor-promoting functions remain largely unknown. Here, it is demonstrated that TGFβ facilitates Tβ4 expression and leads to the activation of myocardin-related transcription factors (MRTF), which are coactivators of serum response factor (SRF) and regulate the expression of genes critical for the epithelial-mesenchymal transition (EMT) and tumor metastasis. In murine mammary gland cells (NMuMG), Tβ4 upregulation is required for full induction of a MRTF-regulated EMT gene expression program after TGFβ stimulation. Tβ4 levels are transcriptionally regulated via the novel cis -acting element AGACAAAG, which interacts with Smad and T-cell factor/lymphoid enhancer factor (TCF/LEF) to synergistically activate the Tβ4 promoter downstream of TGFβ. Murine skin melanoma cells (B16F0 and B16F1) also show the expression regulation of Tβ4 by Smad and TCF/LEF. Tβ4-knockout B16F1 (Tβ4 KO) clones show significantly diminished expression level of tumor-associated genes, which is regulated by the TGFβ/MRTFs pathway. In multiple human cancers, Tβ4 levels correlate positively with TGFβ1 and the tumor-associated gene expression levels through processes that respectively depend on TGFβ receptor 1 (TGFBR1) and MRTF expression. Kaplan-Meier survival analyses demonstrate that high Tβ4 expression associates with poor prognosis in an SRF expression-dependent manner in several cancers. In mice, Tβ4 KO clones show significantly decreased experimental metastatic potential; furthermore, ectopic expression of constitutively active MRTF-A fully restores the diminished metastatic activity. In conclusion, the TGFβ/Tβ4/MRTF/SRF pathway is critical for metastasis and tumor progression. Implications: These findings define a molecular mechanism underlying a tumor-promoting function of thymosin β4 through activation of MRTF/SRF signaling. Mol Cancer Res; 16(5); 880-93. ©2018 AACR . ©2018 American Association for Cancer Research.

Matrix Rigidity Activates Wnt Signaling through Down-regulation of Dickkopf-1 Protein*

PubMed Central

Barbolina, Maria V.; Liu, Yiuying; Gurler, Hilal; Kim, Mijung; Kajdacsy-Balla, Andre A.; Rooper, Lisa; Shepard, Jaclyn; Weiss, Michael; Shea, Lonnie D.; Penzes, Peter; Ravosa, Matthew J.; Stack, M. Sharon

2013-01-01

Cells respond to changes in the physical properties of the extracellular matrix with altered behavior and gene expression, highlighting the important role of the microenvironment in the regulation of cell function. In the current study, culture of epithelial ovarian cancer cells on three-dimensional collagen I gels led to a dramatic down-regulation of the Wnt signaling inhibitor dickkopf-1 with a concomitant increase in nuclear β-catenin and enhanced β-catenin/Tcf/Lef transcriptional activity. Increased three-dimensional collagen gel invasion was accompanied by transcriptional up-regulation of the membrane-tethered collagenase membrane type 1 matrix metalloproteinase, and an inverse relationship between dickkopf-1 and membrane type 1 matrix metalloproteinase was observed in human epithelial ovarian cancer specimens. Similar results were obtained in other tissue-invasive cells such as vascular endothelial cells, suggesting a novel mechanism for functional coupling of matrix adhesion with Wnt signaling. PMID:23152495

Matrix rigidity activates Wnt signaling through down-regulation of Dickkopf-1 protein.

PubMed

Barbolina, Maria V; Liu, Yiuying; Gurler, Hilal; Kim, Mijung; Kajdacsy-Balla, Andre A; Rooper, Lisa; Shepard, Jaclyn; Weiss, Michael; Shea, Lonnie D; Penzes, Peter; Ravosa, Matthew J; Stack, M Sharon

2013-01-04

Cells respond to changes in the physical properties of the extracellular matrix with altered behavior and gene expression, highlighting the important role of the microenvironment in the regulation of cell function. In the current study, culture of epithelial ovarian cancer cells on three-dimensional collagen I gels led to a dramatic down-regulation of the Wnt signaling inhibitor dickkopf-1 with a concomitant increase in nuclear β-catenin and enhanced β-catenin/Tcf/Lef transcriptional activity. Increased three-dimensional collagen gel invasion was accompanied by transcriptional up-regulation of the membrane-tethered collagenase membrane type 1 matrix metalloproteinase, and an inverse relationship between dickkopf-1 and membrane type 1 matrix metalloproteinase was observed in human epithelial ovarian cancer specimens. Similar results were obtained in other tissue-invasive cells such as vascular endothelial cells, suggesting a novel mechanism for functional coupling of matrix adhesion with Wnt signaling.

A Field and Simulator Evaluation of All-Red Clearance Intervals for Use in Left-Turn Applications

DOT National Transportation Integrated Search

2018-03-01

As the implementation of the novel flashing yellow arrow (FYA) traffic control device advances throughout the country, agencies continually seek ways to improve intersection operations and safety, especially on left turns. For example, permissive lef...

Response of linear and cyclic electron flux to moderate high temperature and high light stress in tomato*

PubMed Central

Lu, Tao; Shi, Jie-wei; Sun, Zhou-ping; Qi, Ming-fang; Liu, Yu-feng; Li, Tian-lai

2017-01-01

Objective: To evaluate the possible photoprotection mechanisms of cyclic and linear electron flux (CEF and LEF) under specific high temperature and high light (HH) stress. Methods: Six-leaf-stage tomato seedlings (“Liaoyuanduoli”, n=160) were divided into four parts: Part 1, served as control under 25 °C, 500 μmol/(m2·s); Part 2, spayed with distilled water (H2O) under 35 °C, 1000 μmol/(m2·s) (HH); Part 3, spayed with 100 μmol/L diuron (DCMU, CEF inhibitor) under HH; Part 4, spayed with 60 μmol/L methyl viologen (MV, LEF inhibitor) under HH. Energy conversion, photosystem I (PSI), and PSII activity, and trans-thylakoid membrane proton motive force were monitored during the treatment of 5 d and of the recovering 10 d. Results: HH decreased photochemical reaction dissipation (P) and the maximal photochemical efficiency of PSII (F v/F m), and increased the excitation energy distribution coefficient of PSII (β); DCMU and MV aggravated the partition imbalance of the excitation energy (γ) and the photoinhibition degree. With prolonged DCMU treatment time, electron transport rate and quantum efficiency of PSI (ETRI and Y I) significantly decreased whereas acceptor and donor side limitation of PSI (Y NA and Y ND) increased. MV led to a significant decline and accession of yield of regulated and non-regulated energy Y NPQ and Y NO, respectively. Membrane integrity and ATPase activity were reduced by HH stress, and DCMU and MV enhanced inhibitory actions. Conclusions: The protective effects of CEF and LEF were mediated to a certain degree by meliorations in energy absorption and distribution as well as by maintenance of thylakoid membrane integrity and ATPase activity. PMID:28681588

Targeted Training: An Integrated Initiative.

ERIC Educational Resources Information Center

Valvasori, Joe

The Learning Enrichment Foundation (LEF) in Toronto, Ontario (Canada) offers 12 targeted training programs that have successfully helped "hard-to-serve" clients return to the workforce. Compared with traditional training, targeted training has a much narrower focus and adapts quickly to industry trends to meet employers' changing…

Ciliate Paramecium is a natural reservoir of Legionella pneumophila.

PubMed

Watanabe, Kenta; Nakao, Ryo; Fujishima, Masahiro; Tachibana, Masato; Shimizu, Takashi; Watarai, Masahisa

2016-04-15

Legionella pneumophila, the causative agent of Legionnaires' disease, replicates within alveolar macrophages and free-living amoebae. However, the lifestyle of L. pneumophila in the environment remains largely unknown. Here we established a novel natural host model of L. pneumophila endosymbiosis using the ciliate Paramecium caudatum. We also identified Legionella endosymbiosis-modulating factor A (LefA), which contributes to the change in life stage from endosymbiosis to host lysis, enabling escape to the environment. We isolated L. pneumophila strains from the environment, and they exhibited cytotoxicity toward P. caudatum and induced host lysis. Acidification of the Legionella-containing vacuole (LCV) was inhibited, and enlarged LCVs including numerous bacteria were observed in P. caudatum infected with L. pneumophila. An isogenic L. pneumophila lefA mutant exhibited decreased cytotoxicity toward P. caudatum and impaired the modification of LCVs, resulting in the establishment of endosymbiosis between them. Our results suggest that L. pneumophila may have a mechanism to switch their endosymbiosis in protistan hosts in the environment.

Ciliate Paramecium is a natural reservoir of Legionella pneumophila

PubMed Central

Watanabe, Kenta; Nakao, Ryo; Fujishima, Masahiro; Tachibana, Masato; Shimizu, Takashi; Watarai, Masahisa

2016-01-01

Legionella pneumophila, the causative agent of Legionnaires’ disease, replicates within alveolar macrophages and free-living amoebae. However, the lifestyle of L. pneumophila in the environment remains largely unknown. Here we established a novel natural host model of L. pneumophila endosymbiosis using the ciliate Paramecium caudatum. We also identified Legionella endosymbiosis-modulating factor A (LefA), which contributes to the change in life stage from endosymbiosis to host lysis, enabling escape to the environment. We isolated L. pneumophila strains from the environment, and they exhibited cytotoxicity toward P. caudatum and induced host lysis. Acidification of the Legionella-containing vacuole (LCV) was inhibited, and enlarged LCVs including numerous bacteria were observed in P. caudatum infected with L. pneumophila. An isogenic L. pneumophila lefA mutant exhibited decreased cytotoxicity toward P. caudatum and impaired the modification of LCVs, resulting in the establishment of endosymbiosis between them. Our results suggest that L. pneumophila may have a mechanism to switch their endosymbiosis in protistan hosts in the environment. PMID:27079173

Ciliate Paramecium is a natural reservoir of Legionella pneumophila

NASA Astrophysics Data System (ADS)

Watanabe, Kenta; Nakao, Ryo; Fujishima, Masahiro; Tachibana, Masato; Shimizu, Takashi; Watarai, Masahisa

2016-04-01

Legionella pneumophila, the causative agent of Legionnaires’ disease, replicates within alveolar macrophages and free-living amoebae. However, the lifestyle of L. pneumophila in the environment remains largely unknown. Here we established a novel natural host model of L. pneumophila endosymbiosis using the ciliate Paramecium caudatum. We also identified Legionella endosymbiosis-modulating factor A (LefA), which contributes to the change in life stage from endosymbiosis to host lysis, enabling escape to the environment. We isolated L. pneumophila strains from the environment, and they exhibited cytotoxicity toward P. caudatum and induced host lysis. Acidification of the Legionella-containing vacuole (LCV) was inhibited, and enlarged LCVs including numerous bacteria were observed in P. caudatum infected with L. pneumophila. An isogenic L. pneumophila lefA mutant exhibited decreased cytotoxicity toward P. caudatum and impaired the modification of LCVs, resulting in the establishment of endosymbiosis between them. Our results suggest that L. pneumophila may have a mechanism to switch their endosymbiosis in protistan hosts in the environment.

Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts

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

Ohnaka, Keizo; Tanabe, Mizuho; Kawate, Hisaya

2005-04-01

To explore the mechanism of glucocorticoid-induced osteoporosis, we investigated the effect of glucocorticoid on canonical Wnt signaling that emerged as a novel key pathway for promoting bone formation. Wnt3a increased the T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-dependent transcriptional activity in primary cultured human osteoblasts. Dexamethasone suppressed this transcriptional activity in a dose-dependent manner, while 1,25-dihydroxyvitamin D3 increased this transcriptional activity. LiCl, an inhibitor of glycogen synthase kinase-3{beta}, also enhanced the Tcf/Lef-dependent transcriptional activity, which was, however, not inhibited by dexamethasone. The addition of anti-dickkopf-1 antibody partially restored the transcriptional activity suppressed by dexamethasone. Dexamethasone decreased the cytosolic amount of {beta}-cateninmore » accumulated by Wnt3a and also inhibited the nuclear translocation of {beta}-catenin induced by Wnt3a. These data suggest that glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts, partially through the enhancement of the dickkopf-1 production.« less

An assessment of climate change in the Luquillo Mountains of Puerto Rico.

Treesearch

F. N. Scatena

1998-01-01

Change in the surface temperature of the coastal plain of 1 to 2C and/or a 11 to 33% change in annual rainfall could dramatically alter the distribution of forest vegetation within the Luquillo Experimental Forest(LEF) of northeastern Puerto Rico.

Evaluation of LA DOTD traffic load data for determination of traffic load equivalency factors

DOT National Transportation Integrated Search

2001-07-01

This study updates Louisiana's Equivalency Factor (LEF) tables, which are used as an integral part of the State's highway design and rehabilitation effort. This study was required because the tables have not been updated in over 15 years and are, as ...

The Role of DN-GSK3beta in Mammary Tumorigenesis

DTIC Science & Technology

2006-07-01

factors and dramatically increases their transcriptional activity. Genes up- regulated by TCF/LEF include embryologic genes, such as siamois and engrailed...and increased apoptosis occurs in the mammary epithelia (33). Overexpression of the regulator CK2a also promotes mammary tumorigenesis (34). In this

Evaluation of LADOTD traffic load data for determination of traffic load equivalency factors.

DOT National Transportation Integrated Search

2001-07-01

This study updates Louisiana's Load Equivalency Factor (LEF) tables, which are used as an integral part of the State's highway design and rehabilitation effort. This study was required because the tables have not been updated in over 15 years and are...

Fibrin-Enhanced Canonical Wnt Signaling Directs Plasminogen Expression in Cementoblasts

PubMed Central

Rahman, Saeed Ur; Ryoo, Hyun-Mo

2017-01-01

Cementum is a mineralized layer on the tooth’s root surface and facilitates the biomechanical anchoring of fibrous connective tissues as a part of tooth-supportive complexes. Previously, we observed that OCCM30 cementoblasts cultured on fibrin matrices underwent apoptosis due to fibrin degradation through the expression of proteases. Here, we demonstrated that OCCM30 on fibrin matrices (OCCM30-fibrin) enhanced canonical Wnt signaling, which directed to plasminogen expression. The OCCM30-fibrin showed higher levels of Wnt3a expression, nuclear translocation of β-catenin, and T-cell factor (TCF) optimal motif (TOP) reporter activity than the cells on tissue culture dishes (OCCM30-TCD), indicating that the OCCM30-fibrin enhanced canonical Wnt/β-catenin signaling. Also, OCCM30-fibrin expressed biomineralization-associated markers at higher levels than OCCM30-TCD, of which levels were further increased with LiCl, a Wnt signaling activator. The OCCM30 cementoblasts simultaneously showed that high levels of plasminogen, a critical component of fibrinolysis, were expressed in the OCCM30-fibrin. Activation of canonical Wnt signaling with LiCl treatment or with forced lymphoid enhancer factor 1 (LEF1)-expression increased the expression of plasminogen. On the contrary, the inhibition of canonical Wnt signaling with siRNAs against Wnt3a or β-catenin abrogated fibrin-enhanced plasminogen expression. Furthermore, there are three conserved putative response elements for the LEF1/β-catenin complex in the plasminogen proximal promoter regions (−900 to +54). Site-directed mutations and chromatin immunoprecipitation indicated that canonical Wnt signaling directed plasminogen expression. Taken together, this study suggests that fibrin-based materials can modulate functional periodontal formations in controlling cementoblast differentiation and fibrin degradation. PMID:29120400

DNA microarrays of baculovirus genomes: differential expression of viral genes in two susceptible insect cell lines.

PubMed

Yamagishi, J; Isobe, R; Takebuchi, T; Bando, H

2003-03-01

We describe, for the first time, the generation of a viral DNA chip for simultaneous expression measurements of nearly all known open reading frames (ORFs) in the best-studied members of the family Baculoviridae, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV). In this study, a viral DNA chip (Ac-BmNPV chip) was fabricated and used to characterize the viral gene expression profile for AcMNPV in different cell types. The viral chip is composed of microarrays of viral DNA prepared by robotic deposition of PCR-amplified viral DNA fragments on glass for ORFs in the NPV genome. Viral gene expression was monitored by hybridization to the DNA fragment microarrays with fluorescently labeled cDNAs prepared from infected Spodoptera frugiperda, Sf9 cells and Trichoplusia ni, TnHigh-Five cells, the latter a major producer of baculovirus and recombinant proteins. A comparison of expression profiles of known ORFs in AcMNPV elucidated six genes (ORF150, p10, pk2, and three late gene expression factor genes lef-3, p35 and lef- 6) the expression of each of which was regulated differently in the two cell lines. Most of these genes are known to be closely involved in the viral life cycle such as in DNA replication, late gene expression and the release of polyhedra from infected cells. These results imply that the differential expression of these viral genes accounts for the differences in viral replication between these two cell lines. Thus, these fabricated microarrays of NPV DNA which allow a rapid analysis of gene expression at the viral genome level should greatly speed the functional analysis of large genomes of NPV.

ACCUMULATION AND DISPOSAL OF LEFTOVER MEDICATIONS: A KEY ASPECT OF PHARMECOVIGILANCE

EPA Science Inventory

In this paper, we focus on one of the aspects of pharmEcovigilance that has been receiving growing attention, especially in the U.S. — the accumulation and disposal of unwanted, leftover medications. The magnitude of drug stockpiling and accumulation, and eventual disposal of lef...

Incorporation of photobiomodulation therapy into a therapeutic exercise program for knee osteoarthritis: A placebo-controlled, randomized, clinical trial.

PubMed

de Paula Gomes, Cid A F; Leal-Junior, Ernesto C P; Dibai-Filho, Almir V; de Oliveira, Adriano R; Bley, André S; Biasotto-Gonzalez, Daniela A; de Tarso Camillo de Carvalho, Paulo

2018-05-07

To investigate the clinical effects of incorporation of phototherapy in a therapeutic exercise program for individuals with knee osteoarthritis (OA) when compared to a group that received exercise alone and to a group that received exercise + placebo phototherapy. This is a randomized, blinded and placebo-controlled trial. Thus, sixty male and female individuals aged 40-80 years with knee pain in the previous 6 months participated of the study, with diagnosis of unilateral knee OA based on the criteria established by the American College of Rheumatology and radiographic confirmation and Grades 2 or 3 of the Kellgren-Lawrence Classification. The individuals were equally divided in the groups exercise alone, exercise + active phototherapy (nine-diode cluster device: one 905 nm super-pulsed diode laser, four 875 nm LED and four 640 nm LED; energy per quadrant: 7.85 J; total energy: 23.55 J per session), or exercise + placebo phototherapy. Treatments were performed twice a week for 5 consecutive weeks. Patients were evaluated before and after the sessions of treatment. The outcome measures were: Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Lower Extremity Functional Scale (LEFS), Numerical Rating Pain Scale (NRPS), pressure pain threshold (PPT) in two points of knee, muscle strength, and the Functional Reach Test (FRT). Exercise + active phototherapy was significantly more effective than exercise alone (mean difference [MD] = 2.75, 95% confidence interval [CI] = 3.17 to 2.32) and exercise + placebo phototherapy (MD = 2.38, 95% CI = 2.79 to 1.96) only with regard to the NRPS, considering minimal clinically important difference. No clinical significant results were found for function, the pressure pain threshold, muscle strength or balance. The combination of phototherapy and an exercise program is effective at reducing pain intensity among individuals with knee osteoarthritis than exercise alone or exercise + placebo phototherapy in a short-term protocol. Lasers Surg. Med. 9999: 1-10, 2018 © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Exploration and Evaluation of Nanometer Low-power Multi-core VLSI Computer Architectures

DTIC Science & Technology

2015-03-01

ICC, the Milkway database was created using the command: milkyway –galaxy –nogui –tcl –log memory.log one.tcl As stated previously, it is...EDA tools. Typically, Synopsys® tools use Milkway databases, whereas, Cadence Design System® use Layout Exchange Format (LEF) formats. To help

Genetic variation and biological activity of isolates of lymantria dispar multiple nucleopolyhedrovirus from north america, europe, and asia

USDA-ARS?s Scientific Manuscript database

Little is known about genetic variation of Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV; Baculoviridae: Alphabaculovirus) at the nucleotide sequence level. To obtain a more comprehensive view of genetic diversity among isolates of LdMNPV, partial sequences of the lef-8 gene were generated...

Sharp low-energy feature in single-particle spectra due to forward scattering in d-wave cuprate superconductors.

PubMed

Hong, Seung Hwan; Bok, Jin Mo; Zhang, Wentao; He, Junfeng; Zhou, X J; Varma, C M; Choi, Han-Yong

2014-08-01

There is an enormous interest in the renormalization of the quasiparticle (qp) dispersion relation of cuprate superconductors both below and above the critical temperature T_{c} because it enables the determination of the fluctuation spectrum to which the qp's are coupled. A remarkable discovery by angle-resolved photoemission spectroscopy (ARPES) is a sharp low-energy feature (LEF) in qp spectra well below the superconducting energy gap but with its energy increasing in proportion to T_{c} and its intensity increasing sharply below T_{c}. This unexpected feature needs to be reconciled with d-wave superconductivity. Here, we present a quantitative analysis of ARPES data from Bi_{2}Sr_{2}CaCu_{2}O_{8+δ} (Bi2212) using Eliashberg equations to show that the qp scattering rate due to the forward scattering impurities far from the Cu-O planes is modified by the energy gap below T_{c} and shows up as the LEF. This is also a necessary step to analyze ARPES data to reveal the spectrum of fluctuations promoting superconductivity.

Subsonic Maneuvering Effectiveness of High Performance Aircraft Which Employ Quasi-Static Shape Change Devices

NASA Technical Reports Server (NTRS)

Montgomery, Raymond C.; Scott, Michael A.; Weston, Robert P.

1998-01-01

This paper represents an initial study on the use of quasi-static shape change devices in aircraft maneuvering. The macroscopic effects and requirements for these devices in flight control are the focus of this study. Groups of devices are postulated to replace the conventional leading-edge flap (LEF) and the all-moving wing tip (AMT) on the tailless LMTAS-ICE (Lockheed Martin Tactical Aircraft Systems - Innovative Control Effectors) configuration. The maximum quasi-static shape changes are 13.8% and 7.7% of the wing section thickness for the LEF and AMT replacement devices, respectively. A Computational Fluid Dynamics (CFD) panel code is used to determine the control effectiveness of groups of these devices. A preliminary design of a wings-leveler autopilot is presented. Initial evaluation at 0.6 Mach at 15,000 ft. altitude is made through batch simulation. Results show small disturbance stability is achieved, however, an increase in maximum distortion is needed to statically offset five degrees of sideslip. This only applies to the specific device groups studied, encouraging future research on optimal device placement.

Effects of a tele-prehabilitation program or an in-person prehabilitation program in surgical candidates awaiting total hip or knee arthroplasty: Protocol of a pilot single blind randomized controlled trial.

PubMed

Doiron-Cadrin, Patrick; Kairy, Dahlia; Vendittoli, Pascal-André; Lowry, Véronique; Poitras, Stéphane; Desmeules, François

2016-12-15

The accessibility for total joint arthroplasty often comes up against long wait lists, and may lead to deleterious effects for the awaiting patients. This pilot single blind randomized controlled trial aims to evaluate the impact of a telerehabilitation prehabilitation program before a hip or knee arthroplasty compared to in-person prehabilitation or to usual wait for surgery. Thirty-six patients on a wait list for a total hip or knee arthroplasty will be recruited and randomly assigned to one of three groups. The in-person prehabilitation group (n = 12) will receive a 12-week rehabilitation program (2 sessions/week) including education, exercises of the lower limb and cardiovascular training. Patients in the tele-prehabilitation group (n = 12) will receive the same intervention using a telecommunication software. The control group (n = 12) will be provided with the hospital's usual documentation before surgery. The Lower Extremity Functional Scale (LEFS) will be the primary outcome measure taken at baseline and at 12 weeks. Secondary measures will include self-reported function and quality of life as well as performance tests. A mixed-model, 2-way repeated-measure ANOVA will be used to analyse the effects of the rehabilitation programs. This pilot study is the first to evaluate the feasibility and the impact of a telerehabilitation prehabilitation program for patients awaiting a total joint arthroplasty. The results of this pilot-RCT will set the foundations for further research in the fields of rehabilitation and tele-medicine for patients suffering from lower limb osteoarthritis. ClinicalTrials.gov: NCT02636751.

Forward the Foundation: Local Education Foundations Offer an Alternative Source for School Funding

ERIC Educational Resources Information Center

Brooks-Young, Susan

2007-01-01

February's column "Going Corporate" discussed ideas for approaching private foundations for funding. Some districts take this idea several steps further by partnering with the community and local businesses to establish a not-for-profit foundation, or local education foundation (LEF). It probably comes as no surprise that the idea of forming a LEF…

The Public Education Network Study of LEF Leadership: Report on Baseline Survey Findings.

ERIC Educational Resources Information Center

Raphael, Jacqueline; Anderson, Alissa

A study examined how nonprofit organizations, particularly local education funds, and their leaders address social issues. Local education funds are a set of voluntary, intermediate, and mission-driven organizations at the center of educational and civic capacity building. This report provides the results of the first phase of the Public Education…

Palmoplantar keratoderma with progressive gingivitis and recurrent pyodermas.

PubMed

Moss, Tyler A; Spillane, Anne P; Almquist, Sam F; McCleskey, Patrick E; Wisco, Oliver J

2014-04-01

Papillon-Lefèvre syndrome (PLS) is a rare inherited palmoplantar keratoderma (PPK) that is associated with progressive gingivitis and recurrent pyodermas. We present a case exhibiting classic features of this autosomal-recessive condition and review the current understanding of its pathophysiology, diagnosis, and treatment. Additionally, a review of pertinent transgredient PPKs is undertaken, with key and distinguishing features of each syndrome highlighted.

78 FR 28576 - Notice of Petitions by Firms for Determination of Eligibility To Apply for Trade Adjustment...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-15

... Kimball, NE 69145. electrical components and parts for alarms and security systems. AGY Aiken, LLC 2556... 28451. machine components and various injection molded parts. L.E.F., Inc 9401 E. 54th Street, 5/9/2013..., and electrical apparatus. Any party having a substantial interest in these proceedings may request a...

The complete genome sequence of a third distinct baculovirus isolated from the true armyworm, Mythimna unipuncta, contains two copies of the lef-7 gene

USDA-ARS?s Scientific Manuscript database

A baculovirus isolate from a USDA Forest Service collection was examined by electron microscopy and analysis of its genome sequence. The isolate, formerly referred to as Pseudoletia (Mythimna) sp. nucleopolyhedrovirus #7 (MyspNPV#7), was determined by barcoding PCR to derive from the host species My...

U.S. EPA, Pesticide Product Label, PRENTOX 35% MALATHION OIL SOLUBLE CONC. - REFINED, 10/03/1983

EPA Pesticide Factsheets

2011-04-14

... 1. ~':}l.lt .tt.%r C1lP llll dat.a leciulrfA(~ tul It.'(ji&t.Illtiull/ It!rt:'glf;:tldt.lOH (It Y0UI l·rOduct und~r i·l ... ..A t;ec .. )(c) (~) "t.er. tl.e I .. (.:t I.('j' lef';\\lllt.! .. :li. ...

Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1.

PubMed

Li, Fengyin; He, Bing; Ma, Xiaoke; Yu, Shuyang; Bhave, Rupali R; Lentz, Steven R; Tan, Kai; Guzman, Monica L; Zhao, Chen; Xue, Hai-Hui

2017-09-07

Effective treatment of chronic myelogenous leukemia (CML) largely depends on the eradication of CML leukemic stem cells (LSCs). We recently showed that CML LSCs depend on Tcf1 and Lef1 factors for self-renewal. Using a connectivity map, we identified prostaglandin E1 (PGE1) as a small molecule that partly elicited the gene expression changes in LSCs caused by Tcf1/Lef1 deficiency. Although it has little impact on normal hematopoiesis, we found that PGE1 treatment impaired the persistence and activity of LSCs in a pre-clinical murine CML model and a xenograft model of transplanted CML patient CD34 + stem/progenitor cells. Mechanistically, PGE1 acted on the EP4 receptor and repressed Fosb and Fos AP-1 factors in a β-catenin-independent manner. Misoprostol, an FDA-approved EP4 agonist, conferred similar protection against CML. These findings suggest that activation of this PGE1-EP4 pathway specifically targets CML LSCs and that the combination of PGE1/misoprostol with conventional tyrosine-kinase inhibitors could provide effective therapy for CML. Copyright © 2017 Elsevier Inc. All rights reserved.

Late-onset Papillon-Lefèvre syndrome without alteration of the cathepsin C gene.

PubMed

Pilger, Ulrike; Hennies, Hans Christian; Truschnegg, Astrid; Aberer, Elisabeth

2003-11-01

Mutations in the cathepsin C gene have recently been detected in Papillon-Lefèvre syndrome (PLS). Until now, 5 cases with the late-onset variation of this disease have been reported in the literature. The genetic background of this type of PLS is still unknown. We describe a 46-year-old woman with late-onset transgredient palmar hyperkeratosis and a 10-year history of severe periodontal disease. Histology of skin biopsy specimens revealed a psoriasiform pattern. Dental examination showed severe gingival inflammation with loss of alveolar bone. Dental plaque investigated by a polymerase chain reaction method revealed DNA signals of 5 different dental bacteria. DNA from EDTA blood was investigated for mutations in the cathepsin C gene by polymerase chain reaction analysis and direct sequencing. A silent variation in the codon for proline-459 was detected but interpreted as a polymorphism of this gene. All genetic linkage and mutation studies for PLS performed so far have shown that PLS is genetically homogeneous. Our patient with late-onset variation of PLS, however, did not show a mutation in the cathepsin C gene. Thus, we suspect that there is another genetic cause for the late-onset forms of PLS.

Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer.

PubMed

Sprowl-Tanio, Stephanie; Habowski, Amber N; Pate, Kira T; McQuade, Miriam M; Wang, Kehui; Edwards, Robert A; Grun, Felix; Lyou, Yung; Waterman, Marian L

2016-01-01

There is increasing evidence that oncogenic Wnt signaling directs metabolic reprogramming of cancer cells to favor aerobic glycolysis or Warburg metabolism. In colon cancer, this reprogramming is due to direct regulation of pyruvate dehydrogenase kinase 1 ( PDK1 ) gene transcription. Additional metabolism genes are sensitive to Wnt signaling and exhibit correlative expression with PDK1. Whether these genes are also regulated at the transcriptional level, and therefore a part of a core metabolic gene program targeted by oncogenic WNT signaling, is not known. Here, we identify monocarboxylate transporter 1 (MCT-1; encoded by SLC16A1 ) as a direct target gene supporting Wnt-driven Warburg metabolism. We identify and validate Wnt response elements (WREs) in the proximal SLC16A1 promoter and show that they mediate sensitivity to Wnt inhibition via dominant-negative LEF-1 (dnLEF-1) expression and the small molecule Wnt inhibitor XAV939. We also show that WREs function in an independent and additive manner with c-Myc, the only other known oncogenic regulator of SLC16A1 transcription. MCT-1 can export lactate, the byproduct of Warburg metabolism, and it is the essential transporter of pyruvate as well as a glycolysis-targeting cancer drug, 3-bromopyruvate (3-BP). Using sulforhodamine B (SRB) assays to follow cell proliferation, we tested a panel of colon cancer cell lines for sensitivity to 3-BP. We observe that all cell lines are highly sensitive and that reduction of Wnt signaling by XAV939 treatment does not synergize with 3-BP, but instead is protective and promotes rapid recovery. We conclude that MCT-1 is part of a core Wnt signaling gene program for glycolysis in colon cancer and that modulation of this program could play an important role in shaping sensitivity to drugs that target cancer metabolism.

The canonical Wnt pathway regulates the metastasis-promoting mucin MUC4 in pancreatic ductal adenocarcinoma.

PubMed

Pai, Priya; Rachagani, Satyanarayana; Lakshmanan, Imayavaramban; Macha, Muzafar A; Sheinin, Yuri; Smith, Lynette M; Ponnusamy, Moorthy P; Batra, Surinder K

2016-02-01

Aberrant Wnt signaling frequently occurs in pancreatic cancer (PC) and contributes to disease progression/metastases. Likewise, the transmembrane-mucin MUC4 is expressed de novo in early pancreatic intraepithelial neoplasia (PanINs) and incrementally increases with PC progression, contributing to metastasis. To determine the mechanism of MUC4 upregulation in PC, we examined factors deregulated in early PC progression, such as Wnt/β-catenin signaling. MUC4 promoter analysis revealed the presence of three putative TCF/LEF-binding sites, leading us to hypothesize that MUC4 can be regulated by β-catenin. Immunohistochemical (IHC) analysis of rapid autopsy PC tissues showed a correlation between MUC4 and cytosolic/nuclear β-catenin expression. Knock down (KD) of β-catenin in CD18/HPAF and T3M4 cell lines resulted in decreased MUC4 transcript and protein. Three MUC4 promoter luciferase constructs, p3778, p3000, and p2700, were generated. The construct p3778, encompassing the entire MUC4 promoter, elicited increased luciferase activity in the presence of stabilized β-catenin. Mutation of the TCF/LEF site closest to the transcription start site (i.e., -2629/-2612) and furthest from the start site (i.e., -3425/-3408) reduced MUC4 promoter luciferase activity. Transfection with dominant negative TCF4 decreased MUC4 transcript and protein levels. Chromatin immunoprecipitation confirmed enrichment of β-catenin on -2629/-2612 and -3425/-3408 of the MUC4 promoter in CD18/HPAF. Functionally, CD18/HPAF and T3M4 β-catenin KD cells showed decreased migration and decreased Vimentin, N-cadherin, and pERK1/2 expression. Tumorigenicity studies in athymic nude mice showed CD18/HPAF β-catenin KD cells significantly reduced primary tumor sizes and metastases compared to scrambled control cells. We show for the first time that β-catenin directly governs MUC4 in PC. Published by Elsevier B.V.

Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis.

PubMed

Beaton, Hayley; Andrews, Darrell; Parsons, Martin; Murphy, Mary; Gaffney, Andrew; Kavanagh, David; McKay, Gareth J; Maxwell, Alexander P; Taylor, Cormac T; Cummins, Eoin P; Godson, Catherine; Higgins, Debra F; Murphy, Paula; Crean, John

2016-07-01

Diabetic nephropathy is the most common microvascular complication of diabetes mellitus, manifesting as mesangial expansion, glomerular basement membrane thickening, glomerular sclerosis, and progressive tubulointerstitial fibrosis leading to end-stage renal disease. Here we describe the functional characterization of Wnt6, whose expression is progressively lost in diabetic nephropathy and animal models of acute tubular injury and renal fibrosis. We have shown prominent Wnt6 and frizzled 7 (FzD7) expression in the mesonephros of the developing mouse kidney, suggesting a role for Wnt6 in epithelialization. Importantly, TCF/Lef reporter activity is also prominent in the mesonephros. Analysis of Wnt family members in human renal biopsies identified differential expression of Wnt6, correlating with severity of the disease. In animal models of tubular injury and fibrosis, loss of Wnt6 was evident. Wnt6 signals through the canonical pathway in renal epithelial cells as evidenced by increased phosphorylation of GSK3β (Ser9), nuclear accumulation of β-catenin and increased TCF/Lef transcriptional activity. FzD7 was identified as a putative receptor of Wnt6. In vitro Wnt6 expression leads to de novo tubulogenesis in renal epithelial cells grown in three-dimensional culture. Importantly, Wnt6 rescued epithelial cell dedifferentiation in response to transforming growth factor-β (TGF-β); Wnt6 reversed TGF-β-mediated increases in vimentin and loss of epithelial phenotype. Wnt6 inhibited TGF-β-mediated p65-NF-κB nuclear translocation, highlighting cross talk between the two pathways. The critical role of NF-κB in the regulation of vimentin expression was confirmed in both p65(-/-) and IKKα/β(-/-) embryonic fibroblasts. We propose that Wnt6 is involved in epithelialization and loss of Wnt6 expression contributes to the pathogenesis of renal fibrosis. Copyright © 2016 the American Physiological Society.

Three-dimensional culture using a radial flow bioreactor induces matrix metalloprotease 7-mediated EMT-like process in tumor cells via TGFbeta1/Smad pathway.

PubMed

Shibata, Shun-Ichi; Marushima, Hideki; Asakura, Tadashi; Matsuura, Tomokazu; Eda, Homare; Aoki, Katsuhiko; Matsudaira, Hiroshi; Ueda, Kazu; Ohkawa, Kiyoshi

2009-05-01

To confirm the usefulness of the radial flow type bioreactor (RFB) for a three-dimensional (3D) culture system, which provides a tissue architecture and molecular function mimicking the in vivo environment, molecular expression in the A431 human squamous carcinoma cell line during culture were analyzed under the physically different environments of 3D culture in the RFB, 2D culture in a monolayer as well as in nude mice. Time-dependent accumulation of autocrine transforming growth factor (TGF) beta1 was found in spent culture media obtained only from 3D cultured A431 cancer cells, which grew well with a stratified-sheet morphology. Cells in the RFB overexpressed matrix metalloproteinase 7 (MMP7) and showed an increased release of soluble 80-kDa fragments of E-cadherin into the media time-dependently, resulting in the reduction of E-cadherin protein at the cell surface without down-regulation of the mRNA. beta-Catenin and its nuclear partner, LEF1, were up-regulated and Wnt protein secretion was also accelerated. Additional up-regulation of the transcriptional factors, HMGA2 and down-stream Slug, was noted. TGFbeta1-dependent, MMP7-mediated up-regulation of beta-catenin/LEF1 signaling and TGFbeta1-activated HMGA2 pathways consequently converged with Slug overexpression, due to disassembly and further repression of E-cadherin expression, which was reproducible in the epithelial mesenchymal transition process without any manipulation. Other transcriptional factors, Notch/HEY1 and NF-kappaB, were also up-regulated in 3D-cultured cells. These signals recruited molecules related to extracellular matrix-cell remodeling and angiogenesis. Expression of several representative molecules in the 3D cultured cells was parallel with that in xenotransplanted A431 tumor tissues in nude mice. 3D culture of tumor cells in the RFB is a useful tool for cancer experimental biology and evaluation of cancer therapeutic-like systems in nude mice.

Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells.

PubMed

Jaiswal, Aruna S; Marlow, Benjamin P; Gupta, Nirupama; Narayan, Satya

2002-12-05

The development of nontoxic natural agents with chemopreventive activity against colon cancer is the focus of investigation in many laboratories. Curcumin (feruylmethane), a natural plant product, possesses such chemopreventive activity, but the mechanisms by which it prevents cancer growth are not well understood. In the present study, we examined the mechanisms by which curcumin treatment affects the growth of colon cancer cells in vitro. Results showed that curcumin treatment causes p53- and p21-independent G(2)/M phase arrest and apoptosis in HCT-116(p53(+/+)), HCT-116(p53(-/-)) and HCT-116(p21(-/-)) cell lines. We further investigated the association of the beta-catenin-mediated c-Myc expression and the cell-cell adhesion pathways in curcumin-induced G(2)/M arrest and apoptosis in HCT-116 cells. Results described a caspase-3-mediated cleavage of beta-catenin, decreased transactivation of beta-catenin/Tcf-Lef, decreased promoter DNA binding activity of the beta-catenin/Tcf-Lef complex, and decreased levels of c-Myc protein. These activities were linked with decreased Cdc2/cyclin B1 kinase activity, a function of the G(2)/M phase arrest. The decreased transactivation of beta-catenin in curcumin-treated HCT-116 cells was unpreventable by caspase-3 inhibitor Z-DEVD-fmk, even though the curcumin-induced cleavage of beta-catenin was blocked in Z-DEVD-fmk pretreated cells. The curcumin treatment also induced caspase-3-mediated degradation of cell-cell adhesion proteins beta-catenin, E-cadherin and APC, which were linked with apoptosis, and this degradation was prevented with the caspase-3 inhibitor. Our results suggest that curcumin treatment impairs both Wnt signaling and cell-cell adhesion pathways, resulting in G(2)/M phase arrest and apoptosis in HCT-116 cells.

Tbx1 Regulates Progenitor Cell Proliferation in the Dental Epithelium by Modulating PITX2 Activation of p21

PubMed Central

Cao, Huojun; Florez, Sergio; Amen, Melanie; Huynh, Tuong; Skobe, Ziedonis; Baldini, Antonio; Amendt, Brad A.

2012-01-01

Tbx1−/− mice present with phenotypic effects observed in DiGeorge syndrome patients however, the molecular mechanisms of Tbx1 regulating craniofacial and tooth development are unclear. Analyses of the Tbx1 null mice reveal incisor microdontia, small cervical loops and BrdU labeling reveals a defect in epithelial cell proliferation. Furthermore, Tbx1 null mice molars are lacking normal cusp morphology. Interestingly, p21 (associated with cell cycle arrest) is up regulated in the dental epithelium of Tbx1−/− embryos. These data suggest that Tbx1 inhibits p21 expression to allow for cell proliferation in the dental epithelial cervical loop, however Tbx1 does not directly regulate p21 expression. A new molecular mechanism has been identified where Tbx1 inhibits Pitx2 transcriptional activity and decreases the expression of Pitx2 target genes, p21, Lef-1 and Pitx2c. p21 protein is increased in PITX2C transgenic mouse embryo fibroblasts (MEF) and chromatin immunoprecipitation assays demonstrate endogenous Pitx2 binding to the p21 promoter. Tbx1 attenuates PITX2 activation of endogenous p21 expression and Tbx1 null MEFs reveal increased Pitx2a and activation of Pitx2c isoform expression. Tbx1 physically interacts with the PITX2 C-terminus and represses PITX2 transcriptional activation of the p21, LEF-1, and Pitx2c promoters. Tbx1−/+/Pitx2−/+ double heterozygous mice present with an extra premolar-like tooth revealing a genetic interaction between these factors. The ability of Tbx1 to repress PITX2 activation of p21 may promote cell proliferation. In addition, PITX2 regulation of p21 reveals a new role for PITX2 in repressing cell proliferation. These data demonstrate new functional mechanisms for Tbx1 in tooth morphogenesis and provide a molecular basis for craniofacial defects in DiGeorge syndrome patients. PMID:20816801

Tbx1 regulates progenitor cell proliferation in the dental epithelium by modulating Pitx2 activation of p21.

PubMed

Cao, Huojun; Florez, Sergio; Amen, Melanie; Huynh, Tuong; Skobe, Ziedonis; Baldini, Antonio; Amendt, Brad A

2010-11-15

Tbx1(-/-) mice present with phenotypic effects observed in DiGeorge syndrome patients however, the molecular mechanisms of Tbx1 regulating craniofacial and tooth development are unclear. Analyses of the Tbx1 null mice reveal incisor microdontia, small cervical loops and BrdU labeling reveals a defect in epithelial cell proliferation. Furthermore, Tbx1 null mice molars are lacking normal cusp morphology. Interestingly, p21 (associated with cell cycle arrest) is up regulated in the dental epithelium of Tbx1(-/-) embryos. These data suggest that Tbx1 inhibits p21 expression to allow for cell proliferation in the dental epithelial cervical loop, however Tbx1 does not directly regulate p21 expression. A new molecular mechanism has been identified where Tbx1 inhibits Pitx2 transcriptional activity and decreases the expression of Pitx2 target genes, p21, Lef-1 and Pitx2c. p21 protein is increased in PITX2C transgenic mouse embryo fibroblasts (MEF) and chromatin immunoprecipitation assays demonstrate endogenous Pitx2 binding to the p21 promoter. Tbx1 attenuates PITX2 activation of endogenous p21 expression and Tbx1 null MEFs reveal increased Pitx2a and activation of Pitx2c isoform expression. Tbx1 physically interacts with the PITX2 C-terminus and represses PITX2 transcriptional activation of the p21, LEF-1, and Pitx2c promoters. Tbx1(-/+)/Pitx2(-/+) double heterozygous mice present with an extra premolar-like tooth revealing a genetic interaction between these factors. The ability of Tbx1 to repress PITX2 activation of p21 may promote cell proliferation. In addition, PITX2 regulation of p21 reveals a new role for PITX2 in repressing cell proliferation. These data demonstrate new functional mechanisms for Tbx1 in tooth morphogenesis and provide a molecular basis for craniofacial defects in DiGeorge syndrome patients. Copyright © 2010 Elsevier Inc. All rights reserved.

Does the addition of hip strengthening exercises improve outcomes following total knee arthroplasty? A study protocol for a randomized trial.

PubMed

Schache, Margaret B; McClelland, Jodie A; Webster, Kate E

2016-06-13

Total knee arthroplasty (TKA) is effective in reducing pain and improving function for end-stage knee osteoarthritis. However, muscle weakness and functional limitations persist despite assistance from post-operative rehabilitation programs that traditionally focus on quadriceps strengthening and range of movement exercises. Hip abductor muscle weakness is evident in knee osteoarthritis and hip muscle strengthening reduces knee pain in this group. Following TKA, people with weak hip abductor strength perform more poorly on measures of physical function. However, very little is known of the effectiveness of including hip abductor strengthening exercises in post-operative rehabilitation. The aim of this trial is to compare the effects of targeted hip abductor strengthening to those of traditional care in a TKA rehabilitation program on muscle strength, patient reported outcomes and functional performance measures. This protocol describes a single-blinded randomized controlled trial, where 104 participants referred for inpatient rehabilitation following TKA will be recruited. Participants will be randomized using computer-generated numbers to one of two groups: usual care or usual care with additional hip strengthening exercises. Participants will attend physiotherapy daily during their inpatient length of stay, and will then attend between six and eight physiotherapy sessions as an outpatient. Primary outcomes are isometric hip abductor strength and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes are stair climb test, 6 min walk test, timed up and go, 40 m fast-paced walk test, 30 second chair stand test, isometric quadriceps strength, Lower Extremity Functional Scale (LEFS) and SF-12. Outcome measures will be recorded at baseline (admission to inpatient rehabilitation), and then 3 weeks, 6 weeks and 6 months post admission to rehabilitation. The findings of this study will determine whether the addition of targeted hip strengthening to usual care rehabilitation improves physical performance and patient reported outcomes following TKA when compared to usual care rehabilitation. This will then determine whether targeted hip strengthening exercises should be included in traditional rehabilitation programs to improve the outcomes following total knee arthroplasty. The trial protocol was registered with the Australian Clinical Trial Registry ( ACTRN12615000863538 ) on 18 August 2015.

Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer

PubMed Central

Fancy, Stephen P.J.; Harrington, Emily P.; Baranzini, Sergio E.; Silbereis, John C.; Shiow, Lawrence R.; Yuen, Tracy J.; Huang, Eric J.; Lomvardas, Stavros; Rowitch, David H.

2014-01-01

In colon cancer, mutation of the Wnt repressor Adenomatous polyposis coli (APC) leads to a state of aberrant and unrestricted “high-activity” signaling. However, relevance of high Wnt tone in non-genetic human disease is unknown. Here we demonstrate that distinct Wnt activity functional states determine oligodendrocyte precursor (OPC) differentiation and myelination. Murine OPCs with genetic Wnt dysregulation (high tone) express multiple genes in common with colon cancer including Lef1, SP5, Ets2, Rnf43 and Dusp4. Surprisingly, we find that OPCs in lesions of hypoxic human neonatal white matter injury upregulate markers of high Wnt activity and lack expression of APC. Finally, we show lack of Wnt repressor tone promotes permanent white matter injury after mild hypoxic insult. These findings suggest a state of pathological high-activity Wnt signaling in human disease tissues that lack pre-disposing genetic mutation. PMID:24609463

A contrasting function for miR-137 in embryonic mammogenesis and adult breast carcinogenesis

PubMed Central

Kim, Eun-Jung; Tang, Qinghuang; Kim, Kye-Seong; Tickle, Cheryll; Jung, Han-Sung

2015-01-01

MicroRNAs are differentially expressed in breast cancer cells and have been implicated in cancer formation, tumour invasion and metastasis. We investigated the miRNA expression profiles in the developing mammary gland. MiR-137 was expressed prominently in the developing mammary gland. When the miR-137 was over-expressed in the embryo, the mammary epithelium became thickened. Moreover, genes associated with mammary gland formation such as Tbx3 and Lef1 were not expressed. This suggests that miR-137 induces gland formation and invasion. When miR-137 was over-expressed in MDA-MB-231 cells, their ability to form tumours in adult mice was significantly reduced. These data support miR-137 decides epithelial cell behavior in the human breast cancer. It also suggests that miR-137 is a potential therapeutic target for amelioration of breast cancer progression. PMID:26215676

Regulation of MHC class I expression by Foxp3 and its effect on Treg cell function

PubMed Central

Mu, Jie; Tai, Xuguang; Iyer, Shankar S.; Weissman, Jocelyn D.; Singer, Alfred; Singer, Dinah S.

2014-01-01

Expression of MHC class I molecules, which provide immune surveillance against intracellular pathogens, is higher on lymphoid cells than on any other cell types. In T cells, this is a result of activation of class I transcription by the T cell enhanceosome consisting of Runx1, CBFβ and LEF1. We now report that MHC class I transcription in T cells also is enhanced by Foxp3, resulting in higher levels of class I in CD4+CD25+ T regulatory cells than in conventional CD4+CD25− T cells. Interestingly, the effect of Foxp3 regulation of MHC class I transcription is cell-type specific: Foxp3 increases MHC class I expression in T cells but represses it in epithelial tumor cells. In both cell types, Foxp3 targets the upstream IRE and downstream core promoter of the class I gene. Importantly, expression of MHC class I contributes to the function of CD4+CD25+ T regulatory cells by enhancing immune suppression, both in in vitro and in vivo. These findings identify MHC class I genes as direct targets of Foxp3 whose expression augments regulatory T cell function. PMID:24523508

Sox2 acts in a dose-dependent fashion to regulate proliferation of cortical progenitors.

PubMed

Hagey, Daniel W; Muhr, Jonas

2014-12-11

Organ formation and maintenance depends on slowly self-renewing stem cells that supply an intermediate population of rapidly dividing progenitors, but how this proliferative hierarchy is regulated is unknown. By performing genome-wide single-cell and functional analyses in the cortex, we demonstrate that reduced Sox2 expression is a key regulatory signature of the transition between stem cells and rapidly dividing progenitors. In stem cells, Sox2 is expressed at high levels, which enables its repression of proproliferative genes, of which Cyclin D1 is the most potent target. Sox2 confers this function through binding to low-affinity motifs, which facilitate the recruitment of Gro/Tle corepressors in synergy with Tcf/Lef proteins. Upon differentiation, proneural factors reduce Sox2 expression, which derepresses Cyclin D1 and promotes proliferation. Our results show how concentration-dependent Sox2 occupancy of DNA motifs of varying affinities translates into recruitment of repressive complexes, which regulate the proliferative dynamics of neural stem and progenitor cells. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Forest structure and composition in the lower montane rain forest of the Luquillo Mountains, Puerto Rico

Treesearch

Peter L. Weaver

2010-01-01

Six groups of three plots stratified by aspect and topography and varying in elevation were used to sample forest structure and tree species composition within the lower montane rain forest (tabonuco forest) of the Luquillo Experimental Forest (LEF) in Puerto Rico. Stem density, tree height, and total above ground biomass varied by site. Significant differences in...

El Toro Wilderness, Luqillo Experimental Forest, Puerto Rico

Treesearch

Peter L. Weaver

2011-01-01

The El Toro Wilderness, designated by Congress in 2005, occupies about 36 percent of the 11,300 ha Luquillo Experimental Forest (LEF) in northeastern Puerto Rico. It is the only tropical forest in the wilderness system managed by the U.S. Department of Agriculture. El Toro extends from 370 to 1,074 m in elevation, and is occupied by four forest types found in the...

Expression of myogenes in longissimus dorsi muscle during prenatal development in commercial and local Piau pigs.

PubMed

Reis, Evelyze Pinheiro Dos; Paixão, Débora Martins; Brustolini, Otávio José Bernardes; Silva, Fabyano Fonseca E; Silva, Walmir; Araújo, Flávio Marcos Gomes de; Salim, Anna Christina de Matos; Oliveira, Guilherme; Guimarães, Simone Eliza Facioni

2016-01-01

This study used qRT-PCR to examine variation in the expression of 13 myogenes during muscle development in four prenatal periods (21, 40, 70 and 90 days post-insemination) in commercial (the three-way Duroc, Landrace and Large-White cross) and local Piau pig breeds that differ in muscle mass. There was no variation in the expression of the CHD8, EID2B, HIF1AN, IKBKB, RSPO3, SOX7 and SUFU genes at the various prenatal ages or between breeds. The MAP2K1 and RBM24 genes showed similar expression between commercial and Piau pigs but greater expression (p < 0.05) in at least one prenatal period. Pair-wise comparisons of prenatal periods in each breed showed that only the CSRP3, LEF1, MRAS and MYOG genes had higher expression (p < 0.05) in at least one prenatal period in commercial and Piau pigs. Overall, these results identified the LEF1 gene as a primary candidate to account for differences in muscle mass between the pig breeds since activation of this gene may lead to greater myoblast fusion in the commercial breed compared to Piau pigs. Such fusion could explain the different muscularity between breeds in the postnatal periods.

Expression of myogenes in longissimus dorsi muscle during prenatal development in commercial and local Piau pigs

PubMed Central

dos Reis, Evelyze Pinheiro; Paixão, Débora Martins; Brustolini, Otávio José Bernardes; Silva, Fabyano Fonseca e; Silva, Walmir; de Araújo, Flávio Marcos Gomes; Salim, Anna Christina de Matos; Oliveira, Guilherme; Guimarães, Simone Eliza Facioni

2016-01-01

Abstract This study used qRT-PCR to examine variation in the expression of 13 myogenes during muscle development in four prenatal periods (21, 40, 70 and 90 days post-insemination) in commercial (the three-way Duroc, Landrace and Large-White cross) and local Piau pig breeds that differ in muscle mass. There was no variation in the expression of the CHD8, EID2B, HIF1AN, IKBKB, RSPO3, SOX7 and SUFU genes at the various prenatal ages or between breeds. The MAP2K1 and RBM24 genes showed similar expression between commercial and Piau pigs but greater expression (p < 0.05) in at least one prenatal period. Pair-wise comparisons of prenatal periods in each breed showed that only the CSRP3, LEF1, MRAS and MYOG genes had higher expression (p < 0.05) in at least one prenatal period in commercial and Piau pigs. Overall, these results identified the LEF1 gene as a primary candidate to account for differences in muscle mass between the pig breeds since activation of this gene may lead to greater myoblast fusion in the commercial breed compared to Piau pigs. Such fusion could explain the different muscularity between breeds in the postnatal periods. PMID:27801482

Temporal and spatial stability of red-tailed hawk territories in the Luquillo Experimental Forest, Puerto Rico

USGS Publications Warehouse

Boal, C.W.; Snyder, H.A.; Bibles, Brent D.; Estabrook, T.S.

2003-01-01

We mapped Red-tailed Hawk (Buteo jamaicensis) territories in the Luquillo Experimental Forest (LEF) of Puerto Rico in 1998. We combined our 1998 data with that collected during previous studies of Red-tailed Hawks in the LEF to examine population numbers and spatial stability of territorial boundaries over a 26-yr period. We also investigated potential relationships between Red-tailed Hawk territory sizes and topographic and climatic factors. Mean size of 16 defended territories during 1998 was 124.3 ?? 12.0 ha, which was not significantly different from our calculations of mean territory sizes derived from data collected in 1974 and 1984. Aspect and slope influenced territory size with the smallest territories having high slope and easterly aspects. Territory size was small compared to that reported for other parts of the species' range. In addition, there was remarkably little temporal change in the spatial distribution, area, and boundaries of Red-tailed Hawk territories among the study periods. Further, there was substantial boundary overlap (21-27%) between defended territories among the different study periods. The temporal stability of the spatial distribution of Red-tailed Hawk territories in the study area leads us to believe the area might be at or near saturation.

European Leucoma salicis NPV is closely related to North American Orgyia pseudotsugata MNPV.

PubMed

Jakubowska, Agata; van Oers, Monique M; Cory, Jenny S; Ziemnicka, Jadwiga; Vlak, Just M

2005-02-01

The satin moth Leucoma salicis L. (Lepidoptera, Lymantriidae) is a frequent defoliator of poplar trees (Populus spp.) in Europe and Asia (China, Japan). Around 1920 the insect was introduced into the USA and Canada. In this paper, a multicapsid nucleopolyhedrovirus isolated from L. salicis larvae in Poland (LesaNPV) was characterized and appeared to be a variant of Orgyia pseudotsugata (Op) MNPV. O. pseudotsugata, the Douglas fir tussock moth (Lepidoptera, Lymantriidae), occurs exclusively in North America. Sequences of three conserved baculovirus genes, polyhedrin, lef-8, and pif-2, were amplified in polymerase chain reactions using degenerate primer sets, and revealed a high degree of homology to OpMNPV. Restriction enzyme analysis confirmed the close relationship between LesaNPV and OpMNPV, although a number of restriction fragment length polymorphisms were observed. The lef-7 gene, encoding late expression factor 7, and the ctl-2 gene, encoding a conotoxin-like protein, were chosen as putative molecular determinants of the respective viruses. The ctl-2 region appeared suitable for unequivocal identification of either virus as LesaNPV lacked a dUTPase gene in this region. Our observations may suggest that LesaNPV, along with L. salicis, was introduced into O. pseudotsugata after introduction of the former insect into North America in the 1920s.

Ion Composition of Titan's Ionosphere Observed During T9 Magnetotail Crossing

NASA Technical Reports Server (NTRS)

Sittler, Edward; Hartle, Richard; Cooper, John; Shappirio, Marcus; Johnson, Robert; Simpson, David

2011-01-01

In a recent paper, Sittler et al., (2010) presented new results on the T9 encounter by the Cassini spacecraft when it passed through Titan s induced magnetotail. Two crossings were observed, but the first crossing, event 1, is thought to be out flowing ionosphere plasma. T9 is ideal for CAPS IMS probing of the ionosphere, since the ion densities at the higher altitudes of the T9 flyby approx. 10,000 km, allows measurements to be made down to 1 eV without saturating its detectors. Sittler et al., (2010) reported possible detection of NH4+ ions, but favored the detection of CH5+ and C2H5+ ions. In this report we investigate both the medium mass resolution (straight through (ST)) and high mass resolution (linear electric field (LEF)) composition data from the Cassini Plasma Spectrometer (CAPS) Ion Mass Spectrometer (IMS). We present a more in depth analysis of the composition data and make comparisons with ionospheric models including nitrogen chemistry such as that by Vuitton et al. (2007). The LEF data does not support NH4+ identification, but favors a CH5+ and C2H5+ identification, but also molecular ions C2N+ and CH2NH2+ are chemically allowed possibilities.

The genome sequence of Agrotis segetum granulovirus, isolate AgseGV-DA, reveals a new Betabaculovirus species of a slow killing granulovirus.

PubMed

Gueli Alletti, Gianpiero; Eigenbrod, Marina; Carstens, Eric B; Kleespies, Regina G; Jehle, Johannes A

2017-06-01

The European isolate Agrotis segetum granulovirus DA (AgseGV-DA) is a slow killing, type I granulovirus due to low dose-mortality responses within seven days post infection and a tissue tropism of infection restricted solely to the fat body of infected Agrotis segetum host larvae. The genome of AgseGV-DA was completely sequenced and compared to the whole genome sequences of the Chinese isolates AgseGV-XJ and AgseGV-L1. All three isolates share highly conserved genomes. The AgseGV-DA genome is 131,557bp in length and encodes for 149 putative open reading frames, including 37 baculovirus core genes and the per os infectivity factor ac110. Comprehensive investigations of repeat regions identified one putative non-hr like origin of replication in AgseGV-DA. Phylogenetic analysis based on concatenated amino acid alignments of 37 baculovirus core genes as well as pairwise distances based on the nucleotide alignments of partial granulin, lef-8 and lef-9 sequences with deposited betabaculoviruses confirmed AgseGV-DA, AgseGV-XJ and AgseGV-L1 as representative isolates of the same Betabaculovirus species. AgseGV encodes for a distinct putative enhancin, distantly related to enhancins from other granuloviruses. Copyright © 2017. Published by Elsevier Inc.

Compact Graphical Representation of Phylogenetic Data and Metadata with GraPh1An

DTIC Science & Technology

2016-09-12

pipelines . This allows for a higher degree of analysis reproducibility, but the software must correspondingly be available for local installation and callable...these operations are available in the GraPhlAn software repository). Reproducible integration with existing analysis tools and pipelines Graphical...from different analysis pipelines , generating the necessary input files for GraPhlAn. Export2graphlan directly supports MetaPhlAn2, LEfSe, and HUMAnN

Wnt/β-catenin signaling stimulates the expression and synaptic clustering of the autism-associated Neuroligin 3 gene.

PubMed

Medina, Matías A; Andrade, Víctor M; Caracci, Mario O; Avila, Miguel E; Verdugo, Daniela A; Vargas, Macarena F; Ugarte, Giorgia D; Reyes, Ariel E; Opazo, Carlos; De Ferrari, Giancarlo V

2018-03-05

Synaptic abnormalities have been described in individuals with autism spectrum disorders (ASD). The cell-adhesion molecule Neuroligin-3 (Nlgn3) has an essential role in the function and maturation of synapses and NLGN3 ASD-associated mutations disrupt hippocampal and cortical function. Here we show that Wnt/β-catenin signaling increases Nlgn3 mRNA and protein levels in HT22 mouse hippocampal cells and primary cultures of rat hippocampal neurons. We characterized the activity of mouse and rat Nlgn3 promoter constructs containing conserved putative T-cell factor/lymphoid enhancing factor (TCF/LEF)-binding elements (TBE) and found that their activity is significantly augmented in Wnt/β-catenin cell reporter assays. Chromatin immunoprecipitation (ChIP) assays and site-directed mutagenesis experiments revealed that endogenous β-catenin binds to novel TBE consensus sequences in the Nlgn3 promoter. Moreover, activation of the signaling cascade increased Nlgn3 clustering and co- localization with the scaffold PSD-95 protein in dendritic processes of primary neurons. Our results directly link Wnt/β-catenin signaling to the transcription of the Nlgn3 gene and support a functional role for the signaling pathway in the dysregulation of excitatory/inhibitory neuronal activity, as is observed in animal models of ASD.

Association of β-catenin with P-Smad3 but not LEF-1 dissociates in vitro profibrotic from anti-inflammatory effects of TGF-β1.

PubMed

Tian, Xinrui; Zhang, Jianlin; Tan, Thian Kui; Lyons, J Guy; Zhao, Hong; Niu, Bo; Lee, So Ra; Tsatralis, Tania; Zhao, Ye; Wang, Ya; Cao, Qi; Wang, Changqi; Wang, Yiping; Lee, Vincent W S; Kahn, Michael; Zheng, Guoping; Harris, David C H

2013-01-01

Transforming growth factor β1 (TGF-β1) is known to be both anti-inflammatory and profibrotic. Cross-talk between TGF-β/Smad and Wnt/β-catenin pathways in epithelial-mesenchymal transition (EMT) suggests a specific role for β-catenin in profibrotic effects of TGF-β1. However, no such mechanistic role has been demonstrated for β-catenin in the anti-inflammatory effects of TGF-β1. In the present study, we explored the role of β-catenin in the profibrotic and anti-inflammatory effects of TGF-β1 by using a cytosolic, but not membrane, β-catenin knockdown chimera (F-TrCP-Ecad) and the β-catenin/CBP inhibitor ICG-001. TGF-β1 induced nuclear Smad3/β-catenin complex, but not β-catenin/LEF-1 complex or TOP-flash activity, during EMT of C1.1 (renal tubular epithelial) cells. F-TrCP-Ecad selectively degraded TGF-β1-induced cytoplasmic β-catenin and blocked EMT of C1.1 cells. Both F-TrCP-Ecad and ICG-001 blocked TGF-β1-induced Smad3/β-catenin and Smad reporter activity in C1.1 cells, suggesting that TGF-β1-induced EMT depends on β-catenin binding to Smad3, but not LEF-1 downstream of Smad3, through canonical Wnt. In contrast, in J774 macrophages, the β-catenin level was low and was not changed by interferon-γ (IFN-γ) or lipopolysaccharide (LPS) with or without TGF-β1. TGF-β1 inhibition of LPS-induced TNF-α and IFN-γ-stimulated inducible NO synthase (iNOS) expression was not affected by F-TrCP-Ecad, ICG-001 or by overexpression of wild-type β-catenin in J774 cells. Inhibition of β-catenin by either F-TrCP-Ecad or ICG-001 abolished LiCl-induced TOP-flash, but not TGF-β1-induced Smad reporter, activity in J774 cells. These results demonstrate for the first time that β-catenin is required as a co-factor of Smad in TGF-β1-induced EMT of C1.1 epithelial cells, but not in TGF-β1 inhibition of macrophage activation. Targeting β-catenin may dissociate the TGF-β1 profibrotic and anti-inflammatory effects.

The PAX2-null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium

PubMed Central

Ning, Gang; Bijron, Jonathan G.; Yamamoto, Yusuke; Wang, Xia; Howitt, Brooke E.; Herfs, Michael; Yang, Eric; Hong, Yue; Cornille, Maxence; Wu, Lingyan; Hanamornroongruang, Suchanan; McKeon, Frank D.; Crum, Christopher P.; Xian, Wa

2014-01-01

The oviducts contain high grade serous cancer (HGSC) precursors (serous tubal intraepithelial neoplasia or STINs), which are γ-H2AXp- and TP53 mutation-positive. Although they express wild type p53, secretory cell outgrowths (SCOUTs) are associated with older age and serous cancer; moreover both STINs and SCOUTs share a loss of PAX2 expression (PAX2n). We evaluated PAX2 expression in proliferating adult and embryonic oviductal cells, normal mucosa, SCOUTs, Walthard cell nests (WCNs), STINs and HGSCs, and the expression of genes chosen empirically or from SCOUT expression arrays. Clones generated in vitro from embryonic gynecologic tract and adult fallopian tube were Krt7p/PAX2n/EZH2p and underwent ciliated (PAX2n/EZH2n/FOXJ1p) and basal (Krt7n/EZH2n/Krt5p) differentiation. Similarly non-ciliated cells in normal mucosa were PAX2p but became PAX2n in multilayered epithelium undergoing ciliated or basal (Walthard cell nests or WCN) cell differentiation. PAX2n SCOUTs fell into two groups; Type I were secretory or secretory/ciliated with a “tubal” phenotype and were ALDH1n and β-cateninmem (membraneous only). Type II displayed a columnar to pseudostratified (endometrioid) phenotype, with an EZH2p, ALDH1p, β-cateninnc (nuclear and cytoplasmic), stathminp, LEF1p, RCN1p and RUNX2p expression signature. STINs and HGSCs shared the Type I immunophenotype of PAX2n, ALDH1n, β-cateninmem, but highly expressed EZH2p, LEF1p, RCN1p, and stathminp. This study, for the first time, links PAX2n with proliferating fetal and adult oviductal cells undergoing basal and ciliated differentiation and shows that this expression state is maintained in SCOUTs, STINs and HGSCs. All three entities can demonstrate a consistent perturbation of genes involved in potential tumor suppressor gene silencing (EZH2), transcriptional regulation (LEF1), regulation of differentiation (RUNX2), calcium binding (RCN1) and oncogenesis (stathmin). This shared expression signature between benign and neoplastic entities links normal progenitor cell expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a common pathway that could be a target for early prevention. PMID:25130537

Ground-Truthing Moderate Resolution Satellite Imagery with Near-Surface Canopy Images in Hawai'i's Tropical Cloud Forests

NASA Astrophysics Data System (ADS)

Bergstrom, R.; Miura, T.; Lepczyk, C.; Giambelluca, T. W.; Nullet, M. A.; Nagai, S.

2012-12-01

Phenological studies are gaining importance globally as the onset of climate change is impacting the timing of green up and senescence in forest canopies and agricultural regions. Many studies use and analyze land surface phenology (LSP) derived from satellite vegetation index time series (VI's) such as those from Moderate Resolution Imaging Spectroradiometer (MODIS) to monitor changes in phenological events. Seasonality is expected in deciduous temperate forests, while tropical regions are predicted to show more static reflectance readings given their stable and steady state. Due to persistent cloud cover and atmospheric interference in tropical regions, satellite VI time series are often subject to uncertainties and thus require near surface vegetation monitoring systems for ground-truthing. This study has been designed to assess the precision of MODIS phenological signatures using above-canopy, down-looking digital cameras installed on flux towers on the Island of Hawai'i. The cameras are part of the expanding Phenological Eyes Network (PEN) which has been implementing a global network of above-canopy, hemispherical digital cameras for forest and agricultural phenological monitoring. Cameras have been installed at two locations in Hawaii - one on a flux tower in close proximity to the Thurston Lave Tube (HVT) in Hawai'i Volcanoes National Park and the other on a weather station in a section of the Hawaiian Tropical Experimental Forest in Laupaphoehoe (LEF). HVT consists primarily of a single canopy species, ohi'a lehua (Metrosideros polymorpha), with an understory of hapu'u ferns (Cibotium spp), while LEF is similarly comprised with an additional dominant species, Koa (Acacia Koa), included in the canopy structure. Given these species' characteristics, HVT is expected to show little seasonality, while LEF has the potential to deviate slightly during periods following dry and wet seasons. MODIS VI time series data are being analyzed and will be compared to images from the cameras which will have VI's extracted from their RGB image planes and will be normalized to be comparable with MODIS VI's. Given Hawai'i's susceptibility to invasion and delicacy of its endemic species, results from this study will provide necessary site specific detail in determining the reliability of satellite based inference in similar tropical phenology studies. Should satellite images provide adequate information, results from this study will allow for extrapolation across similar understudied tropical forests.

Phosphorylation of PPP(S/T)P motif of the free LRP6 intracellular domain is not required to activate the Wnt/beta-catenin pathway and attenuate GSK3beta activity.

PubMed

Beagle, Brandon; Mi, Kaihong; Johnson, Gail V W

2009-11-01

The canonical Wnt/beta-catenin signaling pathway plays a critical role in numerous physiological and pathological processes. LRP6 is an essential co-receptor for Wnt/beta-catenin signaling; as transduction of the Wnt signal is strongly dependent upon GSK3beta-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane-anchored LRP6 intracellular domain. Previously, we showed that the free LRP6 intracellular domain (LRP6-ICD) can activate the Wnt/beta-catenin pathway in a beta-catenin and TCF/LEF-1 dependent manner, as well as interact with and attenuate GSK3beta activity. However, it is unknown if the ability of LRP6-ICD to attenuate GSK3beta activity and modulate activation of the Wnt/beta-catenin pathway requires phosphorylation of the LRP6-ICD PPP(S/T)P motifs, in a manner similar to the membrane-anchored LRP6 intracellular domain. Here we provide evidence that the LRP6-ICD does not have to be phosphorylated at its PPP(S/T)P motif by GSK3beta to stabilize endogenous cytosolic beta-catenin resulting in activation of TCF/LEF-1 and the Wnt/beta-catenin pathway. LRP6-ICD and a mutant in which all 5 PPP(S/T)P motifs were changed to PPP(A)P motifs equivalently interacted with and attenuated GSK3beta activity in vitro, and both constructs inhibited the in situ GSK3beta-mediated phosphorylation of beta-catenin and tau to the same extent. These data indicate that the LRP6-ICD attenuates GSK3beta activity similar to other GSK3beta binding proteins, and is not a result of it being a GSK3beta substrate. Our findings suggest the functional and regulatory mechanisms governing the free LRP6-ICD may be distinct from membrane-anchored LRP6, and that release of the LRP6-ICD may provide a complimentary signaling cascade capable of modulating Wnt-dependent gene expression. (c) 2009 Wiley-Liss, Inc.

A DNA Binding Protein Is Required for Viral Replication and Transcription in Bombyx mori Nucleopolyhedrovirus.

PubMed

Zhao, Cui; Zhang, Chen; Chen, Bin; Shi, Yanghui; Quan, Yanping; Nie, Zuoming; Zhang, Yaozhou; Yu, Wei

2016-01-01

A DNA-binding protein (DBP) [GenBank accession number: M63416] of Bombyx mori nuclear polyhedrosis virus (BmNPV) has been reported to be a regulatory factor in BmNPV, but its detailed functions remain unknown. In order to study the regulatory mechanism of DBP on viral proliferation, genome replication, and gene transcription, a BmNPV dbp gene knockout virus dbp-ko-Bacmid was generated by the means of Red recombination system. In addition, dbp-repaired virus dbp-re-Bacmid was constructed by the means of the Bac to Bac system. Then, the Bacmids were transfected into BmN cells. The results of this viral titer experiment revealed that the TCID50 of the dbp-ko-Bacmid was 0; however, the dbp-re-Bacmid was similar to the wtBacmid (p>0.05), indicating that the dbp-deficient would lead to failure in the assembly of virus particles. In the next step, Real-Time PCR was used to analyze the transcriptional phases of dbp gene in BmN cells, which had been infected with BmNPV. The results of the latter experiment revealed that the transcript of dbp gene was first detected at 3 h post-infection. Furthermore, the replication level of virus genome and the transcriptional level of virus early, late, and very late genes in BmN cells, which had been transfected with 3 kinds of Bacmids, were analyzed by Real-Time PCR. The demonstrating that the replication level of genome was lower than that of wtBacmid and dbp-re-Bacmid (p<0.01). The transcriptional level of dbp-ko-Bacmid early gene lef-3, ie-1, dnapol, late gene vp39 and very late gene p10 were statistically significantly lower than dbp-re-Bacmid and wtBacmid (p<0.01). The results presented are based on Western blot analysis, which indicated that the lack of dbp gene would lead to low expressions of lef3, vp39, and p10. In conclusion, dbp was not only essential for early viral replication, but also a viral gene that has a significant impact on transcription and expression during all periods of baculovirus life cycle.

Comparison of rumen bacteria distribution in original rumen digesta, rumen liquid and solid fractions in lactating Holstein cows.

PubMed

Ji, Shoukun; Zhang, Hongtao; Yan, Hui; Azarfar, Arash; Shi, Haitao; Alugongo, Gibson; Li, Shengli; Cao, Zhijun; Wang, Yajing

2017-01-01

Original rumen digesta, rumen liquid and solid fractions have been frequently used to assess the rumen bacterial community. However, bacterial profiles in rumen original digesta, liquid and solid fractions vary from each other and need to be better established. To compare bacterial profiles in each fraction, samples of rumen digesta from six cows fed either a high fiber diet (HFD) or a high energy diet (HED) were collected via rumen fistulas. Rumen digesta was then squeezed through four layers of cheesecloth to separate liquid and solid fractions. The bacterial profiles of rumen original digesta, liquid and solid fractions were analyzed with High-throughput sequencing technique. Rumen bacterial diversity was mainly affected by diet and individual cow ( P  > 0.05) rather than rumen fraction. Bias distributed bacteria were observed in solid and liquid fractions of rumen content using Venn diagram and LEfSe analysis. Fifteen out of 16 detected biomarkers (using LEfSe analysis) were found in liquid fraction, and these 15 biomarkers contributed the most to the bacterial differences among rumen content fractions. Similar results were found when using samples of original rumen digesta, rumen liquid or solid fractions to assess diversity of rumen bacteria; however, more attention should be draw onto bias distributed bacteria in different ruminal fractions, especially when liquid fraction has been used as a representative sample for rumen bacterial study.

Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women.

PubMed

Dareng, E O; Ma, B; Famooto, A O; Adebamowo, S N; Offiong, R A; Olaniyan, O; Dakum, P S; Wheeler, C M; Fadrosh, D; Yang, H; Gajer, P; Brotman, R M; Ravel, J; Adebamowo, C A

2016-01-01

In this study, we evaluated the association between high-risk human papillomavirus (hrHPV) and the vaginal microbiome. Participants were recruited in Nigeria between April and August 2012. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Roche Linear Array® HPV genotyping test. We used exact logistic regression models to evaluate the association between community state types (CSTs) of vaginal microbiota and hrHPV infection, weighted UniFrac distances to compare the vaginal microbiota of individuals with prevalent hrHPV to those without prevalent hrHPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm to characterize bacteria associated with prevalent hrHPV infection. We observed four CSTs: CST IV-B with a low relative abundance of Lactobacillus spp. in 50% of participants; CST III (dominated by L. iners) in 39·2%; CST I (dominated by L. crispatus) in 7·9%; and CST VI (dominated by proteobacteria) in 2·9% of participants. LEfSe analysis suggested an association between prevalent hrHPV infection and a decreased abundance of Lactobacillus sp. with increased abundance of anaerobes particularly of the genera Prevotella and Leptotrichia in HIV-negative women (P < 0·05). These results are hypothesis generating and further studies are required.

Chloroplastic ATP synthase optimizes the trade-off between photosynthetic CO2 assimilation and photoprotection during leaf maturation.

PubMed

Huang, Wei; Tikkanen, Mikko; Cai, Yan-Fei; Wang, Ji-Hua; Zhang, Shi-Bao

2018-06-11

In the present study, we studied the role of chloroplastic ATP synthase in photosynthetic regulation during leaf maturation. We measured gas exchange, chlorophyll fluorescence, P700 redox state, and the electrochromic shift signal in mature and immature leaves. Under high light, the immature leaves displayed high levels of non-photochemical quenching (NPQ) and P700 oxidation ratio, and higher values for proton motive force (pmf) and proton gradient (ΔpH) across the thylakoid membranes but lower values for the activity of chloroplastic ATP synthase (g H + ) than the mature leaves. Furthermore, g H + was significantly and positively correlated with CO 2 assimilation rate and linear electron flow (LEF), but negatively correlated with pmf and ΔpH. ΔpH was significantly correlated with LEF and the P700 oxidation ratio. These results indicated that g H + was regulated to match photosynthetic capacity during leaf maturation, and the formation of pmf and ΔpH was predominantly regulated by the alterations in g H + . In the immature leaves, the high steady-state ΔpH increased lumen acidification, which, in turn, stimulated photoprotection for the photosynthetic apparatus via NPQ induction and photosynthetic control. Our results highlighted the importance of chloroplastic ATP synthase in optimizing the trade-off between CO 2 assimilation and photoprotection during leaf maturation. Copyright © 2018. Published by Elsevier B.V.

Metabolic activity of uncultivated magnetotactic bacteria revealed by NanoSIMS

NASA Astrophysics Data System (ADS)

He, M.; Zhang, W.; Gu, L.; Pan, Y.; Lin, W.

2017-12-01

Microorganisms that exhibit magnetotaxis behavior, collectively known as the magnetotactic bacteria (MTB), are those whose motility is influenced by the Earth's magnetic field. MTB are a physiologically diverse group of bacteria with a unique feature of intracellular biomineralization of magnetosomes (Fe3O4 and/or Fe3S4) (Bazylinski et al., 2013). However, the ecophysiology of uncultivated MTB, especially those within the Nitrospirae phylum forming hundreds of bullet-shaped magnetite magnetosomes per cell, is still not well characterized (Lin et al., 2014). Nanoscale secondary ion mass spectrometry (NanoSIMS) is a powerful tool for revealing element distribution in nanometer-scale resolution, which opens exciting possibilities for the study of interactions between microorganisms and environments (Gao et al., 2016; Musat et al., 2016). Here we applied NanoSIMS to investigate the dynamics of carbon and nitrogen assimilations in two magnetotactic Nitrospirae populations at single cell level. Our NanoSIMS results confirmed the metabolic potential of Nitrospirae MTB proposed by genomic and metagenomic analysis and provided additional insights into the ecophysiology of uncultivated MTB. This study suggests that NanoSIMS-based analyses are powerful approaches for investigating and characterizing the ecological function of environmental microorganisms. References: Bazylinski D A., Lefèvre, C T., Schüler D., 2013. Magnetotactic Bacteria. 453-494.Lin W, Bazylinski DA, Xiao T, Wu L- F, Pan Y., 2014. Life with compass: diversity and biogeography of magnetotactic bacteria. Environ Microbiol, 16: 1462-2920.Gao D., Huang X., Tao Y., 2016. A critical review of NanoSIMS in analysis of microbial metabolic activities at single-cell level. Crit Rev Biotechnol, 36: 884-890.Musat N., Musat F., Weber PK., Pett-Ridge J., 2016. Tracking microbial interactions with NanoSIMS. Curr Opin Biotechnol, 41: 114-121.

Managing mobility outcomes in vulnerable seniors ( MMOVeS): a randomized controlled pilot study.

PubMed

Figueiredo, Sabrina; Morais, Jose A; Mayo, Nancy

2017-12-01

To estimate feasibility and potential for efficacy of an individualized, exercise-focused, self-management program (i.e. Managing Mobility Outcomes In Vulnerable Seniors ( MMOVeS)), in comparison to exercise information in improving mobility after six months among seniors recently discharged from hospital. Randomized pilot study. Two McGill University-teaching hospitals. Community dwelling seniors, aged 70 years and older, recently discharged from either participating hospitals. The physiotherapy-facilitated intervention consisted of (1) evaluation of mobility capacity, (2) setting short- and long-term goals, (3) delineation of an exercise treatment plan, (4) an educational booklet to enhance mobility self-management skills, and (5) six monthly telephone calls. Control group received a booklet with information on exercises targeting mobility limitations in seniors. Mobility, pain, and health status were assessed at baseline and at six months using multiple indicators drawn from Disabilities of the Arm, Shoulder, and Hand (DASH) Score, Lower Extremity Functional Scale (LEFS) and Short-Form (SF)-36. In all, 26 people were randomized to the intervention (mean age: 81 ± 8; 39% women), and 23 were randomized to the control (mean age: 79 ± 7; 33% women). The odds ratio for the mobility outcomes combined was 3.08 and the 95% confidence interval excluded 1 (1.65-5.77). The odds ratio for pain and health perception favored the MMOVeS group, but the 95% confidence interval included the null value. This feasibility study highlights the potential for efficacy of an individualized, exercise-focused, self-management program in comparison to exercise information in improving mobility outcome for seniors. Furthermore, a home-program combining self-management skills and exercise taught with minimal supervision prove to be feasible. Finally, data from this study can be used to estimate sample size for a confirmatory trial.

Three-dimensional turbulence-resolving modeling of the Venusian cloud layer and induced gravity waves

NASA Astrophysics Data System (ADS)

Lefèvre, Maxence; Spiga, Aymeric; Lebonnois, Sébastien

2017-04-01

The impact of the cloud convective layer of the atmosphere of Venus on the global circulation remains unclear. The recent observations of gravity waves at the top of the cloud by the Venus Express mission provided some answers. These waves are not resolved at the scale of global circulation models (GCM), therefore we developed an unprecedented 3D turbulence-resolving Large-Eddy Simulations (LES) Venusian model (Lefèvre et al, 2016 JGR Planets) using the Weather Research and Forecast terrestrial model. The forcing consists of three different heating rates : two radiative ones for solar and infrared and one associated with the adiabatic cooling/warming of the global circulation. The rates are extracted from the Laboratoire de Météorlogie Dynamique (LMD) Venus GCM using two different cloud models. Thus we are able to characterize the convection and associated gravity waves in function of latitude and local time. To assess the impact of the global circulation on the convective layer, we used rates from a 1D radiative-convective model. The resolved layer, taking place between 1.0 105 and 3.8 104 Pa (48-53 km), is organized as polygonal closed cells of about 10 km wide with vertical wind of several meters per second. The convection emits gravity waves both above and below the convective layer leading to temperature perturbations of several tenths of Kelvin with vertical wavelength between 1 and 3 km and horizontal wavelength from 1 to 10 km. The thickness of the convective layer and the amplitudes of waves are consistent with observations, though slightly underestimated. The global dynamics heating greatly modify the convective layer.

Identification of the Transformational Properties and Transcriptional Targets of the Oncogenic SRY Transcription Factor SOX4

DTIC Science & Technology

2009-01-01

has also been implicated in tumorigenesis of multiple tumor types and has been shown by our lab to be upregulated in prostate cancer. However, the...mobility group (HMG) DNA-binding domain (DBD) related to the TCF/LEF family of transcription factors. Our lab has previously shown SOX4 mRNA and...protein to be overexpressed in prostate cancer, and this expression is correlated with increasing Gleason score. Other labs have shown SOX4 mRNA to be

β-Catenin is required for intrinsic but not extrinsic BCR-ABL1 kinase-independent resistance to tyrosine kinase inhibitors in chronic myeloid leukemia.

PubMed

Eiring, A M; Khorashad, J S; Anderson, D J; Yu, F; Redwine, H M; Mason, C C; Reynolds, K R; Clair, P M; Gantz, K C; Zhang, T Y; Pomicter, A D; Kraft, I L; Bowler, A D; Johnson, K; Partlin, M Mac; O'Hare, T; Deininger, M W

2015-12-01

Activation of nuclear β-catenin and expression of its transcriptional targets promotes chronic myeloid leukemia (CML) progression, tyrosine kinase inhibitor (TKI) resistance, and leukemic stem cell self-renewal. We report that nuclear β-catenin has a role in leukemia cell-intrinsic but not -extrinsic BCR-ABL1 kinase-independent TKI resistance. Upon imatinib inhibition of BCR-ABL1 kinase activity, β-catenin expression was maintained in intrinsically resistant cells grown in suspension culture and sensitive cells cultured in direct contact (DC) with bone marrow (BM) stromal cells. Thus, TKI resistance uncouples β-catenin expression from BCR-ABL1 kinase activity. In β-catenin reporter assays, intrinsically resistant cells showed increased transcriptional activity versus parental TKI-sensitive controls, and this was associated with restored expression of β-catenin target genes. In contrast, DC with BM stromal cells promoted TKI resistance, but had little effects on Lef/Tcf reporter activity and no consistent effects on cytoplasmic β-catenin levels, arguing against a role for β-catenin in extrinsic TKI resistance. N-cadherin or H-cadherin blocking antibodies abrogated DC-based resistance despite increasing Lef/Tcf reporter activity, suggesting that factors other than β-catenin contribute to extrinsic, BM-derived TKI resistance. Our data indicate that, while nuclear β-catenin enhances survival of intrinsically TKI-resistant CML progenitors, it is not required for extrinsic resistance mediated by the BM microenvironment.

Activation of Wnt/β-catenin signaling is involved in hair growth-promoting effect of 655-nm red light and LED in in vitro culture model.

PubMed

Han, Le; Liu, Ben; Chen, Xianyan; Chen, Haiyan; Deng, Wenjia; Yang, Changsheng; Ji, Bin; Wan, Miaojian

2018-04-01

Activation of the Wnt/β-catenin signaling pathway plays an important role in hair follicle morphogenesis and hair growth. Recently, low-level laser therapy (LLLT) was evaluated for stimulating hair growth in numerous clinical studies, in which 655-nm red light was found to be most effective and practical for stimulating hair growth. We evaluated whether 655-nm red light + light-emitting diode (LED) could promote human hair growth by activating Wnt/β-catenin signaling. An in vitro culture of human hair follicles (HFs) was irradiated with different intensities of 655-nm red light + LED, 21 h7 (an inhibitor of β-catenin), or both. Immunofluorescence staining was performed to assess the expression of β-catenin, GSK3β, p-GSK3β, and Lef1 in the Wnt/β-catenin signaling. The 655-nm red light + LED not only enhanced hair shaft elongation, but also reduced catagen transition in human hair follicle organ culture, with the greatest effectiveness observed at 5 min (0.839 J/cm 2 ). Additionally, 655-nm red light + LED enhanced the expression of β-catenin, p-GSK3β, and Lef1, signaling molecules of the Wnt/β-catenin pathway, in the hair matrix. Activation of Wnt/β-catenin signaling is involved in hair growth-promoting effect of 655-nm red light and LED in vitro and therefore may serve as an alternative therapeutic option for alopecia.

Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin

PubMed Central

Tong, Tao; Kim, Nahyun; Park, Taesun

2015-01-01

We observed that oleuropein, the main constituent of the leaves and unprocessed olive drupes of Olea europaea, protected mice from high-fat diet-induced adiposity by up-regulation of genes involved in Wnt10b-mediated signaling in adipose tissue. The activation of Wnt/β-catenin pathway is also well established to positively regulate the anagen phase of hair growth cycle in mice skin. Methodology and Principal Findings Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day) to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression. Conclusions and Significance These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue. PMID:26060936

Understanding Tropical Forest Abiotic Responses to Canopy Loss and Biomass Deposition from an Experimental Hurricane Manipulation

NASA Astrophysics Data System (ADS)

Van Beusekom, A.; González, G.; Stankavitch, S.; Zimmerman, J. K.

2017-12-01

Understanding the nature and duration of the response of tropical forests to the extreme weather events of hurricanes is critical to understanding future forest regimes, as hurricanes are expected to increase in frequency with climate change. Here we present results from a manipulative experiment on hurricane disturbance effects in the Luquillo Experimental Forest (LEF) in Puerto Rico. The LEF is an example of a forest that would be in a frequent-hurricane region in Earth System Models (ESMs). Thus, the Canopy Trimming Experiment (CTE) was designed to study the key mechanisms behind such a forest's response after a major hurricane (category 4), and guide how repeated hurricanes might be expected to alter such ecosystems using these key mechanisms. Furthermore, with explicit forest manipulation instead of natural occurrence, it is possible to separate out which aspects of hurricane disturbance are most important to be accurately included in ESMs. Phase one of the experiments ran from 2005-2012, where it was found that short-term biotic responses of the forests were driven by canopy openness rather than by debris deposition. In phase two, running from 2014 through the present, we focus here on the abiotic changes forcing the overall response of the ecosystem. The manner in which these abiotic characteristics are disturbed and the speed at which they recover will be key to the continued existence of tropical forests under a climate with more frequent hurricane activity.

β-Catenin Up-regulates Atoh1 Expression in Neural Progenitor Cells by Interaction with an Atoh1 3′ Enhancer*

PubMed Central

Shi, Fuxin; Cheng, Yen-fu; Wang, Xiaohui L.; Edge, Albert S. B.

2010-01-01

Atoh1, a basic helix-loop-helix transcription factor, plays a critical role in the differentiation of several epithelial and neural cell types. We found that β-catenin, the key mediator of the canonical Wnt pathway, increased expression of Atoh1 in mouse neuroblastoma cells and neural progenitor cells, and baseline Atoh1 expression was decreased by siRNA directed at β-catenin. The up-regulation of Atoh1 was caused by an interaction of β-catenin with the Atoh1 enhancer that could be demonstrated by chromatin immunoprecipitation. We found that two putative Tcf-Lef sites in the 3′ enhancer of the Atoh1 gene displayed an affinity for β-catenin and were critical for the activation of Atoh1 transcription because mutation of either site decreased expression of a reporter gene downstream of the enhancer. Tcf-Lef co-activators were found in the complex that bound to these sites in the DNA together with β-catenin. Inhibition of Notch signaling, which has previously been shown to induce bHLH transcription factor expression, increased β-catenin expression in progenitor cells of the nervous system. Because this could be a mechanism for up-regulation of Atoh1 after inhibition of Notch, we tested whether siRNA to β-catenin prevented the increase in Atoh1 and found that β-catenin expression was required for increased expression of Atoh1 after Notch inhibition. PMID:19864427

Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via Activation of the Wnt/β-Catenin Signaling Pathway After Spinal Cord Injury.

PubMed

Shen, Zhaoliang; Zhou, Zipeng; Gao, Shuang; Guo, Yue; Gao, Kai; Wang, Haoyu; Dang, Xiaoqian

2017-08-01

The spinal cord is highly sensitive to spinal cord injury (SCI) by external mechanical damage, resulting in irreversible neurological damage. Activation of the Wnt/β-catenin signaling pathway can effectively reduce apoptosis and protect against SCI. Melatonin, an indoleamine originally isolated from bovine pineal tissue, exerts neuroprotective effects after SCI through activation of the Wnt/β-catenin signaling pathway. In this study, we demonstrated that melatonin exhibited neuroprotective effects on neuronal apoptosis and supported functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. We found that melatonin administration after SCI significantly upregulated the expression of low-density lipoprotein receptor related protein 6 phosphorylation (p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and β-catenin protein in the spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord ventral horn and improved the locomotor functions of rats after SCI. Melatonin administration after SCI also reduced the expression levels of Bax and cleaved caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cells, but increased the expression level of Bcl-2. These results suggest that melatonin attenuated SCI by activating the Wnt/β-catenin signaling pathway.

Dynamic succession of substrate-associated bacterial composition and function during Ganoderma lucidum growth

PubMed Central

Li, Qiang; Zou, Jie; Tan, Hao; Tan, Wei; Peng, Weihong

2018-01-01

Background Ganoderma lucidum, a valuable medicinal fungus, is widely distributed in China. It grows alongside with a complex microbial ecosystem in the substrate. As sequencing technology advances, it is possible to reveal the composition and functions of substrate-associated bacterial communities. Methods We analyzed the bacterial community dynamics in the substrate during the four typical growth stages of G. lucidum using next-generation sequencing. Results The physicochemical properties of the substrate (e.g. acidity, moisture, total nitrogen, total phosphorus and total potassium) changed between different growth stages. A total of 598,771 sequences from 12 samples were obtained and assigned to 22 bacterial phyla. Proteobacteria and Firmicutes were the dominant phyla. Bacterial community composition and diversity significantly differed between the elongation stage and the other three growth stages. LEfSe analysis revealed a large number of bacterial taxa (e.g. Bacteroidetes, Acidobacteria and Nitrospirae) with significantly higher abundance at the elongation stage. Functional pathway prediction uncovered significant abundance changes of a number of bacterial functional pathways between the elongation stage and other growth stages. At the elongation stage, the abundance of the environmental information processing pathway (mainly membrane transport) decreased, whereas that of the metabolism-related pathways increased. Discussion The changes in bacterial community composition, diversity and predicted functions were most likely related to the changes in the moisture and nutrient conditions in the substrate with the growth of G. lucidum, particularly at the elongation stage. Our findings shed light on the G. lucidum-bacteria-substrate relationships, which should facilitate the industrial cultivation of G. lucidum. PMID:29915697

Experimental Research Into High Barometric Oxygen Prevention of Guinea Pig Hearing Loss,

DTIC Science & Technology

1992-08-28

PREVENTION OF GUINEA PIG HEARING LOSS by Yin Jiacai, Sun Fang ren, et al. DTIC MLECTE •<• EP 2 9 1992 Approved for public release, Distribution unlimited...PREVENTION OF GUINEA PIG HEARING LOSS By: Yin Jiacai, Sun Fang ren, et al. English pages: 9 Source: Chung-Hua I Shueh Tsa Chih, Vol. 65, Nr. 11, Nov.eember...Distributionf._DL~~~t .•b • / or __ Dlist szeccat .lef ’ ~1 EXPERIMENTAL RESEARCH INTO HIGH BAROMETRIC OXYGEN PREVENTION OF GUINEA PIG HEARING LOSS BY: Yin

MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway

PubMed Central

Ahmed, Mohammed I.; Alam, Majid; Emelianov, Vladimir U.; Poterlowicz, Krzysztof; Patel, Ankit; Sharov, Andrey A.; Mardaryev, Andrei N.

2014-01-01

Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging. PMID:25422376

Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivo.

PubMed

Costa, Mónica; Cruz, Eugénia; Oliveira, Susana; Benes, Vladimir; Ivacevic, Tomi; Silva, Maria João; Vieira, Inês; Dias, Francisco; Fonseca, Sónia; Gonçalves, Marta; Lima, Margarida; Leitão, Catarina; Muckenthaler, Martina U; Pinto, Jorge; Porto, Graça

2015-01-01

Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe-/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe-/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe-/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH.

Lymphocyte Gene Expression Signatures from Patients and Mouse Models of Hereditary Hemochromatosis Reveal a Function of HFE as a Negative Regulator of CD8+ T-Lymphocyte Activation and Differentiation In Vivo

PubMed Central

Costa, Mónica; Cruz, Eugénia; Oliveira, Susana; Benes, Vladimir; Ivacevic, Tomi; Silva, Maria João; Vieira, Inês; Dias, Francisco; Fonseca, Sónia; Gonçalves, Marta; Lima, Margarida; Leitão, Catarina; Muckenthaler, Martina U.; Pinto, Jorge; Porto, Graça

2015-01-01

Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe -/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe -/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe -/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH. PMID:25880808

The subgingival microbiota of Papillon-Lefèvre syndrome.

PubMed

Albandar, Jasim M; Khattab, Razan; Monem, Fawza; Barbuto, Sara M; Paster, Bruce J

2012-07-01

There is little information about the microbiologic profiles of periodontal lesions in Papillon-Lefèvre syndrome (PLS) and the significance of bacteria in the pathogenesis of periodontitis in these patients. This comprehensive analysis of the subgingival microbiota in patients with PLS used 16S ribosomal RNA (rRNA) clonal analysis and the 16S rRNA-based Human Oral Microbe Identification Microarray (HOMIM). Thirteen patients with PLS from seven unrelated families volunteered for this microbiologic study. Subgingival plaque was collected with sterile paper points from multiple sites with ≥5 mm probing depth, and whole genomic DNA was extracted. The 16S rRNA genes were amplified, cloned, and sequenced. The samples were then probed for ≈300 predominant oral bacterial species using the HOMIM. The most commonly detected phylotypes in the clonal analysis were Gemella morbillorum, Gemella haemolysans, Granulicatella adiacens, Lachnospiraceae OT 100 (EI074), Parvimonas micra, Selenomonas noxia, and Veillonella parvula. As a group, streptococci were commonly detected in these individuals. In the HOMIM analysis, a total of 170 bacterial species/phylotypes were detected, with a range of 40 to 80 species per patient with PLS. Of these, 12 bacterial species were detected in medium to high levels in ≥50% of the individuals. The high-frequency strains were clustered into eight groups: Aggregatibacter actinomycetemcomitans, Campylobacter spp., Capnocytophaga granulosa, G. morbillorum, P. micra, Porphyromonas endodontalis, Streptococcus spp., and Tannerella forsythia. The subgingival microbiota in PLS is diverse. Periodontal pathogens commonly associated with chronic and aggressive periodontitis and opportunistic pathogens may be associated with the development of severe periodontitis in patients with PLS.

Organized Emergence of Multiple-Generations of Teeth in Snakes Is Dysregulated by Activation of Wnt/Beta-Catenin Signalling

PubMed Central

Gaete, Marcia; Tucker, Abigail S.

2013-01-01

In contrast to mammals, most reptiles constantly regenerate their teeth. In the snake, the epithelial dental lamina ends in a successional lamina, which proliferates and elongates forming multiple tooth generations, all linked by a permanent dental lamina. To investigate the mechanisms used to control the initiation of new tooth germs in an ordered sequential pattern we utilized the polyphodont (multiple-generation) corn snake (Pantherophis guttatus). We observed that the dental lamina expressed the transcription factor Sox2, a multipotent stem cell marker, whereas the successional lamina cells expressed the transcription factor Lef1, a Wnt/β-catenin pathway target gene. Activation of the Wnt/β-catenin pathway in culture increased the number of developing tooth germs, in comparison to control untreated cultures. These additional tooth germs budded off from ectopic positions along the dental lamina, rather than in an ordered sequence from the successional lamina. Wnt/β-catenin activation enhanced cell proliferation, particularly in normally non-odontogenic regions of the dental lamina, which widely expressed Lef1, restricting the Sox2 domain. This suggests an expansion of the successional lamina at the expense of the dental lamina. Activation of the Wnt/β-catenin pathway in cultured snake dental organs, therefore, led to changes in proliferation and to the molecular pattern of the dental lamina, resulting in loss of the organised emergence of tooth germs. These results suggest that epithelial compartments are critical for the arrangement of organs that develop in sequence, and highlight the role of Wnt/β-catenin signalling in such processes. PMID:24019968

Role of thymosin beta 4 in hair growth.

PubMed

Gao, Xiao-Yu; Hou, Fang; Zhang, Zhi-Peng; Nuo, Ming-Tu; Liang, Hao; Cang, Ming; Wang, Zhi-Gang; Wang, Xin; Xu, Teng; Yan, Le-Yan; Guo, Xu-Dong; Liu, Dong-Jun

2016-08-01

Although thymosin beta 4 (Tβ4) is known to play a role in hair growth, its mechanism of action is unclear. We examined the levels of key genes in a Tβ4 epidermal-specific over-expressing mouse model and Tβ4 global knockout mouse model to explore how Tβ4 affects hair growth. By depilation and histological examination of the skin, we confirmed the effect of Tβ4 on hair growth, the number of hair shafts and hair follicle (HF) structure. The mRNA and protein expression of several genes involved in hair growth were detected by real-time PCR and western blotting, respectively. Changes in the expression of β-catenin and Lef-1, the two key molecules in the Wnt signaling pathway, were similar to the changes observed in Tβ4 expression. We also found that compared to the control mice, the mRNA and protein expression of MMP-2 and VEGF were increased in the Tβ4 over-expressing mice, while the level of E-cadherin (E-cad) remained the same. Further, in the Tβ4 global knockout mice, the mRNA and protein levels of MMP-2 and VEGF decreased dramatically and the level of E-cad was stable. Based on the above results, we believe that Tβ4 may regulate the levels of VEGF and MMP-2 via the Wnt/β-catenin/Lef-1 signaling pathway to influence the growth of blood vessels around HFs and to activate cell migration. Tβ4 may have potential for the treatment of hair growth problems in adults, and its effects should be further confirmed in future studies.

Isolation and characterization of the DNA-binding protein (DBP) of the Autographa californica multiple nucleopolyhedrovirus

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

Mikhailov, Victor S.; N. K. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow 117808; Vanarsdall, Adam L.

2008-01-20

DNA-binding protein (DBP) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) was expressed as an N-terminal His{sub 6}-tag fusion using a recombinant baculovirus and purified to near homogeneity. Purified DBP formed oligomers that were crosslinked by redox reagents resulting in predominantly protein dimers and tetramers. In gel retardation assays, DBP showed a high affinity for single-stranded oligonucleotides and was able to compete with another baculovirus SSB protein, LEF-3, for binding sites. DBP binding protected ssDNA against hydrolysis by a baculovirus alkaline nuclease AN/LEF-3 complex. Partial proteolysis by trypsin revealed a domain structure of DBP that is required for interaction with DNA andmore » that can be disrupted by thermal treatment. Binding to ssDNA, but not to dsDNA, changed the pattern of proteolytic fragments of DBP indicating adjustments in protein structure upon interaction with ssDNA. DBP was capable of unwinding short DNA duplexes and also promoted the renaturation of long complementary strands of ssDNA into duplexes. The unwinding and renaturation activities of DBP, as well as the DNA binding activity, were sensitive to sulfhydryl reagents and were inhibited by oxidation of thiol groups with diamide or by alkylation with N-ethylmaleimide. A high affinity of DBP for ssDNA and its unwinding and renaturation activities confirmed identification of DBP as a member of the SSB/recombinase family. These activities and a tight association with subnuclear structures suggests that DBP is a component of the virogenic stroma that is involved in the processing of replicative intermediates.« less

Growth retardation induced by avian leukosis virus subgroup J associated with down-regulated Wnt/β-catenin pathway.

PubMed

Feng, Weiguo; Zhou, Defang; Meng, Wei; Li, Gen; Zhuang, Pingping; Pan, Zhifang; Wang, Guihua; Cheng, Ziqiang

2017-03-01

Avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, induces growth retardation and neoplasia in chickens, leading to enormous economic losses in poultry industry. Increasing evidences showed several signal pathways involved in ALV-J infection. However, what signaling pathway involved in growth retardation is largely unknown. To explore the possible signaling pathway, we tested the cell proliferation and associated miRNAs in ALV-J infected CEF cells by CCK-8 and Hiseq, respectively. The results showed that cell proliferation was significantly inhibited by ALV-J and three associated miRNAs were identified to target Wnt/β-catenin pathway. To verify the Wnt/β-catenin pathway involved in cell growth retardation, we analyzed the key molecules of Wnt pathway in ALV-J infected CEF cells. Our data demonstrated that protein expression of β-catenin was decreased significantly post ALV-J infection compared with the normal (P < 0.05). The impact of this down-regulation caused low expression of known target genes (Axin2, CyclinD1, Tcf4 and Lef1). Further, to obtain in vivo evidence, we set up an ALV-J infection model. Post 7 weeks infection, ALV-J infected chickens showed significant growth retardation. Subsequent tests showed that the expression of β-catenin, Tcf1, Tcf4, Lef1, Axin2 and CyclinD1 were down-regulated in muscles of growth retardation chickens. Taken together, all data demonstrated that chicken growth retardation caused by ALV-J associated with down-regulated Wnt/β-catenin signaling pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genomic analysis of Oryctes rhinoceros virus reveals genetic relatedness to Heliothis zea virus 1.

PubMed

Wang, Y; van Oers, M M; Crawford, A M; Vlak, J M; Jehle, J A

2007-01-01

Oryctes rhinoceros virus (OrV) is an unassigned invertebrate dsDNA virus with enveloped and rod-shaped virions. Two cloned PstI fragments, C and D, of OrV DNA have been sequenced, consisting of 19,805 and 17,146 bp, respectively, and comprising about 30% of the OrV genome. For each of the two fragments, 20 open reading frames (ORFs) of 150 nucleotides or greater with no or minimal overlap were predicted. Ten of the predicted 40 ORFs revealed significant similarities to Heliothis zea virus 1 (HzV-1) ORFs, of which five, lef-4, lef-5, pif-2, dnapol and ac81, are homologues of conserved core genes in the family Baculoviridae, and one is homologous to baculovirus rr1. A baculovirus odv-e66 homologue is also present in OrV. Five ORFs encode proteins homologous to cellular thymidylate synthase (TS), patatin-like phospholipase, mitochondrial carrier protein, Ser/Thr protein phosphatase, and serine protease, respectively. TS is phylogenetically related to those of eukarya and nucleo-cytoplasmic large dsDNA viruses. However, the remaining 25 ORFs have poor or no sequence matches with the current databases. Both the gene content of the sequenced fragments and the phylogenetic analyses of the viral DNA polymerase suggest that OrV is most closely related to HzV-1. These findings and the re-evaluation of the relationship of HzV-1 to baculoviruses suggest that a new virus genus, Nudivirus, should be established, containing OrV and HzV-1, which are genetically related to members of the family Baculoviridae.

Periodontal disease associated to systemic genetic disorders.

PubMed

Nualart Grollmus, Zacy Carola; Morales Chávez, Mariana Carolina; Silvestre Donat, Francisco Javier

2007-05-01

A number of systemic disorders increase patient susceptibility to periodontal disease, which moreover evolves more rapidly and more aggressively. The underlying factors are mainly related to alterations in immune, endocrine and connective tissue status. These alterations are associated with different pathologies and syndromes that generate periodontal disease either as a primary manifestation or by aggravating a pre-existing condition attributable to local factors. This is where the role of bacterial plaque is subject to debate. In the presence of qualitative or quantitative cellular immune alterations, periodontal disease may manifest early on a severe localized or generalized basis--in some cases related to the presence of plaque and/or specific bacteria (severe congenital neutropenia or infantile genetic agranulocytosis, Chediak-Higiashi syndrome, Down syndrome and Papillon-Lefévre syndrome). In the presence of humoral immune alterations, periodontal damage may result indirectly as a consequence of alterations in other systems. In connective tissue disorders, bacterial plaque and alterations of the periodontal tissues increase patient susceptibility to gingival inflammation and alveolar resorption (Marfan syndrome and Ehler-Danlos syndrome). The management of periodontal disease focuses on the control of infection and bacterial plaque by means of mechanical and chemical methods. Periodontal surgery and even extraction of the most seriously affected teeth have also been suggested. There are variable degrees of consensus regarding the background systemic disorder, as in the case of Chediak-Higiashi syndrome, where antibiotic treatment proves ineffective; in severe congenital neutropenia or infantile genetic agranulocytosis, where antibiotic prophylaxis is suggested; and in Papillon-Lefévre syndrome, where an established treatment protocol is available.

Biological and molecular characterization of a multicapsid nucleopolyhedrovirus from Thysanoplusia orichalcea (L.) (Lepidoptera: Noctuidae).

PubMed

Cheng, Xiao-Wen; Carner, Gerald R; Lange, Martin; Jehle, Johannes A; Arif, Basil M

2005-02-01

A multicapsid nucleopolyhedrovirus (ThorMNPV) that was co-isolated with a single nucleocapid ThorSNPV from mixed infected larvae of Thysanoplusia orichalcea L. (Lepidoptea: Noctuidae) is characterized. Scanning electron microscopy of ThorMNPV showed a dodecahedral-shaped occlusion body (OB). The occluded virions contained one to as many as eight nucleocapsids/virion. Virion band profiles in gradient centrifugation were consistent in at least 10 rounds of centrifugation from different virion sample preparations. The ThorMNPV had high virulence to third instar Trichoplusia ni and Pseudoplusia includens with LD50 values of 17 and 242OBs per larva, respectively. However, ThorMNPV did not cause mortality in Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridania, Anticarsia gemmatalis, and Helicoverpa zea. ThorMNPV replicates in cells of various tissues such as the fat body and tracheal epithelium cells. T. ni High 5 cells were permissive to ThorMNPV in terms of infection and viral DNA transfection, but SF-21 was less permissive and the infection process was slower. Production of OBs by ThorMNPV in the nuclei of SF-21 was not well pronounced. The genome size of ThorMNPV was estimated to be 136 kb. The polyhedrin gene open reading frame (ORF) was cloned and completely sequenced. The promoter sequence is identical to that of Autographa californica MNPV. Phylogenetic analyses using partial sequences of the polh, lef-8, and lef-9 revealed that ThorMNPV is a member of the Group I NPVs and is related but distinct from the AcMNPV/Rachiplusia ou NPV/Bombyx mori NPV cluster.

Prospective evaluation of pain, swelling, and disability from copperhead envenomation.

PubMed

Roth, Brett; Sharma, Kapil; Onisko, Nancy; Chen, Tiffany

2016-03-01

In light of the existing controversy regarding antivenin treatment for copperhead envenomation, a more detailed analysis of the disability from this species is needed. Our objective was to prospectively determine the duration of pain, swelling, and functional disability, i.e., residual venom effects, in patients with copperhead envenomation. Patients with venomous snakebite reported to the North Texas Poison Center between April 2009 and November 2011 were assessed. Patients with confirmed envenomations were contacted by a specialist in poison information. Day zero was the day of the bite and verbal phone consent for study enrollment was obtained at that time. The patient (or their guardian) was contacted by phone daily thereafter, and asked to rate their pain, edema/swelling, and disability using the modified DASH and LEFS scales. Patients were followed to resolution of all symptoms or return to baseline. About 104 cases of venomous snakebite were followed; of which 17 were excluded due to being a dry bites (5) or for having insufficient data during follow-up (11) or due to coagulopathy (1). Overall, residual venom effects from copperhead bites for most patients last between 7 and 13 days. Median time to complete pain resolution was 7 days (mean = 10.7 days). Median length of time to resolution of swelling was 10 days (mean = 13 days) and median length of time to resolution of functional disability was 9 days (mean = 12.2 days). Residual venom effects from copperhead envenomation in this study had a slightly shorter duration than some other studies. Data are skewed due to outliers where residual venom effects lasted for up to 89 days. Initial reoccurrence of some symptoms may be seen. Antivenom (AV) is currently being used for a large percentage of patients with copperhead envenomation. Finally, no differences in duration of venom effects were seen based on age or location of bite. Our study suggests that residual venom effects from copperhead species persist for between 10 and 13 days but may persist for months. Future studies are necessary to identify risk factors for severe/prolonged injury and to define the benefit of AV in patients with copperhead envenomation.

Wnt/Myc interactions in intestinal cancer: partners in crime.

PubMed

Myant, Kevin; Sansom, Owen J

2011-11-15

Loss of the APC (adenomatous polyposis coli) gene in colorectal cancer leads to a rapid deregulation of TCF/LEF target genes. Of all these target genes, the transcription factor c-MYC appears the most critical. In this review we will discuss the interplay of Wnt and c-MYC signaling during intestinal homeostasis and transformation. Furthermore, we will discuss recent data showing that further deregulation of c-MYC levels during colorectal carcinogenesis may drive tumor progression. Moreover, understanding these additional control mechanisms may allow targeting of c-MYC during colorectal carcinogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

Physiological factors that regulate skin pigmentation

PubMed Central

Yamaguchi, Yuji; Hearing, Vincent J.

2009-01-01

More than 150 genes have been identified that affect skin color either directly or indirectly, and we review current understanding of physiological factors that regulate skin pigmentation. We focus on melanosome biogenesis, transport and transfer, melanogenic regulators in melanocytes and factors derived from keratinocytes, fibroblasts, endothelial cells, hormones, inflammatory cells and nerves. Enzymatic components of melanosomes include tyrosinase, tyrosinase-related protein 1 and dopachrome tautomerase, which depend on the functions of OA1, P, MATP, ATP7A and BLOC-1 to synthesize eumelanins and pheomelanins. The main structural component of melanosomes is Pmel17/gp100/Silv, whose sorting involves adaptor protein 1A (AP1A), AP1B, AP2 and spectrin, as well as a chaperone-like component, MART-1. During their maturation, melanosomes move from the perinuclear area toward the plasma membrane. Microtubules, dynein, kinesin, actin filaments, Rab27a, melanophilin, myosin Va and Slp2-a are involved in melanosome transport. Foxn1 and p53 up-regulate skin pigmentation via bFGF and POMC derivatives including α-MSH and ACTH, respectively. Other critical factors that affect skin pigmentation include MC1R, CREB, ASP, MITF, PAX3, SOX9/10, LEF-1/TCF, PAR-2, DKK1, SCF, HGF, GM-CSF, endothelin-1, prostaglandins, leukotrienes, thromboxanes, neurotrophins and neuropeptides. UV radiation up-regulates most factors that increase melanogenesis. Further studies will elucidate the currently unknown functions of many other pigment genes/proteins. PMID:19449448

Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skin.

PubMed

Qiao, W; Li, A G; Owens, P; Xu, X; Wang, X-J; Deng, C-X

2006-01-12

Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFbeta and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFbeta/BMP pathway, which interacts with the Pten signaling pathway.

microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest

PubMed Central

Zhao, Zhenze; Ma, Xiuye; Sung, Derek; Li, Monica; Kosti, Adam; Lin, Gregory; Chen, Yidong; Pertsemlidis, Alexander; Hsiao, Tzu-Hung; Du, Liqin

2015-01-01

microRNA-449a (miR-449a) has been identified to function as a tumor suppressor in several types of cancers. However, the role of miR-449a in neuroblastoma has not been intensively investigated. We recently found that the overexpression of miR-449a significantly induces neuroblastoma cell differentiation, suggesting its potential tumor suppressor function in neuroblastoma. In this study, we further investigated the mechanisms underlying the tumor suppressive function of miR-449a in neuroblastoma. We observed that miR-449a inhibits neuroblastoma cell survival and growth through 2 mechanisms—inducing cell differentiation and cell cycle arrest. Our comprehensive investigations on the dissection of the target genes of miR-449a revealed that 3 novel targets- MFAP4, PKP4 and TSEN15 -play important roles in mediating its differentiation-inducing function. In addition, we further found that its function in inducing cell cycle arrest involves down-regulating its direct targets CDK6 and LEF1. To determine the clinical significance of the miR-449a-mediated tumor suppressive mechanism, we examined the correlation between the expression of these 5 target genes in neuroblastoma tumor specimens and the survival of neuroblastoma patients. Remarkably, we noted that high tumor expression levels of all the 3 miR-449a target genes involved in regulating cell differentiation, but not the target genes involved in regulating cell cycle, are significantly correlated with poor survival of neuroblastoma patients. These results suggest the critical role of the differentiation-inducing function of miR-449a in determining neuroblastoma progression. Overall, our study provides the first comprehensive characterization of the tumor-suppressive function of miR-449a in neuroblastoma, and reveals the potential clinical significance of the miR-449a-mediated tumor suppressive pathway in neuroblastoma prognosis. PMID:25760387

The inductive effect of ginsenoside F2 on hair growth by altering the WNT signal pathway in telogen mouse skin.

PubMed

Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Song, Hyun-Geun; Mavlonov, Gafurjon T; Yi, Tae-Hoo

2014-05-05

This study was conducted to confirm the possibility of using minor ginseng saponin F2 by oral administration on hair anagen induction effects. The signaling pathway and anagen induction effect of ginsenoside F2 were investigated and compared with finasteride on the effect of hair growth induction. The cell-based MTT assay results indicated that the proliferation rates of HHDPC and HaCaT treated with F2 significantly increased by 30% compared with the finasteride-treated group. A western blot study showed that the expression of β-catenin Lef-1 and DKK-1 increased by 140, 200% and decreased by 40% in the F2-treated group, respectively compared to that of finasteride-treated group. C57BL/6 mice were subjected to the same treatments. The hair growth promotion rates were compared with groups treated with finasteride, which was 20% higher in the F2-treated group. Tissue histological analysis results showed the number of hair follicles, thickness of the epidermis, and follicles of the anagen phase which increased in the F2-treated group, compared with the finasteride-treated groups. Moreover, the effect of F2 on hair growth was confirmed through the immunofluorescence (IF) methods indicating the expression aspect of Wnt signal pathway-related factors in the tissue of C57BL/6 mouse. Our results considered the expression increase in β-catenin, Lef-1 which was suggested as a major factor related to the development and growth of hair follicle and the decrease in DKK-1 when entering catagen by F2. As the data showed, F2 might be a potential new therapeutic source for anagen induction and hair growth through the Wnt signal pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

Corrigendum to "Acute and repeated exposure to social stress reduces gut microbiota diversity in Syrian hamsters" [Behav. Brain Res. 345 (2018) 39-48].

PubMed

Partrick, Katherine A; Chassaing, Benoit; Beach, Linda Q; McCann, Katharine E; Gewirtz, Andrew T; Huhman, Kim L

2018-08-01

Social stress can promote a variety of neuropsychiatric illnesses, many of which have a high co-morbidity with gastrointestinal disorders. Recent data indicate that gastrointestinal microbiota can affect their host's brain and behavior. Syrian hamsters are ideal subjects for social stress research because they are territorial, aggressive, and rapidly form dominant/subordinate relationships. The purpose of this study was to determine if exposure to social stress in hamsters alters gut microbiota in dominants and subordinates after an agonistic encounter and if pre-stress gut microbiota composition is correlated with the outcome of such a conflict. Microbiota composition was assessed via 16S mRNA Illumina sequencing on fecal samples. One agonistic encounter caused a decrease in alpha diversity in both dominant and subordinate animals with a more pronounced decrease after repeated encounters. PERMANOVA analysis of the unweighted unifrac distance revealed a distinct change in beta diversity after one and nine encounters in both dominants and subordinates. Linear discriminant analysis (LEfSE) showed bacteria from the order Lactobacillales were significantly reduced following social stress in both dominants and subordinates, and both groups exhibited increases in phyla Bacteroidetes and decreases in phyla Firmicutes following repeated encounters. LEfSE analysis on samples collected prior to social interaction revealed that some microbial taxa were correlated with a hamster achieving dominant or subordinate status. These data suggest that even an acute exposure to social stress can impact gastrointestinal microbiota and that the state of the microbial community before social stress may predict dominant/subordinate status following a subsequent agonistic encounter. Copyright © 2018.

Lacanobia oleracea nucleopolyhedrovirus (LaolNPV): A new European species of alphabaculovirus with a narrow host range

PubMed Central

Erlandson, Martin A.; Frayssinet, Marie; Williams, Trevor; Theilmann, David A.; Volkoff, Anne-Nathalie; Caballero, Primitivo

2017-01-01

During an insect sampling program in alfalfa crops near Montpellier, France in 2011, Lacanobia oleracea larvae were collected that died due to nucleopolyhedrovirus infection (LaolNPV). This virus was subjected to molecular and biological characterization. The virus was a multiple nucleocapsid NPV that showed similar restriction profiles to Mamestra configurata NPV-A (MacoNPV-A) but with significant differences. Polypeptide analysis demonstrated similar proteins in occlusion bodies and occlusion derived virions, to those observed in NPVs from Mamestra spp. Terminal sequencing revealed that the genome organization shared similarity with that of MacoNPV-A. The most homologous virus was MacoNPV-A 90/2 isolate (95.63% identity and 96.47% similarity), followed by MacoNPV-A 90/4 strain (95.37% and 96.26%), MacoNPV-B (89.21% and 93.53%) and M. brassicae MNPV (89.42% and 93.74%). Phylogenetic analysis performed with lef-8, lef-9, polh and a concatenated set of genes showed that LaolNPV and the Mamestra spp. NPVs clustered together with HaMNPV, but with a closer genetic distance to MacoNPV-A strains. The Kimura 2-parameter (K-2-P) distances of the complete genes were greater than 0.05 between LaolNPV and the MbMNPV/MacoNPV-B/HaMNPV complex, which indicates that LaolNPV is a distinct species. K-2-P distances were in the range 0.015–0.050 for comparisons of LaolNPV with MacoNPV-A strains, such that additional biological characteristics should be evaluated to determine species status. While MacoNPV-A was pathogenic to seven lepidopteran species tested, LaolNPV was only pathogenic to Chrysodeixis chalcites. Given these findings, Lacanobia oleracea nucleopolyhedrovirus should be considered as a new species in the Alphabaculovirus genus. PMID:28426736

Gut Microbial Community Structure and Complications Following Kidney Transplantation: A Pilot Study

PubMed Central

Lee, John R.; Muthukumar, Thangamani; Dadhania, Darshana; Toussaint, Nora C.; Ling, Lilan; Pamer, Eric; Suthanthiran, Manikkam

2014-01-01

Background The gut microbiome plays a role in the regulation of the immune system. Methods We prospectively enrolled 26 kidney transplant recipients and collected serial fecal specimens (N=85) during the first three months of transplantation. We characterized bacterial composition by PCR amplification of the 16S rRNA V4-V5 variable region and deep sequencing using the Illumina® MiSeq platform. Results An increase in the relative abundance of Proteobacteria was observed in the post-transplantation specimens compared to pre-transplantation specimens (P=0.04, Wilcoxon signed-rank test). In patients with post-transplant diarrhea, the mean(±SD) Shannon diversity index was lower in those with diarrhea (N=6) than those without diarrhea (N=9) (2.5±0.3 vs. 3.4±0.8, P=0.02, Wilcoxon rank-sum test). Principal coordinate analysis (PCoA) showed clear separation between the two groups, and linear discriminant analysis effect size (LEfSe) method revealed that Bacteroides, Ruminococcus, Coprococcus, and Dorea were significantly lower in the patients with diarrhea. PCoA analysis also showed clear separation between the acute rejection (AR) group (N=3) and the no AR group (N=23) and LEfSe method revealed several significant differences between the two groups. Fecal abundance of Enterococcus was associated with Enterococcus urinary tract infection (UTI). The median Enterococcus fecal abundance was 24% (Range: 8% to 95%) in the 3 patients with Enterococcus UTI compared to 0% in the 23 patients without Enterococcus UTI (Interquartile range: 0.00% to 0.08%)(P=0.005, Wilcoxon rank-sum test). Conclusions Our pilot study identified significant alterations in the gut microbiota following kidney transplantation. Moreover, distinct microbiota structures were observed in allograft recipients with post-transplant diarrhea, AR, and Enterococcus UTI. PMID:25289916

Analysis of differentially co-expressed genes based on microarray data of hepatocellular carcinoma.

PubMed

Wang, Y; Jiang, T; Li, Z; Lu, L; Zhang, R; Zhang, D; Wang, X; Tan, J

2017-01-01

Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide. Although great progress in diagnosis and management of HCC have been made, the exact molecular mechanisms remain poorly understood. The study aims to identify potential biomarkers for HCC progression, mainly at transcription level. In this study, chip data GSE 29721 was utilized, which contains 10 HCC samples and 10 normal adjacent tissue samples. Differentially expressed genes (DEGs) between two sample types were selected by t-test method. Following, the differentially co-expressed genes (DCGs) and differentially co-expressed Links (DCLs) were identified by DCGL package in R with the threshold of q < 0.25. Afterwards, pathway enrichment analysis of the DCGs was carried out by DAVID. Then, DCLs were mapped to TRANSFAC database to reveal associations between relevant transcriptional factors (TFs) and their target genes. Quantitative real-time RT-PCR was performed for TFs or genes of interest. As a result, a total of 388 DCGs and 35,771 DCLs were obtained. The predominant pathways enriched by these genes were Cytokine-cytokine receptor interaction, ECM-receptor interaction and TGF-β signaling pathway. Three TF-target interactions, LEF1-NCAM1, EGR1-FN1 and FOS-MT2A were predicted. Compared with control, expressions of the TF genes EGR1, FOS and ETS2 were all up-regulated in the HCC cell line, HepG2; while LEF1 was down-regulated. Except NCAM1, all the target genes were up-regulated in HepG2. Our findings suggest these TFs and genes might play important roles in the pathogenesis of HCC and may be used as therapeutic targets for HCC management.

Effect of cumulative exposure to corticosteroid and DMARD on radiographic progression in rheumatoid arthritis: results from the ESPOIR cohort.

PubMed

Louveau, Baptiste; De Rycke, Yann; Lafourcade, Alexandre; Saraux, Alain; Guillemin, Francis; Tubach, Florence; Fautrel, Bruno; Hajage, David

2018-05-22

Several authors have tried to predict the risk of radiographic progression in RA according to baseline characteristics, considering exposure to treatment only as a binary variable (Treated: Yes/No). This study aims to model the risk of 5-year radiographic progression taking into account both baseline characteristics and the cumulative time-varying exposure to corticosteroids or DMARDs. The study population consisted of 403 patients of the Etude et Suivi des Polyarthrites Indifférenciées Récentes cohort meeting the 1987 ACR or 2010 ACR/EULAR criteria for RA at inclusion and having complete radiographic data at baseline and 5 years. Radiographic progression was defined at 5 years as a significant increase of the Sharp/van der Heidje score (smallest detectable difference ⩾5). The best logistic regression model was selected from the following: model including only clinico-biological baseline characteristics; model considering baseline characteristics and treatments as binary variables; and model considering baseline characteristics and treatments as weighted cumulative exposure variables. Radiographic progression occurred in 143 (35.5%) patients. The best model combined anti-citrullinated peptide antibody positivity, ESR, swollen joint count >14 and erosion score at baseline, as well as corticosteroids, MTX/LEF (MTX or LEF) and biologic DMARDs (bDMARDs) as weighted cumulative exposure variables. Recent cumulative exposure to high doses of corticosteroids (⩽ 3months) was significantly associated with the risk of 5-year radiographic progression and a significant protective association was highlighted for a 36-month exposure to bDMARDs. Corticosteroids and bDMARDs play an important role in radiographic progression. Accounting for treatment class and intensity of exposure is a major concern in predictive models of radiographic progression in RA patients.

Putative signaling action of amelogenin utilizes the Wnt/beta-catenin pathway.

PubMed

Matsuzawa, M; Sheu, T-J; Lee, Y-J; Chen, M; Li, T-F; Huang, C T; Holz, J D; Puzas, J E

2009-06-01

While it has long been known that amelogenin is essential for the proper development of enamel, its role has generally been seen as structural in nature. However, our new data implicate this protein in the regulation of cell signaling pathways in periodontal ligament cells and osteoblasts. In this article we report the successful purification of a recombinant mouse amelogenin protein and demonstrate that it has signaling activity in isolated mouse calvarial cells and human periodontal ligament cells. To determine the regulatory function of canonical Wnt signaling by amelogenin, we used TOPGAL transgenic mice. These mice express a beta-galactosidase transgene under the control of a LEF/TCF and beta-catenin-inducible promoter. To investigate in greater detail the molecular mechanisms involved in the beta-catenin signaling pathway, isolated osteoblasts and periodontal ligament cells were exposed to full-length recombinant mouse amelogenin and were evaluated for phenotypic changes and beta-catenin signaling using a TOPFLASH construct and the LacZ reporter gene. In these in vitro models, we showed that amelogenin can activate beta-catenin signaling. Using the TOPGAL transgenic mouse we showed that amelogenin expression in vivo is localized mainly around the root, the periodontal ligament and the alveolar bone.

Cross-Cultural Adaptation and Measurement Properties of the Brazilian Portuguese Version of the Victorian Institute of Sport Assessment-Achilles (VISA-A) Questionnaire.

PubMed

de Mesquita, Gabriel Nunes; de Oliveira, Marcela Nicácio Medeiros; Matoso, Amanda Ellen Rodrigues; Filho, Alberto Galvão de Moura; de Oliveira, Rodrigo Ribeiro

2018-04-24

Study Design Clinical measurement study. Background Achilles tendon disorders are very common among athletes and it is important to objectively measure symptoms and functional limitations related to Achilles tendinopathy using outcome measures that have been validated in the language of the target population. Objectives To perform a cross-cultural adaptation and to evaluate the measurement properties of the Brazilian version of the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire. Methods We adapted the VISA-A questionnaire to Brazilian Portuguese (VISA-A-Br). The questionnaire was applied on 2 occasions with an interval of 5 to 14 days. We evaluated the following measurement properties: internal consistency, test-retest reliability, measurement error, construct validity, and ceiling and floor effects. Results The VISA-A-Br showed good internal consistency (Cronbach's alpha = 0.79; after excluding 1 item at a time, Cronbach's α = 0.73 to 0.84), good test-retest reliability (ICC agreement2,1 = 0.84, 95% confidence interval = 0.71-0.91), an acceptable measurement error (standard error of measurement = 3.25 points and Smallest Detectable Change= 9.02 points), good construct validity (Spearman's coefficient with LEFS= 0.73 and FAOS in its 5 subscales; Pain= 0.66, other Symptoms=0.48, Function in daily living (ADL)= 0.59, Function in sport and recreation=0.67, and foot and ankle-related Quality of Life = 0.7), and no ceiling and floor effects. Conclusion The VISA-A-Br is equivalent to the original version; it has been validated and confirmed as reliable to measure pain and function among the Brazilian population with Achilles tendinopathy, and it can be used in clinical and scientific settings. J Orthop Sports Phys Ther, Epub 24 Apr 2018. doi:10.2519/jospt.2018.7897.

Technology Insertion-Engineering Services Process Characterization Task Order No. 1. Book 2 of 3. Database Documentation Book. OO-ALC MANPGP (Wheels - WCD’S)

DTIC Science & Technology

1989-12-15

RElOVE MASKINE TAPE .00!91 .002 000 Al RCB-OH-W2 1.00 REMY WHL HLF F/PAINT CONVYOR .00833 .010 0040 E RWr- BBP -0 1.00 BALPOCE WEEL HALF .0773 .093 0050 5...16S601-819 16W6-35-3-2 15 ART SHE 160 PULTIPLE LA-10 L"L R/H AIM 9 1441--1-M -36A 7 472-M 1L--11. z.I-- PARK AN)E 161814, LEf-N sE. r& ffA t- 1450-00-. b

Sleep quality in children: questionnaires available in Brazil.

PubMed

Cavalheiro, Maria Gabriela; Corrêa, Camila de Castro; Maximino, Luciana Paula; Weber, Silke Anna Theresa

2017-01-01

The purpose of this paper was to evaluate and compare the questionnaires regarding sleep quality among children aged up to 12 years old, used in the Portuguese language in Brazil. A search at the literature databases of Lilacs, Scielo and Pubmed was performed using keywords "sleep quality" and "children". Selected Articles were analysed for age of the studied population, the number of questions and the issues addressed thereby, who realized the application, the analysis of the results, and content. Out of 9377 titles, 11 studies were included, performing 7 different questionnaires: Questionnaire to measure quality of life among children with enlarged palatine and pharyngeal tonsils (translation of OSD-6) (1); Inventory of Sleep Habits for Preschool Children (2); the Questionnaire on Obstructive Sleep Apnoea-18 (OSA-18) (3), Sleep Questionnaire by Reimão and Lefévre - QRL (4); the Questionnaire on Sleep Behaviour Patterns (5) and the translation of the Sleep Disturbance Scale for Children (6); Brief Infant Sleep Questionnaire - BISQ (7) . Six of the questionnaires have covered the following issues: snoring and daytime sleepiness. A total of 7 protocols were found to be available in Brazil, the most commonly mentioned being OSA-18 and OSD-6. The use of protocols as a guided interview helps to define diagnosis and treatment among the paediatric population, but its large variability makes it difficult to compare a standardised monitoring process.

Physiological factors that regulate skin pigmentation.

PubMed

Yamaguchi, Yuji; Hearing, Vincent J

2009-01-01

More than 150 genes have been identified that affect skin color either directly or indirectly, and we review current understanding of physiological factors that regulate skin pigmentation. We focus on melanosome biogenesis, transport and transfer, melanogenic regulators in melanocytes, and factors derived from keratinocytes, fibroblasts, endothelial cells, hormones, inflammatory cells, and nerves. Enzymatic components of melanosomes include tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase, which depend on the functions of OA1, P, MATP, ATP7A, and BLOC-1 to synthesize eumelanins and pheomelanins. The main structural component of melanosomes is Pmel17/gp100/Silv, whose sorting involves adaptor protein 1A (AP1A), AP1B, AP2, and spectrin, as well as a chaperone-like component, MART-1. During their maturation, melanosomes move from the perinuclear area toward the plasma membrane. Microtubules, dynein, kinesin, actin filaments, Rab27a, melanophilin, myosin Va, and Slp2-a are involved in melanosome transport. Foxn1 and p53 up-regulate skin pigmentation via bFGF and POMC derivatives including alpha-MSH and ACTH, respectively. Other critical factors that affect skin pigmentation include MC1R, CREB, ASP, MITF, PAX3, SOX9/10, LEF-1/TCF, PAR-2, DKK1, SCF, HGF, GM-CSF, endothelin-1, prostaglandins, leukotrienes, thromboxanes, neurotrophins, and neuropeptides. UV radiation up-regulates most factors that increase melanogenesis. Further studies will elucidate the currently unknown functions of many other pigment genes/proteins. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.

Therapeutic utility and medicinal chemistry of cathepsin C inhibitors.

PubMed

Guay, Daniel; Beaulieu, Christian; Percival, M David

2010-01-01

The lysosomal cysteine protease cathepsin C (Cat C), also known as dipeptidyl peptidase I, activates a number of granule-associated serine proteases with pro-inflammatory and immune functions by removal of their inhibitory N-terminal dipeptides. Thus, Cat C is a therapeutic target for the treatment of a number of inflammatory and autoimmune diseases. Cathepsin C null mice and humans with Cat C loss of function mutations (Papillon-Lefèvre syndrome) show deficiencies in disease-relevant proteases including neutrophil elastase, cathepsin G, chymases and granzymes and the Cat C mice are protected in a number of disease models. Several methodologies have been recently reported for assessing the effects of Cat C inhibitors on serine protease activities in cellular assays and prolonged treatment of rats with a reversible, selective Cat C inhibitor reduced the activity of three leukocyte serine proteases. Nearly all potent and selective Cat C inhibitors described are based on the preferred dipeptide substrates bearing either irreversible (e.g. diazomethylketone, acyloxymethyl ketone, o-acyl hydroxamic acid and vinyl sulfone) or reversible (e.g. semicarbazide, nitrile and cyanamide) electrophilic warheads. While potent and highly selective, the best inhibitors described to date still have poor stability and/or rodent pharmacokinetics, likely resulting from their peptidic nature. The lack of selective compounds with appropriate rodent pharmacokinetic properties has hampered the assessment of the effects of Cat C inhibitors on the activation of disease-relevant proteases in vivo and the full evaluation of the therapeutic utility of Cat C inhibitors.

Negative Declaration of Environmental Effects of Leith Creek Scotland County, North Carolina, Flood Control Project.

DTIC Science & Technology

1977-01-01

area is limited to that 1.97 mile portion of Leith Creek between Gill Street and the L & S Railroad just above State Road . 1645 ( Fertilizer Plant...yj0 U.L e QC e kt V C S L-Co L. U’L -Lb’L r C, CL :, IUI -j.’ y( auo intcet -Ui p o v Id ia q ’:F cc~ Lc s ;It uet ’c C 4 a ’iC 0 dis"tLssed the Le~f...34 - Sites and Methods of more fill due to the access required than the Disposal proposed action. Pumping of the excavated mate- rial is possible

Geochemical normalization of magnetic susceptibility - a simple tool for distinction the sediment provenance and post-depositional processes in floodplain sediments

NASA Astrophysics Data System (ADS)

Famera, Martin; Matys Grygar, Tomas; Elznicova, Jitka

2017-04-01

Magnetic susceptibility is highly appreciated in sedimentary and environmental geology. It may also reflect provenance of the sediment and post-depositional changes therein, including soil-forming processes. We studied the applicability of Fe-normalization of mass-specific magnetic susceptibility (MS) and Ti-normalization of Fe concentrations in description of fluvial sediments from five different catchments. We dealt with two catchments with some "mafic" source rocks (Fe-rich rocks) and three almost purely "felsic" catchments (source rocks with dominant quartz and feldspars). The fine-grained floodplain sediments (from clayey silts to fine sands) were obtained by drill coring and analysed for Fe and Ti concentrations using X-ray fluorescence spectroscopy (EDXRF) and MS using kappabridge. To correct MS for the sedimentological grain-size effects and possible magnetic enrichment, we used background functions constructed in the same way like for heavy metals. The representative profiles downward the floodplain sediments demonstrate the following MS stratigraphy: (1) 15-50 cm thick top stratum A, usually with MS and heavy metal enrichment, (2) underlying stratum B with stable values of MS, MS/Fe and Fe/Ti and (3) the lowermost stratum C with variable Fe concentrations and MS and high-chroma reductimorphic features due to micro-accumulations of Fe and Mn oxides in discoloured matrix, or grey colour due to permanently removed Fe(III) oxide pigment. The boundary between strata B and C can be at a depth of several decimetres to more than 1 metre depending on the thickness of floodplain fines, site-specific river incision and water table fluctuation. For the construction of MS background functions we used Fe concentrations as an independent variable (a predictor). It allows for calculation of MS of sediments as it would not be affected by post-depositional changes and pollution. Pristine MS is than predicted for any sample using formula MS_PRISTINE = const·cFe + const', where cFe is concentration of Fe. Background functions must be obtained empirically from collection of samples of stratum B that needs qualified sampling strategy and informed data evaluation. Local enrichment factor of MS is then defined as LEF MS = MS/MS_PRISTINE. LEF MS is useful for study of MS depth profiles in both strata A and C. Floodplain sediments in river systems with catchment with "mafic" rock outcrops have MSPRISTINE by up to two orders of magnitude larger in comparison to systems with "felsic" source rocks. The carriers of magnetic signal in the "mafic" rock-derived sediments are affected by soil-forming processes, which gradually decrease their original MS, in particular in strata B and C. Post-depositional processes including pedogenesis, in particular reductimorphic processes, may thus alter MS/Fe. The reductimorphic processes in floodplain sediments may be revealed by "erratic" variations or a permanent increase of the Fe/Ti ratio. The advantage of using geochemical normalization of MS is that chemical analyses are currently nearly routinely performed in geochemical and pollution mapping studies and thus Fe concentrations are thus available for data processing. The combination of the mentioned handy proxies (MS and element composition) would definitely deserve broader use in environmental geology and monitoring.

Non-conventional Frizzled ligands and Wnt receptors.

PubMed

Hendrickx, Marijke; Leyns, Luc

2008-05-01

The Wnt family of secreted signaling factors plays numerous roles in embryonic development and in stem cell biology. In the adult, Wnt signaling is involved in tissue homeostasis and mutations that lead to the overexpression of Wnt can be linked to cancer. Wnt signaling is transduced intracellularly by the Frizzled (Fzd) family of receptors. In the canonical pathway, accumulation of beta-catenin and the subsequent formation of a complex with T cell factors (TCF) or lymphoid enhancing factors (Lef) lead to target gene activation. The identification of Ryk as an alternative Wnt receptor and the discovery of the novel Fzd ligands Norrie disease protein (NDP) and R-Spondin, changed the traditional view of Wnts binding to Fzd receptors. Mouse R-Spondin cooperates with Wnt signaling and Low density lipoprotein (LDL) receptor related protein (LRP) to activate beta-catenin dependent gene expression and is involved in processes such as limb and placental development in the mouse. NDP is the product of the Norrie disease gene and controls vascular development in the retina, inner ear and in the female reproductive system during pregnancy. In this review a functional overview of the interactions of the different Wnt and non-Wnt ligands with the Fzd receptors is given as well as a survey of Wnts binding to Ryk and we discuss the biological significance of these interactions.

The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism.

PubMed

Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

2011-10-01

Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA.

The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism

PubMed Central

Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

2011-01-01

Background: Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Methods: Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. Results: The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. Conclusion: We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA. PMID:23556096

TCF7L2 mediates the cellular and behavioral response to chronic lithium treatment in animal models.

PubMed

Misztal, Katarzyna; Brozko, Nikola; Nagalski, Andrzej; Szewczyk, Lukasz M; Krolak, Marta; Brzozowska, Katarzyna; Kuznicki, Jacek; Wisniewska, Marta B

2017-02-01

The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear is whether therapeutic levels of lithium activate β-catenin in the brain, and whether this activation could have a therapeutic significance. To address this issue we chronically treated mice with lithium. Although the level of non-phospho-β-catenin increased in all of the brain areas examined, β-catenin translocated into cellular nuclei only in the thalamus. Similar results were obtained when thalamic and cortical neurons were treated with a therapeutically relevant concentration of lithium in vitro. We tested if TCF7L2, a member of LEF1/TCF family that is highly expressed in the thalamus, facilitated the activation of β-catenin. Silencing of Tcf7l2 in thalamic neurons prevented β-catenin from entering the nucleus, even when the cells were treated with lithium. Conversely, when Tcf7l2 was ectopically expressed in cortical neurons, β-catenin shifted to the nucleus, and lithium augmented this process. Lastly, we silenced tcf7l2 in zebrafish and exposed them to lithium for 3 days, to evaluate whether TCF7L2 is involved in the behavioral response. Lithium decreased the dark-induced activity of control zebrafish, whereas the activity of zebrafish with tcf7l2 knockdown was unaltered. We conclude that therapeutic levels of lithium activate β-catenin selectively in thalamic neurons. This effect is determined by the presence of TCF7L2, and potentially contributes to the therapeutic response. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation.

PubMed

Ji, Hua; Xu, Linhao; Wang, Zheng; Fan, Xinli; Wu, Lihui

2018-03-01

Glyphosate is the active ingredient in numerous herbicide formulations. The role of glyphosate in neurotoxicity has been reported in human and animal models. However, the detailed mechanism of the role of glyphosate in neuronal development remains unknown. Recently, several studies have reported evidence linking neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. The current group previously identified microRNAs (miRNAs) that are associated with the etiology of NDDs, but their expression levels in the developing brain following glyphosate exposure have not been characterized. In the present study, miRNA expression patterns were evaluated in the prefrontal cortex (PFC) of 28 postnatal day mouse offspring following glyphosate exposure during pregnancy and lactation. An miRNA microarray detected 55 upregulated and 19 downregulated miRNAs in the PFC of mouse offspring, and 20 selected deregulated miRNAs were further evaluated by quantitative polymerase chain reaction (PCR). A total of 11 targets of these selected deregulated miRNAs were analyzed using bioinformatics. Gene Ontology (GO) terms associated with the relevant miRNAs included neurogenesis (GO:0050769), neuron differentiation (GO:0030182) and brain development (GO:0007420). The genes Cdkn1a, Numbl, Notch1, Fosl1 and Lef1 are involved in the Wnt and Notch signaling pathways, which are closely associated with neural development. PCR arrays for the mouse Wnt and Notch signaling pathways were used to validate the effects of glyphosate on the expression pattern of genes involved in the Wnt and Notch pathways. Nr4a2 and Wnt7b were downregulated, while Dkk1, Dixdc1, Runx1, Shh, Lef-1 and Axin2 were upregulated in the PFC of mice offspring following glyphosate exposure during pregnancy and lactation. These results indicated abnormalities of the Wnt/β-catenin and Notch pathways. These findings may be of particular interest for understanding the mechanism of glyphosate-induced neurotoxicity, as well as helping to clarify the association between glyphosate and NDDs.

Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts.

PubMed

Kretschmer, Inga; Freudenberger, Till; Twarock, Sören; Yamaguchi, Yu; Grandoch, Maria; Fischer, Jens W

2016-02-19

The aim of this study was to characterize the interaction of KYSE-410, an esophageal squamous cell carcinoma cell line, and fibroblasts with respect to the extracellular matrix component hyaluronan (HA) and chemokine expression. KYSE-410 cells induced the mRNA expression of HA synthase 2 (Has2) in normal skin fibroblasts (SF) only in direct co-cultures. Parallel to Has2 mRNA, Has2 antisense RNA (Has2os2) was up-regulated in co-cultures. Knockdown of LEF1, a downstream target of Wnt signaling, abrogated Has2 and Has2os2 induction. After knockdown of Has2 in SF, significantly less α-smooth muscle actin expression was detected in co-cultures. Moreover, it was investigated whether the phenotype of KYSE-410 was affected in co-culture with SF and whether Has2 knockdown in SF had an impact on KYSE-410 cells in co-culture. However, no effects on epithelial-mesenchymal transition markers, proliferation, and migration were detected. In addition to Has2 mRNA, the chemokine CCL5 was up-regulated and CCL11 was down-regulated in SF in co-culture. Furthermore, co-cultures of KYSE-410 cells and cancer-associated fibroblasts (CAF) were investigated. Similar to SF, Has2 and Ccl5 were up-regulated and Ccl11 was down-regulated in CAF in co-culture. Importantly and in contrast to SF, inhibiting HA synthesis by 4-methylumbelliferone abrogated the effect of co-culture on Ccl5 in CAF. Moreover, HA was found to promote adhesion of CD4(+) but not CD8(+) cells to xenogaft tumor tissues. In conclusion, direct co-culture of esophageal squamous cell carcinoma and fibroblasts induced stromal HA synthesis via Wnt/LEF1 and altered the chemokine profile of stromal fibroblasts, which in turn may affect the tumor immune response. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts*

PubMed Central

Kretschmer, Inga; Freudenberger, Till; Twarock, Sören; Yamaguchi, Yu; Grandoch, Maria; Fischer, Jens W.

2016-01-01

The aim of this study was to characterize the interaction of KYSE-410, an esophageal squamous cell carcinoma cell line, and fibroblasts with respect to the extracellular matrix component hyaluronan (HA) and chemokine expression. KYSE-410 cells induced the mRNA expression of HA synthase 2 (Has2) in normal skin fibroblasts (SF) only in direct co-cultures. Parallel to Has2 mRNA, Has2 antisense RNA (Has2os2) was up-regulated in co-cultures. Knockdown of LEF1, a downstream target of Wnt signaling, abrogated Has2 and Has2os2 induction. After knockdown of Has2 in SF, significantly less α-smooth muscle actin expression was detected in co-cultures. Moreover, it was investigated whether the phenotype of KYSE-410 was affected in co-culture with SF and whether Has2 knockdown in SF had an impact on KYSE-410 cells in co-culture. However, no effects on epithelial-mesenchymal transition markers, proliferation, and migration were detected. In addition to Has2 mRNA, the chemokine CCL5 was up-regulated and CCL11 was down-regulated in SF in co-culture. Furthermore, co-cultures of KYSE-410 cells and cancer-associated fibroblasts (CAF) were investigated. Similar to SF, Has2 and Ccl5 were up-regulated and Ccl11 was down-regulated in CAF in co-culture. Importantly and in contrast to SF, inhibiting HA synthesis by 4-methylumbelliferone abrogated the effect of co-culture on Ccl5 in CAF. Moreover, HA was found to promote adhesion of CD4+ but not CD8+ cells to xenogaft tumor tissues. In conclusion, direct co-culture of esophageal squamous cell carcinoma and fibroblasts induced stromal HA synthesis via Wnt/LEF1 and altered the chemokine profile of stromal fibroblasts, which in turn may affect the tumor immune response. PMID:26699196

Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation

PubMed Central

Ji, Hua; Xu, Linhao; Wang, Zheng; Fan, Xinli; Wu, Lihui

2018-01-01

Glyphosate is the active ingredient in numerous herbicide formulations. The role of glyphosate in neurotoxicity has been reported in human and animal models. However, the detailed mechanism of the role of glyphosate in neuronal development remains unknown. Recently, several studies have reported evidence linking neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. The current group previously identified microRNAs (miRNAs) that are associated with the etiology of NDDs, but their expression levels in the developing brain following glyphosate exposure have not been characterized. In the present study, miRNA expression patterns were evaluated in the prefrontal cortex (PFC) of 28 postnatal day mouse offspring following glyphosate exposure during pregnancy and lactation. An miRNA microarray detected 55 upregulated and 19 downregulated miRNAs in the PFC of mouse offspring, and 20 selected deregulated miRNAs were further evaluated by quantitative polymerase chain reaction (PCR). A total of 11 targets of these selected deregulated miRNAs were analyzed using bioinformatics. Gene Ontology (GO) terms associated with the relevant miRNAs included neurogenesis (GO:0050769), neuron differentiation (GO:0030182) and brain development (GO:0007420). The genes Cdkn1a, Numbl, Notch1, Fosl1 and Lef1 are involved in the Wnt and Notch signaling pathways, which are closely associated with neural development. PCR arrays for the mouse Wnt and Notch signaling pathways were used to validate the effects of glyphosate on the expression pattern of genes involved in the Wnt and Notch pathways. Nr4a2 and Wnt7b were downregulated, while Dkk1, Dixdc1, Runx1, Shh, Lef-1 and Axin2 were upregulated in the PFC of mice offspring following glyphosate exposure during pregnancy and lactation. These results indicated abnormalities of the Wnt/β-catenin and Notch pathways. These findings may be of particular interest for understanding the mechanism of glyphosate-induced neurotoxicity, as well as helping to clarify the association between glyphosate and NDDs. PMID:29467848

O2(a1Δg) dayglow limb observations on Mars by SPICAM IR on Mars-Express and connection to water vapor distribution

NASA Astrophysics Data System (ADS)

Guslyakova, S.; Fedorova, A. A.; Lefèvre, F.; Korablev, O. I.; Montmessin, F.; Bertaux, J.-L.

2014-09-01

The 1.27-μm O2(a1Δg) dayglow on Mars is a product of the ozone photolysis by solar UV radiation. The intensity of the O2(a1Δg) emission rate depends on ozone concentration, atmospheric density and kinetic parameters of involved photochemical reactions. In turn, the distribution of ozone is sensitive to the vertical and spatial distribution of water vapor, which is an effective destructor of O3. SPICAM IR on the Mars-Express mission measures the O2(1Δg) dayglow with spectral resolving power of 2200. The results of 147 limb observations from 2004 to 2013 are reported. Limb resolution of the instrument is variable and exceeds the scale height of the atmosphere. The slant emission rate reaches a maximum at the high Northern latitudes at northern and southern springs Ls = 0-50° and 160-190°, respectively and a minimum in middle and low latitudes at southern summer Ls = 200-300°. We have compared the SPIVAM O2(a1Δg) limb profiles with the General Circulation Model simulation by the Laboratoire de Meteorologie Dynamique (LMD GCM, Lefèvre, F., Lebonnois, S., Montmessin, F., Forget, F. [2004]. J. Geophys. Res. 109, E07004. http://dx.doi.org/10.1029/2004JE002268; Lefèvre, F., et al. [2008]. Nature 454(7207), 971-975) reduced to the vertical resolution of the instrument. The GCM includes the radiative effect of the water clouds and an interactive dust scheme, and well reproduces Martian Climate Sounder (MCS) temperature profiles (Clancy, R. Todd et al. [2012]. J. Geophys. Res. 117, 10. http://dx.doi.org/10.1029/2011JE004018). The model underestimates the emission for Ls = 0-50°, Ls = 160-180° and overestimates it from Ls = 60° to Ls = 150° at high Northern latitudes. In the Southern hemisphere the model underestimates the emission for Ls = 170-200° and overestimates it for Ls = 200-230° at high Southern latitudes. The disagreement could be related to the water vapor distribution as the model reproduces it. The most recent version of the LMD GCM including microphysical representation of cloud formation taking into account the effect of dust scavenging by water ice clouds (Navarro, T., Madeleine, J.-B., Montmessin, F., Forget, F., Spiga, A., Millour, E. [2013]. Modeling of the martian water cycle with an improved representation of water ice clouds. European Planetary Science Congress 2013, EPSC Abstracts, vol. 8, EPSC2013-203) gives much better agreement with SPICAM O2(a1Δg) dayglow limb observations. Characterization of the Mars water cycle by GCMs continues to improve, and the observations of the O2(a1Δg) dayglow offer a powerful tool for its validation.

Bacterial Diversity and Community Structure of Supragingival Plaques in Adults with Dental Health or Caries Revealed by 16S Pyrosequencing

PubMed Central

Xiao, Cuicui; Ran, Shujun; Huang, Zhengwei; Liang, Jingping

2016-01-01

Dental caries has a polymicrobial etiology within the complex oral microbial ecosystem. However, the overall diversity and structure of supragingival plaque microbiota in adult dental health and caries are not well understood. Here, 160 supragingival plaque samples from patients with dental health and different severities of dental caries were collected for bacterial genomic DNA extraction, pyrosequencing by amplification of the 16S rDNA V1–V3 hypervariable regions, and bioinformatic analysis. High-quality sequences (2,261,700) clustered into 10,365 operational taxonomic units (OTUs; 97% identity), representing 453 independent species belonging to 122 genera, 66 families, 34 orders, 21 classes, and 12 phyla. All groups shared 7522 OTUs, indicating the presence of a core plaque microbiome. α diversity analysis showed that the microbial diversity in healthy plaques exceeded that of dental caries, with the diversity decreasing gradually with the severity of caries. The dominant phyla of plaque microbiota included Bacteroidetes, Actinobacteria, Proteobacteria, Firmicutes, Fusobacteria, and TM7. The dominant genera included Capnocytophaga, Prevotella, Actinomyces, Corynebacterium, Neisseria, Streptococcus, Rothia, and Leptotrichia. β diversity analysis showed that the plaque microbial community structure was similar in all groups. Using LEfSe analysis, 25 differentially abundant taxa were identified as potential biomarkers. Key genera (27) that potentially contributed to the differential distributions of plaque microbiota between groups were identified by PLS-DA analysis. Finally, co-occurrence network analysis and function predictions were performed. Treatment strategies directed toward modulating microbial interactions and their functional output should be further developed. PMID:27499752

Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells

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

Fox, Simon A., E-mail: s.fox@curtin.edu.au; Richards, Alex K.; Kusumah, Ivonne

Highlights: •Expression profile of Wnt pathway related genes in mesothelioma cells. •Differential expression of key Wnt pathway molecules and regulators. •Wnt3a stimulated mesothelioma growth whereas sFRP4 was inhibitory. •Targeting β-Catenin can sensitise mesothelioma cells to cytotoxic drugs. -- Abstract: Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer associated with asbestos exposure, which currently presents an intractable clinical challenge. Wnt signaling has been reported to play a role in the neoplastic properties of mesothelioma cells but has not been investigated in detail in this cancer. We surveyed expression of Wnts, their receptors, and other key molecules in this pathwaymore » in well established in vitro mesothelioma models in comparison with primary mesothelial cultures. We also tested the biological response of MM cell lines to exogenous Wnt and secreted regulators, as well as targeting β-catenin. We detected frequent expression of Wnt3 and Wnt5a, as well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4 was inhibitory. Furthermore, directly targeting β-catenin expression could sensitise MM cells to cytotoxic drugs. These results provide evidence for altered expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt signaling in MM may prove a means of targeting proliferation and drug resistance in this cancer.« less

Comparison Between the Fecal Bacterial Microbiota of Healthy and Diarrheic Captive Musk Deer

PubMed Central

Li, Yimeng; Hu, Xiaolong; Yang, Shuang; Zhou, Juntong; Qi, Lei; Sun, Xiaoning; Fan, Mengyuan; Xu, Shanghua; Cha, Muha; Zhang, Meishan; Lin, Shaobi; Liu, Shuqiang; Hu, Defu

2018-01-01

Diarrhea constitutes one of the most common diseases affecting the survival of captive musk deer and is usually caused by an imbalance in intestinal microbiota. Currently, research regarding the structure and function of intestinal microbiota in diarrheic musk deer is lacking. Therefore, in the present study, high-throughput 16S-rRNA gene sequencing was used to analyze the intestinal microbiota in feces of healthy captive musk deer (HMD) (n = 8) and musk deer with mild (MMD) (n = 8), and severe (n = 5) (SMD) diarrhea to compare the difference in intestinal microbiota of musk deer under various physiological conditions. The results showed that the diversity of HMD fecal microbiota was significantly higher than that of the two diarrhea samples. β Diversity results indicated that there were extremely significant differences in bacterial communities between the HMD sample and the MMD and SMD samples. However, no significant difference was found between the two diarrhea samples. LefSe analysis showed that the degree of intestinal physiological dysfunction in musk deer was correlated with the types of major pathogens. The main pathogen in the MMD group is Escherichia–Shigella, whereas Fusobacterium is the main pathogen in the SMD group. PICRUSt functional profile prediction indicated that the intestinal microbiota disorder could also lead to changes in the abundance of genes in metabolic pathways of the immune system. Altogether, this study provides a theoretical basis for the exploration of treatments for diarrhea in captive musk deer, which is of considerable significance to the implementation of the musk deer release into the wild program. PMID:29551996

GRG5/AES interacts with T-cell factor 4 (TCF4) and downregulates Wnt signaling in human cells and zebrafish embryos.

PubMed

Costa, Angela M Sousa; Pereira-Castro, Isabel; Ricardo, Elisabete; Spencer, Forrest; Fisher, Shannon; da Costa, Luís Teixeira

2013-01-01

Transcriptional control by TCF/LEF proteins is crucial in key developmental processes such as embryo polarity, tissue architecture and cell fate determination. TCFs associate with β-catenin to activate transcription in the presence of Wnt signaling, but in its absence act as repressors together with Groucho-family proteins (GRGs). TCF4 is critical in vertebrate intestinal epithelium, where TCF4-β-catenin complexes are necessary for the maintenance of a proliferative compartment, and their abnormal formation initiates tumorigenesis. However, the extent of TCF4-GRG complexes' roles in development and the mechanisms by which they repress transcription are not completely understood. Here we characterize the interaction between TCF4 and GRG5/AES, a Groucho family member whose functional relationship with TCFs has been controversial. We map the core GRG interaction region in TCF4 to a 111-amino acid fragment and show that, in contrast to other GRGs, GRG5/AES-binding specifically depends on a 4-amino acid motif (LVPQ) present only in TCF3 and some TCF4 isoforms. We further demonstrate that GRG5/AES represses Wnt-mediated transcription both in human cells and zebrafish embryos. Importantly, we provide the first evidence of an inherent repressive function of GRG5/AES in dorsal-ventral patterning during early zebrafish embryogenesis. These results improve our understanding of TCF-GRG interactions, have significant implications for models of transcriptional repression by TCF-GRG complexes, and lay the groundwork for in depth direct assessment of the potential role of Groucho-family proteins in both normal and abnormal development.

Department of the Air Force Supporting Data for Fiscal Year 1995 Research, Development, Test and Evaluation Descriptive Summaries

DTIC Science & Technology

1994-02-01

c CLIOU 0 V ONj 00 . ca % 4 .) en 4...AD-A279 096 oci 00 o Io lef 1-4 00 .00 >~-4 C ) .tU E4.~ -4; ’.) .0 4-- -. Eu ca--- CU. >0 LU .e >. 060 U.U> m W CA *0E c00 &MU)%~ z ~0 0 U co o w) 0...0O o E~ ’= C E . M u-L od \\cu~ CU-L 4w) uC~ >0 oo CQ O 0 t ~ C /) ~ C MI 0 U *-’-’ cu. Cu~ 0%oU .E O 4uC). 0 0cl .20 0ý 0uU (U ~ U) toU 00 -Z 0 a 0

Complex modulation of androgen responsive gene expression by methoxyacetic acid

PubMed Central

2011-01-01

Background Optimal androgen signaling is critical for testicular development and spermatogenesis. Methoxyacetic acid (MAA), the primary active metabolite of the industrial chemical ethylene glycol monomethyl ether, disrupts spermatogenesis and causes testicular atrophy. Transcriptional trans-activation studies have indicated that MAA can enhance androgen receptor activity, however, whether MAA actually impacts the expression of androgen-responsive genes in vivo, and which genes might be affected is not known. Methods A mouse TM3 Leydig cell line that stably expresses androgen receptor (TM3-AR) was prepared and analyzed by transcriptional profiling to identify target gene interactions between MAA and testosterone on a global scale. Results MAA is shown to have widespread effects on androgen-responsive genes, affecting processes ranging from apoptosis to ion transport, cell adhesion, phosphorylation and transcription, with MAA able to enhance, as well as antagonize, androgenic responses. Moreover, testosterone is shown to exert both positive and negative effects on MAA gene responses. Motif analysis indicated that binding sites for FOX, HOX, LEF/TCF, STAT5 and MEF2 family transcription factors are among the most highly enriched in genes regulated by testosterone and MAA. Notably, 65 FOXO targets were repressed by testosterone or showed repression enhanced by MAA with testosterone; these include 16 genes associated with developmental processes, six of which are Hox genes. Conclusions These findings highlight the complex interactions between testosterone and MAA, and provide insight into the effects of MAA exposure on androgen-dependent processes in a Leydig cell model. PMID:21453523

Sleep quality in children: questionnaires available in Brazil

PubMed Central

Cavalheiro, Maria Gabriela; Corrêa, Camila de Castro; Maximino, Luciana Paula; Weber, Silke Anna Theresa

2017-01-01

Introduction The purpose of this paper was to evaluate and compare the questionnaires regarding sleep quality among children aged up to 12 years old, used in the Portuguese language in Brazil. Material and methods A search at the literature databases of Lilacs, Scielo and Pubmed was performed using keywords “sleep quality” and “children”. Selected Articles were analysed for age of the studied population, the number of questions and the issues addressed thereby, who realized the application, the analysis of the results, and content. Results Out of 9377 titles, 11 studies were included, performing 7 different questionnaires: Questionnaire to measure quality of life among children with enlarged palatine and pharyngeal tonsils (translation of OSD-6) (1); Inventory of Sleep Habits for Preschool Children (2); the Questionnaire on Obstructive Sleep Apnoea-18 (OSA-18) (3), Sleep Questionnaire by Reimão and Lefévre - QRL (4); the Questionnaire on Sleep Behaviour Patterns (5) and the translation of the Sleep Disturbance Scale for Children (6); Brief Infant Sleep Questionnaire - BISQ (7) . Six of the questionnaires have covered the following issues: snoring and daytime sleepiness. Conclusions A total of 7 protocols were found to be available in Brazil, the most commonly mentioned being OSA-18 and OSD-6. The use of protocols as a guided interview helps to define diagnosis and treatment among the paediatric population, but its large variability makes it difficult to compare a standardised monitoring process. PMID:29410747

Antibiotic resistome in a large-scale healthy human gut microbiota deciphered by metagenomic and network analyses.

PubMed

Feng, Jie; Li, Bing; Jiang, Xiaotao; Yang, Ying; Wells, George F; Zhang, Tong; Li, Xiaoyan

2018-01-01

The human gut microbiota is an important reservoir of antibiotic resistance genes (ARGs). A metagenomic approach and network analysis were used to establish a comprehensive antibiotic resistome catalog and to obtain co-occurrence patterns between ARGs and microbial taxa in fecal samples from 180 healthy individuals from 11 different countries. In total, 507 ARG subtypes belonging to 20 ARG types were detected with abundances ranging from 7.12 × 10 -7 to 2.72 × 10 -1 copy of ARG/copy of 16S-rRNA gene. Tetracycline, multidrug, macrolide-lincosamide-streptogramin, bacitracin, vancomycin, beta-lactam and aminoglycoside resistance genes were the top seven most abundant ARG types. The multidrug ABC transporter, aadE, bacA, acrB, tetM, tetW, vanR and vanS were shared by all 180 individuals, suggesting their common occurrence in the human gut. Compared to populations from the other 10 countries, the Chinese population harboured the most abundant ARGs. Moreover, LEfSe analysis suggested that the MLS resistance type and its subtype 'ermF' were representative ARGs of the Chinese population. Antibiotic inactivation, antibiotic target alteration and antibiotic efflux were the dominant resistance mechanism categories in all populations. Procrustes analysis revealed that microbial phylogeny structured the antibiotic resistome. Co-occurrence patterns obtained via network analysis implied that 12 species might be potential hosts of 58 ARG subtypes. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal.

PubMed

Yan, Kelley S; Janda, Claudia Y; Chang, Junlei; Zheng, Grace X Y; Larkin, Kathryn A; Luca, Vincent C; Chia, Luis A; Mah, Amanda T; Han, Arnold; Terry, Jessica M; Ootani, Akifumi; Roelf, Kelly; Lee, Mark; Yuan, Jenny; Li, Xiao; Bolen, Christopher R; Wilhelmy, Julie; Davies, Paige S; Ueno, Hiroo; von Furstenberg, Richard J; Belgrader, Phillip; Ziraldo, Solongo B; Ordonez, Heather; Henning, Susan J; Wong, Melissa H; Snyder, Michael P; Weissman, Irving L; Hsueh, Aaron J; Mikkelsen, Tarjei S; Garcia, K Christopher; Kuo, Calvin J

2017-05-11

The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands. For example, individual mutations in Wnt ligands have not revealed homeostatic phenotypes in the intestinal epithelium-an archetypal canonical, Wnt pathway-dependent, rapidly self-renewing tissue, the regeneration of which is fueled by proliferative crypt Lgr5 + intestinal stem cells (ISCs). R-spondin ligands (RSPO1-RSPO4) engage distinct LGR4-LGR6, RNF43 and ZNRF3 receptor classes, markedly potentiate canonical Wnt/β-catenin signalling, and induce intestinal organoid growth in vitro and Lgr5 + ISCs in vivo. However, the interchangeability, functional cooperation and relative contributions of Wnt versus RSPO ligands to in vivo canonical Wnt signalling and ISC biology remain unknown. Here we identify the functional roles of Wnt and RSPO ligands in the intestinal crypt stem-cell niche. We show that the default fate of Lgr5 + ISCs is to differentiate, unless both RSPO and Wnt ligands are present. However, gain-of-function studies using RSPO ligands and a new non-lipidated Wnt analogue reveal that these ligands have qualitatively distinct, non-interchangeable roles in ISCs. Wnt proteins are unable to induce Lgr5 + ISC self-renewal, but instead confer a basal competency by maintaining RSPO receptor expression that enables RSPO ligands to actively drive and specify the extent of stem-cell expansion. This functionally non-equivalent yet cooperative interaction between Wnt and RSPO ligands establishes a molecular precedent for regulation of mammalian stem cells by distinct priming and self-renewal factors, with broad implications for precise control of tissue regeneration.

Irx1 regulates dental outer enamel epithelial and lung alveolar type II epithelial differentiation

PubMed Central

Yu, Wenjie; Li, Xiao; Eliason, Steven; Romero-Bustillos, Miguel; Ries, Ryan J.; Cao, Huojun; Amendt, Brad A.

2017-01-01

The Iroquois genes (Irx) appear to regulate fundamental processes that lead to cell proliferation, differentiation, and maturation during development. In this report, the Iroquois homeobox 1 (Irx1) transcription factor was functionally disrupted using a LacZ insert and LacZ expression demonstrated stage-specific expression during embryogenesis. Irx1 is highly expressed in the brain, lung, digits, kidney, testis and developing teeth. Irx1 null mice are neonatal lethal and this lethality it due to pulmonary immaturity. Irx1−/− mice show delayed lung maturation characterized by defective surfactant protein secretion and Irx1 marks a population of SP-C expressing alveolar type II cells. Irx1 is specifically expressed in the outer enamel epithelium (OEE), stellate reticulum (SR) and stratum intermedium (SI) layers of the developing tooth. Irx1 mediates dental epithelial cell differentiation in the lower incisors resulting in delayed growth of the lower incisors. Irx1 is specifically and temporally expressed during developmental stages and we have focused on lung and dental development in this report. Irx1+ cells are unique to the development of the incisor outer enamel epithelium, patterning of Lef-1+ and Sox2+ cells as well as a new marker for lung alveolar type II cells. Mechanistically, Irx1 regulates Foxj1 and Sox9 to control cell differentiation during development. PMID:28746823

Irx1 regulates dental outer enamel epithelial and lung alveolar type II epithelial differentiation.

PubMed

Yu, Wenjie; Li, Xiao; Eliason, Steven; Romero-Bustillos, Miguel; Ries, Ryan J; Cao, Huojun; Amendt, Brad A

2017-09-01

The Iroquois genes (Irx) appear to regulate fundamental processes that lead to cell proliferation, differentiation, and maturation during development. In this report, the Iroquois homeobox 1 (Irx1) transcription factor was functionally disrupted using a LacZ insert and LacZ expression demonstrated stage-specific expression during embryogenesis. Irx1 is highly expressed in the brain, lung, digits, kidney, testis and developing teeth. Irx1 null mice are neonatal lethal and this lethality it due to pulmonary immaturity. Irx1 -/- mice show delayed lung maturation characterized by defective surfactant protein secretion and Irx1 marks a population of SP-C expressing alveolar type II cells. Irx1 is specifically expressed in the outer enamel epithelium (OEE), stellate reticulum (SR) and stratum intermedium (SI) layers of the developing tooth. Irx1 mediates dental epithelial cell differentiation in the lower incisors resulting in delayed growth of the lower incisors. Irx1 is specifically and temporally expressed during developmental stages and we have focused on lung and dental development in this report. Irx1+ cells are unique to the development of the incisor outer enamel epithelium, patterning of Lef-1+ and Sox2+ cells as well as a new marker for lung alveolar type II cells. Mechanistically, Irx1 regulates Foxj1 and Sox9 to control cell differentiation during development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Anti-CXCL4 monoclonal antibody accelerates telogen to anagen transition and attenuates apoptosis of the hair follicle in mice

PubMed Central

Guan, Wen; Yu, Xiaolan; Li, Jingjing; Deng, Qing; Zhang, Yang; Gao, Jing; Xia, Peng; Yuan, Yunsheng; Gao, Jin; Zhou, Liang; Han, Wei; Yu, Yan

2017-01-01

Although hair loss or alopecia is a common disease, its exact mechanisms are not yet well understood. The present study investigated the hypothesis that the homeostatic regulation of genes during hair regeneration may participate in hair loss, based on the cyclicity of hair growth. A cluster of such genes was identified by an expression gene-array from the dorsal skin in a depilated mouse model, and CXCL4 was identified as a significantly regulated gene during the hair regeneration process. To elucidate the function of CXCL4 in hair growth, CXCL4 activity was blocked by the administration of an anti-CXCL4 monoclonal antibody (mAb). Histomorphometric analysis indicated that anti-CXCL4 mAb induced an earlier anagen phase and delayed hair follicle regression, in contrast with that in the control group. Moreover, CXCL4 mAb upregulated the transcription levels of several hair growth-related genes, including Lef1, Wnt10b, Bmp4 and Bmp2. In addition, CXCL4 mAb increased the levels of the proliferation-related protein PCNA and Bcl-2 during the anagen phase, while it reduced the expression of pro-apoptotic protein Bax and cleaved caspase-3 during the catagen phase. These findings reveal that CXCL4 plays an important role in hair growth, and that blockade of CXCL4 activity promotes hair growth. PMID:28810552

Anti-CXCL4 monoclonal antibody accelerates telogen to anagen transition and attenuates apoptosis of the hair follicle in mice.

PubMed

Guan, Wen; Yu, Xiaolan; Li, Jingjing; Deng, Qing; Zhang, Yang; Gao, Jing; Xia, Peng; Yuan, Yunsheng; Gao, Jin; Zhou, Liang; Han, Wei; Yu, Yan

2017-08-01

Although hair loss or alopecia is a common disease, its exact mechanisms are not yet well understood. The present study investigated the hypothesis that the homeostatic regulation of genes during hair regeneration may participate in hair loss, based on the cyclicity of hair growth. A cluster of such genes was identified by an expression gene-array from the dorsal skin in a depilated mouse model, and CXCL4 was identified as a significantly regulated gene during the hair regeneration process. To elucidate the function of CXCL4 in hair growth, CXCL4 activity was blocked by the administration of an anti-CXCL4 monoclonal antibody (mAb). Histomorphometric analysis indicated that anti-CXCL4 mAb induced an earlier anagen phase and delayed hair follicle regression, in contrast with that in the control group. Moreover, CXCL4 mAb upregulated the transcription levels of several hair growth-related genes, including Lef1, Wnt10b, Bmp4 and Bmp2. In addition, CXCL4 mAb increased the levels of the proliferation-related protein PCNA and Bcl-2 during the anagen phase, while it reduced the expression of pro-apoptotic protein Bax and cleaved caspase-3 during the catagen phase. These findings reveal that CXCL4 plays an important role in hair growth, and that blockade of CXCL4 activity promotes hair growth.

Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus.

PubMed

Shobahah, Jauharotus; Xue, Shengjie; Hu, Dongbing; Zhao, Cui; Wei, Ming; Quan, Yanping; Yu, Wei

2017-06-19

Bombyx mori has become an important model organism for many fundamental studies. Bombyx mori nucleopolyhedrovirus (BmNPV) is a significant pathogen to Bombyx mori, yet also an efficient vector for recombinant protein production. A previous study indicated that acetylation plays many vital roles in several cellular processes of Bombyx mori while global phosphorylation pattern upon BmNPV infection remains elusive. Employing tandem mass tag (TMT) labeling and phosphorylation affinity enrichment followed by high-resolution LC-MS/MS analysis and intensive bioinformatics analysis, the quantitative phosphoproteome in Bombyx mori cells infected by BmNPV at 24 hpi with an MOI of 10 was extensively examined. Totally, 6480 phosphorylation sites in 2112 protein groups were identified, among which 4764 sites in 1717 proteins were quantified. Among the quantified proteins, 81 up-regulated and 25 down-regulated sites were identified with significant criteria (the quantitative ratio above 1.3 was considered as up-regulation and below 0.77 was considered as down-regulation) and with significant p-value (p < 0.05). Some proteins of BmNPV were also hyperphosphorylated during infection, such as P6.9, 39 K, LEF-6, Ac58-like protein, Ac82-like protein and BRO-D. The phosphorylated proteins were primary involved in several specific functions, out of which, we focused on the binding activity, protein synthesis, viral replication and apoptosis through kinase activity.

Sonic boom (human response and atmospheric effects) outdoor-to-indoor response to minimized sonic booms

NASA Technical Reports Server (NTRS)

Brown, David; Sutherland, Louis C.

1992-01-01

The preferred descriptor to define the spectral content of sonic booms is the Sound Exposure Spectrum Level, LE(f). This descriptor represents the spectral content of the basic noise descriptors used for describing any single event--the Sound Exposure Level, LE. The latter is equal to ten times the logarithms, to the base ten, of the integral, over the duration of the event, of the square of the instantaneous acoustic pressure, divided by the square of the reference pressure, 20 micro-Pa. When applied to the evaluation of community response to sonic booms, it is customary to use the so-called C-Weighted Sound Exposure Level, LCE, for which the frequency content of the instantaneous acoustic pressure is modified by the C-Weighting curve.

The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis.

PubMed

Derakhshani, Hooman; De Buck, Jeroen; Mortier, Rienske; Barkema, Herman W; Krause, Denis O; Khafipour, Ehsan

2016-01-01

Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that this dynamic network of microorganisms had an active role in intestinal homeostasis.

The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase

PubMed Central

Yu, Zheyong; Schneider, Claus; Boeglin, William E.; Marnett, Lawrence J.; Brash, Alan R.

2003-01-01

Lipoxygenase (LOX) enzymes form fatty acid hydroperoxides used in membrane remodeling and cell signaling. Mammalian epidermal LOX type 3 (eLOX3) is distinctive in totally lacking this typical oxygenase activity. Surprisingly, genetic evidence has linked mutations in eLOX3 or a colocalizing enzyme, 12R-LOX, to disruption of the normal permeability barrier of the skin [Jobard, F., Lefèvre, C., Karaduman, A., Blanchet-Bardon, C., Emre, S., Weissenbach, J., Özgüc, M., Lathrop, M., Prud'homme, J. F. & Fischer, J. (2002) Hum. Mol. Genet. 11, 107–113]. Herein we identify a logical link of the biochemistry to the genetics. eLOX3 functions as a hydroperoxide isomerase (epoxyalcohol synthase) by using the product of 12R-LOX as the preferred substrate. 12R-Hydroperoxyeicosatetraenoic acid (12R-HPETE) is converted to 8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid, one of the isomers of hepoxilin A3, and to 12-ketoeicosatetraenoic acid in a 2:1 ratio. Other hydroperoxides, including 8R-HPETE, 12S-HPETE, and 15S-HPETE, as well as the 13S- and 13R-hydroperoxides of linoleic acid are converted less efficiently. Mass spectrometric analysis of the epoxyalcohol formed from [18O]15S-HPETE showed that both hydroperoxy oxygens are retained in the product. We propose that the ferrous form of eLOX3 initiates a redox cycle, unprecedented among LOX in being autocatalytic, in which the hydroperoxy substrate is isomerized to the epoxyalcohol or keto product. Our results provide strong biochemical evidence for a functional linkage of 12R-LOX and eLOX3 and clues into skin biochemistry and the etiology of ichthyosiform diseases in humans. PMID:12881489

GRG5/AES Interacts with T-Cell Factor 4 (TCF4) and Downregulates Wnt Signaling in Human Cells and Zebrafish Embryos

PubMed Central

Costa, Ângela M. Sousa; Pereira-Castro, Isabel; Ricardo, Elisabete; Spencer, Forrest; Fisher, Shannon; da Costa, Luís Teixeira

2013-01-01

Transcriptional control by TCF/LEF proteins is crucial in key developmental processes such as embryo polarity, tissue architecture and cell fate determination. TCFs associate with β-catenin to activate transcription in the presence of Wnt signaling, but in its absence act as repressors together with Groucho-family proteins (GRGs). TCF4 is critical in vertebrate intestinal epithelium, where TCF4-β-catenin complexes are necessary for the maintenance of a proliferative compartment, and their abnormal formation initiates tumorigenesis. However, the extent of TCF4-GRG complexes’ roles in development and the mechanisms by which they repress transcription are not completely understood. Here we characterize the interaction between TCF4 and GRG5/AES, a Groucho family member whose functional relationship with TCFs has been controversial. We map the core GRG interaction region in TCF4 to a 111-amino acid fragment and show that, in contrast to other GRGs, GRG5/AES-binding specifically depends on a 4-amino acid motif (LVPQ) present only in TCF3 and some TCF4 isoforms. We further demonstrate that GRG5/AES represses Wnt-mediated transcription both in human cells and zebrafish embryos. Importantly, we provide the first evidence of an inherent repressive function of GRG5/AES in dorsal-ventral patterning during early zebrafish embryogenesis. These results improve our understanding of TCF-GRG interactions, have significant implications for models of transcriptional repression by TCF-GRG complexes, and lay the groundwork for in depth direct assessment of the potential role of Groucho-family proteins in both normal and abnormal development. PMID:23840876

Impairment of holistic face perception following right occipito-temporal damage in prosopagnosia: converging evidence from gaze-contingency.

PubMed

Van Belle, Goedele; Busigny, Thomas; Lefèvre, Philippe; Joubert, Sven; Felician, Olivier; Gentile, Francesco; Rossion, Bruno

2011-09-01

Gaze-contingency is a method traditionally used to investigate the perceptual span in reading by selectively revealing/masking a portion of the visual field in real time. Introducing this approach in face perception research showed that the performance pattern of a brain-damaged patient with acquired prosopagnosia (PS) in a face matching task was reversed, as compared to normal observers: the patient showed almost no further decrease of performance when only one facial part (eye, mouth, nose, etc.) was available at a time (foveal window condition, forcing part-based analysis), but a very large impairment when the fixated part was selectively masked (mask condition, promoting holistic perception) (Van Belle, De Graef, Verfaillie, Busigny, & Rossion, 2010a; Van Belle, De Graef, Verfaillie, Rossion, & Lefèvre, 2010b). Here we tested the same manipulation in a recently reported case of pure prosopagnosia (GG) with unilateral right hemisphere damage (Busigny, Joubert, Felician, Ceccaldi, & Rossion, 2010). Contrary to normal observers, GG was also significantly more impaired with a mask than with a window, demonstrating impairment with holistic face perception. Together with our previous study, these observations support a generalized account of acquired prosopagnosia as a critical impairment of holistic (individual) face perception, implying that this function is a key element of normal human face recognition. Furthermore, the similar behavioral pattern of the two patients despite different lesion localizations supports a distributed network view of the neural face processing structures, suggesting that the key function of human face processing, namely holistic perception of individual faces, requires the activity of several brain areas of the right hemisphere and their mutual connectivity. Copyright © 2011 Elsevier Ltd. All rights reserved.

MUC4 is negatively regulated through the Wnt/β-catenin pathway via the Notch effector Hath1 in colorectal cancer

PubMed Central

Pai, Priya; Rachagani, Satyanarayana; Dhawan, Punita; Sheinin, Yuri M.; Mallya, Kavita; Pothuraju, Ramesh; Batra, Surinder K.

2016-01-01

MUC4 is a transmembrane mucin lining the normal colonic epithelium. The aberrant/de novo over-expression of MUC4 is well documented in malignancies of the pancreas, ovary and breast. However, studies have reported the loss of MUC4 expression in the majority of colorectal cancers (CRCs). A MUC4 promoter analysis showed the presence of three putative TCF/LEF sites, implying a possible regulation by the Wnt/β-catenin pathway, which has been shown to drive CRC progression. Thus, the objective of our study was to determine whether MUC4 is regulated by β-catenin in CRC. We first knocked down (KD) β-catenin in three CRC cell lines; LS180, HCT-8 and HCT116, which resulted in increased MUC4 transcript and MUC4 protein. Additionally, the overexpression of stabilized mutant β-catenin in LS180 and HCT-8 resulted in a decrease in MUC4 expression. Immunohistochemistry (IHC) of mouse colon tissue harboring tubular adenomas and high grade dysplasia showed dramatically reduced Muc4 in lesions relative to adjacent normal tissue, with increased cytosolic/nuclear β-catenin. Luciferase assays with the complete MUC4 promoter construct p3778 showed increased MUC4 promoter luciferase activity in the absence of β-catenin (KD). Mutation of all three putative TCF/LEF sites showed that MUC4 promoter luciferase activity was increased relative to the un-mutated promoter. Interestingly, it was observed that MUC4 expressing CRC cell lines also expressed high levels of Hath1, a transcription factor repressed by both active Wnt/β-catenin and Notch signaling. The KD of β-catenin and/or treatment with a Notch γ-secretase inhibitor, Dibenzazepine (DBZ) resulted in increased Hath1 and MUC4 in LS180, HCT-8 and HCT116. Furthermore, overexpression of Hath1 in HCT-8 and LS180 caused increased MUC4 transcript and MUC4 protein. Taken together, our results indicate that the Wnt/β-catenin pathway suppresses the Notch pathway effector Hath1, resulting in reduced MUC4 in CRC. PMID:27551331

MUC4 is negatively regulated through the Wnt/β-catenin pathway via the Notch effector Hath1 in colorectal cancer.

PubMed

Pai, Priya; Rachagani, Satyanarayana; Dhawan, Punita; Sheinin, Yuri M; Macha, Muzafar A; Qazi, Asif Khurshid; Chugh, Seema; Ponnusamy, Moorthy P; Mallya, Kavita; Pothuraju, Ramesh; Batra, Surinder K

2016-05-01

MUC4 is a transmembrane mucin lining the normal colonic epithelium. The aberrant/de novo over-expression of MUC4 is well documented in malignancies of the pancreas, ovary and breast. However, studies have reported the loss of MUC4 expression in the majority of colorectal cancers (CRCs). A MUC4 promoter analysis showed the presence of three putative TCF/LEF sites, implying a possible regulation by the Wnt/β-catenin pathway, which has been shown to drive CRC progression. Thus, the objective of our study was to determine whether MUC4 is regulated by β-catenin in CRC. We first knocked down (KD) β-catenin in three CRC cell lines; LS180, HCT-8 and HCT116, which resulted in increased MUC4 transcript and MUC4 protein. Additionally, the overexpression of stabilized mutant β-catenin in LS180 and HCT-8 resulted in a decrease in MUC4 expression. Immunohistochemistry (IHC) of mouse colon tissue harboring tubular adenomas and high grade dysplasia showed dramatically reduced Muc4 in lesions relative to adjacent normal tissue, with increased cytosolic/nuclear β-catenin. Luciferase assays with the complete MUC4 promoter construct p3778 showed increased MUC4 promoter luciferase activity in the absence of β-catenin (KD). Mutation of all three putative TCF/LEF sites showed that MUC4 promoter luciferase activity was increased relative to the un-mutated promoter. Interestingly, it was observed that MUC4 expressing CRC cell lines also expressed high levels of Hath1, a transcription factor repressed by both active Wnt/β-catenin and Notch signaling. The KD of β-catenin and/or treatment with a Notch γ-secretase inhibitor, Dibenzazepine (DBZ) resulted in increased Hath1 and MUC4 in LS180, HCT-8 and HCT116. Furthermore, overexpression of Hath1 in HCT-8 and LS180 caused increased MUC4 transcript and MUC4 protein. Taken together, our results indicate that the Wnt/β-catenin pathway suppresses the Notch pathway effector Hath1, resulting in reduced MUC4 in CRC.

Minoxidil activates β-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect.

PubMed

Kwack, Mi Hee; Kang, Bo Mi; Kim, Moon Kyu; Kim, Jung Chul; Sung, Young Kwan

2011-06-01

It is believed that the length of the actively growing phase of the anagen hair cycle mainly contributes to hair length. Recent studies showed that maintenance of β-catenin activity in the dermal papilla cells (DPCs) enables hair follicles to keep actively growing. Topical minoxidil treatment promotes hair growth in men with androgenetic alopecia, suggesting that minoxidil may prolong the actively growing phase of the anagen hair cycle. To investigate whether minoxidil prolongs the anagen hair cycle in mice and, if so, to investigate whether minoxidil activates β-catenin pathway in human DPCs. Dorsal skins of C57BL/6 mice were depilated to synchronize the hair cycle. After 10 days, 3% minoxidil were topically applied daily for 10 days. Sections of back skins were stained with hematoxylin and eosin. Hair follicles were graded and hair cycle score (HCS) was calculated. Cultured human DPCs were transiently transfected with the β-catenin responsive TCF reporter plasmid (pTopflash) and corresponding negative control reporter (pFopflash) to assess the activity of β-catenin signaling by minoxidil. Immunofluorescence staining and immunoblot were performed to examine the expression and localization of β-catenin in the presence or absence of minoxidil. Phosphorylation of GSK3β, PKA and PKB were also examined by immunoblot after minoxidil treatment. RT-PCR analysis and immunoblot were employed to investigate the expression of β-catenin pathway targets in DPCs, such as Axin2, Lef-1, and EP2. Modest extension of anagen phase thereby delay of catagen progression was observed by application of minoxidil in mice. Minoxidil stimulated the transcriptional activity of pTopflash but not pFopflash. Nuclear accumulation of β-catenin was also observed after minoxidil treatment. Immunoblot further showed that minoxidil treatment increases the phosphorylation of GSK3β, PKA and PKB. Moreover, minoxidil induced Axin2, Lef-1, and EP2 expression. Our results strongly suggest that minoxidil extends the anagen phase by activating β-catenin activity in the DPCs. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Daily global mapping of Mars ozone column abundances with MARCI UV band imaging

NASA Astrophysics Data System (ADS)

Todd Clancy, R.; Wolff, Michael J.; Lefèvre, Franck; Cantor, Bruce A.; Malin, Michael C.; Smith, Michael D.

2016-03-01

Since November of 2006, The Mars Color Imager (MARCI) onboard the Mars Reconnaissance Orbiter (MRO) has obtained multiple-filter daily global images of Mars centered upon a local time (LT) of 3 pm. Ultraviolet imaging bands placed within (260 nm) and longward (320 nm) of Hartley band (240-300 nm) ozone (O3) absorption support retrievals of atmospheric ozone columns, with detection limits (∼1 μm-atm) appropriate to mapping elevated O3 abundances at low latitudes around Mars aphelion, and over mid-to-high latitudes during fall/winter/spring seasons. MARCI O3 maps for these regions reveal the detailed spatial (∼1° lat/long, for 8 × 8 pixel binned resolution) and temporal (daily, with substantial LT coverage at pole) behaviors of water vapor saturation conditions that force large variations in water vapor photolysis products (HOx-OH, HO2, and H) responsible for the catalytic destruction of O3 in the Mars atmosphere. A detailed description of the MARCI O3 data set, including measurement and retrieval characteristics, is provided in conjunction with comparisons to Mars Express SPICAM ozone measurements (Perrier, S. et al. [2006]. J. Geophys. Res. (Planets) 111) and LMD GCM simulated O3 abundances (Lefèvre, F. [2004]. J. Geophys. Res. (Planets) 109). Presented aspects of the MARCI ozone mapping data set include aphelion increases in low latitude O3, dynamically evolving high latitude O3 maxima associated with planetary waves and weather fronts during northern early spring, and distinctive winter/spring O3 and CO increases within the Hellas Basin associated with transport of condensation-enhanced south polar air mass. Comparisons of coincident MARCI measurements and LMD simulations for ice cloud and O3 columns are considered in the context of potential heterogeneous photochemical processes (Lefèvre, F. [2008]. Nature 454, 971-975), which are not strongly evidenced in the MARCI observations. Modest interannual variations are exhibited, most notably a 20% reduction in aphelion low latitude O3 columns following the 2007 perihelic global dust storm.

National Program for Inspection of Non-Federal Dams. Union Meadows Dam, (N.H. 00222), State Number 241.05, Piscataqua River Basin, Wakefield, New Hampshire. Phase I Inspection Report.

DTIC Science & Technology

1979-11-01

inspection, Union Meadows Dam is in good 3-1 condition. Trees growing on thc - e-ast bar-,k of tne discharge channel between the damn and State Route 16T...Vernon A. Know ttOn On the mornin, 01 Novem-,ber 14, 1 9t8, 1 - isitedl L:nion eaw to check a leak oni the lef-t abutmentL ol: thc spillw;oy Thke...8217t 1 .Ce ev-:-r: f ive ye -rs. c)ai.,i3tanft ri1th -. ,m pt~qnt ijlt&vi.-i~ 1-s-’ctor is na ex-oert an ’-i-t~~i~~r~.iK"., cbd sinflt you wiII be

Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X.

PubMed

Brunner, Magdalena A T; Jagannathan, Vidhya; Waluk, Dominik P; Roosje, Petra; Linek, Monika; Panakova, Lucia; Leeb, Tosso; Wiener, Dominique J; Welle, Monika M

2017-01-01

Alopecia X is a hair cycle arrest disorder in Pomeranians. Histologically, kenogen and telogen hair follicles predominate, whereas anagen follicles are sparse. The induction of anagen relies on the activation of hair follicle stem cells and their subsequent proliferation and differentiation. Stem cell function depends on finely tuned interactions of signaling molecules and transcription factors, which are not well defined in dogs. We performed transcriptome profiling on skin biopsies to analyze altered molecular pathways in alopecia X. Biopsies from five affected and four non-affected Pomeranians were investigated. Differential gene expression revealed a downregulation of key regulator genes of the Wnt (CTNNB1, LEF1, TCF3, WNT10B) and Shh (SHH, GLI1, SMO, PTCH2) pathways. In mice it has been shown that Wnt and Shh signaling results in stem cell activation and differentiation Thus our findings are in line with the lack of anagen hair follicles in dogs with Alopecia X. We also observed a significant downregulation of the stem cell markers SOX9, LHX2, LGR5, TCF7L1 and GLI1 whereas NFATc1, a quiescence marker, was upregulated in alopecia X. Moreover, genes coding for enzymes directly involved in the sex hormone metabolism (CYP1A1, CYP1B1, HSD17B14) were differentially regulated in alopecia X. These findings are in agreement with the so far proposed but not yet proven deregulation of the sex hormone metabolism in this disease.

Inhibition of human melanoma cell growth by dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels

PubMed Central

Syed, Deeba N.; Afaq, Farrukh; Maddodi, Nityanand; Johnson, Jeremy J.; Sarfaraz, Sami; Ahmad, Adeel; Setaluri, Vijayasaradhi; Mukhtar, Hasan

2011-01-01

The prognosis of advanced melanoma remains poor in spite of treatment advances, emphasizing the importance of additional preventive measures. Flavonoids, natural components of our diet are being investigated for their chemopreventive/therapeutic properties. Microphthalmia-associated transcription factor (Mitf), downstream of Wnt/β-catenin pathway has become an important prognostic marker of melanoma. Here, we show that treatment of 451Lu melanoma cells with the dietary flavonoid fisetin resulted in decreased cell viability with G1-phase arrest and disruption of Wnt/β-catenin signaling. This was accompanied with a decrease in expression of Wnt protein and its co-receptors and a parallel increase in the expression of endogenous Wnt inhibitors. Fisetin-treated cells showed increased cytosolic levels of Axin and β-TrCP and decreased phosphorylation of GSK3-β assocaited with decreased β-catenin stabilization. Fisetin-mediated interference with the functional cooperation between β-catenin and LEF/TCF-2 resulted in downregulation of positively regulated TCF targets such as c-myc, Brn-2 and Mitf. Flowcytometric analysis of Mitf overexpressing cells showed that fisetin repressed Mitf-induced cell proliferation. Finally, administration of fisetin to 451Lu xenografted nude mice resulted in inhibition of tumor development and decreased Mitf expression. Our data suggest that fisetin can be developed as an effective agent against melanoma due to its potential inhibitory effect on β-catenin/Mitf signaling. PMID:21346776

Controlled levels of canonical Wnt signaling are required for neural crest migration.

PubMed

Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

2016-09-01

Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations.

PubMed

O'Connell, Amy E; Zhou, Fanny; Shah, Manasvi S; Murphy, Quinn; Rickner, Hannah; Kelsen, Judith; Boyle, John; Doyle, Jefferson J; Gangwani, Bharti; Thiagarajah, Jay R; Kamin, Daniel S; Goldsmith, Jeffrey D; Richmond, Camilla; Breault, David T; Agrawal, Pankaj B

2018-06-04

Homozygous nonsense mutations in WNT2B were identified in three individuals from two unrelated families with severe, neonatal-onset osmotic diarrhea after whole-exome sequencing was performed on trios from the two families. Intestinal biopsy samples from affected individuals were used for histology and immunofluorescence and to generate enteroids ex vivo. Histopathologic evaluation demonstrated chronic inflammatory changes in the stomach, duodenum, and colon. Immunofluorescence demonstrated diminished staining for OLFM4, a marker for intestinal stem cells (ISCs). The enteroids generated from WNT2B-deficient intestinal epithelium could not be expanded and did not survive passage. Addition of CHIR-99021 (a GSK3A and GSK3B inhibitor and activator of canonical WNT/β-CATENIN signaling) could not rescue WNT2B-deficient enteroids. Addition of supplemental recombinant murine WNT2B was able to perpetuate small enteroids for multiple passages but failed to expand their number. Enteroids showed a 10-fold increase in the expression of LEF1 mRNA and a 100-fold reduction in TLR4 expression, compared with controls by quantitative RT-PCR, indicating alterations in canonical WNT and microbial pattern-recognition signaling. In summary, individuals with homozygous nonsense mutations in WNT2B demonstrate severe intestinal dysregulation associated with decreased ISC number and function, likely explaining their diarrheal phenotype. WNT2B deficiency should be considered for individuals with neonatal-onset diarrhea. Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Bombyx mori Nucleopolyhedrovirus Encodes a DNA-Binding Protein Capable of Destabilizing Duplex DNA

PubMed Central

Mikhailov, Victor S.; Mikhailova, Alla L.; Iwanaga, Masashi; Gomi, Sumiko; Maeda, Susumu

1998-01-01

A DNA-binding protein (designated DBP) with an apparent molecular mass of 38 kDa was purified to homogeneity from BmN cells (derived from Bombyx mori) infected with the B. mori nucleopolyhedrovirus (BmNPV). Six peptides obtained after digestion of the isolated protein with Achromobacter protease I were partially or completely sequenced. The determined amino acid sequences indicated that DBP was encoded by an open reading frame (ORF16) located at nucleotides (nt) 16189 to 17139 in the BmNPV genome (GenBank accession no. L33180). This ORF (designated dbp) is a homolog of Autographa californica multicapsid NPV ORF25, whose product has not been identified. BmNPV DBP is predicted to contain 317 amino acids (calculated molecular mass of 36.7 kDa) and to have an isoelectric point of 7.8. DBP showed a tendency to multimerization in the course of purification and was found to bind preferentially to single-stranded DNA. When bound to oligonucleotides, DBP protected them from hydrolysis by phage T4 DNA polymerase-associated 3′→5′ exonuclease. The sizes of the protected fragments indicated that a binding site size for DBP is about 30 nt per protein monomer. DBP, but not BmNPV LEF-3, was capable of unwinding partial DNA duplexes in an in vitro system. This helix-destabilizing ability is consistent with the prediction that DBP functions as a single-stranded DNA binding protein in virus replication. PMID:9525636

Neutrophil Elastase, Proteinase 3, and Cathepsin G as Therapeutic Targets in Human Diseases

PubMed Central

Horwitz, Marshall S.; Jenne, Dieter E.; Gauthier, Francis

2010-01-01

Polymorphonuclear neutrophils are the first cells recruited to inflammatory sites and form the earliest line of defense against invading microorganisms. Neutrophil elastase, proteinase 3, and cathepsin G are three hematopoietic serine proteases stored in large quantities in neutrophil cytoplasmic azurophilic granules. They act in combination with reactive oxygen species to help degrade engulfed microorganisms inside phagolysosomes. These proteases are also externalized in an active form during neutrophil activation at inflammatory sites, thus contributing to the regulation of inflammatory and immune responses. As multifunctional proteases, they also play a regulatory role in noninfectious inflammatory diseases. Mutations in the ELA2/ELANE gene, encoding neutrophil elastase, are the cause of human congenital neutropenia. Neutrophil membrane-bound proteinase 3 serves as an autoantigen in Wegener granulomatosis, a systemic autoimmune vasculitis. All three proteases are affected by mutations of the gene (CTSC) encoding dipeptidyl peptidase I, a protease required for activation of their proform before storage in cytoplasmic granules. Mutations of CTSC cause Papillon-Lefèvre syndrome. Because of their roles in host defense and disease, elastase, proteinase 3, and cathepsin G are of interest as potential therapeutic targets. In this review, we describe the physicochemical functions of these proteases, toward a goal of better delineating their role in human diseases and identifying new therapeutic strategies based on the modulation of their bioavailability and activity. We also describe how nonhuman primate experimental models could assist with testing the efficacy of proposed therapeutic strategies. PMID:21079042

Comparison of gizzard and intestinal microbiota of wild neotropical birds

PubMed Central

Shin, Hakdong; Sanz, Virginia; Lentino, Miguel; Martínez, L. Margarita; Contreras, Monica; Michelangeli, Fabian; Domínguez-Bello, María Gloria

2018-01-01

Gut bacterial communities have been shown to be influenced by diet, host phylogeny and anatomy, but most of these studies have been done in captive animals. Here we compare the bacterial communities in the digestive tract of wild birds. We characterized the gizzard and intestinal microbiota among 8 wild Neotropical bird species, granivorous or frugivorous species of the orders Columbiformes and Passeriformes. We sequenced the V4 region of the 16S rRNA gene in 94 collected samples from 32 wild birds from 5 localities, and compared bacterial communities by foraging guild, organ, locality and bird taxonomy. 16S rRNA gene-based sequencing data were examined using QIIME with linear discriminant analysis effect size (LEfSe) and metabolic pathways were predicted using PICRUSt algorism. We identified 8 bacterial phyla, dominated by Firmicutes, Actinobacteria and Proteobacteria. Beta diversity analyses indicated significant separation of gut communities by bird orders (Columbiformes vs. Passerifomes) and between bird species (p<0.01). In lower intestine, PICRUSt shows a predominance of carbohydrate metabolism in granivorous birds and xenobiotics biodegradation pathways in frugivorous birds. Gizzard microbiota was significantly richer in granivorous, in relation to frugivorous birds (Chao 1; non-parametric t-test, p<0.05), suggesting a microbial gizzard function, beyond grinding food. The results suggest that the most important factor separating the bacterial community structure was bird taxonomy, followed by foraging guild. However, variation between localities is also likely to be important, but this could not been assessed with our study design. PMID:29579092

AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

PubMed

Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D; Moriggl, Richard; Kenner, Lukas; Tse, William

2015-08-21

AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties.

Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression

PubMed Central

Yoo, Byoung Kwon; Emdad, Luni; Su, Zao-zhong; Villanueva, Augusto; Chiang, Derek Y.; Mukhopadhyay, Nitai D.; Mills, Alan Scott; Waxman, Samuel; Fisher, Robert A.; Llovet, Josep M.; Fisher, Paul B.; Sarkar, Devanand

2009-01-01

Hepatocellular carcinoma (HCC) is a highly aggressive vascular cancer characterized by diverse etiology, activation of multiple signal transduction pathways, and various gene mutations. Here, we have determined a specific role for astrocyte elevated gene-1 (AEG1) in HCC pathogenesis. Expression of AEG1 was extremely low in human hepatocytes, but its levels were significantly increased in human HCC. Stable overexpression of AEG1 converted nontumorigenic human HCC cells into highly aggressive vascular tumors, and inhibition of AEG1 abrogated tumorigenesis by aggressive HCC cells in a xenograft model of nude mice. In human HCC, AEG1 overexpression was associated with elevated copy numbers. Microarray analysis revealed that AEG1 modulated the expression of genes associated with invasion, metastasis, chemoresistance, angiogenesis, and senescence. AEG1 also was found to activate Wnt/β-catenin signaling via ERK42/44 activation and upregulated lymphoid-enhancing factor 1/T cell factor 1 (LEF1/TCF1), the ultimate executor of the Wnt pathway, important for HCC progression. Inhibition studies further demonstrated that activation of Wnt signaling played a key role in mediating AEG1 function. AEG1 also activated the NF-κB pathway, which may play a role in the chronic inflammatory changes preceding HCC development. These data indicate that AEG1 plays a central role in regulating diverse aspects of HCC pathogenesis. Targeted inhibition of AEG1 might lead to the shutdown of key elemental characteristics of HCC and could lead to an effective therapeutic strategy for HCC. PMID:19221438

Hydroxycinnamate Synthesis and Association with Mediterranean Corn Borer Resistance.

PubMed

Santiago, Rogelio; Malvar, Rosa Ana; Barros-Rios, Jaime; Samayoa, Luis Fernando; Butrón, Ana

2016-01-27

Previous results suggest a relationship between maize hydroxycinnamate concentration in the pith tissues and resistance to stem tunneling by Mediterranean corn borer (MCB, Sesamia nonagrioides Lef.) larvae. This study performs a more precise experiment, mapping an F2 derived from the cross between two inbreds with contrasting levels for hydroxycinnamates EP125 × PB130. We aimed to co-localize genomic regions involved in hydroxycinnamate synthesis and resistance to MCB and to highlight the particular route for each hydroxycinnamate component in relation to the better known phenylpropanoid pathway. Seven quantitative trait loci (QTLs) for p-coumarate, two QTLs for ferulate, and seven QTLs for total diferulates explained 81.7, 26.9, and 57.8% of the genotypic variance, respectively. In relation to borer resistance, alleles for increased hydroxycinnamate content (affecting one or more hydroxycinnamate compounds) could be associated with favorable effects on stem resistance to MCB, particularly the putative role of p-coumarate in borer resistance.

Specific Armadillo Repeat Sequences Facilitate β-Catenin Nuclear Transport in Live Cells via Direct Binding to Nucleoporins Nup62, Nup153, and RanBP2/Nup358*

PubMed Central

Sharma, Manisha; Jamieson, Cara; Johnson, Michael; Molloy, Mark P.; Henderson, Beric R.

2012-01-01

β-Catenin transduces the Wnt signal from the membrane to nucleus, and certain gene mutations trigger its nuclear accumulation leading to cell transformation and cancer. β-Catenin shuttles between the nucleus and cytoplasm independent of classical Ran/transport receptor pathways, and this movement was previously hypothesized to involve the central Armadillo (Arm) domain. Fluorescence recovery after photobleaching (FRAP) assays were used to delineate functional transport regions of the Arm domain in living cells. The strongest nuclear import/export activity was mapped to Arm repeats R10–12 using both in vivo FRAP and in vitro export assays. By comparison, Arm repeats R3–8 of β-catenin were highly active for nuclear import but displayed a comparatively weak export activity. We show for the first time using purified components that specific Arm sequences of β-catenin interact directly in vitro with the FG repeats of the nuclear pore complex (NPC) components Nup62, Nup98, and Nup153, indicating an independent ability of β-catenin to traverse the NPC. Moreover, a proteomics screen identified RanBP2/Nup358 as a binding partner of Arm R10–12, and β-catenin was confirmed to interact with endogenous and ectopic forms of Nup358. We further demonstrate that knock-down of endogenous Nup358 and Nup62 impeded the rate of nuclear import/export of β-catenin to a greater extent than that of importin-β. The Arm R10–12 sequence facilitated transport even when β-catenin was bound to the Arm-binding partner LEF-1, and its activity was stimulated by phosphorylation at Tyr-654. These findings provide functional evidence that the Arm domain contributes to regulated β-catenin transport through direct interaction with the NPC. PMID:22110128

The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis

PubMed Central

Derakhshani, Hooman; De Buck, Jeroen; Mortier, Rienske; Barkema, Herman W.; Krause, Denis O.; Khafipour, Ehsan

2016-01-01

Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that this dynamic network of microorganisms had an active role in intestinal homeostasis. PMID:27065983

Conditional ablation of the prorenin receptor in nephron progenitor cells results in developmental programming of hypertension.

PubMed

Song, Renfang; Kidd, Laura; Janssen, Adam; Yosypiv, Ihor V

2018-04-01

Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells (NPCs) of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump V-ATPase. Previously, we demonstrated that conditional ablation of the PRR in Six2 + NPCs in mice (Six2 PRR -/- ) causes early neonatal death. Here, we identified genes that are regulated by PRR in Six2 + NPCs FACS-isolated from Six2 PRR -/- and control kidneys on embryonic day E15.5 using whole-genome expression analysis. Seven genes with expression in CM cells previously shown to direct kidney development, including Notch1, β-catenin, Lef1, Lhx1, Jag1, and p53, were downregulated. The functional groups within the downregulated gene set included genes involved in embryonic and cellular development, renal regeneration, cellular assembly and organization, cell morphology, death and survival. Double-transgenic Six2 PRR -/- /BatGal + mice, a reporter strain for β-catenin transcriptional activity, showed decreased β-catenin activity in the UB in vivo. Reduced PRR gene dosage in heterozygous Six2 PRR +/- mice was associated with decreased glomerular number, segmental thickening of the glomerular basement membrane with focal podocyte foot process effacement, development of hypertension and increased soluble PRR (sPRR) levels in the urine at 2 months of age. Together, these data demonstrate that NPC PRR performs essential functions during nephrogenesis via control of hierarchy of genes that regulate critical cellular processes. Both reduced nephron endowment and augmented urine sPRR likely contribute to programming of hypertension in Six2 PRR +/- mice. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Loss of T-cadherin (CDH-13) regulates AKT signaling and desensitizes cells to apoptosis in melanoma.

PubMed

Bosserhoff, Anja K; Ellmann, Lisa; Quast, Annika S; Eberle, Juergen; Boyle, Glen M; Kuphal, Silke

2014-08-01

An understanding of signaling pathways is a basic requirement for the treatment of melanoma. Currently, kinases are at the center of melanoma therapies. According to our research, additional alternative molecules are equally important for development of melanoma. In this regard, cancer progression is, among other factors, driven by an altered adhesion via cadherins. For instance, the de-regulated expression of the adhesion molecule T-cadherin is found in various cancer types, including melanoma, and influences migration and invasion. T-cadherin is thought to affect cellular function largely through its signaling and not its adhesion properties because the molecule is anchored into the cell membrane by a glycosylphosphatidylinositol (GPI) moiety. However, detailed knowledge about the consequences of the loss of T-cadherin in melanoma is currently lacking. For this reason, we were interested in assessing which signaling pathways are initiated by T-cadherin. The tumor growth of subcutaneously injected T-cadherin-positive melanoma cells was diminished compared with T-cadherin-negative cells in nude mice. The difference in tumor volume was not due to decreased proliferation but rather due to increased apoptosis. After the expression of T-cadherin was induced, we detected V-AKT murine thymoma viral oncogene homolog (AKT) and FoxO3a hypophosphorylation accompanied by the downregulation of the antiapoptotic molecules BCL-2, BCL-x and Clusterin. Furthermore, we detected a diminished transcriptional activity of CREB and AP-1. We demonstrated that T-cadherin functions as a pro-apoptotic tumor suppressor that antagonizes AKT/CREB/AP-1/FoxO3a signaling, whereas NFκB, TCF/LEF and mTOR are not part of the T-cadherin signaling pathway. Notably, we found that the restoration of T-cadherin in melanoma cells causes sensitization to apoptosis induced by CD95/Fas antibody CH-11. © 2013 Wiley Periodicals, Inc.

Loss of Gi G-Protein-Coupled Receptor Signaling in Osteoblasts Accelerates Bone Fracture Healing.

PubMed

Wang, Liping; Hsiao, Edward C; Lieu, Shirley; Scott, Mark; O'Carroll, Dylan; Urrutia, Ashley; Conklin, Bruce R; Colnot, Celine; Nissenson, Robert A

2015-10-01

G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair. © 2015 American Society for Bone and Mineral Research.

Interlocking Nailing Versus Plating in Tibial Shaft Fractures in Adults: A Comparative Study.

PubMed

Mukherjee, Sagnik; Arambam, Mahendra Singh; Waikhom, Sanjib; Santosha; Masatwar, Pranav Vitthal; Maske, Rohan Gautam

2017-04-01

Tibial diaphyseal fractures are the commonest long bone fractures in adults, most commonly managed by intramedullary interlocking nailing. However, several meta-analysis show that locking plate osteosynthesis is equally effective in managing tibial diaphyseal fractures and are associated with less number of complications. To compare the results of fixation of tibial fractures following plating and nailing in terms of union, patient satisfaction and complications. A hospital based non randomized clinical trial was performed from September 2013 to August 2016 where closed or open diaphyseal or metaphyseo- diaphyseal fractures of the tibia (closed or open Gustilo Anderson type 1 through 3B) were included. Simple sequential allocation was used for allotting the patients to two groups, one for interlocking nailing and other for plating. The patients were followed up for clinical, radiographic and functional results. Forty patients with 41 involved limbs completed follow up for one year. The duration of surgery and average blood loss during surgery was 75.45±3.03 minutes and 165.00±5.31 ml respectively in case of nailing and 85.05±2.54 minutes and184.29±5.33 ml respectively in case of plating and their difference was statistically significant. In our study union was achieved in less than 20 weeks in 29 (70.8%) of the patients and 25-30 weeks in nine (22%) cases. The average time of union in our study was 19.55±0.69 weeks in case of interlocking nailing and 20.38±1.39 weeks in case of plating and there was no statistically significant difference between the two. However, there is statistically significant difference in the functional score in between the two groups in terms of Lower Extremity Functional Score (LEFS). Delayed union in one case of nailing and two cases of plating, valgus malunion in one case of nailing and joint stiffness in two cases each of nailing and plating were the major complications observed. There was no difference between the two modalities in terms of fracture union. Complications were lesser but more serious in case of plating. Patient satisfaction was more with plating.

Bmi1 overexpression in the cerebellar granule cell lineage of mice affects cell proliferation and survival without initiating medulloblastoma formation

PubMed Central

Behesti, Hourinaz; Bhagat, Heeta; Dubuc, Adrian M.; Taylor, Michael D.; Marino, Silvia

2013-01-01

SUMMARY BMI1 is a potent inducer of neural stem cell self-renewal and neural progenitor cell proliferation during development and in adult tissue homeostasis. It is overexpressed in numerous human cancers – including medulloblastomas, in which its functional role is unclear. We generated transgenic mouse lines with targeted overexpression of Bmi1 in the cerebellar granule cell lineage, a cell type that has been shown to act as a cell of origin for medulloblastomas. Overexpression of Bmi1 in granule cell progenitors (GCPs) led to a decrease in cerebellar size due to decreased GCP proliferation and repression of the expression of cyclin genes, whereas Bmi1 overexpression in postmitotic granule cells improved cell survival in response to stress by altering the expression of genes in the mitochondrial cell death pathway and of Myc and Lef-1. Although no medulloblastomas developed in ageing cohorts of transgenic mice, crosses with Trp53−/− mice resulted in a low incidence of medulloblastoma formation. Furthermore, analysis of a large collection of primary human medulloblastomas revealed that tumours with a BMI1high TP53low molecular profile are significantly enriched in Group 4 human medulloblastomas. Our data suggest that different levels and timing of Bmi1 overexpression yield distinct cellular outcomes within the same cellular lineage. Importantly, Bmi1 overexpression at the GCP stage does not induce tumour formation, suggesting that BMI1 overexpression in GCP-derived human medulloblastomas probably occurs during later stages of oncogenesis and might serve to enhance tumour cell survival. PMID:23065639

KCTD1 Suppresses Canonical Wnt Signaling Pathway by Enhancing β-catenin Degradation

PubMed Central

Wang, Fangmei; Huang, Wenhuan; Liang, Zhongheng; Xiao, Yuzhong; Wei, Ke; Wan, Zhenxing; Hu, Xiang; Xiang, Shuanglin; Ding, Xiaofeng; Zhang, Jian

2014-01-01

The canonical Wnt signaling pathway controls normal embryonic development, cellular proliferation and growth, and its aberrant activity results in human carcinogenesis. The core component in regulation of this pathway is β-catenin, but molecular regulation mechanisms of β-catenin stability are not completely known. Here, our recent studies have shown that KCTD1 strongly inhibits TCF/LEF reporter activity. Moreover, KCTD1 interacted with β-catenin both in vivo by co-immunoprecipitation as well as in vitro through GST pull-down assays. We further mapped the interaction regions to the 1-9 armadillo repeats of β-catenin and the BTB domain of KCTD1, especially Position Ala-30 and His-33. Immunofluorescence analysis indicated that KCTD1 promotes the cytoplasmic accumulation of β-catenin. Furthermore, protein stability assays revealed that KCTD1 enhances the ubiquitination/degradation of β-catenin in a concentration-dependent manner in HeLa cells. And the degradation of β-catenin mediated by KCTD1 was alleviated by the proteasome inhibitor, MG132. In addition, KCTD1-mediated β-catenin degradation was dependent on casein kinase 1 (CK1)- and glycogen synthase kinase-3β (GSK-3β)-mediated phosphorylation and enhanced by the E3 ubiquitin ligase β-transducin repeat-containing protein (β-TrCP). Moreover, KCTD1 suppressed the expression of endogenous Wnt downstream genes and transcription factor AP-2α. Finally, we found that Wnt pathway member APC and tumor suppressor p53 influence KCTD1-mediated downregulation of β-catenin. These results suggest that KCTD1 functions as a novel inhibitor of Wnt signaling pathway. PMID:24736394

Transcriptome analysis of the couch potato (CPO) protein reveals an expression pattern associated with early development in the salmon louse Caligus rogercresseyi.

PubMed

Gallardo-Escárate, Cristian; Valenzuela-Muñoz, Valentina; Nuñez-Acuña, Gustavo; Chávez-Mardones, Jacqueline; Maldonado-Aguayo, Waleska

2014-02-15

The couch potato (CPO) protein is a key biomolecule involved in regulating diapause through the RNA-binding process of the peripheral and central nervous systems in insects and also recently discovered in a few crustacean species. As such, ectoparasitic copepods are interesting model species that have no evidence of developmental arrest. The present study is the first to report on the cloning of a putative CPO gene from the salmon louse Caligus rogercresseyi (CrCPO), as identified by high-throughput transcriptome sequencing. In addition, the transcription expression in larvae and adults was evaluated using quantitative real-time PCR. The CrCPO cDNA sequence showed 3261 base pairs (bp), consisting of 713bp of 5' UTR, 1741bp of 3' UTR, and an open reading frame of 807bp encoding for 268 amino acids. The highly conserved RNA binding regions RNP2 (LFVSGL) and RNP1 (SPVGFVTF), as well the dimerization site (LEF), were also found. Furthermore, eight single nucleotide polymorphisms located in the untranslated regions and one located in the coding region were detected. Gene transcription analysis revealed that CrCPO has ubiquitous expression across larval stages and in adult individuals, with the highest expression from nauplius to copepodid stages. The present study suggests a putative biological function of CrCPO associated with the development of the nervous system in salmon lice and contributes molecular evidence for candidate genes related to host-parasite interactions. Copyright © 2013 Elsevier B.V. All rights reserved.

Caveolin-1–mediated Suppression of Cyclooxygenase-2 via a β-catenin-Tcf/Lef–dependent Transcriptional Mechanism Reduced Prostaglandin E2 Production and Survivin Expression

PubMed Central

Rodriguez, Diego A.; Tapia, Julio C.; Fernandez, Jaime G.; Torres, Vicente A.; Muñoz, Nicolas; Galleguillos, Daniela; Leyton, Lisette

2009-01-01

Augmented expression of cyclooxygenase-2 (COX-2) and enhanced production of prostaglandin E2 (PGE2) are associated with increased tumor cell survival and malignancy. Caveolin-1 is a scaffold protein that has been proposed to function as a tumor suppressor in human cancer cells, although mechanisms underlying this ability remain controversial. Intriguingly, the possibility that caveolin-1 regulates the expression of COX-2 has not been explored. Here we show that augmented caveolin-1 expression in cells with low basal levels of this protein, such as human colon cancer (HT29, DLD-1), breast cancer (ZR75), and embryonic kidney (HEK293T) cells reduced COX-2 mRNA and protein levels and β-catenin-Tcf/Lef and COX-2 gene reporter activity, as well as the production of PGE2 and cell proliferation. Moreover, COX-2 overexpression or PGE2 supplementation increased levels of the inhibitor of apoptosis protein survivin by a transcriptional mechanism, as determined by PCR analysis, survivin gene reporter assays and Western blotting. Furthermore, addition of PGE2 to the medium prevented effects attributed to caveolin-1–mediated inhibition of β-catenin-Tcf/Lef–dependent transcription. Finally, PGE2 reduced the coimmunoprecipitation of caveolin-1 with β-catenin and their colocalization at the plasma membrane. Thus, by reducing COX-2 expression, caveolin-1 interrupts a feedback amplification loop involving PGE2-induced signaling events linked to β-catenin/Tcf/Lef–dependent transcription of tumor survival genes including cox-2 itself and survivin. PMID:19244345

Electromagnetic scaling functions within the Green's function Monte Carlo approach

DOE PAGES

Rocco, N.; Alvarez-Ruso, L.; Lovato, A.; ...

2017-07-24

We have studied the scaling properties of the electromagnetic response functions of 4He and 12C nuclei computed by the Green's function Monte Carlo approach, retaining only the one-body current contribution. Longitudinal and transverse scaling functions have been obtained in the relativistic and nonrelativistic cases and compared to experiment for various kinematics. The characteristic asymmetric shape of the scaling function exhibited by data emerges in the calculations in spite of the nonrelativistic nature of the model. The results are mostly consistent with scaling of zeroth, first, and second kinds. Our analysis reveals a direct correspondence between the scaling and the nucleon-densitymore » response functions. In conclusion, the scaling function obtained from the proton-density response displays scaling of the first kind, even more evidently than the longitudinal and transverse scaling functions« less

Electromagnetic scaling functions within the Green's function Monte Carlo approach

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

Rocco, N.; Alvarez-Ruso, L.; Lovato, A.

We have studied the scaling properties of the electromagnetic response functions of 4He and 12C nuclei computed by the Green's function Monte Carlo approach, retaining only the one-body current contribution. Longitudinal and transverse scaling functions have been obtained in the relativistic and nonrelativistic cases and compared to experiment for various kinematics. The characteristic asymmetric shape of the scaling function exhibited by data emerges in the calculations in spite of the nonrelativistic nature of the model. The results are mostly consistent with scaling of zeroth, first, and second kinds. Our analysis reveals a direct correspondence between the scaling and the nucleon-densitymore » response functions. In conclusion, the scaling function obtained from the proton-density response displays scaling of the first kind, even more evidently than the longitudinal and transverse scaling functions« less

Improved switching reliability achieved in HfOx based RRAM with mountain-like surface-graphited carbon layer

NASA Astrophysics Data System (ADS)

Tao, Ye; Ding, Wentao; Wang, Zhongqiang; Xu, Haiyang; Zhao, Xiaoning; Li, Xuhong; Liu, Weizhen; Ma, Jiangang; Liu, Yichun

2018-05-01

In this work, we demonstrated an effective method to improve the switching reliability of HfOx based RRAM device by inserting mountain-like surface-graphited carbon (MSGC) layer. The MSGC layer was fabricated through thermal annealing of amorphous carbon (a-C) film with high sp2 proportion (49.7%) under 500 °C on Pt substrate, whose characteristics were validated by XPS and Raman spectrums. The local electric-field (LEF) was enhanced around the nanoscale tips of MSGC layer due to large surface curvature, which leads to simplified CFs and localization of resistive switching region. It takes responsibility to the reduction of high/low resistance states (HRS/LRS) fluctuation from 173.8%/64.9% to 23.6%/6.5%, respectively. In addition, the resulting RRAM devices exhibited fast switching speed (<65 ns), good retention (>104 s at 85 °C) and low cycling degradation. This method could be promising to develop reliable and repeatable high-performance RRAM for practical applications.

TCF and Groucho-related genes influence pituitary growth and development.

PubMed

Brinkmeier, Michelle L; Potok, Mary Anne; Cha, Kelly B; Gridley, Thomas; Stifani, Stefano; Meeldijk, Jan; Clevers, Hans; Camper, Sally A

2003-11-01

Mutations in the prophet of PIT1 gene (PROP1) are the most common cause of multiple pituitary hormone deficiency in humans; however, the mechanism of PROP1 action is not well understood. We report that Prop1 is essential for dorsally restricted expression of a Groucho-related gene, transducin-like enhancer of split 3 (Tle3), which encodes a transcriptional corepressor. Deficiency of a related gene, amino terminal enhancer of split (Aes), causes pituitary anomalies and growth insufficiency. TLE3 and AES have been shown to interact with TCF/LEF (transcripiton factors of the T cell-specific and lymphoid enhancer specific group) family members in cell culture systems. In the absence of TCF4 (Tcf7L2), Prop1 levels are elevated, pituitary hyperplasia ensues and palate closure is abnormal. Thus, we demonstrate that Tcf4 and Aes influence pituitary growth and development, and place Tcf4 and Tle3 in the genetic hierarchy with Prop1.

Conduit for high temperature transfer of molten semiconductor crystalline material

NASA Technical Reports Server (NTRS)

Fiegl, George (Inventor); Torbet, Walter (Inventor)

1983-01-01

A conduit for high temperature transfer of molten semiconductor crystalline material consists of a composite structure incorporating a quartz transfer tube as the innermost member, with an outer thermally insulating layer designed to serve the dual purposes of minimizing heat losses from the quartz tube and maintaining mechanical strength and rigidity of the conduit at the elevated temperatures encountered. The composite structure ensures that the molten semiconductor material only comes in contact with a material (quartz) with which it is compatible, while the outer layer structure reinforces the quartz tube, which becomes somewhat soft at molten semiconductor temperatures. To further aid in preventing cooling of the molten semiconductor, a distributed, electric resistance heater is in contact with the surface of the quartz tube over most of its length. The quartz tube has short end portions which extend through the surface of the semiconductor melt and which are lef bare of the thermal insulation. The heater is designed to provide an increased heat input per unit area in the region adjacent these end portions.

Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia.

PubMed

Forero-Castro, Maribel; Robledo, Cristina; Benito, Rocío; Bodega-Mayor, Irene; Rapado, Inmaculada; Hernández-Sánchez, María; Abáigar, María; Maria Hernández-Sánchez, Jesús; Quijada-Álamo, Miguel; María Sánchez-Pina, José; Sala-Valdés, Mónica; Araujo-Silva, Fernanda; Kohlmann, Alexander; Luis Fuster, José; Arefi, Maryam; de Las Heras, Natalia; Riesco, Susana; Rodríguez, Juan N; Hermosín, Lourdes; Ribera, Jordi; Camos Guijosa, Mireia; Ramírez, Manuel; de Heredia Rubio, Cristina Díaz; Barragán, Eva; Martínez, Joaquín; Ribera, José M; Fernández-Ruiz, Elena; Hernández-Rivas, Jesús-María

2017-07-11

In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genetic alterations associated with poor prognosis is still of importance. We determined the frequency and prognostic impact of somatic mutations in children and adult cases with B-ALL treated with Spanish PETHEMA and SEHOP protocols. Mutational status of hotspot regions of TP53, JAK2, PAX5, LEF1, CRLF2 and IL7R genes was determined by next-generation deep sequencing in 340 B-ALL patients (211 children and 129 adults). The associations between mutation status and clinicopathological features at the time of diagnosis, treatment outcome and survival were assessed. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with overall survival (OS), event-free survival (EFS) and relapse rate (RR). A mutation rate of 12.4% was identified. The frequency of adult mutations was higher (20.2% vs 7.6%, P=0.001). TP53 was the most frequently mutated gene (4.1%), followed by JAK2 (3.8%), CRLF2 (2.9%), PAX5 (2.4%), LEF1 (0.6%) and IL7R (0.3%). All mutations were observed in B-ALL without ETV6-RUNX1 (P=0.047) or BCR-ABL1 fusions (P<0.0001). In children, TP53mut was associated with lower OS (5-year OS: 50% vs 86%, P=0.002) and EFS rates (5-year EFS: 50% vs 78.3%, P=0.009) and higher RR (5-year RR: 33.3% vs 18.6% P=0.037), and was independently associated with higher RR (hazard ratio (HR)=4.5; P=0.04). In adults, TP53mut was associated with a lower OS (5-year OS: 0% vs 43.3%, P=0.019) and a higher RR (5-year RR: 100% vs 61.4%, P=0.029), whereas JAK2mut was associated with a lower EFS (5-year EFS: 0% vs 30.6%, P=0.035) and a higher RR (5-year RR: 100% vs 60.4%, P=0.002). TP53mut was an independent risk factor for shorter OS (HR=2.3; P=0.035) and, together with JAK2mut, also were independent markers of poor prognosis for RR (TP53mut: HR=5.9; P=0.027 and JAK2mut: HR=5.6; P=0.036). TP53mut and JAK2mut are potential biomarkers associated with poor prognosis in B-ALL patients.

NOVEL MECHANISMS FOR THE VITAMIN D RECEPTOR (VDR) IN THE SKIN AND IN SKIN CANCER

PubMed Central

Bikle, Daniel D.; Oda, Yuko; Tu, Chia-Ling; Jiang, Yan

2014-01-01

The VDR acting with or without its principal ligand 1,25(OH)2D regulates two central processes in the skin, interfollicular epidermal (IFE) differentiation and hair follicle cycling (HFC). Calcium is an important co-regulator with 1,25(OH)2 D at least of epidermal differentiation. Knockout of the calcium sensing receptor (CaSR) in addition to VDR accelerates the development of skin cancer in mice on a low calcium diet. Coactivators such as Mediator 1 (aka DRIP205) and steroid receptor coactivator 3 (SRC3) regulate VDR function at different stages of the differentiation process, with Med1 essential for hair follicle differentiation and early stages of epidermal differentiation and proliferation and SRC3 essential for the latter stages of differentiation including formation of the permeability barrier and innate immunity. The corepressor of VDR, hairless (HR), is essential for hair follicle cycling, although its effect on epidermal differentiation in vivo is minimal. In its regulation of HFC and IFE VDR controls two pathways—wnt/β-catenin and sonic hedgehog (Shh). In the absence of VDR these pathways are overexpressed leading to tumor formation. Whereas VDR binding to β-catenin may block its activation of TCF/LEF1 sites, β-catenin binding to VDR may enhance its activation of VDREs. 1,25(OH)2D promotes but may not be required for these interactions. Suppression of Shh expression by VDR, on the other hand, requires 1,25(OH)2D. The major point of emphasis is that the role of VDR in the skin involves a number of novel mechanisms, both 1,25(OH)2D dependent and independent, that when disrupted interfere with IFE differentiation and HFC, predisposing to cancer formation. PMID:25445917

Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review

PubMed Central

Iqbal, Kundan; Kelly, Clive

2015-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5–1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor α agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease. PMID:26622326

Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage.

PubMed

Waraky, Ahmed; Lin, Yingbo; Warsito, Dudi; Haglund, Felix; Aleem, Eiman; Larsson, Olle

2017-11-03

We have previously shown that the insulin-like growth factor 1 receptor (IGF-1R) translocates to the cell nucleus, where it binds to enhancer-like regions and increases gene transcription. Further studies have demonstrated that nuclear IGF-1R (nIGF-1R) physically and functionally interacts with some nuclear proteins, i.e. the lymphoid enhancer-binding factor 1 (Lef1), histone H3, and Brahma-related gene-1 proteins. In this study, we identified the proliferating cell nuclear antigen (PCNA) as a nIGF-1R-binding partner. PCNA is a pivotal component of the replication fork machinery and a main regulator of the DNA damage tolerance (DDT) pathway. We found that IGF-1R interacts with and phosphorylates PCNA in human embryonic stem cells and other cell lines. In vitro MS analysis of PCNA co-incubated with the IGF-1R kinase indicated tyrosine residues 60, 133, and 250 in PCNA as IGF-1R targets, and PCNA phosphorylation was followed by mono- and polyubiquitination. Co-immunoprecipitation experiments suggested that these ubiquitination events may be mediated by DDT-dependent E2/E3 ligases ( e.g. RAD18 and SHPRH/HLTF). Absence of IGF-1R or mutation of Tyr-60, Tyr-133, or Tyr-250 in PCNA abrogated its ubiquitination. Unlike in cells expressing IGF-1R, externally induced DNA damage in IGF-1R-negative cells caused G 1 cell cycle arrest and S phase fork stalling. Taken together, our results suggest a role of IGF-1R in DDT. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

TCF7L1 recruits CtBP and HDAC1 to repress DICKKOPF4 gene expression in human colorectal cancer cells

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

Eshelman, Melanie A.; Shah, Meera; Raup-Konsavage, Wesley M.

The T-cell factor/Lymphoid enhancer factor (TCF/LEF; hereafter TCF) family of transcription factors are critical regulators of colorectal cancer (CRC) cell growth. Of the four TCF family members, TCF7L1 functions predominantly as a repressor of gene expression. Few studies have addressed the role of TCF7L1 in CRC and only a handful of target genes regulated by this repressor are known. By silencing TCF7L1 expression in HCT116 cells, we show that it promotes cell proliferation and tumorigenesis in vivo by driving cell cycle progression. Microarray analysis of transcripts differentially expressed in control and TCF7L1-silenced CRC cells identified genes that control cell cycle kinetics andmore » cancer pathways. Among these, expression of the Wnt antagonist DICKKOPF4 (DKK4) was upregulated when TCF7L1 levels were reduced. We found that TCF7L1 recruits the C-terminal binding protein (CtBP) and histone deacetylase 1 (HDAC1) to the DKK4 promoter to repress DKK4 gene expression. In the absence of TCF7L1, TCF7L2 and β-catenin occupancy at the DKK4 promoter is stimulated and DKK4 expression is increased. These findings uncover a critical role for TCF7L1 in repressing DKK4 gene expression to promote the oncogenic potential of CRCs. - Highlights: • TCF7L1 promotes colorectal cancer cell proliferation and tumorigenesis. • DICKKOPF4 is directly regulated by TCF7L1. • TCF7L1 recruits CtBP and HDAC1 to repress DKK4 gene expression.« less

Scaling within the spectral function approach

NASA Astrophysics Data System (ADS)

Sobczyk, J. E.; Rocco, N.; Lovato, A.; Nieves, J.

2018-03-01

Scaling features of the nuclear electromagnetic response functions unveil aspects of nuclear dynamics that are crucial for interpreting neutrino- and electron-scattering data. In the large momentum-transfer regime, the nucleon-density response function defines a universal scaling function, which is independent of the nature of the probe. In this work, we analyze the nucleon-density response function of 12C, neglecting collective excitations. We employ particle and hole spectral functions obtained within two distinct many-body methods, both widely used to describe electroweak reactions in nuclei. We show that the two approaches provide compatible nucleon-density scaling functions that for large momentum transfers satisfy first-kind scaling. Both methods yield scaling functions characterized by an asymmetric shape, although less pronounced than that of experimental scaling functions. This asymmetry, only mildly affected by final state interactions, is mostly due to nucleon-nucleon correlations, encoded in the continuum component of the hole spectral function.

Validation of the Early Functional Abilities scale: An assessment of four dimensions in early recovery after traumatic brain injury.

PubMed

Poulsen, Ingrid; Kreiner, Svend; Engberg, Aase W

2018-02-13

The Early Functional Abilities scale assesses the restoration of brain function after brain injury, based on 4 dimensions. The primary objective of this study was to evaluate the validity, objectivity, reliability and measurement precision of the Early Functional Abilities scale by Rasch model item analysis. A secondary objective was to examine the relationship between the Early Functional Abilities scale and the Functional Independence Measurement™, in order to establish the criterion validity of the Early Functional Abilities scale and to compare the sensitivity of measurements using the 2 instruments. The Rasch analysis was based on the assessment of 408 adult patients at admission to sub-acute rehabilitation in Copenhagen, Denmark after traumatic brain injury. The Early Functional Abilities scale provides valid and objective measurement of vegetative (autonomic), facio-oral, sensorimotor and communicative/cognitive functions. Removal of one item from the sensorimotor scale confirmed unidimensionality for each of the 4 subscales, but not for the entire scale. The Early Functional Abilities subscales are sensitive to differences between patients in ranges in which the Functional Independence Measurement™ has a floor effect. The Early Functional Abilities scale assesses the early recovery of important aspects of brain function after traumatic brain injury, but is not unidimensional. We recommend removal of the "standing" item and calculation of summary subscales for the separate dimensions.

On the relative importance of pool morphology and woody debris to distributions of shrimp in a Puerto Rican headwater stream

USGS Publications Warehouse

Pyron, M.; Covich, A.P.; Black, R.W.

1999-01-01

In this paper, we report the sizes and distributional orientation of woody debris in a headwater rainforest stream in the Luquillo Experimental Forest (LEF), Puerto Rico. We also provide results of a 4-month study of a wood addition experiment designed to increase cover for benthic macroinvertebrates (freshwater shrimp). We added branch-sized woody debris to 20 pools in three streams. We trapped four species of freshwater shrimp (two species of benthic detritivores and two predatory shrimp species) during each of the 4 months following wood additions. An analysis of pool morphology (maximum depth, surface area and volume) provided a useful predictor of shrimp abundances. In general, numbers of shrimps increased with sizes of stream pools. A repeated measures ANOVA demonstrated no effect of woody debris additions on total numbers of shrimp per pool area. Two detritivore species (Atya lanipes, a filter feeder and Xiphocaris elongata, a shredder) decreased in abundance with increased woody debris and there was no statistical relationship between woody debris additions and predators (Macrobrachium carcinus and M. crenulatum). Small woody debris additions may have altered flow velocities that were important to filter-feeding Atya at the microhabitat scale, although the overall velocities within pools were not altered by wood additions. Lower numbers of Atya and Xiphocaris in two of the three streams may result from the occurrence of two predaceous fishes (American eel and mountain mullet) and more predatory Macrobrachium in these streams. One likely interpretation of the results of this study is that the stream pools in these study reaches had sufficient habitat structure provided by numerous rock crevices (among large rocks and boulders) to provide refuge from predators. Addition of woody debris did not add significantly to the existing structure. These results may not apply to stream channels with sand and gravel substrata where crevices and undercut banks are lacking and where woody debris often plays a major role by providing structure and refuge.

Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.

PubMed

Quagliariello, Andrea; Del Chierico, Federica; Russo, Alessandra; Reddel, Sofia; Conte, Giulia; Lopetuso, Loris R; Ianiro, Gianluca; Dallapiccola, Bruno; Cardona, Francesco; Gasbarrini, Antonio; Putignani, Lorenza

2018-01-01

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides , Odoribacter , and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter . In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.

Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections

PubMed Central

Quagliariello, Andrea; Del Chierico, Federica; Russo, Alessandra; Reddel, Sofia; Conte, Giulia; Lopetuso, Loris R.; Ianiro, Gianluca; Dallapiccola, Bruno; Cardona, Francesco; Gasbarrini, Antonio; Putignani, Lorenza

2018-01-01

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4–8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson’s analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies. PMID:29686658

Interlocking Nailing Versus Plating in Tibial Shaft Fractures in Adults: A Comparative Study

PubMed Central

Arambam, Mahendra Singh; Waikhom, Sanjib; Santosha; Masatwar, Pranav Vitthal; Maske, Rohan Gautam

2017-01-01

Introduction Tibial diaphyseal fractures are the commonest long bone fractures in adults, most commonly managed by intramedullary interlocking nailing. However, several meta-analysis show that locking plate osteosynthesis is equally effective in managing tibial diaphyseal fractures and are associated with less number of complications. Aim To compare the results of fixation of tibial fractures following plating and nailing in terms of union, patient satisfaction and complications. Materials and Methods A hospital based non randomized clinical trial was performed from September 2013 to August 2016 where closed or open diaphyseal or metaphyseo- diaphyseal fractures of the tibia (closed or open Gustilo Anderson type 1 through 3B) were included. Simple sequential allocation was used for allotting the patients to two groups, one for interlocking nailing and other for plating. The patients were followed up for clinical, radiographic and functional results. Results Forty patients with 41 involved limbs completed follow up for one year. The duration of surgery and average blood loss during surgery was 75.45±3.03 minutes and 165.00±5.31 ml respectively in case of nailing and 85.05±2.54 minutes and184.29±5.33 ml respectively in case of plating and their difference was statistically significant. In our study union was achieved in less than 20 weeks in 29 (70.8%) of the patients and 25-30 weeks in nine (22%) cases. The average time of union in our study was 19.55±0.69 weeks in case of interlocking nailing and 20.38±1.39 weeks in case of plating and there was no statistically significant difference between the two. However, there is statistically significant difference in the functional score in between the two groups in terms of Lower Extremity Functional Score (LEFS). Delayed union in one case of nailing and two cases of plating, valgus malunion in one case of nailing and joint stiffness in two cases each of nailing and plating were the major complications observed. Conclusion There was no difference between the two modalities in terms of fracture union. Complications were lesser but more serious in case of plating. Patient satisfaction was more with plating. PMID:28571220

Ten-Year Review of Rating Scales, VII: Scales Assessing Functional Impairment

ERIC Educational Resources Information Center

Winters, Nancy C.; Collett, Brent R.; Myers, Kathleen M.

2005-01-01

Objective: This is the seventh in a series of 10-year reviews of rating scales. Here the authors present scales measuring functional impairment, a sequela of mental illness. The measurement of functional impairment has assumed importance with the recognition that symptom resolution does not necessarily correlate with functional improvement.…

Variable responses of human microbiomes to dietary supplementation with resistant starch.

PubMed

Venkataraman, A; Sieber, J R; Schmidt, A W; Waldron, C; Theis, K R; Schmidt, T M

2016-06-29

The fermentation of dietary fiber to various organic acids is a beneficial function provided by the microbiota in the human large intestine. In particular, butyric acid contributes to host health by facilitating maintenance of epithelial integrity, regulating inflammation, and influencing gene expression in colonocytes. We sought to increase the concentration of butyrate in 20 healthy young adults through dietary supplementation with resistant starch (unmodified potato starch-resistant starch (RS) type 2). Fecal samples were collected from individuals to characterize butyrate concentration via liquid chromatography and composition of the microbiota via surveys of 16S rRNA-encoding gene sequences from the Illumina MiSeq platform. Random Forest and LEfSe analyses were used to associate responses in butyrate production to features of the microbiota. RS supplementation increased fecal butyrate concentrations in this cohort from 8 to 12 mmol/kg wet feces, but responses varied widely between individuals. Individuals could be categorized into three groups based upon butyrate concentrations before and during RS: enhanced, high, and low (n = 11, 3, and 6, respectively). Fecal butyrate increased by 67 % in the enhanced group (from 9 to 15 mmol/kg), while it remained ≥11 mmol/kg in the high group and ≤8 mmol/kg in the low group. Microbiota analyses revealed that the relative abundance of RS-degrading organisms-Bifidobacterium adolescentis or Ruminococcus bromii-increased from ~2 to 9 % in the enhanced and high groups, but remained at ~1.5 % in the low group. The lack of increase in RS-degrading bacteria in the low group may explain why there was no increase in fecal butyrate in response to RS. The microbiota of individuals in the high group were characterized by an elevated abundance of the butyrogenic microbe Eubacterium rectale (~6 % in high vs. 3 % in enhanced and low groups) throughout the study. We document the heterogeneous responses in butyrate concentrations upon RS supplementation and identify characteristic of the microbiota that appear to underlie this variation. This study complements and extends other studies that call for personalized approaches to manage beneficial functions provided by gut microbiomes.

[Study on Microbial Diversity of Peri-implantitis Subgingival by High-throughput Sequencing].

PubMed

Li, Zhi-jie; Wang, Shao-guo; Li, Yue-hong; Tu, Dong-xiang; Liu, Shi-yun; Nie, Hong-bing; Li, Zhi-qiang; Zhang, Ju-mei

2015-07-01

To study microbial diversity of peri-implantitis subgingival with high-throughput sequencing, and investigate microbiological etiology of peri-implantitis. Subgingival plaques were sampled from the patients with peri-implantitis (D group) and non-peri-implantitis subjects (N group). The microbiological diversity of the subgingival plaques was detected by sequencing V4 region of 16S rRNA with Illumina Miseq platform. The diversity of the community structure was analyzed using Mothur software. A total of 156 507 gene sequences were detected in nine samples and 4 402 operational taxonomic units (OTUs) were found. Selenomonas, Pseudomonas, and Fusobacterium were dominant bacteria in D group, while Fusobacterium, Veillonella and Streptococcus were dominant bacteria in N group. Differences between peri-implantitis and non-peri-implantitis bacterial communities were observed at all phylogenetic levels by LEfSe, which was also found in PcoA test. The occurrence of peri-implantitis is not only related to periodontitis pathogenic microbe, but also related with the changes of oral microbial community structure. Treponema, Herbaspirillum, Butyricimonas and Phaeobacte may be closely related to the occurrence and development of peri-implantitis.

Evaluation of the Microbial Diversity in Amyotrophic Lateral Sclerosis Using High-Throughput Sequencing.

PubMed

Fang, Xin; Wang, Xin; Yang, Shaoguo; Meng, Fanjing; Wang, Xiaolei; Wei, Hua; Chen, Tingtao

2016-01-01

More and more evidences indicate that diseases of the central nervous system have been seriously affected by fecal microbes. However, little work is done to explore interaction between amyotrophic lateral sclerosis (ALS) and fecal microbes. In the present study, high-throughput sequencing method was used to compare the intestinal microbial diversity of healthy people and ALS patients. The principal coordinate analysis, Venn and unweighted pair-group method using arithmetic averages (UPGMA) showed an obvious microbial changes between healthy people (group H) and ALS patients (group A), and the average ratios of Bacteroides , Faecalibacterium , Anaerostipes , Prevotella , Escherichia , and Lachnospira at genus level between ALS patients and healthy people were 0.78, 2.18, 3.41, 0.35, 0.79, and 13.07. Furthermore, the decreased Firmicutes/Bacteroidetes ratio at phylum level using LEfSE (LDA > 4.0), together with the significant increased genus Dorea (harmful microorganisms) and significant reduced genus Oscillibacter , Anaerostipes , Lachnospiraceae (beneficial microorganisms) in ALS patients, indicated that the imbalance in intestinal microflora constitution had a strong association with the pathogenesis of ALS.

Inflammation protects copper deficient rats from carbon tetrachloride toxicity

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

Yang, F.L.; Joseph, E.; DiSilvestro, R.A.

1991-03-11

Copper deficient rats show low resistance to CCl{sub 4}, possibly due to low liver Cu-Zn superoxide dismutase (SOD) activities. If Cu-Zn SOD is involved, deficiency effects should be aggravated by inflammation which further lowers Cu-Zn SOD activities in deficient rats. On the contrary, inflammation from 0.1 ml turpentine (im, lef) protected these rats from CCl{sub 4} damage assessed by serum activities of 2 liver enzymes. CCl{sub 4} was given ip at 200 {mu}l/kg, 48 h after turpentine, 24 h before sacrifice. Rats were fed low copper for 40 days before CCl{sub 4} challenge. Inflammation also protected rats fed adequate coppermore » from injury, though injury in noninflamed rats was less than with noninflamed deficients. Protection could result from the large increase observed in liver metallothionein, an induction not restricted by copper deficiency. Alternatively, inflammation may block P-450 activation of CCl{sub 4}. Both explanations are currently under investigation, as is the role, if any, of Cu-Zn SOD in resisting CCl{sub 4} injury.« less

β-catenin induces expression of prohibitin gene in acute leukemic cells

PubMed Central

Kim, Dong Min; Jang, Hanbit; Shin, Myung Geun; Kim, Jeong-Hoon; Shin, Sang Mo; Min, Sang-Hyun; Kim, Il-Chul

2017-01-01

Prohibitin (PHB) is a multifunctional protein conserved in eukaryotic systems and shows various expression levels in tumor cells. However, regulation of PHB is not clearly understood. Here, we focused on the regulation of PHB expression by Wnt signaling, one of dominant regulatory signals in various leukemic cells. High mRNA levels of PHB were found in half of clinical leukemia samples. PHB expression was increased by inhibition of the MAPK pathway and decreased by activation of EGF signal. Although cell proliferating signals downregulated the transcription of PHB, treatment with lithium chloride, an analog of the Wnt signal, induced PHB level in various cell types. We identified the TCF-4/LEF-1 binding motif, CATCTG, in the promoter region of PHB by site-directed mutagenesis and ChIP assay. This β-catenin-mediated activation of PHB expression was independent of c-MYC activation, a product of Wnt signaling. These data indicate that PHB is a direct target of β-catenin and the increased level of PHB in leukemia can be regulated by Wnt signaling. PMID:28440457

Chemical Changes during Maize Tissue Aging and Its Relationship with Mediterranean Corn Borer Resistance.

PubMed

López-Malvar, Ana; Ordás, Bernardo; Souto, Carlos; Encina, Antonio; Malvar, Rosa A; Santiago, Rogelio

2017-10-25

The Mediterranean corn borer (MCB), Sesamia nonagrioides Lef, is an important pest of maize in temperate areas, causing significant stalk lodging and yield losses. The main goals of this study were to determine possible changes in chemical traits (phenols, flavonoids, anthocyanins, sugars, fibers, and lignin) during plant development after the flowering stage and to assess how those traits may differ in diverse genotypes of maize, such as MCB resistant and susceptible. Higher values for some particular traits in more mature tissues seemed to increase their effectiveness against the MCB attack. A decreased amount of borer damage in the field was recorded in the resistant inbred line and in older tissues (7.90 cm vs 31.70 cm as the mean for the stalk tunnel length). In accordance with these results, the resistant inbred line showed a higher degree of hemicellulose cross-linkage (due to ferulic and diferulic acids), higher soluble sugar content, and higher stalk strength. The use of resistant varieties and early sowings is highly recommended as an integrated approach to reduce the yield losses produced by this pest.

The effect of sebocytes cultured from nevus sebaceus on hair growth.

PubMed

Lee, Weon Ju; Cha, Hyun Wuk; Lim, Hyun Jung; Lee, Seok-Jong; Kim, Do Won

2012-10-01

Sebaceous glands are known to affect hair growth. Nevus sebaceus, a sebaceous gland hamartomas, presents as hairless patches. In this study, cultures of nevus sebaceus sebocytes (NSS) and normal scalp hair follicle sebocytes (NS) were used in performance of microarray, RT-PCR, western blot assay and immunofluorescence staining. NSS- and NS-conditioned media were also added to the culture of outer root sheath cells (ORSCs), dermal papilla cells (DPCs) or normal scalp hair follicle sebocytes. Results of this study showed a decrease in the survival rate of ORSCs and DPCs and hair growth in the NSS-conditioned medium-treated group, compared with the control and NS-conditioned medium-treated groups. An increase in expression of fibroblast growth factor (FGF)-5, Dickkopf-1 and inflammatory cytokines and a decrease in expression of Wnt10b and Lef1 were observed. In conclusion, NSS showed an increase in expression of hair growth-suppressing bioactive factors, including FGF-5, and a decrease in expression of hair growth-stimulating factors. © 2012 John Wiley & Sons A/S.

β-catenin is required for taste bud cell renewal and behavioral taste perception in adult mice.

PubMed

Gaillard, Dany; Bowles, Spencer G; Salcedo, Ernesto; Xu, Mingang; Millar, Sarah E; Barlow, Linda A

2017-08-01

Taste stimuli are transduced by taste buds and transmitted to the brain via afferent gustatory fibers. Renewal of taste receptor cells from actively dividing progenitors is finely tuned to maintain taste sensitivity throughout life. We show that conditional β-catenin deletion in mouse taste progenitors leads to rapid depletion of progenitors and Shh+ precursors, which in turn causes taste bud loss, followed by loss of gustatory nerve fibers. In addition, our data suggest LEF1, TCF7 and Wnt3 are involved in a Wnt pathway regulatory feedback loop that controls taste cell renewal in the circumvallate papilla epithelium. Unexpectedly, taste bud decline is greater in the anterior tongue and palate than in the posterior tongue. Mutant mice with this regional pattern of taste bud loss were unable to discern sweet at any concentration, but could distinguish bitter stimuli, albeit with reduced sensitivity. Our findings are consistent with published reports wherein anterior taste buds have higher sweet sensitivity while posterior taste buds are better tuned to bitter, and suggest β-catenin plays a greater role in renewal of anterior versus posterior taste buds.

Isolation of a Novel Human Gene, MARKL1, Homologous to MARK3 and Its Involvement in Hepatocellular Carcinogenesis1

PubMed Central

Kato, Tatsushi; Satoh, Seiji; Okabe, Hiroshi; Kitahara, Osamu; Ono, Kenji; Kihara, Chikashi; Tanaka, Toshihiro; Tsunoda, Tatsuhiko; Yamaoka, Yoshio; Nakamura, Yusuke; Furukawa, Yoichi

2001-01-01

Abstract Activation of the Wnt-signaling pathway is known to play a crucial role in carcinogenesis of various human organs including the colon, liver, prostate, and endometrium. To investigate the mechanisms underlying hepatocellular carcinogenesis, we attempted to identify genes regulated by β-catenin/Tcf complex in a human hepatoma cell line, HepG2, in which an activated form of β-catenin is expressed. By means of cDNA microarray, we isolated a novel human gene, termed MARKL1 (MAP/microtubule affinity-regulating kinase-like 1), whose expression was downregulated in response to decreased Tcf/LEF1 activity. The transcript expressed in liver consisted of 3529 nucleotides that contained an open reading frame of 2256 nucleotides, encoding 752 amino acids homologous to human MARK3 (MAP/microtubule affinity-regulating kinase 3). Expression levels of MARKL1 were markedly elevated in eight of nine HCCs in which nuclear accumulation of β-catenin was observed, which may suggest that MARKL1 plays some role in hepatocellular carcinogenesis. PMID:11326310

The Anti-Helminthic Niclosamide Inhibits Wnt/Frizzled1 Signaling†

PubMed Central

Chen, Minyong; Wang, Jiangbo; Lu, Jiuyi; Bond, Michael C.; Ren, Xiu-Rong; Lyerly, H. Kim; Barak, Larry S.; Chen, Wei

2009-01-01

Wnt proteins bind to seven-transmembrane Frizzled receptors to mediate the important developmental, morphogenetic, and tissue-regenerative effects of Wnt signaling. Dysregulated Wnt signaling is associated with many cancers. Currently there exist no drug candidates, or even tool compounds that modulate Wnt-mediated receptor trafficking, and subsequent Wnt signaling. We examined libraries of FDA-approved drugs for their utility as Frizzled internalization modulators, employing a primary imaged-based GFP-fluorescence assay that uses Frizzled1 endocytosis as the readout. We now report that the anti-helminthic niclosamide, a drug used for the treatment of tapeworm, promotes Frizzled1 endocytosis, down regulates Dishevelled-2 protein, and inhibits Wnt3A-stimulated β-catenin stabilization and LEF/TCF reporter activity. Additionally, following niclosamide mediated internalization, the Frizzled1 receptor co-localizes in vesicles containing Transferrin and agonist-activated β2-adrenergic receptor. Therefore, niclosamide may serve as a negative modulator of Wnt/Frizzled1 signaling by depleting up-stream signaling molecules (i.e. Frizzled and Dishevelled), and moreover may provide a valuable means to study the physiological consequences of Wnt signaling. PMID:19772353

Different effection of p.1125Val>Ala and rs11954856 in APC on Wnt signaling pathway.

PubMed

Li, Fei-Feng; Zhao, Zhi-Xun; Yan, Peng; Wang, Song; Liu, Zheng; Zhang, Qiong; Zhang, Xiao-Ning; Sun, Chang-Hao; Wang, Xi-Shan; Wang, Gui-Yu; Liu, Shu-Lin

2017-09-19

Colorectal cancer (CRC) is among the most common and fatal forms of solid tumors worldwide and more than two thirds of CRC and adenomas patients have APC gene mutations. APC is a key regulator in the Wnt/β-catenin signaling pathway but its roles in CRC remains to be elucidated. In this study, we compared APC genes between CRC patients and controls to determine possible associations of nucleotide changes in the APC gene with the pathways involved in CRC pathogenesis. All participants received physical and enteroscopic examinations. The APC gene was sequenced for 300 Chinese Han CRC patients and 411 normal controls, and the expression levels of genes in the signaling pathway were analyzed using Western Blotting. Statistical analyses were conducted using SPSS (version 19.0) software. We found that rs11954856 in the APC gene was associated with colorectal cancer and could increase the expression levels of APC , β-catenin , TCF7L1 , TCF7L2 and LEF1 genes in the pathway in the CRC patients, demonstrating the involvement of APC in the pathological processes leading to CRC.

Distribution, Community Composition, and Potential Metabolic Activity of Bacterioplankton in an Urbanized Mediterranean Sea Coastal Zone.

PubMed

Richa, Kumari; Balestra, Cecilia; Piredda, Roberta; Benes, Vladimir; Borra, Marco; Passarelli, Augusto; Margiotta, Francesca; Saggiomo, Maria; Biffali, Elio; Sanges, Remo; Scanlan, David J; Casotti, Raffaella

2017-09-01

Bacterioplankton are fundamental components of marine ecosystems and influence the entire biosphere by contributing to the global biogeochemical cycles of key elements. Yet, there is a significant gap in knowledge about their diversity and specific activities, as well as environmental factors that shape their community composition and function. Here, the distribution and diversity of surface bacterioplankton along the coastline of the Gulf of Naples (GON; Italy) were investigated using flow cytometry coupled with high-throughput sequencing of the 16S rRNA gene. Heterotrophic bacteria numerically dominated the bacterioplankton and comprised mainly Alphaproteobacteria , Gammaproteobacteria , and Bacteroidetes Distinct communities occupied river-influenced, coastal, and offshore sites, as indicated by Bray-Curtis dissimilarity, distance metric (UniFrac), linear discriminant analysis effect size (LEfSe), and multivariate analyses. The heterogeneity in diversity and community composition was mainly due to salinity and changes in environmental conditions across sites, as defined by nutrient and chlorophyll a concentrations. Bacterioplankton communities were composed of a few dominant taxa and a large proportion (92%) of rare taxa (here defined as operational taxonomic units [OTUs] accounting for <0.1% of the total sequence abundance), the majority of which were unique to each site. The relationship between 16S rRNA and the 16S rRNA gene, i.e., between potential metabolic activity and abundance, was positive for the whole community. However, analysis of individual OTUs revealed high rRNA-to-rRNA gene ratios for most (71.6% ± 16.7%) of the rare taxa, suggesting that these low-abundance organisms were potentially active and hence might be playing an important role in ecosystem diversity and functioning in the GON. IMPORTANCE The study of bacterioplankton in coastal zones is of critical importance, considering that these areas are highly productive and anthropogenically impacted. Their richness and evenness, as well as their potential activity, are very important to assess ecosystem health and functioning. Here, we investigated bacterial distribution, community composition, and potential metabolic activity in the GON, which is an ideal test site due to its heterogeneous environment characterized by a complex hydrodynamics and terrestrial inputs of varied quantities and quality. Our study demonstrates that bacterioplankton communities in this region are highly diverse and strongly regulated by a combination of different environmental factors leading to their heterogeneous distribution, with the rare taxa contributing to a major proportion of diversity and shifts in community composition and potentially holding a key role in ecosystem functioning. Copyright © 2017 American Society for Microbiology.

Distribution, Community Composition, and Potential Metabolic Activity of Bacterioplankton in an Urbanized Mediterranean Sea Coastal Zone

PubMed Central

Richa, Kumari; Balestra, Cecilia; Piredda, Roberta; Benes, Vladimir; Borra, Marco; Passarelli, Augusto; Margiotta, Francesca; Saggiomo, Maria; Biffali, Elio; Sanges, Remo; Scanlan, David J.

2017-01-01

ABSTRACT Bacterioplankton are fundamental components of marine ecosystems and influence the entire biosphere by contributing to the global biogeochemical cycles of key elements. Yet, there is a significant gap in knowledge about their diversity and specific activities, as well as environmental factors that shape their community composition and function. Here, the distribution and diversity of surface bacterioplankton along the coastline of the Gulf of Naples (GON; Italy) were investigated using flow cytometry coupled with high-throughput sequencing of the 16S rRNA gene. Heterotrophic bacteria numerically dominated the bacterioplankton and comprised mainly Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes. Distinct communities occupied river-influenced, coastal, and offshore sites, as indicated by Bray-Curtis dissimilarity, distance metric (UniFrac), linear discriminant analysis effect size (LEfSe), and multivariate analyses. The heterogeneity in diversity and community composition was mainly due to salinity and changes in environmental conditions across sites, as defined by nutrient and chlorophyll a concentrations. Bacterioplankton communities were composed of a few dominant taxa and a large proportion (92%) of rare taxa (here defined as operational taxonomic units [OTUs] accounting for <0.1% of the total sequence abundance), the majority of which were unique to each site. The relationship between 16S rRNA and the 16S rRNA gene, i.e., between potential metabolic activity and abundance, was positive for the whole community. However, analysis of individual OTUs revealed high rRNA-to-rRNA gene ratios for most (71.6% ± 16.7%) of the rare taxa, suggesting that these low-abundance organisms were potentially active and hence might be playing an important role in ecosystem diversity and functioning in the GON. IMPORTANCE The study of bacterioplankton in coastal zones is of critical importance, considering that these areas are highly productive and anthropogenically impacted. Their richness and evenness, as well as their potential activity, are very important to assess ecosystem health and functioning. Here, we investigated bacterial distribution, community composition, and potential metabolic activity in the GON, which is an ideal test site due to its heterogeneous environment characterized by a complex hydrodynamics and terrestrial inputs of varied quantities and quality. Our study demonstrates that bacterioplankton communities in this region are highly diverse and strongly regulated by a combination of different environmental factors leading to their heterogeneous distribution, with the rare taxa contributing to a major proportion of diversity and shifts in community composition and potentially holding a key role in ecosystem functioning. PMID:28667110

An investigation of the validity of six measures of physical function in people awaiting joint replacement surgery of the hip or knee.

PubMed

Gill, Stephen D; de Morton, Natalie A; Mc Burney, Helen

2012-10-01

To assess and compare the validity of six physical function measures in people awaiting hip or knee joint replacement. Eighty-two people awaiting hip or knee replacement were assessed using six physical function measures including the WOMAC Function scale, SF-36 Physical Function scale, SF-36 Physical Component Summary scale, Patient Specific Functional Scale, 30-second chair stand test, and 50-foot timed walk. Validity was assessed using a head-to-head comparison design. Convergent validity was demonstrated with significant correlations between most measures (Spearman's rho 0.22 to 0.71). The Patient Specific Functional Scale had the lowest correlations with other measures of physical function. Discriminant validity was demonstrated with low correlations between mental health and physical function scores (Spearman's rho -0.12 to 0.33). Only the WOMAC Function scale, 30-second chair stand test, and 50-foot timed walk demonstrated known groups validity when scores for participants who walked with a gait aid were compared with those who did not. Standardized response means and Guyatt's responsiveness indexes indicated that the SF-36 was the least responsive measure. For those awaiting joint replacement surgery of the hip or knee, the current investigation found that the WOMAC Function scale, 30-second chair stand test, and 50-foot timed walk demonstrated the most evidence of validity. The Patient Specific Functional Scale might complement other measures by capturing a different aspect of physical function.

Scale effect on overland flow connectivity, at the interill scale

NASA Astrophysics Data System (ADS)

Penuela Fernandez, A.; Bielders, C.; Javaux, M.

2012-04-01

The relative surface connection function (RSC) was proposed by Antoine et al. (2009) as a functional indicator of runoff flow connectivity. For a given area, it expresses the percentage of the surface connected to the outlet (C) as a function of the degree of filling of the depression storage. This function explicitly integrates the flow network at the soil surface and hence provides essential information regarding the flow paths' connectivity. It has been shown that this function could help improve the modeling of the hydrogram at the square meter scale, yet it is unknown how the scale affects the RSC function, and whether and how it can be extrapolated to other scales. The main objective of this research is to study the scale effect on overland flow connectivity (RSC function). For this purpose, digital elevation data of a real field (9 x 3 m) and three synthetic fields (6 x 6 m) with contrasting hydrological responses was used, and the RSC function was calculated at different scales by changing the length (L) or width (l) of the field. Border effects were observed for the smaller scales. In most of cases, for L or l smaller than 750mm, increasing L or l, resulted in a strong increase or decrease of the maximum depression storage, respectively. There was no scale effect on the RSC function when changing l. On the contrary, a remarkable scale effect was observed in the RSC function when changing L. In general, for a given degree of filling of the depression storage, C decreased as L increased. This change in C was inversely proportional to the change in L. This observation applied only up to approx. 50-70% (depending on the hydrological response of the field) of filling of depression storage, after which no correlation was found between C and L. The results of this study help identify the critical scale to study overland flow connectivity. At scales larger than the critical scale, the RSC function showed a great potential to be extrapolated to other scales.

Quantifying spatial scaling patterns and their local and regional correlates in headwater streams: Implications for resilience

USGS Publications Warehouse

Gothe, Emma; Sandin, Leonard; Allen, Craig R.; Angeler, David G.

2014-01-01

The distribution of functional traits within and across spatiotemporal scales has been used to quantify and infer the relative resilience across ecosystems. We use explicit spatial modeling to evaluate within- and cross-scale redundancy in headwater streams, an ecosystem type with a hierarchical and dendritic network structure. We assessed the cross-scale distribution of functional feeding groups of benthic invertebrates in Swedish headwater streams during two seasons. We evaluated functional metrics, i.e., Shannon diversity, richness, and evenness, and the degree of redundancy within and across modeled spatial scales for individual feeding groups. We also estimated the correlates of environmental versus spatial factors of both functional composition and the taxonomic composition of functional groups for each spatial scale identified. Measures of functional diversity and within-scale redundancy of functions were similar during both seasons, but both within- and cross-scale redundancy were low. This apparent low redundancy was partly attributable to a few dominant taxa explaining the spatial models. However, rare taxa with stochastic spatial distributions might provide additional information and should therefore be considered explicitly for complementing future resilience assessments. Otherwise, resilience may be underestimated. Finally, both environmental and spatial factors correlated with the scale-specific functional and taxonomic composition. This finding suggests that resilience in stream networks emerges as a function of not only local conditions but also regional factors such as habitat connectivity and invertebrate dispersal.

Work-related measures of physical and behavioral health function: Test-retest reliability.

PubMed

Marino, Molly Elizabeth; Meterko, Mark; Marfeo, Elizabeth E; McDonough, Christine M; Jette, Alan M; Ni, Pengsheng; Bogusz, Kara; Rasch, Elizabeth K; Brandt, Diane E; Chan, Leighton

2015-10-01

The Work Disability Functional Assessment Battery (WD-FAB), developed for potential use by the US Social Security Administration to assess work-related function, currently consists of five multi-item scales assessing physical function and four multi-item scales assessing behavioral health function; the WD-FAB scales are administered as Computerized Adaptive Tests (CATs). The goal of this study was to evaluate the test-retest reliability of the WD-FAB Physical Function and Behavioral Health CATs. We administered the WD-FAB scales twice, 7-10 days apart, to a sample of 376 working age adults and 316 adults with work-disability. Intraclass correlation coefficients were calculated to measure the consistency of the scores between the two administrations. Standard error of measurement (SEM) and minimal detectable change (MDC90) were also calculated to measure the scales precision and sensitivity. For the Physical Function CAT scales, the ICCs ranged from 0.76 to 0.89 in the working age adult sample, and 0.77-0.86 in the sample of adults with work-disability. ICCs for the Behavioral Health CAT scales ranged from 0.66 to 0.70 in the working age adult sample, and 0.77-0.80 in the adults with work-disability. The SEM ranged from 3.25 to 4.55 for the Physical Function scales and 5.27-6.97 for the Behavioral Health function scales. For all scales in both samples, the MDC90 ranged from 7.58 to 16.27. Both the Physical Function and Behavioral Health CATs of the WD-FAB demonstrated good test-retest reliability in adults with work-disability and general adult samples, a critical requirement for assessing work related functioning in disability applicants and in other contexts. Copyright © 2015 Elsevier Inc. All rights reserved.

Work-related measures of Physical and Behavioral Health Function: Test-Retest Reliability

PubMed Central

Marino, Molly Elizabeth; Meterko, Mark; Marfeo, Elizabeth E.; McDonough, Christine M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara; Rasch, Elizabeth K.; Brandt, Diane E.; Chan, Leighton

2015-01-01

Background The Work Disability Functional Assessment Battery (WD-FAB), developed for potential use by the US Social Security Administration to assess work-related function, currently consists of five multi-item scales assessing physical function and four multi-item scales assessing behavioral health function; the WD-FAB scales are administered as Computerized Adaptive Tests (CATs). Objective The goal of this study was to evaluate the test-retest reliability of the WD-FAB Physical Function and Behavioral Health CATs. Methods We administered the WD-FAB scales twice, 7–10 days apart, to a sample of 376 working age adults and 316 adults with work-disability. Intraclass correlation coefficients were calculated to measure the consistency of the scores between the two administrations. Standard error of measurement (SEM) and minimal detectable change (MDC90) were also calculated to measure the scales precision and sensitivity. Results For the Physical Function CAT scales, the ICCs ranged from 0.76–0.89 in the working age adult sample, and 0.77–0.86 in the sample of adults with work-disability. ICCs for the Behavioral Health CAT scales ranged from 0.66–0.70 in the working age adult sample, and 0.77–0.80 in the adults with work-disability. The SEM ranged from 3.25–4.55 for the Physical Function scales and 5.27–6.97 for the Behavioral Health function scales. For all scales in both samples, the MDC90 ranged from 7.58–16.27. Conclusion Both the Physical Function and Behavioral Health CATs of the WD-FAB demonstrated good test-retest reliability in adults with work-disability and general adult samples, a critical requirement for assessing work related functioning in disability applicants and in other contexts. PMID:25991419

A scaling theory for linear systems

NASA Technical Reports Server (NTRS)

Brockett, R. W.; Krishnaprasad, P. S.

1980-01-01

A theory of scaling for rational (transfer) functions in terms of transformation groups is developed. Two different four-parameter scaling groups which play natural roles in studying linear systems are identified and the effect of scaling on Fisher information and related statistical measures in system identification are studied. The scalings considered include change of time scale, feedback, exponential scaling, magnitude scaling, etc. The scaling action of the groups studied is tied to the geometry of transfer functions in a rather strong way as becomes apparent in the examination of the invariants of scaling. As a result, the scaling process also provides new insight into the parameterization question for rational functions.

Reliability, construct validity, and responsiveness of the neck disability index, patient-specific functional scale, and numeric pain rating scale in patients with cervical radiculopathy.

PubMed

Young, Ian A; Cleland, Joshua A; Michener, Lori A; Brown, Chris

2010-10-01

To examine the psychometric properties of the Neck Disability Index, Patient-Specific Functional Scale, and the Numeric Pain Rating Scale in a cohort of patients with cervical radiculopathy. A single-group repeated-measures design. Patients (n = 165) presenting to physical therapy with cervical radiculopathy completed the Neck Disability Index, Patient-Specific Functional Scale, and Numeric Pain Rating Scale at the baseline examination and at a follow-up. At the time of follow-up, all patients also completed the Global Rating of Change, which was used to dichotomize patients as improved or stable. Baseline and follow-up scores were used to determine the test-retest reliability, construct validity, and minimal levels of detectable and clinically important change for the Neck Disability Index, Patient-Specific Functional Scale, and Numeric Pain Rating Scale. Both the Neck Disability Index and Numeric Pain Rating Scale exhibited fair test-retest reliability, whereas the Patient-Specific Functional Scale exhibited poor reliability in patients with cervical radiculopathy. All three outcome measures showed adequate responsiveness in this patient population. The minimal detectable change was 13.4 for the Neck Disability Index, 3.3 for the Patient-Specific Functional Scale, and 4.1 for the Numeric Pain Rating Scale. The threshold for the minimal clinically important difference was 8.5 for the Neck Disability Index and 2.2 for both the Patient-Specific Functional Scale and Numeric Pain Rating Scale. In light of the varied distribution of symptoms in patients with cervical radiculopathy, future studies should investigate the psychometric properties of other neck-related disability measures in this patient population.

Scale effect on overland flow connectivity at the plot scale

NASA Astrophysics Data System (ADS)

Peñuela, A.; Javaux, M.; Bielders, C. L.

2012-06-01

A major challenge in present-day hydrological sciences is to enhance the performance of existing distributed hydrological models through a better description of subgrid processes, in particular the subgrid connectivity of flow paths. The relative surface connection function (RSC) was proposed by Antoine et al. (2009) as a functional indicator of runoff flow connectivity. For a given area, it expresses the percentage of the surface connected to the outflow boundary (C) as a function of the degree of filling of the depression storage. This function explicitly integrates the flow network at the soil surface and hence provides essential information regarding the flow paths' connectivity. It has been shown that this function could help improve the modeling of the hydrogram at the square meter scale, yet it is unknown how the scale affects the RSC function, and whether and how it can be extrapolated to other scales. The main objective of this research is to study the scale effect on overland flow connectivity (RSC function). For this purpose, digital elevation data of a real field (9 × 3 m) and three synthetic fields (6 × 6 m) with contrasting hydrological responses were used, and the RSC function was calculated at different scales by changing the length (l) or width (w) of the field. Border effects, at different extents depending on the microtopography, were observed for the smaller scales, when decreasing l or w, which resulted in a strong decrease or increase of the maximum depression storage, respectively. There was no scale effect on the RSC function when changing w. On the contrary, a remarkable scale effect was observed in the RSC function when changing l. In general, for a given degree of filling of the depression storage, C decreased as l increased. This change in C was inversely proportional to the change in l. This observation applied only up to approx. 50-70% (depending on the hydrological response of the field) of filling of depression storage, after which no correlation was found between C and l. The results of this study help identify the minimal scale to study overland flow connectivity. At scales larger than the minimal scale, the RSC function showed a great potential to be extrapolated to other scales.

Scale effect on overland flow connectivity at the plot scale

NASA Astrophysics Data System (ADS)

Peñuela, A.; Javaux, M.; Bielders, C. L.

2013-01-01

A major challenge in present-day hydrological sciences is to enhance the performance of existing distributed hydrological models through a better description of subgrid processes, in particular the subgrid connectivity of flow paths. The Relative Surface Connection (RSC) function was proposed by Antoine et al. (2009) as a functional indicator of runoff flow connectivity. For a given area, it expresses the percentage of the surface connected to the outflow boundary (C) as a function of the degree of filling of the depression storage. This function explicitly integrates the flow network at the soil surface and hence provides essential information regarding the flow paths' connectivity. It has been shown that this function could help improve the modeling of the hydrograph at the square meter scale, yet it is unknown how the scale affects the RSC function, and whether and how it can be extrapolated to other scales. The main objective of this research is to study the scale effect on overland flow connectivity (RSC function). For this purpose, digital elevation data of a real field (9 × 3 m) and three synthetic fields (6 × 6 m) with contrasting hydrological responses were used, and the RSC function was calculated at different scales by changing the length (l) or width (w) of the field. To different extents depending on the microtopography, border effects were observed for the smaller scales when decreasing l or w, which resulted in a strong decrease or increase of the maximum depression storage, respectively. There was no scale effect on the RSC function when changing w, but a remarkable scale effect was observed in the RSC function when changing l. In general, for a given degree of filling of the depression storage, C decreased as l increased, the change in C being inversely proportional to the change in l. However, this observation applied only up to approx. 50-70% (depending on the hydrological response of the field) of filling of depression storage, after which no correlation was found between C and l. The results of this study help identify the minimal scale to study overland flow connectivity. At scales larger than the minimal scale, the RSC function showed a great potential to be extrapolated to other scales.

Association between executive and food functions in the acute phase after stroke.

PubMed

Mourão, Aline Mansueto; Vicente, Laélia Cristina Caseiro; Abreu, Mery Natali Silva; Chaves, Tatiana Simões; Sant'Anna, Romeu Vale; Braga, Marcela Aline Fernandes; Meira, Fidel Castro Alves de; de Souza, Leonardo Cruz; Miranda, Aline Silva de; Rachid, Milene Alvarenga; Teixeira, Antônio Lucio

2018-03-01

Purpose To investigate potential associations among executive, physical and food functions in the acute phase after stroke. Methods This is a cross-sectional study that evaluated 63 patients admitted to the stroke unit of a public hospital. The exclusion criteria were other neurological and/or psychiatric diagnoses. The tools for evaluation were: Mini-Mental State Examination and Frontal Assessment Battery for cognitive functions; Alberta Stroke Program Early CT Score for quantification of brain injury; National Institutes of Health Stroke Scale for neurological impairment; Modified Rankin Scale for functionality, and the Functional Oral Intake Scale for food function. Results The sample comprised 34 men (54%) and 29 women with a mean age of 63.6 years. The Frontal Assessment Battery was significantly associated with the other scales. In multivariate analysis, executive function was independently associated with the Functional Oral Intake Scale. Conclusion Most patients exhibited executive dysfunction that significantly compromised oral intake.

Scale-space measures for graph topology link protein network architecture to function.

PubMed

Hulsman, Marc; Dimitrakopoulos, Christos; de Ridder, Jeroen

2014-06-15

The network architecture of physical protein interactions is an important determinant for the molecular functions that are carried out within each cell. To study this relation, the network architecture can be characterized by graph topological characteristics such as shortest paths and network hubs. These characteristics have an important shortcoming: they do not take into account that interactions occur across different scales. This is important because some cellular functions may involve a single direct protein interaction (small scale), whereas others require more and/or indirect interactions, such as protein complexes (medium scale) and interactions between large modules of proteins (large scale). In this work, we derive generalized scale-aware versions of known graph topological measures based on diffusion kernels. We apply these to characterize the topology of networks across all scales simultaneously, generating a so-called graph topological scale-space. The comprehensive physical interaction network in yeast is used to show that scale-space based measures consistently give superior performance when distinguishing protein functional categories and three major types of functional interactions-genetic interaction, co-expression and perturbation interactions. Moreover, we demonstrate that graph topological scale spaces capture biologically meaningful features that provide new insights into the link between function and protein network architecture. Matlab(TM) code to calculate the scale-aware topological measures (STMs) is available at http://bioinformatics.tudelft.nl/TSSA © The Author 2014. Published by Oxford University Press.

Burke-Fahn-Marsden dystonia severity, Gross Motor, Manual Ability, and Communication Function Classification scales in childhood hyperkinetic movement disorders including cerebral palsy: a 'Rosetta Stone' study.

PubMed

Elze, Markus C; Gimeno, Hortensia; Tustin, Kylee; Baker, Lesley; Lumsden, Daniel E; Hutton, Jane L; Lin, Jean-Pierre S-M

2016-02-01

Hyperkinetic movement disorders (HMDs) can be assessed using impairment-based scales or functional classifications. The Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) evaluates dystonia impairment, but may not reflect functional ability. The Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) are widely used in the literature on cerebral palsy to classify functional ability, but not in childhood movement disorders. We explore the concordance of these three functional scales in a large sample of paediatric HMDs and the impact of dystonia severity on these scales. Children with HMDs (n=161; median age 10y 3mo, range 2y 6mo-21y) were assessed using the BFM-M, GMFCS, MACS, and CFCS from 2007 to 2013. This cross-sectional study contrasts the information provided by these scales. All four scales were strongly associated (all Spearman's rank correlation coefficient rs >0.72, p<0.001), with worse dystonia severity implying worse function. Secondary dystonias had worse dystonia and less function than primary dystonias (p<0.001). A longer proportion of life lived with dystonia is associated with more severe dystonia (rs =0.42, p<0.001). The BFM-M is strongly linked with the GMFCS, MACS, and CFCS, irrespective of aetiology. Each scale offers interrelated but complementary information and is applicable to all aetiologies. Movement disorders including cerebral palsy can be effectively evaluated using these scales. © 2015 Mac Keith Press.

Relationship between alcohol-related expectancies and anterior brain functioning in young men at risk for developing alcoholism.

PubMed

Deckel, A W; Hesselbrock, V; Bauer, L

1995-04-01

This experiment examined the relationship between anterior brain functioning and alcohol-related expectancies. Ninety-one young men at risk for developing alcoholism were assessed on the Alcohol Expectancy Questionnaire (AEQ) and administered neuropsychological and EEG tests. Three of the scales on the AEQ, including the "Enhanced Sexual Functioning" scale, the "Increased Social Assertiveness" scale, and items from the "Global/Positive Change scale," were used, because each of these scales has been found to discriminate alcohol-based expectancies adequately by at least two separate sets of investigators. Regression analysis found that anterior neuropsychological tests (including the Wisconsin Card Sorting test, the Porteus Maze test, the Controlled Oral Word Fluency test, and the Luria-Nebraska motor functioning tests) were predictive of the AEQ scale scores on regression analysis. One of the AEQ scales, "Enhanced Sexual Functioning," was also predicted by WAIS-R-Verbal scales, whereas the "Global/Positive" AEQ scale was predicted by the WAIS-R Performance scales. Regression analysis using EEG power as predictors found that left versus right hemisphere "difference" scores obtained from frontal EEG leads were predictive of the three AEQ scales. Conversely, parietal EEG power did not significantly predict any of the expectancy scales. It is concluded that anterior brain any of the expectancy scales. It is concluded that anterior brain functioning is associated with alcohol-related expectancies. These findings suggest that alcohol-related expectancy may be, in part, biologically determined by frontal/prefrontal systems, and that dysfunctioning in these systems may serve as a risk factor for the development of alcohol-related behaviors.

The Relationship between Symptom Relief and Psychosocial Functional Improvement during Acute Electroconvulsive Therapy for Patients with Major Depressive Disorder.

PubMed

Lin, Ching-Hua; Yang, Wei-Cheng

2017-07-01

We aimed to compare the degree of symptom relief to psychosocial functional (abbreviated as "functional") improvement and explore the relationships between symptom relief and functional improvement during acute electroconvulsive therapy for patients with major depressive disorder. Major depressive disorder inpatients (n=130) requiring electroconvulsive therapy were recruited. Electroconvulsive therapy was generally performed for a maximum of 12 treatments. Symptom severity, using the 17-item Hamilton Depression Rating Scale, and psychosocial functioning (abbreviated as "functioning"), using the Modified Work and Social Adjustment Scale, were assessed before electroconvulsive therapy, after every 3 electroconvulsive therapy treatments, and after the final electroconvulsive therapy. Both 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale scores were converted to T-score units to compare the degrees of changes between depressive symptoms and functioning after electroconvulsive therapy. Structural equation modeling was used to test the relationships between 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale during acute electroconvulsive therapy. One hundred sixteen patients who completed at least the first 3 electroconvulsive therapy treatments entered the analysis. Reduction of 17-item Hamilton Depression Rating Scale T-scores was significantly greater than that of Modified Work and Social Adjustment Scale T-scores at assessments 2, 3, 4, and 5. The model analyzed by structural equation modeling satisfied all indices of goodness-of-fit (chi-square = 32.882, P =.107, TLI = 0.92, CFI = 0.984, RMSEA = 0.057). The 17-item Hamilton Depression Rating Scale change did not predict subsequent Modified Work and Social Adjustment Scale change. Functioning improved less than depressive symptoms during acute electroconvulsive therapy. Symptom reduction did not predict subsequent functional improvement. Depressive symptoms and functional impairment are distinct domains and should be assessed independently to accurately reflect the effectiveness of electroconvulsive therapy. © The Author 2017. Published by Oxford University Press on behalf of CINP.

The universal function in color dipole model

NASA Astrophysics Data System (ADS)

Jalilian, Z.; Boroun, G. R.

2017-10-01

In this work we review color dipole model and recall properties of the saturation and geometrical scaling in this model. Our primary aim is determining the exact universal function in terms of the introduced scaling variable in different distance than the saturation radius. With inserting the mass in calculation we compute numerically the contribution of heavy productions in small x from the total structure function by the fraction of universal functions and show the geometrical scaling is established due to our scaling variable in this study.

Creation and Initial Validation of the International Dysphagia Diet Standardisation Initiative Functional Diet Scale

PubMed Central

Steele, Catriona M.; Namasivayam-MacDonald, Ashwini M.; Guida, Brittany T.; Cichero, Julie A.; Duivestein, Janice; MRSc; Hanson, Ben; Lam, Peter; Riquelme, Luis F.

2018-01-01

Objective To assess consensual validity, interrater reliability, and criterion validity of the International Dysphagia Diet Standardisation Initiative Functional Diet Scale, a new functional outcome scale intended to capture the severity of oropharyngeal dysphagia, as represented by the degree of diet texture restriction recommended for the patient. Design Participants assigned International Dysphagia Diet Standardisation Initiative Functional Diet Scale scores to 16 clinical cases. Consensual validity was measured against reference scores determined by an author reference panel. Interrater reliability was measured overall and across quartile subsets of the dataset. Criterion validity was evaluated versus Functional Oral Intake Scale (FOIS) scores assigned by survey respondents to the same case scenarios. Feedback was requested regarding ease and likelihood of use. Setting Web-based survey. Participants Respondents (NZ170) from 29 countries. Interventions Not applicable. Main Outcome Measures Consensual validity (percent agreement and Kendall t), criterion validity (Spearman rank correlation), and interrater reliability (Kendall concordance and intraclass coefficients). Results The International Dysphagia Diet Standardisation Initiative Functional Diet Scale showed strong consensual validity, criterion validity, and interrater reliability. Scenarios involving liquid-only diets, transition from nonoral feeding, or trial diet advances in therapy showed the poorest consensus, indicating a need for clear instructions on how to score these situations. The International Dysphagia Diet Standardisation Initiative Functional Diet Scale showed greater sensitivity than the FOIS to specific changes in diet. Most (>70%) respondents indicated enthusiasm for implementing the International Dysphagia Diet Standardisation Initiative Functional Diet Scale. Conclusions This initial validation study suggests that the International Dysphagia Diet Standardisation Initiative Functional Diet Scale has strong consensual and criterion validity and can be used reliably by clinicians to capture diet texture restriction and progression in people with dysphagia. PMID:29428348

Creation and Initial Validation of the International Dysphagia Diet Standardisation Initiative Functional Diet Scale.

PubMed

Steele, Catriona M; Namasivayam-MacDonald, Ashwini M; Guida, Brittany T; Cichero, Julie A; Duivestein, Janice; Hanson, Ben; Lam, Peter; Riquelme, Luis F

2018-05-01

To assess consensual validity, interrater reliability, and criterion validity of the International Dysphagia Diet Standardisation Initiative Functional Diet Scale, a new functional outcome scale intended to capture the severity of oropharyngeal dysphagia, as represented by the degree of diet texture restriction recommended for the patient. Participants assigned International Dysphagia Diet Standardisation Initiative Functional Diet Scale scores to 16 clinical cases. Consensual validity was measured against reference scores determined by an author reference panel. Interrater reliability was measured overall and across quartile subsets of the dataset. Criterion validity was evaluated versus Functional Oral Intake Scale (FOIS) scores assigned by survey respondents to the same case scenarios. Feedback was requested regarding ease and likelihood of use. Web-based survey. Respondents (N=170) from 29 countries. Not applicable. Consensual validity (percent agreement and Kendall τ), criterion validity (Spearman rank correlation), and interrater reliability (Kendall concordance and intraclass coefficients). The International Dysphagia Diet Standardisation Initiative Functional Diet Scale showed strong consensual validity, criterion validity, and interrater reliability. Scenarios involving liquid-only diets, transition from nonoral feeding, or trial diet advances in therapy showed the poorest consensus, indicating a need for clear instructions on how to score these situations. The International Dysphagia Diet Standardisation Initiative Functional Diet Scale showed greater sensitivity than the FOIS to specific changes in diet. Most (>70%) respondents indicated enthusiasm for implementing the International Dysphagia Diet Standardisation Initiative Functional Diet Scale. This initial validation study suggests that the International Dysphagia Diet Standardisation Initiative Functional Diet Scale has strong consensual and criterion validity and can be used reliably by clinicians to capture diet texture restriction and progression in people with dysphagia. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Functional assessment of a series of paediatric patients receiving neurointensive treatment: New Functional status scale.

PubMed

Madurga-Revilla, P; López-Pisón, J; Samper-Villagrasa, P; Garcés-Gómez, R; García-Íñiguez, J P; Domínguez-Cajal, M; Gil-Hernández, I; Viscor-Zárate, S

2017-11-01

Functional health, a reliable parameter of the impact of disease, should be used systematically to assess prognosis in paediatric intensive care units (PICU). Developing scales for the assessment of functional health is therefore essential. The Paediatric Overall and Cerebral Performance Category (POPC, PCPC) scales have traditionally been used in paediatric studies. The new Functional Status Scale (FSS) was designed to provide more objective results. This study aims to confirm the validity of the FSS compared to the classic POPC and PCPC scales, and to evaluate whether it may also be superior to the latter in assessing of neurological function. We conducted a retrospective descriptive study of 266 children with neurological diseases admitted to intensive care between 2012 and 2014. Functional health at discharge and at one year after discharge was evaluated using the PCPC and POPC scales and the new FSS. Global FSS scores were found to be well correlated with all POPC scores (P<.001), except in category 5 (coma/vegetative state). Global FSS score dispersion increases with POPC category. The neurological versions of both scales show a similar correlation. Comparison with classic POPC and PCPC categories suggests that the new FSS scale is a useful method for evaluating functional health in our setting. The dispersion of FSS values underlines the poor accuracy of POPC-PCPC compared to the new FSS scale, which is more disaggregated and objective. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Statistical scaling of pore-scale Lagrangian velocities in natural porous media.

PubMed

Siena, M; Guadagnini, A; Riva, M; Bijeljic, B; Pereira Nunes, J P; Blunt, M J

2014-08-01

We investigate the scaling behavior of sample statistics of pore-scale Lagrangian velocities in two different rock samples, Bentheimer sandstone and Estaillades limestone. The samples are imaged using x-ray computer tomography with micron-scale resolution. The scaling analysis relies on the study of the way qth-order sample structure functions (statistical moments of order q of absolute increments) of Lagrangian velocities depend on separation distances, or lags, traveled along the mean flow direction. In the sandstone block, sample structure functions of all orders exhibit a power-law scaling within a clearly identifiable intermediate range of lags. Sample structure functions associated with the limestone block display two diverse power-law regimes, which we infer to be related to two overlapping spatially correlated structures. In both rocks and for all orders q, we observe linear relationships between logarithmic structure functions of successive orders at all lags (a phenomenon that is typically known as extended power scaling, or extended self-similarity). The scaling behavior of Lagrangian velocities is compared with the one exhibited by porosity and specific surface area, which constitute two key pore-scale geometric observables. The statistical scaling of the local velocity field reflects the behavior of these geometric observables, with the occurrence of power-law-scaling regimes within the same range of lags for sample structure functions of Lagrangian velocity, porosity, and specific surface area.

Development and Psychometric Properties of the OCD Family Functioning (OFF) Scale

PubMed Central

Stewart, S. Evelyn; Hu, Yu-Pei; Hezel, Dianne M.; Proujansky, Rachel; Lamstein, Abby; Walsh, Casey; Ben-Joseph, Elana Pearl; Gironda, Christina; Jenike, Michael; Geller, Daniel A.; Pauls, David L.

2013-01-01

Obsessive–compulsive disorder (OCD) influences not only patients but also family members. Although the construct of family accommodation has received attention in OCD literature, no measures of overall family functioning are currently available. The OCD Family Functioning (OFF) Scale was developed to explore the context, extent, and perspectives of functional impairment in families affected by OCD. It is a three-part, self-report measure capturing independent perspectives of patients and relatives. A total of 400 subjects were enrolled between 2008 and 2010 from specialized OCD clinics and OCD research studies. Psychometric properties of this scale were examined including internal consistency, test–retest reliability, convergent and divergent validity, and exploratory factor analyses. Both patient and relative versions of the OFF Scale demonstrated excellent internal consistency (Cronbach’s alpha coefficient = 0.96). The test–retest reliability was also adequate (ICC = 0.80). Factor analyses determined that the OFF Scale comprises a family functioning impairment factor and four OCD symptom factors that were consistent with previously reported OCD symptom dimension studies. The OFF Scale demonstrated excellent convergent validity with the Family Accommodation Scale and the Work and Social Adjustment Scale. Information gathered regarding emotional impact and family role-specific impairment was novel and not captured by other examined scales. The OFF Scale is a reliable and valid instrument for the clinical and research assessment of family functioning in pediatric and adult OCD. This will facilitate the exploration of family functioning impairment as a potential risk factor, as a moderator and as a treatment outcome measure in OCD. PMID:21553962

Disappearance of Anisotropic Intermittency in Large-amplitude MHD Turbulence and Its Comparison with Small-amplitude MHD Turbulence

NASA Astrophysics Data System (ADS)

Yang, Liping; Zhang, Lei; He, Jiansen; Tu, Chuanyi; Li, Shengtai; Wang, Xin; Wang, Linghua

2018-03-01

Multi-order structure functions in the solar wind are reported to display a monofractal scaling when sampled parallel to the local magnetic field and a multifractal scaling when measured perpendicularly. Whether and to what extent will the scaling anisotropy be weakened by the enhancement of turbulence amplitude relative to the background magnetic strength? In this study, based on two runs of the magnetohydrodynamic (MHD) turbulence simulation with different relative levels of turbulence amplitude, we investigate and compare the scaling of multi-order magnetic structure functions and magnetic probability distribution functions (PDFs) as well as their dependence on the direction of the local field. The numerical results show that for the case of large-amplitude MHD turbulence, the multi-order structure functions display a multifractal scaling at all angles to the local magnetic field, with PDFs deviating significantly from the Gaussian distribution and a flatness larger than 3 at all angles. In contrast, for the case of small-amplitude MHD turbulence, the multi-order structure functions and PDFs have different features in the quasi-parallel and quasi-perpendicular directions: a monofractal scaling and Gaussian-like distribution in the former, and a conversion of a monofractal scaling and Gaussian-like distribution into a multifractal scaling and non-Gaussian tail distribution in the latter. These results hint that when intermittencies are abundant and intense, the multifractal scaling in the structure functions can appear even if it is in the quasi-parallel direction; otherwise, the monofractal scaling in the structure functions remains even if it is in the quasi-perpendicular direction.

Translation, cultural adaptation and reproducibility of the Cochin Hand Functional Scale questionnaire for Brazil

PubMed Central

Chiari, Aline; de Souza Sardim, Carla Caires; Natour, Jamil

2011-01-01

OBJECTIVE: To translate, to perform a cultural adaptation of and to test the reproducibility of the Cochin Hand Functional Scale questionnaire for Brazil. METHODS: First, the Cochin Hand Functional Scale questionnaire was translated into Portuguese and was then back-translated into French. These translations were reviewed by a committee to establish a Brazilian version of the questionnaire to be tested. The validity and reproducibility of the Cochin Hand Functional Scale questionnaire was evaluated. Patients of both sexes, who were aged 18 to 60 years and presented with rheumatoid arthritis affecting their hands, were interviewed. The patients were initially interviewed by two observers and were later interviewed by a single rater. First, the Visual Analogue Scale for hand pain, the Arm, Shoulder and Hand Disability questionnaire and the Health Assessment Questionnaire were administered. The third administration of the Cochin Hand Functional Scale was performed fifteen days after the first administration. Ninety patients were assessed in the present study. RESULTS: Two questions were modified as a result of the assessment of cultural equivalence. The Cronbach's alpha value for this assessment was 0.93. The intraclass intraobserver and interobserver correlation coefficients were 0.76 and 0.96, respectively. The Spearman's coefficient indicated that there was a low level of correlation between the Cochin Hand Functional Scale and the Visual Analogue Scale for pain (0.46) and that there was a moderate level of correlation of the Cochin Scale with the Health Assessment Questionnaire (0.66) and with the Disability of the Arm, Shoulder and Hand questionnaire (0.63). The average administration time for the Cochin Scale was three minutes. CONCLUSION: The Brazilian version of the Cochin Hand Functional Scale was successfully translated and adapted, and this version exhibited good internal consistency, reliability and construct validity. PMID:21789372

Uniform functional structure across spatial scales in an intertidal benthic assemblage.

PubMed

Barnes, R S K; Hamylton, Sarah

2015-05-01

To investigate the causes of the remarkable similarity of emergent assemblage properties that has been demonstrated across disparate intertidal seagrass sites and assemblages, this study examined whether their emergent functional-group metrics are scale related by testing the null hypothesis that functional diversity and the suite of dominant functional groups in seagrass-associated macrofauna are robust structural features of such assemblages and do not vary spatially across nested scales within a 0.4 ha area. This was carried out via a lattice of 64 spatially referenced stations. Although densities of individual components were patchily dispersed across the locality, rank orders of importance of the 14 functional groups present, their overall functional diversity and evenness, and the proportions of the total individuals contained within each showed, in contrast, statistically significant spatial uniformity, even at areal scales <2 m(2). Analysis of the proportional importance of the functional groups in their geospatial context also revealed weaker than expected levels of spatial autocorrelation, and then only at the smaller scales and amongst the most dominant groups, and only a small number of negative correlations occurred between the proportional importances of the individual groups. In effect, such patterning was a surface veneer overlying remarkable stability of assemblage functional composition across all spatial scales. Although assemblage species composition is known to be homogeneous in some soft-sediment marine systems over equivalent scales, this combination of patchy individual components yet basically constant functional-group structure seems as yet unreported. Copyright © 2015 Elsevier Ltd. All rights reserved.

β-catenin is required for taste bud cell renewal and behavioral taste perception in adult mice

PubMed Central

Gaillard, Dany; Xu, Mingang; Millar, Sarah E.

2017-01-01

Taste stimuli are transduced by taste buds and transmitted to the brain via afferent gustatory fibers. Renewal of taste receptor cells from actively dividing progenitors is finely tuned to maintain taste sensitivity throughout life. We show that conditional β-catenin deletion in mouse taste progenitors leads to rapid depletion of progenitors and Shh+ precursors, which in turn causes taste bud loss, followed by loss of gustatory nerve fibers. In addition, our data suggest LEF1, TCF7 and Wnt3 are involved in a Wnt pathway regulatory feedback loop that controls taste cell renewal in the circumvallate papilla epithelium. Unexpectedly, taste bud decline is greater in the anterior tongue and palate than in the posterior tongue. Mutant mice with this regional pattern of taste bud loss were unable to discern sweet at any concentration, but could distinguish bitter stimuli, albeit with reduced sensitivity. Our findings are consistent with published reports wherein anterior taste buds have higher sweet sensitivity while posterior taste buds are better tuned to bitter, and suggest β-catenin plays a greater role in renewal of anterior versus posterior taste buds. PMID:28846687

The role of computed tomography in detecting splenic arteriovenous fistula and concomitant atrial myxoma.

PubMed

Rroji, Arben; Bilaj, Fatmir; Qirinxhi, Denis; Vucini, Ortencia; Hasimi, Endri; Goda, Artan

2014-01-01

Female, 45 FINAL DIAGNOSIS: Arterio-venous fistula of the splean Symptoms: Lef-side abdominal pain Medication: - Clinical Procedure: - Specialty: Surgery. Rare disease. Splenic arterial-venous fistula and atrial myxoma are not rare cases but the co-existence of both lesions in the same patient is unpublished so far. A 45- year-old woman presented with vague left flank pain. She was initially scanned by B-dimensional echography, which revealed multiple enlarged hypo-echoic lesions in the splenic hilum. To further characterize the lesion, we performed computed tomography angiography (CTA). CTA showed dilatation of the splenic artery, and aneurismal dilatation of the splenic vein, associated with early opacification of the portal system. CTA showed also an intrasplenic venous aneurism, which was presumed to be the site of fistulous communication. Celiac arteriography confirmed the CTA findings. A left atrial mass was detected by cardiac echography, which was evaluated better by CTA, and was consistent with atrial myxoma. The patient underwent open surgery in different stage with resection of the atrial mass and spleen. The postoperative period was uneventful. This is a unique case in the literature, showing the coexistence of a dual-pathology splenic arterial venous fistula and atrial myxoma.

Analysis of the Genome of the Sexually Transmitted Insect Virus Helicoverpa zea Nudivirus 2

PubMed Central

Burand, John P.; Kim, Woojin; Afonso, Claudio L.; Tulman, Edan R.; Kutish, Gerald F.; Lu, Zhiqiang; Rock, Daniel L.

2012-01-01

The sexually transmitted insect virus Helicoverpa zea nudivirus 2 (HzNV-2) was determined to have a circular double-stranded DNA genome of 231,621 bp coding for an estimated 113 open reading frames (ORFs). HzNV-2 is most closely related to the nudiviruses, a sister group of the insect baculoviruses. Several putative ORFs that share homology with the baculovirus core genes were identified in the viral genome. However, HzNV-2 lacks several key genetic features of baculoviruses including the late transcriptional regulation factor, LEF-1 and the palindromic hrs, which serve as origins of replication. The HzNV-2 genome was found to code for three ORFs that had significant sequence homology to cellular genes which are not generally found in viral genomes. These included a presumed juvenile hormone esterase gene, a gene coding for a putative zinc-dependent matrix metalloprotease, and a major facilitator superfamily protein gene; all of which are believed to play a role in the cellular proliferation and the tissue hypertrophy observed in the malformation of reproductive organs observed in HzNV-2 infected corn earworm moths, Helicoverpa zea. PMID:22355451

Analysis of the genome of the sexually transmitted insect virus Helicoverpa zea nudivirus 2.

PubMed

Burand, John P; Kim, Woojin; Afonso, Claudio L; Tulman, Edan R; Kutish, Gerald F; Lu, Zhiqiang; Rock, Daniel L

2012-01-01

The sexually transmitted insect virus Helicoverpa zea nudivirus 2 (HzNV-2) was determined to have a circular double-stranded DNA genome of 231,621 bp coding for an estimated 113 open reading frames (ORFs). HzNV-2 is most closely related to the nudiviruses, a sister group of the insect baculoviruses. Several putative ORFs that share homology with the baculovirus core genes were identified in the viral genome. However, HzNV-2 lacks several key genetic features of baculoviruses including the late transcriptional regulation factor, LEF-1 and the palindromic hrs, which serve as origins of replication. The HzNV-2 genome was found to code for three ORFs that had significant sequence homology to cellular genes which are not generally found in viral genomes. These included a presumed juvenile hormone esterase gene, a gene coding for a putative zinc-dependent matrix metalloprotease, and a major facilitator superfamily protein gene; all of which are believed to play a role in the cellular proliferation and the tissue hypertrophy observed in the malformation of reproductive organs observed in HzNV-2 infected corn earworm moths, Helicoverpa zea.

Taspine derivative 12k suppressed A549 cell migration through the Wnt/β-catenin and EphrinB2 signaling pathway.

PubMed

Dai, Bingling; Ma, Yujiao; Yang, Tianfeng; Wang, Wenjie; Zhang, Yanmin

2017-03-01

12k, a taspine derivative, has been demonstrated to have the potent anti-tumor activity in lung cancer and colorectal cancer. The study aims to further explore the underlying mechanisms of 12k on A549 cell migration in vitro. Our data demonstrated that 12k negatively regulated Wnt signaling pathway by suppressing the phosphorylation of LRP5/6, and inhibiting the expression and nuclear translocation of β-catenin. 12k was shown to downregulate MMP3 and MMP7 expression which regulated by β-catenin interacts with TCF/LEF in the nucleus, and effectively impaired the related migration protein expression of MMP2 and MMP9 in A549 cells. In addition, 12k repressed the EphrinB2 and its PDZ protein, impairing the VEGFR2 and VEGFR3 expression in A549 cells, as well as inhibited the downstream of VEGFR2 included PI3K/AKT/mTOR and ERK/MAPK signaling pathways. Taken together, our findings revealed that 12k suppressed migration of A549 cells through the Wnt/β-catenin signaling pathway and EphrinB2 related signaling pathway. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Wnt/β-catenin pathway regulates Bmp2-mediated differentiation of dental follicle cells

PubMed Central

Silvério, Karina G.; Davidson, Kathryn C.; James, Richard G.; Adams, Allison M.; Foster, Brian L.; Nociti, Francisco H.; Somermam, Martha J.; Moon, Randall T.

2013-01-01

Background and Objectives Bmp2-induced osteogenic differentiation has been shown to occur through the canonical Wnt/β-catenin pathway, whereas factors promoting canonical Wnt signaling in cementoblasts inhibited cell differentiation and promoted cell proliferation in vitro. The aim of this study was to investigate whether putative precursor cells of cementoblasts, dental follicle cells (murine SVF4 cells), when stimulated with Bmp2, would exhibit changes in genes/proteins associated with the Wnt/β-catenin pathway. Materials and Methods SVF4 cells were stimulated with Bmp2, and the following assays were carried out: 1) Wnt/β-catenin pathway activation assessed by western blot, β-catenin/TCF reporter assay, and gene expression of lymphoid enhancer-binding factor-1 (Lef1), transcription factor 7 (Tcf7), Wnt inhibitor factor 1 (Wif1) and Axin2, and 2) cementoblast/osteoblast differentiation assessed by mineralization in vitro, and mRNA levels of runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase (Alp), osteocalcin (Ocn) and bone sialoprotein (Bsp) by qPCR after Wnt3a treatment and knockdown of β-catenin. Results Wnt3a induced β-catenin nuclear translocation and upregulated the transcriptional activity of a canonical Wnt-responsive reporter, suggesting the Wnt/β-catenin pathway functions in SVF4 cells. Activation of Wnt signaling with Wnt3a suppressed Bmp2-mediated induction of cementoblast/osteoblast maturation of SVF4 cells. However, β-catenin knockdown showed that Bmp2-induced expression of cementoblast/osteoblast differentiation markers requires endogenous β-catenin. Wnt3a down-regulated transcripts for Runx2, Alp and Ocn in SVF4 cells compared to untreated cells. In contrast, Bmp2 induction of Bsp transcripts occurred independent of Wnt/β-catenin signaling. Conclusions These data suggest that stabilization of β-catenin by Wnt-3a treatment inhibits Bmp2-mediated induction of cementoblast/osteoblast differentiation in SVF4 cells, although Bmp2 requires endogenous Wnt/β-catenin signaling to promote cell maturation. PMID:22150562

Novel mechanisms for the vitamin D receptor (VDR) in the skin and in skin cancer.

PubMed

Bikle, Daniel D; Oda, Yuko; Tu, Chia-Ling; Jiang, Yan

2015-04-01

The VDR acting with or without its principal ligand 1,25(OH)2D regulates two central processes in the skin, interfollicular epidermal (IFE) differentiation and hair follicle cycling (HFC). Calcium is an important co-regulator with 1,25(OH)2D at least of epidermal differentiation. Knockout of the calcium sensing receptor (CaSR) in addition to VDR accelerates the development of skin cancer in mice on a low calcium diet. Coactivators such as mediator 1 (aka DRIP205) and steroid receptor coactivator 3 (SRC3) regulate VDR function at different stages of the differentiation process, with Med 1 essential for hair follicle differentiation and early stages of epidermal differentiation and proliferation and SRC3 essential for the latter stages of differentiation including formation of the permeability barrier and innate immunity. The corepressor of VDR, hairless (HR), is essential for hair follicle cycling, although its effect on epidermal differentiation in vivo is minimal. In its regulation of HFC and IFE VDR controls two pathways-wnt/β-catenin and sonic hedgehog (SHH). In the absence of VDR these pathways are overexpressed leading to tumor formation. Whereas, VDR binding to β-catenin may block its activation of TCF/LEF1 sites, β-catenin binding to VDR may enhance its activation of VDREs. 1,25(OH)2D promotes but may not be required for these interactions. Suppression of SHH expression by VDR, on the other hand, requires 1,25(OH)2D. The major point of emphasis is that the role of VDR in the skin involves a number of novel mechanisms, both 1,25(OH)2D dependent and independent, that when disrupted interfere with IFE differentiation and HFC, predisposing to cancer formation. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Microtubule actin crosslinking factor 1 promotes osteoblast differentiation by promoting β-catenin/TCF1/Runx2 signaling axis.

PubMed

Hu, Lifang; Su, Peihong; Yin, Chong; Zhang, Yan; Li, Runzhi; Yan, Kun; Chen, Zhihao; Li, Dijie; Zhang, Ge; Wang, Liping; Miao, Zhiping; Qian, Airong; Xian, Cory J

2018-02-01

Osteoblast differentiation is a multistep process delicately regulated by many factors, including cytoskeletal dynamics and signaling pathways. Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes; however, its role in regulating osteoblast differentiation is still needed to be elucidated. To further uncover the functions and mechanisms of action of MACF1 in osteoblast differentiation, we examined effects of MACF1 knockdown (MACF1-KD) in MC3T3-E1 osteoblastic cells on their osteoblast differentiation and associated molecular mechanisms. The results showed that knockdown of MACF1 significantly suppressed mineralization of MC3T3-E1 cells, down-regulated the expression of key osteogenic genes alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and type I collagen α1 (Col Iα1). Knockdown of MACF1 dramatically reduced the nuclear translocation of β-catenin, decreased the transcriptional activation of T cell factor 1 (TCF1), and down-regulated the expression of TCF1, lymphoid enhancer-binding factor 1 (LEF1), and Runx2, a target gene of β-catenin/TCF1. In addition, MACF1-KD increased the active level of glycogen synthase kinase-3β (GSK-3β), which is a key regulator for β-catenin signal transduction. Moreover, the reduction of nuclear β-catenin amount and decreased expression of TCF1 and Runx2 were significantly reversed in MACF1-KD cells when treated with lithium chloride, an agonist for β-catenin by inhibiting GSK-3β activity. Taken together, these findings suggest that knockdown of MACF1 in osteoblastic cells inhibits osteoblast differentiation through suppressing the β-catenin/TCF1-Runx2 axis. Thus, a novel role of MACF1 in and a new mechanistic insight of osteoblast differentiation are uncovered. © 2017 Wiley Periodicals, Inc.

Comprehensive annotation of Glossina pallidipes salivary gland hypertrophy virus from Ethiopian tsetse flies: a proteogenomics approach

PubMed Central

Kariithi, Henry M.; Cousserans, François; Parker, Nicolas J.; İnce, İkbal Agah; Scully, Erin D.; Boeren, Sjef; Geib, Scott M.; Mekonnen, Solomon; Vlak, Just M.; Parker, Andrew G.; Vreysen, Marc J. B.; Bergoin, Max

2016-01-01

Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; family Hytrosaviridae) can establish asymptomatic and symptomatic infection in its tsetse fly host. Here, we present a comprehensive annotation of the genome of an Ethiopian GpSGHV isolate (GpSGHV-Eth) compared with the reference Ugandan GpSGHV isolate (GpSGHV-Uga; GenBank accession number EF568108). GpSGHV-Eth has higher salivary gland hypertrophy syndrome prevalence than GpSGHV-Uga. We show that the GpSGHV-Eth genome has 190 291 nt, a low G+C content (27.9 %) and encodes 174 putative ORFs. Using proteogenomic and transcriptome mapping, 141 and 86 ORFs were mapped by transcripts and peptides, respectively. Furthermore, of the 174 ORFs, 132 had putative transcriptional signals [TATA-like box and poly(A) signals]. Sixty ORFs had both TATA-like box promoter and poly(A) signals, and mapped by both transcripts and peptides, implying that these ORFs encode functional proteins. Of the 60 ORFs, 10 ORFs are homologues to baculovirus and nudivirus core genes, including three per os infectivity factors and four RNA polymerase subunits (LEF4, 5, 8 and 9). Whereas GpSGHV-Eth and GpSGHV-Uga are 98.1 % similar at the nucleotide level, 37 ORFs in the GpSGHV-Eth genome had nucleotide insertions (n = 17) and deletions (n = 20) compared with their homologues in GpSGHV-Uga. Furthermore, compared with the GpSGHV-Uga genome, 11 and 24 GpSGHV ORFs were deleted and novel, respectively. Further, 13 GpSGHV-Eth ORFs were non-canonical; they had either CTG or TTG start codons instead of ATG. Taken together, these data suggest that GpSGHV-Eth and GpSGHV-Uga represent two different lineages of the same virus. Genetic differences combined with host and environmental factors possibly explain the differential GpSGHV pathogenesis observed in different G. pallidipes colonies. PMID:26801744

microRNA-221 Enhances MYCN via Targeting Nemo-like Kinase and Functions as an Oncogene Related to Poor Prognosis in Neuroblastoma.

PubMed

He, Xiao-Yan; Tan, Zheng-Lan; Mou, Qin; Liu, Fang-Jie; Liu, Shan; Yu, Chao-Wen; Zhu, Jin; Lv, Lin-Ya; Zhang, Jun; Wang, Shan; Bao, Li-Ming; Peng, Bin; Zhao, Hui; Zou, Lin

2017-06-01

Purpose: MYCN is one of the most well-characterized genetic markers of neuroblastoma. However, the mechanisms as to how MYCN mediate neuroblastoma tumorigenesis are not fully clear. Increasing evidence has confirmed that the dysregulation of miRNAs is involved in MYCN-mediated neuroblastoma tumorigenesis, supporting their potential as therapeutic targets for neuroblastoma. Although miR-221 has been reported as one of the upregulated miRNAs, the interplay between miR-221 and MYCN-mediated neuroblastoma progression remains largely elusive. Experimental Design: The expression of miR-221 in the formalin-fixed, paraffin-embedded tissues from 31 confirmed patients with neuroblastoma was detected by locked nucleic acid- in situ hybridization and qRT-PCR. The correlation between miR-221 expression and clinical features in patients with neuroblastoma was assessed. The mechanisms as to how miR-221 regulate MYCN in neuroblastoma were addressed. The effect of miR-221 on cellular proliferation in neuroblastoma was determined both in vitro and in vivo Results: miR-221 was significantly upregulated in neuroblastoma tumor cells and tissues that overexpress MYCN, and high expression of miR-221 was positively associated with poor survival in patients with neuroblastoma. Nemo-like kinase (NLK) as a direct target of miR-221 in neuroblastoma was verified. In addition, overexpression of miR-221 decreased LEF1 phosphorylation but increased the expression of MYCN via targeting of NLK and further regulated cell cycle, particularly in S-phase, promoting the growth of neuroblastoma cells. Conclusions: This study provides a novel insight for miR-221 in the control of neuroblastoma cell proliferation and tumorigenesis, suggesting potentials of miR-221 as a prognosis marker and therapeutic target for patients with MYCN overexpressing neuroblastoma. Clin Cancer Res; 23(11); 2905-18. ©2016 AACR . ©2016 American Association for Cancer Research.

Upregulation of MiR-212 Inhibits Migration and Tumorigenicity and Inactivates Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma.

PubMed

Jia, Pengbo; Wei, Guangbing; Zhou, Cancan; Gao, Qi; Wu, Yunhua; Sun, Xuejun; Li, Xuqi

2018-01-01

MicroRNAs are involved in hepatocellular carcinoma metastasis, a principal cause of hepatocellular carcinoma-related death in patients worldwide. MiR-212 is a microRNA that has been identified in several types of cancers and is postulated to influence cell signaling and subsequent malignant pathogenesis. Despite emerging reports suggesting that miR-212 plays a significant role in the onset, progression, and migration of these types of malignant tumors, its involvement in the development of hepatocellular carcinoma has not been fully elucidated. Quantitative reverse transcription polymerase chain reaction, wound healing, transwell migration and invasion assays, Western blotting, and xenograft tumor growth models were performed to test the expression levels and functions of miR-212 in hepatocellular carcinoma. Luciferase reporter assay, quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry were used to identify and verify the target of miR-212. In this study, we identify significant repression of miR-212 in hepatocellular carcinoma and demonstrate that overexpression of miR-212 inhibits the migration of hepatocellular carcinoma cells in vitro and in vivo. Furthermore, we identify forkhead box M1, whose expression is inversely related to that of miR-212, as a direct target of miR-212. Additionally, reexpression of forkhead box M1 rescues the miR-212-mediated inhibition of cell migration. We observed that inhibition of miR-212 activates forkhead box M1 but inhibits the Wnt/β-catenin pathway by suppressing Wnt, LEF-1, c-Myc, and nuclear β-catenin. Finally, in vivo studies confirmed the inhibitory effect of miR-212 on hepatocellular carcinoma growth. Our present findings indicate that miR-212 is a potential prognostic biomarker of hepatocellular carcinoma and that the miR-212/forkhead box M1 regulatory axis may represent a new therapeutic objective for hepatocellular carcinoma treatment.

The up-scaling of ecosystem functions in a heterogeneous world

NASA Astrophysics Data System (ADS)

Lohrer, Andrew M.; Thrush, Simon F.; Hewitt, Judi E.; Kraan, Casper

2015-05-01

Earth is in the midst of a biodiversity crisis that is impacting the functioning of ecosystems and the delivery of valued goods and services. However, the implications of large scale species losses are often inferred from small scale ecosystem functioning experiments with little knowledge of how the dominant drivers of functioning shift across scales. Here, by integrating observational and manipulative experimental field data, we reveal scale-dependent influences on primary productivity in shallow marine habitats, thus demonstrating the scalability of complex ecological relationships contributing to coastal marine ecosystem functioning. Positive effects of key consumers (burrowing urchins, Echinocardium cordatum) on seafloor net primary productivity (NPP) elucidated by short-term, single-site experiments persisted across multiple sites and years. Additional experimentation illustrated how these effects amplified over time, resulting in greater primary producer biomass sediment chlorophyll a content (Chla) in the longer term, depending on climatic context and habitat factors affecting the strengths of mutually reinforcing feedbacks. The remarkable coherence of results from small and large scales is evidence of real-world ecosystem function scalability and ecological self-organisation. This discovery provides greater insights into the range of responses to broad-scale anthropogenic stressors in naturally heterogeneous environmental settings.

The up-scaling of ecosystem functions in a heterogeneous world

PubMed Central

Lohrer, Andrew M.; Thrush, Simon F.; Hewitt, Judi E.; Kraan, Casper

2015-01-01

Earth is in the midst of a biodiversity crisis that is impacting the functioning of ecosystems and the delivery of valued goods and services. However, the implications of large scale species losses are often inferred from small scale ecosystem functioning experiments with little knowledge of how the dominant drivers of functioning shift across scales. Here, by integrating observational and manipulative experimental field data, we reveal scale-dependent influences on primary productivity in shallow marine habitats, thus demonstrating the scalability of complex ecological relationships contributing to coastal marine ecosystem functioning. Positive effects of key consumers (burrowing urchins, Echinocardium cordatum) on seafloor net primary productivity (NPP) elucidated by short-term, single-site experiments persisted across multiple sites and years. Additional experimentation illustrated how these effects amplified over time, resulting in greater primary producer biomass sediment chlorophyll a content (Chla) in the longer term, depending on climatic context and habitat factors affecting the strengths of mutually reinforcing feedbacks. The remarkable coherence of results from small and large scales is evidence of real-world ecosystem function scalability and ecological self-organisation. This discovery provides greater insights into the range of responses to broad-scale anthropogenic stressors in naturally heterogeneous environmental settings. PMID:25993477

Decorrelation scales for Arctic Ocean hydrography - Part I: Amerasian Basin

NASA Astrophysics Data System (ADS)

Sumata, Hiroshi; Kauker, Frank; Karcher, Michael; Rabe, Benjamin; Timmermans, Mary-Louise; Behrendt, Axel; Gerdes, Rüdiger; Schauer, Ursula; Shimada, Koji; Cho, Kyoung-Ho; Kikuchi, Takashi

2018-03-01

Any use of observational data for data assimilation requires adequate information of their representativeness in space and time. This is particularly important for sparse, non-synoptic data, which comprise the bulk of oceanic in situ observations in the Arctic. To quantify spatial and temporal scales of temperature and salinity variations, we estimate the autocorrelation function and associated decorrelation scales for the Amerasian Basin of the Arctic Ocean. For this purpose, we compile historical measurements from 1980 to 2015. Assuming spatial and temporal homogeneity of the decorrelation scale in the basin interior (abyssal plain area), we calculate autocorrelations as a function of spatial distance and temporal lag. The examination of the functional form of autocorrelation in each depth range reveals that the autocorrelation is well described by a Gaussian function in space and time. We derive decorrelation scales of 150-200 km in space and 100-300 days in time. These scales are directly applicable to quantify the representation error, which is essential for use of ocean in situ measurements in data assimilation. We also describe how the estimated autocorrelation function and decorrelation scale should be applied for cost function calculation in a data assimilation system.

Universal scaling function in discrete time asymmetric exclusion processes

NASA Astrophysics Data System (ADS)

Chia, Nicholas; Bundschuh, Ralf

2005-03-01

In the universality class of the one dimensional Kardar-Parisi-Zhang surface growth, Derrida and Lebowitz conjectured the universality of not only the scaling exponents, but of an entire scaling function. Since Derrida and Lebowitz' original publication this universality has been verified for a variety of continuous time systems in the KPZ universality class. We study the Derrida-Lebowitz scaling function for multi-particle versions of the discrete time Asymmetric Exclusion Process. We find that in this discrete time system the Derrida-Lebowitz scaling function not only properly characterizes the large system size limit, but even accurately describes surprisingly small systems. These results have immediate applications in searching biological sequence databases.

Rasch analysis of the Italian Lower Extremity Functional Scale: insights on dimensionality and suggestions for an improved 15-item version.

PubMed

Bravini, Elisabetta; Giordano, Andrea; Sartorio, Francesco; Ferriero, Giorgio; Vercelli, Stefano

2017-04-01

To investigate dimensionality and the measurement properties of the Italian Lower Extremity Functional Scale using both classical test theory and Rasch analysis methods, and to provide insights for an improved version of the questionnaire. Rasch analysis of individual patient data. Rehabilitation centre. A total of 135 patients with musculoskeletal diseases of the lower limb. Patients were assessed with the Lower Extremity Functional Scale before and after the rehabilitation. Rasch analysis showed some problems related to rating scale category functioning, items fit, and items redundancy. After an iterative process, which resulted in the reduction of rating scale categories from 5 to 4, and in the deletion of 5 items, the psychometric properties of the Italian Lower Extremity Functional Scale improved. The retained 15 items with a 4-level response format fitted the Rasch model (internal construct validity), and demonstrated unidimensionality and good reliability indices (person-separation reliability 0.92; Cronbach's alpha 0.94). Then, the analysis showed differential item functioning for six of the retained items. The sensitivity to change of the Italian 15-item Lower Extremity Functional Scale was nearly equal to the one of the original version (effect size: 0.93 and 0.98; standardized response mean: 1.20 and 1.28, respectively for the 15-item and 20-item versions). The Italian Lower Extremity Functional Scale had unsatisfactory measurement properties. However, removing five items and simplifying the scoring from 5 to 4 levels resulted in a more valid measure with good reliability and sensitivity to change.

A test of the cross-scale resilience model: Functional richness in Mediterranean-climate ecosystems

USGS Publications Warehouse

Wardwell, D.A.; Allen, Craig R.; Peterson, G.D.; Tyre, A.J.

2008-01-01

Ecological resilience has been proposed to be generated, in part, in the discontinuous structure of complex systems. Environmental discontinuities are reflected in discontinuous, aggregated animal body mass distributions. Diversity of functional groups within body mass aggregations (scales) and redundancy of functional groups across body mass aggregations (scales) has been proposed to increase resilience. We evaluate that proposition by analyzing mammalian and avian communities of Mediterranean-climate ecosystems. We first determined that body mass distributions for each animal community were discontinuous. We then calculated the variance in richness of function across aggregations in each community, and compared observed values with distributions created by 1000 simulations using a null of random distribution of function, with the same n, number of discontinuities and number of functional groups as the observed data. Variance in the richness of functional groups across scales was significantly lower in real communities than in simulations in eight of nine sites. The distribution of function across body mass aggregations in the animal communities we analyzed was non-random, and supports the contentions of the cross-scale resilience model. ?? 2007 Elsevier B.V. All rights reserved.

Environmental filtering structures tree functional traits combination and lineages across space in tropical tree assemblages.

PubMed

Asefa, Mengesha; Cao, Min; Zhang, Guocheng; Ci, Xiuqin; Li, Jie; Yang, Jie

2017-03-09

Environmental filtering consistently shapes the functional and phylogenetic structure of species across space within diverse forests. However, poor descriptions of community functional and lineage distributions across space hamper the accurate understanding of coexistence mechanisms. We combined environmental variables and geographic space to explore how traits and lineages are filtered by environmental factors using extended RLQ and fourth-corner analyses across different spatial scales. The dispersion patterns of traits and lineages were also examined in a 20-ha tropical rainforest dynamics plot in southwest China. We found that environmental filtering was detected across all spatial scales except the largest scale (100 × 100 m). Generally, the associations between functional traits and environmental variables were more or less consistent across spatial scales. Species with high resource acquisition-related traits were associated with the resource-rich part of the plot across the different spatial scales, whereas resource-conserving functional traits were distributed in limited-resource environments. Furthermore, we found phylogenetic and functional clustering at all spatial scales. Similar functional strategies were also detected among distantly related species, suggesting that phylogenetic distance is not necessarily a proxy for functional distance. In summary, environmental filtering considerably structured the trait and lineage assemblages in this species-rich tropical rainforest.

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

Friar, James Lewis; Goldman, Terrance J.; Pérez-Mercader, J.

In this paper, we apply the Law of Total Probability to the construction of scale-invariant probability distribution functions (pdf's), and require that probability measures be dimensionless and unitless under a continuous change of scales. If the scale-change distribution function is scale invariant then the constructed distribution will also be scale invariant. Repeated application of this construction on an arbitrary set of (normalizable) pdf's results again in scale-invariant distributions. The invariant function of this procedure is given uniquely by the reciprocal distribution, suggesting a kind of universality. Finally, we separately demonstrate that the reciprocal distribution results uniquely from requiring maximum entropymore » for size-class distributions with uniform bin sizes.« less

Stressful Parental-Bonding Exaggerates the Functional and Emotional Disturbances of Primary Dysmenorrhea.

PubMed

Xu, Kai; Chen, Liuxi; Fu, Lingyun; Xu, Shaofang; Fan, Hongying; Gao, Qianqian; Xu, You; Wang, Wei

2016-08-01

Some evidence suggests that women with primary dysmenorrhea (or painful period) often have traumatic experience with parental attachments, but the exact relationship is still unclear. This study aims to investigate associations between styles of the parental bonding and the detailed aspects of the disorder in Chinese university-student women. From university-student women, we have invited 50 primary dysmenorrhea patients and 111 healthy volunteers, to undergo tests of the Functional and Emotional Measure of Dysmenorrhea (FEMD), the Family Relationship Questionnaire (FRQ), and the visual analogue scale for the pain intensity experienced. Besides the high scores of the FEMD Functional and Emotional scales, the dysmenorrhea patients also scored significantly higher than the healthy controls on the FRQ scales of Paternal Dominance and Maternal Abuse. In patients, the FEMD Emotional scale was negatively predicted by the Paternal Freedom Release scale, and the FEMD Functional scale was positively predicted by the Maternal Dominance scale. Inappropriate parental bonding or chronic traumatic attachment styles have respective relationships with the functional and emotional disturbances experienced by the primary dysmenorrhea patients.

Dimensions of functional social support and psychological symptoms.

PubMed

Schonfeld, I S

1991-11-01

In the summer following graduation a sample of 125 female college graduates (mean age = 28) completed Cohen & Wills' ISEL (1985) which includes scales measuring four social support functions: belonging (social companionship), appraisal (availability of confidants), tangible (instrumental), and self-esteem support. In the summer and fall subject status on two outcome scales was ascertained: the Psychophysiologic Symptom Scale and the Center for Epidemiologic Studies Depression Scale (CES-D). Reliability of the difference scores suggested that the ISEL scales do not measure entirely different constructs and the ISEL Self-esteem Scale is operationally redundant with the Rosenberg Self-esteem scale and the CES-D. Cross-sectional analyses indicated that the ISEL scales were related to symptoms. By contrast, standard longitudinal and prospective MLR analyses indicated that only the Belonging Scale was significantly related to future symptoms. The issues of confounding support with symptoms and the dimensionality of the subscales were discussed. The study suggests that specific functions of support take on greater importance during major life transitions and that any one supportive behaviour often serves multiple functions.

Retinotopic patterns of functional connectivity between V1 and large-scale brain networks during resting fixation

PubMed Central

Griffis, Joseph C.; Elkhetali, Abdurahman S.; Burge, Wesley K.; Chen, Richard H.; Bowman, Anthony D.; Szaflarski, Jerzy P.; Visscher, Kristina M.

2016-01-01

Psychophysical and neurobiological evidence suggests that central and peripheral vision are specialized for different functions. This specialization of function might be expected to lead to differences in the large-scale functional interactions of early cortical areas that represent central and peripheral visual space. Here, we characterize differences in whole-brain functional connectivity among sectors in primary visual cortex (V1) corresponding to central, near-peripheral, and far-peripheral vision during resting fixation. Importantly, our analyses reveal that eccentricity sectors in V1 have different functional connectivity with non-visual areas associated with large-scale brain networks. Regions associated with the fronto-parietal control network are most strongly connected with central sectors of V1, regions associated with the cingulo-opercular control network are most strongly connected with near-peripheral sectors of V1, and regions associated with the default mode and auditory networks are most strongly connected with far-peripheral sectors of V1. Additional analyses suggest that similar patterns are present during eyes-closed rest. These results suggest that different types of visual information may be prioritized by large-scale brain networks with distinct functional profiles, and provide insights into how the small-scale functional specialization within early visual regions such as V1 relates to the large-scale organization of functionally distinct whole-brain networks. PMID:27554527

Beta-diversity of ectoparasites at two spatial scales: nested hierarchy, geography and habitat type.

PubMed

Warburton, Elizabeth M; van der Mescht, Luther; Stanko, Michal; Vinarski, Maxim V; Korallo-Vinarskaya, Natalia P; Khokhlova, Irina S; Krasnov, Boris R

2017-06-01

Beta-diversity of biological communities can be decomposed into (a) dissimilarity of communities among units of finer scale within units of broader scale and (b) dissimilarity of communities among units of broader scale. We investigated compositional, phylogenetic/taxonomic and functional beta-diversity of compound communities of fleas and gamasid mites parasitic on small Palearctic mammals in a nested hierarchy at two spatial scales: (a) continental scale (across the Palearctic) and (b) regional scale (across sites within Slovakia). At each scale, we analyzed beta-diversity among smaller units within larger units and among larger units with partitioning based on either geography or ecology. We asked (a) whether compositional, phylogenetic/taxonomic and functional dissimilarities of flea and mite assemblages are scale dependent; (b) how geographical (partitioning of sites according to geographic position) or ecological (partitioning of sites according to habitat type) characteristics affect phylogenetic/taxonomic and functional components of dissimilarity of ectoparasite assemblages and (c) whether assemblages of fleas and gamasid mites differ in their degree of dissimilarity, all else being equal. We found that compositional, phylogenetic/taxonomic, or functional beta-diversity was greater on a continental rather than a regional scale. Compositional and phylogenetic/taxonomic components of beta-diversity were greater among larger units than among smaller units within larger units, whereas functional beta-diversity did not exhibit any consistent trend regarding site partitioning. Geographic partitioning resulted in higher values of beta-diversity of ectoparasites than ecological partitioning. Compositional and phylogenetic components of beta-diversity were higher in fleas than mites but the opposite was true for functional beta-diversity in some, but not all, traits.

Revised upper limb module for spinal muscular atrophy: Development of a new module.

PubMed

Mazzone, Elena S; Mayhew, Anna; Montes, Jacqueline; Ramsey, Danielle; Fanelli, Lavinia; Young, Sally Dunaway; Salazar, Rachel; De Sanctis, Roberto; Pasternak, Amy; Glanzman, Allan; Coratti, Giorgia; Civitello, Matthew; Forcina, Nicola; Gee, Richard; Duong, Tina; Pane, Marika; Scoto, Mariacristina; Pera, Maria Carmela; Messina, Sonia; Tennekoon, Gihan; Day, John W; Darras, Basil T; De Vivo, Darryl C; Finkel, Richard; Muntoni, Francesco; Mercuri, Eugenio

2017-06-01

There is a growing need for a robust clinical measure to assess upper limb motor function in spinal muscular atrophy (SMA), as the available scales lack sensitivity at the extremes of the clinical spectrum. We report the development of the Revised Upper Limb Module (RULM), an assessment specifically designed for upper limb function in SMA patients. An international panel with specific neuromuscular expertise performed a thorough review of scales currently available to assess upper limb function in SMA. This review facilitated a revision of the existing upper limb function scales to make a more robust clinical scale. Multiple revisions of the scale included statistical analysis and captured clinically relevant changes to fulfill requirements by regulators and advocacy groups. The resulting RULM scale shows good reliability and validity, making it a suitable tool to assess upper extremity function in the SMA population for multi-center clinical research. Muscle Nerve 55: 869-874, 2017. © 2016 Wiley Periodicals, Inc.

Determination of the Time-Space Magnetic Correlation Functions in the Solar Wind

NASA Astrophysics Data System (ADS)

Weygand, J. M.; Matthaeus, W. H.; Kivelson, M.; Dasso, S.

2013-12-01

Magnetic field data from many different intervals and 7 different solar wind spacecraft are employed to estimate the scale-dependent time decorrelation function in the interplanetary magnetic field in both the slow and fast solar wind. This estimation requires correlations varying with both space and time lags. The two point correlation function with no time lag is determined by correlating time series data from multiple spacecraft separated in space and for complete coverage of length scales relies on many intervals with different spacecraft spatial separations. In addition we employ single spacecraft time-lagged correlations, and two spacecraft time lagged correlations to access different spatial and temporal correlation data. Combining these data sets gives estimates of the scale-dependent time decorrelation function, which in principle tells us how rapidly time decorrelation occurs at a given wavelength. For static fields the scale-dependent time decorrelation function is trivially unity, but in turbulence the nonlinear cascade process induces time-decorrelation at a given length scale that occurs more rapidly with decreasing scale. The scale-dependent time decorrelation function is valuable input to theories as well as various applications such as scattering, transport, and study of predictability. It is also a fundamental element of formal turbulence theory. Our results are extension of the Eulerian correlation functions estimated in Matthaeus et al. [2010], Weygand et al [2012; 2013].

Interpretability of the PedsQL gastrointestinal symptoms scales and gastrointestinal worry scales in pediatric patients with functional and organic gastrointestinal diseases

USDA-ARS?s Scientific Manuscript database

The present study investigates the clinical interpretability of the Pediatric Quality of Life Inventor (PedsQL) Gastrointestinal Symptoms Scales and Worry Scales in pediatric patients with functional gastrointestinal disorders or organic gastrointestinal diseases in comparison with healthy controls....

Assessment of personality-related levels of functioning: a pilot study of clinical assessment of the DSM-5 level of personality functioning based on a semi-structured interview.

PubMed

Thylstrup, Birgitte; Simonsen, Sebastian; Nemery, Caroline; Simonsen, Erik; Noll, Jane Fjernestad; Myatt, Mikkel Wanting; Hesse, Morten

2016-08-25

The personality disorder categories in the Diagnostic and Statistical Manual of Mental Disorders IV have been extensively criticized, and there is a growing consensus that personality pathology should be represented dimensionally rather than categorically. The aim of this pilot study was to test the Clinical Assessment of the Level of Personality Functioning Scale, a semi-structured clinical interview, designed to assess the Level of Personality Functioning Scale of the DSM-5 (Section III) by applying strategies similar to what characterizes assessments in clinical practice. The inter-rater reliability of the assessment of the four domains and the total impairment in the Level of Personality Functioning Scale were measured in a patient sample that varied in terms of severity and type of pathology. Ratings were done independently by the interviewer and two experts who watched a videotaped Clinical Assessment of the Level of Personality Functioning Scale interview. Inter-rater reliability coefficients varied between domains and were not sufficient for clinical practice, but may support the use of the interview to assess the dimensions of personality functioning for research purposes. While designed to measure the Level of Personality Functioning Scale with a high degree of similarity to clinical practice, the Clinical Assessment of the Level of Personality Functioning Scale had weak reliabilities and a rating based on a single interview should not be considered a stand-alone assessment of areas of functioning for a given patient.

Effect of Finite Computational Domain on Turbulence Scaling Law in Both Physical and Spectral Spaces

NASA Technical Reports Server (NTRS)

Hou, Thomas Y.; Wu, Xiao-Hui; Chen, Shiyi; Zhou, Ye

1998-01-01

The well-known translation between the power law of energy spectrum and that of the correlation function or the second order structure function has been widely used in analyzing random data. Here, we show that the translation is valid only in proper scaling regimes. The regimes of valid translation are different for the correlation function and the structure function. Indeed, they do not overlap. Furthermore, in practice, the power laws exist only for a finite range of scales. We show that this finite range makes the translation inexact even in the proper scaling regime. The error depends on the scaling exponent. The current findings are applicable to data analysis in fluid turbulence and other stochastic systems.

Rasch measurement: the Arm Activity measure (ArmA) passive function sub-scale.

PubMed

Ashford, Stephen; Siegert, Richard J; Alexandrescu, Roxana

2016-01-01

To evaluate the conformity of the Arm Activity measure (ArmA) passive function sub-scale to the Rasch model. A consecutive cohort of patients (n = 92) undergoing rehabilitation, including upper limb rehabilitation and spasticity management, at two specialist rehabilitation units were included. Rasch analysis was used to examine scaling and conformity to the model. Responses were analysed using Rasch unidimensional measurement models (RUMM 2030). The following aspects were considered: overall model and individual item fit statistics and fit residuals, internal reliability, item response threshold ordering, item bias, local dependency and unidimensionality. ArmA contains both active and passive function sub-scales, but in this analysis only the passive function sub-scale was considered. Four of the seven items in the ArmA passive function sub-scale initially had disordered thresholds. These items were rescored to four response options, which resulted in ordered thresholds for all items. Once the items with disordered thresholds had been rescored, item bias was not identified for age, global disability level or diagnosis, but with a small difference in difficulty between males and females for one item of the scale. Local dependency was not observed and the unidimensionality of the sub-scale was supported and good fit to the Rasch model was identified. The person separation index (PSI) was 0.95 indicating that the scale is able to reliably differentiate at least two groups of patients. The ArmA passive function sub-scale was shown in this evaluation to conform to the Rasch model once disordered thresholds had been addressed. Using the logit scores produced by the Rasch model it was possible to convert this back to the original scale range. Implications for Rehabilitation The ArmA passive function sub-scale was shown, in this evaluation, to conform to the Rasch model once disordered thresholds had been addressed and therefore to be a clinically applicable and potentially useful hierarchical measure. Using Rasch logit scores it has be possible to convert back to the original ordinal scale range and provide an indication of real change to enable evaluation of clinical outcome of importance to patients and clinicians.

The Brief Impairment Scale (Bis): A Multidimensional Scale of Functional Impairment for Children and Adolescents.

ERIC Educational Resources Information Center

Bird, Hector R.; Canino, Glorisa J.; Davies, Mark; Ramirez, Rafael; Chavez, Ligia; Duarte, Cristiane; Shen, Sa

2005-01-01

Objective: This article provides the results of the psychometric testing of the Brief Impairment Scale (BIS). The BIS is a 23-item instrument that evaluates three domains of functioning: interpersonal relations, school/work functioning, and self-care/self-fulfilment. It capitalizes on the strengths of existing global measures while addressing some…

Scaling functional status within the interRAI suite of assessment instruments

PubMed Central

2013-01-01

Background As one ages, physical, cognitive, and clinical problems accumulate and the pattern of loss follows a distinct progression. The first areas requiring outside support are the Instrumental Activities of Daily Living and over time there is a need for support in performing the Activities of Daily Living. Two new functional hierarchies are presented, an IADL hierarchical capacity scale and a combination scale integrating both IADL and ADL hierarchies. Methods A secondary analyses of data from a cross-national sample of community residing persons was conducted using 762,023 interRAI assessments. The development of the new IADL Hierarchy and a new IADL-ADL combined scale proceeded through a series of interrelated steps first examining individual IADL and ADL item scores among persons receiving home care and those living independently without services. A factor analysis demonstrated the overall continuity across the IADL-ADL continuum. Evidence of the validity of the scales was explored with associative analyses of factors such as a cross-country distributional analysis for persons in home care programs, a count of functional problems across the categories of the hierarchy, an assessment of the hours of informal and formal care received each week by persons in the different categories of the hierarchy, and finally, evaluation of the relationship between cognitive status and the hierarchical IADL-ADL assignments. Results Using items from interRAI’s suite of assessment instruments, two new functional scales were developed, the interRAI IADL Hierarchy Scale and the interRAI IADL-ADL Functional Hierarchy Scale. The IADL Hierarchy Scale consisted of 5 items, meal preparation, housework, shopping, finances and medications. The interRAI IADL-ADL Functional Hierarchy Scale was created through an amalgamation of the ADL Hierarchy (developed previously) and IADL Hierarchy Scales. These scales cover the spectrum of IADL and ADL challenges faced by persons in the community. Conclusions An integrated IADL and ADL functional assessment tool is valuable. The loss in these areas follows a general hierarchical pattern and with the interRAI IADL-ADL Functional Hierarchy Scale, this progression can be reliably and validly assessed. Used across settings within the health continuum, it allows for monitoring of individuals from relative independence through episodes of care. PMID:24261417

Critical Casimir force scaling functions of the two-dimensional Ising model at finite aspect ratios

NASA Astrophysics Data System (ADS)

Hobrecht, Hendrik; Hucht, Alfred

2017-02-01

We present a systematic method to calculate the universal scaling functions for the critical Casimir force and the according potential of the two-dimensional Ising model with various boundary conditions. Therefore we start with the dimer representation of the corresponding partition function Z on an L× M square lattice, wrapped around a torus with aspect ratio ρ =L/M . By assuming periodic boundary conditions and translational invariance in at least one direction, we systematically reduce the problem to a 2× 2 transfer matrix representation. For the torus we first reproduce the results by Kaufman and then give a detailed calculation of the scaling functions. Afterwards we present the calculation for the cylinder with open boundary conditions. All scaling functions are given in form of combinations of infinite products and integrals. Our results reproduce the known scaling functions in the limit of thin films ρ \\to 0 . Additionally, for the cylinder at criticality our results confirm the predictions from conformal field theory.

Minimum important differences for the patient-specific functional scale, 4 region-specific outcome measures, and the numeric pain rating scale.

PubMed

Abbott, J Haxby; Schmitt, John

2014-08-01

Multicenter, prospective, longitudinal cohort study. To investigate the minimum important difference (MID) of the Patient-Specific Functional Scale (PSFS), 4 region-specific outcome measures, and the numeric pain rating scale (NPRS) across 3 levels of patient-perceived global rating of change in a clinical setting. The MID varies depending on the external anchor defining patient-perceived "importance." The MID for the PSFS has not been established across all body regions. One thousand seven hundred eight consecutive patients with musculoskeletal disorders were recruited from 5 physical therapy clinics. The PSFS, NPRS, and 4 region-specific outcome measures-the Oswestry Disability Index, Neck Disability Index, Upper Extremity Functional Index, and Lower Extremity Functional Scale-were assessed at the initial and final physical therapy visits. Global rating of change was assessed at the final visit. MID was calculated for the PSFS and NPRS (overall and for each body region), and for each region-specific outcome measure, across 3 levels of change defined by the global rating of change (small, medium, large change) using receiver operating characteristic curve methodology. The MID for the PSFS (on a scale from 0 to 10) ranged from 1.3 (small change) to 2.3 (medium change) to 2.7 (large change), and was relatively stable across body regions. MIDs for the NPRS (-1.5 to -3.5), Oswestry Disability Index (-12), Neck Disability Index (-14), Upper Extremity Functional Index (6 to 11), and Lower Extremity Functional Scale (9 to 16) are also reported. We reported the MID for small, medium, and large patient-perceived change on the PSFS, NPRS, Oswestry Disability Index, Neck Disability Index, Upper Extremity Functional Index, and Lower Extremity Functional Scale for use in clinical practice and research.

Comparisons of severity classification systems for oropharyngeal dysfunction in children with cerebral palsy: Relations with other functional profiles.

PubMed

Goh, Yu-Ra; Choi, Ja Young; Kim, Seon Ah; Park, Jieun; Park, Eun Sook

2018-01-01

This study aimed to investigate the relationships between various classification systems assessing the severity of oropharyngeal dysphagia and communication function and other functional profiles in children with cerebral palsy (CP). This is a prospective, cross-sectional, study in a university-affiliated, tertiary-care hospital. We recruited 151 children with CP (mean age 6.11 years, SD 3.42, range 3-18yr). The Eating and Drinking Ability Classification System (EDACS) and the dysphagia scales of Functional Oral Intake Scale (FOIS), Swallow Function Scales (SFS), and Food Intake Level Scale (FILS) were used. The Communication Function Classification System (CFCS) and Viking Speech Scale (VSS) were employed to classify communication function and speech intelligibility, respectively. The Pediatric Evaluation of Disability Inventory (PEDI) with the Gross Motor Function Classification System (GFMCS) and the Manual Ability Classification System (MACS) level were also assessed. Spearman correlation analysis to investigate the associations between measures and univariate and multivariate logistic regression models to identify significant factors were used. Median GMFCS level of participants was III (interquartile range II-IV). Significant dysphagia based on EDACS level III-V was noted in 23 children (15.2%). There were strong to very strong relationships between the EDACS level with the dysphagia scales. The EDACS presented strong associations with MACS, CFCS, and VSS, a moderate association with GMFCS level, and a moderate to strong association with each domain of the PEDI. In multivariate analysis, poor functioning in EDACS were associated with poor functioning in gross motor and communication functions. Copyright © 2017. Published by Elsevier Ltd.

Transcriptomics Modeling of the Late-Gestation Fetal Pituitary Response to Transient Hypoxia

PubMed Central

Wood, Charles E.; Chang, Eileen I.; Richards, Elaine M.; Rabaglino, Maria Belen; Keller-Wood, Maureen

2016-01-01

Background The late-gestation fetal sheep responds to hypoxia with physiological, neuroendocrine, and cellular responses that aid in fetal survival. The response of the fetus to hypoxia represents a coordinated effort to maximize oxygen transfer from the mother and minimize wasteful oxygen consumption by the fetus. While there have been many studies aimed at investigating the coordinated physiological and endocrine responses to hypoxia, and while immunohistochemical or in situ hybridization studies have revealed pathways supporting the endocrine function of the pituitary, there is little known about the coordinated cellular response of the pituitary to the hypoxia. Results Thirty min hypoxia (from 17.0±1.7 to 8.0±0.8 mm Hg, followed by 30 min normoxia) upregulated 595 and downregulated 790 genes in fetal pituitary (123–132 days’ gestation; term = 147 days). Network inference of up- and down- regulated genes revealed a high degree of functional relatedness amongst the gene sets. Gene ontology analysis revealed upregulation of cellular metabolic processes (e.g., RNA synthesis, response to estrogens) and downregulation of protein phosphorylation, protein metabolism, and mitosis. Genes found to be at the center of the network of upregulated genes included genes important for purine binding and signaling. At the center of the downregulated network were genes involved in mRNA processing, DNA repair, sumoylation, and vesicular trafficking. Transcription factor analysis revealed that both up- and down-regulated gene sets are enriched for control by several transcription factors (e.g., SP1, MAZ, LEF1, NRF1, ELK1, NFAT, E12, PAX4) but not for HIF-1, which is known to be an important controller of genomic responses to hypoxia. Conclusions The multiple analytical approaches used in this study suggests that the acute response to 30 min of transient hypoxia in the late-gestation fetus results in reduced cellular metabolism and a pattern of gene expression that is consistent with cellular oxygen and ATP starvation. In this early time point, we see a vigorous gene response. But, like the hypothalamus, the transcriptomic response is not consistent with mediation by HIF-1. If HIF-1 is a significant controller of gene expression in the fetal pituitary after hypoxia, it must be at a later time. PMID:26859870

Status of the Topside Vary-Chap Ionospheric Model

NASA Astrophysics Data System (ADS)

Reinisch, Bodo; Nsumei, Patrick; Huang, Xueqin; Bilitza, Dieter

Status of the Topside Vary-Chap Ionospheric Model The general alpha-Chapman function for a multi-constituent gas which includes a continuously varying scale height and was therefore dubbed the Vary-Chap function, can present the topside electron density profiles in analytical form. The Vary-Chap profile is defined by the scale height function H(h) and the height and density of the F2 layer peak. By expressing 80,000 ISIS-2 measured topside density profiles as Vary-Chap functions we derived 80,000 scale height functions, which form the basis for the topside density profile modeling. The normalized scale height profiles Hn = H(h)/Hm were grouped according to season, MLAT, and MLT for each 50 km height bin from 200 km to 1400 km, and the median, lower, and upper quartiles for each bin were calculated. Hm is the scale height at the F2 layer peak. The resulting Hn functions are modeled in terms of hyperbolic tangent functions using 5 parameters that are determined by multivariate least squares, including the transition height hT where the scale height gradient has a maximum. These normalized scale height functions, representing the model of the topside electron density profiles from hmF2 to 1,400 km altitude, are independent of hmF2 and NmF2 and can therefore be directly used for the topside Ne profile in IRI. Similarly, this model can extend measured bottomside profiles to the topside, replacing the simple alpha-Chapman function with constant scale height that is currently used for construction of the topside profile in the Digisondes / ARTIST of the Global Ionospheric Radio Observatory (GIRO). It turns out that Hm(top) calculated from the topside profiles is generally several times larger than Hm(bot) derived from the bottomside profiles. This follows necessarily from the difference in the definition of the scale height functions for the topside and bottomside profiles. The diurnal variations of the ratio Hm(top) / Hm(bot) has been determined for different latitudes which makes it now possible to specify the topside profile for any given bottomside profile.

Ubiquity of Benford's law and emergence of the reciprocal distribution

DOE PAGES

Friar, James Lewis; Goldman, Terrance J.; Pérez-Mercader, J.

2016-04-07

In this paper, we apply the Law of Total Probability to the construction of scale-invariant probability distribution functions (pdf's), and require that probability measures be dimensionless and unitless under a continuous change of scales. If the scale-change distribution function is scale invariant then the constructed distribution will also be scale invariant. Repeated application of this construction on an arbitrary set of (normalizable) pdf's results again in scale-invariant distributions. The invariant function of this procedure is given uniquely by the reciprocal distribution, suggesting a kind of universality. Finally, we separately demonstrate that the reciprocal distribution results uniquely from requiring maximum entropymore » for size-class distributions with uniform bin sizes.« less

Fine-Granularity Functional Interaction Signatures for Characterization of Brain Conditions

PubMed Central

Hu, Xintao; Zhu, Dajiang; Lv, Peili; Li, Kaiming; Han, Junwei; Wang, Lihong; Shen, Dinggang; Guo, Lei; Liu, Tianming

2014-01-01

In the human brain, functional activity occurs at multiple spatial scales. Current studies on functional brain networks and their alterations in brain diseases via resting-state functional magnetic resonance imaging (rs-fMRI) are generally either at local scale (regionally confined analysis and inter-regional functional connectivity analysis) or at global scale (graph theoretic analysis). In contrast, inferring functional interaction at fine-granularity sub-network scale has not been adequately explored yet. Here our hypothesis is that functional interaction measured at fine-granularity subnetwork scale can provide new insight into the neural mechanisms of neurological and psychological conditions, thus offering complementary information for healthy and diseased population classification. In this paper, we derived fine-granularity functional interaction (FGFI) signatures in subjects with Mild Cognitive Impairment (MCI) and Schizophrenia by diffusion tensor imaging (DTI) and rsfMRI, and used patient-control classification experiments to evaluate the distinctiveness of the derived FGFI features. Our experimental results have shown that the FGFI features alone can achieve comparable classification performance compared with the commonly used inter-regional connectivity features. However, the classification performance can be substantially improved when FGFI features and inter-regional connectivity features are integrated, suggesting the complementary information achieved from the FGFI signatures. PMID:23319242

Species richness and biomass explain spatial turnover in ecosystem functioning across tropical and temperate ecosystems.

PubMed

Barnes, Andrew D; Weigelt, Patrick; Jochum, Malte; Ott, David; Hodapp, Dorothee; Haneda, Noor Farikhah; Brose, Ulrich

2016-05-19

Predicting ecosystem functioning at large spatial scales rests on our ability to scale up from local plots to landscapes, but this is highly contingent on our understanding of how functioning varies through space. Such an understanding has been hampered by a strong experimental focus of biodiversity-ecosystem functioning research restricted to small spatial scales. To address this limitation, we investigate the drivers of spatial variation in multitrophic energy flux-a measure of ecosystem functioning in complex communities-at the landscape scale. We use a structural equation modelling framework based on distance matrices to test how spatial and environmental distances drive variation in community energy flux via four mechanisms: species composition, species richness, niche complementarity and biomass. We found that in both a tropical and a temperate study region, geographical and environmental distance indirectly influence species richness and biomass, with clear evidence that these are the dominant mechanisms explaining variability in community energy flux over spatial and environmental gradients. Our results reveal that species composition and trait variability may become redundant in predicting ecosystem functioning at the landscape scale. Instead, we demonstrate that species richness and total biomass may best predict rates of ecosystem functioning at larger spatial scales. © 2016 The Author(s).

Family-specific scaling laws in bacterial genomes.

PubMed

De Lazzari, Eleonora; Grilli, Jacopo; Maslov, Sergei; Cosentino Lagomarsino, Marco

2017-07-27

Among several quantitative invariants found in evolutionary genomics, one of the most striking is the scaling of the overall abundance of proteins, or protein domains, sharing a specific functional annotation across genomes of given size. The size of these functional categories change, on average, as power-laws in the total number of protein-coding genes. Here, we show that such regularities are not restricted to the overall behavior of high-level functional categories, but also exist systematically at the level of single evolutionary families of protein domains. Specifically, the number of proteins within each family follows family-specific scaling laws with genome size. Functionally similar sets of families tend to follow similar scaling laws, but this is not always the case. To understand this systematically, we provide a comprehensive classification of families based on their scaling properties. Additionally, we develop a quantitative score for the heterogeneity of the scaling of families belonging to a given category or predefined group. Under the common reasonable assumption that selection is driven solely or mainly by biological function, these findings point to fine-tuned and interdependent functional roles of specific protein domains, beyond our current functional annotations. This analysis provides a deeper view on the links between evolutionary expansion of protein families and the functional constraints shaping the gene repertoire of bacterial genomes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Characteristics of bacterial community in cloud water at Mt Tai: similarity and disparity under polluted and non-polluted cloud episodes

NASA Astrophysics Data System (ADS)

Wei, Min; Xu, Caihong; Chen, Jianmin; Zhu, Chao; Li, Jiarong; Lv, Ganglin

2017-04-01

Bacteria are widely distributed in atmospheric aerosols and are indispensable components of clouds, playing an important role in the atmospheric hydrological cycle. However, limited information is available about the bacterial community structure and function, especially for the increasing air pollution in the North China Plain. Here, we present a comprehensive characterization of bacterial community composition, function, variation, and environmental influence for cloud water collected at Mt Tai from 24 July to 23 August 2014. Using Miseq 16S rRNA gene sequencing, the highly diverse bacterial community in cloud water and the predominant phyla of Proteobacteria, Bacteroidetes, Cyanobacteria, and Firmicutes were investigated. Bacteria that survive at low temperature, radiation, and poor nutrient conditions were found in cloud water, suggesting adaption to an extreme environment. The bacterial gene functions predicted from the 16S rRNA gene using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) suggested that the pathways related to metabolism and disease infections were significantly correlated with the predominant genera. The abundant genera Acinetobacter, Stenotrophomonas, Pseudomonas, and Empedobacter originated from a wide range of habitats including cloud condensation nuclei and ice nuclei active species, opportunistic pathogens, and functional species, demonstrating the importance of ecology and health in cloud water. Cluster analysis including hierarchical cluster (Hcluster) and principal coordinate analysis (PCoA) indicated a significant disparity between polluted and non-polluted samples. Linear discriminant analysis effect size (LEfSe) demonstrated that potential pathogens were enriched in the polluted cloud samples, whereas the diverse ecological function groups were significant in the non-polluted samples. Discrepant community structure determined by redundancy analysis (RDA) indicated that the major ions in cloud water and PM2. 5 in the atmosphere have a negative impact on bacteria, playing a vital role in shaping microbial community structure. The major ions might provide nutrition to bacteria and directly influence the bacterial community, whereas PM2. 5 in air has an indirect impact on bacterial community structure. During wet deposition, soluble particulate matter was dissolved in water droplets resulting in elevated concentration in cloud water. PM2. 5 was possibly associated with different origins and pathways of air mass as determined using source tracking by the backward trajectory, mainly related to long-range transport. This work enhanced our understanding of the characteristics of bacterial ecology in the atmospheric aqueous phase, highlighting the potential influence of environmental variables on the bacterial community in cloud processes. It may provide fundamental information of the bacterial community response in cloud water under increasing pollution. However, due to the limited sample size (13 samples) collected at the summit of Mt Tai, these issues need in-depth discussion. Further studies based on an annual series of field observation experiments and laboratory simulations will continue to track these issues.

[Kennedy V Axis assessment in an Italian outpatient and inpatient population].

PubMed

Mundo, Emanuela; Bonalume, Laura; Del Corno, Franco; Madeddu, Fabio; Lang, Margherita

2010-01-01

Kennedy Axis V or K Axis acts is an alternative tool to the DSM-IVTR Global Assessment of Functioning (GAF) Scale, that many researchers describe as a scale with poor inter-rater reliability and clinical utility. Unlike the GAF scale, K Axis provides a multidimensional and multiaxial approach to measure personal, social and interpersonal functioning in psychiatric outpatients and inpatients. In this study, we examined K Axis's inter-raters reliability by using it with an Italian clinical population. Clinicians used Kennedy Axis V to assess global functioning among 180 inpatients, in 9 psychiatric services in Lombardia and Piemonte. Patients were divided into 4 different diagnostic groups, according to the DSM-IV-TR criteria. Intraclass correlations between two independent raters's scores reveal high level of interrater reliability for all K Axis scales (0,633 < ICC < 0,813). Highly significant results in the Kruskal-Wallis test demonstrate that the patient diagnosis influence all the scales scores. Significant differences in patients functioning profiles in all K Axis scales, apart from Violence one, were noted between different diagnosis groups. In this study high level of raters agreement was noted, even if K Axis scales were used in different mental health services from different clinicians. K Axis scales provide a useful profile of patient global functioning, in line with the specific pathology.

How does social functioning in the early stages of psychosis relate to depression and social anxiety?

PubMed

Chudleigh, Catherine; Naismith, Sharon L; Blaszczynski, Alex; Hermens, Daniel F; Hodge, M Antoinette Redoblado; Hickie, Ian B

2011-08-01

The study aims to compare social functioning in young people considered to be at risk of psychosis with those meeting criteria for first episode psychosis (FEP) and controls, and to determine the association between social functioning and positive and negative symptoms, depressive symptoms, and social anxiety. This study examined social functioning in 20 individuals at risk of psychosis, 20 FEP patients and 20 healthy controls. Social functioning was measured using the Social Functioning Scale and World Health Organization Disability Assessment Scale. Psychiatric variables were also measured using the Comprehensive Assessment of At-Risk Mental States, the Brief Psychiatric Rating Scale, the Brief Social Phobia Scale, and the Depression Anxiety and Stress Scale. At-risk individuals had comparable social deficits to the FEP group, and both patient groups had significantly poorer social functioning than controls. Importantly, social functioning was most strongly associated with depressive and social anxiety symptoms and to a lesser extent with positive symptoms. However, negative symptoms did not appear to relate to social functioning. Social functioning impairments precede the onset of full-threshold psychosis and may therefore be a significant marker for the illness. Additionally, associated psychiatric symptoms such as depression and social anxiety may provide an avenue for early interventions of social functioning deficits in psychosis. © 2011 Blackwell Publishing Asia Pty Ltd.

Sexual function in Italian women with systemic sclerosis is affected by disease-related and psychological concerns.

PubMed

Maddali Bongi, Susanna; Del Rosso, Angela; Mikhaylova, Svetlana; Baccini, Marco; Matucci Cerinic, Marco

2013-10-01

In patients with systemic sclerosis (SSc), sexual function is somewhat impaired. Our aim was to evaluate sexual function in women with SSc in comparison to controls, and to investigate the association with sociodemographic and disease characteristics, and physical and psychological variables. Forty-six women with SSc and 46 healthy women were assessed for sociodemographic characteristics and gynecological development and administered the Female Sexual Function Index (FSFI), Medical Outcomes Study Short Form-36 (SF-36), Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale (HADS), Rosenberg Self-Esteem Scale, Coping Orientation to Problems Experienced-New Italian Version, and Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Patients were also assessed for disease duration and subset, Female Sexual Function in SSc, Hand Mobility in Scleroderma test (HAMIS), Cochin Hand Functional Disability Scale, Mouth Handicap in Systemic Sclerosis Scale (MHISS), Disability Sexual and Body Esteem Scale (PDSBE); and fist closure, hand opening, and mouth opening. In patients with SSc, only FSFI desire subscale score was significantly lower (p = 0.035) versus controls. Total FSFI score, similar to controls, was related with Medical Outcomes Study Short Form-36 mental component, HAQ (p = 0.022), MHISS (p = 0.038), and HAMIS (p = 0.037). In SSc, the main factors independently associated with sexual functioning were vaginal dryness [regression coefficient (B) = -0.72; p < 0.001], PDSBE (B = 0.42; p = 0.001), and HADS depression scale (B = -0.23; p = 0.035). Together, these variables explained 70% of the variance in the FSFI total score. In SSc, sexual function, although not different from controls, is influenced by specific disease-related and psychological concerns. Thus it should be included in patient evaluations and assessed in daily clinical practice.

[Development of the theoretical framework and the item pool of the peri-operative recovery scale for integrative medicine].

PubMed

Su, Bi-ying; Liu, Shao-nan; Li, Xiao-yan

2011-11-01

To study the train of thoughts and procedures for developing the theoretical framework and the item pool of the peri-operative recovery scale for integrative medicine, thus making preparation for the development of this scale and psychometric testing. Under the guidance for Chinese medicine theories and the guidance for developing psychometric scale, the theoretical framework and the item pool of the scale were initially laid out by literature retrieval, and expert consultation, etc. The scale covered the domains of physical function, mental function, activity function, pain, and general assessment. Besides, social function is involved, which is suitable for pre-operative testing and long-term therapeutic efficacy testing after discharge from hospital. Each domain should cover correlated Zang-Fu organs, qi, blood, and the patient-reported outcomes. Totally 122 items were initially covered in the item pool according to theoretical framework of the scale. The peri-operative recovery scale of integrative medicine was the embodiment of the combination of Chinese medicine theories and patient-reported outcome concepts. The scale could reasonably assess the peri-operative recovery outcomes of patients treated by integrative medicine.

The impact of fatigue and energy on work functioning and impairment in patients with major depressive disorder treated with desvenlafaxine.

PubMed

Sarfati, David; Evans, Vanessa C; Tam, Edwin M; Woo, Cindy; Iverson, Grant L; Yatham, Lakshmi N; Lam, Raymond W

2017-11-01

Fatigue and low energy are cardinal symptoms of major depressive disorder (MDD) that have an impact on work functioning. Antidepressants with noradrenergic activity have been hypothesized to improve symptoms of fatigue and low energy. We examined the impact of these symptoms on work functioning in patients with MDD treated with the serotonin and noradrenaline reuptake inhibitor, desvenlafaxine. A secondary analysis was carried out from a study of employed adult outpatients (n=35) with MDD and subjective cognitive complaints treated with desvenlafaxine 50-100 mg/day for 8 weeks. Multiple regression analyses modeled improvement in work functioning measures (Lam Employment Absence and Productivity Scale, Health and Work Performance Questionnaire, Sheehan Disability Scale) with measures of fatigue (Patient-Reported Outcomes Measurement Information System Fatigue scale and 20-item Hopkins Symptom Check List Energy scale). Patients showed a significant improvement in Montgomery-Åsberg Depression Rating Scale scores as well as in fatigue and work functioning measures following treatment. Fatigue measures were significantly associated with improvement in some (Lam Employment Absence and Productivity Scale, Sheehan Disability Scale), but not all (Health and Work Performance Questionnaire) work functioning measures, independent of improvement in overall depressive symptoms. The limitations of this study include the small sample size and the lack of a placebo or a comparison group. Fatigue and low energy are important symptoms that are associated with occupational impairment in MDD. Treatments that improve these symptoms are likely to improve work functioning.

Studies on combined model based on functional objectives of large scale complex engineering

NASA Astrophysics Data System (ADS)

Yuting, Wang; Jingchun, Feng; Jiabao, Sun

2018-03-01

As various functions were included in large scale complex engineering, and each function would be conducted with completion of one or more projects, combined projects affecting their functions should be located. Based on the types of project portfolio, the relationship of projects and their functional objectives were analyzed. On that premise, portfolio projects-technics based on their functional objectives were introduced, then we studied and raised the principles of portfolio projects-technics based on the functional objectives of projects. In addition, The processes of combined projects were also constructed. With the help of portfolio projects-technics based on the functional objectives of projects, our research findings laid a good foundation for management of large scale complex engineering portfolio management.

Biodiversity-ecosystem functioning relationships in long-term time series and palaeoecological records: deep sea as a test bed.

PubMed

Yasuhara, Moriaki; Doi, Hideyuki; Wei, Chih-Lin; Danovaro, Roberto; Myhre, Sarah E

2016-05-19

The link between biodiversity and ecosystem functioning (BEF) over long temporal scales is poorly understood. Here, we investigate biological monitoring and palaeoecological records on decadal, centennial and millennial time scales from a BEF framework by using deep sea, soft-sediment environments as a test bed. Results generally show positive BEF relationships, in agreement with BEF studies based on present-day spatial analyses and short-term manipulative experiments. However, the deep-sea BEF relationship is much noisier across longer time scales compared with modern observational studies. We also demonstrate with palaeoecological time-series data that a larger species pool does not enhance ecosystem stability through time, whereas higher abundance as an indicator of higher ecosystem functioning may enhance ecosystem stability. These results suggest that BEF relationships are potentially time scale-dependent. Environmental impacts on biodiversity and ecosystem functioning may be much stronger than biodiversity impacts on ecosystem functioning at long, decadal-millennial, time scales. Longer time scale perspectives, including palaeoecological and ecosystem monitoring data, are critical for predicting future BEF relationships on a rapidly changing planet. © 2016 The Author(s).

[Development of a Japanese version of the TALE scale].

PubMed

Ochiai, Tsutomu; Oguchi, Takashi

2013-12-01

The Thinking About Life Experiences (TALE) Scale (Bluck & Alea, 2011) has three subscales that assess the self, social, and directive functions of autobiographical memory. This study constructs a Japanese version of the TALE Scale and examines its reliability and validity. Fifteen items that assess the three functions of autobiographical memory were translated into Japanese. We conducted an online investigation with 600 men and women between 20-59 years of age. In Study 1, exploratory and confirmatory factor analysis identified that the three-factor structure of the Japanese version of the TALE Scale was the same as the original TALE Scale. Sufficient internal consistency of the scale was found, and the construct validity of the scale was supported by correlation analysis. Study 2 confirmed that the test-retest reliabilities of the three subscales were sufficient. Thus, this Japanese version of the TALE Scale is useful to assess autobiographical memory functions in Japan.

Multiscale functions, scale dynamics, and applications to partial differential equations

NASA Astrophysics Data System (ADS)

Cresson, Jacky; Pierret, Frédéric

2016-05-01

Modeling phenomena from experimental data always begins with a choice of hypothesis on the observed dynamics such as determinism, randomness, and differentiability. Depending on these choices, different behaviors can be observed. The natural question associated to the modeling problem is the following: "With a finite set of data concerning a phenomenon, can we recover its underlying nature? From this problem, we introduce in this paper the definition of multi-scale functions, scale calculus, and scale dynamics based on the time scale calculus [see Bohner, M. and Peterson, A., Dynamic Equations on Time Scales: An Introduction with Applications (Springer Science & Business Media, 2001)] which is used to introduce the notion of scale equations. These definitions will be illustrated on the multi-scale Okamoto's functions. Scale equations are analysed using scale regimes and the notion of asymptotic model for a scale equation under a particular scale regime. The introduced formalism explains why a single scale equation can produce distinct continuous models even if the equation is scale invariant. Typical examples of such equations are given by the scale Euler-Lagrange equation. We illustrate our results using the scale Newton's equation which gives rise to a non-linear diffusion equation or a non-linear Schrödinger equation as asymptotic continuous models depending on the particular fractional scale regime which is considered.

Genetic algorithms - What fitness scaling is optimal?

NASA Technical Reports Server (NTRS)

Kreinovich, Vladik; Quintana, Chris; Fuentes, Olac

1993-01-01

A problem of choosing the best scaling function as a mathematical optimization problem is formulated and solved under different optimality criteria. A list of functions which are optimal under different criteria is presented which includes both the best functions empirically proved and new functions that may be worth trying.

Measuring the relative resilience of subarctic lakes to global change: redundancies of functions within and across temporal scales

USGS Publications Warehouse

Angeler, David G.; Allen, Craig R.; Johnson, Richard K.

2013-01-01

1. Ecosystems at high altitudes and latitudes are expected to be particularly vulnerable to the effects of global change. We assessed the responses of littoral invertebrate communities to changing abiotic conditions in subarctic Swedish lakes with long-term data (1988–2010) and compared the responses of subarctic lakes with those of more southern, hemiboreal lakes. 2. We used a complex systems approach, based on multivariate time-series modelling, and identified dominant and distinct temporal frequencies in the data; that is, we tracked community change at distinct temporal scales. We determined the distribution of functional feeding groups of invertebrates within and across temporal scales. Within and cross-scale distributions of functions have been considered to confer resilience to ecosystems, despite changing environmental conditions. 3. Two patterns of temporal change within the invertebrate communities were identified that were consistent across the lakes. The first pattern was one of monotonic change associated with changing abiotic lake conditions. The second was one of showing fluctuation patterns largely unrelated to gradual environmental change. Thus, two dominant and distinct temporal frequencies (temporal scales) were present in all lakes analysed. 4. Although the contribution of individual feeding groups varied between subarctic and hemiboreal lakes, they shared overall similar functional attributes (richness, evenness, diversity) and redundancies of functions within and between the observed temporal scales. This highlights similar resilience characteristics in subarctic and hemiboreal lakes. 5. Synthesis and applications. The effects of global change can be particularly strong at a single scale in ecosystems. Over time, this can cause monotonic change in communities and eventually lead to a loss of important ecosystem services upon reaching a critical threshold. Dynamics at other spatial or temporal scales can be unrelated to environmental change. The relative ‘intactness’ of these scales that are unaffected by global change and the persistence of functions at those scales may safeguard the whole system from the potential loss of functions at the scale at which global change impacts can be substantial. Thus, an understanding of scale-specific processes provides managers with a realistic assessment of vulnerabilities and the relative resilience of ecosystems to environmental change. Explicit consideration of ‘intact’ and ‘affected’ scales in analyses of global change impacts provides opportunities to tailor more specific management plans.

Asymptotic stability and instability of large-scale systems. [using vector Liapunov functions

NASA Technical Reports Server (NTRS)

Grujic, L. T.; Siljak, D. D.

1973-01-01

The purpose of this paper is to develop new methods for constructing vector Lyapunov functions and broaden the application of Lyapunov's theory to stability analysis of large-scale dynamic systems. The application, so far limited by the assumption that the large-scale systems are composed of exponentially stable subsystems, is extended via the general concept of comparison functions to systems which can be decomposed into asymptotically stable subsystems. Asymptotic stability of the composite system is tested by a simple algebraic criterion. By redefining interconnection functions among the subsystems according to interconnection matrices, the same mathematical machinery can be used to determine connective asymptotic stability of large-scale systems under arbitrary structural perturbations.

The use of discontinuities and functional groups to assess relative resilience in complex systems

USGS Publications Warehouse

Allen, Craig R.; Gunderson, Lance; Johnson, A.R.

2005-01-01

It is evident when the resilience of a system has been exceeded and the system qualitatively changed. However, it is not clear how to measure resilience in a system prior to the demonstration that the capacity for resilient response has been exceeded. We argue that self-organizing human and natural systems are structured by a relatively small set of processes operating across scales in time and space. These structuring processes should generate a discontinuous distribution of structures and frequencies, where discontinuities mark the transition from one scale to another. Resilience is not driven by the identity of elements of a system, but rather by the functions those elements provide, and their distribution within and across scales. A self-organizing system that is resilient should maintain patterns of function within and across scales despite the turnover of specific elements (for example, species, cities). However, the loss of functions, or a decrease in functional representation at certain scales will decrease system resilience. It follows that some distributions of function should be more resilient than others. We propose that the determination of discontinuities, and the quantification of function both within and across scales, produce relative measures of resilience in ecological and other systems. We describe a set of methods to assess the relative resilience of a system based upon the determination of discontinuities and the quantification of the distribution of functions in relation to those discontinuities. ?? 2005 Springer Science+Business Media, Inc.

Validation of the XDP-MDSP rating scale for the evaluation of patients with X-linked dystonia-parkinsonism.

PubMed

Pasco, Paul Matthew D; Jamora, Roland Dominic G; Rosales, Raymond L; Diesta, Cid Czarina E; Ng, Arlene R; Teleg, Rosalia A; Go, Criscely L; Lee, Lillian; Fernandez, Hubert H

2017-01-01

X-linked dystonia-parkinsonism(XDP) is a neurodegenerative disorder endemic to the Philippines. A rating scale was developed by the authors under the guidance of the Movement Disorder Society of the Philippines (MDSP) to assess XDP severity and progression, functional impact, and response to treatment in future clinical trials. Our main objective was to validate our new scale, the XDP-MDSP scale. The initial validation process included pragmatic testing to XDP patients followed by a modified Delphi procedure with an international advisory panel of dystonia, parkinsonism and scale development experts. Pearson correlation was used to assess construct validity of our new scale versus the assess construct validity of our new scale versus standard dystonia, parkinsonism, non-motor and functional scales; and also to assess divergent validity against behavioral and cognitive scales. The 37-item XDP-MDSP scale has five parts: I-dystonia, II-parkinsonism, III-non-motor features, IV-ADL, and V-global impression. After initial validation, the scale was administered to 204 XDP patients. Inter-domain correlation for the first four parts was acceptable. The correlation between these domains and the global rating was slightly lower. Correlations between Parts I, II, III, and IV versus standard dystonia, parkinsonism, non-motor and functional scales were acceptable with values ranging from 0.323 to 0.428. For divergent validity, a significant correlation was seen with behavioral scales. No significant correlation was noted with the cognitive scale. The proposed XDP-MDSP scale is internally valid but the global rating subscale may need to be modified or eliminated. While there is convergent validity, divergent validation was successful only on cognitive and not behavioral scales. The frequent co-occurrence of anxiety and depression, and its effect on the motor and functional state, may explain this finding.

A randomized controlled trial reporting functional outcomes of cognitive-behavioural therapy in medication-treated adults with ADHD and comorbid psychopathology.

PubMed

Young, Susan; Emilsson, Brynjar; Sigurdsson, Jon Fridrik; Khondoker, Mizanur; Philipp-Wiegmann, Florence; Baldursson, Gisli; Olafsdottir, Halldora; Gudjonsson, Gisli

2017-04-01

Studies assessing psychological treatment of attention deficit hyperactivity disorder (ADHD) in adults are increasingly reported. However, functional outcomes are often neglected in favour of symptom outcomes. We investigated functional outcomes in 95 adults with ADHD who were already treated with medication and randomized to receive treatment as usual (TAU/MED) or psychological treatment (CBT/MED) using a cognitive-behavioural programme, R&R2ADHD, which employs both group and individual modalities. RATE-S functional outcomes associated with ADHD symptoms, social functioning, emotional control and antisocial behaviour were given at baseline, end of treatment and three-month follow-up. The Total composite score of these scales is associated with life satisfaction. In addition, independent evaluator ratings of clinicians who were blind to treatment arm were obtained on the Clinical Global Impression scale at each time point. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater functional improvement on all scales. Post-group treatment effects were maintained at follow-up with the exception of emotional control and the Total composite scales, which continued to improve. The largest treatment effect was for the RATE-S Total composite scale, associated with life satisfaction. CGI significantly correlated with all outcomes except for social functioning scale at follow-up. The study provides further evidence for the effectiveness of R&R2ADHD and demonstrates the importance of measuring functional outcomes. The key mechanism associated with improved functional outcomes is likely to be behavioural control.

Scaling up the diversity-resilience relationship with trait databases and remote sensing data: the recovery of productivity after wildfire.

PubMed

Spasojevic, Marko J; Bahlai, Christie A; Bradley, Bethany A; Butterfield, Bradley J; Tuanmu, Mao-Ning; Sistla, Seeta; Wiederholt, Ruscena; Suding, Katharine N

2016-04-01

Understanding the mechanisms underlying ecosystem resilience - why some systems have an irreversible response to disturbances while others recover - is critical for conserving biodiversity and ecosystem function in the face of global change. Despite the widespread acceptance of a positive relationship between biodiversity and resilience, empirical evidence for this relationship remains fairly limited in scope and localized in scale. Assessing resilience at the large landscape and regional scales most relevant to land management and conservation practices has been limited by the ability to measure both diversity and resilience over large spatial scales. Here, we combined tools used in large-scale studies of biodiversity (remote sensing and trait databases) with theoretical advances developed from small-scale experiments to ask whether the functional diversity within a range of woodland and forest ecosystems influences the recovery of productivity after wildfires across the four-corner region of the United States. We additionally asked how environmental variation (topography, macroclimate) across this geographic region influences such resilience, either directly or indirectly via changes in functional diversity. Using path analysis, we found that functional diversity in regeneration traits (fire tolerance, fire resistance, resprout ability) was a stronger predictor of the recovery of productivity after wildfire than the functional diversity of seed mass or species richness. Moreover, slope, elevation, and aspect either directly or indirectly influenced the recovery of productivity, likely via their effect on microclimate, while macroclimate had no direct or indirect effects. Our study provides some of the first direct empirical evidence for functional diversity increasing resilience at large spatial scales. Our approach highlights the power of combining theory based on local-scale studies with tools used in studies at large spatial scales and trait databases to understand pressing environmental issues. © 2015 John Wiley & Sons Ltd.

Standardization of a spinal cord lesion model and neurologic evaluation using mice

PubMed Central

Borges, Paulo Alvim; Cristante, Alexandre Fogaça; de Barros-Filho, Tarcísio Eloy Pessoa; Natalino, Renato Jose Mendonça; dos Santos, Gustavo Bispo; Marcon, Raphael Marcus

2018-01-01

OBJECTIVE: To standardize a spinal cord lesion mouse model. METHODS: Thirty BALB/c mice were divided into five groups: four experimental groups and one control group (sham). The experimental groups were subjected to spinal cord lesion by a weight drop from different heights after laminectomy whereas the sham group only underwent laminectomy. Mice were observed for six weeks, and functional behavior scales were applied. The mice were then euthanized, and histological investigations were performed to confirm and score spinal cord lesion. The findings were evaluated to prove whether the method of administering spinal cord lesion was effective and different among the groups. Additionally, we correlated the results of the functional scales with the results from the histology evaluations to identify which scale is more reliable. RESULTS: One mouse presented autophagia, and six mice died during the experiment. Because four of the mice that died were in Group 5, Group 5 was excluded from the study. All the functional scales assessed proved to be significantly different from each other, and mice presented functional evolution during the experiment. Spinal cord lesion was confirmed by histology, and the results showed a high correlation between the Basso, Beattie, Bresnahan Locomotor Rating Scale and the Basso Mouse Scale. The mouse function scale showed a moderate to high correlation with the histological findings, and the horizontal ladder test had a high correlation with neurologic degeneration but no correlation with the other histological parameters evaluated. CONCLUSION: This spinal cord lesion mouse model proved to be effective and reliable with exception of lesions caused by a 10-g drop from 50 mm, which resulted in unacceptable mortality. The Basso, Beattie, Bresnahan Locomotor Rating Scale and Basso Mouse Scale are the most reliable functional assessments, and but the horizontal ladder test is not recommended. PMID:29561931

Small scale homelike special care units and traditional special care units: effects on cognition in dementia; a longitudinal controlled intervention study.

PubMed

Kok, Jeroen S; van Heuvelen, Marieke J G; Berg, Ina J; Scherder, Erik J A

2016-02-16

Evidence shows that living in small scale homelike Special Care Units (SCU) has positive effects on behavioural and psychological symptoms of patients with dementia. Effects on cognitive functioning in relation to care facilities, however, are scarcely investigated. The purpose of this study is to gain more insight into the effects of living in small scale homelike Special Care Units, compared to regular SCU's, on the course of cognitive functioning in dementia. A group of 67 patients with dementia who moved from a regular SCU to a small scale homelike SCU and a group of 48 patients with dementia who stayed in a regular SCU participated in the study. Cognitive and behavioural functioning was assessed by means of a neuropsychological test battery and observation scales one month before (baseline), as well as 3 (post) and 6 months (follow-up) after relocation. Comparing the post and follow-up measurement with the baseline measurement, no significant differences on separate measures of cognitive functioning between both groups were found. Additional analyses, however, on 'domain clusters' revealed that global cognitive functioning of the small scale homelike SCU group showed significantly less cognitive decline three months after the transfer (p < 0.05). Effect sizes (95% CI) show a tendency for better aspects of cognition in favour of the homelike small scaled SCU group, i.e., visual memory, picture recognition, cognitive decline as observed by representatives and the clustered domains episodic memory and global cognitive functioning. While there is no significant longitudinal effect on the progression of cognitive decline comparing small scaled homelike SCU's with regular SCU's for patients with dementia, analyses on the domain clusters and effect sizes cautiously suggest differences in favour of the small scaled homelike SCU for different aspects of cognition.

Validity of patient-reported swallowing and speech outcomes in relation to objectively measured oral function among patients treated for oral or oropharyngeal cancer.

PubMed

Rinkel, R N P M; Verdonck-de Leeuw, I M; de Bree, R; Aaronson, N K; Leemans, C R

2015-04-01

The objective of this study was to test the construct validity of the patient-reported outcomes Swallowing Quality of Life Questionnaire (SWAL-QOL) and Speech Handicap Index (SHI) in relation to objectively measured oral function among patients treated for oral or oropharyngeal cancer. The study sample consisted of patients treated for oral or oropharyngeal cancer. Outcome measures were the SWAL-QOL and the SHI, and the Functional Rehabilitation Outcomes Grade (FROG), a test to measure oral and shoulder function. Spearman's rank correlation coefficient was used to test associations between the SHI and SWAL-QOL scales, and the FROG scales. During a study period of 3 months, 38 patients (21 males, 17 females; mean age 54 years) were included who visited the outpatient clinic for follow-up care 6-155 months after surgical treatment (n = 14) or combined surgery and radiotherapy (n = 24) for oral (n = 21) or oropharyngeal cancer (n = 17). Most SWAL-QOL and SHI scales (except the SWAL-QOL Fatigue scale) correlated significantly with one or more FROG oral function scales. None of the SWAL-QOL and SHI scales correlated significantly with the FROG shoulder function scale. These results support the construct validity of the SWAL-QOL and SHI questionnaires for assessing speech and swallowing problems in daily life that are moderately but significantly related to oral function. A multidimensional assessment protocol is recommended for use in clinical practice and for research purposes for measuring oral function and swallowing- and speech-related problems in daily life among head and neck cancer patients.

The Work Disability Functional Assessment Battery (WD-FAB): Feasibility and Psychometric Properties

PubMed Central

Meterko, Mark; Marfeo, Elizabeth E.; McDonough, Christine M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara; Rasch, Elizabeth K; Brandt, Diane E.; Chan, Leighton

2015-01-01

Objectives To assess the feasibility and psychometric properties of eight scales covering two domains of the newly developed Work Disability Functional Assessment Battery (WD-FAB): physical function (PF) and behavioral health (BH) function. Design Cross-sectional. Setting Community. Participants Adults unable to work due to a physical (n=497) or mental (n=476) disability. Interventions None. Main Outcome Measures Each disability group responded to a survey consisting of the relevant WD-FAB scales and existing measures of established validity. The WD-FAB scales were evaluated with regard to data quality (score distribution; percent “I don’t know” responses), efficiency of administration (number of items required to achieve reliability criterion; time required to complete the scale) by computerized adaptive testing (CAT), and measurement accuracy as tested by person fit. Construct validity was assessed by examining both convergent and discriminant correlations between the WD-FAB scales and scores on same-domain and cross-domain established measures. Results Data quality was good and CAT efficiency was high across both WD-FAB domains. Measurement accuracy was very good for the PF scales; BH scales demonstrated more variability. Construct validity correlations, both convergent and divergent, between all WD-FAB scales and established measures were in the expected direction and range of magnitude. Conclusions The data quality, CAT efficacy, person fit and construct validity of the WD-FAB scales were well supported and suggest that the WD-FAB could be used to assess physical and behavioral health function related to work disability. Variation in scale performance suggests the need for future work on item replenishment and refinement, particularly regarding the Self-Efficacy scale. PMID:25528263

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity.

PubMed

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N

2015-01-01

To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen-Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure-function relationships but requires further validation in other populations of CP.

Local loss and spatial homogenization of plant diversity reduce ecosystem multifunctionality.

PubMed

Hautier, Yann; Isbell, Forest; Borer, Elizabeth T; Seabloom, Eric W; Harpole, W Stanley; Lind, Eric M; MacDougall, Andrew S; Stevens, Carly J; Adler, Peter B; Alberti, Juan; Bakker, Jonathan D; Brudvig, Lars A; Buckley, Yvonne M; Cadotte, Marc; Caldeira, Maria C; Chaneton, Enrique J; Chu, Chengjin; Daleo, Pedro; Dickman, Christopher R; Dwyer, John M; Eskelinen, Anu; Fay, Philip A; Firn, Jennifer; Hagenah, Nicole; Hillebrand, Helmut; Iribarne, Oscar; Kirkman, Kevin P; Knops, Johannes M H; La Pierre, Kimberly J; McCulley, Rebecca L; Morgan, John W; Pärtel, Meelis; Pascual, Jesus; Price, Jodi N; Prober, Suzanne M; Risch, Anita C; Sankaran, Mahesh; Schuetz, Martin; Standish, Rachel J; Virtanen, Risto; Wardle, Glenda M; Yahdjian, Laura; Hector, Andy

2018-01-01

Biodiversity is declining in many local communities while also becoming increasingly homogenized across space. Experiments show that local plant species loss reduces ecosystem functioning and services, but the role of spatial homogenization of community composition and the potential interaction between diversity at different scales in maintaining ecosystem functioning remains unclear, especially when many functions are considered (ecosystem multifunctionality). We present an analysis of eight ecosystem functions measured in 65 grasslands worldwide. We find that more diverse grasslands-those with both species-rich local communities (α-diversity) and large compositional differences among localities (β-diversity)-had higher levels of multifunctionality. Moreover, α- and β-diversity synergistically affected multifunctionality, with higher levels of diversity at one scale amplifying the contribution to ecological functions at the other scale. The identity of species influencing ecosystem functioning differed among functions and across local communities, explaining why more diverse grasslands maintained greater functionality when more functions and localities were considered. These results were robust to variation in environmental drivers. Our findings reveal that plant diversity, at both local and landscape scales, contributes to the maintenance of multiple ecosystem services provided by grasslands. Preserving ecosystem functioning therefore requires conservation of biodiversity both within and among ecological communities.

On the saturation of the refractive index structure function. II - Influence of the correlation length on astronomical 'seeing'

NASA Technical Reports Server (NTRS)

Venkatakrishnan, P.

1987-01-01

A physical length scale in the wavefront corresponding to the parameter (r sub 0) characterizing the loss in detail in a long exposure image is identified, and the influence of the correlation scale of turbulence as r sub 0 approaches this scale is shown. Allowing for the effect of 2-point correlations in the fluctuations of the refractive index, Venkatakrishnan and Chatterjee (1987) proposed a modified law for the phase structure function. It is suggested that the departure of the phase structure function from the 5/3 power law for length scales in the wavefront approaching the correlation scale of turbulence may lead to better 'seeing' at longer wavelengths.

Spanish adaptation of the internal functioning of the Work Teams Scale (QFI-22).

PubMed

Ficapal-Cusí, Pilar; Boada-Grau, Joan; Torrent-Sellens, Joan; Vigil-Colet, Andreu

2014-05-01

The aim of this article is to develop the Spanish adaptation of the internal functioning of Work Teams Scale (QFI-22). The scale was adapted from the French version, and was applied to a sample of 1,055 employees working for firms operating in Spain. The article analyses the internal structure (exploratory and confirmatory factor analysis) and internal consistency, and provides convergent validity evidence of the scale. The QFI-22 scale shows the same internal structure as the original. Factor analysis confirmed the existence of two factors: interpersonal support and team work management, with good internal consistency coefficients (α1 = .93, α2 = .92). Regarding validity evidence, the QFI-22 scale has significant correlations with other correlates and alternative scales used for comparison purposes. The two factors correlated positively with team vision, participation safety, task orientation and support for innovation (Team Climate Inventory, TCI scale), with progressive culture (Organisational Culture, X-Y scale), and with creating change, customer focus and organisational learning (Denison Organizational Culture Survey, DOCS scale). In contrast, the two factors correlated negatively with traditional culture (X-Y scale). The QFI-22 scale is a useful instrument for assessing the internal functioning of work teams.

Scaled Quantum Mechanical scale factors for vibrational calculations using alternate polarized and augmented basis sets with the B3LYP density functional calculation model

NASA Astrophysics Data System (ADS)

Legler, C. R.; Brown, N. R.; Dunbar, R. A.; Harness, M. D.; Nguyen, K.; Oyewole, O.; Collier, W. B.

2015-06-01

The Scaled Quantum Mechanical (SQM) method of scaling calculated force constants to predict theoretically calculated vibrational frequencies is expanded to include a broad array of polarized and augmented basis sets based on the split valence 6-31G and 6-311G basis sets with the B3LYP density functional. Pulay's original choice of a single polarized 6-31G(d) basis coupled with a B3LYP functional remains the most computationally economical choice for scaled frequency calculations. But it can be improved upon with additional polarization functions and added diffuse functions for complex molecular systems. The new scale factors for the B3LYP density functional and the 6-31G, 6-31G(d), 6-31G(d,p), 6-31G+(d,p), 6-31G++(d,p), 6-311G, 6-311G(d), 6-311G(d,p), 6-311G+(d,p), 6-311G++(d,p), 6-311G(2d,p), 6-311G++(2d,p), 6-311G++(df,p) basis sets are shown. The double d polarized models did not perform as well and the source of the decreased accuracy was investigated. An alternate system of generating internal coordinates that uses the out-of plane wagging coordinate whenever it is possible; makes vibrational assignments via potential energy distributions more meaningful. Automated software to produce SQM scaled vibrational calculations from different molecular orbital packages is presented.

Scaling theory of topological phase transitions

NASA Astrophysics Data System (ADS)

Chen, Wei

2016-02-01

Topologically ordered systems are characterized by topological invariants that are often calculated from the momentum space integration of a certain function that represents the curvature of the many-body state. The curvature function may be Berry curvature, Berry connection, or other quantities depending on the system. Akin to stretching a messy string to reveal the number of knots it contains, a scaling procedure is proposed for the curvature function in inversion symmetric systems, from which the topological phase transition can be identified from the flow of the driving energy parameters that control the topology (hopping, chemical potential, etc) under scaling. At an infinitesimal operation, one obtains the renormalization group (RG) equations for the driving energy parameters. A length scale defined from the curvature function near the gap-closing momentum is suggested to characterize the scale invariance at critical points and fixed points, and displays a universal critical behavior in a variety of systems examined.

Characterization of Carrier Transport Properties in Strained Crystalline Si Wall-Like Structures as a Function of Scaling into the Quasi-Quantum Regime

DTIC Science & Technology

2017-05-03

AS A FUNCTION OF SCALING INTO THE QUASI -QUANTUM REGIME Naz Islam University of Missouri Electrical and Computer Engineering 319 Engineering...Carrier Transport Properties in Strained Crystalline Si Wall-Like Structures as a Function of Scaling into the Quasi -Quantum Regime 5b. GRANT NUMBER...curves) and their comparisons with experimental data (black dots in both panels......................................... 16 Approved for public

Quality of Life Scale: A Measure of Function for People with Pain

MedlinePlus

Quality Of Life Scale A Measure Of Function For People With Pain 0 Non-functioning 1 2 3 4 ... the week Active on weekends 9 10 Normal Quality of Life Work/volunteer/be active eight hours daily Take ...

A Functional Model for Management of Large Scale Assessments.

ERIC Educational Resources Information Center

Banta, Trudy W.; And Others

This functional model for managing large-scale program evaluations was developed and validated in connection with the assessment of Tennessee's Nutrition Education and Training Program. Management of such a large-scale assessment requires the development of a structure for the organization; distribution and recovery of large quantities of…

Structure function analysis of two-scale Scalar Ramps. Part II: Coherent structure scaling and surface renewal applications

USDA-ARS?s Scientific Manuscript database

Structure functions are used to study the dissipation and inertial range scales of turbulent energy, to parameterize remote turbulence measurements, and to characterize ramp features in the turbulent field. The ramp features are associated with turbulent coherent structures, which dominate energy a...

Development and validation of the Vellore Occupational Therapy Evaluation Scale to assess functioning in people with mental illness.

PubMed

Samuel, Reema; Russell, Paul Ss; Paraseth, Tapan Kumar; Ernest, Sharmila; Jacob, K S

2016-08-26

Available occupational therapy assessment scales focus on specific areas of functioning. There is a need for comprehensive evaluation of diverse aspects of functioning in people with mental illness. To develop a comprehensive assessment scale to evaluate diverse aspects of functioning among people with mental illness and to assess its validity and reliability. Available instruments, which evaluate diverse aspects of functioning in people with mental illness, were retrieved. Relevant items, which evaluate specific functions, were selected by a committee of mental health experts and combined to form a comprehensive instrument. Face and content validity and feasibility were assessed and the new instrument was piloted among 60 patients with mental illness. The final version of the instrument was employed in 151 consecutive clients, between 18 and 60 years of age, who were also assessed using Global Assessment of Functioning (GAF), Occupational Therapy Task Observation Scale (OTTOS), Social Functioning Questionnaire (SFQ), Rosenberg Self Esteem Scale (RSES) and Pai and Kapur Family Burden Interview Schedule (FBIS) by two therapists. The inter-rater reliability and test-retest reliability of the new instrument (Vellore Occupational Therapy Evaluation Scale (VOTES)) were also evaluated. The new scale had good internal consistency (Cronbach's alpha = .817), inter-rater reliability .928 (.877-.958) and test-retest reliability .928 (.868-.961). The correlation between the general behaviour domain (Pearson's Correlation Coefficient [PCC] = -.763, p = .000), task behaviour (PCC = -.829, p = .000), social skills (PCC = -.351, p = .000), intrapersonal skills (PCC = -.208, p = .010), instrumental activities of daily living (IADL) (PCC = -.329, p = .038) and leisure activities (PCC = -.433, p = .005) scores of VOTES with the corresponding domains in the scales used for comparison was statistically significant. The correlation between the total score of VOTES and the total scores of OTTOS, SFQ and RSES was also statistically significant suggesting convergent validity. The correlation between the total score of VOTES with the total score of FBI is not statistically significant, implying good divergent validity. VOTES seems to be a promising tool to assess overall functioning of people with mental illness. © The Author(s) 2016.

Comparison between objective measures and parental behavioral rating scales of memory and attention in pediatric endocrinology patients.

PubMed

Limbers, Christine; Young, Danielle; Jernigan, Stephanie; Bryant, William; Stephen, Matt

2017-01-01

Behavioral rating scales represent one potential method for screening of cognitive functioning in routine clinical care. It is not yet known if objective performance based measures and behavioral rating scales of cognitive functioning completed by parents yield similar information in pediatric endocrinology patients. The purpose of the present study was to evaluate the associations between performance-based measures and behavioral rating scales of memory and attention/concentration completed by parents of pediatric patients with Type 1 Diabetes or obesity. The sample consisted of 73 pediatric patients with Type 1 Diabetes or obesity (BMI > 95th percentile) ages 6-16 years (mean age = 12.29 years) referred to an outpatient pediatric endocrinology clinic. Youth were administered the Wide Range Assessment of Memory and Learning (WRAML-2). Parents completed the Child Behavior Checklist (CBCL) and the PedsQL Cognitive Functioning Scale. Pearson's Product Moment Correlations were examined among the performance-based measures and behavioral rating scales. All intercorrelations between the performance-based measures and behavioral rating scales completed by parents were in the small range. The only statistically significant (P < 0.05) and approaching medium correlation was between the PedsQL Cognitive Functioning Scale and WRAML-2 Verbal Memory Index (r = 0.28). On behavioral rating scales and performance-based measures of visual memory and attention/concentration, our sample exhibited greater difficulties than healthy youth from previously published data (P < 0.05). One possible explanation for our findings is that behavioral rating scales of attention/concentration and memory completed by parents measure different aspects of cognitive functioning than performance based measures in pediatric patients with Type 1 Diabetes or obesity.

Major depressive disorder: gender differences in symptoms, life quality, and sexual function.

PubMed

Lai, Chien-Han

2011-02-01

To investigate the gender differences of symptoms, life quality, functional impairment, and sexual function of patients with moderately severe major depressive disorder (MDD). One hundred forty-six outpatients with MDD were enrolled into this study with specific selection criteria (male, 57; female, 89; mean ± SD age, 38.30 ± 11.69 years). All the patients self-rated the Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR16) and the Integral Inventory for Depression (IID) for the assessment of symptoms assessment as well as the EuroQol life quality scale (EQ5D) was for the subjective life quality, the Sheehan disability scale was for the functional impairments, and the Arizona Sexual Experience Scale was for sexual function evaluation. All data were analyzed to estimate correlation and gender difference. Female patients had higher scores of the QIDS-SR16, IID, and Arizona Sexual Experience scales. Significant gender differences of sadness, sleep, appetite, calmness, painful symptoms, and sexual functioning were observed. The female-specific sexual dysfunctions included lower sexual drive, lower sexual arousal, lower horny feelings, lower orgasms, and lower satisfaction of orgasm. The MDD episodes were related to the EuroQol life quality scale and the SDS. Interepisode years were associated with the IID. The Sheehan disability scale was correlated with QIDS-SR16 with statistical significance. Patients with MDD showed a correlation between symptoms and functional impairment. Female patients might be more sexually impaired, more vegetative, more depressed, and experiencing more sadness and physical pain.

Programmable gradational micropatterning of functional materials using maskless lithography controlling absorption.

PubMed

Jung, Yushin; Lee, Howon; Park, Tae-Joon; Kim, Sungsik; Kwon, Sunghoon

2015-10-22

The demand for patterning functional materials precisely on surfaces of stimuli-responsive devices has increased in many research fields. In situ polymerization technology is one of the most convenient ways to place the functional materials on a desired location with micron-scale accuracy. To fabricate stimuli-responsive surfaces, controlling concentration of the functional material is much as important as micropatterning them. However, patterning and controlling concentration of the functional materials simultaneously requires an additional process, such as preparing multiple co-flow microfluidic structures and numbers of solutions with various concentrations. Despite applying these processes, fabricating heterogeneous patterns in large scale (millimeter scale) is still impossible. In this study, we propose an advanced in situ polymerization technique to pattern the surface in micron scale in a concentration-controlled manner. Because the concentration of the functional materials is manipulated by self-assembly on the surface, a complex pattern could be easily fabricated without any additional procedure. The complex pattern is pre-designed with absorption amount of the functional material, which is pre-determined by the duration of UV exposure. We show that the resolution reaches up to 2.5 μm and demonstrate mm-scale objects, maintaining the same resolution. We also fabricated Multi-bit barcoded micro particles verify the flexibility of our system.

A Rating Scale for the Functional Assessment of Patients with Familial Dysautonomia (Riley Day Syndrome)

PubMed Central

Axelrod, Felicia B.; Rolnitzky, Linda; von Simson, Gabrielle Gold; Berlin, Dena; Kaufmann, Horacio

2012-01-01

Objective To develop a reliable rating scale to assess functional capacity in children with familial dysautonomia, evaluate changes over time and determine whether severity within a particular functional category at a young age affected survival. Study design Ten functional categories were retrospectively assessed in 123 patients with familial dysautonomia at age 7 years ± 6 months. Each of the ten Functional Severity Scale (FuSS) categories (motor development, cognitive ability, psychological status, expressive speech, balance, oral coordination, frequency of dysautonomic crisis, respiratory, cardiovascular and nutritional status) was scored from 1 (worst or severely affected) to 5 (best or no impairment). Changes over time were analyzed further in 22 of the 123 patients who were also available at ages 17 and 27 years. Results Severely impaired cardiovascular function and high frequency of dysautonomic crisis negatively affected survival (p<0.005 and p<0.001, respectively). In the 22 individuals followed up to age 27 years, psychological status significantly worsened (p=0.01), and expressive speech improved (p=0.045). From age 17 to 27 years, balance worsened markedly (p =0.048). Conclusion The FuSS scale is a reliable tool to measure functional capacity in patients with familial dysautonomia. The scale may prove useful in providing prognosis and as a complementary endpoint in clinical trials. PMID:22727867

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites

PubMed Central

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results provide insight into pigment phenotypes in pythons. PMID:27698666

Transcriptional suppression of microRNA-27a contributes to laryngeal cancer differentiation via GSK-3β-involved Wnt/β-catenin pathway

PubMed Central

Chen, Sheng; Sun, Yuan-Yuan; Zhang, Zhao-Xiong; Li, Yun-Hui; Xu, Zhen-Ming; Fu, Wei-Neng

2017-01-01

miR-27a regulates cell differentiation in a variety of diseases. However, whether and how miR-27a participates in laryngeal cancer cell differentiation remains unknown. Therefore, we explored role and molecular mechanism of miR-27a in laryngeal cancer differentiation in the study. We found that miR-27a expression was inversely correlated with laryngeal cancer differentiation degree based on the clinical pathological diagnosis of each patient. miR-27 asignificantly rescued differentiation and inhibited β-catenin, LEF1, OCT4 and SOX2 in Wnt/β-catenin pathway in all-trans-retinoic acid (ATRA)-induced laryngeal cancer cells. Bindings of RARα to miR-27a and miR-27a to GSK-3β were confirmed by ChIP and Luciferase reporter assays, respectively. In conclusion, miR-27a is a negative regulator in laryngeal cancer differentiation. RARα-mediated miR-27a transcriptional inactivation releases the inhibition of miR-27a on GSK-3β leading to laryngeal cancer differentiation through GSK-3β-involved Wnt/β-catenin pathway, suggesting that miR-27a is a usefully therapeutic target at least in ATRA-induced laryngeal cancer differentiation. PMID:28122350

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites.

PubMed

Irizarry, Kristopher J L; Bryden, Randall L

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus . Our results provide insight into pigment phenotypes in pythons.

Overexpression of {alpha}-catenin increases osteoblastic differentiation in mouse mesenchymal C3H10T1/2 cells

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

Kim, Dohee; Yang, Jae-Yeon; Shin, Chan Soo, E-mail: csshin@snu.ac.kr

2009-05-15

{alpha}- and {beta}-Catenin link cadherins to the actin-based cytoskeleton at adherens junctions and regulate cell-cell adhesion. Although roles of cadherins and canonical Wnt-/{beta}-catenin-signaling in osteoblastic differentiation have been extensively studied, the role of {alpha}-catenin is not known. Murine embryonic mesenchymal stem cells, C3H10T1/2 cells, were transduced with retrovirus encoding {alpha}-catenin (MSCV-{alpha}-catenin-HA-GFP). In the presence of Wnt-3A conditioned medium or osteogenic medium ({beta}-glycerol phosphate and ascorbic acid), cells overexpressing {alpha}-catenin showed enhanced osteoblastic differentiation as measured by alkaline phosphatase (ALP) staining and ALP activity assay compared to cells transduced with empty virus (MSCV-GFP). In addition, mRNA expression of osteocalcin and Runx2more » was significantly increased compared to control. Cell aggregation assay revealed that {alpha}-catenin overexpression has significantly increased cell-cell aggregation. However, cellular {beta}-catenin levels (total, cytoplasmic-nuclear ratio) and {beta}-catenin-TCF/LEF transcriptional activity did not change by overexpression of {alpha}-catenin. Knock-down of {alpha}-catenin using siRNA decreased osteoblastic differentiation as measured by ALP assay. These results suggest that {alpha}-catenin overexpression increases osteoblastic differentiation by increasing cell-cell adhesion rather than Wnt-/{beta}-catenin-signaling.« less

Genetics, gene expression and bioinformatics of the pituitary gland.

PubMed

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2009-04-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown aetiology. These studies reveal critical roles for Wnt signalling pathways, including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic protein antagonists and targets of notch signalling. Current studies are investigating the roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for the identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. Copyright 2009 S. Karger AG, Basel.

Genetics, Gene Expression and Bioinformatics of the Pituitary Gland

PubMed Central

Davis, Shannon W; Potok, Mary Anne; Brinkmeier, Michelle L; Carninci, Piero; Lyons, Robert H; MacDonald, James W.; Fleming, Michelle T; Mortensen, Amanda H; Egashira, Noboru; Ghosh, Debashis; Steel, Karen P.; Osamura, Robert Y; Hayashizaki, Yoshihide; Camper, Sally A

2011-01-01

Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown etiology. These studies reveal critical roles for Wnt signalling pathways including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic proteins antagonists, and targets of notch signalling. Current studies are investigating roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers. PMID:19407506

Phytochemicals as Innovative Therapeutic Tools against Cancer Stem Cells.

PubMed

Scarpa, Emanuele-Salvatore; Ninfali, Paolino

2015-07-10

The theory that several carcinogenetic processes are initiated and sustained by cancer stem cells (CSCs) has been validated, and specific methods to identify the CSCs in the entire population of cancer cells have also proven to be effective. This review aims to provide an overview of recently acquired scientific knowledge regarding phytochemicals and herbal extracts, which have been shown to be able to target and kill CSCs. Many genes and proteins that sustain the CSCs' self-renewal capacity and drug resistance have been described and applications of phytochemicals able to interfere with these signaling systems have been shown to be operatively efficient both in vitro and in vivo. Identification of specific surface antigens, mammosphere formation assays, serial colony-forming unit assays, xenograft transplantation and label-retention assays coupled with Aldehyde dehydrogenase 1 (ALDH1) activity evaluation are the most frequently used techniques for measuring phytochemical efficiency in killing CSCs. Moreover, it has been demonstrated that EGCG, curcumin, piperine, sulforaphane, β-carotene, genistein and the whole extract of some plants are able to kill CSCs. Most of these phytochemicals act by interfering with the canonical Wnt (β-catenin/T cell factor-lymphoid enhancer factor (TCF-LEF)) pathway implicated in the pathogenesis of several cancers. Therefore, the use of phytochemicals may be a true therapeutic strategy for eradicating cancer through the elimination of CSCs.

Function Invariant and Parameter Scale-Free Transformation Methods

ERIC Educational Resources Information Center

Bentler, P. M.; Wingard, Joseph A.

1977-01-01

A scale-invariant simple structure function of previously studied function components for principal component analysis and factor analysis is defined. First and second partial derivatives are obtained, and Newton-Raphson iterations are utilized. The resulting solutions are locally optimal and subjectively pleasing. (Author/JKS)

A machine learning approach for efficient uncertainty quantification using multiscale methods

NASA Astrophysics Data System (ADS)

Chan, Shing; Elsheikh, Ahmed H.

2018-02-01

Several multiscale methods account for sub-grid scale features using coarse scale basis functions. For example, in the Multiscale Finite Volume method the coarse scale basis functions are obtained by solving a set of local problems over dual-grid cells. We introduce a data-driven approach for the estimation of these coarse scale basis functions. Specifically, we employ a neural network predictor fitted using a set of solution samples from which it learns to generate subsequent basis functions at a lower computational cost than solving the local problems. The computational advantage of this approach is realized for uncertainty quantification tasks where a large number of realizations has to be evaluated. We attribute the ability to learn these basis functions to the modularity of the local problems and the redundancy of the permeability patches between samples. The proposed method is evaluated on elliptic problems yielding very promising results.

The Functional Dysphagia Scale Is a Useful Tool for Predicting Aspiration Pneumonia in Patients With Parkinson Disease.

PubMed

Lee, Jong Hwa; Lee, Kyeong Woo; Kim, Sang Beom; Lee, Sook Joung; Chun, Sang Myung; Jung, Sung Moon

2016-06-01

To describe the correlation between the functional dysphagia scale and aspiration pneumonia and which characteristics influence the occurrence of aspiration pneumonia in patients with idiopathic Parkinson disease. Fifty-three patients with idiopathic Parkinson disease were prospectively evaluated in this study. Disease severity and functional status were measured by modified Hoehn and Yahr (H&Y) staging, Schwab and England activities of daily living (S-E ADL) scale and Korean version of Mini-Mental State Examination (K-MMSE). Swallowing function was evaluated by the functional dysphagia scale (FDS) and the penetration-aspiration scale (PAS) based on a videofluoroscopic swallowing study. The patients were followed up for 3 months and divided into two groups according to the occurrence of aspiration pneumonia. The correlation between the variables and aspiration pneumonia was analyzed. Eight patients of the 53 patients were allocated to the aspiration pneumonia group and 45 patients to the non-aspiration pneumonia group. The patients in the aspiration pneumonia group had significantly higher H&Y staging, and scored lower on S-E ADL scale and K-MMSE. The patients in the aspiration pneumonia group had significantly higher scores on FDS and PAS. A multiple logistic regression analysis showed that the S-E ADL scale and the FDS were associated with the occurrence of aspiration pneumonia in the patients with Parkinson disease. Given that the FDS can quantitatively assess the functional problems associated with dysphagia, it can be clinically effective in predicting the occurrence of aspiration pneumonia, and the FDS and the S-E ADL scale could be predictive variables for aspiration pneumonia in patients with Parkinson disease.

Using the Positive and Negative Syndrome Scale (PANSS) to Define Different Domains of Negative Symptoms

PubMed Central

Khan, Anzalee; Keefe, Richard S. E.

2017-01-01

Background: Reduced emotional experience and expression are two domains of negative symptoms. The authors assessed these two domains of negative symptoms using previously developed Positive and Negative Syndrome Scale (PANSS) factors. Using an existing dataset, the authors predicted three different elements of everyday functioning (social, vocational, and everyday activities) with these two factors, as well as with performance on measures of functional capacity. Methods: A large (n=630) sample of people with schizophrenia was used as the data source of this study. Using regression analyses, the authors predicted the three different aspects of everyday functioning, first with just the two Positive and Negative Syndrome Scale factors and then with a global negative symptom factor. Finally, we added neurocognitive performance and functional capacity as predictors. Results: The Positive and Negative Syndrome Scale reduced emotional experience factor accounted for 21 percent of the variance in everyday social functioning, while reduced emotional expression accounted for no variance. The total Positive and Negative Syndrome Scale negative symptom factor accounted for less variance (19%) than the reduced experience factor alone. The Positive and Negative Syndrome Scale expression factor accounted for, at most, one percent of the variance in any of the functional outcomes, with or without the addition of other predictors. Implications: Reduced emotional experience measured with the Positive and Negative Syndrome Scale, often referred to as “avolition and anhedonia,” specifically predicted impairments in social outcomes. Further, reduced experience predicted social impairments better than emotional expression or the total Positive and Negative Syndrome Scale negative symptom factor. In this cross-sectional study, reduced emotional experience was specifically related with social outcomes, accounting for essentially no variance in work or everyday activities, and being the sole meaningful predictor of impairment in social outcomes. PMID:29410933

Towards an integrated understanding of how micro scale processes shape groundwater ecosystem functions.

PubMed

Schmidt, Susanne I; Cuthbert, Mark O; Schwientek, Marc

2017-08-15

Micro scale processes are expected to have a fundamental role in shaping groundwater ecosystems and yet they remain poorly understood and under-researched. In part, this is due to the fact that sampling is rarely carried out at the scale at which microorganisms, and their grazers and predators, function and thus we lack essential information. While set within a larger scale framework in terms of geochemical features, supply with energy and nutrients, and exchange intensity and dynamics, the micro scale adds variability, by providing heterogeneous zones at the micro scale which enable a wider range of redox reactions. Here we outline how understanding micro scale processes better may lead to improved appreciation of the range of ecosystems functions taking place at all scales. Such processes are relied upon in bioremediation and we demonstrate that ecosystem modelling as well as engineering measures have to take into account, and use, understanding at the micro scale. We discuss the importance of integrating faunal processes and computational appraisals in research, in order to continue to secure sustainable water resources from groundwater. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional Status Change Among Children With Extracorporeal Membrane Oxygenation to Support Cardiopulmonary Resuscitation in a Pediatric Cardiac ICU: A Single Institution Report.

PubMed

Beshish, Asaad G; Baginski, Mathew R; Johnson, Thomas J; Deatrick, Barry K; Barbaro, Ryan P; Owens, Gabe E

2018-04-13

The purpose of this study is to describe the functional status of survivors from extracorporeal cardiopulmonary resuscitation instituted during in-hospital cardiac arrest using the Functional Status Scale. We aimed to determine risk factors leading to the development of new morbidity and unfavorable functional outcomes. This was a single-center retrospective chart review abstracting patient characteristics/demographic data, duration of cardiopulmonary resuscitation, duration of extracorporeal membrane oxygenation support, as well as maximum lactate levels within 2 hours before and after extracorporeal cardiopulmonary resuscitation. Cardiac arrest was defined as the administration of chest compressions for a nonperfusing cardiac rhythm. Extracorporeal cardiopulmonary resuscitation was defined by instituting extracorporeal membrane oxygenation during active chest compressions. Functional Status Scale scores were calculated at admission and on hospital discharge for patients who survived. Patients admitted in the pediatric cardiac ICU at C.S. Mott Children's Hospital from January 1, 2005, to December 31, 2015. Children less than 18 years who underwent extracorporeal cardiopulmonary resuscitation. Not applicable. Of 608 extracorporeal membrane oxygenation events during the study period, 80 were extracorporeal cardiopulmonary resuscitation (14%). There were 40 female patients (50%). Median age was 40 days (interquartile range, 9-342 d). Survival to hospital discharge was 48% (38/80). Median Functional Status Scale score at admission was 6 (interquartile range, 6-6) and at hospital discharge 9 (interquartile range, 8-11). Out of 38 survivors, 19 (50%) had a change of Functional Status Scale score greater than or equal to 3, that is consistent with new morbidity, and 26 (68%) had favorable functional outcomes with a change in Functional Status Scale score of less than 5. This is the first extracorporeal cardiopulmonary resuscitation report to examine changes in Functional Status Scale from admission (baseline) to discharge as a measure of overall functional outcome. Half of surviving patients (19/38) had new morbidity, while 68% (26/38) had favorable outcomes. Lactate levels, duration of cardiopulmonary resuscitation, and duration of extracorporeal membrane oxygenation were not found to be risk factors for the development of new morbidity and poor functional outcomes. Functional Status Scale may be used as a metric to monitor improvement of extracorporeal cardiopulmonary resuscitation outcomes and help guide research initiatives to decrease morbidity in this patient population.

Development of a Screening Scale for High-Functioning Pervasive Developmental Disorders Using the Tokyo Child Development Schedule and Tokyo Autistic Behavior Scale

ERIC Educational Resources Information Center

Suzuki, Mayo; Tachimori, Hisateru; Saito, Mari; Koyama, Tomonori; Kurita, Hiroshi

2011-01-01

This study aimed to compile a screening scale for high-functioning pervasive developmental disorders (PDD), using the Tokyo Child Development Schedule (TCDS) and Tokyo Autistic Behavior Scale (TABS). The 72 participants (IQ greater than or equal to 70) were divided into 3 groups after IQ matching depending on their diagnoses: i.e., PDD,…

Species, functional groups, and thresholds in ecological resilience

USGS Publications Warehouse

Sundstrom, Shana M.; Allen, Craig R.; Barichievy, Chris

2012-01-01

The cross-scale resilience model states that ecological resilience is generated in part from the distribution of functions within and across scales in a system. Resilience is a measure of a system's ability to remain organized around a particular set of mutually reinforcing processes and structures, known as a regime. We define scale as the geographic extent over which a process operates and the frequency with which a process occurs. Species can be categorized into functional groups that are a link between ecosystem processes and structures and ecological resilience. We applied the cross-scale resilience model to avian species in a grassland ecosystem. A species’ morphology is shaped in part by its interaction with ecological structure and pattern, so animal body mass reflects the spatial and temporal distribution of resources. We used the log-transformed rank-ordered body masses of breeding birds associated with grasslands to identify aggregations and discontinuities in the distribution of those body masses. We assessed cross-scale resilience on the basis of 3 metrics: overall number of functional groups, number of functional groups within an aggregation, and the redundancy of functional groups across aggregations. We assessed how the loss of threatened species would affect cross-scale resilience by removing threatened species from the data set and recalculating values of the 3 metrics. We also determined whether more function was retained than expected after the loss of threatened species by comparing observed loss with simulated random loss in a Monte Carlo process. The observed distribution of function compared with the random simulated loss of function indicated that more functionality in the observed data set was retained than expected. On the basis of our results, we believe an ecosystem with a full complement of species can sustain considerable species losses without affecting the distribution of functions within and across aggregations, although ecological resilience is reduced. We propose that the mechanisms responsible for shaping discontinuous distributions of body mass and the nonrandom distribution of functions may also shape species losses such that local extinctions will be nonrandom with respect to the retention and distribution of functions and that the distribution of function within and across aggregations will be conserved despite extinctions.

Computational Thermochemistry: Scale Factor Databases and Scale Factors for Vibrational Frequencies Obtained from Electronic Model Chemistries.

PubMed

Alecu, I M; Zheng, Jingjing; Zhao, Yan; Truhlar, Donald G

2010-09-14

Optimized scale factors for calculating vibrational harmonic and fundamental frequencies and zero-point energies have been determined for 145 electronic model chemistries, including 119 based on approximate functionals depending on occupied orbitals, 19 based on single-level wave function theory, three based on the neglect-of-diatomic-differential-overlap, two based on doubly hybrid density functional theory, and two based on multicoefficient correlation methods. Forty of the scale factors are obtained from large databases, which are also used to derive two universal scale factor ratios that can be used to interconvert between scale factors optimized for various properties, enabling the derivation of three key scale factors at the effort of optimizing only one of them. A reduced scale factor optimization model is formulated in order to further reduce the cost of optimizing scale factors, and the reduced model is illustrated by using it to obtain 105 additional scale factors. Using root-mean-square errors from the values in the large databases, we find that scaling reduces errors in zero-point energies by a factor of 2.3 and errors in fundamental vibrational frequencies by a factor of 3.0, but it reduces errors in harmonic vibrational frequencies by only a factor of 1.3. It is shown that, upon scaling, the balanced multicoefficient correlation method based on coupled cluster theory with single and double excitations (BMC-CCSD) can lead to very accurate predictions of vibrational frequencies. With a polarized, minimally augmented basis set, the density functionals with zero-point energy scale factors closest to unity are MPWLYP1M (1.009), τHCTHhyb (0.989), BB95 (1.012), BLYP (1.013), BP86 (1.014), B3LYP (0.986), MPW3LYP (0.986), and VSXC (0.986).

Dissociation in undergraduate students: disruptions in executive functioning.

PubMed

Giesbrecht, Timo; Merckelbach, Harald; Geraerts, Elke; Smeets, Ellen

2004-08-01

The concept of dissociation refers to disruptions in attentional control. Attentional control is an executive function. Few studies have addressed the link between dissociation and executive functioning. Our study investigated this relationship in a sample of undergraduate students (N = 185) who completed the Dissociative Experiences Scale and the Random Number Generation Task. We found that minor disruptions in executive functioning were related to a subclass of dissociative experiences, notably dissociative amnesia and the Dissociative Experiences Scale Taxon. However, the two other subscales of the Dissociative Experiences Scale, measuring depersonalization and absorption, were unrelated to executive functioning. Our findings suggest that a failure to inhibit previous responses might contribute to the pathological memory manifestations of dissociation.

Using the Positive and Negative Syndrome Scale (PANSS) to Define Different Domains of Negative Symptoms: Prediction of Everyday Functioning by Impairments in Emotional Expression and Emotional Experience.

PubMed

Harvey, Philip D; Khan, Anzalee; Keefe, Richard S E

2017-12-01

Background: Reduced emotional experience and expression are two domains of negative symptoms. The authors assessed these two domains of negative symptoms using previously developed Positive and Negative Syndrome Scale (PANSS) factors. Using an existing dataset, the authors predicted three different elements of everyday functioning (social, vocational, and everyday activities) with these two factors, as well as with performance on measures of functional capacity. Methods: A large (n=630) sample of people with schizophrenia was used as the data source of this study. Using regression analyses, the authors predicted the three different aspects of everyday functioning, first with just the two Positive and Negative Syndrome Scale factors and then with a global negative symptom factor. Finally, we added neurocognitive performance and functional capacity as predictors. Results: The Positive and Negative Syndrome Scale reduced emotional experience factor accounted for 21 percent of the variance in everyday social functioning, while reduced emotional expression accounted for no variance. The total Positive and Negative Syndrome Scale negative symptom factor accounted for less variance (19%) than the reduced experience factor alone. The Positive and Negative Syndrome Scale expression factor accounted for, at most, one percent of the variance in any of the functional outcomes, with or without the addition of other predictors. Implications: Reduced emotional experience measured with the Positive and Negative Syndrome Scale, often referred to as "avolition and anhedonia," specifically predicted impairments in social outcomes. Further, reduced experience predicted social impairments better than emotional expression or the total Positive and Negative Syndrome Scale negative symptom factor. In this cross-sectional study, reduced emotional experience was specifically related with social outcomes, accounting for essentially no variance in work or everyday activities, and being the sole meaningful predictor of impairment in social outcomes.

On the constrained minimization of smooth Kurdyka—Łojasiewicz functions with the scaled gradient projection method

NASA Astrophysics Data System (ADS)

Prato, Marco; Bonettini, Silvia; Loris, Ignace; Porta, Federica; Rebegoldi, Simone

2016-10-01

The scaled gradient projection (SGP) method is a first-order optimization method applicable to the constrained minimization of smooth functions and exploiting a scaling matrix multiplying the gradient and a variable steplength parameter to improve the convergence of the scheme. For a general nonconvex function, the limit points of the sequence generated by SGP have been proved to be stationary, while in the convex case and with some restrictions on the choice of the scaling matrix the sequence itself converges to a constrained minimum point. In this paper we extend these convergence results by showing that the SGP sequence converges to a limit point provided that the objective function satisfies the Kurdyka-Łojasiewicz property at each point of its domain and its gradient is Lipschitz continuous.

Choice of resolution by functional trait or taxonomy affects allometric scaling in soil food webs.

PubMed

Sechi, Valentina; Brussaard, Lijbert; De Goede, Ron G M; Rutgers, Michiel; Mulder, Christian

2015-01-01

Belowground organisms often display a shift in their mass-abundance scaling relationships due to environmental factors such as soil chemistry and atmospheric deposition. Here we present new empirical data that show strong differences in allometric scaling according to whether the resolution at the local scale is based on a taxonomic or a functional classification, while only slight differences arise according to soil environmental conditions. For the first time, isometry (an inverse 1:1 proportion) is recognized in mass-abundance relationships, providing a functional signal for constant biomass distribution in soil biota regardless of discrete trophic levels. Our findings are in contrast to those from aquatic ecosystems, in that higher trophic levels in soil biota are not a direct function of increasing body mass.

The MIMIC Method with Scale Purification for Detecting Differential Item Functioning

ERIC Educational Resources Information Center

Wang, Wen-Chung; Shih, Ching-Lin; Yang, Chih-Chien

2009-01-01

This study implements a scale purification procedure onto the standard MIMIC method for differential item functioning (DIF) detection and assesses its performance through a series of simulations. It is found that the MIMIC method with scale purification (denoted as M-SP) outperforms the standard MIMIC method (denoted as M-ST) in controlling…

Spatial variability in intertidal macroalgal assemblages on the North Portuguese coast: consistence between species and functional group approaches

NASA Astrophysics Data System (ADS)

Veiga, P.; Rubal, M.; Vieira, R.; Arenas, F.; Sousa-Pinto, I.

2013-03-01

Natural assemblages are variable in space and time; therefore, quantification of their variability is imperative to identify relevant scales for investigating natural or anthropogenic processes shaping these assemblages. We studied the variability of intertidal macroalgal assemblages on the North Portuguese coast, considering three spatial scales (from metres to 10 s of kilometres) following a hierarchical design. We tested the hypotheses that (1) spatial pattern will be invariant at all the studied scales and (2) spatial variability of macroalgal assemblages obtained by using species will be consistent with that obtained using functional groups. This was done considering as univariate variables: total biomass and number of taxa as well as biomass of the most important species and functional groups and as multivariate variables the structure of macroalgal assemblages, both considering species and functional groups. Most of the univariate results confirmed the first hypothesis except for the total number of taxa and foliose macroalgae that showed significant variability at the scale of site and area, respectively. In contrast, when multivariate patterns were examined, the first hypothesis was rejected except at the scale of 10 s of kilometres. Both uni- and multivariate results indicated that variation was larger at the smallest scale, and thus, small-scale processes seem to have more effect on spatial variability patterns. Macroalgal assemblages, both considering species and functional groups as surrogate, showed consistent spatial patterns, and therefore, the second hypothesis was confirmed. Consequently, functional groups may be considered a reliable biological surrogate to study changes on macroalgal assemblages at least along the investigated Portuguese coastline.

Community assembly of the ferns of Florida.

PubMed

Sessa, Emily B; Chambers, Sally M; Li, Daijiang; Trotta, Lauren; Endara, Lorena; Burleigh, J Gordon; Baiser, Benjamin

2018-03-01

Many ecological and evolutionary processes shape the assembly of organisms into local communities from a regional pool of species. We analyzed phylogenetic and functional diversity to understand community assembly of the ferns of Florida at two spatial scales. We built a phylogeny for 125 of the 141 species of ferns in Florida using five chloroplast markers. We calculated mean pairwise dissimilarity (MPD) and mean nearest taxon distance (MNTD) from phylogenetic distances and functional trait data for both spatial scales and compared the results to null models to assess significance. Our results for over vs. underdispersion in functional and phylogenetic diversity differed depending on spatial scale and metric considered. At the county scale, MPD revealed evidence for phylogenetic overdispersion, while MNTD revealed phylogenetic and functional underdispersion, and at the conservation area scale, MPD revealed phylogenetic and functional underdispersion while MNTD revealed evidence only of functional underdispersion. Our results are consistent with environmental filtering playing a larger role at the smaller, conservation area scale. The smaller spatial units are likely composed of fewer local habitat types that are selecting for closely related species, with the larger-scale units more likely to be composed of multiple habitat types that bring together a larger pool of species from across the phylogeny. Several aspects of fern biology, including their unique physiology and water relations and the importance of the independent gametophyte stage of the life cycle, make ferns highly sensitive to local, microhabitat conditions. © 2018 The Authors. American Journal of Botany is published by Wiley Periodicals, Inc. on behalf of the Botanical Society of America.

Questionnaire-based assessment of executive functioning: Psychometrics.

PubMed

Castellanos, Irina; Kronenberger, William G; Pisoni, David B

2018-01-01

The psychometric properties of the Learning, Executive, and Attention Functioning (LEAF) scale were investigated in an outpatient clinical pediatric sample. As a part of clinical testing, the LEAF scale, which broadly measures neuropsychological abilities related to executive functioning and learning, was administered to parents of 118 children and adolescents referred for psychological testing at a pediatric psychology clinic; 85 teachers also completed LEAF scales to assess reliability across different raters and settings. Scores on neuropsychological tests of executive functioning and academic achievement were abstracted from charts. Psychometric analyses of the LEAF scale demonstrated satisfactory internal consistency, parent-teacher inter-rater reliability in the small to large effect size range, and test-retest reliability in the large effect size range, similar to values for other executive functioning checklists. Correlations between corresponding subscales on the LEAF and other behavior checklists were large, while most correlations with neuropsychological tests of executive functioning and achievement were significant but in the small to medium range. Results support the utility of the LEAF as a reliable and valid questionnaire-based assessment of delays and disturbances in executive functioning and learning. Applications and advantages of the LEAF and other questionnaire measures of executive functioning in clinical neuropsychology settings are discussed.

Wetlands as large-scale nature-based solutions: status and future challenges for research and management

NASA Astrophysics Data System (ADS)

Thorslund, Josefin; Jarsjö, Jerker; Destouni, Georgia

2017-04-01

Wetlands are often considered as nature-based solutions that can provide a multitude of services of great social, economic and environmental value to humankind. The services may include recreation, greenhouse gas sequestration, contaminant retention, coastal protection, groundwater level and soil moisture regulation, flood regulation and biodiversity support. Changes in land-use, water use and climate can all impact wetland functions and occur at scales extending well beyond the local scale of an individual wetland. However, in practical applications, management decisions usually regard and focus on individual wetland sites and local conditions. To understand the potential usefulness and services of wetlands as larger-scale nature-based solutions, e.g. for mitigating negative impacts from large-scale change pressures, one needs to understand the combined function multiple wetlands at the relevant large scales. We here systematically investigate if and to what extent research so far has addressed the large-scale dynamics of landscape systems with multiple wetlands, which are likely to be relevant for understanding impacts of regional to global change. Our investigation regards key changes and impacts of relevance for nature-based solutions, such as large-scale nutrient and pollution retention, flow regulation and coastal protection. Although such large-scale knowledge is still limited, evidence suggests that the aggregated functions and effects of multiple wetlands in the landscape can differ considerably from those observed at individual wetlands. Such scale differences may have important implications for wetland function-effect predictability and management under large-scale change pressures and impacts, such as those of climate change.

Linear Scaling Density Functional Calculations with Gaussian Orbitals

NASA Technical Reports Server (NTRS)

Scuseria, Gustavo E.

1999-01-01

Recent advances in linear scaling algorithms that circumvent the computational bottlenecks of large-scale electronic structure simulations make it possible to carry out density functional calculations with Gaussian orbitals on molecules containing more than 1000 atoms and 15000 basis functions using current workstations and personal computers. This paper discusses the recent theoretical developments that have led to these advances and demonstrates in a series of benchmark calculations the present capabilities of state-of-the-art computational quantum chemistry programs for the prediction of molecular structure and properties.

Self-consistent implementation of meta-GGA functionals for the ONETEP linear-scaling electronic structure package.

PubMed

Womack, James C; Mardirossian, Narbe; Head-Gordon, Martin; Skylaris, Chris-Kriton

2016-11-28

Accurate and computationally efficient exchange-correlation functionals are critical to the successful application of linear-scaling density functional theory (DFT). Local and semi-local functionals of the density are naturally compatible with linear-scaling approaches, having a general form which assumes the locality of electronic interactions and which can be efficiently evaluated by numerical quadrature. Presently, the most sophisticated and flexible semi-local functionals are members of the meta-generalized-gradient approximation (meta-GGA) family, and depend upon the kinetic energy density, τ, in addition to the charge density and its gradient. In order to extend the theoretical and computational advantages of τ-dependent meta-GGA functionals to large-scale DFT calculations on thousands of atoms, we have implemented support for τ-dependent meta-GGA functionals in the ONETEP program. In this paper we lay out the theoretical innovations necessary to implement τ-dependent meta-GGA functionals within ONETEP's linear-scaling formalism. We present expressions for the gradient of the τ-dependent exchange-correlation energy, necessary for direct energy minimization. We also derive the forms of the τ-dependent exchange-correlation potential and kinetic energy density in terms of the strictly localized, self-consistently optimized orbitals used by ONETEP. To validate the numerical accuracy of our self-consistent meta-GGA implementation, we performed calculations using the B97M-V and PKZB meta-GGAs on a variety of small molecules. Using only a minimal basis set of self-consistently optimized local orbitals, we obtain energies in excellent agreement with large basis set calculations performed using other codes. Finally, to establish the linear-scaling computational cost and applicability of our approach to large-scale calculations, we present the outcome of self-consistent meta-GGA calculations on amyloid fibrils of increasing size, up to tens of thousands of atoms.

Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration

PubMed Central

Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W.; Jackson, Mary Lou

2018-01-01

Purpose Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. Methods We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Results Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). Conclusion In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL. PMID:29746512

Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration.

PubMed

Roh, Miin; Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W; Jackson, Mary Lou

2018-01-01

Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL.

Self-consistent implementation of meta-GGA functionals for the ONETEP linear-scaling electronic structure package

NASA Astrophysics Data System (ADS)

Womack, James C.; Mardirossian, Narbe; Head-Gordon, Martin; Skylaris, Chris-Kriton

2016-11-01

Accurate and computationally efficient exchange-correlation functionals are critical to the successful application of linear-scaling density functional theory (DFT). Local and semi-local functionals of the density are naturally compatible with linear-scaling approaches, having a general form which assumes the locality of electronic interactions and which can be efficiently evaluated by numerical quadrature. Presently, the most sophisticated and flexible semi-local functionals are members of the meta-generalized-gradient approximation (meta-GGA) family, and depend upon the kinetic energy density, τ, in addition to the charge density and its gradient. In order to extend the theoretical and computational advantages of τ-dependent meta-GGA functionals to large-scale DFT calculations on thousands of atoms, we have implemented support for τ-dependent meta-GGA functionals in the ONETEP program. In this paper we lay out the theoretical innovations necessary to implement τ-dependent meta-GGA functionals within ONETEP's linear-scaling formalism. We present expressions for the gradient of the τ-dependent exchange-correlation energy, necessary for direct energy minimization. We also derive the forms of the τ-dependent exchange-correlation potential and kinetic energy density in terms of the strictly localized, self-consistently optimized orbitals used by ONETEP. To validate the numerical accuracy of our self-consistent meta-GGA implementation, we performed calculations using the B97M-V and PKZB meta-GGAs on a variety of small molecules. Using only a minimal basis set of self-consistently optimized local orbitals, we obtain energies in excellent agreement with large basis set calculations performed using other codes. Finally, to establish the linear-scaling computational cost and applicability of our approach to large-scale calculations, we present the outcome of self-consistent meta-GGA calculations on amyloid fibrils of increasing size, up to tens of thousands of atoms.

Broadband Structural Dynamics: Understanding the Impulse-Response of Structures Across Multiple Length and Time Scales

DTIC Science & Technology

2010-08-18

Spectral domain response calculated • Time domain response obtained through inverse transform Approach 4: WASABI Wavelet Analysis of Structural Anomalies...differences at unity scale! Time Function Transform Apply Spectral Domain Transfer Function Time Function Inverse Transform Transform Transform  mtP

A Comparison of Intellectual and Behavioral Functioning in Older Persons.

ERIC Educational Resources Information Center

Smith, Michael C.; Kramer, Nanette A.

In order to ascertain the extent to which older persons' levels of behavioral functioning parallel their levels of intellectual functioning, 42 female patients, aged 61-99, of an outpatient comprehensive care geriatric clinic, completed the Wechsler Adult Intelligence Scale (WAIS), the Instrumental Activities of Daily Living Scale (IADL), the…

FAPRS Manual: Manual for the Functional Analytic Psychotherapy Rating Scale

ERIC Educational Resources Information Center

Callaghan, Glenn M.; Follette, William C.

2008-01-01

The Functional Analytic Psychotherapy Rating Scale (FAPRS) is behavioral coding system designed to capture those essential client and therapist behaviors that occur during Functional Analytic Psychotherapy (FAP). The FAPRS manual presents the purpose and rules for documenting essential aspects of FAP. The FAPRS codes are exclusive and exhaustive…

Gender-, age-, and race/ethnicity-based differential item functioning analysis of the movement disorder society-sponsored revision of the Unified Parkinson's disease rating scale.

PubMed

Goetz, Christopher G; Liu, Yuanyuan; Stebbins, Glenn T; Wang, Lu; Tilley, Barbara C; Teresi, Jeanne A; Merkitch, Douglas; Luo, Sheng

2016-12-01

Assess MDS-UPDRS items for gender-, age-, and race/ethnicity-based differential item functioning. Assessing differential item functioning is a core rating scale validation step. For the MDS-UPDRS, differential item functioning occurs if item-score probability among people with similar levels of parkinsonism differ according to selected covariates (gender, age, race/ethnicity). If the magnitude of differential item functioning is clinically relevant, item-score interpretation must consider influences by these covariates. Differential item functioning can be nonuniform (covariate variably influences an item-score across different levels of parkinsonism) or uniform (covariate influences an item-score consistently over all levels of parkinsonism). Using the MDS-UPDRS translation database of more than 5,000 PD patients from 14 languages, we tested gender-, age-, and race/ethnicity-based differential item functioning. To designate an item as having clinically relevant differential item functioning, we required statistical confirmation by 2 independent methods, along with a McFadden pseudo-R 2 magnitude statistic greater than "negligible." Most items showed no gender-, age- or race/ethnicity-based differential item functioning. When differential item functioning was identified, the magnitude statistic was always in the "negligible" range, and the scale-level impact was minimal. The absence of clinically relevant differential item functioning across all items and all parts of the MDS-UPDRS is strong evidence that the scale can be used confidently. As studies of Parkinson's disease increasingly involve multinational efforts and the MDS-UPDRS has several validated non-English translations, the findings support the scale's broad applicability in populations with varying gender, age, and race/ethnicity distributions. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Measuring fatigue in people living with HIV/AIDS: psychometric characteristics of the HIV-Related Fatigue Scale

PubMed Central

BW, Pence; Barroso, J.; Leserman, J.; Harmon, J.L.; Salahuddin, N.

2008-01-01

In the era of life-prolonging antiretroviral therapy, chronic fatigue is one of the most prevalent and disabling symptoms of people living with HIV/AIDS, yet its measurement remains challenging. No instruments have been developed specifically to describe HIV-related fatigue. We assessed the reliability and construct validity of the HIV-Related Fatigue Scale (HRFS), a 56-item self-report instrument developed through formative qualitative research and designed to measure the intensity and consequences of fatigue as well as the circumstances surrounding fatigue in people living with HIV. The HRFS has three main scales, which measure fatigue intensity, the responsiveness of fatigue to circumstances and fatigue-related impairment of functioning. The functioning scale can be further divided into subscales measuring impairment of activities of daily living, impairment of mental functioning and impairment of social functioning. Each scale demonstrated high internal consistency (Cronbach’s alpha=0.93, 0.91 and 0.97 for the intensity, responsiveness and functioning scales, respectively). The HRFS scales also demonstrated satisfactory convergent validity when compared to other fatigue measures. HIV-Related Fatigue Scales were moderately correlated with quality of nighttime sleep (rho = 0.46, 0.47 and 0.35) but showed only weak correlations with daytime sleepiness (rho = 0.20, 0.33 and 0.18). The scales were also moderately correlated with general mental and physical health as measured by the SF-36 Health Survey (rho ranged from 0.30 to 0.68 across the 8 SF-36 subscales with most >0.40). The HRFS is a promising tool to help facilitate research on the prevalence, etiology and consequences of fatigue in people living with HIV. PMID:18608084

Measuring fatigue in people living with HIV/AIDS: psychometric characteristics of the HIV-related fatigue scale.

PubMed

Pence, B W; Barroso, J; Leserman, J; Harmon, J L; Salahuddin, N

2008-08-01

In the era of life-prolonging antiretroviral therapy, chronic fatigue is one of the most prevalent and disabling symptoms of people living with HIV/AIDS, yet its measurement remains challenging. No instruments have been developed specifically to describe HIV-related fatigue. We assessed the reliability and construct validity of the HIV-Related Fatigue Scale (HRFS), a 56-item self-report instrument developed through formative qualitative research and designed to measure the intensity and consequences of fatigue as well as the circumstances surrounding fatigue in people living with HIV. The HRFS has three main scales, which measure fatigue intensity, the responsiveness of fatigue to circumstances and fatigue-related impairment of functioning. The functioning scale can be further divided into subscales measuring impairment of activities of daily living, impairment of mental functioning and impairment of social functioning. Each scale demonstrated high internal consistency (Cronbach's alpha=0.93, 0.91 and 0.97 for the intensity, responsiveness and functioning scales, respectively). The HRFS scales also demonstrated satisfactory convergent validity when compared to other fatigue measures. HIV-Related Fatigue Scales were moderately correlated with quality of nighttime sleep (rho=0.46, 0.47 and 0.35) but showed only weak correlations with daytime sleepiness (rho=0.20, 0.33 and 0.18). The scales were also moderately correlated with general mental and physical health as measured by the SF-36 Health Survey (rho ranged from 0.30 to 0.68 across the 8 SF-36 subscales with most >0.40). The HRFS is a promising tool to help facilitate research on the prevalence, etiology and consequences of fatigue in people living with HIV.

Influence of anisotropy on anomalous scaling of a passive scalar advected by the Navier-Stokes velocity field.

PubMed

Jurcisinová, E; Jurcisin, M; Remecký, R

2009-10-01

The influence of weak uniaxial small-scale anisotropy on the stability of the scaling regime and on the anomalous scaling of the single-time structure functions of a passive scalar advected by the velocity field governed by the stochastic Navier-Stokes equation is investigated by the field theoretic renormalization group and operator-product expansion within one-loop approximation of a perturbation theory. The explicit analytical expressions for coordinates of the corresponding fixed point of the renormalization-group equations as functions of anisotropy parameters are found, the stability of the three-dimensional Kolmogorov-like scaling regime is demonstrated, and the dependence of the borderline dimension d(c) is an element of (2,3] between stable and unstable scaling regimes is found as a function of the anisotropy parameters. The dependence of the turbulent Prandtl number on the anisotropy parameters is also briefly discussed. The influence of weak small-scale anisotropy on the anomalous scaling of the structure functions of a passive scalar field is studied by the operator-product expansion and their explicit dependence on the anisotropy parameters is present. It is shown that the anomalous dimensions of the structure functions, which are the same (universal) for the Kraichnan model, for the model with finite time correlations of the velocity field, and for the model with the advection by the velocity field driven by the stochastic Navier-Stokes equation in the isotropic case, can be distinguished by the assumption of the presence of the small-scale anisotropy in the systems even within one-loop approximation. The corresponding comparison of the anisotropic anomalous dimensions for the present model with that obtained within the Kraichnan rapid-change model is done.

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

Nottale, Laurent; Célérier, Marie-Noëlle

One of the main results of scale relativity as regards the foundation of quantum mechanics is its explanation of the origin of the complex nature of the wave function. The scale relativity theory introduces an explicit dependence of physical quantities on scale variables, founding itself on the theorem according to which a continuous and non-differentiable space-time is fractal (i.e., scale-divergent). In the present paper, the nature of the scale variables and their relations to resolutions and differential elements are specified in the non-relativistic case (fractal space). We show that, owing to the scale-dependence which it induces, non-differentiability involves a fundamentalmore » two-valuedness of the mean derivatives. Since, in the scale relativity framework, the wave function is a manifestation of the velocity field of fractal space-time geodesics, the two-valuedness of velocities leads to write them in terms of complex numbers, and yields therefore the complex nature of the wave function, from which the usual expression of the Schrödinger equation can be derived.« less

Effect of filter type on the statistics of energy transfer between resolved and subfilter scales from a-priori analysis of direct numerical simulations of isotropic turbulence

NASA Astrophysics Data System (ADS)

Buzzicotti, M.; Linkmann, M.; Aluie, H.; Biferale, L.; Brasseur, J.; Meneveau, C.

2018-02-01

The effects of different filtering strategies on the statistical properties of the resolved-to-subfilter scale (SFS) energy transfer are analysed in forced homogeneous and isotropic turbulence. We carry out a-priori analyses of the statistical characteristics of SFS energy transfer by filtering data obtained from direct numerical simulations with up to 20483 grid points as a function of the filter cutoff scale. In order to quantify the dependence of extreme events and anomalous scaling on the filter, we compare a sharp Fourier Galerkin projector, a Gaussian filter and a novel class of Galerkin projectors with non-sharp spectral filter profiles. Of interest is the importance of Galilean invariance and we confirm that local SFS energy transfer displays intermittency scaling in both skewness and flatness as a function of the cutoff scale. Furthermore, we quantify the robustness of scaling as a function of the filtering type.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

PubMed Central

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S.; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N.

2015-01-01

Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen–Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP. PMID:26106533

Patient-Reported Esthetic and Functional Outcomes of Primary Total Laparoscopic Intestinal Vaginoplasty in Transgender Women With Penoscrotal Hypoplasia.

PubMed

Bouman, Mark-Bram; van der Sluis, Wouter B; van Woudenberg Hamstra, Leonora E; Buncamper, Marlon E; Kreukels, Baudewijntje P C; Meijerink, Wilhelmus J H J; Mullender, Margriet G

2016-09-01

Puberty-suppressing hormonal treatment may result in penoscrotal hypoplasia in transgender women, making standard penile inversion vaginoplasty not feasible. For these patients, intestinal vaginoplasty is a surgical alternative, but knowledge on patient-reported postoperative outcomes and quality of life is lacking. To assess patient-reported functional and esthetic outcomes, quality of life, satisfaction, and sexual well-being after primary total laparoscopic intestinal vaginoplasty in transgender women. A survey study was performed on transgender women who underwent primary total laparoscopic intestinal vaginoplasty with at least 1 year of clinical follow-up. Thirty-one transgender women completed the questionnaires (median age at time of surgery = 19.1 years, range = 18.3-45.0) after a median clinical follow-up of 2.2 years (range = 0.8-7.5). Consenting women were asked to complete a combined questionnaire of the Subjective Happiness Scale, the Satisfaction With Life Scale, Cantril's Ladder of Life Scale, the Female Sexual Function Index, the Female Genital Self-Imaging Scale, the Amsterdam Hyperactive Pelvic Floor Scale-Women, and a questionnaire addressing postoperative satisfaction. Patient-reported functional and esthetic outcomes and postoperative quality of life. Patients graded their life satisfaction a median of 8.0 (range = 4.0-10.0) on Cantril's Ladder of Life Scale. Patients scored a mean total score of 27.7 ± 5.8 on the Satisfaction With Life Scale, which indicated high satisfaction with life, and a mean total score of 5.6 ± 1.4 on the Subjective Happiness Scale. Functionality was graded a median score of 8.0 of 10 (range = 1.0-10.0) and esthetics a score of 8.0 out of 10 (range = 3.0-10.0). The mean Female Sexual Function Index total score of sexually active transgender women was 26.0 ± 6.8. This group of relatively young transgender women reported satisfactory functional and esthetic results of the neovagina and a good quality of life, despite low Female Sexual Function Index scores. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Intermittent particle distribution in synthetic free-surface turbulent flows.

PubMed

Ducasse, Lauris; Pumir, Alain

2008-06-01

Tracer particles on the surface of a turbulent flow have a very intermittent distribution. This preferential concentration effect is studied in a two-dimensional synthetic compressible flow, both in the inertial (self-similar) and in the dissipative (smooth) range of scales, as a function of the compressibility C . The second moment of the concentration coarse grained over a scale r , n_{r};{2} , behaves as a power law in both the inertial and the dissipative ranges of scale, with two different exponents. The shapes of the probability distribution functions of the coarse-grained density n_{r} vary as a function of scale r and of compressibility C through the combination C/r;{kappa} (kappa approximately 0.5) , corresponding to the compressibility, coarse grained over a domain of scale r , averaged over Lagrangian trajectories.

The impact of tics, obsessive-compulsive symptoms, and impulsivity on global functioning in Tourette syndrome.

PubMed

Kano, Yukiko; Kono, Toshiaki; Matsuda, Natsumi; Nonaka, Maiko; Kuwabara, Hitoshi; Shimada, Takafumi; Shishikura, Kurie; Konno, Chizue; Ohta, Masataka

2015-03-30

This study investigated the relationships between tics, obsessive-compulsive symptoms (OCS), and impulsivity, and their effects on global functioning in Japanese patients with Tourette syndrome (TS), using the dimensional approach for OCS. Fifty-three TS patients were assessed using the Yale Global Tic Severity Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Impulsivity Rating Scale, and the Global Assessment of Functioning Scale. Although tic severity scores were significantly and positively correlated with OCS severity scores, impulsivity severity scores were not significantly correlated with either. The global functioning score was significantly and negatively correlated with tic and OCS severity scores. Of the 6 dimensional OCS scores, only aggression scores had a significant negative correlation with global functioning scores. A stepwise multiple regression analysis showed that only OCS severity scores were significantly associated with global functioning scores. Despite a moderate correlation between tic severity and OCS severity, the impact of OCS on global functioning was greater than that of tics. Of the OCS dimensions, only aggression had a significant impact on global functioning. Our findings suggest that it is important to examine OCS using a dimensional approach when analyzing global functioning in TS patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Resilience in Patients With Recent Diagnosis of a Schizophrenia Spectrum Disorder.

PubMed

Bozikas, Vasilis P; Parlapani, Eleni; Holeva, Vasiliki; Skemperi, Eleni; Bargiota, Stavroula I; Kirla, Danai; Rera, Eirini; Garyfallos, Georgios

2016-08-01

This study focused on resilience in patients who recently received a diagnosis of schizophrenia spectrum disorder (SSD). Psychopathological symptoms, depressive symptoms, and hopelessness were considered as sources of stress in the context of psychosis. Forty-eight SSD patients (mean period between diagnosis and recruitment, 20.79 months) were enrolled. Psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale, depression by the Calgary Depression Scale for Schizophrenia, hopelessness by the Beck Hopelessness Scale, and functioning by the Social and Occupational Functioning Scale. Resilience was evaluated by the Connor-Davidson Resilience Scale, which was additionally completed by 81 healthy controls. Patients demonstrated less resilience than did healthy participants. Female patients showed higher resilience levels and functioning than did males. High resilience levels were associated with less severe positive symptoms, general psychopathological symptoms, depression, and hopelessness. Apart from negative symptoms, results indicated that resilience may be a potential moderator of functioning. Thus, resilience-oriented interventions might constitute an additional therapeutic approach for SSD patients.

Functional Independent Scaling Relation for ORR/OER Catalysts

DOE PAGES

Christensen, Rune; Hansen, Heine A.; Dickens, Colin F.; ...

2016-10-11

A widely used adsorption energy scaling relation between OH* and OOH* intermediates in the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), has previously been determined using density functional theory and shown to dictate a minimum thermodynamic overpotential for both reactions. Here, we show that the oxygen–oxygen bond in the OOH* intermediate is, however, not well described with the previously used class of exchange-correlation functionals. By quantifying and correcting the systematic error, an improved description of gaseous peroxide species versus experimental data and a reduction in calculational uncertainty is obtained. For adsorbates, we find that the systematic error largelymore » cancels the vdW interaction missing in the original determination of the scaling relation. An improved scaling relation, which is fully independent of the applied exchange–correlation functional, is obtained and found to differ by 0.1 eV from the original. Lastly, this largely confirms that, although obtained with a method suffering from systematic errors, the previously obtained scaling relation is applicable for predictions of catalytic activity.« less

From symptoms to social functioning: differential effects of antidepressant therapy.

PubMed

Kasper, S

1999-05-01

Significant impairments in social functioning frequently occur simultaneously with depressive symptoms. The implications of such impairments extend beyond the depressed individual to their family, friends and society at large. Classical rating scales such as the Hamilton rating scale for depression primarily assess the core symptoms of depression. A range of rating scales are available, both self-reporting and administered by clinician; however, many have been criticised for their unspecified conceptual background and for being complex and time-consuming. While antidepressants in general appear to improve social functioning, no clear advantage for any single class of agent has been reported. Recently, a new self-report rating scale, the Social Adaptation Self-evaluation Scale, has been developed and used to compare the novel selective noradrenaline reuptake inhibitor, reboxetine, with the selective serotonin re-uptake inhibitor, fluoxetine. The noradrenergic agent, reboxetine, was shown to be significantly more effective in improving social functioning than the serotonergic agent, fluoxetine. These findings are consistent with previous observations that noradrenaline may preferentially improve vigilance, motivation and self-perception.

The typical developmental trajectory of social and executive functions in late adolescence and early adulthood.

PubMed

Taylor, Sophie Jane; Barker, Lynne Ann; Heavey, Lisa; McHale, Sue

2013-07-01

Executive functions and social cognition develop through childhood into adolescence and early adulthood and are important for adaptive goal-oriented behavior (Apperly, Samson, & Humphreys, 2009; Blakemore & Choudhury, 2006). These functions are attributed to frontal networks known to undergo protracted maturation into early adulthood (Barker, Andrade, Morton, Romanowski, & Bowles, 2010; Lebel, Walker, Leemans, Phillips, & Beaulieu, 2008), although social cognition functions are also associated with widely distributed networks. Previously, nonlinear development has been reported around puberty on an emotion match-to-sample task (McGivern, Andersen, Byrd, Mutter, & Reilly, 2002) and for IQ in midadolescence (Ramsden et al., 2011). However, there are currently little data on the typical development of social and executive functions in late adolescence and early adulthood. In a cross-sectional design, 98 participants completed tests of social cognition and executive function, Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999), Positive and Negative Affect Schedule (Watson, Clark, & Tellegen, 1988), Hospital Anxiety and Depression Scale (Zigmond & Snaith, 1983), and measures of pubertal development and demographics at ages 17, 18, and 19. Nonlinear age differences for letter fluency and concept formation executive functions were found, with a trough in functional ability in 18-year-olds compared with other groups. There were no age group differences on social cognition measures. Gender accounted for differences on 1 scale of concept formation, 1 dynamic social interaction scale, and 2 empathy scales. The clinical, developmental, and educational implications of these findings are discussed.

The patch mosaic and ecological decomposition across spatial scales in a managed landscape of northern Wisconsin, USA

Treesearch

Sari C. ​Saunders; Jiquan Chen; Thomas D. Drummer; Thomas R. Crow; Kimberley D. Brosofske; Eric J. Gustafson

2002-01-01

Understanding landscape organization across scales is vital for determining the impacts of management and retaining structurally and functionally diverse ecosystems. We studied the relationships of a functional variable, decomposition, to microclimatic, vegetative and structural features at multiple scales in two distinct landscapes of northern Wisconsin, USA. We hoped...

PedsQL gastrointestinal symptoms scales and gastrointestinal worry scales in pediatric patients with functional and organic gastrointestinal diseases in comparison to healthy controls

USDA-ARS?s Scientific Manuscript database

The primary objective was to compare the gastrointestinal (GI) symptoms and worry of pediatric patients with functional GI disorders (FGIDs) and organic GI diseases to healthy controls utilizing the Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms and Worry Scales for patient s...

Identifying Differential Item Functioning of Rating Scale Items with the Rasch Model: An Introduction and an Application

ERIC Educational Resources Information Center

Myers, Nicholas D.; Wolfe, Edward W.; Feltz, Deborah L.; Penfield, Randall D.

2006-01-01

This study (a) provided a conceptual introduction to differential item functioning (DIF), (b) introduced the multifaceted Rasch rating scale model (MRSM) and an associated statistical procedure for identifying DIF in rating scale items, and (c) applied this procedure to previously collected data from American coaches who responded to the coaching…

Measuring Functional Creativity: Non-Expert Raters and the Creative Solution Diagnosis Scale

ERIC Educational Resources Information Center

Cropley, David H.; Kaufman, James C.

2012-01-01

The Creative Solution Diagnosis Scale (CSDS) is a 30-item scale based on a core of four criteria: Relevance & Effectiveness, Novelty, Elegance, and Genesis. The CSDS offers potential for the consensual assessment of functional product creativity. This article describes an empirical study in which non-expert judges rated a series of mousetrap…

Lower blood pressure and apathy coincide in older persons with poorer functional ability: the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden.

PubMed

Moonen, Justine E F; Bertens, Anne Suzanne; Foster-Dingley, Jessica C; Smit, Roelof A J; van der Grond, Jeroen; de Craen, Anton J M; de Ruijter, Wouter; van der Mast, Roos C

2015-01-01

To examine the association between blood pressure (BP) measures and symptoms of apathy and depression in older adults with various levels of functional ability. Cross-sectional study using baseline data from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden. Primary care setting, the Netherlands. Community-dwelling individuals aged 75 and older (N = 430). Systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were measured during home visits. Symptoms of apathy and depression were assessed using the Apathy Scale and the Geriatric Depression Scale (GDS-15), respectively. Stratified linear regression was performed in participants with better and worse functional ability according to the median of the Groningen Activity Restriction Scale. In participants with lower functional ability, each 10-mmHg lower SBP, DBP, and MAP was associated with higher Apathy Scale scores (0.63, 0.92, and 0.94 points, respectively, all P < .005) but not with GDS-15 scores. In participants with higher functional ability, BP measures were not associated with Apathy Scale or GDS-15 scores. In older participants with poorer functional ability, lower BP was associated with more symptoms of apathy but not depression. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Bioinspired Wood Nanotechnology for Functional Materials.

PubMed

Berglund, Lars A; Burgert, Ingo

2018-05-01

It is a challenging task to realize the vision of hierarchically structured nanomaterials for large-scale applications. Herein, the biomaterial wood as a large-scale biotemplate for functionalization at multiple scales is discussed, to provide an increased property range to this renewable and CO 2 -storing bioresource, which is available at low cost and in large quantities. The Progress Report reviews the emerging field of functional wood materials in view of the specific features of the structural template and novel nanotechnological approaches for the development of wood-polymer composites and wood-mineral hybrids for advanced property profiles and new functions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Risk assessment of salinity and turbidity in Victoria (Australia) to stream insects' community structure does not always protect functional traits.

PubMed

Kefford, Ben J; Schäfer, Ralf B; Metzeling, Leon

2012-01-15

Ecological risk assessments mostly consider measures of community composition (structure) across large spatial scales. These assessments, using species sensitivity distributions (SSDs) or the relative species retention (RSR), may not be protective of ecosystem functions and services at smaller spatial scales. Here we examine how changes in biological traits, as proxy for ecosystem functions/services, at a fine spatial scale relate to larger scale assessment of structure. We use functional traits of stream insect species in south-east Australia in two habitats (riffle and edge/pool). We find that the protection of community structure in terms of 95% of species over multiple sites against adverse effects of salinity (as electrical conductivity) and turbidity will mostly, but not always, protect traits at smaller scales. Considering different combinations of trait modalities, contaminants and habitat, a mean of 17.5% (range 0%-36.8) of cases would result in under-protection of trait modalities despite protecting species composition (in terms of Jaccard's Index). This under-protection of trait modalities is only because of the different spatial scales that community structure and the traits were considered. We recommend that where the protection of biological traits, ecosystem functions or ecosystem services from stressors is a management goal, protective targets should not be solely set using measures of community structure such as SSDs or RSR. To protect both structural and functional attributes separate risk assessments should be done. Copyright © 2011 Elsevier B.V. All rights reserved.

Understanding protected area resilience: a multi-scale, social-ecological approach.

PubMed

Cumming, Graeme S; Allen, Craig R; Ban, Natalie C; Biggs, Duan; Biggs, Harry C; Cumming, David H M; De Vos, Alta; Epstein, Graham; Etienne, Michel; Maciejewski, Kristine; Mathevet, Raphaël; Moore, Christine; Nenadovic, Mateja; Schoon, Michael

2015-03-01

Protected areas (PAs) remain central to the conservation of biodiversity. Classical PAs were conceived as areas that would be set aside to maintain a natural state with minimal human influence. However, global environmental change and growing cross-scale anthropogenic influences mean that PAs can no longer be thought of as ecological islands that function independently of the broader social-ecological system in which they are located. For PAs to be resilient (and to contribute to broader social-ecological resilience), they must be able to adapt to changing social and ecological conditions over time in a way that supports the long-term persistence of populations, communities, and ecosystems of conservation concern. We extend Ostrom's social-ecological systems framework to consider the long-term persistence of PAs, as a form of land use embedded in social-ecological systems, with important cross-scale feedbacks. Most notably, we highlight the cross-scale influences and feedbacks on PAs that exist from the local to the global scale, contextualizing PAs within multi-scale social-ecological functional landscapes. Such functional landscapes are integral to understand and manage individual PAs for long-term sustainability. We illustrate our conceptual contribution with three case studies that highlight cross-scale feedbacks and social-ecological interactions in the functioning of PAs and in relation to regional resilience. Our analysis suggests that while ecological, economic, and social processes are often directly relevant to PAs at finer scales, at broader scales, the dominant processes that shape and alter PA resilience are primarily social and economic.

Understanding protected area resilience: a multi-scale, social-ecological approach

USGS Publications Warehouse

Cumming, Graeme S.; Allen, Craig R.; Ban, Natalie C.; Biggs, Duan; Biggs, Harry C.; Cumming, David H.M; De Vos, Alta; Epstein, Graham; Etienne, Michel; Maciejewski, Kristine; Mathevet, Raphael; Moore, Christine; Nenadovic, Mateja; Schoon, Michael

2015-01-01

Protected areas (PAs) remain central to the conservation of biodiversity. Classical PAs were conceived as areas that would be set aside to maintain a natural state with minimal human influence. However, global environmental change and growing cross-scale anthropogenic influences mean that PAs can no longer be thought of as ecological islands that function independently of the broader social-ecological system in which they are located. For PAs to be resilient (and to contribute to broader social-ecological resilience), they must be able to adapt to changing social and ecological conditions over time in a way that supports the long-term persistence of populations, communities, and ecosystems of conservation concern. We extend Ostrom's social-ecological systems framework to consider the long-term persistence of PAs, as a form of land use embedded in social-ecological systems, with important cross-scale feedbacks. Most notably, we highlight the cross-scale influences and feedbacks on PAs that exist from the local to the global scale, contextualizing PAs within multi-scale social-ecological functional landscapes. Such functional landscapes are integral to understand and manage individual PAs for long-term sustainability. We illustrate our conceptual contribution with three case studies that highlight cross-scale feedbacks and social-ecological interactions in the functioning of PAs and in relation to regional resilience. Our analysis suggests that while ecological, economic, and social processes are often directly relevant to PAs at finer scales, at broader scales, the dominant processes that shape and alter PA resilience are primarily social and economic.

Multi-scale Material Appearance

NASA Astrophysics Data System (ADS)

Wu, Hongzhi

Modeling and rendering the appearance of materials is important for a diverse range of applications of computer graphics - from automobile design to movies and cultural heritage. The appearance of materials varies considerably at different scales, posing significant challenges due to the sheer complexity of the data, as well the need to maintain inter-scale consistency constraints. This thesis presents a series of studies around the modeling, rendering and editing of multi-scale material appearance. To efficiently render material appearance at multiple scales, we develop an object-space precomputed adaptive sampling method, which precomputes a hierarchy of view-independent points that preserve multi-level appearance. To support bi-scale material appearance design, we propose a novel reflectance filtering algorithm, which rapidly computes the large-scale appearance from small-scale details, by exploiting the low-rank structures of Bidirectional Visible Normal Distribution Functions and pre-rotated Bidirectional Reflectance Distribution Functions in the matrix formulation of the rendering algorithm. This approach can guide the physical realization of appearance, as well as the modeling of real-world materials using very sparse measurements. Finally, we present a bi-scale-inspired high-quality general representation for material appearance described by Bidirectional Texture Functions. Our representation is at once compact, easily editable, and amenable to efficient rendering.

Functional profiles reveal unique ecological roles of various biological soil crust organisms

USGS Publications Warehouse

Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

2011-01-01

1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining species-rich BSC communities is crucial to maintain the overall functionality of ecosystems dominated by these organisms, and that dominance and the outcome of competition could be highly influential in the determination of such functionality. ?? 2011 The Authors. Functional Ecology ?? 2011 British Ecological Society.

Test Review: Barkley Deficits in Executive Functioning Scale (BDEFS)

ERIC Educational Resources Information Center

Allee-Smith, Paula J.; Winters, Rebecca R.; Drake, Amanda; Joslin, Amanda K.

2013-01-01

The Barkley Deficits in Executive Functioning Scale (BDEFS), authored by Russell A. Barkley and published by Guilford in 2011, is an individually administered assessment tool that may be used to evaluate adults ages 18 to 81. The purpose of this measure is to screen those who may be experiencing executive functioning (EF) deficits in…

Scaling of muscle architecture and fiber types in the rat hindlimb.

PubMed

Eng, Carolyn M; Smallwood, Laura H; Rainiero, Maria Pia; Lahey, Michele; Ward, Samuel R; Lieber, Richard L

2008-07-01

The functional capacity of a muscle is determined by its architecture and metabolic properties. Although extensive analyses of muscle architecture and fiber type have been completed in a large number of muscles in numerous species, there have been few studies that have looked at the interrelationship of these functional parameters among muscles of a single species. Nor have the architectural properties of individual muscles been compared across species to understand scaling. This study examined muscle architecture and fiber type in the rat (Rattus norvegicus) hindlimb to examine each muscle's functional specialization. Discriminant analysis demonstrated that architectural properties are a greater predictor of muscle function (as defined by primary joint action and anti-gravity or non anti-gravity role) than fiber type. Architectural properties were not strictly aligned with fiber type, but when muscles were grouped according to anti-gravity versus non-anti-gravity function there was evidence of functional specialization. Specifically, anti-gravity muscles had a larger percentage of slow fiber type and increased muscle physiological cross-sectional area. Incongruities between a muscle's architecture and fiber type may reflect the variability of functional requirements on single muscles, especially those that cross multiple joints. Additionally, discriminant analysis and scaling of architectural variables in the hindlimb across several mammalian species was used to explore whether any functional patterns could be elucidated within single muscles or across muscle groups. Several muscles deviated from previously described muscle architecture scaling rules and there was large variability within functional groups in how muscles should be scaled with body size. This implies that functional demands placed on muscles across species should be examined on the single muscle level.

Anisotropic evolution of 5D Friedmann-Robertson-Walker spacetime

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

Middleton, Chad A.; Stanley, Ethan

2011-10-15

We examine the time evolution of the five-dimensional Einstein field equations subjected to a flat, anisotropic Robertson-Walker metric, where the 3D and higher-dimensional scale factors are allowed to dynamically evolve at different rates. By adopting equations of state relating the 3D and higher-dimensional pressures to the density, we obtain an exact expression relating the higher-dimensional scale factor to a function of the 3D scale factor. This relation allows us to write the Friedmann-Robertson-Walker field equations exclusively in terms of the 3D scale factor, thus yielding a set of 4D effective Friedmann-Robertson-Walker field equations. We examine the effective field equations inmore » the general case and obtain an exact expression relating a function of the 3D scale factor to the time. This expression involves a hypergeometric function and cannot, in general, be inverted to yield an analytical expression for the 3D scale factor as a function of time. When the hypergeometric function is expanded for small and large arguments, we obtain a generalized treatment of the dynamical compactification scenario of Mohammedi [Phys. Rev. D 65, 104018 (2002)] and the 5D vacuum solution of Chodos and Detweiler [Phys. Rev. D 21, 2167 (1980)], respectively. By expanding the hypergeometric function near a branch point, we obtain the perturbative solution for the 3D scale factor in the small time regime. This solution exhibits accelerated expansion, which, remarkably, is independent of the value of the 4D equation of state parameter w. This early-time epoch of accelerated expansion arises naturally out of the anisotropic evolution of 5D spacetime when the pressure in the extra dimension is negative and offers a possible alternative to scalar field inflationary theory.« less

Soil Functional Mapping: A Geospatial Framework for Scaling Soil Carbon Cycling

NASA Astrophysics Data System (ADS)

Lawrence, C. R.

2017-12-01

Climate change is dramatically altering biogeochemical cycles in most terrestrial ecosystems, particularly the cycles of water and carbon (C). These changes will affect myriad ecosystem processes of importance, including plant productivity, C exports to aquatic systems, and terrestrial C storage. Soil C storage represents a critical feedback to climate change as soils store more C than the atmosphere and aboveground plant biomass combined. While we know plant and soil C cycling are strongly coupled with soil moisture, substantial unknowns remain regarding how these relationships can be scaled up from soil profiles to ecosystems. This greatly limits our ability to build a process-based understanding of the controls on and consequences of climate change at regional scales. In an effort to address this limitation we: (1) describe an approach to classifying soils that is based on underlying differences in soil functional characteristics and (2) examine the utility of this approach as a scaling tool that honors the underlying soil processes. First, geospatial datasets are analyzed in the context of our current understanding of soil C and water cycling in order to predict soil functional units that can be mapped at the scale of ecosystems or watersheds. Next, the integrity of each soil functional unit is evaluated using available soil C data and mapping units are refined as needed. Finally, targeted sampling is conducted to further differentiate functional units or fill in any data gaps that are identified. Completion of this workflow provides new geospatial datasets that are based on specific soil functions, in this case the coupling of soil C and water cycling, and are well suited for integration with regional-scale soil models. Preliminary results from this effort highlight the advantages of a scaling approach that balances theory, measurement, and modeling.

Psychometric properties of the OARSI/OMERACT osteoarthritis pain and functional impairment scales: ICOAP, KOOS-PS and HOOS-PS.

PubMed

Ruyssen-Witrand, A; Fernandez-Lopez, C J; Gossec, L; Anract, P; Courpied, J P; Dougados, M

2011-01-01

To evaluate the psychometric properties of the OARSI-OMERACT questionnaires in comparison to the existing validated scales. Consecutive hip or knee osteoarthritis patients consulting in an orthopedic department were enrolled in the study. Data collected were pain using the Intermittent and Constant Osteoarthritis Pain (ICOAP), a Numeric Rating Scale (NRS), the Western Ontario McMaster Universities' Osteoarthritis Index (WOMAC) pain subscale, the Lequesne pain subscale; functional impairment using the Knee disability and Osteoarthritis Outcome Score-Physical Function Shortform (KOOS-PS), the Hip disability and Osteoarthritis Outcome Score-Physical Function Shortform (HOOS-PS), a NRS, the WOMAC function sub-scale, the Lequesne function subscale. Validity was assessed by calculating the Spearman's correlation coefficient between all the scales. Reliability was assessed in out-patients with stable disease comparing the data collected within 2 weeks using the intra-class correlation coefficient (ICC). Responsiveness was assessed on the data from hospitalised patients prior to and 12 weeks after a total joint replacement (TJR) using the standardised response mean. Three hundred patients (mean age=68 years, females=62%, hip OA=57%) were included. There was a moderate to good correlation between ICOAP, KOOS-PS, HOOS-PS and the WOMAC, NRS and Lequesne scales. Reliability of the ICOAP hip OA HOOS-PS and KOOS-PS was good (ICC range 0.80-0.81) whereas it was moderate for knee ICOAP (ICC=0.65). Responsiveness of the ICOAP, KOOS-PS and HOOS-PS 12 weeks after TJR was comparable to responsiveness of other scales (SRM range: 0.54-1.82). The psychometric properties of the ICOAP, KOOS-PS and HOOS-PS were comparable to those of the WOMAC, Lequesne and NRS.

A simple scaling law for the equation of state and the radial distribution functions calculated by density-functional theory molecular dynamics

NASA Astrophysics Data System (ADS)

Danel, J.-F.; Kazandjian, L.

2018-06-01

It is shown that the equation of state (EOS) and the radial distribution functions obtained by density-functional theory molecular dynamics (DFT-MD) obey a simple scaling law. At given temperature, the thermodynamic properties and the radial distribution functions given by a DFT-MD simulation remain unchanged if the mole fractions of nuclei of given charge and the average volume per atom remain unchanged. A practical interest of this scaling law is to obtain an EOS table for a fluid from that already obtained for another fluid if it has the right characteristics. Another practical interest of this result is that an asymmetric mixture made up of light and heavy atoms requiring very different time steps can be replaced by a mixture of atoms of equal mass, which facilitates the exploration of the configuration space in a DFT-MD simulation. The scaling law is illustrated by numerical results.

Dimers in Piecewise Temperleyan Domains

NASA Astrophysics Data System (ADS)

Russkikh, Marianna

2018-03-01

We study the large-scale behavior of the height function in the dimer model on the square lattice. Richard Kenyon has shown that the fluctuations of the height function on Temperleyan discretizations of a planar domain converge in the scaling limit (as the mesh size tends to zero) to the Gaussian Free Field with Dirichlet boundary conditions. We extend Kenyon's result to a more general class of discretizations. Moreover, we introduce a new factorization of the coupling function of the double-dimer model into two discrete holomorphic functions, which are similar to discrete fermions defined in Smirnov (Proceedings of the international congress of mathematicians (ICM), Madrid, Spain, 2006; Ann Math (2) 172:1435-1467, 2010). For Temperleyan discretizations with appropriate boundary modifications, the results of Kenyon imply that the expectation of the double-dimer height function converges to a harmonic function in the scaling limit. We use the above factorization to extend this result to the class of all polygonal discretizations, that are not necessarily Temperleyan. Furthermore, we show that, quite surprisingly, the expectation of the double-dimer height function in the Temperleyan case is exactly discrete harmonic (for an appropriate choice of Laplacian) even before taking the scaling limit.

A numerical study of the string function using a primitive equation ocean model

NASA Astrophysics Data System (ADS)

Tyler, R. H.; Käse, R.

We use results from a primitive-equation ocean numerical model (SCRUM) to test a theoretical 'string function' formulation put forward by Tyler and Käse in another article in this issue. The string function acts as a stream function for the large-scale potential energy flow under the combined beta and topographic effects. The model results verify that large-scale anomalies propagate along the string function contours with a speed correctly given by the cross-string gradient. For anomalies having a scale similar to the Rossby radius, material rates of change in the layer mass following the string velocity are balanced by material rates of change in relative vorticity following the flow velocity. It is shown that large-amplitude anomalies can be generated when wind stress is resonant with the string function configuration.

Importance of curvature evaluation scale for predictive simulations of dynamic gas-liquid interfaces

NASA Astrophysics Data System (ADS)

Owkes, Mark; Cauble, Eric; Senecal, Jacob; Currie, Robert A.

2018-07-01

The effect of the scale used to compute the interfacial curvature on the prediction of dynamic gas-liquid interfaces is investigated. A new interface curvature calculation methodology referred to herein as the Adjustable Curvature Evaluation Scale (ACES) is proposed. ACES leverages a weighted least squares regression to fit a polynomial through points computed on the volume-of-fluid representation of the gas-liquid interface. The interface curvature is evaluated from this polynomial. Varying the least squares weight with distance from the location where the curvature is being computed, adjusts the scale the curvature is evaluated on. ACES is verified using canonical static test cases and compared against second- and fourth-order height function methods. Simulations of dynamic interfaces, including a standing wave and oscillating droplet, are performed to assess the impact of the curvature evaluation scale for predicting interface motions. ACES and the height function methods are combined with two different unsplit geometric volume-of-fluid (VoF) schemes that define the interface on meshes with different levels of refinement. We find that the results depend significantly on curvature evaluation scale. Particularly, the ACES scheme with a properly chosen weight function is accurate, but fails when the scale is too small or large. Surprisingly, the second-order height function method is more accurate than the fourth-order variant for the dynamic tests even though the fourth-order method performs better for static interfaces. Comparing the curvature evaluation scale of the second- and fourth-order height function methods, we find the second-order method is closer to the optimum scale identified with ACES. This result suggests that the curvature scale is driving the accuracy of the dynamics. This work highlights the importance of studying numerical methods with realistic (dynamic) test cases and that the interactions of the various discretizations is as important as the accuracy of one part of the discretization.

Synchrony, compensatory dynamics, and the functional trait basis of phenological diversity in a tropical dry forest tree community: effects of rainfall seasonality

NASA Astrophysics Data System (ADS)

Lasky, Jesse R.; Uriarte, María; Muscarella, Robert

2016-11-01

Interspecific variation in phenology is a key axis of functional diversity, potentially mediating how communities respond to climate change. The diverse drivers of phenology act across multiple temporal scales. For example, abiotic constraints favor synchronous reproduction (positive covariance among species), while biotic interactions can favor synchrony or compensatory dynamics (negative covariance). We used wavelet analyses to examine phenology of community flower and seed production for 45 tree species across multiple temporal scales in a tropical dry forest in Puerto Rico with marked rainfall seasonality. We asked three questions: (1) do species exhibit synchronous or compensatory temporal dynamics in reproduction, (2) do interspecific differences in phenology reflect variable responses to rainfall, and (3) is interspecific variation in phenology and response to a major drought associated with functional traits that mediate responses to moisture? Community-level flowering was synchronized at seasonal scales (˜5-6 mo) and at short scales (˜1 mo, following rainfall). However, seed rain exhibited significant compensatory dynamics at intraseasonal scales (˜3 mo), suggesting interspecific variation in temporal niches. Species with large leaves (associated with sensitivity to water deficit) peaked in reproduction synchronously with the peak of seasonal rainfall (˜5 mo scale). By contrast, species with high wood specific gravity (associated with drought resistance) tended to flower in drier periods. Flowering of tall species and those with large leaves was most tightly linked to intraseasonal (˜2 mo scale) rainfall fluctuations. Although the 2015 drought dramatically reduced community-wide reproduction, functional traits were not associated with the magnitude of species-specific declines. Our results suggest opposing drivers of synchronous versus compensatory dynamics at different temporal scales. Phenology associations with functional traits indicated that distinct strategies for coping with seasonality underlie phenological diversity. Observed drought responses highlight the importance of non-linear community responses to climate. Community phenology exhibits scale-specific patterns highlighting the need for multi-scale approaches to community dynamics.

The three-point function as a probe of models for large-scale structure

NASA Astrophysics Data System (ADS)

Frieman, Joshua A.; Gaztanaga, Enrique

1994-04-01

We analyze the consequences of models of structure formation for higher order (n-point) galaxy correlation functions in the mildly nonlinear regime. Several variations of the standard Omega = 1 cold dark matter model with scale-invariant primordial perturbations have recently been introduced to obtain more power on large scales, Rp is approximately 20/h Mpc, e.g., low matter-density (nonzero cosmological constant) models, 'tilted' primordial spectra, and scenarios with a mixture of cold and hot dark matter. They also include models with an effective scale-dependent bias, such as the cooperative galaxy formation scenario of Bower et al. We show that higher-order (n-point) galaxy correlation functions can provide a useful test of such models and can discriminate between models with true large-scale power in the density field and those where the galaxy power arises from scale-dependent bias: a bias with rapid scale dependence leads to a dramatic decrease of the the hierarchical amplitudes QJ at large scales, r is greater than or approximately Rp. Current observational constraints on the three-point amplitudes Q3 and S3 can place limits on the bias parameter(s) and appear to disfavor, but not yet rule out, the hypothesis that scale-dependent bias is responsible for the extra power observed on large scales.

Brief Assessment of Motor Function: Content Validity and Reliability of the Upper Extremity Gross Motor Scale

ERIC Educational Resources Information Center

Cintas, Holly Lea; Parks, Rebecca; Don, Sarah; Gerber, Lynn

2011-01-01

Content validity and reliability of the Brief Assessment of Motor Function (BAMF) Upper Extremity Gross Motor Scale (UEGMS) were evaluated in this prospective, descriptive study. The UEGMS is one of five BAMF ordinal scales designed for quick documentation of gross, fine, and oral motor skill levels. Designed to be independent of age and…

Are Psychophysical Scales of Intensities the Same or Different when Stimuli Vary on Other Dimensions? Theory with Experiments Varying Loudness and Pitch

ERIC Educational Resources Information Center

Luce, R. Duncan; Steingrimsson, Ragnar; Narens, Louis

2010-01-01

Most studies concerning psychological measurement scales of intensive attributes have concluded that these scales are of ratio type and that the psychophysical function is closely approximated by a power function. Experiments show, for such cases, that a commutativity property must hold under either successive increases or successive decreases…

The MMPI-2 in chronic psychiatric illness.

PubMed

Bosch, Peggy; Van Luijtelaar, Gilles; Van Den Noort, Maurits; Schenkwald, Julia; Kueppenbender, Nicole; Lim, Sabina; Egger, Jos; Coenen, Anton

2014-10-01

While previous studies on the MMPI-2 in patients with schizophrenia and depression have used mixed samples of both early stage and chronic psychiatric patients. Here, it is investigated whether chronicity itself might have a differential effect on the MMPI-2 profiles of these patients and whether demoralization 'associated with long-term illness' affects the scales of the MMPI-2. Thirty long-term patients with schizophrenia, 30 long-term patients with depression, and 30 healthy participants completed the MMPI-2. Groups were compared on Clinical Scales and on the Restructured Clinical (RC) Scales. Patients with schizophrenia differed from patients with depression on 14 MMPI-2 scales and from healthy controls on 10 scales, generally showing mean UT-scores < 65, indicating a subjective experience of (near) normal functioning. Patients with depression differed from healthy controls on 17 scales mostly with UT-scores > 65, indicating impaired functioning. Demoralization was higher in patients with depression than in patients with schizophrenia and both psychiatric groups differed from the healthy control group. It is concluded that long-term patients with depression show impaired functioning and high demoralization, while long-term patients with schizophrenia surprisingly show near normal functioning and less demoralization. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Scaling characteristics of one-dimensional fractional diffusion processes in the presence of power-law distributed random noise

NASA Astrophysics Data System (ADS)

Nezhadhaghighi, Mohsen Ghasemi

2017-08-01

Here, we present results of numerical simulations and the scaling characteristics of one-dimensional random fluctuations with heavy-tailed probability distribution functions. Assuming that the distribution function of the random fluctuations obeys Lévy statistics with a power-law scaling exponent, we investigate the fractional diffusion equation in the presence of μ -stable Lévy noise. We study the scaling properties of the global width and two-point correlation functions and then compare the analytical and numerical results for the growth exponent β and the roughness exponent α . We also investigate the fractional Fokker-Planck equation for heavy-tailed random fluctuations. We show that the fractional diffusion processes in the presence of μ -stable Lévy noise display special scaling properties in the probability distribution function (PDF). Finally, we numerically study the scaling properties of the heavy-tailed random fluctuations by using the diffusion entropy analysis. This method is based on the evaluation of the Shannon entropy of the PDF generated by the random fluctuations, rather than on the measurement of the global width of the process. We apply the diffusion entropy analysis to extract the growth exponent β and to confirm the validity of our numerical analysis.

Development of a scale of executive functioning for the RBANS.

PubMed

Spencer, Robert J; Kitchen Andren, Katherine A; Tolle, Kathryn A

2018-01-01

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a cognitive battery that contains scales of several cognitive abilities, but no scale in the instrument is exclusively dedicated to executive functioning. Although the subtests allow for observation of executive-type errors, each error is of fairly low base rate, and healthy and clinical normative data are lacking on the frequency of these types of errors, making their significance difficult to interpret in isolation. The aim of this project was to create an RBANS executive errors scale (RBANS EE) with items comprised of qualitatively dysexecutive errors committed throughout the test. Participants included Veterans referred for outpatient neuropsychological testing. Items were initially selected based on theoretical literature and were retained based on item-total correlations. The RBANS EE (a percentage calculated by dividing the number of dysexecutive errors by the total number of responses) was moderately related to each of seven established measures of executive functioning and was strongly predictive of dichotomous classification of executive impairment. Thus, the scale had solid concurrent validity, justifying its use as a supplementary scale. The RBANS EE requires no additional administration time and can provide a quantified measure of otherwise unmeasured aspects of executive functioning.

Scaling characteristics of one-dimensional fractional diffusion processes in the presence of power-law distributed random noise.

PubMed

Nezhadhaghighi, Mohsen Ghasemi

2017-08-01

Here, we present results of numerical simulations and the scaling characteristics of one-dimensional random fluctuations with heavy-tailed probability distribution functions. Assuming that the distribution function of the random fluctuations obeys Lévy statistics with a power-law scaling exponent, we investigate the fractional diffusion equation in the presence of μ-stable Lévy noise. We study the scaling properties of the global width and two-point correlation functions and then compare the analytical and numerical results for the growth exponent β and the roughness exponent α. We also investigate the fractional Fokker-Planck equation for heavy-tailed random fluctuations. We show that the fractional diffusion processes in the presence of μ-stable Lévy noise display special scaling properties in the probability distribution function (PDF). Finally, we numerically study the scaling properties of the heavy-tailed random fluctuations by using the diffusion entropy analysis. This method is based on the evaluation of the Shannon entropy of the PDF generated by the random fluctuations, rather than on the measurement of the global width of the process. We apply the diffusion entropy analysis to extract the growth exponent β and to confirm the validity of our numerical analysis.

Rank Determination of Mental Functions by 1D Wavelets and Partial Correlation.

PubMed

Karaca, Y; Aslan, Z; Cattani, C; Galletta, D; Zhang, Y

2017-01-01

The main aim of this paper is to classify mental functions by the Wechsler Adult Intelligence Scale-Revised tests with a mixed method based on wavelets and partial correlation. The Wechsler Adult Intelligence Scale-Revised is a widely used test designed and applied for the classification of the adults cognitive skills in a comprehensive manner. In this paper, many different intellectual profiles have been taken into consideration to measure the relationship between the mental functioning and psychological disorder. We propose a method based on wavelets and correlation analysis for classifying mental functioning, by the analysis of some selected parameters measured by the Wechsler Adult Intelligence Scale-Revised tests. In particular, 1-D Continuous Wavelet Analysis, 1-D Wavelet Coefficient Method and Partial Correlation Method have been analyzed on some Wechsler Adult Intelligence Scale-Revised parameters such as School Education, Gender, Age, Performance Information Verbal and Full Scale Intelligence Quotient. In particular, we will show that gender variable has a negative but a significant role on age and Performance Information Verbal factors. The age parameters also has a significant relation in its role on Performance Information Verbal and Full Scale Intelligence Quotient change.

Scaling of the space-time correlation function of particle currents in a suspension of hard-sphere-like particles: exposing when the motion of particles is Brownian.

PubMed

van Megen, W; Martinez, V A; Bryant, G

2009-12-18

The current correlation function is determined from dynamic light scattering measurements of a suspension of particles with hard spherelike interactions. For suspensions in thermodynamic equilibrium we find scaling of the space and time variables of the current correlation function. This finding supports the notion that the movement of suspended particles can be described in terms of uncorrelated Brownian encounters. However, in the metastable fluid, at volume fractions above freezing, this scaling fails.

An Assessment of Mentoring Functions and Barriers to Mentoring

DTIC Science & Technology

1999-12-01

were similarity between mentor and mentee and the quality of the supervisory relationship in terms of LMX and psychosocial and career development ... psychosocial (1985). These broad categories have remained at the core of mentoring from the time they were developed . Career development functions "help...internal consistency reported by Noe for the career development functions scale (7 items) was .89. The psychosocial functions scale, made up of 14 items

The Convergent Validity of the Questions about Behavioral Function Scale and Functional Analysis for Problem Behavior Displayed by Individuals with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Watkins, Nicholas; Rapp, John T.

2013-01-01

Only a few studies have compared the convergent validity of the Questions About Behavioral Function (QABF) scale to the results of functional analyses (FA). In the current study, six participants who emitted problem behaviors participated in either a brief, or a no-interaction-series FA, while each participant's parent completed the QABF. The…

Association between changes on the Negative Symptom Assessment scale (NSA-16) and measures of functional outcome in schizophrenia.

PubMed

Velligan, Dawn I; Alphs, Larry; Lancaster, Scott; Morlock, Robert; Mintz, Jim

2009-09-30

We examined whether changes in negative symptoms, as measured by scores on the 16-item Negative Symptom Assessment scale (NSA-16), were associated with changes in functional outcome. A group of 125 stable outpatients with schizophrenia were assessed at baseline and at 6 months using the NSA-16, the Brief Psychiatric Rating Scale, and multiple measures of functional outcome. Baseline adjusted regression coefficients indicated moderate correlations between negative symptoms and functional outcomes when baseline values of both variables were controlled. Results were nearly identical when we controlled for positive symptoms. Cross-lag panel correlations and Structural Equation Modeling were used to examine whether changes in negative symptoms drove changes in functional outcomes over time. Results indicated that negative symptoms drove the changes in the Social and Occupational Functioning Scale (SOFAS) rather than the reverse. Measures of Quality of Life and measures of negative symptoms may be assessing overlapping constructs or changes in both may be driven by a third variable. Negative symptoms were unrelated over time to scores on a performance-based measure of functional capacity. This study indicates that the relationship between negative symptom change and the change in functional outcomes is complex, and points to potential issues in selection of assessments.

Root structural and functional dynamics in terrestrial biosphere models--evaluation and recommendations.

PubMed

Warren, Jeffrey M; Hanson, Paul J; Iversen, Colleen M; Kumar, Jitendra; Walker, Anthony P; Wullschleger, Stan D

2015-01-01

There is wide breadth of root function within ecosystems that should be considered when modeling the terrestrial biosphere. Root structure and function are closely associated with control of plant water and nutrient uptake from the soil, plant carbon (C) assimilation, partitioning and release to the soils, and control of biogeochemical cycles through interactions within the rhizosphere. Root function is extremely dynamic and dependent on internal plant signals, root traits and morphology, and the physical, chemical and biotic soil environment. While plant roots have significant structural and functional plasticity to changing environmental conditions, their dynamics are noticeably absent from the land component of process-based Earth system models used to simulate global biogeochemical cycling. Their dynamic representation in large-scale models should improve model veracity. Here, we describe current root inclusion in models across scales, ranging from mechanistic processes of single roots to parameterized root processes operating at the landscape scale. With this foundation we discuss how existing and future root functional knowledge, new data compilation efforts, and novel modeling platforms can be leveraged to enhance root functionality in large-scale terrestrial biosphere models by improving parameterization within models, and introducing new components such as dynamic root distribution and root functional traits linked to resource extraction. No claim to original US Government works. New Phytologist © 2014 New Phytologist Trust.