Evidence for the intense exchange of MazG in marine cyanophages by horizontal gene transfer

Background: S-PM2 is a phage capable of infecting strains of unicellular cyanobacteria belonging to the genus Synechococcus. S-PM2, like other myoviruses infecting marine cyanobacteria, encodes a number of bacterial-like genes. Amongst these genes is one encoding a MazG homologue that is hypothesized to be involved in the adaption of the infected host for production of progeny phage. Methodology/Principal Findings: This study focuses on establishing the occurrence of mazG homologues in other cyanophages isolated from different oceanic locations. Degenerate PCR primers were designed using the mazG gene of S-PM2. The mazG gene was found to be widely distributed and highly conserved among Synechococcus myoviruses and podoviruses from diverse oceanic provinces. Conclusions/Significance: This study provides evidence of a globally connected cyanophage gene pool, the cyanophage mazG gene having a small effective population size indicative of rapid lateral gene transfer despite being present in a substantial fraction of cyanophage. The Prochlorococcus and Synechococcus phage mazG genes do not cluster with the host mazG gene, suggesting that their primary hosts are not the source of the mazG gene

International University Students in Canada: Obtaining the Information Needed for Policy Making

International university students represent sources of goodwill and benefits for their host countries. Unfortunately, Canada, although still one of the major receiving countries, has seen a substantial decline in international enrolment during the 1980s. Reasons proposed for this decline include differential fees, insufficient financial support, quotas, and employment restrictions. The problems most frequently encountered by international students in Canada involve immigration procedures, accommodation, language, loneliness, and funding. The formulation of policies concerning these problems and other matters relevant to international university students occurs at the federal, provincial, and institutional levels. Even though the main forces driving such policies are cultural, financial, and political, the policies should take into account information about the needs, desires, and experiences of international students. A comprehensive 1986-87 University of Alberta survey of international students served as a case study to demonstrate how research can better inform policy making in this area. Respondents suggested that they would be helped by being allowed to work in Canada while studying and after graduation, which is a federal policy area, and by having more scholarships available to them and differential fees removed, both of which are provincial and institutional policy areas.Les pays qui reçoivent des étudiants étrangers en retirent bienveillance et avantages. Malheureusement, bien que le Canada soit encore un des pays qui reçoivent le plus, le nombre d'inscriptions venant de l'étranger y a considérable-ment diminué au cours des années 80. Les raisons avancées pour cette baisse comprennent les droits d'inscription différentiels, l'insuffisance de l'appui financier, les quotas et les retrictions d'emploi. Les difficultés auxquelles les étudiants étrangers doivent faire face le plus souvent au Canada se rapportent au processus d'immigrations, au financement, au logement, à la langue et à isolement. La formulation des politiques relatives à toutes ces questions et à d'autres concernant ces étudiants se fait aux niveaux du pays, de la province et de l'établissement. Ces politiques se fondent surtout sur des motifs culturels, économiques et politiques. Elles devraient toutefois tenir compte des besoins, des désirs et de l'expérience des étudiants étrangers. Une enquête détaillée menée auprès des étudiants étrangers par l'Universté de l'Alberta en 1986-1987 a servi pour d'étude de cas pour démontrer comment la recherche peut aider à éclairer les responsables de l'établissement des politiques. Dans cette enquête, les intéressés ont fait savoir qu'il leur serait utile d'avoir la permission de travailler au Canada pendant leurs études et après l'obtention de leur diplome, ce qui est une politique établie au niveau fédéral. Ils désireraient aussi avoir accès à davantage de bourses et voir annuler les frais différentiels, ce qui relève des provinces et des établissements

Coagulation factor VIIa binds to herpes simplex virus 1‐encoded glycoprotein C forming a factor X‐enhanced tenase complex oriented on membranes

BackgroundThe cell membrane‐derived initiators of coagulation, tissue factor (TF) and anionic phospholipid (aPL), are constitutive on the herpes simplex virus type 1 (HSV1) surface, bypassing physiological regulation. TF and aPL accelerate proteolytic activation of factor (F) X to FXa by FVIIa to induce clot formation and cell signaling. Thus, infection in vivo is enhanced by virus surface TF. HSV1‐encoded glycoprotein C (gC) is implicated in this tenase activity by providing viral FX binding sites and increasing FVIIa function in solution.ObjectiveTo examine the biochemical influences of gC on FVIIa‐dependent FX activation.MethodsImmunogold electron microscopy (IEM), kinetic chromogenic assays and microscale thermophoresis were used to dissect tenase biochemistry. Recombinant TF and gC were solubilized (s) by substituting the transmembrane domain with poly‐histidine, which could be orientated on synthetic unilamellar vesicles containing Ni‐chelating lipid (Ni‐aPL). These constructs were compared to purified HSV1 TF±/gC ± variants.ResultsIEM confirmed that gC, TF, and aPL are simultaneously expressed on a single HSV1 particle where the contribution of gC to tenase activity required the availability of viral TF. Unlike viral tenase activity, the cofactor effects of sTF and sgC on FVIIa was additive when bound to Ni‐aPL. FVIIa was found to bind to sgC and this was enhanced by FX. Orientation of sgC on a lipid membrane was critical for FVIIa‐dependent FX activation.ConclusionsThe assembly of gC with FVIIa/FX parallels that of TF and may involve other constituents on the HSV1 envelope with implications in virus infection and pathology.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155933/1/jth14790-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155933/2/jth14790.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155933/3/jth14790_am.pd

Ruminococcal cellulosome systems from rumen to human

This article is protected by copyright. All rights reserved. The authors appreciate the kind assistance of Miriam Lerner (ImmunArray Ltd. Company, Rehovot, Israel) with experiments involving the MicroGrid II arrayer. This research was supported by a grant (No. 1349) to EAB also from the Israel Science Foundation (ISF) and a grant (No. 24/11) issued to RL by The Sidney E. Frank Foundation also through the ISF. Additional support was obtained from the establishment of an Israeli Center of Research Excellence (I-CORE Center No. 152/11) managed by the Israel Science Foundation, from the United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel, by the Weizmann Institute of Science Alternative Energy Research Initiative (AERI) and the Helmsley Foundation. The authors also appreciate the support of the European Union, Area NMP.2013.1.1-2: Self-assembly of naturally occurring nanosystems: CellulosomePlus Project number: 604530 and an ERA-IB Consortium (EIB.12.022), acronym FiberFuel. HF and SHD acknowledge support from the Scottish Government Food Land and People programme and from BBSRC grant no. BB/L009951/1. In addition, EAB is grateful for a grant from the F. Warren Hellman Grant for Alternative Energy Research in Israel in support of alternative energy research in Israel administered by the Israel Strategic Alternative Energy Foundation (I-SAEF). E.A.B. is the incumbent of The Maynard I. and Elaine Wishner Chair of Bio-organic ChemistryPeer reviewedPostprin

Rumen cellulosomics : divergent fiber-degrading strategies revealed by comparative genome-wide analysis of six ruminococcal strains

Peer reviewedPublisher PD

Maintaining Structural Stability of Poly(lactic acid): Effects of Multifunctional Epoxy based Reactive Oligomers

In order to reduce the effects of hydrolytic degradation and to maintain sufficient viscosity during processing of biomass based poly(l-lactic acid) (PLLA), various epoxy functional reactive oligomers have been characterized and incorporated into the degraded fragments as chain extenders. The molecular weight of PLLA increased with the increase in functionality of the reactive oligomers. No further increase in molecular weight was observed for oligomers with functionality of greater than five. Under our experimental conditions, no gelation was found even when the highest functionality reactive oligomers were used. This is attributed to the preferential reaction of the carboxylic acid versus the negligible reactivity of the hydroxyl groups, present at the two ends of the degraded PLLA chains, with the epoxy groups. The study provides a clear understanding of the degradation and chain extension reaction of poly(lactic acid) (PLA) with epoxy functional reactive oligomers. It is also shown that a higher functionality and concentration of the reactive oligomers is needed, to bring about a sufficient increase in the molecular weight and hence the hydrolytic stability in circumstances when PLA chains suffer significant degradation during processing

Expression of Cellulosome Components and Type IV Pili within the Extracellular Proteome of Ruminococcus flavefaciens 007

Funding: The Rowett Institute receives funding from SG-RESAS (Scottish Government Rural and Environmental Science and Analysis Service). Visit of M.V. was supported by research grants from FEMS and Slovene human resources development and scholarship funds. Parts of this work were funded by grants from the United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel – BSF Energy Research grant to E.A.B. and B.A.W. and Regular BSF Research grants to R.L. and B.A.W. – and by the Israel Science Foundation (grant nos 966/09 and 159/07 291/08). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis.

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen

CACHD1 is an α2δ-like protein that modulates CaV3 voltage-gated calcium channel activity

The putative cache (Ca2+ channel and chemotaxis receptor) domain containing 1 (CACHD1) protein has predicted structural similarities to members of the alpha2delta voltage-gated Ca2+ channel (VGCC) auxiliary subunit family. CACHD1 mRNA and protein were highly expressed in the male mammalian CNS, in particular in the thalamus, hippocampus and cerebellum, with a broadly similar tissue distribution to CaV3 subunits, in particular, CaV3.1. In expression studies, CACHD1 increased cell-surface localization of CaV3.1 and these proteins were in close proximity at the cell surface consistent with the formation of CACHD1-CaV3.1 complexes. In functional electrophysiological studies, co-expression of human CACHD1 with CaV3.1, CaV3.2 and CaV3.3 caused a significant increase in peak current density and corresponding increases in maximal conductance. By contrast, alpha2delta-1 had no effect on peak current density or maximal conductance in either CaV3.1, CaV3.2 or CaV3.3. Comparison of CACHD1-mediated increases in CaV3.1 current density and gating currents revealed an increase in channel open probability. In hippocampal neurons from male and female E19 rats, CACHD1 overexpression increased CaV3-mediated action potential (AP) firing frequency and neuronal excitability. These data suggest that CACHD1 is structurally an alpha2delta-like protein that functionally modulates CaV3 voltage-gated calcium channel activity