69 research outputs found
Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms
<p>Abstract</p> <p>Background</p> <p>Data on the evolution of natural SIV infection in chimpanzees (SIVcpz) and on the impact of SIV on local ape populations are only available for Eastern African chimpanzee subspecies (<it>Pan troglodytes schweinfurthii</it>), and no data exist for Central chimpanzees (<it>Pan troglodytes troglodytes</it>), the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a <it>P.t.troglodytes </it>chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection.</p> <p>Results</p> <p>A male chimpanzee (Cam155), 1.5 years, was seized in southern Cameroon in November 2003 and screened SIV positive during quarantine. Clinical follow-up and biological analyses have been performed for 7 years and showed a significant decline of CD4 counts (1,380 cells/mm<sup>3 </sup>in 2004 vs 287 in 2009), a severe thrombocytopenia (130,000 cells/mm<sup>3 </sup>in 2004 vs 5,000 cells/mm<sup>3 </sup>in 2009), a weight loss of 21.8% from August 2009 to January 2010 (16 to 12.5 kg) and frequent periods of infections with diverse pathogens.</p> <p>DNA from PBMC, leftover from clinical follow-up samples collected in 2004 and 2009, was used to amplify overlapping fragments and sequence two full-length SIVcpz<it>Ptt</it>-Cam155 genomes. SIVcpz<it>Ptt</it>-Cam155 was phylogenetically related to other SIVcpz<it>Ptt </it>from Cameroon (SIVcpz<it>Ptt</it>-Cam13) and Gabon (SIVcpz<it>Ptt</it>-Gab1). Ten molecular clones 5 years apart, spanning the V1V4 gp120 <it>env </it>region (1,100 bp), were obtained. Analyses of the <it>env </it>region showed positive selection (dN-dS >0), intra-host length variation and extensive amino acid diversity between clones, greater in 2009. Over 5 years, N-glycosylation site frequency significantly increased (p < 0.0001).</p> <p>Conclusions</p> <p>Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected <it>P.t.troglodytes </it>chimpanzee. The findings show an increasing viral diversity over time and suggest clinical progression to an AIDS-like disease, showing that SIVcpz can be pathogenic in its host, as previously described in <it>P.t.schweinfurthii</it>. Although studying the impact of SIV infection in wild apes is difficult, efforts should be made to better characterize the pathogenicity of the ancestors of HIV-1 in their natural host and to find out whether SIV infection also plays a role in ape population decline.</p
Subatomic movements of a domain wall in the Peierls potential
Movements of individual domain walls in a ferromagnetic garnet were studied
with angstrom resolution. The measurements reveal that domain walls can be
locked between adjacent crystallographic planes and propagate by distinct steps
matching the lattice periodicity. Domain walls are found to be weakly mobile
within valleys of the atomic washboard but become unexpectedly flexible on
Peierls ridges, where they can be kept in a bi-stable state by ac magnetic
field. We describe the latter observation in terms of a single magnetic kink
propagating along a domain wall
Phylogenetic and Pathotypical Analysis of Two Virulent Newcastle Disease Viruses Isolated from Domestic Ducks in China
Two velogenic Newcastle disease viruses (NDV) obtained from outbreaks in domestic ducks in China were characterized in this study. Phylogenetic analysis revealed that both strains clustered with the class II viruses, with one phylogenetically close to the genotype VII NDVs and the other closer to genotype IX. The deduced amino acid sequence of the cleavage site of the fusion (F) protein confirmed that both isolates contained the virulent motif 112RRQK/RRF117 at the cleavage site. The two NDVs had severe pathogenicity in fully susceptible chickens, resulting in 100% mortality. One of the isolates also demonstrated some pathogenicity in domestic ducks. The present study suggests that more than one genotype of NDV circulates in domestic ducks in China and viral transmission may occur among chickens and domestic ducks
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
Work characteristics and determinants of job satisfaction in four age groups: university employeesβ point of view
Contains fulltext :
79843.pdf (publisher's version ) (Closed access)PURPOSE: To investigate (a) differences in work characteristics and (b) determinants of job satisfaction among employees in different age groups. METHODS: A cross-sectional questionnaire was filled in by 1,112 university employees, classified into four age groups. (a) Work characteristics were analysed with ANOVA while adjusting for sex and job classification. (b) Job satisfaction was regressed against job demands and job resources adapted from the Job Demands-Resources model. Results : Statistically significant differences concerning work characteristics between age groups are present, but rather small. Regression analyses revealed that negative association of the job demands workload and conflicts at work with job satisfaction faded by adding job resources. Job resources were most correlated with more job satisfaction, especially more skill discretion and more relations with colleagues. CONCLUSIONS: Skill discretion and relations with colleagues are major determinants of job satisfaction. However, attention should also be given to conflicts at work, support from supervisor and opportunities for further education, because the mean scores of these work characteristics were disappointing in almost all age groups. The latter two characteristics were found to be associated significantly to job satisfaction in older workers
Identification of Estrogen Receptor Dimer Selective Ligands Reveals Growth-Inhibitory Effects on Cells That Co-Express ERΞ± and ERΞ²
Estrogens play essential roles in the progression of mammary and prostatic diseases. The transcriptional effects of estrogens are transduced by two estrogen receptors, ERΞ± and ERΞ², which elicit opposing roles in regulating proliferation: ERΞ± is proliferative while ERΞ² is anti-proliferative. Exogenous expression of ERΞ² in ERΞ±-positive cancer cell lines inhibits cell proliferation in response to estrogen and reduces xenografted tumor growth in vivo, suggesting that ERΞ² might oppose ERΞ±'s proliferative effects via formation of ERΞ±/Ξ² heterodimers. Despite biochemical and cellular evidence of ERΞ±/Ξ² heterodimer formation in cells co-expressing both receptors, the biological roles of the ERΞ±/Ξ² heterodimer remain to be elucidated. Here we report the identification of two phytoestrogens that selectively activate ERΞ±/Ξ² heterodimers at specific concentrations using a cell-based, two-step high throughput small molecule screen for ER transcriptional activity and ER dimer selectivity. Using ERΞ±/Ξ² heterodimer-selective ligands at defined concentrations, we demonstrate that ERΞ±/Ξ² heterodimers are growth inhibitory in breast and prostate cells which co-express the two ER isoforms. Furthermore, using Automated Quantitative Analysis (AQUA) to examine nuclear expression of ERΞ± and ERΞ² in human breast tissue microarrays, we demonstrate that ERΞ± and ERΞ² are co-expressed in the same cells in breast tumors. The co-expression of ERΞ± and ERΞ² in the same cells supports the possibility of ERΞ±/Ξ² heterodimer formation at physio- and pathological conditions, further suggesting that targeting ERΞ±/Ξ² heterodimers might be a novel therapeutic approach to the treatment of cancers which co-express ERΞ± and ERΞ²
In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFΞ²-signaling and WT1
Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibroblasts, which contribute to cardiac repair. To understand what drives epicardial EMT, we used an in vitro model for human adult epicardial cells. These cells have an epithelium-like morphology and markedly express the cell surface marker vascular cell adhesion marker (VCAM-1). In culture, epicardial cells spontaneously undergo EMT after which the spindle-shaped cells now express endoglin. Both epicardial cells before and after EMT express the epicardial marker, Wilms tumor 1 (WT1). Adding transforming growth factor beta (TGFΞ²) induces loss of epithelial character and initiates the onset of mesenchymal differentiation in human adult epicardial cells. In this study, we show that TGFΞ²-induced EMT is dependent on type-1 TGFΞ² receptor activity and can be inhibited by soluble VCAM-1. We also show that epicardial-specific knockdown of Wilms tumor-1 (WT1) induces the process of EMT in human adult epicardial cells, through transcriptional regulation of platelet-derived growth factor receptor alpha (PdgfrΞ±), Snai1 and VCAM-1. These data provide new insights into the process of EMT in human adult epicardial cells, which might provide opportunities to develop new strategies for endogenous cell-based cardiac repair
Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.
The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of Ξ²2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514
SIVagm Infection in Wild African Green Monkeys from South Africa: Epidemiology, Natural History, and Evolutionary Considerations
Pathogenesis studies of SIV infection have not been performed to date in wild monkeys due to difficulty in collecting and storing samples on site and the lack of analytical reagents covering the extensive SIV diversity. We performed a large scale study of molecular epidemiology and natural history of SIVagm infection in 225 free-ranging AGMs from multiple locations in South Africa. SIV prevalence (established by sequencing pol, env, and gag) varied dramatically between infant/juvenile (7%) and adult animals (68%) (p<0.0001), and between adult females (78%) and males (57%). Phylogenetic analyses revealed an extensive genetic diversity, including frequent recombination events. Some AGMs harbored epidemiologically linked viruses. Viruses infecting AGMs in the Free State, which are separated from those on the coastal side by the Drakensberg Mountains, formed a separate cluster in the phylogenetic trees; this observation supports a long standing presence of SIV in AGMs, at least from the time of their speciation to their Plio-Pleistocene migration. Specific primers/probes were synthesized based on the pol sequence data and viral loads (VLs) were quantified. VLs were of 104-106 RNA copies/ml, in the range of those observed in experimentally-infected monkeys, validating the experimental approaches in natural hosts. VLs were significantly higher (107-108 RNA copies/ml) in 10 AGMs diagnosed as acutely infected based on SIV seronegativity (Fiebig II), which suggests a very active transmission of SIVagm in the wild. Neither cytokine levels (as biomarkers of immune activation) nor sCD14 levels (a biomarker of microbial translocation) were different between SIV-infected and SIV-uninfected monkeys. This complex algorithm combining sequencing and phylogeny, VL quantification, serology, and testing of surrogate markers of microbial translocation and immune activation permits a systematic investigation of the epidemiology, viral diversity and natural history of SIV infection in wild African natural hosts. Β© 2013 Ma et al
Action to protect the independence and integrity of global health research
Storeng KT, Abimbola S, Balabanova D, et al. Action to protect the independence and integrity of global health research. BMJ GLOBAL HEALTH. 2019;4(3): e001746
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