134 research outputs found
Cardiac Device‐Related Endocarditis Complicated by Spinal Abscess
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90084/1/j.1540-8159.2011.03288.x.pd
Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2
The current Coronavirus Disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) shows similar pathology to MERS and SARS-CoV, with a current estimated fatality rate of 1.4%. Open reading frame 10 (ORF10) is a unique SARS-CoV-2 accessory protein, which contains eleven cytotoxic T lymphocyte (CTL) epitopes each of nine amino acids in length. Twenty-two unique SARS-CoV-2 ORF10 variants have been identified based on missense mutations found in sequence databases. Some of these mutations are predicted to decrease the stability of ORF10 in silico physicochemical and structural comparative analyses were carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid (aa) homology. Though there is a high degree of ORF10 protein similarity of SARS-CoV-2 and Pangolin-CoV, there are differences of these two ORF10 proteins related to their sub-structure (loop/coil region), solubility, antigenicity and shift from strand to coil at aa position 26 (tyrosine). SARS-CoV-2 ORF10, which is apparently expressed in vivo since reactive T cell clones are found in convalescent patients should be monitored for changes which could correlate with the pathogenesis of COVID-19
MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune response during infection
This work is licensed under a Creative Commons Attribution 4.0 International License.Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that emerged in 2012, causing severe pneumonia and acute respiratory distress syndrome (ARDS), with a case fatality rate of ~36%. When expressed in isolation, CoV accessory proteins have been shown to interfere with innate antiviral signaling pathways. However, there is limited information on the specific contribution of MERS-CoV accessory protein 4b to the repression of the innate antiviral response in the context of infection. We found that MERS-CoV 4b was required to prevent a robust NF-κB dependent response during infection. In wild-type virus infected cells, 4b localized to the nucleus, while NF-κB was retained in the cytoplasm. In contrast, in the absence of 4b or in the presence of cytoplasmic 4b mutants lacking a nuclear localization signal (NLS), NF-κB was translocated to the nucleus leading to the expression of pro-inflammatory cytokines. This indicates that NF-κB repression required the nuclear import of 4b mediated by a specific NLS. Interestingly, we also found that both in isolation and during infection, 4b interacted with α-karyopherin proteins in an NLS-dependent manner. In particular, 4b had a strong preference for binding karyopherin-α4 (KPNA4), which is known to translocate the NF-κB protein complex into the nucleus. Binding of 4b to KPNA4 during infection inhibited its interaction with NF-κB-p65 subunit. Thereby we propose a model where 4b outcompetes NF-κB for KPNA4 binding and translocation into the nucleus as a mechanism of interference with the NF-κB-mediated innate immune response
ECORS - Truc Vert 2008 : Qualification des modèles de houle et de morphodynamique
Cet article présente une campagne expérimentale internationale de grande envergure qui s’est déroulée en Mars-Avril 2008 sur la côte aquitaine. Cette campagne a permis de mettre en oeuvre des instrumentations et méthodes innovantes afin de mesurer une vaste gamme de processus hydrodynamiques, sédimentaires et morphologiques en zone de surf et de jet de rive tout en couvrant des échelles temporelles de la milli secondes à plusieurs semaines et des échelles spatiales subcentimétriques à décamétriques. Cette campagne apportera un jeu de données unique avec des conditions énergétiques très fortes (Hs> 5m) pour comprendre les processus mais également pour améliorer et valider les modèles numériques.The aim of this paper is to present a large international field experiment that took place in March-April 2008 on the French Aquitanian coast. During this field experiment, both very small and large spatial and temporal scales have been explored concerning hydrodynamic, sedimentary and morphodynamic processes in the surf and swash zones using innovative methods. This field experiment, one of the largest to take place in Europe (with the COAST 3D project), will provide a unique data set to explore surf zone and swash processes and improve numerical models in presence of very energetic events (5 storms with Hs > 5m) on macrotidal multi-barred sandy beaches
Influence of omentoplasty on colonic anastomosis in animals submitted to hemorrhagic shock in rats
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.
Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance
INTRODUCTION
Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic.
RATIONALE
We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs).
RESULTS
Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants.
CONCLUSION
Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
Urologic complications of HIV and AIDS
The original publication is available at http://www.nature.com/nrurol/journal/v6/n1/full/ncpuro1273.htmlIn recent years the nature of HIV infection has been dramatically transformed from an invariably fatal disease to a chronic disorder with a relatively benign course. Disease progression from HIV to AIDS and HIV-related mortality can be reduced effectively by several years of treatment with highly active antiretroviral therapy (HAART). For patients who do not have access to HAART, HIV infection continues to be a lethal disorder characterized by opportunistic infection with uncommon organisms (e.g. mycobacteria, fungi, parasites and viruses), as well as lethal malignancies such as Kaposi sarcoma, non-Hodgkin lymphoma and squamous cell carcinoma of the penis or cervix. In patients receiving HAART, urologic complications are likely to be caused by adverse effects of antiretroviral medication (e.g. indinavir urolithiasis) or disorders associated with aging, such as benign prostatic hyperplasia and prostate cancer. Prospective clinical trials have shown that adult male circumcision can reduce the rate of female to male HIV transmission by more than 50%; however, the development of preventive or curative modalities with 100% efficacy remains elusive.Publishers' versio
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