30 research outputs found

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

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    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

    Expression and characterization of Ov-47, a dominant antigen of Onchocerca volvulus

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    The expression and characterization of a recombinant antigen termed Ov-47 are described. Ov-47 was identified and isolated from a lambda gt-11 eDNA expression library derived from adult female Onclrucercu volvukrs mRNA using rabbit antiserum raised against the surface proteins of O. vulvulcw female worms. The antiserum was earlier found to mediate, in vitro, cytoadherence and cytotoxicity reactions to microfilariae in the presence of heat-labile serum factors. The deduced amino acid sequence of the gene was assigned the ENIBL GenBank Accession No. Y t5993. The open reading frame (1077 bp) of the gene was then subcloned into pQE60 and expressed in Escherchia coli JM 109 cells. The gene encodes a protein with an apparent molecular weight of 47,0 Da as revealed by SDS-PAGE. Up to (00 Itg/ml pure Ov-47 recombinant protein could be isolated from E. coli cultures by Ni-agarose affinity chromatography. The 47-kDa protein was recognized by sera from both infected and endemic normal subjects. The parent protein was found to have a molecular weight of 60 kDa. IeG3 subclass responses to Ov-47 were significantly higher in endemic normals than in infected subjects (P < 0.05). In contrast, IgGy responses were higher in infected subjects than in endemic normals (P < 0.05). I?GZ response exhibited marked age dependency with lower responses in younger patients, which rose to higher levels in elderly patients. IgGt, IgG3, and IgG4 responses did not show any age dependency. This study clearly shows that Ov-47 is a dominant antigen of O. volvetlus adult worms with an important role in the host-parasite-interplay

    Expression and regulation of Xenopus CRMP-4 in the developing nervous system.

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    The collaspin response mediator proteins (CRMPs) are a family of cytosolic phosphoproteins which play a critical role in the establishment of neuronal polarity and growth cone guidance. Here, we describe the temporal and spatial expression of CRMP-4 during early Xenopus embryogenesis. CRMP-4 transcripts were first detected by whole mount in situ hybridization at the end of gastrulation in the prospective neuroectoderm. During open neural plate stages, CRMP-4 was expressed broadly throughout the anterior neural plate and in the three bilateral stripes of the posterior neural plate where primary neurons arise. The expression in the territories of primary neurogenesis prefigures that of the post-mitotic neuronal marker N-tubulin. At tadpole stages, expression was maintained throughout the central nervous system and in the retina of the eye. Consistent with the observed expression, CRMP-4 transcripts are positively regulated by X-ngnr-1 and negatively by Notch signaling. The observed expression and regulation of CRMP-4 differ from that of the CRMP-2, which is induced by the events of neural induction.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Examining the Potential Impact of SWOT Observations in an Ocean Analysis–Forecasting System

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    NASA\u27s Surface Water and Ocean Topography (SWOT) satellite, scheduled for launch in 2020, will provide observations of sea surface height anomaly (SSHA) at a significantly higher spatial resolution than current satellite altimeters. This new observation type is expected to improve the ocean model mesoscale circulation. The potential improvement that SWOT will provide is investigated in this work by way of twin-data assimilation experiments using the Navy Coastal Ocean Model four-dimensional variational data assimilation (NCOM-4DVAR) system in its weak constraint formulation. Simulated SWOT observations are sampled from an ocean model run (referred to as the nature run) using an observation-simulator program provided by the SWOT science team. The SWOT simulator provides realistic spatial coverage, resolution, and noise characteristics based on the expected performance of the actual satellite. Twin-data assimilation experiments are run for a two-month period during which simulated observations are assimilated into a separate model (known as the background model) in a series of 96-h windows. The final condition of each analysis window is used to initialize a new 96-h forecast, and each forecast is compared to the nature run to determine the impact of the assimilated data. It is demonstrated here that the simulated SWOT observations help to constrain the model mesoscale to be more consistent with the nature run than the assimilation of traditional altimeter observations alone. The findings of this study suggest that data from SWOT may have a substantial impact on improving the ocean model forecast of mesoscale features and surface ocean velocity

    Mxi1 is essential for neurogenesis in Xenopus and acts by bridging the pan-neural and proneural genes.

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    We have isolated and characterized Xenopus Mxi1, a member of the Myc/Max/Mad family of bHLHZip transcription factors. Xmxi1 transcripts are present during gastrulation and early neurula stages, earlier and in broader domains as compared to the neuronal determination factor neurogenin (X-ngnr-1). Consistent with an early role in neurogenesis, Xmxi1 is positively regulated by Sox3, SoxD, and proneural genes, as well as negatively by the Notch pathway. Loss-of-function experiments demonstrate an essential role for Xmxi1 in the establishment of a mature neural state that can be activated by factors that induce neuronal differentiation, such as SoxD and X-ngnr-1. Overexpression of Xmxi1 in Xenopus embryos results in ectopic activation of Sox3, an early pan-neural marker of proliferating neural precursor cells. Within the neural plate, the neuronal differentiation marker N-tubulin and cell cycle control genes such as XPak3 and p27(Xic1) are inhibited, but the expression of early determination and differentiation markers, including X-ngnr-1 and X-MyT1, is not affected. Inhibition of neuronal differentiation by Xmxi1 is only transient, and, at early tailbud stages, both endogenous and ectopic neurogenesis are observed. While Xmxi1 enhances cell proliferation and apoptosis in the early Xenopus embryo, both activities appear not to be required for the function of Xmxi1 in primary neurogenesis.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

    Sensitivity Analysis in Ocean Acoustic Propagation

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    The sensitivity of acoustic pressure to sound speed is investigated through the application of adjoint-based sensitivity analysis using an acoustic propagation model. The sensitivity analysis is extended to temperature and salinity, by deriving the adjoint of the sound polynomial function of temperature and salinity. Numerical experiments using a range dependent model are carried out in a deep and complex environment at the frequency of 300 Hz. It is shown that through the adjoint sensitivity analysis one can infer reasonable variations of sound speed, and thus temperature and salinity. Successful extension of the sensitivity of acoustic pressure to temperature and salinity implies that acoustic pressure observations in a given range-depth plane can be assimilated into an ocean model using the acoustic propagation model as the observation operator
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