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  • 1
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 378, No. 6615 ( 2022-10-07)
    Abstract: 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. Expanse of SARS-CoV-2 sequencing capacity in Africa. ( A ) African countries (shaded in gray) and institutions (red circles) with on-site sequencing facilities that are capable of producing SARS-CoV-2 whole genomes locally. ( B ) The number of SARS-CoV-2 genomes produced per country and the proportion of those genomes that were produced locally, regionally within Africa, or abroad. ( C ) Decreased turnaround time of sequencing output in Africa to an almost real-time release of genomic data.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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  • 2
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 345, No. 6202 ( 2014-09-12), p. 1369-1372
    Abstract: In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2014
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  • 3
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 36 ( 2023-09-05)
    Abstract: Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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  • 4
    Online Resource
    Online Resource
    Society for Neuroscience ; 2015
    In:  The Journal of Neuroscience Vol. 35, No. 37 ( 2015-09-16), p. 12725-12732
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 35, No. 37 ( 2015-09-16), p. 12725-12732
    Abstract: The study objective was to examine neural correlates of a specific component of human caregiving: maternal mental state talk, reflecting a mother's proclivity to attribute mental states and intentionality to her infant. Using a potent, ecologically relevant stimulus of infant cry during fMRI, we tested hypotheses that postpartum neural response to the cry of “own” versus a standard “other” infant in the right frontoinsular cortex (RFIC) and subcortical limbic network would be associated with independent observations of maternal mental state talk. The sample comprised 76 urban-living, low socioeconomic mothers (82% African American) and their 4-month-old infants. Before the fMRI scan, mothers were filmed in face-to-face interaction with their infant, and maternal behaviors were coded by trained researchers unaware of all other information about the participants. The results showed higher functional activity in the RFIC to own versus other infant cry at the group level. In addition, RFIC and bilateral subcortical neural activity (e.g., thalamus, amygdala, hippocampus, putamen) was associated positively with maternal mental state talk but not with more global aspects of observed caregiving. These findings held when accounting for perceptual and contextual covariates, such as maternal felt distress, urge to help, depression severity, and recognition of own infant cry. Our results highlight the need to focus on specific components of caregiving to advance understanding of the maternal brain. Future work will examine the predictive utility of this neural marker for mother–child function. SIGNIFICANCE STATEMENT The current study advances extant literature examining the neural underpinning of early parenting behavior. The findings highlight the special functional importance of the right frontoinsular cortex–thalamic–limbic network in a mother's proclivity to engage in mental state talk with her preverbal infant, a circumscribed aspect of maternal caregiving purported to be a prerequisite of sensitive and responsive caregiving. These associations existed specifically for maternal mentalizing behavior and were not evident for more generic aspects of caregiving in this urban sample of 76 postpartum mothers. Finally, the findings were robust even when controlling for potential demographic, perceptual, and contextual confounds, supporting the notion that these regions constitute an innate, specialized maternal mentalizing network.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2015
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  • 5
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 1967
    In:  Science Vol. 155, No. 3768 ( 1967-03-17), p. 1430-1432
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 155, No. 3768 ( 1967-03-17), p. 1430-1432
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 1967
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  • 6
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 372, No. 6542 ( 2021-05-07), p. 566-569
    Abstract: Migration of ungulates (hooved mammals) is a fundamental ecological process that promotes abundant herds, whose effects cascade up and down terrestrial food webs. Migratory ungulates provide the prey base that maintains large carnivore and scavenger populations and underpins terrestrial biodiversity (fig. S1). When ungulates move in large aggregations, their hooves, feces, and urine create conditions that facilitate distinct biotic communities. The migrations of ungulates have sustained humans for thousands of years, forming tight cultural links among Indigenous people and local communities. Yet ungulate migrations are disappearing at an alarming rate ( 1 ). Efforts by wildlife managers and conservationists are thwarted by a singular challenge: Most ungulate migrations have never been mapped in sufficient detail to guide effective conservation. Without a strategic and collaborative effort, many of the world's great migrations will continue to be truncated, severed, or lost in the coming decades. Fortunately, a combination of animal tracking datasets, historical records, and local and Indigenous knowledge can form the basis for a global atlas of migrations, designed to support conservation action and policy at local, national, and international levels.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
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  • 7
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2005
    In:  Proceedings of the National Academy of Sciences Vol. 102, No. 9 ( 2005-03), p. 3360-3365
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 9 ( 2005-03), p. 3360-3365
    Abstract: HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule that is primarily expressed at the fetal–maternal interface, where it is thought to play a role in protecting the fetus from the maternal immune response. HLA-G binds a limited repertoire of peptides and interacts with the inhibitory leukocyte Ig-like receptors LIR-1 and LIR-2 and possibly with certain natural killer cell receptors. To gain further insights into HLA-G function, we determined the 1.9-Å structure of a monomeric HLA-G complexed to a natural endogenous peptide ligand from histone H2A (RIIPRHLQL). An extensive network of contacts between the peptide and the antigen-binding cleft reveal a constrained mode of binding reminiscent of the nonclassical HLA-E molecule, thereby providing a structural basis for the limited peptide repertoire of HLA-G. The α3 domain of HLA-G, a candidate binding site for the LIR-1 and -2 inhibitory receptors, is structurally distinct from the α3 domains of classical MHC-I molecules, providing a rationale for the observed affinity differences for these ligands. The structural data suggest a head-to-tail mode of dimerization, mediated by an intermolecular disulfide bond, that is consistent with the observation of HLA-G dimers on the cell surface.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2005
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  • 8
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 32 ( 2015-08-11)
    Abstract: Tools to reliably measure Plasmodium falciparum ( Pf ) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals. Pf -specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates of Pf exposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856 Pf antigens by protein microarray in 186 Ugandan children, for whom detailed Pf exposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual’s recent exposure. Responses to three novel Pf antigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86–0.93), whereas responses to six antigens accurately estimated an individual’s malaria incidence in the prior year. Cross-validated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
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  • 9
    Online Resource
    Online Resource
    Acoustical Society of America (ASA) ; 2006
    In:  The Journal of the Acoustical Society of America Vol. 119, No. 5_Supplement ( 2006-05-01), p. 3367-3367
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 119, No. 5_Supplement ( 2006-05-01), p. 3367-3367
    Abstract: This work was created through experimentation with surround recording and manipulation techniques. A variety of coincident and spaced microphone recording techniques are used to create realistic and immersive recordings of everyday environments. Processing and manipulation are then applied to these recordings to create musical material that plays against the recordings and guides us on a contextualized journey through the landscapes many of us pass though everyday.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
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    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2006
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  • 10
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 103, No. 9 ( 2006-02-28), p. 3286-3291
    Abstract: East Coast fever, caused by the tick-borne intracellular apicomplexan parasite Theileria parva , is a highly fatal lymphoproliferative disease of cattle. The pathogenic schizont-induced lymphocyte transformation is a unique cancer-like condition that is reversible with parasite removal. Schizont-infected cell-directed CD8 + cytotoxic T lymphocytes (CTL) constitute the dominant protective bovine immune response after a single exposure to infection. However, the schizont antigens targeted by T. parva -specific CTL are undefined. Here we show the identification of five candidate vaccine antigens that are the targets of MHC class I-restricted CD8 + CTL from immune cattle. CD8 + T cell responses to these antigens were boosted in T. parva -immune cattle resolving a challenge infection and, when used to immunize naïve cattle, induced CTL responses that significantly correlated with survival from a lethal parasite challenge. These data provide a basis for developing a CTL-targeted anti-East Coast fever subunit vaccine. In addition, orthologs of these antigens may be vaccine targets for other apicomplexan parasites.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2006
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