13 research outputs found

    The genetic architecture of the human cerebral cortex

    Get PDF
    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

    Biology and ecology of the world’s largest invertebrate, the colossal squid (Mesonychoteuthis hamiltoni): a short review

    Get PDF
    The colossal squid Mesonychoteuthis hamiltoni (Robson 1925) is the largest (heaviest) living invertebrate and although it is preyed upon by many top predators, its basic biology and ecology remain one of the ocean’s great mysteries. The present study aims to review the current biological knowledge on this squid. It is considered to be endemic in the Southern Ocean (SO) with a circumpolar distribution spreading from the Antarctic continent up to the Sub-Antarctic Front. Small juveniles (<40 mm mantle length) are mainly found from the surface to 500 m, and the late juvenile stages are assumed to undergo ontogenetic descent to depths reaching 2000 m. Thus, this giant spends most of its life in the meso- and bathypelagic realms, where it can reach a total length of 6 m. The maximum weight recorded so far was 495 kg. M. hamiltoni is presently reported from the diets of 17 different predator species, comprising penguins and other seabirds, fishes and marine mammals, and may feed on various prey types, including myctophids, Patagonian toothfish, sleeper sharks and other squid. Stable isotopic analysis places the colossal squid as one of the top predators in the SO. It is assumed that this squid is not capable of high-speed predator–prey interactions, but it is rather an ambush predator. Its eyes, the largest on the planet, seem to have evolved to detect very large predators (e.g., sperm whales) rather than to detect prey at long distances. The study of this unique invertebrate giant constitutes a valuable source of insight into the biophysical principles behind body-size evolution

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

    Get PDF
    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

    Identification of Carboxylesterase-Dependent Dabigatran Etexilate Hydrolysis

    No full text

    Developing Vulnerability: A Situational Response to the Abuse of Women with Mental Disabilities

    No full text
    In this paper I present a critical analysis of the English law relating to the safeguarding of vulnerable adults, in particular how the law impacts on the sexual lives of adult women with mental disabilities. I consider the discourses of vulnerability that surround the different legal regimes and whether the emerging theoretical vulnerability literature can assist in developing more nuanced legal responses. I argue that the inherent jurisdiction and Care Act 2014 provide an opportunity to move away from the focus on inherent features of vulnerability such as mental disability towards a more nuanced, situational and embodied account of what it means to safeguard ‘vulnerable adults’. This has the potential to be developed in England through the new legal framework of the Care Act and can be achieved through targeting interventions against the situational causes of vulnerability, for example the perpetrators of sexual violence
    corecore