97 research outputs found

    Is a Global Recession Imminent?

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    Global growth prospects have deteriorated significantly since the beginning of the year, raising the specter of global recession. This paper relies on insights gleaned from previous global recessions to analyze the recent evolution of economic activity and policies and presents plausible scenarios for the global economy in 2022–24. We report three major findings. First, every global recession since 1970 was preceded by a significant weakening of global growth in the previous year, as has happened recently. Second, the global economy is in the midst of one of the most internationally synchronous episodes of monetary and fiscal policy tightening of the past five decades. The policy actions in many countries are necessary to contain inflationary pressures, but their mutually compounding effects could have larger impacts than envisioned—both in tightening financial conditions and in steepening the global growth slowdown. Third, if the degree of global monetary policy tightening markets now expect is not enough to reduce inflation to targets, experience from previous global recessions suggests that the additional tightening needed could cause significant financial stress and increase the likelihood of a global recession next year. These findings imply that policymakers need to carefully calibrate, clearly communicate, and credibly implement their policy actions while considering potential international spillovers, especially given the globally synchronous withdrawal of monetary and fiscal policies. They also need to pursue supply-side measures to overcome constraints confronting labor markets, energy markets, and trade networks

    FE65 as a link between VLDLR and APP to regulate their trafficking and processing

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    <p>Abstract</p> <p>Background</p> <p>Several studies found that FE65, a cytoplasmic adaptor protein, interacts with APP and LRP1, altering the trafficking and processing of APP. We have previously shown that FE65 interacts with the ApoE receptor, ApoER2, altering its trafficking and processing. Interestingly, it has been shown that FE65 can act as a linker between APP and LRP1 or ApoER2. In the present study, we tested whether FE65 can interact with another ApoE receptor, VLDLR, thereby altering its trafficking and processing, and whether FE65 can serve as a linker between APP and VLDLR.</p> <p>Results</p> <p>We found that FE65 interacted with VLDLR using GST pull-down and co-immunoprecipitation assays in COS7 cells and in brain lysates. This interaction occurs via the PTB1 domain of FE65. Co-transfection with FE65 and full length VLDLR increased secreted VLDLR (sVLDLR); however, the levels of VLDLR C-terminal fragment (CTF) were undetectable as a result of proteasomal degradation. Additionally, FE65 increased cell surface levels of VLDLR. Moreover, we identified a novel complex between VLDLR and APP, which altered trafficking and processing of both proteins. Furthermore, immunoprecipitation results demonstrated that the presence of FE65 increased the interaction between APP and VLDLR <it>in vitro </it>and <it>in vivo</it>.</p> <p>Conclusions</p> <p>These data suggest that FE65 can regulate VLDLR trafficking and processing. Additionally, the interaction between VLDLR and APP altered both protein's trafficking and processing. Finally, our data suggest that FE65 serves as a link between VLDLR and APP. This novel interaction adds to a growing body of literature indicating trimeric complexes with various ApoE Receptors and APP.</p

    Estimating the Worldwide Extent of Illegal Fishing

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    Illegal and unreported fishing contributes to overexploitation of fish stocks and is a hindrance to the recovery of fish populations and ecosystems. This study is the first to undertake a world-wide analysis of illegal and unreported fishing. Reviewing the situation in 54 countries and on the high seas, we estimate that lower and upper estimates of the total value of current illegal and unreported fishing losses worldwide are between 10bnand10 bn and 23.5 bn annually, representing between 11 and 26 million tonnes. Our data are of sufficient resolution to detect regional differences in the level and trend of illegal fishing over the last 20 years, and we can report a significant correlation between governance and the level of illegal fishing. Developing countries are most at risk from illegal fishing, with total estimated catches in West Africa being 40% higher than reported catches. Such levels of exploitation severely hamper the sustainable management of marine ecosystems. Although there have been some successes in reducing the level of illegal fishing in some areas, these developments are relatively recent and follow growing international focus on the problem. This paper provides the baseline against which successful action to curb illegal fishing can be judged

    Scholarly publishing depends on peer reviewers

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    The peer-review crisis is posing a risk to the scholarly peer-reviewed journal system. Journals have to ask many potential peer reviewers to obtain a minimum acceptable number of peers accepting reviewing a manuscript. Several solutions have been suggested to overcome this shortage. From reimbursing for the job, to eliminating pre- publication reviews, one cannot predict which is more dangerous for the future of scholarly publishing. And, why not acknowledging their contribution to the final version of the article published? PubMed created two categories of contributors: authors [AU] and collaborators [IR]. Why not a third category for the peer-reviewer

    Using Evolutionary Conserved Modules in Gene Networks as a Strategy to Leverage High Throughput Gene Expression Queries

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    Background: Large-scale gene expression studies have not yielded the expected insight into genetic networks that control complex processes. These anticipated discoveries have been limited not by technology, but by a lack of effective strategies to investigate the data in a manageable and meaningful way. Previous work suggests that using a pre-determined seednetwork of gene relationships to query large-scale expression datasets is an effective way to generate candidate genes for further study and network expansion or enrichment. Based on the evolutionary conservation of gene relationships, we test the hypothesis that a seed network derived from studies of retinal cell determination in the fly, Drosophila melanogaster, will be an effective way to identify novel candidate genes for their role in mouse retinal development. Methodology/Principal Findings: Our results demonstrate that a number of gene relationships regulating retinal cell differentiation in the fly are identifiable as pairwise correlations between genes from developing mouse retina. In addition, we demonstrate that our extracted seed-network of correlated mouse genes is an effective tool for querying datasets and provides a context to generate hypotheses. Our query identified 46 genes correlated with our extracted seed-network members. Approximately 54% of these candidates had been previously linked to the developing brain and 33% had been previously linked to the developing retina. Five of six candidate genes investigated further were validated by experiments examining spatial and temporal protein expression in the developing retina. Conclusions/Significance: We present an effective strategy for pursuing a systems biology approach that utilizes an evolutionary comparative framework between two model organisms, fly and mouse. Future implementation of this strategy will be useful to determine the extent of network conservation, not just gene conservation, between species and will facilitate the use of prior biological knowledge to develop rational systems-based hypotheses

    Species composition and habitat preferences of the nearshore fish fauna of Bonne Bay, Newfoundland

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    Determining biodiversity baseline is the first step toward establishing species monitoring and conservation programs. In this study we report on a 10-year survey of the fish fauna of Bonne Bay, a fjord surrounded by the Gros Morne National Park on the west coast of Newfoundland, Canada. The objectives of our study were: 1) to determine the fish fauna of Bonne Bay using standardized sampling methods; 2) to gather information on the habitats of fishes of conservation concern; and 3) to provide baseline information on Bonne Bay as a potential candidate for a National Marine Conservation Area (NMCA). Methods A survey of the fish fauna of the inner Bonne Bay was conducted each summer from 2002 to 2011 at multiple sites representing a range of fish habitats within the fjord. Sampling gears included two types of beach seine, gillnets with various mesh sizes and a bottom trawl. Species composition was statistically compared across sites within the fjord. Results We collected and identified 29 fish species from 17 families. Fish assemblages comprised anadromous, estuarine, and marine fish species, including a late-maturing type of winter skate (Leucoraja ocellata) that is rarely found in the adjacent waters of the northern Gulf of St. Lawrence. Similarity in species composition across sites reflected salinity, substrate composition, and presence of eelgrass (Zostera marina), but not the geographic distance between sites. Conclusions Bonne Bay’s adjacency to a United Nations Educational, Scientific, and Cultural Organization (UNESCO) World Heritage Site, its diverse fish fauna that includes several species of conservation concern, its potential for education and enjoyment, and its stewardship by local people are suggestive of the future candidacy as a NMCA. The data presented here will help managers assess the potential of Bonne Bay as a National Marine Conservation Area

    Mutations in DCHS1 Cause Mitral Valve Prolapse

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    SUMMARY Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals1–3. It can manifest as mitral regurgitation and is the leading indication for mitral valve surgery4,5. Despite a clear heritable component, the genetic etiology leading to non-syndromic MVP has remained elusive. Four affected individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of the linked interval on chromosome 11. We report a missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds) that segregates with MVP in the family. Morpholino knockdown of the zebrafish homolog dachsous1b resulted in a cardiac atrioventricular canal defect that could be rescued by wild-type human DCHS1, but not by DCHS1 mRNA with the familial mutation. Further genetic studies identified two additional families in which a second deleterious DCHS1 mutation segregates with MVP. Both DCHS1 mutations reduce protein stability as demonstrated in zebrafish, cultured cells, and, notably, in mitral valve interstitial cells (MVICs) obtained during mitral valve repair surgery of a proband. Dchs1+/− mice had prolapse of thickened mitral leaflets, which could be traced back to developmental errors in valve morphogenesis. DCHS1 deficiency in MVP patient MVICs as well as in Dchs1+/− mouse MVICs result in altered migration and cellular patterning, supporting these processes as etiological underpinnings for the disease. Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease
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