252 research outputs found

    Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

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    We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

    Neonate Human Remains: A Window of Opportunity to the Molecular Study of Ancient Syphilis

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    Ancient DNA (aDNA) analysis can be a useful tool in bacterial disease diagnosis in human remains. However, while the recovery of Mycobacterium spp. has been widely successful, several authors report unsuccessful results regarding ancient treponemal DNA, casting doubts on the usefulness of this technique for the diagnosis of ancient syphilis. Here, we present results from an analysis of four newborn specimens recovered from the crypt of “La Ermita de la Soledad” (XVI–XVII centuries), located in the province of Huelva in the southwest of Spain. We extracted and analyzed aDNA in three independent laboratories, following specific procedures generally practiced in the aDNA field, including cloning of the amplified DNA fragments and sequencing of several clones. This is the most ancient case, reported to date, from which detection of DNA from T. pallidum subspecies pallidum has been successful in more than one individual, and we put forward a hypothesis to explain this result, taking into account the course of the disease in neonate individuals

    The area-based social patterning of injuries among 10 to 19 year olds Changes over time in the Stockholm County

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    <p>Abstract</p> <p>Background</p> <p>Area-based studies of childhood injuries strongly suggest that neighborhood socio-demographic and economic circumstances impact on various – though not all – types of injuries. The primary aim of this study was to investigate the stability over time of the association between area characteristics and childhood injuries of various causes.</p> <p>Methods</p> <p>Register-based and ecological, the study encompassed Stockholm County's 138 parishes, and considered two time periods (1993–95; 2003–05). Two indices were measured: economic deprivation and social fragmentation, and parishes were allocated to their respective quintile on each index. Data on both unintentional and intentional injuries for children (boys and girls) aged 10–14 and 15–19 respectively were gathered from the County Council's hospital inpatient register. For each period and index, gender, age and cause-specific comparisons were made to assess the rate ratios (with 95% confidence intervals) of being injured using parishes belonging to the best index level as a comparison group. A series of simple and partial Pearson correlations were also calculated to assess the independent contribution of each index.</p> <p>Results</p> <p>Regardless of time period, there were rather few significant rate ratios and, when they occurred, there were both under and excess risks. For instance, in each period, boys from both age groups living in parishes with the highest levels of economic deprivation had lower rate of injury as a motor vehicle rider. Most strikingly, intentional injuries were more frequent during the second time period and in considerable excess among girls aged 15–19 from more economically deprived areas. Also, during that last period, none of the injury causes correlated significantly with the index of social fragmentation after adjustment for economic deprivation (partial correlation).</p> <p>Conclusion</p> <p>Over a ten-year period, differential economic deprivation among parishes has widened more than social fragmentation in Stockholm County. The correlation between those indices is high in both periods of time whilst the association between the levels of each index and injury rates varies depending on group of injuries or time period considered. It is of concern that intentional injuries have increased numerically and are significantly and positively correlated with economic deprivation (net of social fragmentation), in particular among girls.</p

    r84, a Novel Therapeutic Antibody against Mouse and Human VEGF with Potent Anti-Tumor Activity and Limited Toxicity Induction

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    Vascular endothelial growth factor (VEGF) is critical for physiological and pathological angiogenesis. Within the tumor microenvironment, VEGF functions as an endothelial cell survival factor, permeability factor, mitogen, and chemotactic agent. The majority of these functions are mediated by VEGF-induced activation of VEGF receptor 2 (VEGFR2), a high affinity receptor tyrosine kinase expressed by endothelial cells and other cell types in the tumor microenvironment. VEGF can also ligate other cell surface receptors including VEGFR1 and neuropilin-1 and -2. However, the importance of VEGF-induced activation of these receptors in tumorigenesis is still unclear. We report the development and characterization of r84, a fully human monoclonal antibody that binds human and mouse VEGF and selectively blocks VEGF from interacting with VEGFR2 but does not interfere with VEGF∶VEGFR1 interaction. Selective blockade of VEGF binding to VEGFR2 by r84 is shown through ELISA, receptor binding assays, receptor activation assays, and cell-based functional assays. Furthermore, we show that r84 has potent anti-tumor activity and does not alter tissue histology or blood and urine chemistry after chronic high dose therapy in mice. In addition, chronic r84 therapy does not induce elevated blood pressure levels in some models. The ability of r84 to specifically block VEGF∶VEGFR2 binding provides a valuable tool for the characterization of VEGF receptor pathway activation during tumor progression and highlights the utility and safety of selective blockade of VEGF-induced VEGFR2 signaling in tumors

    High-throughput gene discovery in the rat

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    The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3′ ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to ∼50,000 rat UniGene clusters. We have identified, arrayed, and derived 5′ ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI

    Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel

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    Dark matter lighter than 10  GeV/c2 encompasses a promising range of candidates. A conceptual design for a new detector, DarkSide-LowMass, is presented, based on the DarkSide-50 detector and progress toward DarkSide-20k, optimized for a low-threshold electron-counting measurement. Sensitivity to light dark matter is explored for various potential energy thresholds and background rates. These studies show that DarkSide-LowMass can achieve sensitivity to light dark matter down to the solar neutrino fog for GeV-scale masses and significant sensitivity down to 10  MeV/c2 considering the Migdal effect or interactions with electrons. Requirements for optimizing the detector’s sensitivity are explored, as are potential sensitivity gains from modeling and mitigating spurious electron backgrounds that may dominate the signal at the lowest energies

    Measurement of isotopic separation of argon with the prototype of the cryogenic distillation plant Aria for dark matter searches

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    The Aria cryogenic distillation plant, located in Sardinia, Italy, is a key component of the DarkSide-20k experimental program for WIMP dark matter searches at the INFN Laboratori Nazionali del Gran Sasso, Italy. Aria is designed to purify the argon, extracted from underground wells in Colorado, USA, and used as the DarkSide-20k target material, to detector-grade quality. In this paper, we report the first measurement of argon isotopic separation by distillation with the 26&nbsp;m tall Aria prototype. We discuss the measurement of the operating parameters of the column and the observation of the simultaneous separation of the three stable argon isotopes: 36Ar , 38Ar , and 40Ar . We also provide a detailed comparison of the experimental results with commercial process simulation software. This measurement of isotopic separation of argon is a significant achievement for the project, building on the success of the initial demonstration of isotopic separation of nitrogen using the same equipment in 2019

    Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel

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