124 research outputs found

    Accurate measurement of gene copy number for human alpha-defensin DEFA1A3

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    Background: Multi-allelic copy number variants include examples of extensive variation between individuals in the copy number of important genes, most notably genes involved in immune function. The definition of this variation, and analysis of its impact on function, has been hampered by the technical difficulty of large-scale but accurate typing of genomic copy number. The copy-variable alpha-defensin locus DEFA1A3 on human chromosome 8 commonly varies between 4 and 10 copies per diploid genome, and presents considerable challenges for accurate high-throughput typing. Results: In this study, we developed two paralogue ratio tests and three allelic ratio measurements that, in combination, provide an accurate and scalable method for measurement of DEFA1A3 gene number. We combined information from different measurements in a maximum-likelihood framework which suggests that most samples can be assigned to an integer copy number with high confidence, and applied it to typing 589 unrelated European DNA samples. Typing the members of three-generation pedigrees provided further reassurance that correct integer copy numbers had been assigned. Our results have allowed us to discover that the SNP rs4300027 is strongly associated with DEFA1A3 gene copy number in European samples. Conclusions: We have developed an accurate and robust method for measurement of DEFA1A3 copy number. Interrogation of rs4300027 and associated SNPs in Genome-Wide Association Study SNP data provides no evidence that alpha-defensin copy number is a strong risk factor for phenotypes such as Crohn’s disease, type I diabetes, HIV progression and multiple sclerosis

    Weeds in Cover Crops: Context and Management Considerations

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    Cover crops are increasingly being adopted to provide multiple ecosystem services such as improving soil health, managing nutrients, and decreasing soil erosion. It is not uncommon for weeds to emerge in and become a part of a cover crop plant community. Since the role of cover cropping is to supplement ecosystem service provisioning, we were interested in assessing the impacts of weeds on such provisioning. To our knowledge, no research has examined how weeds in cover crops may impact the provision of ecosystem services and disservices. Here, we review services and disservices associated with weeds in annual agroecosystems and present two case studies from the United States to illustrate how weeds growing in fall-planted cover crops can provide ground cover, decrease potential soil losses, and effectively manage nitrogen. We argue that in certain circumstances, weeds in cover crops can enhance ecosystem service provisioning. In other circumstances, such as in the case of herbicide-resistant weeds, cover crops should be managed to limit weed biomass and fecundity. Based on our case studies and review of the current literature, we conclude that the extent to which weeds should be allowed to grow in a cover crop is largely context-dependent.This work was supported by the USDA National Institute of Food and Agriculture, Organic Research and Extension Initiative under Project PENW-2015-07433 (Grant No. 2015-51300-24156, Accession No. 1007156) and the National Science Foundation (Grant No. DGE1255832)

    Towards automated cancer screening: label-free classification of fixed cell samples using wavelength modulated Raman spectroscopy

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    This work was supported by the Engineering and Physical Sciences Research Council and Medical Research Council [EP/L016559/1, EP/P030017/1], and CRUK [A18075 Core Award].The ability to provide quantitative, objective and automated pathological analysis would provide enormous benefits for national cancer screening programmes, in terms of both resource reduction and improved patient wellbeing. The move towards molecular pathology through spectroscopic methods shows great promise, but has been restricted by spectral quality, acquisition times and lack of direct clinical application. In this paper, we present the application of wavelength modulated Raman spectroscopy for the automated label- and fluorescence-free classification of fixed squamous epithelial cells in suspension, such as those produced during a cervical smear test. Direct comparison with standard Raman spectroscopy shows marked improvement of sensitivity and specificity when considering both human papillomavirus (sensitivity +12.0%, specificity +5.3%) and transformation status (sensitivity +10.3%, specificity +11.1%). Studies on the impact of intracellular sampling location and storage effects suggest that wavelength modulated Raman spectroscopy is sufficiently robust to be used in fixed cell classification, but requires further investigations of potential sources of molecular variation in order to improve current clinical tools.Publisher PDFPeer reviewe

    Tuberculosis in badgers where the bovine tuberculosis epidemic is expanding in cattle in England.

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    Bovine tuberculosis (bTB) is an important animal health and economic problem for the cattle industry and a potential zoonotic threat. Wild badgers (Meles meles) play a role on its epidemiology in some areas of high prevalence in cattle, particularly in the UK and Republic of Ireland and increasingly in parts of mainland Europe. However, little is known about the involvement of badgers in areas on the spatial edge of the cattle epidemic, where increasing prevalence in cattle is seen. Here we report the findings of a study of found-dead (mainly road-killed) badgers in six counties on the edge of the English epidemic of bTB in cattle. The overall prevalence of Mycobacterium tuberculosis complex (MTC) infection detected in the study area was 51/610 (8.3%, 95% CI 6.4-11%) with the county-level prevalence ranging from 15 to 4-5%. The MTC spoligotypes of recovered from badgers and cattle varied: in the northern part of the study area spoligotype SB0129 predominated in both cattle and badgers, but elsewhere there was a much wider range of spoligotypes found in badgers than in cattle, in which infection was mostly with the regional cattle spoligotype. The low prevalence of MTC in badgers in much of the study area, and, relative to in cattle, the lower density of sampling, make firm conclusions difficult to draw. However, with the exception of Cheshire (north-west of the study area), little evidence was found to link the expansion of the bTB epidemic in cattle in England to widespread badger infection

    VEG-04: The Effects of Light Quality on Mizuna Mustard Growth, Nutritional Composition, and Organoleptic Acceptability for a Space Diet

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    Growing fresh, nutritious, palatable produce for crew consumption during spaceflight may provide health-promoting, bioavailable nutrients and enhance the astronaut dietary experience as we move toward longer-duration missions. Tending plants may also serve as a countermeasure for crew psychological stresses associated with spaceflight. However, requirements to support consistent growth of a variety of high quality, nutritious crops under spaceflight environmental conditions remain unclear. This study explores the potential to grow crops for consumption on the International Space Station (ISS) using the Veggie vegetable-production system. VEG-04A and B were two flight tests conducted in 2019 with the leafy green crop mizuna mustard. Mizuna was grown in two Veggie chambers simultaneously, with the chambers set to different red-to-blue light formulations; one Veggie was programmed as "red-rich" and the second as "blue-rich." Light quality is known to impact plant growth, nutrition, microbiology, and organoleptic characteristics on Earth, and the Veggie flight tests examined how these impacts might differ in microgravity. VEG-04A, a 35-day growth test with a single harvest, was initiated in June and harvested in July 2019. At harvest, the astronauts froze half of the edible plant tissue to return to Earth and weighed the remaining half using the Mass Measurement Device (MMD). Weighed samples were then cleaned with produce-sanitizing wipes, and consenting crew members participated in organoleptic evaluation of the fresh produce. The remaining sanitized produce was available for crew consumption as desired. Frozen flight samples were returned at the end of August for microbial and chemical analyses to assess food safety and nutritional quality. No pathogens were detected on VEG-04A flight or ground control samples. On average, bacterial and fungal counts were significantly lower on ground control samples than flight samples. VEG-04B, a 56-day test with multiple harvests from the same plants, assessed sustained productivity. VEG-04B was initiated in October 2019 with three harvests at four, six, and eight weeks after initiation. Challenges with the watering program occurred early during VEG-04A, and several plants failed to survive in both the flight and ground control operations. Thus, prior to VEG-04B, an extra test was conducted to tailor water timing and volumes. This test determined that mizuna grew best if the wicks inside the plant pillow were allowed to dry after plants germinated, reducing persistent water around the stem. The wicks changed from being a conduit for water out of the plant pillow to being a conduit for air into the root zone. This test allowed a fine tuning of methods for VEG-04B. It is our hope that these tests on ISS will help mitigate the risk of an inadequate food supply for long-duration missions by adding fresh vegetables to the crew diet. This research was co-funded by the Human Research Program and Space Biology (MTL#1075) in the ILSRA 2015 NRA call

    Focused fluid seepage related to variations in accretionary wedge structure, Hikurangi margin, New Zealand

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    Hydrogeological processes influence the morphology, mechanical behavior, and evolution of subduction margins. Fluid supply, release, migration, and drainage control fluid pressure and collectively govern the stress state, which varies between accretionary and nonaccretionary systems. We compiled over a decade of published and unpublished acoustic data sets and seafloor observations to analyze the distribution of focused fluid expulsion along the Hikurangi margin, New Zealand. The spatial coverage and quality of our data are exceptional for subduction margins globally. We found that focused fluid seepage is widespread and varies south to north with changes in subduction setting, including: wedge morphology, convergence rate, seafloor roughness, and sediment thickness on the incoming Pacific plate. Overall, focused seepage manifests most commonly above the deforming backstop, is common on thrust ridges, and is largely absent from the frontal wedge despite ubiquitous hydrate occurrences. Focused seepage distribution may reflect spatial differences in shallow permeability architecture, while diffusive fluid flow and seepage at scales below detection limits are also likely. From the spatial coincidence of fluids with major thrust faults that disrupt gas hydrate stability, we surmise that focused seepage distribution may also reflect deeper drainage of the forearc, with implications for pore-pressure regime, fault mechanics, and critical wedge stability and morphology. Because a range of subduction styles is represented by 800 km of along-strike variability, our results may have implications for understanding subduction fluid flow and seepage globally
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