495 research outputs found

    DIMBOA levels in hexaploid Brazilian wheat are not associated with antibiosis against the cereal aphids Rhopalosiphum padi and Sitobion avenae.

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    The objective of this study was to evaluate the natural levels of the plant defence compound DIMBOA in young leaves of eight hexaploid Brazilian wheat genotypes and the impact of the genotypes upon development of cereal aphids, Rhopalosiphum padi and Sitobion avenae. HPLC Analysis revealed that the DIMBOA levels varied from 5.376 (in BRS Guabiju) to 30.651 mmol/kgFW (in BRS Timbaúva) with two genotypes outperforming Solstice, a UK variety used as reference. Bioassays were conducted to evaluate the development and fecundity of both aphids when grown on the wheat genotypes. Although BRS Guabiju and BRS Timbaúva were among the genotypes showing the highest and lowest susceptibility respectively, against both aphids, no correlation could be found between DIMBOA levels and antibiosis effects. The cultivar BRS 327 that was among the genotypes showing lower intrinsic rate of population increase for the two aphid species. Elucidating the role of secondary metabolites in plant resistance to aphids and the characterisation of the genotypes that allowed reduced aphid development are important steps to achieve a better natural resistance in hexaploid Brazilian wheat

    MHC-class-II are expressed in a subpopulation of human neural stem cells in vitro in an IFN gamma-independent fashion and during development

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    This work was supported by grants from Great Ormond Street Hospital Children’s Charity, Newlife Foundation, the Antony Nolan Trust, a studentship to CAG from Consejo Nacional de Ciencia y Tecnologia (CONACyT) and Instituto Jaliscience de la Juventud (IJJ), Mexico and GOSH NIHR Biomedical Research Centre. The human embryonic and fetal material was provided by the Human Developmental Biology Resource (http://hdbr.org) jointly funded by the Medical Research Council (grant G070089) and The Wellcome Trust (grant GR082557)

    Targeting Hepatitis B Virus with Zinc Finger Nucleases

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    Despite an existing effective vaccine, hepatitis B virus (HBV) remains a major public health concern. There are effective suppressive therapies for HBV, but they remain expensive and inaccessible to many, and not all patients respond well. Furthermore, HBV can persist as genomic covalently closed circular DNA (cccDNA) that remains in hepatocytes even during otherwise effective therapy and facilitates rebound in patients after treatment has stopped. Therefore, the need for an effective treatment that targets active and persistent HBV infections remains. As a novel approach to treat HBV, we have targeted the HBV genome for disruption to prevent viral reactivation and replication. We generated 3 zinc finger nucleases (ZFNs) that target sequences within the HBV polymerase, core and X genes. Upon the formation of ZFN-induced DNA double strand breaks (DSB), imprecise repair by non-homologous end joining leads to mutations that inactivate HBV genes. We delivered HBV-specific ZFNs using self-complementary adeno-associated virus (scAAV) vectors and tested their anti-HBV activity in HepAD38 cells. HBV-ZFNs efficiently disrupted HBV target sites by inducing site-specific mutations. Cytotoxicity was seen with one of the ZFNs. scAAV-mediated delivery of a ZFN targeting HBV polymerase resulted in complete inhibition of HBV DNA replication and production of infectious HBV virions in HepAD38 cells. This effect was sustained for at least 2 weeks following only a single treatment. Furthermore, high specificity was observed for all ZFNs, as negligible off-target cleavage was seen via high-throughput sequencing of 7 closely matched potential off-target sites. These results show that HBV-targeted ZFNs can efficiently inhibit active HBV replication and suppress the cellular template for HBV persistence, making them promising candidates for eradication therapy

    Phylogeography of the Patagonian otter Lontra provocax: adaptive divergence to marine habitat or signature of southern glacial refugia?

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    <p>Abstract</p> <p>Background</p> <p>A number of studies have described the extension of ice cover in western Patagonia during the Last Glacial Maximum, providing evidence of a complete cover of terrestrial habitat from 41°S to 56°S and two main refugia, one in south-eastern Tierra del Fuego and the other north of the Chiloé Island. However, recent evidence of high genetic diversity in Patagonian river species suggests the existence of aquatic refugia in this region. Here, we further test this hypothesis based on phylogeographic inferences from a semi-aquatic species that is a top predator of river and marine fauna, the huillín or Southern river otter (<it>Lontra provocax</it>).</p> <p>Results</p> <p>We examined mtDNA sequences of the control region, ND5 and Cytochrome-b (2151 bp in total) in 75 samples of <it>L. provocax </it>from 21 locations in river and marine habitats. Phylogenetic analysis illustrates two main divergent clades for <it>L. provocax </it>in continental freshwater habitat. A highly diverse clade was represented by haplotypes from the marine habitat of the Southern Fjords and Channels (SFC) region (43°38' to 53°08'S), whereas only one of these haplotypes was paraphyletic and associated with northern river haplotypes.</p> <p>Conclusions</p> <p>Our data support the hypothesis of the persistence of <it>L. provocax </it>in western Patagonia, south of the ice sheet limit, during last glacial maximum (41°S latitude). This limit also corresponds to a strong environmental change, which might have spurred <it>L. provocax </it>differentiation between the two environments.</p

    Bone regeneration: current concepts and future directions

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    Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

    Measurement of the tt¯tt¯ production cross section in pp collisions at √s=13 TeV with the ATLAS detector

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    A measurement of four-top-quark production using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the ATLAS detector at the Large Hadron Collider corresponding to an integrated luminosity of 139 fb−1 is presented. Events are selected if they contain a single lepton (electron or muon) or an opposite-sign lepton pair, in association with multiple jets. The events are categorised according to the number of jets and how likely these are to contain b-hadrons. A multivariate technique is then used to discriminate between signal and background events. The measured four-top-quark production cross section is found to be 26+17−15 fb, with a corresponding observed (expected) significance of 1.9 (1.0) standard deviations over the background-only hypothesis. The result is combined with the previous measurement performed by the ATLAS Collaboration in the multilepton final state. The combined four-top-quark production cross section is measured to be 24+7−6 fb, with a corresponding observed (expected) signal significance of 4.7 (2.6) standard deviations over the background-only predictions. It is consistent within 2.0 standard deviations with the Standard Model expectation of 12.0 ± 2.4 fb

    Measurements of Higgs bosons decaying to bottom quarks from vector boson fusion production with the ATLAS experiment at √=13TeV

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    The paper presents a measurement of the Standard Model Higgs Boson decaying to b-quark pairs in the vector boson fusion (VBF) production mode. A sample corresponding to 126 fb−1 of s√=13TeV proton–proton collision data, collected with the ATLAS experiment at the Large Hadron Collider, is analyzed utilizing an adversarial neural network for event classification. The signal strength, defined as the ratio of the measured signal yield to that predicted by the Standard Model for VBF Higgs production, is measured to be 0.95+0.38−0.36 , corresponding to an observed (expected) significance of 2.6 (2.8) standard deviations from the background only hypothesis. The results are additionally combined with an analysis of Higgs bosons decaying to b-quarks, produced via VBF in association with a photon

    Muon reconstruction and identification efficiency in ATLAS using the full Run 2 pp collision data set at \sqrt{s}=13 TeV

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    This article documents the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139 \hbox {fb}^{-1} of pp collision data at \sqrt{s}=13 TeV collected between 2015 and 2018 during Run 2 of the LHC. The increased instantaneous luminosity delivered by the LHC over this period required a reoptimisation of the criteria for the identification of prompt muons. Improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution. The availability of large samples of Z\rightarrow \mu \mu and J/\psi \rightarrow \mu \mu decays, and the minimisation of systematic uncertainties, allows the efficiencies of criteria for muon identification, primary vertex association, and isolation to be measured with an accuracy at the per-mille level in the bulk of the phase space, and up to the percent level in complex kinematic configurations. Excellent performance is achieved over a range of transverse momenta from 3 GeV to several hundred GeV, and across the full muon detector acceptance of |\eta |<2.7
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