5,974 research outputs found

    Investigation into the limits of perturbation theory at low Q^2 using HERA deep inelastic scattering data

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    A phenomenological study of the final combined HERA data on inclusive deep inelastic scattering (DIS) has been performed. The data are presented and investigated for a kinematic range extending from values of the four-momentum transfer, Q2Q^2, above 104^4 GeV2^2 down to the lowest values observable at HERA of Q2Q^2 = 0.045 GeV2^2 and Bjorken xx, xBjx_{\rm Bj} = 6 \cdot 107^{-7}. The data are well described by fits based on perturbative quantum chromodynamics (QCD) using collinear factorisation and evolution of the parton densities encompassed in the DGLAP formalism from the highest Q2Q^2 down to Q2Q^2 of a few GeV2^2. The Regge formalism can describe the data up to Q2Q^2 \approx 0.65 GeV2^2. The complete data set can be described by a new fit using the ALLM parameterisation. The region between the Regge and the perturbative QCD regimes is of particular interest.Comment: 38 pages, 13 figure

    Maternal postpartum depression is a risk factor for infant emotional variability at 4 months

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    Maternal postpartum depression (PPD) is a risk for disruption of mother–infant interaction. Infants of depressed mothers have been found to display less positive, more negative, and neutral affect. Other studies have found that infants of mothers with PPD inhibit both positive and negative affect. In a sample of 28 infants of mothers with PPD and 52 infants of nonclinical mothers, we examined the role of PPD diagnosis and symptoms for infants’ emotional variability, measured as facial expressions, vocal protest, and gaze using microanalysis, during a mother–infant face-to-face interaction. PPD symptoms and diagnosis were associated with (a) infants displaying fewer high negative, but more neutral/interest facial affect events, and (b) fewer gaze off events. PPD diagnosis, but not symptoms, was associated with less infant vocal protest. Total duration of seconds of infant facial affective displays and gaze off was not related to PPD diagnosis or symptoms, suggesting that when infants of depressed mothers display high negative facial affect or gaze off, these expressions are more sustained, indicating lower infant ability to calm down and re-engage, interpreted as a disturbance in self-regulation. The findings highlight the importance of not only examining durations, but also frequencies, as the latter may inform infant emotional variability

    Species Trees from Highly Incongruent Gene Trees in Rice

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    Several methods have recently been developed to infer multilocus phylogenies by incorporating information from topological incongruence of the individual genes. In this study, we investigate 2 such methods, Bayesian concordance analysis and Bayesian estimation of species trees. Our test data are a collection of genes from cultivated rice (genus Oryza) and the most closely related wild species, generated using a high-throughput sequencing protocol and bioinformatics pipeline. Trees inferred from independent genes display levels of topological incongruence that far exceed that seen in previous data sets analyzed with these species tree methods. We identify differences in phylogenetic results between inference methods that incorporate gene tree incongruence. Finally, we discuss the challenges of scaling these analyses for data sets with thousands of gene trees and extensive levels of missing data

    Cadmium induces Wnt signaling to upregulate proliferation and survival genes in sub-confluent kidney proximal tubule cells

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    <p>Abstract</p> <p>Background</p> <p>The class 1 carcinogen cadmium (Cd<sup>2+</sup>) disrupts the E-cadherin/β-catenin complex of epithelial adherens junctions (AJs) and causes renal cancer. Deregulation of E-cadherin adhesion and changes in Wnt/β-catenin signaling are known to contribute to carcinogenesis.</p> <p>Results</p> <p>We investigated Wnt signaling after Cd<sup>2+</sup>-induced E-cadherin disruption in sub-confluent cultured kidney proximal tubule cells (PTC). Cd<sup>2+ </sup>(25 μM, 3-9 h) caused nuclear translocation of β-catenin and triggered a Wnt response measured by TOPflash reporter assays. Cd<sup>2+ </sup>reduced the interaction of β-catenin with AJ components (E-cadherin, α-catenin) and increased binding to the transcription factor TCF4 of the Wnt pathway, which was upregulated and translocated to the nucleus. While Wnt target genes (<it>c-Myc</it>, <it>cyclin D1 </it>and <it>ABCB1</it>) were up-regulated by Cd<sup>2+</sup>, electromobility shift assays showed increased TCF4 binding to <it>cyclin D1 </it>and <it>ABCB1 </it>promoter sequences with Cd<sup>2+</sup>. Overexpression of wild-type and mutant TCF4 confirmed Cd<sup>2+</sup>-induced Wnt signaling. Wnt signaling elicited by Cd<sup>2+ </sup>was not observed in confluent non-proliferating cells, which showed increased E-cadherin expression. Overexpression of E-cadherin reduced Wnt signaling, PTC proliferation and Cd<sup>2+ </sup>toxicity. Cd<sup>2+ </sup>also induced reactive oxygen species dependent expression of the pro-apoptotic ER stress marker and Wnt suppressor CHOP/GADD153 which, however, did not abolish Wnt response and cell viability.</p> <p>Conclusions</p> <p>Cd<sup>2+ </sup>induces Wnt signaling in PTC. Hence, Cd<sup>2+ </sup>may facilitate carcinogenesis of PTC by promoting Wnt pathway-mediated proliferation and survival of pre-neoplastic cells.</p

    Epithelial cell–derived secreted and transmembrane 1a signals to activated neutrophils during pneumococcal pneumonia

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    Airway epithelial cell responses are critical to the outcome of lung infection. In this study, we aimed to identify unique contributions of epithelial cells during lung infection. To differentiate genes induced selectively in epithelial cells during pneumonia, we compared genome-wide expression profiles from three sorted cell populations: epithelial cells from uninfected mouse lungs, epithelial cells from mouse lungs with pneumococcal pneumonia, and nonepithelial cells from those same infected lungs. Of 1,166 transcripts that were more abundant in epithelial cells from infected lungs compared with nonepithelial cells from the same lungs or from epithelial cells of uninfected lungs, 32 genes were identified as highly expressed secreted products. Especially strong signals included two related secreted and transmembrane (Sectm) 1 genes, Sectm1a and Sectm1b. Refinement of sorting strategies suggested that both Sectm1 products were induced predominantly in conducting airway epithelial cells. Sectm1 was induced during the early stages of pneumococcal pneumonia, and mutation of NF-kB RelA in epithelial cells did not diminish its expression. Instead, type I IFN signaling was necessary and sufficient for Sectm1 induction in lung epithelial cells, mediated by signal transducer and activator of transcription 1. For target cells, Sectm1a bound to myeloid cells preferentially, in particular Ly6GbrightCD11bbright neutrophils in the infected lung. In contrast, Sectm1a did not bind to neutrophils from uninfected lungs. Sectm1a increased expression of the neutrophil-attracting chemokine CXCL2 by neutrophils from the infected lung. We propose that Sectm1a is an epithelial product that sustains a positive feedback loop amplifying neutrophilic inflammation during pneumococcal pneumonia

    A Small-Molecule Inhibitor of Mps1 Blocks the Spindle-Checkpoint Response to a Lack of Tension on Mitotic Chromosomes

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    SummaryThe spindle checkpoint prevents chromosome loss by preventing chromosome segregation in cells with improperly attached chromosomes [1–3]. The checkpoint senses defects in the attachment of chromosomes to the mitotic spindle [4] and the tension exerted on chromosomes by spindle forces in mitosis [5–7]. Because many cancers have defects in chromosome segregation, this checkpoint may be required for survival of tumor cells and may be a target for chemotherapy. We performed a phenotype-based chemical-genetic screen in budding yeast and identified an inhibitor of the spindle checkpoint, called cincreasin. We used a genome-wide collection of yeast gene-deletion strains and traditional genetic and biochemical analysis to show that the target of cincreasin is Mps1, a protein kinase required for checkpoint function [8]. Despite the requirement for Mps1 for sensing both the lack of microtubule attachment and tension at kinetochores, we find concentrations of cincreasin that selectively inhibit the tension-sensitive branch of the spindle checkpoint. At these concentrations, cincreasin causes lethal chromosome missegregation in mutants that display chromosomal instability. Our results demonstrate that Mps1 can be exploited as a target and that inhibiting the tension-sensitive branch of the spindle checkpoint may be a way of selectively killing cancer cells that display chromosomal instability

    Greater Sage-Grouse Resource Selection Drives Reproductive Fitness Under a Conifer Removal Strategy

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    The link between individual variation in resource selection (e.g., functional response) and fitness creates a foundation for understanding wildlife-habitat relationships. Although many anthropogenic activities adversely affect these relationships, it is largely unknown whether projects implemented to benefit wildlife populations actually achieve this outcome. For sagebrush (Artemisia spp.) obligate species such as the greater sage-grouse (Centrocercus urophasianus; sage-grouse), expansion of juniper (Juniperus spp.) and pinyon-pine (Pinus spp.; conifers) woodlands into sagebrush ecosystems has been identified as a conservation threat. This threat is intensified when a sagebrush ecosystem is bounded by naturally unsuitable habitats. As such, federal, state, and private land managers have implemented landscape-level management to remove conifers on thousands of hectares of sagebrush habitat across the western United States. Despite the scale of contemporary conifer treatments, little was previously known whether sage-grouse will occupy these manipulated landscapes and whether occupancy has consequences on fitness components. To address these questions, we monitored nest and brood success rates for 96 radio-marked sage-grouse from 2012-2015 that inhabited conifer-dominated landscapes in the Box Elder Sage-grouse Management Area in Utah where mechanical conifer removal projects were completed. We then linked sage-grouse resource selection to individual nest (n = 95) and brood (n = 56) success by incorporating random-slope Resource Selection Functions as explanatory predictors in a logistic brood success model. Using the novel approach of random slope covariates, we demonstrated that sage-grouse selected for nest and brooding sites closer to conifer removal areas and that the probability of individual nest and brood success declined (β = − 0.10 and β = − 0.74, respectively) as sage-grouse females selected sites farther from conifer removal areas. Our research provided the first evidence that mechanical conifer removal treatments can increase suitable available breeding habitats for female sage-grouse and that individuals who occupied these areas experienced enhanced nest and brood success
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