576 research outputs found

    Perfluorooctanoate suppresses spheroid attachment on endometrial epithelial cells through peroxisome proliferator-activated receptor alpha and down-regulation of Wnt signaling

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    Exposure of animals to perfluorooctanoic acid (PFOA), a surfactant used in emulsion polymerization processes causes early pregnancy loss, delayed growth and development of fetuses. The mechanisms of action are largely unknown. We studied the effect of PFOA on implantation using an in vitro spheroid-endometrial cell co-culture model. PFOA (10-100μM) significantly reduced Jeg-3 spheroid attachment on RL95-2 endometrial cells. PFOA also suppressed β-catenin expression in Jeg-3 cells. The Wnt agonist Wnt3a stimulated β-catenin expression in Jeg-3 cells and reversed the PFOA suppression of the spheroid attachment. The putative PFOA receptors (PPARα, β, γ) present in both cell lines were not affected by PFOA (0.01-100μM). The PPARα antagonist MK886 restored the β-catenin and E-cadherin expression levels in Jeg-3 cells and reversed the suppression of the spheroid attachment caused by PFOA. Taken together, PFOA suppresses spheroid attachment through PPARα and Wnt signaling pathways via down-regulation of β-catenin and E-cadherin expression.postprin

    Antidepressant use and risk of self-harm among people aged 40 years or older: A population-based cohort and self-controlled case series study

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    Background: Studies on the association between antidepressants and self-harm in adults were mostly conducted over a decade ago and have inconsistent findings. We aimed to compare self-harm risks by antidepressant classes among people aged 40 years or older with depression. Methods: Individuals aged ≥40 years with depression who initiated antidepressant treatment between 2001 and 2015 were retrieved from the Hong Kong Clinical Data Analysis & Reporting system, and were followed up until December 31, 2016. We conducted self-controlled case series (SCCS) analyses to estimate the incidence rate ratio (IRR) of self-harm comparing the pre-exposure (90 days before the first antidepressant use), index exposure (the first antidepressant use), and subsequent exposure (subsequent antidepressant use) periods to nonexposed periods. We applied Cox proportional hazard regressions to estimate the hazard ratio (HR) of self-harm comparing five antidepressant classes (tricyclic and related antidepressant drugs [TCAs], selective serotonin reuptake inhibitors [SSRIs], noradrenergic and specific serotonergic antidepressants [NaSSAs], serotonin–norepinephrine reuptake inhibitors [SNRIs], and others). Findings: A total of 48,724 individuals were identified. SCCS analyses (N = 3,846) found that the increased self-harm risk occurred during the pre-exposure (IRR: 22.24; 95% CI, 20.25-24.42), index exposure (7.03; 6.34-7.80), and subsequent exposure periods (2.47; 2.18-2.79) compared to the unexposed period. Cohort analyses (N = 48,724) found an association of higher self-harm risks in short-term (one year) for NaSSAs vs. TCAs (HR, 2.13; 95% CI, 1.53-2.96), SNRIs vs. TCAs (1.64; 1.01-2.68), and NaSSAs vs. SSRIs (1.75; 1.29-2.36) in the 40-64 years group. The higher risk remained significant in long-term (> one year) for NaSSAs vs. TCAs (1.55; 1.26-1.91) and NaSSAs vs. SSRIs (1.53; 1.26-1.87). In the 65+ group, only short-term differences were observed (SSRIs vs. TCAs [1.31; 1.03-1.66], SNRIs vs. SSRIs [0.44; 0.22-0.87], and SNRIs vs. NaSSAs [0.43; 0.21-0.87]). Interpretation: Within-person comparisons did not suggest that antidepressant exposure is causally associated with an increased risk of self-harm in people with depression. Between-person comparisons revealed differences in self-harm risks between certain pairs of antidepressant classes. These findings may inform clinicians’ benefit-risk assessments when prescribing antidepressants

    Fluorescent Gold Nanoprobes for the Sensitive and Selective Detection for Hg2+

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    A simple, cost-effective yet rapid and sensitive sensor for on-site and real-time Hg2+ detection based on bovine serum albumin functionalized fluorescent gold nanoparticles as novel and environmentally friendly fluorescent probes was developed. Using this probe, aqueous Hg2+ can be detected at 0.1 nM in a facile way based on fluorescence quenching. This probe was also applied to determine the Hg2+ in the lake samples, and the results demonstrate low interference and high sensitivity

    Does the immune reaction cause malignant transformation by disrupting cell-to-cell or cell-to-matrix communications?

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    Tumor progression: In many (perhaps in all) tumor systems, a malignant cancer is preceded by a benign lesion. Most benign lesions do not transform to malignancy and many regress. The final transformative step to malignancy differs from the preceding steps in, among other things, that it often occurs in the absence of the original carcinogenic stimulus. Mechanism of immunostimulation: Relatively low titers of specific immune reactants are known to stimulate, but cell-to-cell or cell-to-matrix interactions appear to be major inhibitors of tumor-growth. Therefore, it seems reasonable to hypothesize that the mechanism of immunostimulation may be an interference with cell-to-cell or cell-to-matrix communication by a sub-lethal immune-reaction. Discussion: While the above hypothesis remains unproven, some evidence suggests that immunity may have a major facilitating effect on tumor growth especially at the time of malignant transformation. There is even some evidence suggesting that transformation in vivo may seldom occur in the absence of immunostimulation of the premalignant lesion. Positive selection by the immune reaction may be the reason that tumors are immunogenic

    Hybridization in human evolution: Insights from other organisms

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    During the late Pleistocene, isolated lineages of hominins exchanged genes thus influencing genomic variation in humans in both the past and present. However, the dynamics of this genetic exchange and associated phenotypic consequences through time remain poorly understood. Gene exchange across divergent lineages can result in myriad outcomes arising from these dynamics and the environmental conditions under which it occurs. Here we draw from our collective research across various organisms, illustrating some of the ways in which gene exchange can structure genomic/phenotypic diversity within/among species. We present a range of examples relevant to questions about the evolution of hominins. These examples are not meant to be exhaustive, but rather illustrative of the diverse evolutionary causes/consequences of hybridization, highlighting potential drivers of human evolution in the context of hybridization including: influences on adaptive evolution, climate change, developmental systems, sex-differences in behavior, Haldane’s rule and the large X-effect, and transgressive phenotypic variation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151330/1/evan21787.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151330/2/evan21787_am.pd

    Analysis of reported error in Monte Carlo rendered images

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    Evaluating image quality in Monte Carlo rendered images is an important aspect of the rendering process as we often need to determine the relative quality between images computed using different algorithms and with varying amounts of computation. The use of a gold-standard, reference image, or ground truth (GT) is a common method to provide a baseline with which to compare experimental results. We show that if not chosen carefully the reference image can skew results leading to significant misreporting of error. We present an analysis of error in Monte Carlo rendered images and discuss practices to avoid or be aware of when designing an experiment

    Y-chromosomal STRs haplotypes in the Taiwanese Paiwan population

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    The distribution of Y-chromosomal short tandem repeat (Y-STR) haplotypes was determined in a population of Taiwanese Paiwan aboriginals. Using 17 Y-STR markers, a total of 135 haplotypes were observed, 102 of which were unique. The overall haplotype diversity for the 17 Y-STR loci tested was 0.9922 and the discrimination capacity was 0.6490. In addition, three novel intermediate alleles at the DYS448 locus were also found

    ICF components of corresponding outcome measures in flexor tendon rehabilitation – a systematic review

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    <p>Abstract</p> <p>Background</p> <p>The International Classification of Functioning, Disability and Health (ICF) delivers a holistic approach to health conditions. The objective of the present study is to provide an overview of flexor tendon rehabilitation outcome measures with respect to ICF components. Furthermore, it aims to investigate to which extent current assessments measure aspects of health according to these components primarily focussing on <it>activity </it>and <it>participation</it>.</p> <p>Methods</p> <p>A systematic literature review was conducted to identify all studies meeting the inclusion criteria. Studies were only included if they assessed more than <it>body function and body structure </it>and referred to the ICF components <it>activity </it>and <it>participation</it>. The outcome measures were analysed and their linkage to the ICF components were investigated to examine to which degree aspects of health outcome as defined by the ICF were considered.</p> <p>Results</p> <p>As anticipated, the application of outcome measures after flexor tendon repair is non conform. In many studies the emphasis still lies on physical impairment neglecting activity limitations and participation restrictions.</p> <p>Aspects of health after flexor tendon repair could be assessed more adequately and cover patients' needs more sufficiently by choosing outcome measures which refer to all aspects of functioning.</p> <p>Conclusion</p> <p>The ICF can help to identify aspects of health which are not being considered. The ICF can help promote further development of adequate outcome measures including activity limitation and participation restrictions by targeting patient centred goals and respecting patients' needs.</p

    Search for rare quark-annihilation decays, B --> Ds(*) Phi

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    We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications
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