578 research outputs found

    Sensitivity of Lake Sturgeon population dynamics and genetics to demographic parameters [Powerpoint Slide]

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    Lake sturgeon Acipenser fulvescens restoration is a priority throughout the Great Lakes basin, where sturgeon have been reduced to less than 1% of historic levels due to habitat degradation, overharvest, and fragmentation of spawning populations. The population parameters most important to long-term lake sturgeon persistence are unknown

    Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1

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    <p>Abstract</p> <p>Background</p> <p>MicroRNA (miRNA)-mediated RNA silencing is integral to virtually every cellular process including cell cycle progression and response to virus infection. The interplay between RNA silencing and HIV-1 is multifaceted, and accumulating evidence posits a strike-counterstrike interface that alters the cellular environment to favor virus replication. For instance, miRNA-mediated RNA silencing of HIV-1 translation is antagonized by HIV-1 Tat RNA silencing suppressor activity. The activity of HIV-1 accessory proteins Vpr/Vif delays cell cycle progression, which is a process prominently modulated by miRNA. The expression profile of cellular miRNA is altered by HIV-1 infection in both cultured cells and clinical samples. The open question stands of what, if any, is the contribution of Tat RNA silencing suppressor activity or Vpr/Vif activity to the perturbation of cellular miRNA by HIV-1.</p> <p>Results</p> <p>Herein, we compared the perturbation of miRNA expression profiles of lymphocytes infected with HIV-1<sup>NL4-3 </sup>or derivative strains that are deficient in Tat RNA silencing suppressor activity (Tat K51A substitution) or ablated of the vpr/vif open reading frames. Microarrays recapitulated the perturbation of the cellular miRNA profile by HIV-1 infection. The miRNA expression trends overlapped ~50% with published microarray results on clinical samples from HIV-1 infected patients. Moreover, the number of miRNA perturbed by HIV-1 was largely similar despite ablation of Tat RSS activity and Vpr/Vif; however, the Tat RSS mutation lessened HIV-1 downregulation of twenty-two miRNAs.</p> <p>Conclusions</p> <p>Our study identified miRNA expression changes attributable to Tat RSS activity in HIV-1<sup>NL4-3</sup>. The results accomplish a necessary step in the process to understand the interface of HIV-1 with host RNA silencing activity. The overlap in miRNA expression trends observed between HIV-1 infected CEMx174 lymphocytes and primary cells supports the utility of cultured lymphocytes as a tractable model to investigate interplay between HIV-1 and host RNA silencing. The subset of miRNA determined to be perturbed by Tat RSS in HIV-1 infection provides a focal point to define the gene networks that shape the cellular environment for HIV-1 replication.</p

    Probing the Evolution of the Galaxy Interaction/Merger Rate Using Collisional Ring Galaxies

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    We present the results from our program to determine the evolution of the galaxy interaction/merger rate with redshift using the unique star-forming characteristics of collisional ring galaxies. We have identified 25 distant collisional ring galaxy candidates (CRGCs) in a total of 162 deep Hubble Space Telescope Wide Field/Planetary Camera-2 images obtained from the HST Archives. Based on measured and estimated redshifts, these 25 CRGCs all lie in the redshift interval of 0.1 < z < 1. Using the local collisional ring galaxy volume density and the new ``standard'' cosmology, we find that in order to account for the number of identified CRGCs in our surveyed fields, the galaxy interaction/merger rate, parameterized as (1 + z)^m, must increase steeply with redshift.We determine a minimum value of m = 5.2 ±\pm 0.7, though m could be as high as 7 or 8. We can rule out a non-evolving (m = 0) and weakly evolving (m = 1-2) galaxy interaction/merger rate at greater than the 4 sigma level of confidence.Comment: Accepted in the Astrophysical Journal (11 pages, 4 figures). Higher resolution version of the figures is available at http://www.astro.cornell.edu/~vassilis/papers

    Type 2 Diabetes Impairs the Ability of Skeletal Muscle Pericytes to Augment Postischemic Neovascularization in db/db Mice

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    Peripheral artery disease is an atherosclerotic occlusive disease that causes limb ischemia and has few effective noninterventional treatments. Stem cell therapy is promising, but concomitant diabetes may limit its effectiveness. We evaluated the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization in wild-type and type 2 diabetic (T2DM) mice. Wild-type C57BL/6J and leptin receptor spontaneous mutation db/db T2DM mice underwent unilateral femoral artery excision to induce limb ischemia. Twenty-four hours after ischemia induction, CD45-CD34-CD146+ skeletal muscle pericytes or vehicle controls were transplanted into ischemic hindlimb muscles. At postoperative day 28, pericyte transplantation augmented blood flow recovery in wild-type mice (79.3 ± 5% vs. 61.9 ± 5%; P = 0.04), but not in T2DM mice (48.6% vs. 46.3 ± 5%; P = 0.51). Pericyte transplantation augmented collateral artery enlargement in wild-type (26.7 ± 2 µm vs. 22.3 ± 1 µm, P = 0.03), but not T2DM mice (20.4 ± 1.4 µm vs. 18.5 ± 1.2 µm, P = 0.14). Pericyte incorporation into collateral arteries was higher in wild-type than in T2DM mice (P = 0.002). Unexpectedly, pericytes differentiated into Schwann cells in vivo. In vitro, Insulin increased Nox2 expression and decreased tubular formation capacity in human pericytes. These insulin-induced effects were reversed by N-acetylcysteine antioxidant treatment. In conclusion, T2DM impairs the ability of pericytes to augment neovascularization via decreased collateral artery enlargement and impaired engraftment into collateral arteries, potentially via hyperinsulinemia-induced oxidant stress. While pericytes show promise as a unique form of stem cell therapy to increase postischemic neovascularization, characterizing the molecular mechanisms by which T2DM impairs their function is essential to achieve their therapeutic potential

    Immunization with the C-domain of α-toxin prevents lethal infection, localizes tissue injury, and promotes host response to challenge with Clostridium perfringens

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    © 2004 by the Infectious Diseases Society of America. All rights reserved.Clostridium perfringens gas gangrene is characterized by rapid tissue destruction, impaired host response, and, often, death. Phospholipase C (α-toxin) is the virulence factor most responsible for these pathologies. The present study investigated the efficacy of active immunization with the C-terminal domain of α-toxin (Cpa247–370) in a murine model of gas gangrene. Primary end points of the study were survival, progression of infection, and tissue perfusion. Secondary end points, which were based on findings of histologic evaluation of tissues, included the extent of tissue destruction and microvascular thrombosis, as well as the magnitude of the tissue inflammatory response. Survival among C-domain–immunized animals was significantly greater than that among sham-immunized control animals. Furthermore, immunization with the C-domain localized the infection and prevented ischemia of the feet. Histopathologic findings demonstrated limited muscle necrosis, reduced microvascular thrombosis, and enhanced granulocytic influx in C-domain–immunized mice. We conclude that immunization with the C-domain of phospholipase C is a viable strategy for the prevention of morbidity and mortality associated with C. perfringens gas gangrene

    The role of emotion in the learning of trustworthiness from eye-gaze : Evidence from facial electromyography.

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    When perception of gaze direction is congruent with the location of a target, attention is facilitated and responses are faster compared to when incongruent. Faces that consistently gaze congruently are also judged trustworthier than faces that consistently gaze incongruently. However, it’s unclear how gaze-cues elicit changes in trust. We measured facial electromyography (EMG) during an identity-contingent gaze-cueing task to examine whether embodied emotional reactions to gaze-cues mediate trust learning. Gaze-cueing effects were found to be equivalent regardless of whether participants showed learning of trust in the expected direction or did not. In contrast, we found distinctly different patterns of EMG activity in these two populations. In a further experiment we showed the learning effects were specific to viewing faces, as no changes in liking were detected when viewing arrows that evoked similar attentional orienting responses. These findings implicate embodied emotion in learning trust from identity-contingent gaze-cueing, possibly due to the social value of shared attention or deception rather than domain-general attentional orienting

    Factors associated with depression, anxiety, and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis

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    Background: Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness. However, factors associated with mental illness are unclear. / Objectives: To synthesise and evaluate all available evidence on factors associated with depression, anxiety, and severe mental illness (SMI) among adults with AE or psoriasis. / Methods: We searched electronic databases, grey literature databases, and clinical trial registries from inception to February 2022 for studies in adults with AE or psoriasis. Eligible studies were randomised controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety, or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesised results narratively, and if at least two studies were sufficiently homogenous, we pooled effect estimates in a random-effects meta-analysis. / Results: We included 21 studies (11 observational, 10 RCT). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety – one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest being female, and psoriatic arthritis, were associated with depression (female sex:OR = 1.62,95%CI = 1.09-2.40,95%PI = 0.62-4.23, I2 = 24.90%, Tau2 = 0.05; psoriatic arthritis:OR = 2.26,95%CI = 1.56-3.25,95%PI = 0.21-24.23, I2 = 0.00%, Tau2 = 0.00) and anxiety (female sex:OR = 2.59,95%CI = 1.32-5.07,95%PI = 0.00-3956.27, I2 = 61.90%, Tau2 = 0.22; psoriatic arthritis:OR = 1.98,95%CI = 1.33-2.94, I2 = 0.00%, Tau2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR = 1.14,95%CI = 1.05-1.25, I2 = 0.00%, Tau2 = 0.00), but not depression. Evidence from RCTs suggested adults with AE or psoriasis given placebo had higher depression and anxiety scores compared to comparators given targeted treatment (e.g., biologic agents). / Conclusions: Our review highlights limited existing research on factors associated with depression, anxiety, and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared to skin disease treated with targeted therapy, however, follow-up was limited, therefore long-term effects on mental health are unclear

    Genital self-sampling compared with cervicovaginal lavage for the diagnosis of female genital schistosomiasis in Zambian women: The BILHIV study

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    Background: Given the potentially causal association of female genital schistosomiasis (FGS) with HIV-1 infection, improved diagnostics are urgently needed to scale-up FGS surveillance. The BILHIV (bilharzia and HIV) study assessed the performance of home-based self-collection methods (cervical and vaginal swabs) compared to cervicovaginal lavage (CVL) for the detection of Schistosoma DNA by real-time polymerase chain reaction (PCR). Methods: Between January and August 2018, a consecutive series of female participants from the Population-Cohort of the previous HIV prevention trial HPTN 071 (PopART), resident in Livingstone, Zambia were invited to take part in BILHIV if they were 18–31 years old, non-pregnant and sexually active. Genital self-collected swabs and a urine specimen were obtained and a questionnaire completed at home visits. CVL was obtained at clinic follow-up. Results: 603 women self-collected genital swabs. Of these, 527 women had CVL performed by a mid-wife during clinic follow-up. Schistosoma DNA was more frequently detected in genital self-collected specimens (24/603, 4.0%) compared to CVL (14/527, 2.7%). Overall, 5.0% (30/603) women had female genital schistosomiasis, defined as a positive PCR by any genital sampling method (cervical swab PCR, vaginal swab PCR, or CVL PCR) and 95% (573/603) did not have a positive genital PCR. The sensitivity of any positive genital self-collected swab against CVL was 57.1% (95% CI 28.9–82.3%), specificity 97.3% (95.5–98.5%). In a subset of participants with active schistosome infection, determined by detectable urine Circulating Anodic Antigen (CAA) (15.1%, 91/601), positive PCR (4.3%, 26/601), or positive microscopy (5.5%, 33/603), the sensitivity of any positive self-collected specimen against CVL was 88.9% (51.8–99.7%). Conclusions: Genital self-sampling increased the overall number of PCR-based FGS diagnoses in a field setting, compared with CVL. Home-based sampling may represent a scalable alternative method for FGS community-based diagnosis in endemic resource limited settings

    SigFuge: Single gene clustering of RNA-seq reveals differential isoform usage among cancer samples

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    High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as biomarkers for improved prognosis and therapy. While many statistical methods have been proposed for identifying novel transcriptional events with RNA-seq, nearly all rely on contrasting known classes of samples, such as tumor and normal. Few tools exist for the unsupervised discovery of such events without class labels. In this paper, we present SigFuge for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. SigFuge combines clustering with hypothesis testing to identify genes exhibiting alternative splicing, or differences in isoform expression. We apply SigFuge to RNA-seq cohorts of 177 lung and 279 head and neck squamous cell carcinoma samples from the Cancer Genome Atlas, and identify several cases of differential isoform usage including CDKN2A, a tumor suppressor gene known to be inactivated in a majority of lung squamous cell tumors. By not restricting attention to known sample stratifications, SigFuge offers a novel approach to unsupervised screening of genetic loci across RNA-seq cohorts. SigFuge is available as an R package through Bioconductor

    Obesity inhibits the osteogenic differentiation of human adipose-derived stem cells

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    Additional file 3: Figure S3. No observable differences in lnASCs and obASCs during early bone regeneration. Critical size calvarial defects were created in the parietal bone of nude mice and assessed after 2 weeks. (A) Representative images of microCT scanning. (B) Quantification of microCT. Scale bar represents 1 mm. Bars, Ă‚Ä… SEM
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