Miracle-dz/UniFAR-FTUs huggingface dataset:
Old cells die hard – sympatholysis and the ageing erythrocyte

Skeletal muscle blood flow is tightly regulated by multiple redundant pathways integrating local vasoconstrictor and vasodilator signals to support optimal function. Insufficiencies in signalling cascades may lead to mismatching of local perfusion and tissue metabolic demand, compromising skeletal muscle’s capacity to perform work. Healthy ageing has been associated with decrements in peripheral vascular function, a subsequent mismanagement of blood flow and reductions in exercise capacity. As exercise capacity is both a predictor of all-cause mortality and a major factor in overall quality of life, elucidating the underpinnings of this dysfunction is vital for the development of new treatments and therapeutic options to combat the decline of vascular function with age. Recently, Hearon and colleagues have conducted a series of studies on the interaction of dilatory and constrictor pathways in regulating muscle blood flow. The latest study in this series, published in this issue of The Journal of Physiology, examined the capacity of the endothelium to modulate adrenergic vasoconstriction in ageing adults (Hearon et al. 2020). The ability of vasculature within exercising skeletal muscle to locally inhibit sympathetic neural vasoconstriction during exercise is known as ‘functional sympatholysis’. Although vasodilatation and sympatholysis exhibit numerous mechanistic similarities such as key chemical mediators and downstream signalling cascades, these processes are each distinct phenomena and the efficacy of one may not be predictive of the other. The health and function of the endothelium has come under scrutiny as a key site of integration and coordination of vascular tone, and for its role in age-associated decrements in peripheral vascular function. While older adults exhibit impaired sympatholysis during exercise, they maintain the ability to blunt sympathetically mediated vasoconstriction during exogenous ATP administration (Kirby et al. 2011). These findings suggest that these sympatholytic pathways are intact in older adults, with age-associated decrements in sympatholysis attributable rather to a reduction in endothelial signalling. Therefore, the authors aimed to test the hypothesis that endothelium-mediated sympatholytic pathways are preserved in healthy ageing.
The relationships between temperature and rate of development in two geographic stocks of Aphidius sonchi in the laboratory

The developmental periods from egg to adult of two stocks of the aphid parasite, Aphidius sonchi Marshall (Hymenoptera: Aphidiidae), were determined under various constant and alternating temperature regimes. The relationship between temperature and rate of development for each of the two stocks under constant conditions was described satisfactorily by the logistic curve. Based on the constant temperature curves, comparisons showed that temperature alternations did not accelerate or decelerate rate of development in either stock. Further analysis indicated that rates of development at extreme temperatures were well described by the logistic curve.
An HSV-2 nucleoside-modified mRNA genital herpes vaccine containing glycoproteins gC, gD, and gE protects mice against HSV-1 genital lesions and latent infection

HSV-1 causes 50% of first-time genital herpes infections in resource-rich countries and affects 190 million people worldwide. A prophylactic herpes vaccine is needed to protect against genital infections by both HSV-1 and HSV-2. Previously our laboratory developed a trivalent vaccine that targets glycoproteins C, D, and E present on the HSV-2 virion. We reported that this vaccine protects animals from genital disease and recurrent virus shedding following lethal HSV-2 challenge. Importantly the vaccine also generates cross-reactive antibodies that neutralize HSV-1, suggesting it may provide protection against HSV-1 infection. Here we compared the efficacy of this vaccine delivered as protein or nucleoside-modified mRNA immunogens against vaginal HSV-1 infection in mice. Both the protein and mRNA vaccines protected mice from HSV-1 disease; however, the mRNA vaccine provided better protection as measured by lower vaginal virus titers post-infection. In a second experiment, we compared protection provided by the mRNA vaccine against intravaginal challenge with HSV-1 or HSV-2. Vaccinated mice were totally protected against death, genital disease and infection of dorsal root ganglia caused by both viruses, but somewhat better protected against vaginal titers after HSV-2 infection. Overall, in the two experiments, the mRNA vaccine prevented death and genital disease in 54/54 (100%) mice infected with HSV-1 and 20/20 (100%) with HSV-2, and prevented HSV DNA from reaching the dorsal root ganglia, the site of virus latency, in 29/30 (97%) mice infected with HSV-1 and 10/10 (100%) with HSV-2. We consider the HSV-2 trivalent mRNA vaccine to be a promising candidate for clinical trials for prevention of both HSV-1 and HSV-2 genital herpes.
FOXO3a acts to suppress DNA double‐strand break‐induced mutations

Genomic instability is one of the hallmarks of aging, and both DNA damage and mutations have been found to accumulate with age in different species. Certain gene families, such as sirtuins and the FoxO family of transcription factors, have been shown to play a role in lifespan extension. However, the mechanism(s) underlying the increased longevity associated with these genes remains largely unknown and may involve the regulation of responses to cellular stressors, such as DNA damage. Here, we report that FOXO3a reduces genomic instability in cultured mouse embryonic fibroblasts (MEFs) treated with agents that induce DNA double‐strand breaks (DSBs), that is, clastogens. We show that DSB treatment of both primary human and mouse fibroblasts upregulates FOXO3a expression. FOXO3a ablation in MEFs harboring the mutational reporter gene lacZ resulted in an increase in genome rearrangements after bleomycin treatment; conversely, overexpression of human FOXO3a was found to suppress mutation accumulation in response to bleomycin. We also show that overexpression of FOXO3a in human primary fibroblasts decreases DSB‐induced γH2AX foci. Knocking out FOXO3a in mES cells increased the frequency of homologous recombination and non‐homologous end‐joining events. These results provide the first direct evidence that FOXO3a plays a role in suppressing genome instability, possibly by suppressing genome rearrangements.
Amino Acid Metabolites and Slow Weight Loss in the Early Postoperative Period after Sleeve Gastrectomy

Background: Profiles of amino acid metabolites (AAMs) have been linked to obesity and energy homeostasis. We investigated whether baseline obesity-related AAMs were associated with weight status in the early postoperative period after sleeve gastrectomy. Methods: In this prospective, single-arm, longitudinal study, 27 bariatric patients underwent sleeve gastrectomy. Twenty obesity-related AAMs were comprehensively quantified prior to surgery, and slow weight loss was defined as the lowest 40% of the percentage excess weight loss (%EWL) at three and six months postoperatively. Linear regression models were used to assess the association between baseline obesity-related AAMs and %EWL, and receiver operating characteristic curves were assessed. Results: Isoleucine and metabolites from the serotonin pathway were significantly associated with the %EWL at three and six months after sleeve gastrectomy. Among the metabolites identified to be significant in the regression analyses, serotonin (area under receiver operating characteristic curves (AUROC): 0.79, 95% confidence interval (CI): 0.59–0.97) and serotonin/5-hydroxytryptophan ratio (AUROC: 0.80, 95% CI: 0.58–1.00) showed superior performance in predicting slow weight loss six months after sleeve gastrectomy. Conclusions: Our findings underscore the importance of baseline AAM profiles, especially serotonin and serotonin/5-hydroxytryptophan ratio, in predicting slow weight loss in the early postoperative period after sleeve gastrectomy.
Influence of blood flow occlusion on muscular recruitment and fatigue during maximal‐effort small muscle‐mass exercise

The heavy‐to‐severe intensity exercise threshold (i.e. critical force) distinguishes between steady‐state and progressive metabolic and neuromuscular responses to exercise. High levels of skeletal muscle sensory feedback related to peripheral fatigue development are thought to restrict motor unit activation and limit exercise tolerance. Utilizing limb blood flow occlusion, we demonstrate that critical force reflects an oxygen‐delivery‐dependent balance between motor unit activation and peripheral fatigue development. Our findings suggest that mechanisms which determine the total force‐producing capacity of exercising skeletal muscle are significantly altered during blood flow occlusion. These findings may have widespread implications for exercise tolerance in patient populations who experience partial vascular occlusion or altered neuromuscular reflexes.
Extracts Characterization and In Vitro Evaluation of Potential Immunomodulatory Activities of the Moss Hypnum cupressiforme Hedw.

Recently, there has been an increasing interest in the chemistry and biological potential of mosses, since a large number of biologically active compounds have been found within these species. This study aimed at examining the chemical composition and immunomodulatory potential (antioxidant, antidiabetic, anti-neuroinflammatory/antineurodegenerative, and antitumor activities) of moss Hypnum cupressiforme Hedw. extracts. Corresponding extracts have been obtained applying Soxhlet extractor. The chemical characterization was performed using spectrophotometric assays and liquid chromatography–mass spectrometry (LC-MS). The extracts were analyzed for antioxidant activity and for inhibitory activities on α-glucosidase, α-amylase, acetylcholinesterase, and tyrosinase. Additionally, extracts were tested against four cell lines—MRC-5, BV2, HCT-116, and MDA-MB-231—for antitumor and anti-inflammatory activities. Chemical analysis of extracts revealed the presence of flavonoids, phenolic acids, and triterpenoids. Major compounds identified by LC-MS in H. cupressiforme were kaempferol and five phenolic acids: p-hydroxybenzoic, protocatechuic, p-coumaric, gallic, and caffeic acid. According to biochemical assays the investigated extracts exhibited significant immunomodulatory potential. Significant antiproliferative potential against MDA-MB-231 cells has been observed together with the promising anti-neuroinflammatory application. The obtained data suggest that moss H. cupressiforme is a valuable natural source of biologically active compounds with potential application in the pharmaceutical industry.
Computational Fluid Dynamics (CFD) as a Tool for Investigating Self-Organized Ascending Bubble-Driven Flow Patterns in Champagne Glasses

Champagne glasses are subjected to complex ascending bubble-driven flow patterns, which are believed to enhance the release of volatile organic compounds in the headspace above the glasses. Based on the Eulerian–Lagrangian approach, computational fluid dynamics (CFD) was used in order to examine how a column of ascending bubbles nucleated at the bottom of a classical champagne glass can drive self-organized flow patterns in the champagne bulk and at the air/champagne interface. Firstly, results from two-dimensional (2D) axisymmetric simulations were compared with a set of experimental data conducted through particle image velocimetry (PIV). Secondly, a three-dimensional (3D) model was developed by using the conventional volume-of-fluid (VOF) multiphase method to resolve the interface between the mixture’s phases (wine–air). In complete accordance with several experimental observations conducted through laser tomography and PIV techniques, CFD revealed a very complex flow composed of surface eddies interacting with a toroidal flow that develops around the ascending bubble column.
Up in Smoke: Exploring the Relationship between Bullying Victimization and E-Cigarette Use in Sexual Minority Youths

Abstract Background E-cigarette use is increasing in popularity for high school students (Singh et al., 2016) and may be accompanied by negative health outcomes (Rankin et al., 2019). Students who identify as sexual minority (lesbian, gay, bisexual, or queer/questioning) may be at an increased risk of bullying victimization and substance use due to their sexual identity (Caputi, 2018). Purpose/Objectives: This study explored the relationship between bullying in school and cyberbullying (i.e. bullying through social media) victimization with past 30-day e-cigarette use for sexual minority youths, an at-risk group for victimization and its negative consequences. Methods: The Youth Risk Behavioral Survey was utilized to study a sample of sexual minority high school students (N = 2302; 69.4% female). Three models were utilized to examine whether bullying in school or cyberbullying victimization were related to e-cigarette use after controlling only for demographics in the demographics model, and then the use of other substances in the substance use model. Cigarette use was combined with e-cigarettes as the dependent variable in the third comparative model. Results: After controlling for age, race, sex, sexual identity, and other substance use, bullying victimization in school and online were significantly related to current e-cigarette use together but not separately. Cyberbullying victimization was significantly related to combined cigarette and e-cigarette use. Conclusions/Importance: These findings suggest that sexual minority students who report cyberbullying victimization may use cigarette products more than their noncyberbullied peers. Cyberbullying prevention and interventions should continue to be targeted in schools, especially for sexual minority youths.
CCAAT/Enhancer-Binding Protein β Isoforms and the Regulation of α-Smooth Muscle Actin Gene Expression by IL-1β1

The role of IL-1β in inflammation is amply documented, but its ability to inhibit myofibroblast differentiation and, in particular, the suppression of α-smooth muscle actin (α-SMA) gene expression is less well understood. Because IL-1β can induce C/EBPβ expression, the role of C/EBPβ isoforms in IL-1β regulation of α-SMA gene expression was investigated in rat lung myofibroblasts. The results showed that IL-1β inhibited α-SMA expression in a dose-dependent manner, which was associated with stimulation of the expression of both C/EBPβ isoforms, liver-enriched activating protein (LAP) and liver-enriched inhibitory protein (LIP). However, a greater increase in LIP relative to LAP expression resulted in a reduced LAP/LIP ratio after IL-1β treatment. Transfection with an LAP-expressing plasmid stimulated, whereas an LIP-expressing plasmid inhibited, α-SMA expression. Cells from C/EBPβ-deficient mice had reduced levels of α-SMA expression and promoter activity, which failed to respond to IL-1β treatment. Sequence analysis identified the presence of a C/EBPβ consensus binding sequence in the α-SMA promoter, which, when mutated, resulted in diminished promoter activity and abolished its responsiveness to IL-1β treatment. EMSA revealed binding of C/EBPβ to this C/EBPβ consensus binding sequence from the α-SMA promoter. Finally, IL-1β enhanced the expression of eukaryotic initiation factor 4E, a stimulator of LIP expression, which may account for a mechanism by which IL-1β could alter the LAP/LIP ratio. These data taken together suggest that C/EBPβ isoforms regulate α-SMA gene expression, and that its inhibition by IL-1β was due to preferential stimulation of LIP expression.
Language in Our Time: An Empirical Analysis of Hashtags

Hashtags in online social networks have gained tremendous popularity during the past five years. The resulting large quantity of data has provided a new lens into modern society. Previously, researchers mainly rely on data collected from Twitter to study either a certain type of hashtags or a certain property of hashtags. In this paper, we perform the first large-scale empirical analysis of hashtags shared on Instagram, the major platform for hashtag-sharing. We study hashtags from three different dimensions including the temporal-spatial dimension, the semantic dimension, and the social dimension. Extensive experiments performed on three large-scale datasets with more than 7 million hashtags in total provide a series of interesting observations. First, we show that the temporal patterns of hashtags can be categorized into four different clusters, and people tend to share fewer hashtags at certain places and more hashtags at others. Second, we observe that a non-negligible proportion of hashtags exhibit large semantic displacement. We demonstrate hashtags that are more uniformly shared among users, as quantified by the proposed hashtag entropy, are less prone to semantic displacement. In the end, we propose a bipartite graph embedding model to summarize users' hashtag profiles, and rely on these profiles to perform friendship prediction. Evaluation results show that our approach achieves an effective prediction with AUC (area under the ROC curve) above 0.8 which demonstrates the strong social signals possessed in hashtags.
Lipid levels and risk of new‐onset atrial fibrillation: A systematic review and dose‐response meta‐analysis

Lipid levels are closely associated with health, but whether lipid levels are associated with atrial fibrillation (AF) remains controversial. We thought that blood lipid levels may influence new‐onset AF. Here, we used a meta‐analysis to examine the overall association between lipid levels and new‐onset AF. PubMed and EMBASE databases were searched up to 20 December 2019. We conducted a systematic review and quantitative meta‐analysis of prospective studies to clarify the association between lipid levels and the risk of new‐onset AF. Sixteen articles with data on 4 032 638 participants and 42 825 cases of AF were included in this meta‐analysis. The summary relative risk (RR) for a 1 mmol/L increment in total cholesterol (TC) was 0.95 (95% CI 0.93‐0.96, I2 = 74.6%, n = 13). Subgroup analyses showed that follow‐up time is a source of heterogeneity; for low‐density lipoprotein cholesterol (LDL‐C), RR was 0.95 (95% CI 0.92‐0.97, I2 = 71.5%, n = 10). Subgroup analyses indicated that adjusting for heart failure explains the source of heterogeneity; for high‐density lipoprotein cholesterol (HDL‐C), RR was 0.97 (95% CI 0.96‐0.99, I2 = 26.1%, n = 11); for triglycerides (TGs), RR was 1.00 (95% CI 0.96‐1.03, I2 = 81.1%, n = 8). Subgroup analysis showed that gender, age, follow‐up time, and adjustment for heart failure are sources of heterogeneity. Higher levels of TC, LDL‐C, and HDL‐C were associated with lower risk of new‐onset AF. TG levels were not associated with new‐onset AF in all subjects.
Single-Atom Electrocatalysts from Multivariate MOFs for Highly Selective Reduction of CO2 at Low Pressures.

Single-atom catalysts (SACs) are of great interest due to their ultrahigh activity and selectivity. However, the lack of general synthetic protocol makes it difficult in the construction of model SACs to discern activity difference of diverse single-atom metal species. Herein, a universal synthetic strategy towards single-atom metal implanted N-doped carbon (M1-N-C; M = Fe, Co, Ni and Cu) has been developed based on multivariate MOFs. The M1-N-C catalysts, featuring identical parameters in chemical environment and support, provide an ideal platform to identify the differentiated activity of single-atom metal species. Upon being employed toward electrocatalytic CO2 reduction, Ni1-N-C exhibits a very high CO faradaic efficiency (FE) up to 96.8%, far surpassing Fe-, Co- and Cu-based M1-N-C. Remarkably, the best-performed Ni1-N-C even possesses excellent CO FE at low CO2 pressures, which is more challenging, demonstrating a promising opportunity for the direct use of dilute CO2 feedstock.
Emergence-Site Selection by the Dragonfly Epitheca spinosa (Hagen)

Abstract Odonates are vulnerable during emergence, when they shed their larval skin (exuvia) to take flight as adults. Emergence-site selection should adapt to the local mortality risks. Here, I characterized emergence-site selection of Epitheca spinosa (Robust Baskettails) by noting the substrate, height, and distance from water of exuviae in a 300 m × 5 m plot at Weston Lake, Congaree National Park, Hopkins, SC. Of the 82 Robust Baskettail exuviae sampled, 52 (63.4%) were found on trees with corky bark (Nyssa aquatica [Water Tupelo], Nyssa biflora [Swamp Tupelo], Fraxinus pennsylvanica [Green Ash]), while no exuviae were found on the peeling, flaky trunks of Taxodium distichum (Bald Cypress) or the smooth, platy trunks of Acer rubrum (Red Maple). However, 26 (31.7%) exuviae were on T. distichum pneumatophores. This pattern was significantly different from the relative abundances of these substrate types (&khgr;2 = 19.8, df = 3, P < 0.001). Most exuviae (93.9%) were on substrates touching the water, suggesting that larvae climb directly from the water to their emergence site. The mean height of exuviae on trees was 3.3 ± 1.37 m, with a range from 1.8–7.7 m. High-climbing by Robust Baskettail larvae may be an adaptation to flooding at Weston Lake; major flood events (>3 m) are common (5 of the last 10 years) during their March–April emergence period.
Evidence of impaired dabigatran absorption following laparoscopic Roux‐en‐Y gastric bypass surgery: the Auckland regional experience (2011–2018)

Additional supporting information may be found online in the Supporting Information section at the end of the article. Fig S1. (A) Unstimulated IFN-c levels (i.e. those measured in NIL Tube) of the 141 paediatric patients (age 0–18 years) tested with QFT-G in 2019 at Bambino Ges u Children’s Hospital (red box indicates outliers). (B) Unstimulated IFNc levels of the 141 paediatric cases by age group (Brown-Forsythe ANOVA test).
Gene therapy and immunotherapy as promising strategies to combat Huntington’s disease-associated neurodegeneration: emphasis on recent updates and future perspectives

ABSTRACT Introduction Modulation of gene expression using gene therapy as well as modulation of immune activation using immunotherapy has attracted considerable attention as rapidly emerging potential therapeutic intervention for the treatment of HD. Several preclinical and clinical trials for gene-based therapy and immunotherapy/antibody-based have been conducted. Areas covered This review focused on the potential use of gene therapy and immuno-based therapies to treat HD, including the current status, the rationale for these approaches as well as preclinical and clinical data supporting it. Growing knowledge of HD pathogenesis has resulted in the discovery of new therapeutic targets, some of which are now in clinical trials. Focus has been allocated to RNA and DNA-based gene therapies for the reduction of mutant huntingtin (mHTT), using Immuno/antibody-based therapies. Expert opinion While safety and efficacy of gene therapy and immunotherapy has been well demonstrated for HD, therefore much focus has now been shifted to disease-modifying therapies. This review defines the current status and future directions of gene therapy and immunotherapies. The review summarizes by what means HD genetic root cause modification and functional restoration of mHtt protein could be achieved by using targeted multimodality gene therapy and immunotherapy to target intracellular and extracellular mHtt.