A Transcriptomic Signature of Mouse Liver Progenitor Cells

Liver progenitor cells (LPCs) can proliferate extensively, are able to differentiate into hepatocytes and cholangiocytes, and contribute to liver regeneration. The presence of LPCs, however, often accompanies liver disease and hepatocellular carcinoma (HCC), indicating that they may be a cancer stem cell. Understanding LPC biology and establishing a sensitive, rapid, and reliable method to detect their presence in the liver will assist diagnosis and facilitate monitoring of treatment outcomes in patients with liver pathologies. A transcriptomic meta-analysis of over 400 microarrays was undertaken to compare LPC lines against datasets of muscle and embryonic stem cell lines, embryonic and developed liver (DL), and HCC. Three gene clusters distinguishing LPCs from other liver cell types were identified. Pathways overrepresented in these clusters denote the proliferative nature of LPCs and their association with HCC. Our analysis also revealed 26 novel markers, LPC markers, including Mcm2 and Ltbp3, and eight known LPC markers, including M2pk and Ncam. These markers specified the presence of LPCs in pathological liver tissue by qPCR and correlated with LPC abundance determined using immunohistochemistry. These results showcase the value of global transcript profiling to identify pathways and markers that may be used to detect LPCs in injured or diseased liver

Concussion-associated gene variants and history of concussion in elite male rugby athletes

Occurrence of and outcomes following a concussion are probably affected by the interaction of multiple genes in a polygenic manner [1,2]. This study investigated whether suspected concussion-associated polygenic profiles of elite rugby athletes with a history of previous concussion (RAC) differed from rugby athletes with no history of previous concussion (RANC). We hypothesised that concussion-associated risk genotypes would be underrepresented in RANC compared to RAC. Participants were from the RugbyGene project, comprising elite male rugby athletes (RA) (185 white males; mean (standard deviation) height 1.86 (0.07) m, mass 102 (12.6) kg, age 26.4 (5.1) yr) competing at an elite level in rugby union (n = 165) and league (n = 20) in the UK, Ireland, Italy and South Africa. Concussion history was collected using a self-reported concussion history questionnaire. PCR of genomic DNA was used to determine genotypes using TaqMan probes, and total genotype scores (TGS) were calculated, then groups were compared using χ2 and odds ratio (OR) statistics. In addition, multifactor dimensionality reduction (MDR) was used to identify genetic interactions. Seventy-eight percent of RA reported a history of sustaining at least one concussion and 54% of RA reported sustaining multiple (≥2) concussions from rugby. For BDNF-AS rs6265, the GG genotype was more common in RAC compared to RANC (69.7% vs 61.0%, P = 0.006, OR = 9.90, 95% CI = 01.81-54.06) (Fig. 1). The GG genotype of BDNF-AS rs6265 was more common in RAC compared to RANC (70.7% vs. 61.0%, P = 0.041, OR 4.44, 95% CI = 1.04-120.97) (Fig. 1). However, TGS did not differ between RANC and RAC (Fig. 2A) recovery duration and family history of neurological conditions (P > 0.05). Receiver operating characteristic curve (ROC) and area under the curve (AUC) analysis confirmed the TGS algorithm could not identify concussion history (AUC = 0.436; 95% CI = 0.338-0.534; P = 0.218; Fig. 2B). MDR could not identify a model to predict concussion history, recovery duration and family history of neurological conditions with a sufficiently powerful cross-validation statistic (P ≤ 0.05). These findings support the growing evidence that incidence and recovery from concussion could be influenced by an athlete’s genetic predisposition. Such knowledge could be used in the future and when additional relevant variants have been identified, to inform individualised management strategies for athletes in possession of risk genotypes.Peer reviewe

Tendon and ligament-associated gene variants and history of soft tissue injury in elite male rugby athletes

There is a genetic component to tendon and ligament injuries which is highly likely to be polygenic in nature (1). Elite rugby has one of the highest reported injury incidences of any professional sport with some of the most severe injuries affecting tendons and ligaments (1). Thus, this study investigated if suspected tendon and ligament injury-associated polygenic profiles of elite rugby athletes (RA) with a history of prior tendon and ligament injury differed from RA with no history of injury. We hypothesised that tendon and ligament injury-associated genotypes and polygenic profiles would be overrepresented in RA with a history of soft tissue injury compared to RA with no history of injury. Participants were from the RugbyGene project, comprising elite male RA (185 white males; mean (standard deviation) height 1.86 (0.07) m, mass 102 (12.6) kg, age 26.4 (5.1) yr) competing at an elite level in rugby union (n = 165) and league (n = 20) in the UK, Ireland, Italy and South Africa. Soft-tissue injury history was collected using a self-reported injury history questionnaire. PCR of genomic DNA was used to determine genotypes using TaqMan probes, and total genotype scores (TGS) from 13 polymorphisms were calculated, then groups were compared using χ2 and odds ratio (OR) statistics. In addition, multifactor dimensionality reduction (MDR) and inferred haplotype analysis were used to identify genetic interactions. For MMP3 rs679620, the C allele was more common in the tendinopathy group (TD) compared to the non-injured tendon group (NIT) (63.5% vs 50.0%, P = 0.02, OR = 1.62, 95% CI = 01.00-2.60). However, the C allele was more common in the non-injured ligament group (NIL) compared to the ligament rupture (LR) group (63.7% v 47.9%, P = 0.02, OR = 1.91, 95% CI = 1.09-3.35). For COL5A1 rs12722 the TT genotype was more common in NIT compared to the tendon rupture group (TR) (25.0% vs. 3.8%, P = 0.006, OR 4.35, 95% CI = 0.49-37.01). TGS differed between NIL and the ligament sprain group (LS) (U=1868.50;P = 0.02). Receiver operating characteristic curve (ROC) and area under the curve (AUC) analysis confirmed the TGS algorithm could identify LS (AUC = 0.61; 95% CI = 0.52-0.72; P = 0.02) . The T-C inferred haplotype frequency of COL5A1 rs12722 and COL5A1 rs3196378 respectively, was higher in TR, LS and the all-injured athlete groups compared to NIT, NIL and the all-non-injured group (P < 0.01) (Fig. 3). MDR could not identify a model to predict any of the injury groups with a sufficiently powerful cross-validation statistic. The current data suggests musculoskeletal soft-tissue injury could be influenced by an athlete’s genetic predisposition. This study provides further insight into the detailed aetiology of musculoskeletal soft tissue injuries within elite rugby and may, in future, be worthy of consideration for managing the interindividual variability of injury risk in rugbyPeer reviewe

Interferometric Observations of RS Ophiuchi and the Origin of the Near-IR Emission

We report observations of the recurrent nova RS Oph using long-baseline near-IR interferometry. We are able to resolve emission from the nova for several weeks after the February 2006 outburst. The near-IR source initially expands to a size of approximately 5 milli-arcseconds. However, beginning around day 10 the IR source appears to begin to shrink, reaching approximately 2 milli-arcseconds by day 100. We combine our measured angular diameters with previously available interferometric and photometric data to derive an emission measure for the source, and hence are able to determine the mass-loss rate of the nova in the days following the outburst.Comment: 17 pages, 4 figures. Accepted for publication in Ap

Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status

Objective: Concussions are common match injuries in elite rugby, and reports exist of reduced cognitive function and long-term health consequences that can interrupt or end a playing career and produce continued ill health. The aim of this study was to investigate the association between elite rugby status and 8 concussion-associated risk polymorphisms. We hypothesized that concussion-associated risk genotypes and alleles would be underrepresented in elite rugby athletes compared with nonathletes. Design: A case-control genetic association study.Setting:  Institutional (university). Participants: Elite White male rugby athletes [n = 668, mean (SD) height 1.85 (0.07) m, mass 102 (12) kg, and age 29 (7) years] and 1015 nonathlete White men and women (48% men). Interventions: Genotype was the independent variable, obtained by PCR of genomic DNA using TaqMan probes.Main Outcome Measure:  Elite athlete status with groups compared using χ2 and odds ratio (OR). Results: The COMT rs4680 Met/Met (AA) genotype, Met allele possession, and Met allele frequency were lower in rugby athletes (24.8%, 74.6%, and 49.7%, respectively) than nonathletes (30.2%, 77.6%, and 54.0%; P &lt; 0.05). The Val/Val (GG) genotype was more common in elite rugby athletes than nonathletes (OR 1.39, 95% confidence interval 1.04-1.86). No other polymorphism was associated with elite athlete status. Conclusions: Elite rugby athlete status is associated with COMT rs4680 genotype that, acting pleiotropically, could affect stress resilience and behavioral traits during competition, concussion risk, and/or recovery from concussion. Consequently, assessing COMT rs4680 genotype might aid future individualized management of concussion risk among athletes.

Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes

Due to the high-velocity collision-based nature of elite rugby league and union, the risk of sustaining a concussion is high. Occurrence of and outcomes following a concussion are probably affected by the interaction of multiple genes in a polygenic manner. This study investigated whether suspected concussion-associated polygenic profiles of elite rugby athletes differed from non-athletes and between rugby union forwards and backs. We hypothesised that a total genotype score (TGS) using eight concussion-associated polymorphisms would be higher in elite rugby athletes than non-athletes, indicating selection for protection against incurring or suffering prolonged effects of, concussion in the relatively high-risk environment of competitive rugby. In addition, multifactor dimensionality reduction was used to identify genetic interactions. Contrary to our hypothesis, TGS did not differ between elite rugby athletes and non-athletes (p ≥ 0.065), nor between rugby union forwards and backs (p = 0.668). Accordingly, the TGS could not discriminate between elite rugby athletes and non-athletes (AUC ~0.5), suggesting that, for the eight polymorphisms investigated, elite rugby athletes do not have a more ‘preferable’ concussion-associated polygenic profile than non-athletes. However, the COMT (rs4680) and MAPT (rs10445337) GC allele combination was more common in rugby athletes (31.7%; p < 0.001) and rugby union athletes (31.8%; p < 0.001) than non-athletes (24.5%). Our results thus suggest a genetic interaction between COMT (rs4680) and MAPT (rs10445337) assists rugby athletes in achieving elite status. These findings need exploration vis-à-vis sport-related concussion injury data and could have implications for the management of inter-individual differences in concussion risk

How society’s negative view of videogames can discourage brands from sponsoring eSports

The purpose of this research was to identify the main motives that contribute to society’s negative view of videogames and that present a risk to the eSports sponsors’ image. To achieve this, an exploratory, qualitative, and integrative literature review was conducted. According to the theoretical data, there are four main reasons why society has a negative perception of videogames. It is commonly believed that: (1) gaming is an unproductive activity, (2) violent videogames incite aggressive behaviors, (3) videogames lead to gaming-addiction, and (4) eSports lead to eSports-related gambling addiction. However, while the literature presents convincing evidence that gaming can create addiction and that eSports can promote gambling addiction, there is no conclusive evidence to assume that violent videogames lead to aggressiveness and there is evidence showing that playing videogames can be a productive activity. Nevertheless, these four beliefs are a threat to the eSports sponsors’ image and may lead them to cancel their existing sponsorships or lead other brands to not want to sponsor eSports to prevent being associated with these negative notions. This research will help expand the minor literature on eSports sponsorships and advance the knowledge of why some eSports sponsorships are terminated and why some brands may be reluctant to sponsor eSports.info:eu-repo/semantics/publishedVersio

Best practice in psychological activities in cardiovascular prevention and rehabilitation: Position Paper

Recent guidelines on cardiovascular disease prevention suggest multimodal behavioral interventions for psychosocial risk factors and referral for psychotherapy in the case of clinically significant symptoms of depression and anxiety overall. Accordingly, psychologists of the Italian Association for Cardiovascular Prevention, Rehabilitation and Epidemiology (GICR-IACPR) have reviewed the key components of psychological activities in cardiovascular prevention and rehabilitation (CPR). The aim of this study was to elaborate a position paper on the best practice in routine psychological activities in CPR based on efficacy, effectiveness and sustainability. The steps followed were: i) a review of the latest international guidelines and position papers; ii) analysis of the evidence-based literature; iii) a qualitative analysis of the psychological services operating in some reference Italian cardiac rehabilitation facilities; iv) classification of the psychological activities in CPR as low or high intensity based on the NICE Guidelines on psychological interventions on anxiety and depression. We confirm the existence of an association between depression, anxiety, social factors, stress, personality and illness onset/outcome and coronary heart disease. Evidence for an association between depression, social factors and disease outcome emerges particularly for chronic heart failure. Some positive psychological variables (e.g., optimism) are associated to illness outcome. Evidence is reported on the impact of psychological activities on \u2018new\u2019 conditions which are now indicated for cardiac rehabilitation: pulmonary hypertension, grown-up congenital heart, end-stage heart failure, implantable cardioverter-defribrillator and mechanical ventricular assist devices, frail and oldest-old patients, and end-of-life care. We also report evidence related to caregivers. The Panel divided evidence-based psychological interventions into: i) low intensity (counseling, psycho-education, self-care, self-management, telemedicine, self-help); or ii) high intensity (individual, couples and/or family and group psychotherapy, such as stress management). The results show that psychotherapy is mainly consisting of cognitive-behavior therapy, interpersonal therapy, and short-term psycho-dynamic therapy. The current data further refine the working tools available for psychological activities in CPR, giving clear directions about the choice of interventions, which should be evidence-based and have at least a minimum standard. This document provides a comprehensive update on new knowledge and new paths for psychologists working in the CPR settings

Gene Variants Previously Associated with Reduced Soft-Tissue Injury Risk: Part 2 - Polygenic Associations with Elite Status in Rugby

Part 1 of this genetic association series highlighted several genetic variants independently associated with elite status in rugby. However, it is highly likely that the genetic influence on elite status is polygenic due to the interaction of multiple genes. Therefore, the aim of the present study was to investigate whether polygenic profiles of elite rugby athletes differed from non-athletes utilising 13 genetic polymorphisms previously associated with tendon/ligament injury. Total genotype score (TGS) was calculated and multifactor dimensionality reduction (MDR) was used to calculate SNP-SNP epistasis interactions. Based on our elite rugby data from Part 1, mean TGS was significantly higher in elite rugby athletes (52.1 ± 10.7) than non-athletes (48.7 ± 10.8). There were more elite rugby athletes (54%) within the upper TGS quartile, and fewer (46%) within the lower quartile, compared to non-athletes (31% and 69%, respectively; P = 5·10-5), and the TGS was able to distinguish between elite rugby athletes and non-athletes (area under the curve = 0.59; 95% confidence interval 0.55-0.63; P = 9·10-7). Furthermore, MDR identified a three-SNP model of COL5A1 rs12722, COL5A1 rs3196378 and MIR608 rs4919510 that was best able to predict elite athlete status, with a greater frequency of the CC-CC-CC genotype combination in elite rugby athletes (9.8%) than non-athletes (5.3%). We propose that elite rugby athletes possess ‘preferable’ musculoskeletal soft-tissue injury-associated polygenic profiles that have helped them achieve success in the high injury risk environment of rugby. These data may, in future, have implications for the individual management of musculoskeletal soft-tissue injury

The JAK-STAT Pathway Controls Plasmodium vivax Load in Early Stages of Anopheles aquasalis Infection

Malaria affects 300 million people worldwide every year and 450,000 in Brazil. In coastal areas of Brazil, the main malaria vector is Anopheles aquasalis, and Plasmodium vivax is responsible for the majority of malaria cases in the Americas. Insects possess a powerful immune system to combat infections. Three pathways control the insect immune response: Toll, IMD, and JAK-STAT. Here we analyze the immune role of the A. aquasalis JAK-STAT pathway after P. vivax infection. Three genes, the transcription factor Signal Transducers and Activators of Transcription (STAT), the regulatory Protein Inhibitors of Activated STAT (PIAS) and the Nitric Oxide Synthase enzyme (NOS) were characterized. Expression of STAT and PIAS was higher in males than females and in eggs and first instar larvae when compared to larvae and pupae. RNA levels for STAT and PIAS increased 24 and 36 hours (h) after P. vivax challenge. NOS transcription increased 36 h post infection (hpi) while this protein was already detected in some midgut epithelial cells 24 hpi. Imunocytochemistry experiments using specific antibodies showed that in non-infected insects STAT and PIAS were found mostly in the fat body, while in infected mosquitoes the proteins were found in other body tissues. The knockdown of STAT by RNAi increased the number of oocysts in the midgut of A. aquasalis. This is the first clear evidence for the involvement of a specific immune pathway in the interaction of the Brazilian malaria vector A. aquasalis with P. vivax, delineating a potential target for the future development of disease controlling strategies