TRIM28-Regulated Transposon Repression Is Required for Human Germline Competency and Not Primed or Naive Human Pluripotency.

Transition from primed to naive pluripotency is associated with dynamic changes in transposable element (TE) expression and demethylation of imprinting control regions (ICRs). In mouse, ICR methylation and TE expression are each regulated by TRIM28; however, the role of TRIM28 in humans is less clear. Here, we show that a null mutation in TRIM28 causes significant alterations in TE expression in both the naive and primed states of human pluripotency, and phenotypically this has limited effects on self-renewal, instead causing a loss of germline competency. Furthermore, we discovered that TRIM28 regulates paternal ICR methylation and chromatin accessibility in the primed state, with no effects on maternal ICRs. Taken together, our study shows that abnormal TE expression is tolerated by self-renewing human pluripotent cells, whereas germline competency is not

Local Magnetic Field Role in Star Formation

We highlight distinct and systematic observational features of magnetic field morphologies in polarized submm dust continuum. We illustrate this with specific examples and show statistical trends from a sample of 50 star-forming regions.Comment: 4 pages, 3 figures; to appear in the EAS Proceedings of the 6th Zermatt ISM Symposium "Conditions and Impact of Star Formation from Lab to Space", September 201

Cross-reactivities and cross-neutralization of different envelope glycoproteins E2 antibodies against different genotypes of classical swine fever virus

Classical swine fever (CSF) is a highly contagious swine disease caused by the classical swine fever virus (CSFV), wreaking havoc on global swine production. The virus is divided into three genotypes, each comprising 4–7 sub-genotypes. The major envelope glycoprotein E2 of CSFV plays an essential role in cell attachment, eliciting immune responses, and vaccine development. In this study, to study the cross-reaction and cross-neutralizing activities of antibodies against different genotypes (G) of E2 glycoproteins, ectodomains of G1.1, G2.1, G2.1d, and G3.4 CSFV E2 glycoproteins from a mammalian cell expression system were generated. The cross-reactivities of a panel of immunofluorescence assay-characterized serum derived from pigs with/without a commercial live attenuated G1.1 vaccination against different genotypes of E2 glycoproteins were detected by ELISA. Our result showed that serum against the LPCV cross-reacted with all genotypes of E2 glycoproteins. To evaluate cross-neutralizing activities, hyperimmune serum from different CSFV E2 glycoprotein-immunized mice was also generated. The result showed that mice anti-E2 hyperimmune serum exhibited better neutralizing abilities against homologous CSFV than heterogeneous viruses. In conclusion, the results provide information on the cross-reactivity of antibodies against different genogroups of CSFV E2 glycoproteins and suggest the importance of developing multi-covalent subunit vaccines for the complete protection of CSF

The effectiveness of adjunct mindfulness-based intervention in treatment of bipolar disorder: A systematic review and meta-analysis

BACKGROUND: Mindfulness-based interventions (MBIs) have been increasingly used as an adjunctive treatment to pharmacotherapy for a few psychiatric disorders. However, few studies have investigated the efficacy of MBIs in bipolar disorder (BD). METHODS: We performed a systematic review and meta-analysis to evaluate the efficacy of MBIs as an adjunctive treatment in BD. Major electronic databases were independently searched by two authors for controlled and uncontrolled studies which examined the effects of MBIs on psychiatric symptoms in subjects with BD. Data from original studies were synthesized by using a random effects model. RESULTS: Twelve trials were eligible for inclusion into current meta-analysis, including three controlled studies (n=132) and nine uncontrolled studies (n=142). In within-group analysis, MBIs significantly reduced depressive (7 studies, n=100, Hedges' g=0.58, p<0.001) and anxiety (4 studies, n=68, Hedges' g=0.34, p=0.043) symptoms, but not manic symptoms (6 studies, n=89, Hedges' g=0.09, p=0.488) and cognition (3 studies, n=43, Hedges' g=0.35, p=0.171), compared to baseline. In between-group analysis (intervention group versus waiting list group, all patients with BD), MBIs did not reduce depressive (3 studies, n=132, Hedges' g=0.46, p=0.315) or anxiety (3 studies, n=132, Hedges' g=0.33, p=0.578) symptoms. LIMITATIONS: Only three controlled trials compared MBIs to control conditions. CONCLUSIONS: Our meta-analysis showed significantly beneficial effects on depressive and anxiety symptoms of BD patients in within-group analysis. However, this significance was not observed in comparison with the control groups. Further clinical trials are warranted to investigate the differences in the benefits of MBIs between treatment and control subjects

Do beta-adrenergic blocking agents increase asthma exacerbation? A network meta-analysis of randomized controlled trials

Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma exacerbation is one of the major adverse effects of beta-blockers. This study aimed to compare the level of risk for an asthma attack in patients receiving various beta-blockers. We searched for randomized controlled trials (RCTs) of either placebo-controlled or active-controlled design. The current network meta-analysis (NMA) was conducted under a frequentist model. The primary outcome was the incidence of asthmatic attack. A total of 24 RCTs were included. Overall NMA revealed that only oral timolol [risk ratio (RR) = 3.35 (95% confidence interval (CI) 1.04–10.85)] and infusion of propranolol [RR = 10.19 (95% CI 1.29–80.41)] were associated with significantly higher incidences of asthma attack than the placebo, whereas oral celiprolol [RR = 0.39 (95% CI 0.04–4.11)], oral celiprolol and propranolol [RR = 0.46 (95% CI 0.02–11.65)], oral bisoprolol [RR = 0.46 (95% CI 0.02–11.65)], oral atenolol [RR = 0.51 (95% CI 0.20–1.28)], infusion of practolol [RR = 0.80 (95% CI 0.03–25.14)], and infusion of sotalol [RR = 0.91 (95% CI 0.08–10.65)] were associated with relatively lower incidences of asthma attack than the placebo. In participants with a baseline asthma history, in addition to oral timolol and infusion of propranolol, oral labetalol, oxprenolol, propranolol, and metoprolol exhibited significantly higher incidences of asthma attack than did the placebo. In conclusion, oral timolol and infusion of propranolol were associated with a significantly higher risk of developing an asthma attack in patients, especially in those with a baseline asthma history, and should be avoided in patients who present a risk of asthma

Low peripheral levels of insulin growth factor-1 are associated with high incidence of delirium among elderly patients: A systematic review and meta-analysis

Introduction: Delirium, a serious condition observed in critically ill patients, clinically presents with impaired cognition and consciousness. The relationship between delirium and peripheral levels of insulin growth factor-1 (IGF-1) is unclear. Thus we conducted a meta-analysis to address this issue. Methods: Seven major electronic databases were searched from inception until October 2, 2017 to obtain relevant clinical variables to compare the difference in IGF-1 levels between delirious and non-delirious elderly in-patients. A random effects meta-analysis was conducted. Results: We studies 10 articles involving 294 delirious patients (mean age 73.0 years) and 604 non-delirious patients (mean age 76.9 years). We found that peripheral levels of IGF-1 in patients with delirium were significantly lower than in those without delirium (Hedges‘ g = −0.209, 95% confidence interval [CI] = −0.393 to −0.026, p = 0.025). Meta-regression analyses found that no variables such as percentage of cognitive impairment, mean age, and female proportion contribute to heterogeneity in terms of the entire population. Conclusions: Our data suggests that lower peripheral levels of IGF-1 could be associated with a higher incidence of delirium among elderly patients. Further prospective studies with larger sample sizes are needed to investigate the association between peripheral levels of IGF-1 and delirium

Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells

Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs and illuminates the comprehensive, interconnected, and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome