Pds5p regulates the maintenance of sister chromatid cohesion and is sumoylated to promote the dissolution of cohesion

Pds5p and the cohesin complex are required for sister chromatid cohesion and localize to the same chromosomal loci over the same cell cycle window. However, Pds5p and the cohesin complex likely have distinct roles in cohesion. We report that pds5 mutants establish cohesion, but during mitosis exhibit precocious sister dissociation. Thus, unlike the cohesin complex, which is required for cohesion establishment and maintenance, Pds5p is required only for maintenance. We identified SMT4, which encodes a SUMO isopeptidase, as a high copy suppressor of both the temperature sensitivity and precocious sister dissociation of pds5 mutants. In contrast, SMT4 does not suppress temperature sensitivity of cohesin complex mutants. Pds5p is SUMO conjugated, with sumoylation peaking during mitosis. SMT4 overexpression reduces Pds5p sumoylation, whereas smt4 mutants have increased Pds5p sumoylation. smt4 mutants were previously shown to be defective in cohesion maintenance during mitosis. These data provide the first link between a protein required for cohesion, Pds5p, and sumoylation, and suggest that Pds5p sumoylation promotes the dissolution of cohesion

Intrinsically disordered regions of tristetraprolin and DCP2 directly interact to mediate decay of ARE-mRNA

The RNA-binding protein tristetraprolin (TTP) is a potent activator of mRNA decay, specifically for transcripts bearing AU-rich elements (AREs) in their 3′-untranslated regions. TTP functions as a mediator for mRNA decay by interacting with the decay machinery and recruiting it to the target ARE-mRNA. In this study, we report a weak, but direct interaction between TTP and the human decapping enzyme DCP2, which impacts the stability of ARE transcripts. The TTP–DCP2 interaction is unusual as it involves intrinsically disordered regions (IDRs) of both binding partners. We show that the IDR of DCP2 has a propensity for oligomerization and liquid–liquid phase separation in vitro. Binding of TTP to DCP2 leads to its partitioning into phase-separated droplets formed by DCP2, suggesting that molecular crowding might facilitate the weak interaction between the two proteins and enable assembly of a decapping-competent mRNA–protein complex on TTP-bound transcripts in cells. Our studies underline the role of weak interactions in the cellular interaction network and their contribution towards cellular functionality

Molecular typing reveals substantial Plasmodium vivax infection in asymptomatic adults in a rural area of Cameroon

BACKGROUND: Malaria in Cameroon is due to infections by Plasmodium falciparum and, to a lesser extent, Plasmodium malariae and Plasmodium ovale, but rarely Plasmodium vivax. A recent report suggested “Plasmodium vivax–like” infections around the study area that remained unconfirmed. Therefore, molecular and antigenic typing was used to investigate the prevalence of P. vivax and Duffy in asymptomatic adults resident in Bolifamba. METHODS: A cross-sectional study was conducted from July 2008 to October 2009. The status of all parasite species was determined by nested PCR in 269 blood samples collected. The P. falciparum and P. vivax anti-MSP/CSP antibody status of each subject was also determined qualitatively by a rapid card assay. Parasite DNA was extracted from a sample infected with three parasite species, purified and sequenced. The Duffy antigen status of 12 subjects infected with P. vivax was also determined by sequencing. In silico web-based tools were used to analyse sequence data for similarities and matches to reference sequences in public DNA databases. RESULTS: The overall malaria parasite prevalence in 269 individuals was 32.3% (87) as determined by PCR. Remarkably, 14.9% (13/87) of infections were caused either exclusively or concomitantly by P. vivax, established both by PCR and microscopic examination of blood smears, in individuals both positive (50%, 6/12) and negative (50%, 6/12) for the Duffy receptor. A triple infection by P. falciparum, P. vivax and P. malariae, was detected in one infected individual. Anti-MSP/CSP antibodies were detected in 72.1% (194/269) of samples, indicating high and continuous exposure to infection through mosquito bites. DISCUSSION: These data provide the first molecular evidence of P. vivax in Duffy positive and negative Cameroonians and suggest that there may be a significant prevalence of P. vivax infection than expected in the study area. Whether the P. vivax cases were imported or due to expansion of a founder effect was not investigated. Notwithstanding, the presence of P. vivax may complicate control efforts if these parasites become hypnozoitic or latent as the liver stage. CONCLUSIONS: These data strongly suggest that P. vivax is endemic to the south-west region of Cameroon and should be taken into account when designing malaria control strategies

The Role of Immune Checkpoint Blockade in Uveal Melanoma

Uveal melanoma (UM) represents the most common intraocular malignancy in adults and accounts for about 5% of all melanomas. Primary disease can be effectively controlled by several local therapy options, but UM has a high potential for metastatic spread, especially to the liver. Despite its clinical and genetic heterogeneity, therapy of metastatic UM has largely been adopted from cutaneous melanoma (CM) with discouraging results until now. The introduction of antibodies targeting CTLA-4 and PD-1 for immune checkpoint blockade (ICB) has revolutionized the field of cancer therapy and has achieved pioneering results in metastatic CM. Thus, expectations were high that patients with metastatic UM would also benefit from these new therapy options. This review provides a comprehensive and up-to-date overview on the role of ICB in UM. We give a summary of UM biology, its clinical features, and how it differs from CM. The results of several studies that have been investigating ICB in metastatic UM are presented. We discuss possible reasons for the lack of efficacy of ICB in UM compared to CM, highlight the pitfalls of ICB in this cancer entity, and explain why other immune-modulating therapies could still be an option for future UM therapies

Bioinformatics for RNA‐Seq Data Analysis

While RNA sequencing (RNA‐seq) has become increasingly popular for transcriptome profiling, the analysis of the massive amount of data generated by large‐scale RNA‐seq still remains a challenge. RNA‐seq data analyses typically consist of (1) accurate mapping of millions of short sequencing reads to a reference genome, including the identification of splicing events; (2) quantifying expression levels of genes, transcripts, and exons; (3) differential analysis of gene expression among different biological conditions; and (4) biological interpretation of differentially expressed genes. Despite the fact that multiple algorithms pertinent to basic analyses have been developed, there are still a variety of unresolved questions. In this chapter, we review the main tools and algorithms currently available for RNA‐seq data analyses, and our goal is to help RNA‐seq data analysts to make an informed choice of tools in practical RNA‐seq data analysis. In the meantime, RNA‐seq is evolving rapidly, and newer sequencing technologies are briefly introduced, including stranded RNA‐seq, targeted RNA‐seq, and single‐cell RNA‐seq

Amateur and Recreational Athletes’ Motivation to Exercise, Stress, and Coping During the Corona Crisis

The COVID-19 pandemic has negatively impacted mobility worldwide. As a corollary, the health of top- and lower-level athletes alike is profoundly reliant on movement and exercise. Thus, the aim of this study is to understand impacts of the COVID-19 pandemic lockdown on athletes’ motivation to exercise and train. In detail, we aim to better understand who (i.e., demographic, sport-specific, and psychological state and trait variables) reported a change in motivation to train due to the lockdown, why they reported lower motivation (i.e., open-ended questions on problems), what they did to help themselves, what support they received from others, and what they are looking forward to after the lockdown (i.e., open questions). Questionnaire data and answers to these open-ended questions were assessed via an online questionnaire, completed by 95 amateur and recreational athletes during the first COVID-19 lockdown in Germany (April to mid-May 2020). Results show that greater numbers of female athletes are less motivated to train in comparison to male athletes (p = 0.029). No differences in motivation were found regarding type of sport (individual vs. team sport) and number of competitions during the year. Also, more motivated to train amateur and recreational athletes showed lower athletic identity than athletes who reported no change in motivation to exercise during the lockdown (p = 0.03). Additionally, differences in state emotional, perceived stress, and personality variables (i.e., orientation to happiness, volition) were found between athletes who stated that they were less motivated to train compared to athletes who reported no changes in motivation. In particular, closure of sports facilities and social distancing measures were perceived to be highly problematic. Even though athletes received emotional support, organized themselves via routines and schedules, and trained using online tools, they predominately stated that they wished that their coaches would have supported them more. Understanding the impacts of a pandemic-related lockdown on athletes’ motivation, athletes’ coping strategies, and their desired support will help better support them in future crises

Airborne RF Measurement System and Analysis of Representative Flight RF Environment

Environmental radio frequency (RF) data over a broad band of frequencies were needed to evaluate the airspace around several airports. An RF signal measurement system was designed using a spectrum analyzer connected to an aircraft VHF/UHF navigation antenna installed on a small aircraft. This paper presents an overview of the RF measurement system and provides analysis of a sample of RF signal measurement data over a frequency range of 30 MHz to 1000 MHz

Predictors of potentially suboptimal treatment of urinary tract infections in long-term care facilities

Background: Suboptimal antibiotic treatment of urinary tract infection (UTI) is high in long-term care facilities (LTCFs) and likely varies between facilities. Large-scale evaluations have not been conducted. Aim: To identify facility-level predictors of potentially suboptimal treatment of UTI in Veterans Affairs (VA) LTCFs and to quantify variation across facilities. Methods: This was a retrospective cohort study of 21,938 residents in 120 VA LTCFs (2013–2018) known as Community Living Centers (CLCs). Potentially suboptimal treatment was assessed from drug choice, dose frequency, and/or treatment duration. To identify facility characteristics predictive of suboptimal UTI treatment, LTCFs with higher and lower rates of suboptimal treatment (≥median, \u3c median) were compared using unconditional logistic regression models. Joinpoint regression models were used to quantify average percentage difference across facilities. Multilevel logistic regression models were used to quantify variation across facilities. Findings: The rate of potentially suboptimal antibiotic treatment varied from 1.7 to 34.2 per 10,000 bed-days across LTCFs. The average percentage difference in rates across facilities was 2.5% (95% confidence interval (CI): 2.4–2.7). The only facility characteristic predictive of suboptimal treatment was the incident rate of UTI per 10,000 bed-days (odds ratio: 4.9; 95% CI: 2.3–10.3). Multilevel models demonstrated that 94% of the variation between facilities was unexplained after controlling for resident and CLC characteristics. The median odds ratio for the full multilevel model was 1.37. Conclusion: Potentially suboptimal UTI treatment was variable across VA LTCFs. However, most of the variation across LTCFs was unexplained. Future research should continue to investigate factors that are driving suboptimal antibiotic treatment in LTCFs