Cell-Cycle Dependence of Transcription Dominates Noise in Gene Expression

The large variability in mRNA and protein levels found from both static and dynamic measurements in single cells has been largely attributed to random periods of transcription, often occurring in bursts. The cell cycle has a pronounced global role in affecting transcriptional and translational output, but how this influences transcriptional statistics from noisy promoters is unknown and generally ignored by current stochastic models. Here we show that variable transcription from the synthetic tetO promoter in S. cerevisiae is dominated by its dependence on the cell cycle. Real-time measurements of fluorescent protein at high expression levels indicate tetO promoters increase transcription rate ~2-fold in S/G2/M similar to constitutive genes. At low expression levels, where tetO promoters are thought to generate infrequent bursts of transcription, we observe random pulses of expression restricted to S/G2/M, which are correlated between homologous promoters present in the same cell. The analysis of static, single-cell mRNA measurements at different points along the cell cycle corroborates these findings. Our results demonstrate that highly variable mRNA distributions in yeast are not solely the result of randomly switching between periods of active and inactive gene expression, but instead largely driven by differences in transcriptional activity between G1 and S/G2/M.GM095733BBBE 103316MIT Startup Fun

Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systematic review and meta-analysis

Background: Cancer-related fatigue (CRF) is the most common and distressing symptom in breast cancer survivors. Approximately 40% to 80% of cancer patients undergoing active treatment suffer from CRF. Exercise improves overall quality of life and CRF; however, the specific effects of the training modalities are not well understood.Methods: This study aimed to determine the pooled effects of supervised exercise interventions on CRF in breast cancer survivors. We searched PubMed/MEDLINE, EMBASE, Scopus, CENTRAL and CINAHL databases between December 2013 and January 2014 without language restrictions. Risk of bias and methodological quality were evaluated using the PEDro score. Pooled effects were calculated with a random-effects model according to the DerSimonian and Laird method. Heterogeneity was evaluated with the I2 test.Results: Nine high-quality studies (n = 1156) were finally included. Supervised aerobic exercise was statistically more effective than conventional care in improving CRF among breast cancer survivors (SMD = −0.51, 95%CI −0.81 to −0.21), with high statistical heterogeneity (P = 0.001; I2 = 75%). Similar effects were found for resistance training on CRF (SMD = −0.41, 95%CI −0.76 to −0.05; P = 0.02; I2 = 64%). Meta-regression analysis revealed that exercise volume parameters are closely related with the effect estimates on CRF. Egger’s test suggested moderate evidence of publication bias (P = 0.04).Conclusions: Supervised exercise reduces CRF and must be implemented in breast cancer rehabilitation settings. High-volume exercises are safe and effective in improving CRF and overall quality of life in women with breast cancer. Further research is encouraged.The authors would like to acknowledge Universidad Santo Tomás, Bogotá for the financial support to the GICAEDS Group (Project: Práctica del autoexamen de seno y los conocimientos, factores de riesgo y estilos de vida relacionados al cáncer de mama en mujeres jóvenes de la USTA – Number: 4110060001-008)

Associations between aerobic exercise levels and physical and mental health outcomes in men with bone metastatic prostate cancer: a cross-sectional investigation.

Cancer patients with bone metastases have previously been excluded from participation in physical activity programmes due to concerns of skeletal fractures. Our aim was to provide initial information on the association between physical activity levels and physical and mental health outcomes in prostate cancer patients with bone metastases. Between 2012 and 2015, 55 prostate cancer patients (mean age 69.7 ± 8.3; BMI 28.6 ± 4.0) with bone metastases (58.2% >2 regions affected) undertook assessments for self-reported physical activity, physical and mental health outcomes (SF-36), objective physical performance measures and body composition by DXA. Sixteen men (29%) met the current aerobic exercise guidelines for cancer survivors, while 39 (71%) reported lower aerobic exercise levels. Men not meeting aerobic exercise guidelines had lower physical functioning (p = .004), role functioning (physical and emotional) (p < .05), general health scores (p = .014) as well all lower measures of physical performance (p < .05). Lower levels of aerobic exercise are associated with reduced physical and mental health outcomes in prostate cancer patients with bone metastases. While previous research has focused primarily in those with non-metastatic disease, our initial results suggest that higher levels of aerobic exercise may preserve physical and mental health outcomes in prostate cancer patients with bone metastases. Clinical Trial Registry: Trial Registration: ACTRN12611001158954

Quality of Life and Symptom Burden Improve in Patients Attending a Multidisciplinary Clinical Service for Cancer Cachexia: A Retrospective Observational Review.

Background Cancer cachexia negatively affects quality of life (QoL) and increases symptom burden. A multimodal treatment approach may optimize cachexia outcomes, including QoL. We evaluated QoL and symptoms over time among patients attending a multidisciplinary clinical service for cancer cachexia. Methods Adults with cancer who attended the clinical service three times between 2017 and 2020 were included. Quality of life and symptoms were assessed using the European Organization for Research and Treatment of Cancer Quality of life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL) and the Functional Assessment Anorexia/Cachexia Therapy (FAACT) questionnaires. Physical function was assessed using the 30s sit-to-stand test and handgrip strength. Results Overall, 162 patients (age = 67.2 ± 12.0 years) were included. Mean six-month weight loss at baseline was 10.4% ± 9.4%. Mean body weight was stable between clinic visits (P = 0.904) and no change in sit-to-stand repetitions (P = 0.133) or handgrip strength (P = 0.734) occurred over time. Improvements in EORTC QLQ-C15-PAL overall QoL (Δ10.7 ± 2.5, P < 0.001), physical function (Δ8.0 ± 2.4, P = 0.003) and emotional function (Δ11.4 ± 2.9, P < 0.001) occurred by the second visit. EORTC QLQ-C15-PAL fatigue (Δ13.8 ± 2.9, P < 0.001), pain (Δ10.3 ± 3.3, P = 0.007), nausea/vomiting (Δ16.1 ± 3.0, P < 0.001) and appetite symptoms (Δ25.9 ± 3.8, P < 0.001) also improved by the second visit. FAACT total score (Δ14.6 ± 2.7, P < 0.001), anorexia-cachexia symptoms (Δ6.6 ± 1.1, P< 0.001), and physical (Δ3.7 ± 0.70, P < 0.001), emotional (Δ1.9 ± 0.60, P = 0.005) and functional wellbeing (Δ2.7 ± 0.71, P = 0.001) improved by the second visit. All improvements in EORTC QLQ-C15-PAL and FAACT outcomes were maintained at the third visit. Conclusion Significant improvements in QoL and symptoms were associated with attending a cancer cachexia clinical service. Our findings support using multidisciplinary, multimodal cancer cachexia treatment approaches to improve patient wellbeing

Black root rot: a long known but little understood disease

Table S1. Hosts reported to be susceptible to black root rot infection.Table S2. Variation in host susceptibility to black root rot infection by the fungus formally known as Thielaviopsis basicola.Black root rot caused by the pathogen Thielaviopsis basicola has been known since the mid 1800s. The disease is important on many agricultural and ornamental plant species and has been found in at least 31 countries. Since its description, the pathogen has had a complex taxonomic history that has resulted in a confused literature. A recent revision of the Ceratocystidaceae following the advent of DNA sequencing technology has made it possible to resolve this confusion. Importantly, it has also shown that there are two pathogens in the Ceratocystidaceae that cause black root rot. They reside in the newly established genus Berkeleyomyces and are now known as B. basicola and B. rouxiae. This review considers the taxonomic history of the black root rot pathogens, and their global distribution. Prospects relating to the serious diseases that they cause and the likely impact that the era of genomics will have on our understanding of the pathogens are also highlighted.The University of Pretoria, the members of Tree Protection Co‐operative Programme (TPCP), the DST‐NRF Centre of Excellence in Tree Health Biotechnology (CTHB) and the National Research Foundation.https://onlinelibrary.wiley.com/journal/136530592020-06-01hj2019BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog