Rates of mRNA synthesis and decay can be measured on a genome-wide scale in yeast by dynamic transcriptome analysis (DTA), which combines non-perturbing metabolic RNA labeling with dynamic kinetic modeling.DTA reveals that most mRNA synthesis rates are around several transcripts per cell and cell cycle, and most mRNA half-lives range around a median of 11 min.DTA realistically monitors the cellular response to osmotic stress with higher sensitivity and temporal resolution than transcriptomics, and can be used to follow changes in RNA metabolism in gene regulatory systems.
Background: Mediator is a general coactivator complex for regulated RNA polymerase II transcription. Results: Mediator is phosphorylated on most subunits, and phosphorylation can contribute to function. Conclusion: Post-translational modifications of a transcription coactivator can contribute to its function in gene regulation. Significance: Transcription coactivators can be strongly modified post-translationally, and this can contribute to function.
265 Background: Healthcare delivery via telemedicine has increased substantially amid COVID-19. The George Washington Cancer Center (GWCC) now provides cancer care services via tele-visits for patients at high risk of morbidity and mortality secondary to COVID-19. This study was performed to assess usability of virtual cancer care delivery for patients and providers across specialties. Methods: Participants included patients and providers surveyed to assess baseline usability after initiating tele-visits. Surveys included demographics, Telehealth Usability Questionnaire (TUQ), and questions on perceived safety and preferences around telemedicine. Subjects also provided open-ended feedback for quality improvement. Results: For patients (n = 105), 96% of surveys sent were completed and analyzed. Most patients were ages 50-59 (22%), 60-69 (25%), 70-79 (25%). Breast cancer (38%) was the most commonly reported cancer type. Median patient TUQ scores were: 5/5 for Interaction Quality (ItQ) and Ease of Use (EU), 4/5 for Usefulness (U), Interface Quality (IfQ) and Satisfaction (S), and 3/5 for Reliability (R). No association was found between TUQ scores and age groups (p = 0.15), sex (p = 0.69), or timing of diagnosis in relation to telemedicine visit (p = 0.67). Compared to in-person visits, 70% of patients agreed/strongly agreed that telemedicine made them feel safer, 63% agreed/strongly agreed that it reduced stress, and 59% expressed interest in using it with other medical specialties. For providers (n = 85), 88% of surveys sent were completed and analyzed. Most providers were ages 30-39 (37%), 50-59 (23%), and 47% had 50 or more experiences with telemedicine. The predominant specialty participating was Internal Medicine (31%). Median provider TUQ scores were 4/5 for ItQ, EU, U, IfQ and S, and 2/5 for R. No association was found between TUQ scores and experience with telemedicine (p = 0.31), though providers aged 60-79 had significantly more negative views of telemedicine (p = 0.02) as compared to other age groups. The majority (97%) agreed/strongly agreed that telemedicine improves access to care, yet 57% expressed concern about missing something they may have caught in person. Conclusions: The use of telemedicine in cancer care was perceived favorably by patients and providers. All patient groups scored highly on perceived safety, reduced stress and improved access, independently of subject characteristics. Providers demonstrated some dissent, particularly in older age groups. These findings provide a useful benchmark for advancement of virtual care delivery in cancer care.
Objectives: Out-of-hospital cardiac arrest (OHCA) is associated with excessively high mortality rates. Recent studies suggest benefits from extracorporeal cardiopulmonary resuscitation (ECPR) performed in selected patients. We sought to present the first results from our interdisciplinary ECPR program with a particular focus on early outcomes and potential risk factors associated with in-hospital mortality. Methods: Between January 2016 and December 2019, 44 patients who underwent ECPR selected according to our institutional ECPR protocol were retrospectively analyzed regarding pre-hospital, in-hospital, and early outcome parameters. Patients were divided into survivors (S) and non-survivors (NS). Statistical analysis of risk factors regarding in-hospital mortality of the patient cohort analyzed was performed. Results: The mean age of the population was 53 ± 12 years, with most patients being male ( n = 40). The leading cause of cardiac arrest (CA) was myocardial infarction ( n = 24, 55%). The median hospital stay was 1 (1;13) day. Twenty-three percent of patients ( n = 10) were discharged from hospital including eight patients (18%) with CPC 1–2. Survivors showed a trend toward shorter pre-hospital CPR duration (60 (59;60) min (S) vs 60 (55;90) min (NS), p = 0.07). Conclusion: Establishing ECPR programs in large population areas offers the option to improve survival rates for OHCA patients. Stringent compliance of institutional criteria (mainly age, witnessed arrest, and time of pre-hospital resuscitation) and providing ECPR to strictly selected patients seems to be a vital factor for such programs’ success. Pre-clinical settings and therapeutic measures must be adjusted in this regard to improve outcomes for this highly demanding patient cohort.
Resilience has become important in disaster preparedness and response. Unfortunately, little is known about resilience at the household level. This study presents the results of a survey into individual and household level preparedness to disaster events in Yangon, Myanmar, which is prone to natural disasters such as tropical cyclones, flooding, and earthquakes. The study aimed to understand societal resilience and to provide information that could be used to develop a holistic framework. In four different Yangon townships, 440 households were interviewed. The results of the survey indicate how risk preparedness could be improved by specific measures related to the following five factors: (1) increasing the general public’s knowledge of first aid and its role in preparedness; (2) improving mobile phone infrastructure and capacity building in its usage so that it can be used for communication during disasters, along with building up a redundant communication structure; (3) better use and organisation of volunteer potential; (4) more specific involvement of religious and public buildings for disaster response; and (5) developing specific measures for improving preparedness in urban areas, where the population often has reduced capacities for coping with food supply insufficiencies due to the high and immediate availability of food, shops and goods in regular times. The findings of this survey have led to specific recommendations for Yangon. The identified measures represent a first step in developing a more general framework. Future research could investigate the transferability of these measures to other areas and thus their suitability as a basis for a framework.
Two phenyl‐substituted λ5‐arsanes were prepared from phenylarsonic acid in two‐step procedures. Their molecular structures were determined by single‐crystal X‐ray diffraction. NBO analyses for the title compounds were conducted.
Protein phosphatase 1 isoforms α, β, and γ (PP1α, PP1β, and PP1γ) are highly homologous in the catalytic domains but have distinct subcellular localizations. In this study, we utilized both primary cell culture and knockout mice to investigate the isoform-specific roles of PP1s in the heart. In both neonatal and adult cardiac myocytes, PP1β was mainly localized in the nucleus, compared to the predominant presence of PP1α and PP1γ in the cytoplasm. Adenovirus-mediated overexpression of PP1α led to decreased phosphorylation of phospholamban, which was not influenced by overexpression of either PP1β or PP1γ. Interestingly, only cardiac-specific knockout of PP1β resulted in increased HDAC7 phosphorylation, consistent with the predominant nuclear localization of PP1β. Functionally, deletion of either PP1 isoform resulted in reduced fractional shortening in aging mice, however only PP1β deletion resulted in interstitial fibrosis in mice as early as 3 weeks of age. Deletion of neither PP1 isoform had any effect on pathological cardiac hypertrophy induced by 2 weeks of pressure overload stimulation. Together, our data suggest that PP1 isoforms have differential localizations to regulate the phosphorylation of their specific substrates for the physiological function in the heart.
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