Connecting Variability in Global Transcription Rate to Mitochondrial Variability

The authors demonstrate a connection between variability in the rate of transcription and differences in cellular mitochondrial content

Physics Laws of Social Science

Economics, and other fields of social science are often criticized as unscientific for their apparent failures to formulate universal laws governing human societies. Whether economics is truly a science is one of the oldest questions. This paper attempts to create such universal laws, and asserts that economics is a branch of quantum physics just like chemistry. Choice is a central concept in economics and other fields of social science, yet there is no corresponding concept of choice in modern physics. This article suggests that by introducing the concept of choice to the existing framework of physics, one can formulate five new physics laws, which establishes a common physics foundation for all fields of social and natural science. Applications in economics, biology, history, and finance prove that these new laws remove the invisible wall, which has been artificially separating social science from natural science. One implication of this article is that to establish a sound scientific foundation for social science requires not only advances in psychology and neurobiology but also a new interpretation of quantum mechanics

Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait

The genetic control of common traits is rarely deterministic, with many genes contributing only to the chance of developing a given phenotype. This incomplete penetrance is poorly understood and is usually attributed to interactions between genes or interactions between genes and environmental conditions. Because many traits such as cancer can emerge from rare events happening in one or very few cells, we speculate an alternative and complementary possibility where some genotypes could facilitate these events by increasing stochastic cell-to-cell variations (or ‘noise’). As a very first step towards investigating this possibility, we studied how natural genetic variation influences the level of noise in the expression of a single gene using the yeast S. cerevisiae as a model system. Reproducible differences in noise were observed between divergent genetic backgrounds. We found that noise was highly heritable and placed under a complex genetic control. Scanning the genome, we mapped three Quantitative Trait Loci (QTL) of noise, one locus being explained by an increase in noise when transcriptional elongation was impaired. Our results suggest that the level of stochasticity in particular molecular regulations may differ between multicellular individuals depending on their genotypic background. The complex genetic architecture of noise buffering couples genetic to non-genetic robustness and provides a molecular basis to the probabilistic nature of complex traits

HIV Promoter Integration Site Primarily Modulates Transcriptional Burst Size Rather Than Frequency

Mammalian gene expression patterns, and their variability across populations of cells, are regulated by factors specific to each gene in concert with its surrounding cellular and genomic environment. Lentiviruses such as HIV integrate their genomes into semi-random genomic locations in the cells they infect, and the resulting viral gene expression provides a natural system to dissect the contributions of genomic environment to transcriptional regulation. Previously, we showed that expression heterogeneity and its modulation by specific host factors at HIV integration sites are key determinants of infected-cell fate and a possible source of latent infections. Here, we assess the integration context dependence of expression heterogeneity from diverse single integrations of a HIV-promoter/GFP-reporter cassette in Jurkat T-cells. Systematically fitting a stochastic model of gene expression to our data reveals an underlying transcriptional dynamic, by which multiple transcripts are produced during short, infrequent bursts, that quantitatively accounts for the wide, highly skewed protein expression distributions observed in each of our clonal cell populations. Interestingly, we find that the size of transcriptional bursts is the primary systematic covariate over integration sites, varying from a few to tens of transcripts across integration sites, and correlating well with mean expression. In contrast, burst frequencies are scattered about a typical value of several per cell-division time and demonstrate little correlation with the clonal means. This pattern of modulation generates consistently noisy distributions over the sampled integration positions, with large expression variability relative to the mean maintained even for the most productive integrations, and could contribute to specifying heterogeneous, integration-site-dependent viral production patterns in HIV-infected cells. Genomic environment thus emerges as a significant control parameter for gene expression variation that may contribute to structuring mammalian genomes, as well as be exploited for survival by integrating viruses

Implementation of an Advanced Practice Registered Nurse-Led Clinic to Improve Follow-up Care for Post-Ischemic Stroke Patients.

AbstractBACKGROUND: Ischemic stroke continues to be a leading cause of serious disability within the United States, affecting 795 000 people annually. Approximately 12% to 21% of post-ischemic stroke patients will be readmitted to the hospital within 30 days of discharge. Studies suggest that implementation of a follow-up appointment within 7 to 14 days of discharge improves 30-day readmission rates; however, implementation of these guidelines is uncommon, and follow-up visits within the recommended window are not often achieved. The purpose of this project was to evaluate the impact of an advanced practice registered nurse (APRN)-led stroke clinic on follow-up care for post-ischemic stroke patients. The aims were to improve time to follow-up visit and reduce 30-day unplanned readmissions. METHODS: A pre/post intervention design was used to evaluate the impact of a process to access the APRN-led stroke clinic. The intervention included a scheduling process redesign, and subsequent APRN and scheduler education. RESULTS: The time to clinic follow-up preintervention averaged 116.9 days, which significantly reduced to 33.6 days post intervention, P = .0001. Unplanned readmissions within 30 days declined from 11.5% to 9.9%; however, it was not statistically significant, P = .149. Age was not statistically different between preintervention and postintervention groups, P = .092, and other demographics were similar between the groups. CONCLUSION: An APRN-led clinic can improve follow-up care and may reduce unplanned 30-day readmissions for post-ischemic stroke patients. Further work is needed to determine the impact of alternative approaches such as telehealth

Protocol for promoting recovery optimization of walking activity in stroke (PROWALKS): a randomized controlled trial

Abstract Background Stroke survivors are more physically inactive than even the most sedentary older adults, and low activity is associated with increased risk of recurrent stroke, medical complications, and mortality. We hypothesize that the combination of a fast walking intervention that improves walking capacity, with a step activity monitoring program that facilitates translation of gains from the clinic to the “real-world”, would generate greater improvements in real world walking activity than with either intervention alone. Methods Using a single-blind randomized controlled experimental design, 225 chronic (> 6 months) stroke survivors complete 12 weeks of fast walking training, a step activity monitoring program or a fast walking training + step activity monitoring program. Main eligibility criteria include: chronic ischemic or hemorrhagic stroke (> 6 months post), no evidence of cerebellar stroke, baseline walking speed between 0.3 m/s and 1.0 m/s, and baseline average steps / day < 8000. The primary (steps per day), secondary (self-selected and fastest walking speed, walking endurance, oxygen consumption) and exploratory (vascular events, blood lipids, glucose, blood pressure) outcomes are assessed prior to initiating treatment, after the last treatment and at a 6 and 12-month follow-up. Moderation of the changes in outcomes by baseline characteristics are evaluated to determine for whom the interventions are effective. Discussion Following completion of this study, we will not only understand the efficacy of the interventions and the individuals for which they are effective, we will have the necessary information to design a study investigating the secondary prevention benefits of improved physical activity post-stroke. This study is, therefore, an important step in the development of both rehabilitative and secondary prevention guidelines for persons with stroke. Trial registration ClinicalTrials.gov Identifier: NCT02835313. First Posted: July 18, 2016