An ultra-conserved poison exon in the Tra2b gene encoding a splicing activator is essential for male fertility and meiotic cell division.

The cellular concentrations of splicing factors (SFs) are critical for controlling alternative splicing. Most serine and arginine-enriched (SR) protein SFs regulate their own concentration via a homeostatic feedback mechanism that involves regulation of inclusion of non-coding 'poison exons' (PEs) that target transcripts for nonsense-mediated decay. The importance of SR protein PE splicing during animal development is largely unknown despite PE ultra-conservation across animal genomes.

Personalizing driver safety interfaces via driver cognitive factors inference.

Recent advances in AI and intelligent vehicle technology hold the promise of revolutionizing mobility and transportation through advanced driver assistance systems (ADAS). Certain cognitive factors, such as impulsivity and inhibitory control have been shown to relate to risky driving behavior and on-road risk-taking. However, existing systems fail to leverage such factors in assistive driving technologies adequately.

High-throughput sensitive screening of small molecule modulators of microexon alternative splicing using dual Nano and Firefly luciferase reporters.

Disruption of alternative splicing frequently causes or contributes to human diseases and disorders. Consequently, there is a need for efficient and sensitive reporter assays capable of screening chemical libraries for compounds with efficacy in modulating important splicing events. Here, we describe a screening workflow employing dual Nano and Firefly luciferase alternative splicing reporters that affords efficient, sensitive, and linear detection of small molecule responses.

Effectively teaching cultural competence in a pre-professional healthcare curriculum.

Background: There has been research documenting the rising numbers of racial and ethnic minority groups in the United States. With this rise, there is increasing concern over the health disparities that often affect these populations. Attention has turned to how clinicians can improve health outcomes and how the need exists to educate healthcare professionals on the practice of cultural competence.

Limits of Ultra: Towards an Interdisciplinary Understanding of Ultra-Endurance Running Performance.

Ultra-endurance running (UER) poses extreme mental and physical challenges that present many barriers to completion, let alone performance. Despite these challenges, participation in UER events continues to increase. With the relative paucity of research into UER training and racing compared with traditional endurance running distance (e.

Total Energy Expenditure and Nutritional Intake in Continuous Multiday Ultramarathon Events.

Continuous multiday ultramarathon competitions are increasingly popular and impose extreme energetic and nutritional demands on competitors. However, few data have been published on energy expenditure during these events. Here, we report doubly labeled water-derived measures of total energy expenditure (in kilocalories per day) and estimated physical activity level (PAL: total energy expenditure/basal metabolic rate) collected from five elite and subelite finishers (four males and one female, age 34.

Variation in human functional eccrine gland density and its implications for the evolution of human sweating.

Objectives: We aim to test three questions regarding human eccrine sweat gland density, which is highly derived yet poorly understood. First, is variation in functional eccrine gland density ("FED") explained by childhood climate, suggesting phenotypic plasticity? Second, is variation in FED explained by genetic similarity (a proxy for "geographic ancestry"), implying divergent evolutionary pathways in this trait of ancestral populations? Third, what is the relationship between FED and sweat production?

Materials And Methods: To test questions one and two, we measured FED in 68 volunteers aged 18-39 with varied childhood climate regimes and geographic ancestries. To test question three, we compared sweat production to FED in our n = 68 sample.

Systematic exploration of dynamic splicing networks reveals conserved multistage regulators of neurogenesis.

Alternative splicing (AS) is a critical regulatory layer; yet, factors controlling functionally coordinated splicing programs during developmental transitions are poorly understood. Here, we employ a screening strategy to identify factors controlling dynamic splicing events important for mammalian neurogenesis. Among previously unknown regulators, Rbm38 acts widely to negatively control neural AS, in part through interactions mediated by the established repressor of splicing, Ptbp1.

Home Monitoring Programs for Patients Testing Positive for SARS-CoV-2: An Integrative Literature Review.

Background: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic threatened to oversaturate hospitals worldwide, necessitating rapid patient discharge to preserve capacity for the most severe cases. This need, as well as the high risk of SARS-CoV-2 transmission, led many hospitals to implement remote patient monitoring (RPM) programs for SARS-CoV-2 positive patients in an effort to provide care that was safe and preserve scarce resources.

Objective: The aim of this study is to provide an integrative review of peer-reviewed literature on different RPM programs that were implemented for SARS-CoV-2 positive patients including their strengths and challenges.

A comparison of proton stopping power measured with proton CT and x-ray CT in fresh postmortem porcine structures.

Purpose: Currently, calculations of proton range in proton therapy patients are based on a conversion of CT Hounsfield units of patient tissues into proton relative stopping power. Uncertainties in this conversion necessitate larger proximal and distal planned target volume margins. Proton CT can potentially reduce these uncertainties by directly measuring proton stopping power.

Why does strength training improve endurance performance?

Objective: The specificity of training principle holds that adaptations to exercise training closely match capacity to the specific demands of the stimulus. Improvements in endurance sport performance gained through strength training are a notable exception to this principle. While the proximate mechanisms for how strength training produces muscular adaptations beneficial to endurance sports are increasingly well understood, the ultimate causes of this phenomenon remain unexplored.

Human chimeric antigen receptor macrophages for cancer immunotherapy.

Chimeric antigen receptor (CAR) T cell therapy has shown promise in hematologic malignancies, but its application to solid tumors has been challenging. Given the unique effector functions of macrophages and their capacity to penetrate tumors, we genetically engineered human macrophages with CARs to direct their phagocytic activity against tumors. We found that a chimeric adenoviral vector overcame the inherent resistance of primary human macrophages to genetic manipulation and imparted a sustained pro-inflammatory (M1) phenotype.

Diversity and evolution of human eccrine sweat gland density.

The human eccrine sweat gland is central to the evolution of the human genus, permitting an enormous thermoregulatory sweating capacity that was essential to the human niche of high physical activity in open, hot, semi-arid environments. Despite a century of research inventorying the structure and function of eccrine glands and the physiological responses of human heat acclimation, we do not have a clear understanding of how intraspecific differences in eccrine density affect thermoregulation. Similarly, existing data does not comprehensively catalogue modern human diversity in this trait, nor do we understand the relative influences of evolutionary forces and phenotypic plasticity in shaping this diversity.

Inferring User Intent using Bayesian Theory of Mind in Shared Avatar-Agent Virtual Environments.

We present a real-time algorithm to infer the intention of a user's avatar in a virtual environment shared with multiple human-like agents. Our algorithm applies the Bayesian Theory of Mind approach to make inferences about the avatar's hidden intentions based on the observed proxemics and gaze-based cues. Our approach accounts for the potential irrationality in human behavior, as well as the dynamic nature of an individual's intentions.

Resection of ruptured hepatic teratoma in an adult.

Introduction: Extragonadal locations of teratomas are uncommonly reported in the literature. Teratomas are neoplasms usually found in the gonadal organs: ovaries and testis. The majority of teratomas are found in the pediatric age group.

Genome-wide CRISPR-Cas9 Interrogation of Splicing Networks Reveals a Mechanism for Recognition of Autism-Misregulated Neuronal Microexons.

Alternative splicing is crucial for diverse cellular, developmental, and pathological processes. However, the full networks of factors that control individual splicing events are not known. Here, we describe a CRISPR-based strategy for the genome-wide elucidation of pathways that control splicing and apply it to microexons with important functions in nervous system development and that are commonly misregulated in autism.

Efficient and Accurate Quantitative Profiling of Alternative Splicing Patterns of Any Complexity on a Laptop.

Alternative splicing (AS) is a widespread process underlying the generation of transcriptomic and proteomic diversity and is frequently misregulated in human disease. Accordingly, an important goal of biomedical research is the development of tools capable of comprehensively, accurately, and efficiently profiling AS. Here, we describe Whippet, an easy-to-use RNA-seq analysis method that rapidly-with hardware requirements compatible with a laptop-models and quantifies AS events of any complexity without loss of accuracy.

The evolution of eccrine sweat glands in human and nonhuman primates.

Sweating is an unusual thermoregulatory strategy for most mammals, yet is critical for humans. This trait is commonly hypothesized to result from human ancestors moving from a forest to a warmer and drier open environment. As soft tissue traits do not typically fossilize, this idea has been difficult to test.

Correction: Trabecular bone in the calcaneus of runners.

[This corrects the article DOI: 10.1371/journal.pone.

Trabecular bone in the calcaneus of runners.

Trabecular bone of the human calcaneus is subjected to extreme repetitive forces during endurance running and should adapt in response to this strain. To assess possible bone functional adaptation in the posterior region of the calcaneus, we recruited forefoot-striking runners (n = 6), rearfoot-striking runners (n = 6), and non-runners (n = 6), all males aged 20-41 for this institutionally approved study. Foot strike pattern was confirmed for each runner using a motion capture system.

Using a novel data resource to explore heart rate during mountain and road running.

Online, accessible performance and heart rate data from running competitions are posted publicly or semi-publicly to social media. We tested the efficacy of one such data resource- Strava- as a tool in exercise physiology investigations by exploring heart rate differences in mountain racing and road racing running events. Heart rate and GPS pace data were gathered from Strava activities posted by 111 males aged 21-49, from two mountain races (Mt.

What did Hadropithecus eat, and why should paleoanthropologists care?

Over 40 years ago, Clifford Jolly noted different ways in which Hadropithecus stenognathus converged in its craniodental anatomy with basal hominins and with geladas. The Malagasy subfossil lemur Hadropithecus departs from its sister taxon, Archaeolemur, in that it displays comparatively large molars, reduced incisors and canines, a shortened rostrum, and thickened mandibular corpus. Its molars, however, look nothing like those of basal hominins; rather, they much more closely resemble molars of grazers such as Theropithecus.

Unravelling the RNA-Binding Properties of SAFB Proteins in Breast Cancer Cells.

Scaffold attachment factor B1 (SAFB1) and SAFB2 proteins are oestrogen (ER) corepressors that bind to and modulate ER activity through chromatin remodelling or interaction with the basal transcription machinery. SAFB proteins also have an internal RNA-recognition motif but little is known about the RNA-binding properties of SAFB1 or SAFB2. We utilised crosslinking and immunoprecipitation (iCLIP) coupled with high-throughput sequencing to enable a transcriptome-wide mapping of SAFB1 protein-RNA interactions in breast cancer MCF-7 cells.

Generating pedestrian trajectories consistent with the fundamental diagram based on physiological and psychological factors.

Pedestrian crowds often have been modeled as many-particle system including microscopic multi-agent simulators. One of the key challenges is to unearth governing principles that can model pedestrian movement, and use them to reproduce paths and behaviors that are frequently observed in human crowds. To that effect, we present a novel crowd simulation algorithm that generates pedestrian trajectories that exhibit the speed-density relationships expressed by the Fundamental Diagram.