Alternative splicing impacts microRNA regulation within coding regions.

MicroRNAs (miRNAs) are small non-coding RNA molecules that bind to target sites in different gene regions and regulate post-transcriptional gene expression. Approximately 95% of human multi-exon genes can be spliced alternatively, which enables the production of functionally diverse transcripts and proteins from a single gene. Through alternative splicing, transcripts might lose the exon with the miRNA target site and become unresponsive to miRNA regulation.

Alternative splicing analysis benchmark with DICAST.

Alternative splicing is a major contributor to transcriptome and proteome diversity in health and disease. A plethora of tools have been developed for studying alternative splicing in RNA-seq data. Previous benchmarks focused on isoform quantification and mapping.

The role of the lower extremity functional scale in predicting surgical outcomes for total joint arthroplasty patients.

Background: The purpose of this study was to evaluate the relationship between lower extremity functional scale (LEFS) scores with postoperative functional outcomes for total joint arthroplasty (TJA) patients and to investigate the utility of this tool to create an individualized plan of care perioperatively.

Methods: Patients undergoing primary TJA at a single institution from 2016 to 2019 was retrospectively reviewed by a univariate analysis in terms of patient characteristics and outcomes across LEFS quartiles. Multivariate regression models were constructed to evaluate the association between the LEFS quartile and outcomes after controlling for confounding factors.

Functional enrichment of alternative splicing events with NEASE reveals insights into tissue identity and diseases.

Alternative splicing (AS) is an important aspect of gene regulation. Nevertheless, its role in molecular processes and pathobiology is far from understood. A roadblock is that tools for the functional analysis of AS-set events are lacking.

Development and Validation of Machine Learning Models to Predict Admission From Emergency Department to Inpatient and Intensive Care Units.

Study Objective: This study aimed to develop and validate 2 machine learning models that use historical and current-visit patient data from electronic health records to predict the probability of patient admission to either an inpatient unit or ICU at each hour (up to 24 hours) of an emergency department (ED) encounter. The secondary goal was to provide a framework for the operational implementation of these machine learning models.

Methods: Data were curated from 468,167 adult patient encounters in 3 EDs (1 academic and 2 community-based EDs) of a large academic health system from August 1, 2015, to October 31, 2018.

ASimulatoR: splice-aware RNA-Seq data simulation.

Summary: A plethora of tools exist for RNA-Seq data analysis with a focus on alternative splicing (AS). However, appropriate data for their comparative evaluation is missing. The R package ASimulatoR simulates gold standard RNA-Seq datasets with fine-grained control over the distribution of AS events, which allow for evaluating alternative splicing tools, e.

Electronic Health Record Use by Sex Among Physicians in an Academic Health Care System.

This cohort study examines the association of sex with electronic health record use among physicians and patient satisfaction.

Liver X receptors are required for thymic resilience and T cell output.

The thymus is a primary lymphoid organ necessary for optimal T cell development. Here, we show that liver X receptors (LXRs)-a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity-critically contribute to thymic integrity and function. LXRαβ-deficient mice develop a fatty, rapidly involuting thymus and acquire a shrunken and prematurely immunoinhibitory peripheral T cell repertoire.

Sleep modulates haematopoiesis and protects against atherosclerosis.

Sleep is integral to life. Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease, we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice.

Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease.

The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways, how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells-integrin β7 natural gut intraepithelial T lymphocytes (natural IELs)-that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism.

Self-reactive CD4 IL-3 T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis.

Acquisition of self-reactive effector CD4 T cells is a major component of the autoimmune response that can occur during myocarditis, an inflammatory form of cardiomyopathy. Although the processes by which self-reactive T cells gain effector function have received considerable attention, how these T cells contribute to effector organ inflammation and damage is less clear. Here, we identified an IL-3-dependent amplification loop that exacerbates autoimmune inflammation.

A Dinner-Table Approach to a Unique Interactive Nutrition Curriculum for Healthcare Professional Students.

Nutrition education is significantly lacking from healthcare provider educational curricula despite its proven benefit for some of the most chronic and challenging diseases facing Americans today. We successfully developed and implemented an interprofessional, experiential nutrition education course for healthcare professional students that emphasizes evidence-based nutrition interventions for patient care.

The infarcted myocardium solicits GM-CSF for the detrimental oversupply of inflammatory leukocytes.

Myocardial infarction (MI) elicits massive inflammatory leukocyte recruitment to the heart. Here, we hypothesized that excessive leukocyte invasion leads to heart failure and death during acute myocardial ischemia. We found that shortly and transiently after onset of ischemia, human and mouse cardiac fibroblasts produce granulocyte/macrophage colony-stimulating factor (GM-CSF) that acts locally and distally to generate and recruit inflammatory and proteolytic cells.

The influence of androgens on hibernation phenology of free-living male arctic ground squirrels.

Free-living ground squirrel species are sexually dimorphic in hibernation phenology. The underlying causes of these differences are not yet known. Androgens, testosterone (T) in particular, inhibit hibernation.

ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression.

Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Here, we report that angiopoietin-like protein 4 (ANGPTL4) is the most highly upregulated gene in foamy macrophages and it's absence in haematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis. Furthermore, hyperlipidemic mice deficient in haematopoietic ANGPTL4 have higher blood leukocyte counts, which is associated with an increase in the common myeloid progenitor (CMP) population.

On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver.

Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity.

Cognitive deficits develop 1month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge.

Unlabelled: Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors.

Lp-PLA2 Antagonizes Left Ventricular Healing After Myocardial Infarction by Impairing the Appearance of Reparative Macrophages.

Background: Healing after myocardial infarction (MI) involves the biphasic accumulation of inflammatory Ly-6C(high) and reparative Ly-6C(low) monocytes/macrophages. Excessive inflammation disrupts the balance between the 2 phases, impairs infarct healing, and contributes to left ventricle remodeling and heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of the phospholipase A2 family of enzymes, produced predominantly by leukocytes, participates in host defenses and disease.

Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis.

Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis.

Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice.

Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury.

IL-4 signaling drives a unique arginase+/IL-1β+ microglia phenotype and recruits macrophages to the inflammatory CNS: consequences of age-related deficits in IL-4Rα after traumatic spinal cord injury.

Alternative activation of microglia/macrophages (M2a) by interleukin (IL)-4 is purported to support intrinsic growth and repair processes after CNS injury. Nonetheless, alternative activation of microglia is poorly understood in vivo, particularly in the context of inflammation, injury, and aging. Here, we show that aged mice (18-19 months) had reduced functional recovery after spinal cord injury (SCI) associated with impaired induction of IL-4 receptor α (IL-4Rα) on microglia.

TGFβ produced by IL-10 redirected astrocytes attenuates microglial activation.

While there clearly is an intimate relationship between astrocytes and microglia, few studies have examined these potentially dynamic interactions. In this study, cytokine-mediated communication between microglia and astrocytes under inflammatory conditions was investigated. We have previously shown that activated microglia produce Interleukin (IL)-10, a regulatory cytokine that plays an important role in resolving neuroinflammation.

Immune activation promotes depression 1 month after diffuse brain injury: a role for primed microglia.

Background: Traumatic brain injury (TBI) is associated with a higher incidence of depression. The majority of individuals who suffer a TBI are juveniles and young adults, and thus, the risk of a lifetime of depressive complications is a significant concern. The etiology of increased TBI-associated depression is unclear but may be inflammatory-related with increased brain sensitivity to secondary inflammatory challenges (e.