Parsing the roles of DExD-box proteins DDX39A and DDX39B in alternative RNA splicing.

DExD-box RNA proteins DDX39A and DDX39B are highly homologous paralogs that are conserved in vertebrates. They are required for energy-driven reactions involved in RNA processing. Although we have some understanding of how their functions overlap in RNA nuclear export, our knowledge of whether or not these proteins have specific or redundant functions in RNA splicing is limited.

Inefficient recruitment of DDX39B impedes pre-spliceosome assembly on introns.

Forkhead box P3 (FOXP3) is the master fate-determining transcription factor in regulatory T (T) cells and is essential for their development, function, and homeostasis. Mutations in cause immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, and aberrant expression of has been implicated in other diseases such as multiple sclerosis and cancer. We previously demonstrated that pre-mRNA splicing of RNAs is highly sensitive to levels of DExD-box polypeptide 39B (DDX39B), and here we investigate the mechanism of this sensitivity.

Bridging Metabolic-Associated Steatotic Liver Disease and Cardiovascular Risk: A Potential Role for Ketogenesis.

The prevalence of cardiovascular diseases (CVDs) is a growing global health concern. Recent advances have demonstrated significant reductions in acute cardiovascular events through the management of modifiable cardiovascular risk factors. However, these factors are responsible for about 50% of the global cardiovascular disease burden.

Role of RNA Alternative Splicing in T Cell Function and Disease.

Alternative RNA splicing, a ubiquitous mechanism of gene regulation in eukaryotes, expands genome coding capacity and proteomic diversity. It has essential roles in all aspects of human physiology, including immunity. This review highlights the importance of RNA alternative splicing in regulating immune T cell function.

Osmotic Demyelination Syndrome in a Normonatremic Patient Under Treatment With Proton Pump Inhibitors.

A 66-year-old woman was admitted to the emergency department with diarrhea, nausea, and vomiting as well as low-grade fever. She was initially treated with ciprofloxacin and metronidazole with symptomatic improvement and was discharged. One week later, she returned to the emergency department for gait instability, dizziness, and vomiting and had a witnessed generalized tonic-clonic seizure in the hospital.

Eosinophilic Granulomatosis With Polyangiitis Presentation After Nandrolone Withdrawal.

A 41-year-old man was admitted to the Emergency Department with bilateral numbness in lower extremities and left femoral palsy. He also reported constitutional symptoms, vomiting and non-bloody diarrhoea for the last several months. He had a previous history of eosinophilic asthma with erratic follow-up.

Early Splicing Complexes and Human Disease.

Over the last decade, our understanding of spliceosome structure and function has significantly improved, refining the study of the impact of dysregulated splicing on human disease. As a result, targeted splicing therapeutics have been developed, treating various diseases including spinal muscular atrophy and Duchenne muscular dystrophy. These advancements are very promising and emphasize the critical role of proper splicing in maintaining human health.

The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate.

Genes associated with increased susceptibility to multiple sclerosis (MS) have been identified, but their functions are incompletely understood. One of these genes codes for the RNA helicase DExD/H-Box Polypeptide 39B (DDX39B), which shows genetic and functional epistasis with interleukin-7 receptor-α gene () in MS-risk. Based on evolutionary and functional arguments, we postulated that DDX39B enhances immune tolerance thereby decreasing MS risk.

The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity.

Mosquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. There is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. Here we report the discovery of high levels of the anti-immune subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito saliva.

Bleeding Complications in Relation to the International Normalized Ratio for Dental Extractions in Patients under Chronic Anticoagulant Therapy - An Evaluative Study.

Introduction: Recent simple dental extraction protocols suggest that therapeutic levels of the anticoagulant drug should be maintained because bleeding complications could be managed with local haemostasis manoeuvres. The aim of the present study was to evaluate the association between bleeding complications and the international normalized ratio (INR) values in patients after dental extractions completed with a plug of bismuth subgallate, without interrupting anticoagulant administration.

Materials And Methods: Patients undergoing oral Vitamin K antagonist chronic anticoagulant therapy requiring simple dental extractions were included in the study.

RNA virus infections and their effect on host alternative splicing.

It is evident that viral infection dramatically alters host gene expression, and these alterations have both pro- and anti-viral functions. While the effects of viral infection on transcription and translation have been comprehensively reviewed, less attention has been paid to the impact on alternative splicing of pre-messenger RNAs. Here we review salient examples of how viral infection leads to changes in alternative splicing and discuss how these changes impact infection.

RNA Viruses, Pandemics and Anticipatory Preparedness.

RNA viruses are likely to cause future pandemics and therefore we must create and organize a deep knowledge of these viruses to prevent and manage this risk. Assuming prevention will fail, at least once, we must be prepared to manage a future pandemic using all resources available. We emphasize the importance of having safe vaccine candidates and safe broad-spectrum antivirals ready for rapid clinical translation.

Essential Topics About the Imaging Diagnosis and Treatment of Hemorrhagic Stroke: A Comprehensive Review of the 2022 AHA Guidelines.

Intracerebral hemorrhage (ICH) is a severe stroke with a high death rate (40% mortality). The prevalence of hemorrhagic stroke has increased globally, with changes in the underlying cause over time as anticoagulant use and hypertension treatment have improved. The fundamental etiology of ICH and the mechanisms of harm from ICH, particularly the complex interaction between edema, inflammation, and blood product toxicity, have been thoroughly revised by the American Heart Association (AHA) in 2022.

Antisense modulation of IL7R splicing to control sIL7R expression in human CD4 T cells.

The interleukin 7 receptor () is strongly associated with increased risk to develop multiple sclerosis (MS), an autoimmune disease of the central nervous system, and this association is likely driven by up-regulation of the soluble isoform of IL7R (sIL7R). Expression of sIL7R is determined by exclusion of the alternative exon 6 from IL7R transcripts, and our previous work revealed that the MS risk allele of the SNP rs6897932 within this exon enhances the expression of sIL7R by promoting exclusion of exon 6. sIL7R potentiates the activity of IL7, leading to enhanced expansion of T cells and increased disability in the experimental autoimmune encephalomyelitis (EAE) murine model of MS.

Y-Box Binding Protein 1 Interacts with Dengue Virus Nucleocapsid and Mediates Viral Assembly.

Infection with dengue virus (DENV) induces vast rearrangements of the endoplasmic reticulum, which allows the compartmentalization of viral RNA replication and particle assembly. Both processes occur in concert with viral and cellular proteins. Prior studies from our group suggest that the host RNA-binding protein (RBP) Y-box binding protein 1 (YBX1) is required for a late step in the DENV replication cycle.

Trigeminal nerve injuries. Four years' experience at a single Argentine referral center and a literature review.

The aim of this retrospective study was to describe the etiology and characteristics of trigeminal nerve injuries referred to a specialized center in Buenos Aires, Argentina. A retrospective analysis was performed of patients referred from February 2016 to January 2020. Age, sex, intervention performed, nerve affected, time elapsed from injury, diagnosis, location, and whether patient had signed informed consent were recorded.

The RNA binding protein Quaking represses splicing of the Fibronectin EDA exon and downregulates the interferon response.

Quaking (QKI) controls RNA metabolism in many biological processes including innate immunity, where its roles remain incompletely understood. To illuminate these roles, we performed genome scale transcriptome profiling in QKI knockout cells with or without poly(I:C) transfection, a double-stranded RNA analog that mimics viral infection. Analysis of RNA-sequencing data shows that QKI knockout upregulates genes induced by interferons, suggesting that QKI is an immune suppressor.

Role of Alternative Splicing in Regulating Host Response to Viral Infection.

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection.

Estimation of Admission D-dimer Cut-off Value to Predict Venous Thrombotic Events in Hospitalized COVID-19 Patients: Analysis of the SEMI-COVID-19 Registry.

Background: Venous thrombotic events (VTE) are frequent in COVID-19, and elevated plasma D-dimer (pDd) and dyspnea are common in both entities.

Objective: To determine the admission pDd cut-off value associated with in-hospital VTE in patients with COVID-19.

Methods: Multicenter, retrospective study analyzing the at-admission pDd cut-off value to predict VTE and anticoagulation intensity along hospitalization due to COVID-19.

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19.

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality).