Exploiting the Achilles' Heel of Viral RNA Processing to Develop Novel Antivirals.

Treatment options for viral infections are limited and viruses have proven adept at evolving resistance to many existing therapies, highlighting a significant vulnerability in our defenses. In response to this challenge, we explored the modulation of cellular RNA metabolic processes as an alternative paradigm to antiviral development. Previously, the small molecule 5342191 was identified as a potent inhibitor of HIV-1 replication by altering viral RNA accumulation at doses that minimally affect host gene expression.

Influence of Sudden Changes in Foot Strikes on Loading Rate Variability in Runners.

Foot strike patterns influence vertical loading rates during running. Running retraining interventions often include switching to a new foot strike pattern. Sudden changes in the foot strike pattern may be uncomfortable and may lead to higher step-to-step variability.

Pulmonary hypertension in patients with chronic obstructive pulmonary disease: Impact of lung hyperinflation on the response to pulmonary hypertension treatment.

Background: Pulmonary hypertension (PH) is common during chronic obstructive pulmonary disease (COPD), particularly in patients with severe COPD. These patients can be classified into different PH groups due to frequent comorbidities. Emphysema is often associated with COPD and is responsible for lung hyperinflation, which may contribute to the development of PH.

Toxin and capsule production by Bacillus cereus biovar anthracis influence pathogenicity in macrophages and animal models.

Bacillus cereus biovar anthracis (Bcbva) causes anthrax-like disease in animals, particularly in the non-human primates and great apes of West and Central Africa. Genomic analyses revealed Bcbva as a member of the B. cereus species that carries two plasmids, pBCXO1 and pBCXO2, which have high sequence homology to the B.

Chitosan-Electrospun Fibers Encapsulating Norfloxacin: The Impact on the Biochemical, Oxidative and Immunological Profile in a Rats Burn Model.

This study investigates the impact of chitosan-based nanofibers on burn wound healing in a rat model. Two formulations of chitosan nanofibers were prepared through electrospinning. The formulations were then incorporated with different amounts of norfloxacin and underwent surface modifications with 2-formylphenylboronic acid.

Characterizing major and trace element concentrations, and radioactivity in bulk glass samples from the trinity atomic test.

Glass fragments (16 green glasses and 2 red glasses) were handpicked from crushed Trinitite. X-ray diffraction studies revealed that these samples were essentially pure glass with the exception of minor amounts (less than 4 wt%) of quartz (which acts as a diluent) in some samples. The concentrations of 45 elements in the Trinity glasses were determined using Instrumental Neutron Activation Analysis.

Identifying practices of information transfer between the hospital and primary care for older adults: a scoping review protocol.

Introduction: Transition of care from hospital to primary care has been recognised globally as a high-risk scenario for older patients' safety by the WHO. Indeed, sub-optimal care transitions are associated with increased mortality, morbidity and adverse events.Improving communication through timely and accurate clinical information transfer has been identified as a key component of optimal care transitions.

NR4A1 and NR4A2 orphan nuclear receptors regulate endothelial-to-hematopoietic transition in mouse hematopoietic stem cell specification.

Hematopoietic stem cells (HSCs) sustain life-long hematopoiesis and emerge during mid-gestation from hemogenic endothelial progenitors via an endothelial-to-hematopoietic transition (EHT). The full scope of molecular mechanisms governing this process remains unclear. The NR4A subfamily of orphan nuclear receptors act as tumor suppressors in myeloid leukemogenesis and have never been implicated in HSC specification.

Turnover of retroelements and satellite DNA drives centromere reorganization over short evolutionary timescales in Drosophila.

Centromeres reside in rapidly evolving, repeat-rich genomic regions, despite their essential function in chromosome segregation. Across organisms, centromeres are rich in selfish genetic elements such as transposable elements and satellite DNAs that can bias their transmission through meiosis. However, these elements still need to cooperate at some level and contribute to, or avoid interfering with, centromere function.

[The benefits of radiotherapy in the treatment of tendinopathies].

Tendinopathies are disorders of the tendons, often caused by overuse. They often affect athletes and manual workers and represent a major medical challenge. Current treatments are numerous, including physiotherapy, anti-inflammatory drugs and sometimes surgery.

Essential mineral elements in roe deer: Associations with parasites and immune phenotypes in two contrasting populations.

Low levels of essential mineral elements such as cobalt, copper, and iron, in organisms reduce immune function, increasing the chances of parasitic infection. This phenomenon has been demonstrated widely in domestic animals but rarely in wildlife. In this study, we used data from 7- to 9-month-old roe deer (), living in two different populations facing contrasting environmental conditions (Trois-Fontaines and Chizé), to investigate whether the parasitic and immunological statuses could be related to essential element status.

Retinoid X Receptor Signaling Mediates Cancer Cell Lipid Metabolism in the Leptomeninges.

Cancer cells metastatic to the leptomeninges encounter a metabolically-challenging extreme microenvironment. To understand adaptations to this space, we subjected leptomeningeal-metastatic (LeptoM) mouse breast and lung cancers isolated from either the leptomeninges or orthotopic primary sites to ATAC-and RNA-sequencing. When inhabiting the leptomeninges, the LeptoM cells demonstrated transcription downstream of retinoid-X-receptors (RXRs).

Mapping multiple RNA modifications simultaneously by proximity barcode sequencing.

RNA is subject to a multitude of different chemical modifications that collectively represent the epitranscriptome. Individual RNA modifications including N6-methyladenosine (mA) on mRNA play essential roles in the posttranscriptional control of gene expression. Recent technological advances have enabled the transcriptome-wide mapping of certain RNA modifications, to reveal their broad relevance and characteristic distribution patterns.

Unveiling the Inflammatory Landscape of Recurrent Glioblastoma through Histological-Based Assessments.

The glioblastoma (GBM) tumor microenvironment consists of a heterogeneous mixture of neoplastic and non-neoplastic cells, including immune cells. Tumor recurrence following standard-of-care therapy results in a rich landscape of inflammatory cells throughout the glioma-infiltrated cortex. Immune cells consisting of glioma-associated macrophages and microglia (GAMMs) overwhelmingly constitute the bulk of the recurrent glioblastoma (rGBM) microenvironment, in comparison to the highly cellular and proliferative tumor microenvironment characteristic of primary GBM.

The dual-specificity kinase DYRK1A interacts with the Hepatitis B virus genome and regulates the production of viral RNA.

The genome of Hepatitis B virus (HBV) persists in infected hepatocytes as a nuclear episome (cccDNA) that is responsible for the transcription of viral genes and viral rebound, following antiviral treatment arrest in chronically infected patients. There is currently no clinically approved therapeutic strategy able to efficiently target cccDNA (Lucifora J 2016). The development of alternative strategies aiming at permanently abrogating HBV RNA production requires a thorough understanding of cccDNA transcriptional and post-transcriptional regulation.

Trends in the Care of Locally Advanced Pancreatic Cancer in the Modern Era of Chemotherapy.

Introduction: Current guidelines for treatment for locally advanced pancreatic cancer recommend chemotherapy ± radiation, or radiation alone when multimodal therapy is contraindicated. In a subset of patients, guideline-recommended treatment (GRT) achieves sufficient response to qualify for potentially curative resection. This study evaluated trends in treatment utilization and aimed to identify barriers to GRT.