SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals.

SARS-CoV-2 nonstructural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in other host species remains elusive, especially in bats which are natural reservoirs of sarbecoviruses and possess a markedly different innate immune system than humans. Here, we reveal that SARS-CoV-2 nsp1 potently inhibits translation in bat cells from Rhinolophus lepidus, belonging to the same genus as known sarbecovirus reservoirs hosts.

Lasing in a femtosecond-laser-written single-scan waveguide fabricated in Tm-doped BGG glass.

We report lasing action in a femtosecond-laser-inscribed waveguide in thulium-doped barium-gallium-germanium oxide (BGG) glass. A laser cavity was assembled with this waveguide that provided a single-mode output of 62 mW when pumped at 1.6 µm.

BIOFILM DAIRY FOODS REVIEW: Microbial Community Tracking from Dairy Farm to Factory: Insights on Biofilm Management for Enhanced Food Safety and Quality.

This review aimed to assess the scope of the literature on tracking the microbial community of biofilms, focusing on the dairy farm and processing environments. The majority of studies focused on either production, storage, transport or processing of milk, while 5 combined the investigation of both production and processing facilities. Factors influencing short-term changes in dairy microbiota such as the occurrence of mastitis and season were distinguished from factors revealed through long-term studies, such as feed and weather, rather than the milking equipment.

Birth weight and head circumference for 22-29 weeks gestation neonates from an international cohort.

Objective: Size at birth is a key indicator of in utero growth. Our objective was to generate sex-specific percentiles for birth weight and head circumference in neonates born between 22 and 29 weeks gestation from pregnancies without hypertension or diabetes and assess differences between vaginal and caesarean births and between singletons and twins.

Methods: We used data from 12 countries participating in the International Network for Evaluating Outcomes in Neonates database from 2007 to 2021.

A multimodal neuroimaging study of cerebrovascular regulation: protocols and insights of combining electroencephalography, functional near-infrared spectroscopy, transcranial Doppler ultrasound, and physiological parameters.

. The current paper describes the creation of a simultaneous trimodal neuroimaging protocol. The authors detail their methodological design for a subsequent large-scale study, demonstrate the ability to obtain the expected physiologically induced responses across cerebrovascular domains, and describe the pitfalls experienced when developing this approach.

Optimization of fs-laser-induced voxels in nonlinear materials via over-correction of spherical aberration.

In this Letter, over-correction of spherical aberration is used to counteract nonlinear effects such as Kerr self-focusing and plasma effects, resulting in more spherical and small-sized femtosecond laser-inscribed voxels within nonlinear materials. By strategically redirecting marginal focusing rays toward the beginning of the laser modification zone, the induced plasma prevents any rays from causing a structural modification beyond this zone, irrespective of any focus elongation caused by nonlinear effects. The method has been effectively validated across a range of materials, including ZnS, ZnSe, BIG, GeS, and SiO.

Ordered ATP hydrolysis in the Hsp90 chaperone is regulated by Aha1 and a conserved post-translational modification.

Hsp90 is a dimeric molecular chaperone that is important for the folding, stabilization, activation, and maturation of hundreds of protein substrates called "clients" in cells. Dozens of co-chaperones and hundreds of post-translational modifications (PTMs) regulate the ATP-dependent client activation cycle. The Aha1 co-chaperone is the most potent stimulator of the ATPase cycle of Hsp90 and phosphorylation of threonine 22 in Hsp90 can regulate the recruitment of Aha1 in cells.

Mechanistic insights into Sindbis virus infection: noncapped genomic RNAs enhance the translation of capped genomic RNAs to promote viral infectivity.

Alphaviruses are globally distributed, vector-borne RNA viruses with high outbreak potential and no clinical interventions, posing a significant global health threat. Previously, the production and packaging of both viral capped and noncapped genomic RNAs (cgRNA and ncgRNA) during infection was reported. Studies have linked ncgRNA production to viral infectivity and pathogenesis, but its precise role remains unclear.

HLA class, calcineurin inhibitor levels, and the risk of graft failure in kidney recipients with donor-specific antibodies.

Introduction: De novo donor-specific HLA antibody (dnDSA) are associated with poor outcomes. Whether this observation applies to both HLA class I and II dnDSA remains unclear.

Methods: We studied 1236 consecutive kidney recipients who had routine anti-HLA antibody surveillance post-transplant.

Discovery of ART0380, a Potent and Selective ATR Kinase Inhibitor Undergoing Phase 2 Clinical Studies for the Treatment of Advanced or Metastatic Solid Cancers.

One of the hallmarks of cancer is high levels of DNA replication stress and defects in the DNA damage response (DDR) pathways, which are critical for maintaining genomic integrity. Ataxia telangiectasia and Rad3-related protein (ATR) is a key regulator of the DDR machinery and an attractive therapeutic target, with multiple ATR inhibitors holding significant promise in ongoing clinical studies. Herein, we describe the discovery and characterization of ART0380 (), a potent and selective ATR inhibitor with a compelling in vitro and in vivo pharmacological profile currently undergoing Phase 2 clinical studies in patients with advanced or metastatic solid tumors as monotherapy and in combination with DNA-damaging agents (NCT04657068 and NCT05798611).

Health Care Utilization After a Visit to a Within-Group Family Physician vs a Walk-In Clinic Physician.

Purpose: Primary care access is a key health system metric, but little research has compared models to provide primary care access when one's regular physician is not available. We compared health system use after a visit with a patient's own family physician group (ie, within-group physician who was not the patient's primary physician) vs a visit with a walk-in clinic physician who was not part of the patient's family physician group.

Methods: We conducted a population-based, retrospective cohort study using administrative data from Ontario, Canada, including all individuals formally enrolled with a family physician, from April 1, 2019 to March 31, 2020.

Nutrient availability in a freshwater-to-marine continuum: Cyanobacterial blooms along the Lake Okeechobee Waterway.

Water from the Lake Okeechobee watershed historically flowed south through the Everglades. Hydrologic alterations created the Lake Okeechobee Waterway, where lake water is periodically shunted east to the St. Lucie Estuary (C-44 canal) and west to the Caloosahatchee River and Estuary (C-43 canal).

Conception and Optimization of Extraction-Free Loop-Mediated Isothermal Amplification Detection of Dry Rot Fungus .

The use of nucleic acid-based detection tools for microorganisms and fungi has become a gold standard. This is particularly the case for wood-decaying fungi like which are hard to discriminate based on macroscopic and microscopic observations. This dry rot is important to detect as it is particularly destructive in an infested building, which requires immediate action to prevent spreading and significant damage to structural elements.

Air pollution exposure in vitrified oocyte donors and male recipient partners in relation to fertilization and embryo quality.

Background: Studies on air pollution and outcomes of in vitro fertilization (IVF) have focused on couples undergoing autologous IVF, in which it is challenging to disentangle maternal and paternal exposures during gametogenesis. We sought to evaluate the independent associations between air pollution exposure during oogenesis and spermatogenesis on fertilization and embryo quality in non-identified donor oocyte IVF cycles.

Methods: Our study included 500 oocyte donors and 915 male recipient partners who contributed 1,095 oocyte thaw cycles (2008-2019).

Local food procurement behavior and overall diet quality among adults in Québec: results from the NutriQuébec project.

Background: Consumption of locally produced foods is generally perceived as being part of a healthy dietary pattern. Accordingly, in 2020, the provincial government of Québec (Canada) promoted the purchase of local foods for economic and health benefits. The present cross-sectional study aimed to document the association between the behavior of local food procurement and overall diet quality in a sample of adults from the province of Québec.

Discovery and Preclinical Characterization of Fulacimstat (BAY 1142524), a Potent and Selective Chymase Inhibitor As a New Profibrinolytic Approach for Safe Thrombus Resolution.

Chymase is a serine-protease produced by mast cells. In the past few decades, its role in fibrotic diseases triggered the search for orally available chymase inhibitors. Aiming at reducing adverse cardiac remodeling after myocardial infarction, our research efforts resulted in the discovery of fulacimstat (BAY 1142524).

[F]NP3-627, a Candidate PET Imaging Agent Targeting the NLRP3 Inflammasome in the Central Nervous System.

We describe the identification of a candidate positron emission tomography (PET) imaging agent for the NLRP3 protein. NLRP3 plays a critical role in the immune system and has proven a difficult target for the development of imaging agents due to its low and cell-specific expression profile. A recently described series of pyridazine-based inhibitors, with improved permeability and brain-penetration properties, was used as a starting point for the development of a suitable PET imaging agent.

Decreased DNA density is a better indicator of a nuclear bleb than lamin B loss.

Nuclear blebs are herniations of the nucleus that occur in diseased nuclei that cause nuclear rupture leading to cellular dysfunction. Chromatin and lamins are two of the major structural components of the nucleus that maintain its shape and function, but their relative roles in nuclear blebbing remain elusive. To determine the composition of nuclear blebs, we compared the immunofluorescence intensity of DNA and lamin B in the main nucleus body to the nuclear bleb across cell types and perturbations.

Quantifying neurovascular coupling through a concurrent assessment of arterial, capillary, and neuronal activation in humans: A multimodal EEG-fNIRS-TCD investigation.

Background: This study explored a novel multimodal neuroimaging approach to assess neurovascular coupling (NVC) in humans using electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), and transcranial Doppler ultrasound (TCD).

Methods: Fifteen participants (nine females; age 19-32) completed concurrent EEG-fNIRS-TCD imaging during motor (finger tapping) and visual ("Where's Waldo?") tasks, with synchronized monitoring of blood pressure, capnography, and heart rate. fNIRS assessed microvascular oxygenation within the frontal, motor, parietal, and occipital cortices, while the middle and posterior cerebral arteries (MCA/PCA) were insonated using TCD.

Cross-cultural adaptation and validation of a French version of the perceived personal control questionnaire as an outcome measure instrument for genetic counseling.

The perceived personal control (PPC) questionnaire serves as an instrument to assess the concept of PPC, which refers to a person's perception of their ability to achieve positive outcomes while avoiding the negative effects of a given situation. Developed and used as a patient-reported outcome measure (PROM) in genetic counseling, the PPC questionnaire has been translated and validated in several languages, but not in French. The aim of this study was to cross-culturally adapt and validate a French version of the PPC questionnaire to evaluate genetic counseling services for hereditary breast and ovarian cancer (HBOC).

Development and validation of the four-item Concise Aging adults Smell Test to screen for olfactory dysfunction in older adults.

Background: Olfactory dysfunction (OD) in the elderly is common and associated with numerous comorbidities, yet often underrecognized. This study sought to develop an instrument for widespread screening of this condition.

Methods: Demographic factors, comorbidities, and olfactory-related questions were examined in a focus group (N = 20) and development cohort (N = 190).