Hypoosmotic stress shifts transcription of circadian genes.

Cells respond to hypoosmotic stress by initial swelling followed by intracellular increases in the number of osmolytes and initiation of gene transcription that allow cells to adapt to the stress. Here, we have studied the genes that change expression under mild hypoosmotic stress for 12 and 24 h in rat cultured smooth muscle cells (WKO-3M22). We find shifts in the transcription of many genes, several of which are associated with circadian rhythm, such as per1, nr1d1, per2, dbp, and Ciart.

Recent Advances in the Management of Acute Severe Ulcerative Colitis.

Acute severe ulcerative colitis is a medical emergency requiring inpatient treatment with intravenous steroids. Approximately one-third of patients do not respond to steroids sufficiently and require medical rescue therapy. Infliximab and cyclosporine are equally effective rescue agents, though infliximab is often preferred by clinicians for ease of use and greater familiarity.

(Dis)connected by design? Using participatory citizen science to uncover environmental determinants of social connectedness for youth in under-resourced neighbourhoods.

Background: Social isolation and loneliness are a growing public health concern. Inadequacies in neighbourhood social infrastructure can undermine social connectedness, particularly for youth, who are dependent on their local environments yet often marginalized from public spaces and city planning. Integrating citizen science with participatory action research, the Youth.

RLIM-specific activity reporters define variant pathogenicity in Tonne-Kalscheuer syndrome.

Tonne-Kalscheuer syndrome (TOKAS; MIM: 300978) is an X-linked recessive disorder with devastating consequences for patients, such as intellectual disability, developmental delay, and multiple congenital abnormalities. TOKAS is associated with hemizygous variants in the RLIM gene, which encodes a RING-type E3 ubiquitin ligase. The current sustained increase in reported RLIM variants of uncertain significance creates an urgent need to develop assays that can screen these variants and experimentally determine their pathogenicity and disease association.

Microplastics at Environmentally Relevant Concentrations Had Minimal Impacts on Pelagic Zooplankton Communities in a Large In-Lake Mesocosm Experiment.

To assess the potential risks of contemporary levels of plastic pollution in freshwater ecosystems, a large-scale experiment was conducted over 10 weeks in a boreal lake at the IISD-Experimental Lakes Area (Ontario, Canada). Fragments of common polymers (polyethylene, polystyrene, and polyethylene terephthalate), each with distinct colors and buoyancies, were added as a single pulse to seven in-lake mesocosms in equal contributions in a range of environmentally relevant nominal concentrations (6-29,240 particles/L). Two additional mesocosms with no added microplastics were used as controls.

Investigating the existence of an osmotic barrier between xylem fibres and vessels in sugar maple (Acer saccharum) using microCT.

Sugar maples (Acer saccharum Marshall) develop elevated stem pressures in springtime through the compression and expansion of gas bubbles present within xylem fibres. The stability of this gas within the fibres is hypothesised to be due to the elevated sugar concentration of maple sap and the presence of an osmotic barrier between fibres and vessels. Without this osmotic barrier gas bubbles are predicted to dissolve rapidly.

Structural and Biochemical Insights into the Mechanism of Action of the Clinical USP1 Inhibitor, KSQ-4279.

DNA damage triggers cell signaling cascades that mediate repair. This signaling is frequently dysregulated in cancers. The proteins that mediate this signaling are potential targets for therapeutic intervention.

Informing the Exposure Landscape: The Fate of Microplastics in a Large Pelagic In-Lake Mesocosm Experiment.

Understanding microplastic exposure and effects is critical to understanding risk. Here, we used large, in-lake closed-bottom mesocosms to investigate exposure and effects on pelagic freshwater ecosystems. This article provides details about the experimental design and results on the transport of microplastics and exposure to pelagic organisms.

Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study.

Background: Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear.

Objectives: We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC.

Design: This is a retrospective, multicentre study of patients admitted with ASUC.

The role of calcium in neuronal membrane tension and synaptic plasticity.

Calcium is a primary second messenger that plays a role in cellular functions including growth, movement and responses to drugs. The role that calcium plays in mediating communication between neurons by synaptic vesicle release is well established. This review focuses on the dependence of the physical properties of neuronal plasma membranes on calcium levels.

Eosinophilic Gastroenteritis Causing Pyloric Stenosis: A Rare Manifestation.

Eosinophilic gastritis is a gastrointestinal disorder characterized by eosinophilic infiltration in the gastric wall. We present a rare case of critical pyloric stenosis secondary to eosinophilic gastritis in a 16-year-old adolescent girl who presented with nausea, vomiting, early satiety, and abdominal pain. Abdominal computed tomography and subsequent esophagogastroduodenoscopy confirmed the anatomical diagnosis, but histological confirmation of the eosinophilic etiology was challenging.

A Multicompartment Assessment of Microplastic Contamination in Semi-remote Boreal Lakes.

Microplastic contamination is ubiquitous across the globe, even in remote locations. Still, the sources and pathways of microplastics to such locations are largely unknown. To investigate microplastic contamination in a semi-remote location, we measured microplastic concentrations in nine oligotrophic lakes within and around the International Institute for Sustainable Development-Experimental Lakes Area in northwestern Ontario, Canada.

variants underlying X-linked intellectual disability disrupt protein function via distinct mechanisms.

Neurodevelopmental disorders with intellectual disability (ND/ID) are a heterogeneous group of diseases driving lifelong deficits in cognition and behavior with no definitive cure. X-linked intellectual disability disorder 105 (XLID105, #300984; OMIM) is a ND/ID driven by hemizygous variants in the gene encoding a protein deubiquitylase with a role in cell proliferation and neural development. Currently, only four genetically diagnosed individuals from two unrelated families have been described with limited clinical data.

Freshwater connectivity transforms spatially integrated signals of biodiversity.

Aquatic ecosystems offer a continuum of water flow from headwater streams to inland lakes and coastal marine systems. This spatial connectivity influences the structure, function and dynamics of aquatic communities, which are among the most threatened and degraded on the Earth. Here, we determine the spatial resolution of environmental DNA (eDNA) in dendritic freshwater networks, which we use as a model for connected metacommunities.

Isotopic-based evidence for reduced benthic contributions to fish after a whole-lake addition of nanosilver.

Silver nanoparticles (AgNPs) are added as antibacterial and anti-odor agents to a wide range of textiles, with high potential for release into aquatic environments via domestic wastewater. Previous work demonstrating the negative impacts of AgNP exposure on periphyton production suggests benthic primary production could be reduced in aquatic ecosystems impacted by AgNP discharge. To evaluate the potential for AgNPs to alter benthic-pelagic coupling in aquatic ecosystems, tissue-stable isotope ratios of carbon and nitrogen from northern pike (Esox lucius) and yellow perch (Perca flavescens) were measured before, during, and after the addition of AgNPs to a whole-lake ecosystem, and compared to those collected from a nearby reference lake.

Determining efficacy of dynamic multimedia bowel preparation instructions versus standard instructions on adenoma detection and patient reported measures (DIGICLEAN trial): a study protocol for a multicentre, colonoscopist-blinded, randomised controlled trial.

Introduction: Colonoscopy plays important roles in bowel cancer screening and treatment. Poor bowel preparation occurs in 20-25% of colonoscopies. This negatively impacts adenoma and sessile serrated lesion detection rates, procedural time, requirement for repeat colonoscopies, healthcare costs and likelihood of patient withdrawal from screening programmes.

Primary and Secondary Psychopathic Traits: Investigating the Role of Attachment and Experiences of Shame.

Primary and secondary psychopathic traits have been documented in the general population and previous research has shown their link to adult insecure attachment and shame. However, there has been a gap in the literature examining the specific role of attachment avoidance and anxiety, and experiences of shame in the expression of these psychopathic traits. This study aimed to explore the associations between the attachment dimensions of anxiety and avoidance, in addition to characterological, behavioral and body shame with primary and secondary psychopathic traits.

Aeolus winds impact on volcanic ash early warning systems for aviation.

Forecasting volcanic ash atmospheric pathways is of utmost importance for aviation. Volcanic ash can interfere with aircraft navigational instruments and can damage engine parts. Early warning systems, activated after volcanic eruptions can alleviate the impacts on aviation by providing forecasts of the volcanic ash plume dispersion.

Examination of embolisms in maple and birch saplings utilising microCT.

We demonstrate the application of synchrotron x-ray microtomography (microCT) to non-invasively examine the internal structure of a maple and birch sapling. We show that, through the use of standard image analysis techniques, embolised vessels can be extracted from reconstructed slices of the stem. By combining these thresholded images with connectivity analysis, we map out the embolisms within the sapling in three dimensions and evaluate the size distribution, showing that large embolisms over 0.

Consumption and activity decline in Northern Pike (Esox lucius) during and after silver nanoparticle addition to a lake.

Silver nanoparticles (AgNPs) are antimicrobial additives in many consumer products with high potential for release into aquatic ecosystems. Though AgNPs have been shown to have negative impacts on fish in laboratory experiments, these effects are rarely observed at ecologically relevant concentrations or in situ in field settings. To evaluate ecosystem-level effects of this contaminant, AgNPs were added to a lake at the IISD Experimental Lakes Area (IISD-ELA) during 2014 and 2015.

Phases of Match-Play in Professional Australian Football: Positional Demands and Match-Related Fatigue.

This study examined the influence of player position and match quarter on activity profiles during the phases of play in Australian Football. Global positioning satellite data was collected for one season from an Australian Football League team for nomadic, key position and ruck players (age: 24.8 ± 4.

Structural and biochemical basis of interdependent FANCI-FANCD2 ubiquitination.

Di-monoubiquitination of the FANCI-FANCD2 (ID2) complex is a central and crucial step for the repair of DNA interstrand crosslinks via the Fanconi anaemia pathway. While FANCD2 ubiquitination precedes FANCI ubiquitination, FANCD2 is also deubiquitinated at a faster rate than FANCI, which can result in a FANCI-ubiquitinated ID2 complex (I D2). Here, we present a 4.

Cryo-EM reveals a mechanism of USP1 inhibition through a cryptic binding site.

Repair of DNA damage is critical to genomic integrity and frequently disrupted in cancers. Ubiquitin-specific protease 1 (USP1), a nucleus-localized deubiquitinase, lies at the interface of multiple DNA repair pathways and is a promising drug target for certain cancers. Although multiple inhibitors of this enzyme, including one in phase 1 clinical trials, have been established, their binding mode is unknown.

Multiple functions of phospholipase Cβ1 at a glance.

Phospholipase Cβ (PLCβ) is the main effector of the Gq family of heterotrimeric G proteins that transduces signals from hormones and neurotransmitters into Ca2+ signals. While PLCβ is critical for Ca2+ responses, recent studies have suggested that PLCβ has additional roles independent of its lipase activity. These novel functions are carried out by a cytosolic population of PLCβ that binds and inhibits the component 3 promoter of RNA-induced silencing complex (C3PO) to impact cytosolic RNA populations.