Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft Partitioning.

Unlabelled: Development of an understanding of membrane nanodomains colloquially known as "lipid rafts" has been hindered by a lack of pharmacological tools to manipulate rafts and protein affinity for rafts. We screened 24,000 small molecules for modulators of the affinity of peripheral myelin protein 22 (PMP22) for rafts in giant plasma membrane vesicles (GPMVs). Hits were counter-screened against another raft protein, MAL, and tested for impact on raft, leading to two classes of compounds.

Clinical disease in British sheep infected with an emerging strain of bluetongue virus serotype 3.

Background: Bluetongue virus serotype 3 (BTV-3) was detected for the first time in cattle and sheep in southern England in 2023, the first UK BTV incursion for more than 15 years. Clinical signs were not observed, yet severe clinical disease and mortality were reported during recent BTV-3 outbreaks in northern Europe.

Methods: To investigate the clinical disease and infection kinetics associated with this UK BTV-3 strain, five British sheep were infected with a UK BTV-3 isolate using Culicoides biting midges.

Novel Curvularia species causing disseminated phaeohyphomycosis in a dog.

Phaeohyphomycosis is an uncommon disease caused by dematiaceous fungi that is almost exclusively found in immunocompromised dogs. Here we describe the case of a dog treated with prednisone (1.1 mg/kg/day) and cyclosporine (11.

An exploration of the role of trust and rapport in enhancing vaccine uptake among Anishinaabe in rural northern Ontario.

This article examines the complicated terrain of immunization acceptance and access among Indigenous peoples in northern Ontario by drawing on conversations held prior to 2019 that explored knowledge about Haemophilus influenzae type a (Hia) infection specifically and attitudes toward vaccines more broadly. In the decade preceding COVID-19, Hia emerged as a leading cause of morbidity and mortality in Indigenous communities in northern Canada. Before developing new vaccines, it is imperative to hold conversations with the communities most affected and to learn more about Indigenous peoples' perceptions of and knowledge about vaccines, both generally and Hia specifically.

Immune profile diversity is achieved with synthetic TLR4 agonists combined with the RG1-VLP vaccine in mice.

The TLR4 (Toll-like receptor 4)-activating agonist MPLA (monophosphoryl lipid A) is a key component of the adjuvant systems AS01 and AS04, utilized in marketed preventive vaccines for several infectious pathogens. As MPLA is a biologically-derived product containing a mixture of several lipid A congeners with a 4' phosphoryl group and varying numbers of acyl chains with distinct activities, extensive efforts to refine its production and immunogenicity are ongoing; notably, the development of the BECC (Bacterial Enzymatic Combinatorial Chemistry) system in which bacteria express lipid A-modifying enzymes to produce a panoply of lipid A congeners. In an effort to characterize the adjuvant activity of these lipid A congeners, we compared biologically-derived and synthetic versions of BECC470 and BECC438 for adjuvant activity in BALB/c mice vaccinated with the HPV (Human papilloma virus) VLP-based vaccine, RG1-VLP.

Running Cadence and the Influence on Frontal Plane Knee Deviations.

Patellofemoral pain is one of the most common injuries in recreational runners, with significant implications for dynamic knee valgus. The knee valgus angle can be corrected surgically or with a more conservative non-operative approach. Increasing running cadence may be an effective biomechanical gait retraining intervention to reduce knee valgus and thus patellofemoral pain.

Assessing the expression of Nectin-4 in solid tumors by immunohistochemistry - what do we know?

Antibody-Drug Conjugates (ADCs) represent a promising class of anti-cancer substances that combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs, hence they enable a new approach of targeted therapy. The use of the ADC Entfortumab Vedotin (EV), which targets the viral receptor Nectin-4, showed an impressive clinical response in metastatic urothelial carcinoma. In this review, we present what is known about the expression of Nectin-4 in various tumor entities, focusing on immunohistochemistry as a diagnostic venue to detect positive expression, as this inexpensive technique is readily available in pathology laboratories.

Microplastic burial potential and ecological risks in mangrove forests of the Amazon River delta.

Coastal mangrove ecosystems have been shown to be important microplastic (MP) sinks. Yet, information regarding their MP sequestration capacity is scant. Here, we characterized the spatial and vertical distribution of MPs in mangrove ecosystems of the Amazon River delta and quantified, for the first time, their MP burial and potential economic value related to their surface water filtering capacity.

Sea-level rise and extreme Indian Ocean Dipole explain mangrove dieback in the Maldives.

Mangrove forests enhance Small Island Developing States' resilience to climate change, yet in 2020, a mangrove dieback impacted ~ 25% of mangrove-containing islands in the Maldives. Using remote sensing, dendrology and sediment geochemistry, we document a significant decrease in mangrove health post-2020 (NDVI: 0.75 ± 0.

A global assessment of mangrove soil organic carbon sources and implications for blue carbon credit.

Mangroves can retain both autochthonous and allochthonous marine and/or terrestrial organic carbon (OC) in sediments. Accurate quantification of these OC sources is essential for the proper allocation of blue C credits. Here, we conduct a global-scale analysis of sediments autochthonous and allochthonous OC contributions in estuarine and marine mangroves using stable isotopes.

Structure-based discovery of first inhibitors targeting the helicase activity of human PIF1.

PIF1 is a conserved helicase and G4 DNA binding and unwinding enzyme, with roles in genome stability. Human PIF1 (hPIF1) is poorly understood, but its functions can become critical for tumour cell survival during oncogene-driven replication stress. Here we report the discovery, via an X-ray crystallographic fragment screen (XChem), of hPIF1 DNA binding and unwinding inhibitors.

Remote monitoring of rheumatoid arthritis (REMORA): study protocol for a stepped wedge cluster randomized trial and process evaluation of an integrated symptom tracking intervention.

Background: Management of rheumatoid arthritis (RA) relies on symptoms reported by patients during infrequent outpatient clinic visits. These reports are often incomplete and inaccurate due to poor recall, leading to suboptimal treatment decisions and outcomes. Asking people to track symptoms in-between visits and integrating the data into clinical pathways may improve this.

Building and Sustaining Public Trust in Health Data Sharing for Musculoskeletal Research: Semistructured Interview and Focus Group Study.

Background: Although many people are supportive of their deidentified health care data being used for research, concerns about privacy, safety, and security of health care data remain. There is low awareness about how data are used for research and related governance. Transparency about how health data are used for research is crucial for building public trust.

The Addition of Transcriptomics to the Bead-Enabled Accelerated Monophasic Multi-Omics Method: A Step toward Universal Sample Preparation.

Omics-based measurements enable the study of biomolecules in a high-throughput fashion, leading to the characterization and quantification of biological systems. Multi-omics methods aim to incorporate several omics measurements for a more holistic approach, which is crucial for advancing our understanding of the diversity and redundancy of biological systems. Current multi-omics sample preparation methods have achieved proteomics, lipidomics, and metabolomics from individual samples; however, the bioinformatic tools currently available for interpreting data generated from these omics are limited.

Soil greenhouse gas fluxes partially reduce the net gains in carbon sequestration in mangroves of the Brazilian Amazon.

There is interest in assessing the potential climate mitigation benefit of coastal wetlands based on the balance between their greenhouse gas (GHG) emissions and carbon sequestration. Here we investigated soil GHG fluxes (CO and CH) on mangroves of the Brazilian Amazon coast, and across common land use impacts including shrimp farms and a pasture. We found greater methane fluxes near the Amazon River mouth (1439 to 3312 μg C m h), which on average are equivalent to 37% of mangrove C sequestration in the region.

Transient MRI changes and neurological deterioration in glioblastoma upon SARS-CoV-2 infection.

Purpose: Little is known about the effect of SARS-CoV-2 infection on glioblastoma (GBM) growth, metabolism, and prognosis. Immunological changes within GBM tissue are potentially symptomatic, underlining the urgent need for a better understanding of this phenomenon. To date, the complex underlying biology has not been fully elucidated.

Effect of saturated and unsaturated fat on the physical properties of plant-based cheese.

In many plant-based meat and dairy alternatives, coconut oil is frequently used to replicate the textural and structural properties of animal fats due to its high saturated fat content. Concerns about the health implications of saturated fat and the sustainability of coconut oil call for an exploration into alternative fat combinations in plant-based foods. The effects of saturated fatty acid (SFA) content on plant-based cheese physical characteristics were evaluated through five different ratios of coconut oil (CO) to sunflower oil (SO): 100%, 90%, 75%, 60%, 50%, 40%, 25%, 10%, and 0%.

Real-world data on the prevalence of BRCA1/2 and HRR gene mutations in patients with primary and metastatic castration resistant prostate cancer.

Purpose: This study seeks to contribute real-world data on the prevalence of BRCA1/2 and HRR gene mutations in prostate cancer.

Methods: We compiled sequencing data of 197 cases of primary and metastatic prostate cancer, in which HRR mutation analysis was performed upon clinical request within the last 5 years. All cases were analyzed using a targeted NGS BRCAness multigene panel, including 8 HRR genes (ATM, BRCA1, BRCA2, CDK12, CHEK2, FANCA, HDAC2, PALB2).

Specific antibody responses to Qβ-displayed Plasmodium falciparum-derived UB05 and MSP3 proteins in mother-neonate couples.

Malaria blood-stage parasite is a critical pathogenic stage responsible for serious adverse outcomes in pregnant women and their neonates. Immunoglobulin G (IgG) antibody responses specific to various asexual blood-stage antigens were well reported in non-pregnant individuals. However, little is still known during placental malaria.

Feature-agnostic metabolomics for determining effective subcytotoxic doses of common pesticides in human cells.

Although classical molecular biology assays can provide a measure of cellular response to chemical challenges, they rely on a single biological phenomenon to infer a broader measure of cellular metabolic response. These methods do not always afford the necessary sensitivity to answer questions of subcytotoxic effects, nor do they work for all cell types. Likewise, boutique assays such as cardiomyocyte beat rate may indirectly measure cellular metabolic response, but they too, are limited to measuring a specific biological phenomenon and are often limited to a single cell type.

Exploring the experiences and preferences of South Asian patients' of primary care in England since COVID-19.

Introduction: Remote (digital and/or telephone) access and consultation models are being driven by national policy with the goal being that the National Health Service operate on a remote-first (digital-first) basis by 2029. Previous research has suggested that remote methods of access to care and consulting may act to widen health inequalities for certain patients and/or groups such as those from ethnic minorities. South Asian (SA) patients comprise the largest ethnic minority group in England.

Spatial and seasonal variability in benthic impact of mussel farms: Predicting and mitigating impacts using ambient oxygen conditions.

Environmental impacts are a cause for concern when developing and expanding aquaculture and to be sustainable potential negative effects need to be addressed. The intensity and extent of these impacts likely vary among sites and seasons, depending on multiple factors including the physical and biological setting and operational aspects. Using a combination of sampling techniques, we investigated the spatial variability in epibenthic impacts in eleven commercial mussel farms, on the Swedish west coast.