Disordered Ferlin C2A-C2B Linkers Bind Membranes and Encode Small Linear Motifs.

Ferlins are vesicle trafficking proteins composed of folded C2 domains conjugated by linkers which are largely disordered. Although a role for the C2 domains as calcium sensors has been established it remains unclear whether the linkers function beyond acting as passive spacers. We examined the C2A-C2B linker sequences of vertebrate ferlins and found both putative short linear motifs (SLiMs) as well as membrane binding sequences for members of the protein family.

An integrated, tiered microplastic workflow, supporting rapid broadscale detection options.

With growing concerns regarding microplastic pollution, there is an urgent need to improve understanding of their presence, distribution, and environmental impacts. This necessitates more coordinated and harmonised large-scale microplastic monitoring initiatives. However, such assessments are traditionally expensive, labour-intensive, and hindered by a lack of standardised sampling and analytical protocols, which impede rapid, yet accurate identification of microplastic sources and ecological risks.

AgileMultiIdeogram: Rapid Identification and Visualization of Autozygous Regions Using Illumina Short-Read Sequencing Data.

Rare autosomal recessive diseases are a major cause of mortality and morbidity. They occur more frequently in individuals with consanguineous parents, in which case the pathogenic variants are often located within regions of genetic identity by descent. A well-established and effective way of identifying these "autozygous" genomic regions has been to search for runs of homozygous genotypes in microarray SNP data.

The RNA splicing factor PRPF8 is required for left-right organiser cilia function and determination of cardiac left-right asymmetry via regulation of splicing.

Cilia function in the left-right organizer (LRO) is critical for determining internal organ asymmetry in vertebrates. To further understand the genetics of left-right asymmetry, we isolated a mouse mutant with laterality defects, from a random mutagenesis screen. mutants carry a missense mutation in the pre-mRNA processing factor, .

Cleavage of the Meckel-Gruber syndrome protein TMEM67 by ADAMTS9 uncouples Wnt signaling and ciliogenesis.

TMEM67 mutations cause Meckel-Gruber syndrome and other related ciliopathies. TMEM67 is involved in both ciliary transition zone assembly, and non-canonical Wnt signaling mediated by its extracellular domain. How TMEM67 performs these two separate functions is not known.

Biosourced Functional Hydroxybenzoate--Lactide Polymers with Antimicrobial Activity.

Antimicrobial resistance is an urgent global health challenge, and compounds that address this issue have attracted significant attention. In particular, bioderived molecules that possess natural antimicrobial properties can be useful to prepare active macromolecules that are degradable. In this work, a 4-(methyl/allyl/benzyl)oxy-6-(H/alkyl)-2-oxy-benzoate--lactide-based polymer library was designed and studied for antimicrobial activity.

Microbial biosynthesis of rare cannabinoids.

∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol are the most abundant natural cannabinoids isolated from the different cultivars of the Cannabis plant. Other natural ∆9-THC analogs, especially those with different alkyl chain substitutions, display different and potent bioactivity. However, these rare cannabinoids are typically isolated in minuscule amounts and are difficult to synthesize.

Microscale velocity-dependent unbinding generates a macroscale performance-efficiency tradeoff in actomyosin systems.

Myosin motors are fundamental biological actuators that power diverse mechanical tasks in eukaryotic cells via ATP hydrolysis. Previous work has linked myosin's velocity-dependent detachment rate to macroscopic scale muscle dynamics described by Hill's model, yet its impact on energetic flows - power consumption, output, and efficiency - remains unclear. We develop an analytical model relating myosin unbinding, quantified by a dimensionless parameter α, to energetics.

Drug and siRNA screens identify ROCK2 as a therapeutic target for ciliopathies.

Background: Primary cilia mediate vertebrate development and growth factor signalling. Defects in primary cilia cause inherited developmental conditions termed ciliopathies. Ciliopathies often present with cystic kidney disease, a major cause of early renal failure.

Synthetic Biology in Natural Product Biosynthesis.

Synthetic biology has played an important role in the renaissance of natural products research during the post-genomics era. The development and integration of new tools have transformed the workflow of natural product discovery and engineering, generating multidisciplinary interest in the field. In this review, we summarize recent developments in natural product biosynthesis from three different aspects.

Characterizing air pollution exposure methodologies in rhinology: a scoping review.

ABST RACTCharacterization of air pollution assessment methodologies in rhinologic disease research is lacking. A scoping review was thus conducted to survey exposure methods in studies examining common rhinologic conditions: allergic rhinitis (AR) and chronic rhinosinusitis (CRS). Several medical databases were queried for variables relating to (1) adults with a diagnosis of CRS or AR and (2) air pollution exposure.

Biosynthesis of the C-Glycosylated Depside Arenicolin B.

We uncovered the biosynthetic pathway of the C-glycosylated depside arenicolin B from Phialomyces arenicola through genome mining, heterologous reconstitution and biochemical characterization. The biosynthetic gene cluster (BGC) of arenicolin B is comprised of a HRPKS, a NRPKS, and a C-glycosyltransferase. Through biochemical dissection and evaluation, we demonstrate the NRPKS thioesterase (TE) domain catalyses depside formation.

Varying circumstances surrounding opioid toxicity deaths across ethno-racial groups in Ontario, Canada: a population-based descriptive cross-sectional study.

Introduction: The North American toxic drug crisis has been framed as an epidemic primarily affecting white people. However, evidence suggests that deaths are rising among racialised people. Accordingly, we sought to describe and compare characteristics and circumstances of opioid toxicity deaths across ethno-racial groups.

The role of MEGF10 in myoblast fusion and hypertrophic response to overload of skeletal muscle.

Biallelic mutations in multiple EGF domain protein 10 (MEGF10) gene cause EMARDD (early myopathy, areflexia, respiratory distress and dysphagia) in humans, a severe recessive myopathy, associated with reduced numbers of PAX7 positive satellite cells. To better understand the role of MEGF10 in satellite cells, we overexpressed human MEGF10 in mouse H-2k-tsA58 myoblasts and found that it inhibited fusion. Addition of purified extracellular domains of human MEGF10, with (ECD) or without (EGF) the N-terminal EMI domain to H-2k-tsA58 myoblasts, showed that the ECD was more effective at reducing myoblast adhesion and fusion by day 7 of differentiation, yet promoted adhesion of myoblasts to non-adhesive surfaces, highlighting the importance of the EMI domain in these behaviours.

Phenotypes of Pelvic Organ Prolapse.

Importance: The Pelvic Organ Prolapse Quantification (POP-Q) stages do not correlate with symptoms or characterize important prolapse subtypes.

Objectives: We hypothesize that clinically meaningful prolapse "phenotypes" utilizing POP-Q measurements can be defined. The primary aim was to define the phenotypes and their frequency.

Threonine and tyrosine kinase (TTK) mRNA and protein expression in breast cancer; prognostic significance in the neoadjuvant setting.

Aims: Threonine and tyrosine kinase (TTK) is up-regulated in triple-negative breast cancer (TNBC), yet its expression in patients undergoing neoadjuvant chemotherapy (NACT) remains unexplored. This investigation aims to assess TTK protein expression in treatment-naïve pre-treatment cores and paired pre- and post-NACT breast cancer (BC) cohorts, as well as its correlation with microcephaly 1 (MCPH1) protein expression.

Methods And Results: Transcriptomic data were sourced from the Gene Expression Omnibus microarray database for mRNA expression analysis.

Molecular diagnoses and candidate gene identification in the congenital heart disease cohorts of the 100,000 genomes project.

Congenital heart disease (CHD) describes a structural cardiac defect present from birth. A cohort of participants recruited to the 100,000 Genomes Project (100 kGP) with syndromic CHD (286 probands) and familial CHD (262 probands) were identified. "Tiering" following genome sequencing data analysis prioritised variants in gene panels linked to participant phenotype.

Faecal contamination determines bacterial assemblages over natural environmental parameters within intermittently opened and closed lagoons (ICOLLs) during high rainfall.

Intermittently closed and opened lakes and lagoons (ICOLLs) provide important ecosystem services, including food provision and nutrient cycling. These ecosystems generally experience low watershed outflow, resulting in substantial fluctuations in physicochemical parameters that are often compounded by anthropogenic contamination, however, how this impacts the patterns in microbiology within these environments remains uncharacterised. Therefore, we aimed to determine how seasonal heterogeneity in the physicochemical parameters, in comparison to faecal contamination, alter the dynamics of bacterial communities inhabiting ICOLLs on the eastern Australian coast.

Two functional forms of the Meckel-Gruber syndrome protein TMEM67 generated by proteolytic cleavage by ADAMTS9 mediate Wnt signaling and ciliogenesis.

mutations are the major cause of Meckel-Gruber syndrome. TMEM67 is involved in both ciliary transition zone assembly, and non-canonical Wnt signaling mediated by its extracellular domain. How TMEM67 performs these two separate functions is not known.

Electric buses as an air pollution and meteorological observation network: Methodology and preliminary results.

Many local agencies in the United States and other countries are tasked to install air pollution monitoring systems of highly accurate sensors that have high acquisition, operating, and maintenance costs. The need for expanded coverage of air quality measurements across Salt Lake County (SLCO), Utah is being met by mounting air quality and temperature sensors on an expanding fleet of battery electric buses (BEBs). Monitoring air quality from a mobile sensor network provides real-time insights into air pollution patterns at high temporal and spatial resolution.