A CADASIL NOTCH3 mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878H hematopoietic clones.

Clonal hematopoiesis (CH) is nearly universal in the elderly. The molecular and cellular mechanisms driving CH and the clinical consequences of carrying clonally derived mutant mature blood cells are poorly understood. We recently identified a C223Y mutation in the extracellular domain (ECD) of NOTCH3 as a putative CH driver in mice.

Wheat MYOSIN-RESEMBLING CHLOROPLAST PROTEIN controls B-type starch granule initiation timing during endosperm development.

Molecular factors that contribute to the diverse spatial and temporal patterns of starch granule initiation between species and organs are poorly understood. Wheat (Triticum sp.) endosperm contains both large A-type granules initiated during early grain development and small B-type granules that initiate about 10 to 15 days later.

Analysis of clozapine prescribing in the over-65s: 5-year retrospective study.

Aims And Method: Patients prescribed clozapine are increasingly living into old age. However, there is a lack of studies to guide prescribing in this age group. We sought to identify all clozapine patients in Hertfordshire Partnership NHS Foundation Trust over a 5-year period and review side-effect burden and co-prescribing in all patients aged over 65 years.

Functional analysis of epilepsy-associated GABA receptor mutations using Caenorhabditis elegans.

Objective: GABA receptor subunit mutations pose a significant risk for genetic generalized epilepsy; however, there are over 150 identified variants, many with unknown or unvalidated pathogenicity. We aimed to develop in vivo models for testing GABA receptor variants using the model organism, Caenorhabditis elegans.

Methods: CRISPR-Cas9 gene editing was used to create a complete deletion of unc-49, a C.

Tissue distribution of cysteine string protein/DNAJC5 in C. elegans analysed by CRISPR/Cas9-mediated tagging of endogenous DNJ-14.

Cysteine string protein (CSP) is a member of the DnaJ/Hsp40 family of molecular chaperones. CSP is enriched in neurons, where it mainly localises to synaptic vesicles. Mutations in CSP-encoding genes in flies, worms, mice and humans result in neuronal dysfunction, neurodegeneration and reduced lifespan.

Proximity labelling reveals effects of disease-causing mutation on the DNAJC5/cysteine string protein α interactome.

Cysteine string protein α (CSPα), also known as DNAJC5, is a member of the DnaJ/Hsp40 family of co-chaperones. The name derives from a cysteine-rich domain, palmitoylation of which enables localization to intracellular membranes, notably neuronal synaptic vesicles. Mutations in the DNAJC5 gene that encodes CSPα cause autosomal dominant, adult-onset neuronal ceroid lipofuscinosis (ANCL), a rare neurodegenerative disease.

Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis.

Biological pathways between alcohol consumption and alcohol liver disease (ALD) are not fully understood. We selected genes with known effect on (1) alcohol consumption, (2) liver function, and (3) gene expression. Expression of the orthologs of these genes in Caenorhabditis elegans and Drosophila melanogaster was suppressed using mutations and/or RNA interference (RNAi).

Increasing amyloplast size in wheat endosperm through mutation of PARC6 affects starch granule morphology.

The determination of starch granule morphology in plants is poorly understood. The amyloplasts of wheat endosperm contain large discoid A-type granules and small spherical B-type granules. To study the influence of amyloplast structure on these distinct morphological types, we isolated a mutant in durum wheat (Triticum turgidum) defective in the plastid division protein PARC6, which had giant plastids in both leaves and endosperm.

Brassinosteroid coordinates cell layer interactions in plants via cell wall and tissue mechanics.

Growth coordination between cell layers is essential for development of most multicellular organisms. Coordination may be mediated by molecular signaling and/or mechanical connectivity between cells, but how genes modify mechanical interactions between layers is unknown. Here we show that genes driving brassinosteroid synthesis promote growth of internal tissue, at least in part, by reducing mechanical epidermal constraint.

(Protein Kinase D1) mutants have age-dependent defects in locomotion and neuromuscular transmission.

Changes in neuronal function that occur with age are an area of increasing importance. A potential significant contributor to age-dependent decline may be alterations to neurotransmitter release. Protein kinases, such as Protein Kinase C and Protein Kinase A, are well characterised modulators of neuronal function and neurotransmission.

Conglomerate Crystallization in the Cambridge Structural Database (2020-2021).

Conglomerate crystals are materials capable of undergoing spontaneous resolution and were responsible for the discovery of molecular chirality. Their relevance to modern chemical and crystallographic sciences has been hindered by the difficulty in identifying and searching materials with this characteristic ability to spontaneously bias their own enantioenrichment. With the release of the November 2021 distribution of the Cambridge Structural Database (CSD) (version 5.

Identifying a Hidden Conglomerate Chiral Pool in the CSD.

Conglomerate crystallization is the spontaneous generation of individually enantioenriched crystals from a nonenantioenriched material. This behavior is responsible for spontaneous resolution and the discovery of molecular chirality by Pasteur. The phenomenon of conglomerate crystallization of chiral organic molecules has been left largely undocumented, with no actively curated list available in the literature.

A Caenorhabditis elegans model of autosomal dominant adult-onset neuronal ceroid lipofuscinosis identifies ethosuximide as a potential therapeutic.

Autosomal dominant adult-onset neuronal ceroid lipofuscinosis (ANCL) is a rare neurodegenerative disorder characterized by progressive dementia and premature death. Four ANCL-causing mutations have been identified, all mapping to the DNAJC5 gene that encodes cysteine string protein α (CSPα). Here, using Caenorhabditis elegans, we describe an animal model of ANCL in which disease-causing mutations are introduced into their endogenous chromosomal locus, thereby mirroring the human genetic disorder.

Data-driven learning of narcosis mode of action identifies a CNS transcriptional signature shared between whole organism Caenorhabditis elegans and a fish gill cell line.

With the large numbers of man-made chemicals produced and released in the environment, there is a need to provide assessments on their potential effects on environmental safety and human health. Current regulatory frameworks rely on a mix of both hazard and risk-based approaches to make safety decisions, but the large number of chemicals in commerce combined with an increased need to conduct assessments in the absence of animal testing makes this increasingly challenging. This challenge is catalysing the use of more mechanistic knowledge in safety assessment from both in silico and in vitro approaches in the hope that this will increase confidence in being able to identify modes of action (MoA) for the chemicals in question.

Responding to eruptive transitions during the 2020-2021 eruption of La Soufrière volcano, St. Vincent.

A critical challenge during volcanic emergencies is responding to rapid changes in eruptive behaviour. Actionable advice, essential in times of rising uncertainty, demands the rapid synthesis and communication of multiple datasets with prognoses. The 2020-2021 eruption of La Soufrière volcano exemplifies these challenges: a series of explosions from 9-22 April 2021 was preceded by three months of effusive activity, which commenced with a remarkably low level of detected unrest.

The Mechanical Properties of Canine Skeletal Muscle.

This study was undertaken to determine if fiber arrangement was responsible for differences in the whole muscle mechanical properties. Experiments were carried out in blood perfused dog skeletal muscles at approximately normal body temperature between 36° and 38°C. The following mechanical relationships were studied using a pneumatic muscle lever to measure Tension (P), length (L) and dP/dt and dL/dt with a high frequency oscillograph (500-1000 Hz): 1.

Disaster aid? Mapping historical responses to volcanic eruptions from 1800-2000 in the English-speaking Eastern Caribbean: their role in creating vulnerabilities.

This paper uses volcanic eruptions on the Caribbean islands of Montserrat and Saint Vincent to explore the role that British colonial rule in the past and near past (1800-2000) has played in response to and recovery from hazardous events, and in turn, the influence that the nature of the hazards has on these responses. It shows that systemic vulnerabilities to natural hazards have been created by inadequate aid responses and longer-term chronic problems and demonstrates that hazard impacts are compounded by them. Vulnerabilities could be reduced by analysing integrated hazard impacts to generate mitigative measures across hazards and identify actions that more closely match timescales of political decision-making.

Cultivation of ammonia-oxidising archaea on solid medium.

Ammonia-oxidising archaea (AOA) are environmentally important microorganisms involved in the biogeochemical cycling of nitrogen. Routine cultivation of AOA is exclusively performed in liquid cultures and reports on their growth on solid medium are scarce. The ability to grow AOA on solid medium would be beneficial for not only the purification of enrichment cultures but also for developing genetic tools.

Technical Feasibility and Safety of Repeated Computed Tomography-Guided Transthoracic Intratumoral Injection of Gene-Modified Cellular Immunotherapy in Metastatic NSCLC.

Introduction: To assess the technical feasibility and safety of repeated percutaneous computed tomography (CT)-guided transthoracic biopsies and intratumoral injections of gene-modified dendritic cells in metastatic NSCLC.

Methods: A total of 15 patients with 15 NSCLC lesions measuring greater than 1.0 cm underwent two cycles of intratumoral biopsies and CCL21 dendritic cell injections separated by 7 days.

Adherence to Dietary and Physical Activity Guidelines in Australian Undergraduate Biomedical Students and Associations with Body Composition and Metabolic Health: A Cross-Sectional Study.

There is a paucity of data on whether Australian university students are meeting specific nutrient guidelines, and the relationship between diet and physical activity patterns with body composition and metabolic health. In this study, biomedical students from The University of Queensland were recruited (150 males and 211 females, 19-25 years), and nutritional intake (ASA24-Australia) and physical activity levels (Active Australia Survey) quantified. Body composition (height, waist circumference, body mass, BMI, and percentage body fat; BOD POD) and metabolic health (oral glucose tolerance test) were also measured.

Proteomic analysis of dietary restriction in yeast reveals a role for Hsp26 in replicative lifespan extension.

Dietary restriction (DR) has been shown to increase lifespan in organisms ranging from yeast to mammals. This suggests that the underlying mechanisms may be evolutionarily conserved. Indeed, upstream signalling pathways, such as TOR, are strongly linked to DR-induced longevity in various organisms.

Prevalence of unmasked and improperly masked behavior in indoor public areas during the COVID-19 pandemic: Analysis of a stratified random sample from Louisville, Kentucky.

Wearing a facial mask can limit COVID-19 transmission. Measurements of communities' mask use behavior have mostly relied on self-report. This study's objective was to devise a method to measure the prevalence of improper mask use and no mask use in indoor public areas without relying on self-report.

Recommendations for Preventing Medication Diversion and Misuse in Hospice Care: A Modified Delphi Study.

Context: Recommendations are needed to help minimize the risks of medication diversion and misuse in the hospice setting.

Objective: To identify recommendations that could help prevent medication diversion and misuse in hospice care.

Methods: A modified Delphi method was utilized.

Ectopic expression of Triticum polonicum VRT-A2 underlies elongated glumes and grains in hexaploid wheat in a dosage-dependent manner.

Flower development is an important determinant of grain yield in crops. In wheat (Triticum spp.), natural variation for the size of spikelet and floral organs is particularly evident in Triticum turgidum ssp.