Phosphorylation of N-glycans in the brain: The case for a non-canonical pathway?

Asparagine-linked glycosylation (N-glycosylation) is a common co- and post-translational modification that refers to the addition of complex carbohydrates, called N-linked glycans (N-glycans), to asparagine residues within defined sequons of polypeptide acceptors. Some N-glycans can be modified by the addition of phosphate moieties to their monosaccharide residues, thus forming phospho-N-glycans (PNGs). The most prominent such carbohydrate modification is mannose-6-phosphate (M6P) which plays a well-established role in trafficking of acid hydrolases to lysosomes.

Higher hospital volume reduces early failure rates in single-stage revision TKR for infection: An analysis of the United Kingdom National Joint Registry and National Administrative Databases.

Purpose: Revision knee replacement (RevKR) for infection is rare but increasing. It is hypothesised that higher hospital volume reduces adverse outcomes. The aim was to estimate the association of surgical unit volume with outcomes following first, single-stage RevKR for infection.

Quantitative approaches for studying G protein-coupled receptor signalling and pharmacology.

G protein-coupled receptor (GPCR) signalling pathways underlie numerous physiological processes, are implicated in many diseases and are major targets for therapeutics. There are more than 800 GPCRs, which together transduce a vast array of extracellular stimuli into a variety of intracellular signals via heterotrimeric G protein activation and multiple downstream effectors. A key challenge in cell biology research and the pharmaceutical industry is developing tools that enable the quantitative investigation of GPCR signalling pathways to gain mechanistic insights into the varied cellular functions and pharmacology of GPCRs.

Photo-Rechargeable Sodium-Ion Batteries with a Two-Dimensional MoSe Crystal Cathode.

Combining energy harvesting with energy storage systems in a single device could offer great advantages for continuous power supply in both indoor and outdoor electric applications. In this work, we demonstrate a photochargeable sodium-ion battery (PSIB) based on a photoactive cathode of two-dimensional crystals of MoSe. This photocathode enables spontaneous photodriven charging of a sodium-ion battery cathode under illumination and an increase in the reversible capacity to 29% at 600 mA g compared to that under dark conditions during galvanostatic cycling.

Cannabis Use Cessation and the Risk of Psychotic Disorders: A Case-Control Analysis from the First Episode Case-Control EU-GEI WP2 Study: L'arrêt de l'utilisation du cannabis et le risque de troubles psychotiques: Une analyse cas-témoins tirée de l'étude cas-témoins EU-GEI WP2 centrée sur les premiers épisodes psychotiques.

Objectives: To establish whether the risk of psychotic disorders in cannabis users changes with time following cannabis cessation using data from the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI) case-control study.

Methods: The EU-GEI case-control study collected data from first episode psychosis patients and population controls across sites in Europe and Brazil between May 2010 and April 2015. Adjusted logistic regressions were applied to examine whether the odd of psychosis case status changed: (1) with time following cannabis cessation and (2) across different cannabis use groups.

Anxiety disorders presenting as gastrointestinal symptoms in children - a scoping review.

Functional gastrointestinal disorders (FGID) and their association with anxiety disorders in children significantly impact a child's functioning and treatment response. This study aimed to scope the evidence of anxiety disorders manifesting as FGID in children up to 16 years old. A comprehensive search strategy was conducted on Embase (1974-2024), Medline (via EBSCOHost 1946-2024), and APA PsycINFO (via EBSCOHost 1967-2024).

Associations of Atopic Dermatitis in Late Adolescence with Occupation, Mental Health, Income from Work and Marital Status: A National Longitudinal Study.

The main aim of this study was to evaluate longitudinal associations between atopic dermatitis (AD) in late adolescence and occupational socioeconomic group, labour market participation, income from work, and marital status later in adult life. Using Swedish population-based registry data a total of 205,394 men were included, born between 1952 and 1956 in Sweden and who underwent military conscription examination including assessment of atopic dermatitis (AD) and AD severity. The associations between AD and AD severity in late adolescence and labour market participation, income from work, marital status, and medication for anxiety and depression later in adult life were examined.

Synaptic Targets and Cellular Sources of CB1 Cannabinoid Receptor and Vesicular Glutamate Transporter-3 Expressing Nerve Terminals in Relation to GABAergic Neurons in the Human Cerebral Cortex.

Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunoreactive axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3.

Alterations in cardiac function correlate with a disruption in fatty acid metabolism in a mouse model of SMA.

Spinal Muscular Atrophy is an autosomal dominant disease caused by mutations and deletions within the SMN1 gene, with predominantly childhood onset. Although primarily a motor neuron disease, defects in non-neuronal tissues are described in both patients and mouse models. Here, we have undertaken a detailed study of the heart in the Smn2B/- mouse models of SMA, and reveal a thinning of the ventriclar walls as previously described in more severe mouse models of SMA.

Effects of Altered Haptic Feedback Gain Upon Balance Are Explained by Sensory Conflict Estimation.

Lightly touching a solid object reduces postural sway. Here, we determine the effect of artificially modifying haptic feedback for balance. Participants stood with their eyes closed, lightly gripping a manipulandum that moved synchronously with body sway to systematically enhance or attenuate feedback gain between +2 and -2, corresponding to motion in the same or opposite direction to the body, respectively.

Contagious Crying Revisited: A Cross-Cultural Investigation Into Infant Emotion Contagion Using Infrared Thermal Imaging.

Contagious crying in infants has been considered an early marker of their sensitivity to others' emotions, a form of emotional contagion, and an early basis for empathy. However, it remains unclear whether infant distress in response to peer distress is due to the emotional content of crying or acoustically aversive properties of crying. Additionally, research remains severely biased towards samples from Europe and North America.

SenPred: a single-cell RNA sequencing-based machine learning pipeline to classify deeply senescent dermal fibroblast cells for the detection of an in vivo senescent cell burden.

Background: Senescence classification is an acknowledged challenge within the field, as markers are cell-type and context dependent. Currently, multiple morphological and immunofluorescence markers are required. However, emerging scRNA-seq datasets have enabled an increased understanding of senescent cell heterogeneity.

Eating disorders in minority ethnic populations in Australia, Canada, Aotearoa New Zealand and the UK: a scoping review.

Background: Historically, eating disorder (ED) research has largely focused on White girls and women, with minority ethnic populations underrepresented. Most research exploring EDs in minority ethnic populations has been conducted in the United States (US). The aim of this scoping review, the first of its kind, was to systematically examine research on disordered eating and EDs among minority ethnic populations in Australia, Canada, Aotearoa New Zealand and the United Kingdom (UK), four countries with shared sociocultural and healthcare characteristics.

Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons.

Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals.

The value-for-money assessment and funding arrangements for high-priced drugs in an era of uncertainty: a comparative analysis of national health technology assessment agencies in South Korea, England, Australia, and Canada.

Background: Innovative health technologies have increasingly emerged as a promising solution for patients with untreatable or challenging conditions. However, these technologies often come with expensive costs and limited evidence at the time of launch. This study assessed how these high-priced drugs with limited evidence were appraised and introduced in South Korea, England, Australia, and Canada, where cost-effectiveness analysis (CEA) generally plays a central role in pricing and reimbursement decisions.

Exploring the barriers to cervical screening and perspectives on new self-sampling methods amongst under-served groups.

Background: Cervical screening rates have fallen in recent years in the UK, representing a health inequity for some under-served groups. Self-sampling alternatives to cervical screening may be useful where certain barriers prohibit access to routine cervical screening. However, there is limited evidence on whether self-sampling methods address known barriers to cervical screening and subsequently increase uptake amongst under-screened groups.

Service delivery and the role of clinical pharmacists in UK primary care for older people, including people with dementia: a scoping review.

Objective: As populations age globally, there is increasing prevalence of multiple long-term conditions, such as dementia, leading to many challenges. The burden on health and care services, economic pressures, and the necessity for innovative policies to better support older people and people with dementia becomes paramount. This review explores how clinical pharmacists working in UK primary care support older people and people with dementia.

Don't assume, ask! A focus group study on end-of-life care planning with people with intellectual disabilities from minoritised ethnic groups.

Background: People with intellectual disabilities are less likely to have access to palliative care, and the evidence shows that their deaths are often unanticipated, unplanned for, and poorly managed. Within the general population, people from minoritised ethnic groups are under-represented within palliative care services. End-of-life care planning with people with intellectual disabilities from minoritised ethnic groups may be a way to address these issues.

Enantioselective OTUD7B fragment discovery through chemoproteomics screening and high-throughput optimisation.

Deubiquitinating enzymes (DUBs) are key regulators of cellular homoeostasis, and their dysregulation is associated with several human diseases. The ovarian tumour protease (OTU) family of DUBs are biochemically well-characterised and of therapeutic interest, yet only a few tool compounds exist to study their cellular function and therapeutic potential. Here we present a chemoproteomics fragment screening platform for identifying novel DUB-specific hit matter, that combines activity-based protein profiling with high-throughput chemistry direct-to-biology optimisation to enable rapid elaboration of initial fragment hits against OTU DUBs.

Cryo-EM structure and evolutionary history of the conjugation surface exclusion protein TraT.

Conjugation plays a major role in dissemination of antimicrobial resistance genes. Following transfer of IncF-like plasmids, recipients become refractory to a second wave of conjugation with the same plasmid via entry (TraS) and surface (TraT) exclusion mechanisms. Here, we show that TraT from the pKpQIL and F plasmids (TraT and TraT) exhibits plasmid surface exclusion specificity.

Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests.

Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants.

Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications.

Early life microbial succession in the gut follows common patterns in humans across the globe.

Characterizing the dynamics of microbial community succession in the infant gut microbiome is crucial for understanding child health and development, but no normative model currently exists. Here, we estimate child age using gut microbial taxonomic relative abundances from metagenomes, with high temporal resolution (±3 months) for the first 1.5 years of life.

GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding.

The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic, owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor. Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conduct a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells.