Information sharing within a social network is key to behavioral flexibility-Lessons from mice tested under seminaturalistic conditions.

Being part of a social structure offers chances for social learning vital for survival and reproduction. Nevertheless, studying the neural mechanisms of social learning under laboratory conditions remains challenging. To investigate the impact of socially transmitted information about rewards on individual behavior, we used Eco-HAB, an automated system monitoring the voluntary behavior of group-housed mice under seminaturalistic conditions.

Bayesian Effect Size Ranking to Prioritise Genetic Risk Variants in Common Diseases for Follow-Up Studies.

Biological datasets often consist of thousands or millions of variables, e.g. genetic variants or biomarkers, and when sample sizes are large it is common to find many associated with an outcome of interest, for example, disease risk in a GWAS, at high levels of statistical significance, but with very small effects.

Molecular and spatial analysis of tertiary lymphoid structures in Sjogren's syndrome.

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures.

Remodelling of the immune landscape by IFNγ counteracts IFNγ-dependent tumour escape in mouse tumour models.

Loss of IFNγ-sensitivity by tumours is thought to be a mechanism enabling evasion, but recent studies suggest that IFNγ-resistant tumours can be sensitised for immunotherapy, yet the underlying mechanism remains unclear. Here, we show that IFNγ receptor-deficient B16-F10 mouse melanoma tumours are controlled as efficiently as WT tumours despite their lower MHC class I expression. Mechanistically, IFNγ receptor deletion in B16-F10 tumours increases IFNγ availability, triggering a remodelling of the immune landscape characterised by inflammatory monocyte infiltration and the generation of 'mono-macs'.

Glial-immune interactions in barrier organs.

Neuro-immune interactions within barrier organs, such as lung, gut, and skin, are crucial in regulating tissue homeostasis, inflammatory responses, and host defence. Our rapidly advancing understanding of peripheral neuroimmunology is transforming the field of barrier tissue immunology, offering a fresh perspective for developing therapies for complex chronic inflammatory disorders affecting barrier organs. However, most studies have primarily examined interactions between the peripheral nervous system and the immune system from a neuron-focused perspective, while glial cells, the nonneuronal cells of the nervous system, have received less attention.

Dynamic human gut microbiome and immune shifts during an immersive psychosocial intervention program.

Background: Although depression is a leading cause of disability worldwide, the pathophysiological mechanisms underlying this disorder-particularly those involving the gut microbiome-are poorly understood.

Method: To investigate, we conducted a community-based observational study to explore complex associations between changes in the gut microbiome, cytokine levels, and depression symptoms in 52 participants (M = 49.56, SD = 13.

Asparagine availability controls germinal center B cell homeostasis.

The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2.

Dysregulation of MMP2-dependent TGF-ß2 activation impairs fibrous cap formation in type 2 diabetes-associated atherosclerosis.

Type 2 diabetes is associated with cardiovascular disease, possibly due to impaired vascular fibrous repair. Yet, the mechanisms are elusive. Here, we investigate alterations in the fibrous repair processes in type 2 diabetes atherosclerotic plaque extracellular matrix by combining multi-omics from the human Carotid Plaque Imaging Project cohort and functional studies.

Observation of E-cadherin adherens junction dynamics with metal-induced energy transfer imaging and spectroscopy.

Epithelial cadherin (E-cad) mediated cell-cell junctions play a crucial role in the establishment and maintenance of tissues and organs. In this study, we employed metal-induced energy transfer imaging and spectroscopy to investigate variations in intermembrane distance during adhesion between two model membranes adorned with E-cad. By correlating the measured intermembrane distances with the distinct E-cad junction states, we probed the dynamic behavior and diversity of E-cad junctions across different binding pathways.

Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis.

Infectious disease is the result of interactions between host and pathogen and can depend on genetic variations in both. We conduct a genome-to-genome study of paired human and Mycobacterium tuberculosis genomes from a cohort of 1556 tuberculosis patients in Lima, Peru. We identify an association between a human intronic variant (rs3130660, OR = 10.

A multi-omic atlas of human embryonic skeletal development.

Human embryonic bone and joint formation is determined by coordinated differentiation of progenitors in the nascent skeleton. The cell states, epigenetic processes and key regulatory factors that underlie lineage commitment of these cells remain elusive. Here we applied paired transcriptional and epigenetic profiling of approximately 336,000 nucleus droplets and spatial transcriptomics to establish a multi-omic atlas of human embryonic joint and cranium development between 5 and 11 weeks after conception.

Development of methodology to support molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: The STEpUP OA consortium.

Objectives: To develop a protocol for largescale analysis of synovial fluid proteins, for the identification of biological networks associated with subtypes of osteoarthritis.

Methods: Synovial Fluid To detect molecular Endotypes by Unbiased Proteomics in Osteoarthritis (STEpUP OA) is an international consortium utilising clinical data (capturing pain, radiographic severity and demographic features) and knee synovial fluid from 17 participating cohorts. 1746 samples from 1650 individuals comprising OA, joint injury, healthy and inflammatory arthritis controls, divided into discovery (n = 1045) and replication (n = 701) datasets, were analysed by SomaScan Discovery Plex V4.

Avoiding "a piece of paper on the wall that everyone ignores": A qualitative study on the barriers for implementing open fracture guidelines.

Background: Ortho-plastic evidence-based clinical guidelines for open fractures have demonstrated to standardise care and improve outcomes for patients admitted following lower extremity trauma. Despite its benefits, very few countries have introduced such guidance. The aim of this study was to explore the attitudes, barriers and limitations to the development and implementation of guidelines for lower limb open fractures METHODS: Twelve renowned orthopaedic and plastic surgeons, based in countries with no guidelines at present, underwent semi-structured interviews.

Quality of Life after Open Extremity Trauma (QUINTET) study: An international, multicentric, observational, cohort study of quality of life following lower extremity open fractures.

Introduction: Open lower limb fractures are severe injuries with long-lasting consequences. Limited research has been conducted on the impact of these injuries on quality of life (QoL), internationally.

Methods: The Quality of Life after Open Extremity Trauma (QUINTET) study was designed as an international, multicentric, observational, cohort study of patients presented with open lower limb fractures.

A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease.

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences.

Population and transmission dynamics model to determine WHO targets for eliminating Hepatitis C virus in Thailand.

Background: Hepatitis C Virus is endemic to many areas of Thailand, whose population structure is tending towards older age groups as birth rate and mortality decrease. With around 790,000 cases in 2019, prevalence is still relatively high, but the World Health Organisation has called for elimination of HCV by 2030.

Methods: An age structured compartmental transmission model was used to explore the effectiveness of screening strategies with respect to WHO elimination goals, as well as the effect of changing population structure on the success or failure of such strategies.