The structure of the IL-11 signalling complex provides insight into receptor variants associated with craniosynostosis.

Interleukin 11 (IL-11), a member of the IL-6 family of cytokines, has roles in haematopoiesis, inflammation, bone metabolism, and craniofacial development. IL-11 also has pathological roles in chronic inflammatory diseases, fibrosis, and cancer. In this structural snapshot, we explore our recently published cryo-EM structure of the human IL-11 signalling complex to understand the molecular mechanisms of complex formation and disease-associated mutations.

Multi-biomarker approach for estimating population size in a national-scale wastewater-based epidemiology study.

This study identifies biochemical markers (BCIs) that can be used as population markers in wastewater-based epidemiology (WBE) and compares their estimates with other established population size estimation (PE) methods, including census data (PE). Several groups of BCIs (64 targets: genetic and chemical markers) were investigated in an intercity study, including 10 cities/towns within England equating to a population of ∼7 million people. Several selection criteria were applied to identify the best BCIs to provide robust estimation of population size at a catchment level: (1) excellent performance with analytical methods; (2) excellent fit of the linear regression model which indicates PE-driven BCI daily loads; (3) low temporal variability in usage; (4) human-linked origin.

Outcomes for centenarian patients admitted with orthopaedic trauma.

Introduction: The United Kingdom (UK) and world's population is aging with patients living longer, often with many co-morbidities. It is expected that patients of extreme old age would have poor outcomes following trauma; however, this assumption is not clearly evidenced. This study aims to present the outcomes of patients aged 100 or older admitted to a single hospital trust following admission for orthopaedic trauma.

Pump-driven clinical infusions: laboratory comparison of pump types, fluid composition and flow rates on model drug delivery applying a new quantitative tool, the pharmacokinetic coefficient of short-term variation (PK-CV).

Critically ill or anesthetized patients commonly receive pump-driven intravenous infusions of potent, fast-acting, short half-life medications for managing hemodynamics. Stepwise dosing, e.g.

Performance of a Continuous Subcutaneous Insulin Infusion (CSII) Pump With Acoustic Volume and Flow Sensing in Simulated High-Consequence Situations.

An insulin pump's failure to deliver insulin in the right amount at the right time is a preventable cause of hospitalization. We evaluated key performance metrics of a novel insulin pump that prevents "silent insulin non-delivery" caused by blockage, delivery of air and site leakage. This is accomplished via an acoustic sensor that measures the volume of insulin delivered with each pulse in real-time.

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan.

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark. Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK-AMPK-mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies.

Direct activation of PI3K in osteoblasts and osteocytes strengthens murine bone through sex-specific actions on cortical surfaces.

Intracellular phosphoinositide 3-kinase (PI3K) signaling is activated by multiple bone-active receptors. Genetic mutations activating PI3K signaling are associated with clinical syndromes of tissue overgrowth in multiple organs, often including the skeleton. While one formation is increased by removing the PI3K inhibitor (phosphatase and TENsin homolog deleted on chromosome 10 (PTEN)), the effect of direct PI3K activation in the osteoblast lineage has not been reported.

Fetal growth delay caused by loss of non-canonical imprinting is resolved late in pregnancy and culminates in offspring overgrowth.

Germline epigenetic programming, including genomic imprinting, substantially influences offspring development. Polycomb Repressive Complex 2 (PRC2) plays an important role in Histone 3 Lysine 27 trimethylation (H3K27me3)-dependent imprinting, loss of which leads to growth and developmental changes in mouse offspring. In this study, we show that offspring from mouse oocytes lacking the PRC2 protein Embryonic Ectoderm Development (EED) were initially developmentally delayed, characterised by low blastocyst cell counts and substantial growth delay in mid-gestation embryos.

Enrichable consortia of microbial symbionts degrade macroalgal polysaccharides in fish.

Coastal herbivorous fishes consume macroalgae, which is then degraded by microbes along their digestive tract. However, there is scarce genomic information about the microbiota that perform this degradation. This study explores the potential of gastrointestinal microbial symbionts to collaboratively degrade and ferment polysaccharides from red, green, and brown macroalgae through study of carbohydrate-active enzyme and sulfatase sequences.

Loss of maternal calcitriol reversibly alters early offspring growth and skeletal development in mice.

Ablation of Cyp27b1 eliminates calcitriol but does not disturb fetal mineral homeostasis or skeletal development. However, independent of fetal genotypes, maternal loss of Cyp27b1 altered fetal mineral and hormonal levels compared to offspring of WT dams. We hypothesized that these maternal influences would alter postnatal skeletal development.

Severe Osteoporosis With Pathogenic Variant.

A 24-year-old female patient was diagnosed with osteoporosis after presenting with numerous fractures throughout her childhood and adolescence. Risk factors included chronic constipation, severe vitamin D deficiency, and long-term high-dose steroid use for severe eczema. Metabolic bone disorder clinical exome screening (limited panel of metabolic bone disorders and gastrointestinal disorders) was undertaken and revealed a class 4 likely pathogenic variant in the gene known to cause osteoporosis.

Craniosynostosis-associated variants in the IL-11R complex: new insights and questions.

Skull growth involves the expansion of both the flat calvarial bones of the skull and the fibrous marginal zones, termed sutures, between them. This process depends on co-ordinated proliferation of mesenchymal-derived progenitor cells within the sutures, and their differentiation to osteoblasts which produce the bone matrix required to expand the size of the bony plates. Defects lead to premature closure of these sutures, termed craniosynostosis, resulting in heterogeneous head shape differences due to restricted growth of one or more sutures.

Preclinical Rodent Models for Human Bone Disease, Including a Focus on Cortical Bone.

Preclinical models (typically ovariectomized rats and genetically altered mice) have underpinned much of what we know about skeletal biology. They have been pivotal for developing therapies for osteoporosis and monogenic skeletal conditions, including osteogenesis imperfecta, achondroplasia, hypophosphatasia, and craniodysplasias. Further therapeutic advances, particularly to improve cortical strength, require improved understanding and more rigorous use and reporting.

Oncostatin M: Dual Regulator of the Skeletal and Hematopoietic Systems.

Purpose Of The Review: The bone and hematopoietic tissues coemerge during development and are functionally intertwined throughout mammalian life. Oncostatin M (OSM) is an inflammatory cytokine of the interleukin-6 family produced by osteoblasts, bone marrow macrophages, and neutrophils. OSM acts via two heterodimeric receptors comprising GP130 with either an OSM receptor (OSMR) or a leukemia inhibitory factor receptor (LIFR).

Enrichable consortia of microbial symbionts degrade macroalgal polysaccharides in fish.

Coastal herbivorous fishes consume macroalgae, which is then degraded by microbes along their digestive tract. However, there is scarce foundational genomic work on the microbiota that perform this degradation. This study explores the potential of gastrointestinal microbial symbionts to collaboratively degrade and ferment polysaccharides from red, green, and brown macroalgae through study of carbohydrate-active enzyme and sulfatase sequences.

Tropical Red Macroalgae Cultivation with a Focus on Compositional Analysis.

To create carbon efficient sources of bioenergy feedstocks and feedstuff for aquaculture and terrestrial livestock, it is critical to develop and commercialize the most efficient seaweed cultivation approach with a sustainable nutrient input supply. Here, we present data for a novel, onshore tropical macroalgae cultivation system, based on influent deep seawater as the nutrient and carbon sources. Two red algal species were selected, and as the basis for growth optimization.

Exploring the experiences of parents of Autistic children when attending the diagnostic imaging department for an X-ray examination.

Introduction: Autism is a neuro-developmental condition which affects the social-emotional skills, behaviour, language, communication skills and flexibility of thoughts of an individual and their sensory processing. This can result in Autistic service users finding it difficult to navigate current healthcare provision and cope with the unpredictable environment. This paper explores the experiences of parents of Autistic children when attending the diagnostic imaging department for an X-ray examination.

Wastewater profiling of illicit drugs, an estimation of community consumption: A case study of eThekwini Metropolitan Municipality, South Africa.

Estimation of community-wide consumption of illicit drugs through wastewater analysis is a new concept in Africa although widely applied in developed nations as wastewater-based epidemiology (WBE). It is an important tool that can be used in understanding supply and demand patterns of illicit drug use on a local, national, and international scale. Information on illicit drug use is currently limited in Africa, because of a lack of monitoring structures by governments and financial constraints.

Antimicrobials and antimicrobial resistance genes in a one-year city metabolism longitudinal study using wastewater-based epidemiology.

This longitudinal study tests correlations between antimicrobial agents (AA) and corresponding antimicrobial resistance genes (ARGs) generated by a community of >100 k people inhabiting one city (Bath) over a 13 month randomised monitoring programme of community wastewater. Several AAs experienced seasonal fluctuations, such as the macrolides erythromycin and clarithromycin that were found in higher loads in winter, whilst other AA levels, including sulfamethoxazole and sulfapyridine, stayed consistent over the study period. Interestingly, and as opposed to AAs, ARGs prevalence was found to be less variable, which indicates that fluctuations in AA usage might either not directly affect ARG levels or this process spans beyond the 13-month monitoring period.

Increasing muscle contractility through low-frequency stimulation alters tibial bone geometry and reduces bone strength in and dystrophic mice.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations or deletions in the dystrophin gene, for which there remains no cure. As DMD patients also develop bone fragility because of muscle weakness and immobilization, better understanding of the pathophysiological mechanisms of dystrophin deficiency will help develop therapies to improve musculoskeletal health. Since alterations in muscle phenotype can influence bone structure, we investigated whether modifying muscle contractile activity through low-frequency stimulation (LFS) could alter bone architecture in mouse models of DMD.

Herbivorous Fish Microbiome Adaptations to Sulfated Dietary Polysaccharides.

Marine herbivorous fish that feed primarily on macroalgae, such as those from the genus are essential for maintaining coral health and abundance on tropical reefs. Here, deep metagenomic sequencing and assembly of gut compartment-specific samples from three sympatric, macroalgivorous Hawaiian kyphosid species have been used to connect host gut microbial taxa with predicted protein functional capacities likely to contribute to efficient macroalgal digestion. Bacterial community compositions, algal dietary sources, and predicted enzyme functionalities were analyzed in parallel for 16 metagenomes spanning the mid- and hindgut digestive regions of wild-caught fishes.

Multi-strain compatibility polymorphism between a parasite and its snail host, a neglected vector of schistosomiasis in Africa.

Interactions between and its snail host are understood primarily through experimental work with one South American vector species, . However, 90% of schistosomiasis transmission occurs in Africa, where a diversity of species may serve as vectors. With the long-term goal of determining the genetic and ecological determinants of infection in African snail hosts, we developed genetic models of , a principal vector in the African Great Lakes.