Knowledge discovery by analysis of community wastewater reveals factors driving public health risks.

This study tested a wide range of biological and chemical biomarker groups (BCIs) in wastewater from 10 cities in England to gain a better understanding of community exposure to chemicals and health outcomes and to unravel potential associations between disease prevalence, lifestyle choices and key risk factors. For example, viral BCIs showed relatively few correlations, except for norovirus gene abundance which correlated with antibiotic concentrations. Positive correlations between nicotine/cotinine and pharma BCIs indicated smoking as widely reported risk factor in diabetes, asthma/allergies and cardiovascular diseases.

Bridging spectroscopy and advanced molecular orientation analysis with new 4＋ angle polarization toolbox in Quasar.

Anisotropy plays a critical role in governing the mechanical, thermal, electrical, magnetic, and optical properties of materials, influencing their behavior across diverse applications. Probing and quantifying this directional dependence is crucial for advancing materials science and biomedical research, as it provides a deeper understanding of structural orientations at the molecular level, encompassing both scientific and industrial benefits. This study introduces the "4＋ Angle Polarization" widget, an innovative extension to the open-source Quasar platform (https://quasar.

Bone marrow neutrophil progenitors suppress osteoclast formation in murine cortical and trabecular bone.

In inflammation, circulating neutrophils indirectly damage the skeleton by inducing formation of bone-resorbing osteoclasts. However, neutrophil progenitors in marrow have no known physiological function. A bone-protective role for the neutrophil lineage was recently suggested when a profound defect in bone structure was observed in mice with neutropenia due to Granulocyte Colony Stimulating Factor (G-CSF) deletion coupled with STAT3 hyperactivation in bone cells.

Stress-induced fetal programming contributes to the manifestation of Duchenne muscular dystrophy in mice.

Prenatal stress predisposes offspring to neurocognitive, metabolic, and cardiovascular complications in adulthood, but the programming effects on the presentation of hereditary diseases are unknown. We investigate this in a mouse model of Duchenne muscular dystrophy (DMD), an X-linked neuromuscular disease that widely affects the central nervous system and peripheral tissues. Simulating the inheritance patterns of DMD by mating -heterozygous females with wildtype males, we compare the central, autonomic, and peripheral phenotypes of healthy and DMD-affected () male offspring born from mothers that were either stressed or non-stressed during gestation.

Isolation, Purification, Generation, and Culture of Osteocytes.

Osteocytes reside within the bone matrix and produce both paracrine and endocrine factors that influence the skeleton and other tissues. Despite their abundance and physiological importance, osteocytes have been challenging to study in vitro because they are difficult to extract and purify and do not retain their phenotype in standard culture conditions. New techniques for this purpose are emerging.

A partnership between the Australian and New Zealand Bone and Mineral Society (ANZBMS) and Bone: Highlights from the 2024 annual scientific meeting.

The Australian and New Zealand Bone and Mineral Society (ANZBMS) is a leading bone research society in the Asia-Pacific region and has been recognised for outstanding contributions to clinical and biomedical musculoskeletal research. To showcase the research being undertaken by ANZBMS members, a joint initiative between ANZBMS and the journal Bone via a special issue was developed to further enhance international collaboration. This editorial serves as an introduction to this initiative, where three past ANZBMS presidents have shared their clinical and fundamental highlights from the 2024 ANZBMS annual scientific meeting in Adelaide, held in conjunction with the Endocrine Society of Australia and the Society for Reproductive Biology.

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.

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.

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).

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.

Community infectious disease treatment with antimicrobial agents - A longitudinal one year study of antimicrobials in two cities via wastewater-based epidemiology.

Antimicrobial resistance (AMR) is one of the most significant global health threats. Inappropriate and over-usage of antimicrobial agents (AAs) is a major driver for AMR. Wastewater-based epidemiology (WBE) is a promising tool for monitoring AA usage in communities which is, for the first time, explored in this large scale, longitudinal study.

Wastewater-based epidemiology for comprehensive community health diagnostics in a national surveillance study: Mining biochemical markers in wastewater.

This manuscript showcases results from a large scale and comprehensive wastewater-based epidemiology (WBE) study focussed on multi-biomarker suite analysis of both chemical and biological determinants in 10 cities and towns across England equating to a population of ∼7 million people. Multi-biomarker suite analysis, describing city metabolism, can provide a holistic understanding to encompass all of human, and human-derived, activities of a city in a single model: from lifestyle choices (e.g.