Bone and muscle are coupled through developmental, mechanical, paracrine, and autocrine signals. Genetic variants at the CPED1-WNT16 locus are dually associated with bone- and muscle-related traits. While Wnt16 is necessary for bone mass and strength, this fails to explain pleiotropy at this locus. Here, we show wnt16 is required for spine and muscle morphogenesis in zebrafish. In embryos, wnt16 is expressed in dermomyotome and developing notochord, and contributes to larval myotome morphology and notochord elongation. Later, wnt16 is expressed at the ventral midline of the notochord sheath, and contributes to spine mineralization and osteoblast recruitment. Morphological changes in wnt16 mutant larvae are mirrored in adults, indicating that wnt16 impacts bone and muscle morphology throughout the lifespan. Finally, we show that wnt16 is a gene of major effect on lean mass at the CPED1-WNT16 locus. Our findings indicate that Wnt16 is secreted in structures adjacent to developing bone (notochord) and muscle (dermomyotome) where it affects the morphogenesis of each tissue, thereby rendering wnt16 expression into dual effects on bone and muscle morphology. This work expands our understanding of wnt16 in musculoskeletal development and supports the potential for variants to act through WNT16 to influence bone and muscle via parallel morphogenetic processes.

No abstract

Identifying the mechanisms by which genetic variants exert pleiotropic effects on muscle and bone is a promising strategy to reveal molecular pathways that stimulate coupled bone and muscle growth, and which can be targeted to treat osteoporosis and sarcopenia simultaneously. Previously, it has been shown that genetic variants at the CPED1-WNT16 locus have pleiotropic effects on bone mineral density (BMD) and lean tissue mass in humans. While it is known that WNT16 is required for normal bone mass, our current functional understanding of WNT16 cannot account for dual effects on bone and lean mass at this locus. Using single cell analysis, microCT imaging, and genetic approaches, we reveal that wnt16 exerts pleiotropic effects on bone and lean tissue in zebrafish. We show an early influence of wnt16 on axial bone and lean tissue during skeletogenesis, and provide evidence that wnt16+ cells are myogenic precursors during embryonic development. We also show that wnt16 is a gene of major effect at the CPED1-WNT16 locus. Our findings indicate a critical function for wnt16 in muscle and lean tissue development and support WNT16 as the principal gene driving pleiotropic effects on bone and lean mass at this locus.

Background Stroke is the most common acquired neurological disease in the adult population worldwide with an incidence of 16 million new cases every year responsible for about 6.1 million deaths and 130.6 million disability-adjusted life-years (DALYs). The objectives of this work were to study the level of stroke awareness and the proper response for suspected stroke patients in urban and rural areas of Tanta City, Egypt. The study was conducted on 1869 Egyptian Citizens; 908 and 961 reside in urban and rural areas, respectively, who were submitted to a face-to-face interview using the stroke awareness questionnaire (Arabic version). Results Rural participants showed a significant reduction in acute cerebrovascular stroke (CVS) awareness and knowledge including the most affected organ by CVS, what are the risk factors, what are the early stroke symptoms, is there specific treatment for acute ischemic stroke, and what is the proper reaction when confronted with a case of acute CVS? Conclusion Urban populations have better recognition of stroke risk factors, early stroke symptoms, and the proper response when confronted with a case of acute CVS when compared with rural people possibly due to better socioeconomic status and higher educational levels.

A US federal court recently ruled against requiring health insurers to cover HIV pre-exposure prophylaxis (PrEP) under the Affordable Care Act. For every 10% decrease in PrEP coverage resulting from this ruling among US men who have sex with men, we estimate an additional 1,140 HIV infections in the following year in that population.