Risk factors for acute abdominal pain (colic) in the adult horse: A scoping review of risk factors, and a systematic review of the effect of management-related changes

Acute abdominal pain (colic) is the most common reason for emergency veterinary treatment in the horse. Consolidation of data through a systematic review is important to inform evidence-based medicine and clinical guidelines, but there are currently no published systematic reviews on colic in the horse. The aim of this study was to identify, categorize and appraise the evidence on factors associated with increased risk of developing abdominal pain (colic) due to gastrointestinal disease in the adult horse. A scoping review was performed to identify and categorize evidence on all risk factors for colic. A systematic review of management-related risk factors was then performed following PRISMA guidelines. Both searches were conducted in Medline, CAB Abstracts and Web of Science databases, and publications were assessed against inclusion and exclusion criteria. For the scoping review, study and participant characteristics of included publications and key results were extracted and tabulated. For the systematic review, cohort, case-control or cross-sectional studies investigating acute abdominal pain in horses within two weeks of management changes were assessed. Study characteristics, participant characteristics and study results of included publications for the systematic review were extracted and tabulated. Included publications were appraised using the Joanna Briggs Institute Critical Appraisal Tools for cohort, case-control and cross-sectional studies. The scoping review search identified 3,756 publications. Fifty eight studies met final inclusion criteria, and 22 categories of risk factors were identified. These were grouped into three broad areas: horse-related factors, management-related factors and environment-related factors. The largest body of evidence related to management change. The systematic review of management change identified 410 publications: 14 met inclusion criteria for analysis. These consisted of one cohort, eight case-control and five cross-sectional studies. The studies were conducted between 1990–2008, and the majority of studies were located in the USA (8/14) or UK (3/14). The risk factors related to management change that were assessed were feed, carer, exercise, pasture, water and housing. The largest bodies of evidence for increased risk of colic associated with management change were changes in feed (5/14 publications) and recent change in housing (3/14). Most studies (8/14) did not meet the JBI criterion on confounding factors. There was marked heterogeneity of study methodologies and measures. This is the first study to use a combined scoping and systematic review to analyse evidence for modifiable risk factors for a common condition in the horse. It provides a comprehensive review that will be a key resource for researchers, veterinary practitioners and horse owners. It identified modifiable risk factors associated with an increased risk of colic which should be a key target for preventative health programmes. The findings from the critical appraisal were used to develop recommendations for future research to improve the quality of evidence-based veterinary medicine

Protein kinase Cα (PKCα) Regulates Bone Architecture and Osteoblast Activity*

Bones' strength is achieved and maintained through adaptation to load bearing. The role of the protein kinase PKCα in this process has not been previously reported. However, we observed a phenotype in the long bones of Prkca−/− female but not male mice, in which bone tissue progressively invades the medullary cavity in the mid-diaphysis. This bone deposition progresses with age and is prevented by disuse but unaffected by ovariectomy. Castration of male Prkca−/− but not WT mice results in the formation of small amounts of intramedullary bone. Osteoblast differentiation markers and Wnt target gene expression were up-regulated in osteoblast-like cells derived from cortical bone of female Prkca−/− mice compared with WT. Additionally, although osteoblastic cells derived from WT proliferate following exposure to estradiol or mechanical strain, those from Prkca−/− mice do not. Female Prkca−/− mice develop splenomegaly and reduced marrow GBA1 expression reminiscent of Gaucher disease, in which PKC involvement has been suggested previously. From these data, we infer that in female mice, PKCα normally serves to prevent endosteal bone formation stimulated by load bearing. This phenotype appears to be suppressed by testicular hormones in male Prkca−/− mice. Within osteoblastic cells, PKCα enhances proliferation and suppresses differentiation, and this regulation involves the Wnt pathway. These findings implicate PKCα as a target gene for therapeutic approaches in low bone mass conditions

The First Mid-infrared Detection of HNC in the Interstellar Medium: Probing the Extreme Environment toward the Orion Hot Core

We present the first mid-infrared (MIR) detections of HNC and H13CN in the interstellar medium, and numerous, resolved HCN rovibrational transitions. Our observations span 12.8 to 22.9 micron towards the hot core Orion IRc2, obtained with the Echelon-Cross-Echelle Spectrograph aboard the Stratospheric Observatory for Infrared Astronomy (SOFIA). Exceptional, ~5 km/s, resolution distinguishes individual rovibrational transitions of the HNC and HCN P, Q, and R branches; and the H13CN R branch. This allows direct measurement of the species' excitation temperatures, column densities, and relative abundances. HNC and H13CN exhibit a local standard rest velocity of -7 km/s that may be associated with an outflow from nearby radio source I and an excitation temperature of about 100 K. We resolve two velocity components for HCN, the primary component also being at -7 km/s with temperature 165 K. The hottest component, which had never before been observed, is at 1 km/s with temperature 309 K. This is the closest component to the hot core's centre measured to date. The derived 12C/13C=13 is below expectation for Orion's Galactocentric distance, but the derived HCN/HNC=72 is expected for this extreme environment. Compared to previous sub-mm and mm observations, our SOFIA line survey of this region shows that the resolved MIR molecular transitions are probing a distinct physical component and isolating the chemistry closest to the hot core

Investigating Gene Functions and Single-Cell Expression Profiles of De Novo Variants in Orofacial Clefts

Orofacial clefts (OFCs) are common congenital birth defects with various etiologies, including genetic variants. Online Mendelian Inheritance in Man (OMIM) annotated several hundred genes involving OFCs. Furthermore, several hundreds of de novo variants (DNVs) have been identified from individuals with OFCs. Some DNVs are related to known OFC genes or pathways, but there are still many DNVs whose relevance to OFC development is unknown. To explore novel gene functions and their cellular expression profiles, we focused on DNVs in genes that were not listed in OMIM. We collected 960 DNVs in 853 genes from published studies and curated these genes, based on the DNVs\u27 deleteriousness, into 230 and 23 genes related to cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), respectively. For comparison, we curated 178 CL/P and 277 CPO genes from OMIM. In CL/P, the pathways enriched in DNV and OMIM genes were significantly overlapped (p = 0.002). Single-cell RNA sequencing (scRNA-seq) analysis of mouse lip development revealed that both gene sets had abundant expression in the ectoderm (DNV genes: adjusted p = 0.032, OMIM genes: adjusted p \u3c 0.0002), while only DNV genes were enriched in the endothelium (adjusted p = 0.032). Although we did not achieve significant findings using CPO gene sets, which was mainly due to the limited number of DNV genes, scRNA-seq analysis implicated various expression patterns among DNV and OMIM genes. Our results suggest that combinatory pathway and scRNA-seq data analyses are helpful for contextualizing genes in OFC development

Modular metabolite assembly in C. elegans lysosome-related organelles

Signaling molecules derived from attachment of diverse primary metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that lysosome-related organelles (LROs) are required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Both modular glucosides and ascarosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism. We further show that cholinesterase (cest) homologs that localize to the LROs are required for assembly of both modular ascarosides and glucosides, mediating formation of ester and amide linkages between subsets of building blocks. Their specific biosynthesis suggests that modular glucosides, like ascarosides, serve dedicated signaling functions. Further exploration of LRO function and cest homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms

Modular metabolite assembly in C. elegans lysosome-related organelles

Signaling molecules derived from attachment of diverse primary metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that lysosome-related organelles (LROs) are required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Both modular glucosides and ascarosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism. We further show that cholinesterase (cest) homologs that localize to the LROs are required for assembly of both modular ascarosides and glucosides, mediating formation of ester and amide linkages between subsets of building blocks. Their specific biosynthesis suggests that modular glucosides, like ascarosides, serve dedicated signaling functions. Further exploration of LRO function and cest homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms

Modular metabolite assembly in Caenorhabditis elegans depends on carboxylesterases and formation of lysosome-related organelles

Signaling molecules derived from attachment of diverse metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that a pathway mediating formation of intestinal lysosome-related organelles (LROs) is required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Similar to modular ascarosides, the modular glucosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism, suggesting that modular glucosides, like the ascarosides, may serve signaling functions. We further show that carboxylesterases that localize to intestinal organelles are required for the assembly of both modular ascarosides and glucosides via ester and amide linkages. Further exploration of LRO function and carboxylesterase homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms

Modular metabolite assembly in Caenorhabditis elegans depends on carboxylesterases and formation of lysosome-related organelles

Signaling molecules derived from attachment of diverse metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that a pathway mediating formation of intestinal lysosome-related organelles (LROs) is required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Similar to modular ascarosides, the modular glucosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism, suggesting that modular glucosides, like the ascarosides, may serve signaling functions. We further show that carboxylesterases that localize to intestinal organelles are required for the assembly of both modular ascarosides and glucosides via ester and amide linkages. Further exploration of LRO function and carboxylesterase homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve