Rare Variant Enrichment analysis Supports

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, onl

Development of Early-Warning Model for Intensive Pig Breeding

International audienceFollowing the rapid development of intensive pig breeding in China, the impact of environmental factors on the production and health of pigs has become increasingly apparent, and the monitoring of these environmental factors recognized as critical for improved breeding productivity. Based on the effects of environmental factors on pig growth, this paper established an early-warning model of the piggery environment. Using the model and the environmental factors, which were obtained in real time from a piggery, it was possible to obtain timely warning information, conducive to both creating an appropriate breeding environment for pigs and reducing the incidence of disease. In this article, we established the environmental early-warning indicators relating to pig breeding and then demonstrated the method based on single-factor and fuzzy comprehensive multi-factor models of the piggery environment. Finally, the two models were analyzed based on the experimental results, which showed that the fuzzy comprehensive early-warning model performed better than the single-factor model, and that it could be applied in an intensive farming environment to provide timely warning of environmental deterioration, to maintain the safety of the pig-breeding environment

Self-Calibrated Multi-Floor Localization Based on Wi-Fi Ranging/Crowdsourced Fingerprinting and Low-Cost Sensors

Crowdsourced localization using geo-spatial big data has become an effective approach for constructing smart-city-based location services with the fast growing number of Internet of Things terminals. This paper presents a self-calibrated multi-floor indoor positioning framework using a combination of Wi-Fi ranging, crowdsourced fingerprinting and low-cost sensors (SM-WRFS). The localization parameters, such as heading and altitude biases, step-length scale factor, and Wi-Fi ranging bias are autonomously calibrated to provide a more accurate forward 3D localization performance. In addition, the backward smoothing algorithm and a novel deep-learning model are applied in order to construct an autonomous and efficient crowdsourced Wi-Fi fingerprinting database using the detected quick response (QR) code-based landmarks. Finally, the adaptive extended Kalman filter is adopted to combine the corresponding location sources using different integration models to provide a precise multi-source fusion based multi-floor indoor localization performance. The real-world experiments demonstrate that the presented SM-WRFS is proven to realize precise 3D indoor positioning under different environments, and the meter-level positioning accuracy can be acquired in Wi-Fi ranging supported indoor areas

Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking

iallelic variants in genes for seven out of eight subunits of the conserved oligomeric Golgi complex (COG) are known to cause recessive congenital disorders of glycosylation (CDG) with variable clinical manifestations. COG3 encodes a constituent subunit of the COG complex that has not been associated with disease traits in humans. Herein, we report two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families that co-segregated with COG3-CDG presentations. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings. Biochemical analysis of serum transferrin from one family showed the loss of a single sialic acid. Western blotting on patient-derived fibroblasts revealed reduced COG3 and COG4. Further experiments showed delayed retrograde vesicular recycling in patient cells. This report adds to the knowledge of the COG-CDG network by providing collective evidence for a COG3-CDG rare disease trait and implicating a likely pathology of the disorder as the perturbation of Golgi traffickin

Immunoglobulin G inhibits glucocorticoid-induced osteoporosis through occupation of FcγRI.

Glucocorticoid-induced osteoporosis (GIOP) is a severe and common complication of long-term usage of glucocorticoids (GCs) and lacks of efficient therapy. Here, we investigated the mechanism of anti-inflammation effect and osteoclastogenesis side effect of GCs and immunoglobulin G (IgG) treatment against GIOP. GCs inhibited SLE IgG-induced inflammation, while IgG inhibited GCs-induced osteoclastogenesis. FcγRI and glucocorticoid receptor (GR) were found directly interacted with each other. GCs and IgG could reduce the expression of FcγRI on macrophages. The deficiency of FcγRI affected osteoclastogenesis by GCs and systemic lupus erythematosus (SLE) IgG-induced inflammation. Also, IgG efficiently reduced GIOP in mice. These data showed that GCs could induce osteoporosis and inhibit IgG-induced inflammation through FcγRI while IgG efficiently suppressed osteoporosis induced by GCs through FcγRI. Hence, our findings may help in developing a feasible therapeutic strategy against osteoporosis, such as GIOP

Identification and Functional Study of a New Missense Mutation in the Motor Head Domain of Myosin VIIA in a Family with Autosomal Dominant Hearing Impairment (DFNA11)

<div><p>The <em>MYO7A</em> encodes a protein classified as an unconventional myosin. Here, we present a family with non-syndromic autosomal dominant hearing impairment that clinically resembles other previously published DFNA11 families. Affected members of the family present with an ascending audiogram affecting low and middle frequencies at young ages and then affecting all frequencies with increasing age. Genome-wide linkage analysis using Illumina Cyto-12 Chip mapped the disease locus to the DFNA11 interval in the family. A c.2003G→A (p.R668H) mutation of the <em>MYO7A</em>, is heterozygous in all affected family members and absent in 100 healthy individuals. Arg668His is located in a region of the myosin VIIA motor domain that is highly conserved among different species. Molecular modeling predicts that the conserved R668 residue plays important structural role in linking different lobes of motor domain together. In the actin-activated ATPase activity assay, the rate of NADH oxidation was higher in the wild-type myosin VIIA, indicating that the ATPase activity in the p.R668H mutant myosin VIIA was significantly destroyed.</p> </div