Stilesvang7356

The EMC1 gene, located on 1p36.13, encodes the subunit 1 of the endoplasmic reticulum-membrane protein complex, a highly conserved and ubiquitous multiprotein transmembrane complex. Pathogenic monoallelic and biallelic variants in EMC1 in humans have been reported only in six families, causing isolated visual impairment or in association with psychomotor retardation and cerebellar atrophy. We report a ten-year-old boy, born to unrelated parents, with early-onset severe global development delay due to novel EMC1 biallelic pathogenic variants. A truncating variant, p.(Tyr378*) and a missense variant, p.(Phe953Ser), located in read more and 23 of EMC1 gene respectively, have been found by reanalysis of exome sequencing data. The proband's phenotype included several signs that overlap with the phenotype of previously reported patients, associating severe global developmental delay, abnormal ophthalmological examination, and postnatal slow-down of the head circumference growth. Some distinguishing clinical signs were observed in comparison to patients from literature, such as autism spectrum disorder, absence of seizures, scoliosis or facial dysmorphic features, thus extending the spectrum of EMC1-related phenotypes. Similarly, brain MRI, performed at 2 years, showed normal cerebellar volume and structure, whereas cerebellar atrophy was described in literature. Moreover, difficulties of clinical differential diagnosis between EMC1-associated disease and other etiologies of global development delay support the importance of large-scale genetic investigations. Our diagnostic approach, through reanalysis of exome sequencing data, highlights the importance of reconsidering initial negative results for patients with a strong suspicion of genetic disease, and to update analytic pipelines in order to improve the diagnostic yield of exome sequencing. BACKGROUND/AIMS Health stakeholders are interested in the promise of healthy food incentives to improve dietary quality. The Smart Cart Study tested whether targeting healthful food incentives based on customer preferences and purchase history was effective for improving grocery purchase quality. DESIGN Randomized controlled crossover design of 224 adults who shopped at an independent supermarket for ≥50% of their groceries, participated in the store's loyalty program, and completed validated diet and sociodemographic/behavioral questionnaires. Participants were randomized using 11 blocked randomization; all participants received a 5% discount on their purchases with their loyalty card. For the first 13-weeks, the intervention group received individually-targeted weekly coupons (valued up to $10) with brief nutrition education to improve grocery purchase quality. The study team developed healthy food coupons, and the study algorithm allocated targeted coupons to participants' loyalty cards using purchase history, dietary preferences/allergies, and baseline diet quality. Control participants received weekly untargeted nutrition education and occasional generic coupons. Following a 2-4 week washout period, the two groups crossed over. The primary study outcomes were purchases of targeted products and grocery purchase quality measured using the validated Grocery Purchase Quality Index-2016; the study was powered to detect a minimum 3% difference in purchase quality. CONCLUSIONS The Smart Cart Study tested a novel application of automated individually-targeted marketing using customer purchase history, dietary quality, and preferences to identify and deliver targeted incentives to improve grocery purchase quality. Future research could scale this program through collaboration between multiple stakeholders, including supermarkets, workplace wellness initiatives and insurance companies. Feature extraction is one of the most important preprocessing steps in predicting the interactions between RNAs and proteins by applying machine learning approaches. Despite many efforts in this area, still, no suitable structural feature extraction tool has been designed. #link# Therefore, an online toolbox, named RPINBASE which can be applied to different scopes of biological applications, is introduced in this paper. This toolbox employs efficient nested queries that enhance the speed of the requests and produces desired features in the form of positive and negative samples. To show the capabilities of the proposed toolbox, the developed toolbox was investigated in the aptamer design problem, and the obtained results are discussed. RPINBASE is an online toolbox and is accessible at http//rpinbase.com. Skeletal muscle atrophy is a serious health condition that can arise due to aging, cancer, corticosteroid exposure, and denervation. Previous work comparing gene expression profiles in control and denervated muscle tissue revealed for the first time that Fam83d is expressed in skeletal muscle and is significantly induced in response to denervation. Quantitative PCR and Western blot analysis found that Fam83d is more highly expressed in proliferating myoblasts compared to differentiated myotubes. Characterization of the transcriptional regulation of Fam83d showed that ectopic expression of myogenic regulatory factors inhibits Fam83d reporter gene activity. To assess where Fam83d is localized in the cell, Fam83d was fused with green fluorescent protein, expressed in C2C12 cells, and found to localize in a punctate manner to the cytoplasm of muscle cells. To assess function, Fam83d was ectopically expressed in cultured muscle cells and markers of muscle cell differentiation, the MAP Kinase signaling pathway, and the AKT signaling pathway were analyzed. Fam83d overexpression resulted in significant repression of myosin heavy chain and myogenin expression, while phosphorylated ERK and AKT were also significantly repressed. Interestingly, inhibition of the 26S proteasome and the MAP kinase signaling pathway both resulted in stabilization of Fam83d during muscle cell differentiation. Finally, Fam83d has a putative phospholipase D-like domain that appears to be necessary for destabilizing casein kinase Iα and inhibiting ERK phosphorylation in cultured myoblasts. The discovery that Fam83d is expressed in skeletal muscle combined with the observation that Fam83d, a potential modulator of MAP kinase and AKT signaling, is induced in response to neurogenic atrophy helps further our understanding of the molecular and cellular events of skeletal muscle wasting.