Predicting Affect Classification in Mental Status Examination Using Machine Learning Face Action Recognition System: A Pilot Study in Schizophrenia Patients

Classifying patients’ affect is a pivotal part of the mental status examination. However, this common practice is often widely inconsistent between raters. Recent advances in the field of Facial Action Recognition (FAR) have enabled the development of tools that can act to identify facial expressions from videos. In this study, we aimed to explore the potential of using machine learning techniques on FAR features extracted from videotaped semi-structured psychiatric interviews of 25 male schizophrenia inpatients (mean age 41.2 years, STD = 11.4). Five senior psychiatrists rated patients’ affect based on the videos. Then, a novel computer vision algorithm and a machine learning method were used to predict affect classification based on each psychiatrist affect rating. The algorithm is shown to have a significant predictive power for each of the human raters. We also found that the eyes facial area contributed the most to the psychiatrists’ evaluation of the patients’ affect. This study serves as a proof-of-concept for the potential of using the machine learning FAR system as a clinician-supporting tool, in an attempt to improve the consistency and reliability of mental status examination

The role of UDP-Glc:glycoprotein glucosyltransferase 1 in the maturation of an obligate substrate prosaposin

A natural substrate for UGT1 is confirmed, revealing how the enzyme functions in the calnexin chaperone system as a quality control step in protein folding

Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia

Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) encompasses a group of disorders characterized by renal tubular and interstitial abnormalities, leading to slow progressive loss of kidney function requiring dialysis and kidney transplantation. Mutations in UMOD, MUC1, and REN are responsible for many, but not all, cases of ADTKD. We report on two families with ADTKD and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. Ultrasound and kidney biopsy revealed small dysplastic kidneys with cysts and tubular atrophy with secondary glomerular sclerosis, respectively. Exclusion of known ADTKD genes coupled with linkage analysis, whole-exome sequencing, and targeted re-sequencing identified heterozygous missense variants in SEC61A1—c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly)—both affecting functionally important and conserved residues in SEC61. Both transiently expressed SEC6A1A variants are delocalized to the Golgi, a finding confirmed in a renal biopsy from an affected individual. Suppression or CRISPR-mediated deletions of sec61al2 in zebrafish embryos induced convolution defects of the pronephric tubules but not the pronephric ducts, consistent with the tubular atrophy observed in the affected individuals. Human mRNA encoding either of the two pathogenic alleles failed to rescue this phenotype as opposed to a complete rescue by human wild-type mRNA. Taken together, these findings provide a mechanism by which mutations in SEC61A1 lead to an autosomal-dominant syndromic form of progressive chronic kidney disease. We highlight protein translocation defects across the endoplasmic reticulum membrane, the principal role of the SEC61 complex, as a contributory pathogenic mechanism for ADTKD

Selective re-routing of prion protein to proteasomes and alteration of its vesicular secretion prevent PrPSc formation

Conversion of the cellular prion protein (PrPC) into the abnormal scrapie isoform (PrPSc) is the hallmark of prion diseases, which are fatal and transmissible neurodegenerative disorders. ER-retained anti-prion recombinant single-chain Fv fragments have been proved to be an effective tool for inhibition of PrPC trafficking to the cell surface and antagonize PrPSc formation and infectivity. In the present study, we have generated the secreted version of 8H4 intrabody (Sec-8H4) in order to compel PrPC outside the cells. The stable expression of the Sec-8H4 intrabodies induces proteasome degradation of endogenous prion protein but does not influence its glycosylation profile and maturation. Moreover, we found a dramatic diverting of PrPC traffic from its vesicular secretion and, most importantly, a total inhibition of PrPSc accumulation in NGF-differentiated Sec-8H4 PC12 cells. These results confirm that perturbing the intracellular traffic of endogenous PrPC is an effective strategy to inhibit PrPSc accumulation and provide convincing evidences for application of intracellular antibodies in prion diseases

Pathogen evasion strategies for the major histocompatibility complex class I assembly pathway

Major histocompatibility complex (MHC) class I molecules bind and present short antigenic peptides from endogenously or exogenously derived sources to CD8+ cytotoxic T lymphocytes (CTL), with recognition of a foreign peptide normally targeting the cell for lysis. It is generally thought that the high level of MHC polymorphism, which is concentrated mostly within the peptide-binding groove, is driven by the ‘evolutionary arms race’ against pathogens. Many pathogens have developed novel and intriguing mechanisms for evading the continuous sampling of the intracellular and intercellular environments by MHC molecules, none more so than viruses. The characterization of immunoevasion mechanisms has improved our understanding of MHC biology. This review will highlight our current understanding of the MHC class I biosynthetic pathway and how it has been exploited by pathogens, especially viruses, to potentially evade CTL recognition

EDEM1 reveals a quality control vesicular transport pathway out of the endoplasmic reticulum not involving the COPII exit sites

Immature and nonnative proteins are retained in the endoplasmic reticulum (ER) by the quality control machinery. Folding-incompetent glycoproteins are eventually targeted for ER-associated protein degradation (ERAD). EDEM1 (ER degradation-enhancing α-mannosidase-like protein 1), a putative mannose-binding protein, targets misfolded glycoproteins for ERAD. We report that endogenous EDEM1 exists mainly as a soluble glycoprotein. By high-resolution immunolabeling and serial section analysis, we find that endogenous EDEM1 is sequestered in buds that form along cisternae of the rough ER at regions outside of the transitional ER. They give rise to ≈150-nm vesicles scattered throughout the cytoplasm that are lacking a recognizable COPII coat. About 87% of the immunogold labeling was over the vesicles and ≈11% over the ER lumen. Some of the EDEM1 vesicles also contain Derlin-2 and the misfolded Hong Kong variant of α-1-antitrypsin, a substrate for EDEM1 and ERAD. Our results demonstrate the existence of a vesicle budding transport pathway out of the rough ER that does not involve the canonical transitional ER exit sites and therefore represents a previously unrecognized passageway to remove potentially harmful misfolded luminal glycoproteins from the ER