O-GlcNAcase contributes to cognitive function in Drosophila

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Chemical fingerprints of emotional body odor

Chemical communication is common among animals. In humans, the chemical basis of social communication has remained a black box, despite psychological and neural research showing distinctive physiological, behavioral, and neural consequences of body odors emitted during emotional states like fear and happiness. We used a multidisciplinary approach to examine whether molecular cues could be associated with an emotional state in the emitter. Our research revealed that the volatile molecules transmitting different emotions to perceivers also have objectively different chemical properties. Chemical analysis of underarm sweat collected from the same donors in fearful, happy, and emotionally neutral states was conducted using untargeted two-dimensional (GC×GC) coupled with time of flight (ToF) MS-based profiling. Based on the multivariate statistical analyses, we find that the pattern of chemical volatiles (N = 1655 peaks) associated with fearful state is clearly different from that associated with (pleasant) neutral state. Happy sweat is also significantly different from the other states, chemically, but shows a bipolar pattern of overlap with fearful as well as neutral state. Candidate chemical classes associated with emotional and neutral sweat have been identified, specifically, linear aldehydes, ketones, esters, and cyclic molecules (5 rings). This research constitutes a first step toward identifying the chemical fingerprints of emotion.info:eu-repo/semantics/publishedVersio

Intracellular Lipid Accumulation and Mitochondrial Dysfunction Accompanies Endoplasmic Reticulum Stress Caused by Loss of the Co-chaperone DNAJC3.

Recessive mutations in DNAJC3, an endoplasmic reticulum (ER)-resident BiP co-chaperone, have been identified in patients with multisystemic neurodegeneration and diabetes mellitus. To further unravel these pathomechanisms, we employed a non-biased proteomic approach and identified dysregulation of several key cellular pathways, suggesting a pathophysiological interplay of perturbed lipid metabolism, mitochondrial bioenergetics, ER-Golgi function, and amyloid-beta processing. Further functional investigations in fibroblasts of patients with DNAJC3 mutations detected cellular accumulation of lipids and an increased sensitivity to cholesterol stress, which led to activation of the unfolded protein response (UPR), alterations of the ER-Golgi machinery, and a defect of amyloid precursor protein. In line with the results of previous studies, we describe here alterations in mitochondrial morphology and function, as a major contributor to the DNAJC3 pathophysiology. Hence, we propose that the loss of DNAJC3 affects lipid/cholesterol homeostasis, leading to UPR activation, β-amyloid accumulation, and impairment of mitochondrial oxidative phosphorylation

Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders

The number of individuals suffering from neuropsychiatric disorders (NPDs) has increased worldwide, with 3 million disability-adjusted life-years calculated in 2019. Though research using various approaches including genetics, imaging, clinical and animal models has advanced our knowledge regarding NPDs, we still lack basic knowledge regarding the underlying pathophysiological mechanisms. Moreover, there is an urgent need for highly effective therapeutics for NPDs i. Human induced pluripotent stem cells (hiPSCs) generated from somatic cells enabled scientists to create brain cells in a patient-specific manner. However, there are challenges to the use of hiPSCs that need to be addressed. In the current paper, consideration of best practices for neuropharmacological and neuropsychiatric research using hiPSCs will be discussed. Specifically, we provide recommendations for best practice in patient recruitment, including collecting demographic, clinical, medical (before and after treatment and response), diagnostic (incl. scales) and genetic data from the donors. We highlight considerations regarding donor genetics and sex, in addition to discussing biological and technical replicates. Furthermore, we present our views on selecting control groups/lines, experimental designs, and considerations for conducting neuropharmacological studies using hiPSC-based models in the context of NPDs. In doing so, we explore key issues in the field concerning reproducibility, statistical analysis, and how to translate in vitro studies into clinically relevant observations. The aim of this article is to provide a key resource for hiPSC researchers to perform robust and reproducible neuropharmacological studies, with the ultimate aim of improving identification and clinical translation of novel therapeutic drugs for NPDs

Reply: A homozygous GDAP2 loss-of-function variant in a patient with adult-onset cerebellar ataxia; and Novel GDAP2 pathogenic variants cause autosomal recessive spinocerebellar ataxia-27 (SCAR27) in a Chinese family

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