Abramsleblanc9899

Functional neurological (conversion) disorder (FND) is a neuropsychiatric condition whereby individuals present with sensorimotor symptoms incompatible with other neurological disorders. Early-life maltreatment (ELM) is a risk factor for developing FND, yet few studies have investigated brain network-trauma relationships in this population. In this neuroimaging-gene expression study, we used two graph theory approaches to elucidate ELM subtype effects on resting-state functional connectivity architecture in 30 patients with motor FND. Twenty-one individuals with comparable depression, anxiety, and ELM scores were used as psychiatric controls. Thereafter, we compared trauma endophenotypes in FND with regional differences in transcriptional gene expression as measured by the Allen Human Brain Atlas (AHBA). In FND patients only, we found that early-life physical abuse severity, and to a lesser extent physical neglect, correlated with corticolimbic weighted-degree functional connectivity. Connectivity profiles influenced by physical abuse occurred in limbic (amygdalar-hippocampal), paralimbic (cingulo-insular and ventromedial prefrontal), and cognitive control (ventrolateral prefrontal) areas, as well as in sensorimotor and visual cortices. These findings held adjusting for individual differences in depression/anxiety, PTSD, and motor phenotypes. In FND, physical abuse also correlated with amygdala and insula coupling to motor cortices. In exploratory analyses, physical abuse correlated connectivity maps overlapped with the AHBA spatial expression of three gene clusters (i) neuronal morphogenesis and synaptic transmission genes in limbic/paralimbic areas; (ii) locomotory behavior and neuronal generation genes in left-lateralized structures; and (iii) nervous system development and cell motility genes in right-lateralized structures. These circuit-specific architectural profiles related to individual differences in childhood physical abuse burden advance our understanding of the pathophysiology of FND.Methamphetamine (METH) is a potent stimulant that induces a euphoric state but also causes cognitive impairment, neurotoxicity and neurodevelopmental deficits. Yet, the molecular mechanisms by which METH causes neurodevelopmental defects have remained elusive. Here we utilized human cerebral organoids and single-cell RNA sequencing (scRNA-seq) to study the effects of prenatal METH exposure on fetal brain development. We analyzed 20,758 cells from eight untreated and six METH-treated cerebral organoids and found that the organoids developed from embryonic stem cells contained a diverse array of glial and neuronal cell types. Thiomyristoyl mouse We further identified transcriptionally distinct populations of astrocytes and oligodendrocytes within cerebral organoids. Treatment of organoids with METH-induced marked changes in transcription in multiple cell types, including astrocytes and neural progenitor cells. METH also elicited novel astrocyte-specific gene expression networks regulating responses to cytokines, and inflammasome. Moreover, upregulation of immediate early genes, complement factors, apoptosis, and immune response genes suggests a neuroinflammatory program induced by METH regulating neural stem cell proliferation, differentiation, and cell death. Finally, we observed marked METH-induced changes in neuroinflammatory and cytokine gene expression at the RNA and protein levels. Our data suggest that human cerebral organoids represent a model system to study drug-induced neuroinflammation at single-cell resolution.Rab5 is a master regulator for endosome biogenesis and transport while its in vivo physiological function remains elusive. Here, we find that Rab5a is upregulated in several in vivo and in vitro myogenesis models. By generating myogenic Rab5a-deficient mice, we uncover the essential roles of Rab5a in regulating skeletal muscle regeneration. We further reveal that Rab5a promotes myoblast differentiation and directly interacts with insulin receptor substrate 1 (IRS1), an essential scaffold protein for propagating IGF signaling. Rab5a interacts with IRS1 in a GTP-dependent manner and this interaction is enhanced upon IGF-1 activation and myogenic differentiation. We subsequently identify that the arginine 207 and 222 of IRS1 and tyrosine 82, 89, and 90 of Rab5a are the critical amino acid residues for mediating the association. Mechanistically, Rab5a modulates IRS1 activation by coordinating the association between IRS1 and the IGF receptor (IGFR) and regulating the intracellular membrane targeting of IRS1. Both myogenesis-induced and IGF-evoked AKT-mTOR signaling are dependent on Rab5a. Myogenic deletion of Rab5a also reduces the activation of AKT-mTOR signaling during skeletal muscle regeneration. Taken together, our study uncovers the physiological function of Rab5a in regulating muscle regeneration and delineates the novel role of Rab5a as a critical switch controlling AKT-mTOR signaling by activating IRS1.We present a new technique for designing angle-sensing, long-wave infrared (LWIR) detectors. Angle detection in the proposed detector is achieved by measuring the ratio of the absorbed power in two closely-spaced, directive infrared antennas. Each directive LWIR antenna is in the form of a three-element Yagi-Uda array sharing a common reflector element with its neighbor. The structure of each antenna is optimized to act both as the collector of the infrared energy from the desired direction and as a distributed bolometer that senses the received radiation. The resistivity of each bolometer-antenna changes as a function of the absorbed power by the antenna. This change of resistance is sensed by biasing each antenna with a constant DC voltage and measuring the change of current passing through the antenna. Following this approach, by measuring the ratio of the resistance change in the two antennas, the angle of arrival of the LWIR signal can be determined. We present the design, fabrication, and measurement results of an angle-sensing detector optimized to operate at the wavelength of λ = 10.6 μm. The proposed detector has subwavelength dimensions occupying an aperture having dimensions of approximately 0.6 λ0 × 0.4λ0. The response of the detector was measured and shows the angle sensing dynamic range of 22 dB within the field of view of ±60°.