Summary The chromatin remodeling gene CHD8 represents a central node in neurodevelopmental gene networks implicated in autism. We examined the impact of germline heterozygous frameshift Chd8 mutation on neurodevelopment in mice. Chd8+/del5 mice displayed normal social interactions with no repetitive behaviors but exhibited cognitive impairment correlated with increased regional brain volume, validating that phenotypes of Chd8+/del5 mice overlap pathology reported in humans with CHD8 mutations. We applied network analysis to characterize neurodevelopmental gene expression, revealing widespread transcriptional changes in Chd8+/del5 mice across pathways disrupted in neurodevelopmental disorders, including neurogenesis, synaptic processes and neuroimmune signaling. We identified a co-expression module with peak expression in early brain development featuring dysregulation of RNA processing, chromatin remodeling and cell-cycle genes enriched for promoter binding by Chd8, and we validated increased neuronal proliferation and developmental splicing perturbation in Chd8+/del5 mice. This integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency on brain development.

Developing systems to identify the cell type-specific functions regulated by genes linked to type 2 diabetes (T2D) risk could transform our understanding of the genetic basis of this disease. However, in vivo systems for efficiently discovering T2D risk gene functions relevant to human cells are currently lacking. Here we describe powerful interdisciplinary approaches combining Drosophila genetics and physiology with human islet biology to address this fundamental gap in diabetes research. We identify Drosophila orthologs of T2D-risk genes that regulate insulin output. With human islets, we perform genetic studies and identify cognate human T2D-risk genes that regulate human beta cell function. Loss of BCL11A, a transcriptional regulator, in primary human islet cells leads to enhanced insulin secretion. Gene expression profiling reveals BCL11A-dependent regulation of multiple genes involved in insulin exocytosis. Thus, genetic and physiological systems described here advance the capacity to identify cell-specific T2D risk gene functions.

Highlights We present a report on continuous EEG (cEEG) findings in COVID-19 patients. cEEG revealed findings consistent with encephalopathy independent of IV anesthetics. Acute symptomatic seizures were noted in two patients.

Background and objectives:Although the international community collectively seeks to reduce global temperature rise to under 1.5ºC before 2100, irreversible environmental changes have already occurred, and as the planet warms these changes will continue to occur. As we witness the effects of a warming planet on human health, it is imperative that neurologists anticipate how the epidemiology and incidence of neurologic disease may change. In this review, we organized our analysis around three key themes related to climate change and neurologic health: extreme weather events and temperature fluctuations, emerging neuro-infectious diseases, and pollutant impacts. Across each of these themes, we appraised and reviewed recent literature relevant to neurological disease and practice.Methods:Studies were identified using search terms relating to climate change, pollutants, and neurologic disease in PubMed, OVID MEDLINE, Embase, PsycInfo, and grey literature. Studies published between 1990 and 2022 were included if they pertained to human incidence or prevalence of disease, were in English, and were relevant to neurologic disease.Results:We identified a total of 364 articles, grouped into the three key themes of our study; extreme weather events and temperature fluctuations (38 studies), emerging neuro-infectious diseases (37 studies), and pollutant impacts (289 studies). The included studies highlighted the relationships between neurologic symptom exacerbation and temperature variability, tick-borne infections and warming climates, and airborne pollutants and cerebrovascular disease incidence and severity.Discussion:Temperature extremes and variability both associated with stroke incidence and severity, migraine headaches, hospitalization in dementia patients, and multiple sclerosis exacerbations. Exposure to airborne pollutants, especially PM2.5 and nitrates, associated with stroke incidence and severity, headaches, dementia risk, Parkinson’s disease, and MS exacerbation. Climate change has demonstrably expanded favorable conditions for zoonotic diseases beyond traditional borders, and poses the risk of disease in new, susceptible populations. Articles were biased towards resource-rich regions, suggesting a discordance between where research occurs and where changes are most acute. As such, three key priorities emerged for further study; neuro-infectious disease risk mitigation, understanding the pathophysiology of airborne pollutants on the nervous system, and methods to improve delivery of neurologic care in the face of climate-related disruptions.