Background: Microdeletions of the MEF2C gene are linked to a syndromic form of autism termed MEF2C Haploinsufficiency Syndrome (MCHS). MEF2C hypofunction in neurons is presumed to underlie most of the MCHS symptoms. However, it is unclear in which cell populations MEF2C functions to regulate neurotypical development.Methods: Multiple biochemical, molecular, electrophysiological, behavioral and transgenic mouse approaches were used to characterize MCHS-relevant synaptic, behavioral and gene expression changes in mouse models of MCHS. Results:We show here that MCHS-associated missense mutations cluster in the conserved DNA binding domain and disrupt MEF2C DNA binding. DNA binding-deficient global Mef2c heterozygous mice (Mef2c-Het) display numerous MCHS-related behaviors, including autism-*

Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep-loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss in C57BL/6J mice. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function.

Guidelines for neonatal skin care are scarce, and there is no consensus on the best management practices for neonatal skin breakdown. This review presents the pathology and phases of wound healing, reasons for neonatal skin fragility, and approaches to recognition of commonly encountered neonatal wounds. This review also provides general strategies for neonatal wound prevention, care, dressing, and management to avoid further damage to the fragile neonatal skin. The importance and role of retaining moisture in expediting wound healing is discussed, as well as updated classifications on how to grade and assess pressure ulcers and the role of negative pressure wound therapy and silver dressings. Lastly, this review discusses prevention and treatment options for surgical wounds, intravenous extravasation wounds, congenital wounds, and thermal injuries, in addition to how to differentiate these wounds from the common diaper dermatitis and contact dermatitis.

Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain 25 differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep loss response are not well understood. We show that sleep-loss regulates MEF2C phosphorylation, a key mechanism regulating MEF2C transcriptional 30 activity, and that MEF2C function in postnatal excitatory forebrain neurons is required for the biological events in response to sleep loss. These include altered gene expression, the increase and recovery of synaptic strength, and the rebound and resolution of SWS-SWA, which implicate MEF2C as an essential regulator of sleep function. 35 One Sentence Summary: MEF2C is critical to the response to sleep loss. Main Text:Sleep abnormalities are commonly observed in numerous neurological disorders, 40 including autism spectrum disorder, major depressive disorder, bipolar disorder, posttraumatic stress disorder, neurodegenerative disorders and many others, but our understanding of sleep need and its regulation and resolution is poorly understood. Following an extended period of waking, or sleep deprivation (SD), the mammalian cortex shows an altered pattern of EEG activity characterized by rebound slow wave power 45 (delta power in the frequency range of 0.5-4.5Hz) during the ensuing slow wave sleep 2

Microdeletions of the MEF2C gene are linked to a syndromic form of autism termed MEF2C 2 haploinsufficiency syndrome (MCHS). Here, we show that MCHS-associated missense mutations cluster 3 in the conserved DNA binding domain and disrupt MEF2C DNA binding. DNA binding-deficient global 4 Mef2c heterozygous mice (Mef2c-Het) display numerous MCHS-like behaviors, including autism-related 5 behaviors, as well as deficits in cortical excitatory synaptic transmission. We find that hundreds of genes 6 are dysregulated in Mef2c-Het cortex, including significant enrichments of autism risk and excitatory 7 neuron genes. In addition, we observe an enrichment of upregulated microglial genes, but not due to 8 neuroinflammation in the Mef2c-Het cortex. Importantly, conditional Mef2c heterozygosity in forebrain 9 excitatory neurons reproduces a subset of the Mef2c-Het phenotypes, while conditional Mef2c 10 heterozygosity in microglia reproduces social deficits and repetitive behavior. Together our findings 11 suggest that MEF2C regulates typical brain development and function through multiple cell types, 12 including excitatory neuronal and neuroimmune populations.13 14