Near-edge x-ray absorption fine structure investigation of graphene

We report the near-edge x-ray absorption fine structure (NEXAFS) spectrum of a single layer of graphite (graphene) obtained by micromechanical cleavage of Highly Ordered Pyrolytic Graphite (HOPG) on a SiO2 substrate. We utilized a PhotoEmission Electron Microscope (PEEM) to separately study single- double- and few-layers graphene (FLG) samples. In single-layer graphene we observe a splitting of the pi* resonance and a clear signature of the predicted interlayer state. The NEXAFS data illustrate the rapid evolution of the electronic structure with the increased number of layers.Comment: 5 pages, 4 figure

De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136530/1/cge12854_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136530/2/cge12854.pd

How to schedule night shift work in order to reduce health and safety risks

Objectives This discussion paper aims to provide scientifically based recommendations on night shift schedules, including consecutive shifts, shift intervals and duration of shifts, which may reduce health and safety risks. Short-term physiological effects in terms of circadian disruption, inadequate sleep duration and quality, and fatigue were considered as possible links between night shift work and selected health and safety risks, namely, cancer, cardio-metabolic disease, injuries, and pregnancy-related outcomes. Method In early 2020, 15 experienced shift work researchers participated in a workshop where they identified relevant scientific literature within their main research area. Results Knowledge gaps and possible recommendations were discussed based on the current evidence. The consensus was that schedules which reduce circadian disruption may reduce cancer risk, particularly for breast cancer, and schedules that optimize sleep and reduce fatigue may reduce the occurrence of injuries. This is generally achieved with fewer consecutive night shifts, sufficient shift intervals, and shorter night shift duration. Conclusions Based on the limited, existing literature, we recommend that in order to reduce the risk of injuries and possibly breast cancer, night shift schedules have: (i) ≤3 consecutive night shifts; (ii) shift intervals of ≥11 hours; and (iii) ≤9 hours shift duration. In special cases – eg, oil rigs and other isolated workplaces with better possibilities to adapt to daytime sleep – additional or other recommendations may apply. Finally, to reduce risk of miscarriage, pregnant women should not work more than one night shift in a weekpublishedVersio

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

New Insights Into the Clinical and Molecular Spectrum of the Novel CYFIP2-Related Neurodevelopmental Disorder and Impairment of the WRC-Mediated Actin Dynamics

Purpose: A few de novo missense variants in the cytoplasmic FMRP-interacting protein 2 (CYFIP2) gene have recently been described as a novel cause of severe intellectual disability, seizures, and hypotonia in 18 individuals, with p.Arg87 substitutions in the majority. Methods: We assembled data from 19 newly identified and all 18 previously published individuals with CYFIP2 variants. By structural modeling and investigation of WAVE-regulatory complex (WRC)-mediated actin polymerization in six patient fibroblast lines we assessed the impact of CYFIP2 variants on the WRC. Results: Sixteen of 19 individuals harbor two previously described and 11 novel (likely) disease-associated missense variants. We report p.Asp724 as second mutational hotspot (4/19 cases). Genotype–phenotype correlation confirms a consistently severe phenotype in p.Arg87 patients but a more variable phenotype in p.Asp724 and other substitutions. Three individuals with milder phenotypes carry putative loss-of-function variants, which remain of unclear pathogenicity. Structural modeling predicted missense variants to disturb interactions within the WRC or impair CYFIP2 stability. Consistent with its role in WRC-mediated actin polymerization we substantiate aberrant regulation of the actin cytoskeleton in patient fibroblasts. Conclusion: Our study expands the clinical and molecular spectrum of CYFIP2-related neurodevelopmental disorder and provides evidence for aberrant WRC-mediated actin dynamics as contributing cellular pathomechanism

Novel fibronectin mutations and expansion of the phenotype in spondylometaphyseal dysplasia with “corner fractures”

Heterozygous pathogenic variants in the FN1 gene, encoding fibronectin (FN), have recently been shown to be associated with a skeletal disorder in some individuals affected by spondylometaphyseal dysplasia with “corner fractures” (SMD-CF). The most striking feature characterizing SMD-CF is irregularly shaped metaphyses giving the appearance of “corner fractures”. An array of secondary features, including developmental coxa vara, ovoid vertebral bodies and severe scoliosis, may also be present. FN is an important extra cellular matrix component for bone and cartilage development. Here we report five patients affected by this subtype of SMD-CF caused by five novel FN1 missense mutations: p.Cys123Tyr, p.Cys169Tyr, p.Cys213Tyr, p.Cys231Trp and p.Cys258Tyr. All individuals shared a substitution of a cysteine residue, disrupting disulfide bonds in the FN type-I assembly domains located in the N-terminal assembly region. The abnormal metaphyseal ossification and “corner fracture” appearances were the most remarkable clinical feature in these patients. In addition, generalized skeletal fragility with low-trauma bilateral femoral fractures was identified in one patient. Interestingly, the distal femoral changes in this patient healed with skeletal maturation. Our report expands the phenotypic and genetic spectrum of the FN1-related SMD-CF and emphasizes the importance of FN in bone formation and possibly also in the maintenance of bone strength.Peer reviewe