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TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. PTX inhibitor order This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands.Mumps virus is one of the main cause of respiratory illnesses in humans, especially children. Among the viral surface glycoproteins, the hemagglutinin - neuraminidase, MuV-HN, plays key roles in virus entry into host cells and infectivity, thus representing an ideal target for the design of novel inhibitors. Here we report the detailed analysis of the molecular recognition of host cell surface sialylated glycans by the viral glycoprotein MuV-HN. By a combined use of NMR, docking, molecular modelling and CORCEMA-ST, the structural features of sialoglycans/MuV-HN complexes were revealed. Evidence for a different enzyme activity toward longer and complex substrates compared to unbranched ligands was also examined by an accurate NMR kinetic analysis. Our results provide the basis for the structure-based design of effective drugs against mumps-induced diseases.Accumulation of damaged proteins is a hallmark of ageing, occurring in organisms ranging from bacteria and yeast to mammalian cells. During cell division in Saccharomyces cerevisiae, damaged proteins are retained within the mother cell, resulting in an ageing mother while a new daughter cell exhibits full replicative potential. The cell-specific features determining the ageing remain elusive. It has been suggested that the replicative ageing is dependent on the ability of the cell to repair and retain pre-existing damage. To deepen the understanding of how these factors influence the life of individual cells, we developed and experimentally validated a dynamic model of damage accumulation accounting for replicative ageing on the single cell level. The model includes five essential properties cell growth, damage formation, damage repair, cell division and cell death, represented in a theoretical framework describing the conditions allowing for replicative ageing, starvation, immortality or clonal senescence. We introduce the resilience to damage, which can be interpreted as the difference in volume between an old and a young cell. We show that the capacity to retain damage deteriorates with high age, that asymmetric division allows for retention of damage, and that there is a trade-off between retention and the resilience property. Finally, we derive the maximal degree of asymmetry as a function of resilience, proposing that asymmetric cell division is beneficial with respect to replicative ageing as it increases the lifespan of a given organism. The proposed model contributes to a deeper understanding of the ageing process in eukaryotic organisms.Predicting the effects of invasive ecosystem engineering species in new bioregions has proved elusive. In part this is because separating biological effects from purely physical mechanisms has been little studied and yet could help predict potentially damaging bioinvasions. Here we tested the effects of a large bio-engineering fanworm Sabella spallanzanii (Sabella) versus worm-like structures (mimics) on gas and nutrient fluxes in a marine soft bottom sediment. Experimental plots of sediment in Hauraki Gulf (New Zealand) were used to test the hypothesis that ecosystem engineers negatively influence benthic ecosystem function through autogenic mechanisms, facilitating activity by biofouling organisms and competitive exclusion of native infauna. Enhanced physical structure associated with Sabella and mimics increased nitrogen fluxes, community metabolism and reduced denitrification from 23 μmol m-2 h-1 to zero at densities greater than 25 m2. Sabella plots on average had greater respiration (29%), NH4 release (33%), and greater NO3 release (52%) compared to mimics, suggesting allogenic (biological) mechanisms occur, but play a secondary role to autogenic (physical) mechanisms. The dominance of autogenic mechanisms indicates that bio-engineers are likely to cause significant impacts when established, regardless of fundamental differences in recipient regions or identity of the introduced bio-engineer. In the case of Sabella spallanzanii, compromised denitrification has the potential to tip the balance of net solute and gas exchanges and cause further ecological degradation in an already eutrophic system.Modulation of T-cell responses has played a key role in treating cancers and autoimmune diseases. Therefore, understanding how different receptors on T cells impact functional outcomes is crucial. The influence of B7-H7 (HHLA2) and CD28H (TMIGD2) on T-cell activation remains controversial. Here we examined global transcriptomic changes in human T cells induced by B7-H7. Stimulation through TCR with OKT3 and B7-H7 resulted in modest fold changes in the expression of select genes; however, these fold changes were significantly lower than those induced by OKT3 and B7-1 stimulation. The transcriptional changes induced by OKT3 and B7-H7 were insufficient to provide functional stimulation as measured by evaluating T-cell proliferation and cytokine production. Interestingly, B7-H7 was coinhibitory when simultaneously combined with TCR and CD28 stimulation. This inhibitory activity was comparable to that observed with PD-L1. Finally, in physiological assays using T cells and APCs, blockade of B7-H7 enhanced T-cell activation and proliferation, demonstrating that this ligand acts as a break signal.