Prenatal exposure to TAK242 affects the childhood autism in offspring in animal models of autism spectrum disorder

Objective(s): To evaluate whether prenatal exposure to TAK242 affects childhood autism in the offspring in animal models of autism spectrum disorder (ASD). Materials and Methods:The pregnant rats were pseudo-randomly divided into three groups, the ASD model group, the TAK242 treatment group, and the control group. The ASD model was constructed by injecting IP with LPS. The blood samples from 1-month-old offspring were collected for cytokine evaluation and the social interaction test was used in the offspring of ASD rats. Rats were killed and the hippocampus, cerebral cortex, and cerebellum were used for the immunohistochemical study. Results: As compared to the control, the levels of IFN-γ, IL-1β, IL-2, and IL-6 were significantly increased (

Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency

5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency is a folate metabolism disorder known as a rare autosomal recessive neurodevelopmental disorder (MIM: #618367). With central nervous system involvements, it is mainly characterized by developmental delay, epilepsy, microcephaly, hypertonia, and cranial nerves involvement. Here, we report three new cases with MTHFS deficiency from two non-consanguineous Chinese families. All patients showed white matter dysplasia and global developmental delay, of which only patient 1 and 2 manifested tonic-clonic seizures. Moreover, patient 2 had severe eczema and patient 3 had recurrent diarrhea. Both phenotypic features are firstly found in MTHFS deficiency. Trio whole-exome sequencing and sanger sequencing were used to identify four novel variants, p.Y169Tfs*17, p.S53F, c.117+1delG, and p.E61G in the MTHFS gene. The identification of four novel pathogenic variants and varied clinical features in three affected patients expands the genotype and phenotype spectrum of MTHFS deficiency. We also reviewed all cases of MTHFS deficiency that had previously been reported. The experience of diagnosis and treatment from these cases provides us a more comprehensive understanding of this rare disease

Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV), and human cytomegalovirus (HCMV). In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man9GlcNAc2Asn (Man9)-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn). These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation