Autism spectrum disorder: a neuro-immunometabolic hypothesis of the developmental origins

Fetal neuroinflammation and prenatal stress (PS) may contribute to lifelong neurological disabilities. Astrocytes and microglia play a pivotal role, but the mechanisms are poorly understood. Here, we test the hypothesis that via gene-environment interactions, fetal neuroinflammation and PS may reprogram glial immunometabolic phenotypes which impact neurodevelopment and neurobehavior. This glial-neuronal interplay increases the risk for clinical manifestation of autism spectrum disorder (ASD) in at-risk children. Drawing on genomic data from the recently published series of ovine and rodent glial transcriptome analyses with fetuses exposed to neuroinflammation or PS, we conducted a secondary analysis against the Simons Foundation Autism Research Initiative (SFARI) Gene database. We confirmed 21 gene hits. Using unsupervised statistical network analysis, we then identified six clusters of probable protein-protein interactions mapping onto the immunometabolic and stress response networks and epigenetic memory. These findings support our hypothesis. We discuss the implications for ASD etiology, early detection, and novel therapeutic approaches.Comment: Supplemental Table and Data: https://github.com/martinfrasch/ASD_origins_hypothesis. arXiv admin note: text overlap with arXiv:1812.06617 | This is a different study with related research context (relevance to ASD

Measurement induced criticality in quasiperiodic modulated random hybrid circuits

We study one-dimensional hybrid quantum circuits perturbed by quenched quasiperiodic (QP) modulations across the measurement-induced phase transition (MIPT). Considering non-Pisot QP structures, characterized by unbounded fluctuations, allows us to tune the wandering exponent $\beta$ to exceed the Luck bound $\nu \ge 1/(1-\beta)$ for the stability of the MIPT where $\nu\cong 4/3$. Via large-scale numerical simulations of random Clifford circuits interleaved with local projective measurements, we find that sufficiently large QP structural fluctuations destabilize the MIPT and induce a flow to a broad family of critical dynamical phase transitions of the infinite QP type that is governed by the wandering exponent, $\beta$. We numerically determine the associated critical properties, including the correlation length exponent consistent with saturating the Luck bound, and a universal activated dynamical scaling with activation exponent $\psi \cong \beta$, finding excellent agreement with the conclusions of real space renormalization group calculations.Comment: 14 pages, 13 figure

Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients