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Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders.

Microcephaly is an important sign of neurological malformation and a predictor of future disability. The 2015–16 outbreak of Zika virus and congenital Zika infection brought the world's attention to links between Zika infection and microcephaly. However, Zika virus is only one of the infectious causes of microcephaly and, although the contexts in which they occur vary greatly, all are of concern. In this Review, we summarise important aspects of major congenital infections that can cause microcephaly, and describe the epidemiology, transmission, clinical features, pathogenesis, management, and long-term consequences of these infections. We include infections that cause substantial impairment: cytomegalovirus, herpes simplex virus, rubella virus, Toxoplasma gondii, and Zika virus. We highlight potential issues with classification of microcephaly and show how some infants affected by congenital infection might be missed or incorrectly diagnosed. Although Zika virus has brought the attention of the world to the problem of microcephaly, prevention of all infectious causes of microcephaly and appropriately managing its consequences remain important global public health priorities.

Post-zygotic mutations that generate tissue mosaicism are increasingly associated with severe congenital defects, including those arising from failed neural tube closure. Here we report that neural fold elevation during mouse spinal neurulation is vulnerable to deletion of the VANGL planar cell polarity protein 2 ( Vangl2 ) gene in as few as 16% of neuroepithelial cells. Vangl2 -deleted cells are typically dispersed throughout the neuroepithelium, and each non-autonomously prevents apical constriction by an average of five Vangl2 -replete neighbours. This inhibition of apical constriction involves diminished myosin-II localisation on neighbour cell borders and shortening of basally-extending microtubule tails, which are known to facilitate apical constriction. Vangl2 -deleted neuroepithelial cells themselves continue to apically constrict and preferentially recruit myosin-II to their apical cell cortex rather than to apical cap localisations. Such non-autonomous effects can explain how post-zygotic mutations affecting a minority of cells can cause catastrophic failure of morphogenesis leading to clinically important birth defects. Mutations that cause tissue mosaicism have been identified in individuals with severe congenital defects. Here, the authors show that mosaic deletion of Vangl2 in the murine neuroepithlium causes spina bifida by preventing apical constriction via reduced myosin II and tubulin organisation.

Pathological antibodies have been demonstrated to play a key role in type II immune hypersensitivity reactions, resulting in the destruction of healthy tissues and leading to considerable morbidity for the patient. Unfortunately, current treatments present significant iatrogenic risk while still falling short for many patients in achieving clinical remission. In the present work, we explored the capability of target cell membrane-coated nanoparticles to abrogate the effect of pathological antibodies in an effort to minimize disease burden, without the need for drug-based immune suppression. Inspired by antibody-driven pathology, we used intact RBC membranes stabilized by biodegradable polymeric nanoparticle cores to serve as an alternative target for pathological antibodies in an antibody-induced anemia disease model. Through both in vitro and in vivo studies, we demonstrated efficacy of RBC membrane-cloaked nanoparticles to bind and neutralize anti-RBC polyclonal IgG effectively, and thus preserve circulating RBCs.

Misinformation about COVID-19 is common and has been spreading rapidly across the globe through social media platforms and other information systems. Understanding what the public knows about COVID-19 and identifying beliefs based on misinformation can help shape effective public health communications to ensure efforts to reduce viral transmission are not undermined. This study aimed to investigate the prevalence and factors associated with COVID-19 misinformation in Australia and their changes over time. This prospective, longitudinal national survey was completed by adults (18 years and above) across April (n=4362), May (n=1882), and June (n=1369) 2020. Stronger agreement with misinformation was associated with younger age, male gender, lower education level, and language other than English spoken at home (P<.01 for all). After controlling for these variables, misinformation beliefs were significantly associated (P<.001) with lower levels of digital health literacy, perceived threat of COVID-19, confidence in government, and trust in scientific institutions. Analyses of specific government-identified misinformation revealed 3 clusters: prevention (associated with male gender and younger age), causation (associated with lower education level and greater social disadvantage), and cure (associated with younger age). Lower institutional trust and greater rejection of official government accounts were associated with stronger agreement with COVID-19 misinformation. The findings of this study highlight important gaps in communication effectiveness, which must be addressed to ensure effective COVID-19 prevention.

Gap closure is a common morphogenetic process. In mammals, failure to close the embryonic hindbrain neuropore (HNP) gap causes fatal anencephaly. We observed that surface ectoderm cells surrounding the mouse HNP assemble high-tension actomyosin purse strings at their leading edge and establish the initial contacts across the embryonic midline. Fibronectin and laminin are present, and tensin 1 accumulates in focal adhesion-like puncta at this leading edge. The HNP gap closes asymmetrically, faster from its rostral than caudal end, while maintaining an elongated aspect ratio. Cell-based physical modeling identifies two closure mechanisms sufficient to account for tissue-level HNP closure dynamics: purse-string contraction and directional cell motion implemented through active crawling. Combining both closure mechanisms hastens gap closure and produces a constant rate of gap shortening. Purse-string contraction reduces, whereas crawling increases gap aspect ratio, and their combination maintains it. Closure rate asymmetry can be explained by asymmetric embryo tissue geometry, namely a narrower rostral gap apex, whereas biomechanical tension inferred from laser ablation is equivalent at the gaps’ rostral and caudal closure points. At the cellular level, the physical model predicts rear-rangements of cells at the HNP rostral and caudal extremes as the gap shortens. These behaviors are reproducibly live imaged in mouse embryos. Thus, mammalian embryos coordinate cellular-and tissue-level mechanics to achieve this critical gap closure event.

Autonomous vehicles (AV) promise a reduction in the number of deadly traffic accidents. However, should accidents occur, attributions of responsibility are complicated by the fact that there is a human agent (driver) and a non-human agent (AV), and thus responsibility is likely shared between parties. In two studies, participants ( n  = 310 and n  = 260) read a vignette modeled after an actual lethal AV accident. Across four experimental conditions, participants were told that the human driver either needed to maintain oversight of the AV; did not need to maintain oversight of the AV; did not specify whether the human needed to maintain oversight of the AV; or the artificial intelligence was turned off and the human driver was fully in control. Participants assigned responsibility to the human driver, the AV company, the pedestrian, and an act of God, and determined whether the human driver and company CEO should be held criminally responsible in court. Consistent with previous research, the human driver was held most responsible regardless of oversight condition. However, companies were not absolved of responsibility, even when they required the human driver to maintain oversight of the AV. Implications of these findings for the introduction and legal regulation of AVs are discussed.

Key Points Neurulation is a well-known morphogenetic event of embryonic development that has important clinical consequences. The failure of neural tube closure leads to a group of common and severe malformations that are called neural tube defects (NTDs). Although the morphology and cell biology of neurulation are well described, the underlying molecular mechanisms remain poorly understood. More than 80 mutant mouse genes disrupt neurulation and lead to the development of NTDs. Analysis of these mutants allows an in-depth analysis of the developmental mechanisms that underlie neurulation. This review identifies the main categories of genes that are required for each successive event of neurulation, and relates these functional gene groups to probable neurulation mechanisms. Crucial molecular mechanisms of neurulation include the planar cell-polarity pathway, which is essential for the initiation of neural tube closure, and the sonic hedgehog signalling pathway, which regulates neural plate bending in the spinal region and probably also in the brain. Other developmental mechanisms seem to be essential solely for cranial neurulation. These include contraction of apical actin microfilaments, emigration of the cranial neural crest, precisely regulated programmed cell death and a balance between neuroepithelial cell proliferation and differentiation. The mutant mice also offer an opportunity to unravel the mechanisms by which folic acid prevents NTDs, and to develop new therapies for folate-resistant defects. NTDs in some mutant mouse strains can be prevented by folic acid, whereas, in one particular strain, folate is ineffective but inositol can prevent NTDs. More than 80 mutant mouse genes disrupt neurulation and allow an in-depth analysis of the underlying developmental mechanisms. Although many of the genetic mutants have been studied in only rudimentary detail, several molecular pathways can already be identified as crucial for normal neurulation. These include the planar cell-polarity pathway, which is required for the initiation of neural tube closure, and the sonic hedgehog signalling pathway that regulates neural plate bending. Mutant mice also offer an opportunity to unravel the mechanisms by which folic acid prevents neural tube defects, and to develop new therapies for folate-resistant defects.

Glycine decarboxylase (GLDC) acts in the glycine cleavage system to decarboxylate glycine and transfer a one-carbon unit into folate one-carbon metabolism. GLDC mutations cause a rare recessive disease non-ketotic hyperglycinemia (NKH). Mutations have also been identified in patients with neural tube defects (NTDs); however, the relationship between NKH and NTDs is unclear. We show that reduced expression of Gldc in mice suppresses glycine cleavage system activity and causes two distinct disease phenotypes. Mutant embryos develop partially penetrant NTDs while surviving mice exhibit post-natal features of NKH including glycine accumulation, early lethality and hydrocephalus. In addition to elevated glycine, Gldc disruption also results in abnormal tissue folate profiles, with depletion of one-carbon-carrying folates, as well as growth retardation and reduced cellular proliferation. Formate treatment normalizes the folate profile, restores embryonic growth and prevents NTDs, suggesting that Gldc deficiency causes NTDs through limiting supply of one-carbon units from mitochondrial folate metabolism. Mutations in the enzyme glycine decarboxylase (GLDC) are associated with neural tube closure defects and non-ketotic hyperglycinemia in humans. Here the authors generate a mouse model with reduced Gldc expression and activity and study the direct effect of the enzyme in these diseases and the mechanisms responsible for neural tube closure defects.