Issues

Summary: This Review highlights the challenging but rewarding search for somatic mutations in the noncoding genome, and how such variants nucleate aberrant enhancers and promoters that drive the expression of proto-oncogenes.

Summary: Neural tube defects in a folic-acid-responsive, folate-sensitive mouse model are associated with a localised proliferation defect in the neuroepithelium. Supplemental folic acid stimulates progression through S phase to correct this abnormality.

Summary: Whole-brain immunolabeling, mapping and absolute quantification of tyrosine hydroxylase neurons in the adult mouse brain provides a useful tool for studying changes in dopaminergic signaling in a mouse model of PD.

Summary: Elucidating the role of Bax inhibitor 1 (BI-1) and its mechanisms in the pathophysiology of hypoxic ischemic encephalopathy may help provide a basis for BI-1 as a potential therapeutic target in clinics.

Summary: Glymphatic CSF circulation and development of the cerebral cortex are impaired in our new genetic rat model of neonatal hydrocephalus with the onset of parenchymal inflammation and hemorrhage.

Summary: The authors identified and characterized a medaka mutation in titin that leads to a phenotype similar to hypertrophic cardiomyopathy. Similar mutations were also observed in human patients.

Summary: Encephalocele is a severe congenital brain defect that arises after neural tube closure, but can share a common genetic cause with defects of cranial and spinal neural tube closure.

Summary: Wfdc2 is vitally important in preventing atelectasis and dysfunction of barrier mechanisms such as mucociliary clearance, intercellular junction formation and anti-inflammatory activity.

Summary: Temporal and dose-specific enhancement of regional neurovascular signaling improves germinal matrix vessel development and demonstrates, in principle, a new approach for germinal matrix hemorrhage intervention.

Summary: The authors present a novel in vivo genetic model of idiopathic epilepsy in zebrafish (gabrg2^−/−) to aid the study of ictogenesis and provide a convenient genetic tool for drug screening.

Editor's choice: Drug repurposing screens using worm and patient fibroblast models of PMM2-CDG led to the discovery of epalrestat, the first activator of PMM2 that targets the root cause of disease.

Summary: Using worm and fly models of an ultra-rare congenital disorder of glycosylation, we performed repurposing screens and identified the FDA-approved drug aripiprazole as a clinical candidate.

Summary: A novel observation point of a familiar scenario: proteomic quantification of over 6200 proteins as a resource to further explore endoplasmic reticulum stress.