Search

The transcriptional regulation of oligodendrocytes has an essential role in myelin formation and maintenance. Here, the authors identify the transcription factor Tfii-i as a regulator of myelin genes expression in the nervous system and show that its loss enhances myelin thickness and nerve conduction.

Maltese et al. show in mice that experiencing an adverse event affects future interaction with others experiencing the same stressor. These self-experience socioemotional reactions are orchestrated by the corticotropin-releasing factor system in the medial prefrontal cortex.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

Astrocytic glycogen dynamics is necessary to support neuronal transmission of long-term inflammatory pain signals in the spinal cord.

The hypothalamic neuropeptide oxytocin exerts analgesic effects, but the underlying pathways remain largely elusive. Here, the authors describe an analgesic pathway formed by oxytocin neurons projecting to the periaqueductal grey, where axonally released oxytocin activates oxytocin-receptor expressing GABA neurons and subsequently reduces pain-like behaviors in both female and male rats.

Wall et al. describe the selective activation of an adenosine A1 receptor-mediated intracellular pathway that provides potent analgesia in the absence of sedation or cardiorespiratory depression, paving the way for novel medicines based on the far-reaching concept of selective Gα agonism.

Prosaposin (PSAP) variants are linked to Parkinson’s disease (PD). Here, the authors report PSP changes in PD and lipid dyshomeostasis and PD-like phenotypes in mice lacking PSAP in dopamine neurons; PSAP overexpression counteracts experimental PD.

The brain is a complex biological machine that results from the birth, migration and differentiation of neurons. This paper reports that Vps15 enables the migration and survival of neurons, and implicates the gene in neurodevelopmental disease.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

In humans, copy-number variants of the CYFIP1 gene have been associated with autism spectrum disorders and schizophrenia. Here, the authors characterize Cyfip1-heterozygous mice, revealing that they display deficits in brain white matter structure and functional connectivity along with abnormal behaviours.

The authors describe cortical projections mediating the modulation of social behavior. Neural projections from the medial prefrontal cortex to the dorsal periaqueductal gray play a critical role in the behavioral adaptation to social defeat in mice.

Mutations in the gene encoding Shrm4 are associated with epilepsy and intellectual disability. The authors show that Shrm4 interacts with GABA_Breceptors and regulates tonic inhibition in the hippocampus, and knockdown of Shrm4 in rats leads to anxiety-like behaviour and seizures.

Chronic pain is sustained by alterations in gene transcription. Here, the authors show that increased expression of Organic Anionic Transporter 1 in the spinal cord is epigenetically controlled and key to hypersensitivity in pathological pain.

The authors show that decreased synaptic efficacy onto raphe-projecting lateral habenula neurons supports opiate withdrawal-induced sociability deficits, and they demonstrate a role for TNF-α signaling in this process.

Huntington’s disease (HD) is a neurodegenerative disease that shows selective regional vulnerability. Here, the authors show that postmortem brain HD astrocytes are regionally diverse, with a striatal disease-associated state and a cortical compensatory state that mitigated neural death.

Whole-genome sequencing of chronic lymphocytic leukemia from 485 patients identifies putative coding and noncoding drivers of disease. Genomically defined subgroups show distinct clinical and biological characteristics.

Zika virus (ZIKV), the causative agent of virus-induced brain damage in newborns, is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus. Here, Obadia et al. characterize ZIKV vector competence of 50 mosquito populations from six species collected in 12 different countries to inform about epidemic risk. They find that African ZIKV strain shows higher transmission efficiency compared to American and Asian ZIKV strains and that Ae. aegypti mosquitoes have highest susceptibility to infections, while Culexmosquitoes are largely non-susceptible.

Yellow fever is absent from the Asia/Pacific region, despite presence of the mosquito vector. Here, the authors demonstrate that mosquitoes collected from field sites across the region are capable of transmitting yellow fever virus, indicating that vector competence is not a barrier to disease spread.

Fine-tuning the RoseTTAFold structure prediction network on protein structure denoising tasks yields a generative model for protein design that achieves outstanding performance on a wide range of protein structure and function design challenges.

Intragenic DNA methylation, dependent on Dnmt3b, protects the gene body from spurious entry of RNA Polymerase II and aberrant transcription initiation events.

Structural variants (SV) can accumulate in repeat-rich parts of the genome and transform them in unexpected ways. Here, with their new assembly-based genotyper (NAHRwhals), the authors verify multi-step SVs in 37 human loci and identify alleles at risk for copy-number variation.

Though tractography is widely used, it has not been systematically validated. Here, authors report results from 20 groups showing that many tractography algorithms produce both valid and invalid bundles.

BAG3 is found in the serum of pancreatic cancer patients and can be used as a marker of disease, but its role in cancer is unclear. Here, the authors show that BAG3 secreted from tumour cells binds to and activates macrophages, which in turn promotes cell growth, and an antibody blocking BAG3 binding reduces tumour formation in mice.

Centralized infrastructure to support analyses involving complexity beyond genome-wide association studies is broadly needed. Here, Ritchie and colleagues develop PLATO, a software tool to process and integrate various methods for this task.