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Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Spillover of avian influenza H5N1 from birds to mammals have been increasingly detected, but reports of cases in humans remain limited. Here, the authors find serological evidence of human exposure to influenza H5N1 in Malaysian Borneo, an important stopover site for migratory shorebirds.

Reynolds and colleagues examine a biochemically-mediated epistatic interaction between metabolic enzymes involved in folate metabolism and show that biochemical coupling shapes the range of enzyme activities sufficient to rescue cell growth.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

The record-breaking 2023 wildfire season in Canada ( ~ 15 Mha burned) was enabled by early snowmelt, drought, and extreme weather. It had profound impacts that included evacuation of >200 communities, millions exposed to hazardous smoke, and a strain on fire-fighting resources.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Mature B cell survival requires signals from the BCR and from the BLyS receptor BR3. Michael Cancro and colleagues demonstrate crosstalk between these pathways, as BCR signals supply a substrate needed for BR3 signal transmission.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Parkinson’s disease (PD) is linked to environmental factors. Through quantitative epidemiology, this study ties 53 pesticides to PD. An innovative human stem cell platform revealed that 10 of these were directly toxic to human dopamine neurons.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

On 27 ̶ 29 July 2021, the National Institute of Allergy and Infectious Diseases (NIAID) hosted a virtual workshop on the topic of secondary vaccine effects to discuss existing evidence, potential immunological mechanisms and associated public health implications.

Little is known about the genetic landscape of people living in the Nile region prior to the Islamic migrations of the late 1st millennium CE. Here, the authors report genome-wide data for 66 ancient individuals to investigate the genetic ancestry of a Christian Period group from Kulubnarti.

Ion channels driven by light have provided electrophysiologists with unprecedented control over the activity state of neurons; here Deisseroth and colleagues introduce new molecules that offer a similar level of control over signalling pathways to biochemists. Opsin/GPCR chimaeras were engineered, enabling the authors to modulate G-protein activity via light, which in turn could influence neuronal firing; activating these molecules expressed in vivo could drive conditioned place preference in behaving mice

High-speed tracking of effortful responses and neuronal activity in rats during a forced swim test identifies medial prefrontal cortex (mPFC) neurons that respond during escape-related swimming but not normal locomotion, and optogenetics shows that mPFC neurons projecting to the brainstem dorsal raphe nucleus, which is implicated in depression, modulate this behavioural response to challenge

The amygdala, a brain region important for learning fearful memories, is thought to have a role in generalized anxiety, but the critical subregions and connections are unknown. This paper shows that optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala of rats with channelrhodopsin has an anxiolytic effect, whereas inhibition of the same projection with eNpHR3.0 increases anxiety related behaviours. These effects were not observed with direct optogenetic control of BLA somata themselves, indicating that selective activation of certain connections can have different effects.

From a therapeutic standpoint, one of the main drawbacks of artificial electrical stimulation of muscle is that large, fatigable motor units are recruited before smaller units, which is opposite to the normal physiological recruitment pattern. Researchers from Stanford University have circumvented this problem by stimulating muscle optically rather than electrically, providing enhanced functional performance and potential applications for the technique in neuromuscular physiology, neuroprosthetics and neurorehabilitation.

Tracking data from 17 marine predator species in the Southern Ocean are used to identify Areas of Ecological Significance, the protection of which could help to mitigate increasing pressures on Southern Ocean ecosystems.

Intraspecies response to climate change is expected to align with genetic affinity. Using the American pika as a case study suggests that divisions of species distributions best explain intraspecific heterogeneity in climate relationships.

In children, adolescents and adults with mutated ALK-driven relapsed or refractory neuroblastoma, a third-generation ALK inhibitor with or without chemotherapy was well tolerated, and recommended phase 2 doses were successfully identified in all patient groups.

Wildlife are central to nature’s contributions to people (NCP) but are often overlooked in NCP policy and management. This Perspective presents evidence for the integral role of wildlife in supporting human well-being and proposes their recognition and incorporation into conservation decision-making as wildlife’s contributions to people (WCP).

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.

Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

A manufacturable platform for quantum computing with photons is introduced and a set of monolithically integrated silicon-photonics-based modules is benchmarked, demonstrating dual-rail photonic qubits with performance close to thresholds required for operation.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

When people are isolated, they crave social interactions. Midbrain craving regions were activated by food in hungry people, and by social interactions in people mandated to be isolated.

In rodent models of type 2 diabetes, sustained remission of hyperglycemia can be induced by FGF1 action in the mediobasal hypothalamus. Here, the authors show that FGF1-injection is followed by marked changes in glial cell populations and that the sustained glycemic response is dependent on intact melanocortin signaling.

Factors controlling the transfer of microbes from the ocean to the atmosphere are unclear. Here, Michaud et al. study this process in an enclosed ocean-atmosphere facility, and show that the degree of aerosolization of bacteria and viruses is taxon-specific.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeldet al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.

A comprehensive characterisation of Omicron-BA.1 and VOC Delta in numerous in vitro and in vivo models uncovers the factors that led to its global dominance.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

A genome-wide-association meta-analysis of 18,381 austim spectrum disorder (ASD) cases and 27,969 controls identifies five risk loci. The authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.

Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.