Search

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

As well as superconductivity, cuprate perovskites can exhibit many different exotic spin and charge ordering states. Adding to this, Rosen et al.identify a stark difference in the electronic structure of the cuprate Bi2201 between its surface and its bulk.

The authors analyzed the whole-exome sequences of over 16,000 individuals and found that very rare variants predicted to disrupt the SETD1A gene confer substantial risk for schizophrenia. Damaging variants in SETD1A were also associated with diverse, severe developmental disorders, providing an important genetic link between schizophrenia and other neurodevelopmental disorders.

Dysfunction of autophagy in plaque macrophages aggravates atherosclerosis. Here the authors show that induction of macrophage autophagy–lysosomal biogenesis either genetically by overexpression of the master transcriptional regulator of this process, TFEB, or pharmacologically with trehalose is atheroprotective.

The robust attraction between a bacterial protein and vitamin H could boost the sensitivity of immuno assays, improve DNA probes and aid in protein purifications. Its role in nature remains a mystery.

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

Antiferromagnets are promising candidates to build terahertz spintronic devices. However, manipulating and detecting their terahertz spin dynamics remains key challenges. Here, Rongione et al. demonstrate both broadband and narrowband terahertz emission from an antiferromagnet/heavy metal heterostructure using spin-phonon interactions.

ILC3s expressing MHC class II control the fate of inflammatory versus tolerogenic T cells that respond to the microbiota by selecting for antigen-specific RORγt⁺ T_reg cells and against T_H17 cells, establishing intestinal homoeostasis.

G protein-coupled receptors are a large family of signalling proteins that mediate cellular responses primarily via G proteins or arrestins, and they are targets of one-third of the current clinically used drugs; here, an active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin-1 is determined, revealing unique structural features that may constitute essential elements for arrestin-biased signalling.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

A genome-wide association study of mosaic loss of chromosome Y (LOY) in UK Biobank participants identifies 156 genetic determinants of LOY, showing that LOY is associated with cancer and non-haematological health outcomes.

Owen Rackham, Jose Polo, Julian Gough and colleagues present a method, Mogrify, for predicting sets of transcription factors that can induce transdifferentiation between cell types. They show that Mogrify is able to predict known factors for published cell conversions and experimentally validate factors for two new conversions.

A study of hospitalized patients infected with SARS-CoV-2 and who have liquid or solid cancer suggests that hematologic malignancy is an independent risk factor for mortality and that CD8⁺ T cells might limit infection in this setting irrespective of humoral immunity.

A nearly 175 Ma granite body in West Antarctica reveals ice flowed across the southern Hudson Mountains at the Last Glacial Maximum, resulting in erratics derived from local subglacial bedrock, as revealed through an integration of age and lithology from glacial erratics with geophysical modelling.

Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension.

Specific deletion of group 2 innate lymphoid cells in mice shows these cells have roles in the recruitment of eosinophils and in mounting immune and epithelial type 2 responses.

Forms of cell death besides apoptosis and necrosis are becoming increasingly well understood, and are relevant to many disease contexts. Here, Conradet al. describe the mechanisms underlying regulated forms of necrosis — including necroptosis, ferroptosis, parthanatos and cyclophilin D-mediated necrosis — and efforts to induce or prevent them in disease.

The pyruvate dehydrogenase complex (PDC) is a multienzyme complex connecting glycolysis to mitochondrial oxidation of pyruvate. Cryo-EM analysis of PDC from Neurospora crassa reveals localization of fungi-specific protein X (PX) and confirms that it functions like the mammalian E3BP, recruiting the E3 component of PDC.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

Excitation of whistler-mode waves by cyclotron instability is considered as the likely generation process of the waves. Here, the authors show direct observational evidence for locally ongoing secular energy transfer from the resonant electrons to the whistler-mode waves in Earth’s magnetosheath.

Cervicovaginal inflammation and human papillomavirus (HPV) are separately associated with increased risk of HIV acquisition. Here the authors longitudinally profile 48 cervicovaginal cytokines and HPV status in a large observational HIV high-risk cohort, and show the same cytokines associate with HPV infection and HIV risk.

Mark Samuels and colleagues report the identification of mutations in mitochondrial carrier family member SLC25A38 in nonsyndromic autosomal recessive congenital sideroblastic anemia.

Sander and colleagues show that antigen-presenting cells detect bacterial RNA from live bacteria via TLR8 and promote T_FH cell differentiation and vaccine responses through the induction of a specific cytokine profile.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Liquid water on equatorial Mars is inconsistent with large-scale climatic conditions. Humidity and temperature measurements by the Curiosity rover support the formation of subsurface liquid brines by hydration of perchlorates during the night.

Using meta-analysis of previous genome-wide association studies against the latest reference variant databases, this work identifies five new risk loci for glioblastoma and non-glioblastoma type of glioma.

Late-onset Alzheimer's disease (LOAD) is a complex multi-factorial disorder. Here, the authors perform a data-driven analysis of LOAD progression, including multimodal brain imaging, plasma and CSF biomarkers, and find vascular dysfunction is among the earliest and strongest altered events.

In many cuprates the high temperature superconducting state competes with a charge ordered phase that has been difficult to investigate in detail. Here the authors show three-dimensional charge order can be stabilized in YBCO films and studied without using the high magnetic fields that are necessary in the bulk material.

McrBC is a bacterial antiphage defense system that cleaves methylated DNA and is composed of the AAA+ GTPase motor McrB and the endonuclease McrC. Here, the authors present the cryo-EM structure of E. coli McrBC that reveals how McrC inserts a stalk-like structure into the pore of the ring-shaped McrB hexamer and discuss mechanistic implications.