Search

A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

The flightless emu wings have a striking resemblance to immobilization phenotypes. Here, authors report that cell death of dual-identity muscle progenitors during embryonic development contributes to distal muscle absence, linked to skeletal shortening and asymmetry in this vestigial structure.

Placement of an m⁷G cap internally on circular RNAs promotes their translation in vivo.

Cyanobacteria use both chlorophylls and phycobilins to absorb light energy, and authors here use cultivation experiments, numerical simulations and protein phylogenetics to argue that cyanobacteria evolved in a green-light environment during the Archaean era in which green-specialized phycobilins would have been selectively advantageous.

Live-cell-imaging-based screens identify RasGEFX as an essential component of the pathway that triggers spontaneous Ras excitation for basal cell migration in combination with RasGEFB/M/U and for macropinocytic cup formation and fluid uptake.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Trivalent PROTACs are reported as a strategy to increase protein degradation efficacy and therapeutic window by combining avidity of target engagement with cooperativity to form highly favorable and productive ternary complexes.

Carboxylesterases catalyze the enantioselective synthesis of chiral carboxylic acids and esters but exhibit limited enantioselectivity, particularly toward ethyl 3-cyclohexene-1- carboxylate (CHCE). Here, the authors establish a high-throughput method to generate a high-quality dataset for carboxylesterase AcEst1 from Acinetobacter sp. JNU9335 using CHCE as the substrate, use it to train a machine learning predictor and design two stereocomplementary mutants to synthesize both enantiomers of chiral CHCE.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

This study identifies TTTCA- and TTTTA-repeat expansions in benign adult familial myoclonic epilepsy. Cortical neurons from affected people exhibit RNA foci containing these expanded repeats, suggesting RNA toxicity as the mechanism underlying disease pathogenesis.

In C-glycosides the sugar moiety is linked through a carbon-carbon bond to the non-sugar moiety, which can be cleaved by intestinal microbes. Here, the authors use bioinformatics analysis to identify C-glycoside deglycosidase enzymes in intestinal and soil bacteria, biochemically characterise them and determine their structures and probe catalytic important residues in mutagenesis experiments.

It is becoming increasingly clear that the three-dimensional organization of chromatin within the nucleus plays a role in regulating gene expression. Here, Ito et al.demonstrate that the disruption of chromocenter clustering in mature neuronal cells results in specific transcriptional and behavioural defects in mice.

Non-human primates are useful models for understanding the human brain but application of optogenetics to non-human primates is challenging. The authors used optogenetic intracortical microstimulation in the primary motor cortex of macaques to elicit distinct forelimb movements and muscle activity.

The structure of the Golgi and the localization of glycosylation enzymes remain largely elusive. Here, the authors use super-resolution microscopy to show that the Golgi is composed of small dynamic units which have rapidly moving zones of glycosylation enzymes.

Forward genetics analyses and targeted genetic manipulation in mice show that regulation of sleep quantity and quality is mediated by the LKB1–SIK3–HDAC4–HDAC5 pathway.

Non-alcoholic fatty liver disease is more common among older individuals. Here, the authors show that senescent cells in the liver promote fat accumulation and steatosis in the liver, and that clearance of senescent cells reduces hepatic steatosis in old, obese or diabetic mice.

Long-read sequencing identifies a GGC repeat expansion in NOTCH2NLC that is associated with neuronal intranuclear inclusion disease, a progressive neurodegenerative disorder. The expansion results in abnormal anti-sense transcripts that could contribute to disease pathogenesis.

Sulfation of chondroitin sulfate and heparan sulfate dictates their abilities to promote axon growth via regulating the binding to the phosphatase PTPRσ and the consequences on phosphorylation of the cortactin component of the autophagy machinery.

Excitatory spiny stellate neurons in the somatosensory cortex are shaped by innervating thalamic inputs and unique expression of genes. Here, the authors show that these neurons play a crucial role in processing distinct whisker signals and forming specialized circuits for sensory perception.

Plants develop shoots and roots to access light, carbon dioxide, water and nutrients. Light intensity and quality are suggested to affect root nutrient uptake. Now, the researchers identify a mechanistic link between red light and phosphorus uptake by investigating 200 natural accessions of Arabidopsis.

The near-atomic-level structure of a complete bacterial light-harvesting antenna–reaction centre (LH1–RC) complex is described here; the structure reveals how energy is transferred from the LH1 to the RC in a highly efficient way and suggests how ubiquinone might cross a closed LH1 barrier.

Iron nitride (Fe₄N) is detected on magnetite particles within the Ryugu sample returned by Hayabusa2. It is probably the product of impacts of nitrogen-rich dust from the outer Solar System on the surface of Ryugu, indicative of a flux of N-rich dust in the inner Solar System.

Different membrane proteins dynamically polarize to organize signal transduction, but the underlying mechanism is unclear. Here, the authors show that a differential diffusion mediated partitioning process is sufficient to drive such spatiotemporal patterning of membrane-associated signaling proteins.

DNMT1 is an essential for maintaining genomic DNA methylation. Here, we report the cryo-EM structure of DNMT1 bound to ubiquitinated H3 and hemimethylated DNA, revealing structural insight into the activation mechanism of DNMT1.

Mitochondria are involved in ageing but exactly how they are involved is controversial. Here the authors show that optimal assembly of mitochondrial complex I predicts longevity in mice, whereas partial complex I assembly increases the production of reactive oxygen species.

The mechanisms by which pathogen effector proteins target host defence responses remain poorly understood. Here, Ishikawa et al. show that XopP_Xoo, a rice pathogen effector, suppresses host plant immunity by inhibiting the activity of an E3 ubiquitin ligase.

The TRPV2 calcium channel can be activated by mechanical stretch and may act as a mechanoreceptor in tissues. Here the authors deplete the TRPV2 calcium channel from the hearts of adult mice, showing that TRPV2 is important for the maintenance of cardiac structure and function.

The molecular mechanisms of neurotrophin receptor trafficking are only partially understood. Here the authors show that ARHGAP33 interacts with SORT1 to regulate TrkB trafficking, the dysfunction of which impairs synapse development and leads to schizophrenia-related behavioural abnormalities in mice.

Mutations in the EZH2 gene are found in myelodysplastic syndrome (MDS) and are often accompanied by mutations in RUNX1. Here, the authors develop a mouse model of MDS and show that EZH2loss enhances the RUNX1-mediated MDS pathology.

In vertebrates, unfertilized eggs arrest at metaphase of meiosis II via Emi2, which inhibits APC/C ubiquitin ligase. Here, Sako et al.show that on fertilization the degradation of Emi2 allows binding between APC/C and the C-terminal tail of the ubiquitin-conjugating enzyme Ube2S, thus releasing the meiotic arrest.

Sensitive and label-free imaging methods to visualize nerve degeneration are currently lacking. Here authors show that stimulated Raman scattering (SRS) microscopy can be used to monitor peripheral nerve degeneration in mouse models of amyotrophic lateral sclerosis (ALS) and in postmortem tissue from ALS patients.

Channelrhodopsins are light-activated ion channels that mediate cation permeation across cell membranes upon light absorption. Here, the authors report the crystal structure of the most red-shifted channelrhodopsin from the algae Chlamydomonas noctigama at 2.6 Å resolution.

Chemogenetic inactivation of the subthalamic nucleus in monkeys increases spike train variability in the pallidum and prolongs movement time, suggesting its role in stabilizing pallidal spike trains to achieve stable motor control.

In this study, Yoshimi et al. report on the mechanisms of CRISPR-Cas3 non-specific cleavage of single-stranded DNA and target-specific degradation of double stranded DNA. They employ high-speed AFM to capture images of type I CRISPR priming and interference.

Despite being key drivers of protective antibodies against malaria, little is known regarding the host and parasite factors that influence CD4 T-follicular helper cell and antibody development. Authors utilise samples from a study of children living in an area of high malaria transmission in Uganda, to characterize Tfh cells and functional antibodies to multiple parasites stages.

Hirano et al. develop a heart failure diagnosis of triglyceride deposit cardiomyovasculopathy based on defective lipolysis and show long-term survival and patient recovery after tricaprin treatment.