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How plants mitigate the negative effects of exposure to continuous, moderately high temperatures remains underexplored. Here, the authors report the role of chelation-based iron uptake in mitigating prolonged high-temperature in cool-season grasses, specifically Brachypodium distachyon and wheat.

How individual organs are specifically regulated by the sympathetic neurons at the cellular level remains not fully understood. Here, authors identify two molecularly distinct sympathetic pathways that independently control the adrenal medulla and intestine.

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.

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.

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.

The glutamate transporter GLAST in astrocyte regulates synapse function by glutamate clearance. Here, the authors show that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synaptogenesis through the intercellular association with GLAST in the developing cerebellum.

Mutations in ryanodine receptor 1 (RyR1), a Ca2+ release channel in skeletal muscle, cause malignant hyperthermia (MH) and are involved in heat stroke. Here, the authors show that an oxolinic acid-derivative RyR1 inhibitor effectively prevents and treats MH and heat stroke in various MH mouse models.

By using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, unique evolutionary histories of breast cancers harbouring a common driver alteration are shown, providing new insight into how breast cancer evolves.

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.

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.

GABAergic neuron progenitors in the cerebellum give rise to Purkinje cells and GABAergic interneurons. Here the authors show that the transcription factors Olig2 and Gsx1 regulate an identity transition from Purkinje cell progenitors to interneuron progenitors during mouse development.

Viral vectors with intense and long-lasting transgene expression are essential for manipulating and imaging of neuronal activity in the primate brain. Here, the authors created a mosaic vector composed of capsid proteins derived from AAV1 and AAV2 that exhibits improved transgene expression and neuronal specificity.

Pharmacological and surgical treatments of epilepsy can have unsatisfactory outcomes, so a more targeted and on-demand approach is desirable. Here, the authors demonstrate the usage of inhibitory chemogenetics in male nonhuman primates to attenuate the magnitude and spread of cortical seizures and subsequent body convulsions.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The authors show that shortening of the basal process in neural progenitor cells by depletion of TAG-1 results in overcrowding in the periventricular space and, eventually, delamination and aberrant migration. These results suggest that one of the functions of interkinetic nuclear migration is to prevent progenitor congestion and mechanical stress.

iPSCs from three endangered avian species (including Okinawa rail, Japanese ptarmigan, and Blakiston’s fish owl) are developed and characterized as a potential resource for their conservation.

B cells reactive against self antigens can cause autoimmune disease, but are normally suppressed by regulatory T cells (Tregs). Here the authors show that a subset of Tregs can suppress lupus in a mouse model by making TGF-β3 cytokine and by engaging an inhibitory PD-1 receptor on B cells.

Yukiko Inagaki-Kawata et al. report an analysis of germline variants in breast cancer susceptibility genes in 1,995 Japanese breast cancer patients. They find that 5.1% of the patients carry germline variants in cancer-linked genes and investigate the characteristics of patients with germline mutations in BRCA1/2.

The controlled activation of proteins inside living cells is an important goal in protein design research. Now, a strategy for allosteric activation using coordination chemistry has been demonstrated for two different kinds of neurotransmitter receptors, an ion-channel and a G-protein coupled glutamate receptor.

Deschloroclozapine (DCZ) is a broadly useful chemogenetic agonist for studies using nonhuman primates and mice. DCZ rapidly and reversibly activates DREADDs, and its binding can be visualized noninvasively by positron emission tomography.

Hiraga et al. generate knockout mice lacking type II cadherins Cdh6, Cdh8 and Cdh11 to elucidate their role in the developing CNS. Whereas no phenotype is observed in single knockouts, the analysis of double and triple knockouts show that type II cadherins serve essential and shared roles in compartmentalization and neurulation.