Search

Adoptive regulatory T cell (Treg) therapy holds promise for the treatment of a range of immunopathological conditions. Here the authors explore the HLA engineering of allogenic Treg products that avoid T cell and NK cell attack and maintain immunomodulatory function in a human skin-xenograft model.

The placenta plays vital roles in supporting fetal development. Here, Richards et al. develop a high-throughput bioprinted trophoblast organoid model to recapitulate the microenvironment of the early placenta, enabling investigation of placenta development and evaluation of therapeutics for placenta dysfunction disorders.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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.

Widely cited studies have claimed that musical training is associated with enhanced neural encoding for sound at early stages of the auditory system. Results from this large-scale multisite study do not support this earlier claim.

Here, Brown et al show that sewage-associated antibiotics in wastewater treatment plants select for antibiotic resistance via horizontal gene transfer.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Halbrook et al. report two metabolic subgroups of pancreatic ductal adenocarcinoma cells defined by differential integrated stress response and asparagine production that permit symbiosis and phenformin resistance.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Viral infection is a common risk for immune-compromised individuals, particularly pediatric patients receiving hematopoietic stem cell transplants. Here the authors report a phase II trial testing adoptive transfer of third party, virus-specific T cells on the feasibility, safety, clinical responses, as well as homeostasis of antiviral immunity in the recipients.

Ultrathin and flat crystals of bismuth are grown between the atomically flat layers of a van der Waals material. These crystals exhibit outstanding electronic properties, including gate-tunable quantum oscillations of the magnetoresistance.

Breakdown of the blood–brain barrier in individuals carrying the ε4 allele of the APOE gene, but not the ε3 allele, increases with and predicts cognitive impairment and is independent of amyloid β or tau pathology.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

In the I-SPY2.2 trial, patients with high-risk stage 2/3 breast cancer received neoadjuvant datopotamab–deruxtecan plus durvalumab, followed by sequential chemotherapy with or without targeted therapy, with the option of early surgical resection after each block of therapy, showing that de-escalation of therapy is possible for several patient subgroups without compromising outcome and avoiding toxicity of standard chemotherapy.

A spatially extensive survey of lake CH₄ and CO₂ emissions in Arctic Alaska shows the source material to be primarily relatively young organic matter (up to about 3,500 years old). Contributions from ancient C sources were twice as large in fine textured sediments.

The difference between children and adults in response to SARS-CoV-2 infection is not clearly established. Here the authors use gene expression analysis of nasopharyngeal samples from children and adults and show a higher level of immune response in children compared to adults, including of B and T cell activation.

Functional CRISPR screens in patient-matched pre-treatment and post-treatment glioblastoma models identify the PTP4A–ROBO1 axis as a driver of tumorigenicity and enriched ROBO1 expression in recurrent glioblastoma that can be targeted with CAR T cell therapy.

Mosaic chromosomal alterations (mCAs) in peripheral blood leukocytes are associated with an increased risk of malignancy. Here, the authors use genome-wide genotyping array data to investigate the prevalence of mCAs in sub-Saharan African children with versus those without Burkitt lymphoma.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Fast spiking interneurons provide perisomatic inhibition in the cortex. Here, Baohan et al. show the failure to develop perisomatic inhibition in heterozygous PTENnull mutant mouse and the underlying mechanism to EphB4 reduction in an experience-dependent manner.

Safety and equity concerns prompt some journals and scientific societies to hasten use of new names on transgender authors’ works.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

Astroblastoma (AB) is an uncommon brain tumour and its origin remains unknown. Here, the authors perform integrative molecular analysis of 35 AB-like tumours and provide evidence that these arise in the context of epigenetic and genetic changes in neural progenitors occurring during brain development.

This study presents a predictive equation for total energy expenditure derived from doubly labelled water measurements. Applying this equation to two large datasets (the National Diet and Nutrition Survey and National Health and Nutrition Examination Survey) shows that the misreporting of total energy intake is greater than 50%, with important implications for macronutrient availability.

Environmental conditions during pregnancy contribute to offspring metabolic disease. Here, the authors show that immune cells reprogrammed in utero by maternal vitamin D deficiency increase lifetime diabetes risk in the offspring and are sufficient to transplant diabetes.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

Data-driven discovery in complex neurological disorders has potential to extract meaningful knowledge from large, heterogeneous datasets. Here the authors apply topological data analysis to assess therapeutic effects in preclinical traumatic brain injury and spinal cord injury research studies.

Results from a comprehensive evaluation of the function of BRCA2 variants, particularly variants of uncertain significance, provide a useful resource to improve the clinical management of individuals who carry such genetic variants.

DNA repair in response to DSBs in the preimplantation embryo is hard to analyze. Here the authors show that over 25% of pre-existing heterozygous loci in control single blastomere samples appeared as homozygous after whole genome amplification, therefore, they validated gene editing seen in human embryos in ESCs.

Advances in single-cell imaging bring opportunities for physicists, biologists and chemists alike.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

The 2009 H1N1 influenza pandemic exposed major gaps in our knowledge of the spatial ecology and evolution of swine influenza A viruses. Here Nelson et al. perform an extensive phylogenetic analysis of these viruses and show that the global trade of live swine strongly predicts their spatial dissemination.

The re-epithelialization phase in skin wound repair involves epidermal cell migration into the wound, proliferation and differentiation. Here the authors describe a role for the transcription factor Tcf3 and its target, the secreted factor lipocalin2, in cell migration during wound healing in mice.

The features of astrocytes surrounding CNS lesions are unclear. Here the authors show that after spinal cord injury or stroke in mice, mature astrocytes dedifferentiate, proliferate and are reprogrammed to adopt features of wound repair cells and form borders, re-establishing CNS integrity.

REV-ERBs, nuclear hormone receptors that regulate transcription as part of the circadian clock cell machinery, inhibit autophagy and lipogenesis in premalignant and malignant cells and impair tumour growth in vivo.

Whole blood signatures have served as the potential biomarkers for TB but failed to meet World Health Organization’s (WHO) optimal target product profiles (TPP). By employing cohorts from multiple countries, the authors identify a diagnostic 6-gene signature from cell free RNA which outperforms TPP requirement in distinguishing TB from non-TB.