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A bivalent biparatopic nanobody penetrates the brain, binds to and potentiates the activity of homodimeric metabotropic glutamate receptor 2, correcting cognitive deficits in two preclinical mouse models with endophenotypes resulting from NMDA receptor hypofunction.

Pseudo-overdominance describes haplotypic combinations of recessive deleterious alleles complement each other and result in enhanced fitness in heterozygotes compared to homozygotes. Here, the authors show the role of pseudo-overdominance in maintaining genetic diversity in populations of cultivated pearl millet.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

This study documents the evolution of antibiotic resistance and major growth defects in Yersinia enterocolitica in a patient over 14 years, revealing genetic changes that shed light on bacterial adaptation to infection and therapy.

East, South, and Southeast Asia are key regions in the dissemination of seasonal influenza viruses, but major perturbations (e.g., pandemics) may disrupt their role. Here, the authors demonstrate the impact of the 2009 H1N1 and COVID-19 pandemics on seasonal influenza circulation and evolution within Southeastern Asia.

Feeding an increasing world population in the context of climate change is one of the grand challenges faced by our generation. Here, the authors show that external application of synthetic complementary peptides can increase the abundance of target proteins to modulate plant growth or stress resistance.

The final report of the phase 1/2 lentiviral gene therapy trial in severe β-hemoglobinopathies, HGB-205, shows a long-term safety profile and sustained reduction of transfusion requirements in patients with β-thalassemia and of sickle cell crises in patients with sickle cell disease.

Phages can use ACR proteins that inhibit the adaptive immunity activities of bacterial CRISPR-Cas systems. Here, Philippe et al. show that these systems can block ACR-containing phages by targeting the acr gene, and this can select for phage mutants carrying a deletion within acr that does not block DNA cleavage (interference) but prevents the addition of new immunity (spacer acquisition).

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

Philippe Froguel and colleauges present a genome-wide association study for early-onset and morbid adult obesity, reporting three new genetic associations to obesity.

Whole genome data for 221 geo-referenced cultivated and wild accessions of pearl millet reveals their domestication centre in the western Sahara, 4,900 years ago.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

This study identifies a novel immune checkpoint in senescent cells that is linked to the ganglioside GD3 and that contributes to the evasion of immune clearance by these cells and to aging and age-related diseases.

A central goal of spintronics is electric control of magnetism. One particularly promising method makes use of spin-orbit torques which arise due to the combination of electric current, and the intrinsic spin-orbit effect in a material. Here, Grezes et al demonstrate non-volatile electrical control of the spin-orbit torque generated at the interface between an oxide and a metal.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Regulatory T cells (T_reg) develop in the thymus via two pathways including CD25⁻Foxp3^lo and CD25⁺Foxp3⁻ cells. Here, the authors show that lymphotoxin acts as an inhibitory checkpoint of thymic T_reg development, fine-tuning the Foxp3^lo precursor pathway by limiting IL-4 production in medullary thymic epithelial cells.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

GnRH neurons control their own connectivity and function as well as the sexual maturation of the individual by using prostaglandin D₂ DP1 signaling to recruit and stably associate with newborn astrocytes in the preoptic region during infancy in rodents.

Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Isabelle Plo, Christine Bellanné-Chantelot, William Vainchenker and colleagues report a 700-kb germline duplication including the ATG2B and GSKIP genes in four related families with myeloid malignancy predisposition. Using induced pluripotent stem cells and primary cells, they demonstrate that ATG2B and GSKIP enhance hematopoietic progenitor differentiation.

R2TP is an HSP90 co-chaperone composed of an RPAP3-PIH1D1 heterodimer, which binds two essential AAA+ ATPases RUVBL1/RUVBL2. Here authors use a structural approach to study RPAP3 and find an RPAP3-like protein (SPAG1) which also forms a co-chaperone complex with PIH1D2 and RUVBL1/2 enriched in testis.

Replacement of local crops with alternative varieties adapted to future conditions may improve food security under climate change. Here the authors apply landscape genomics and ensemble climate modelling to pearl millet in West Africa, supporting the potential of transfrontier assisted seed exchange.

Diet-induced changes in the microbiome have been associated with obesity. Here, using a mouse model, the authors show that a mixed protein source found in western diets exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling via microbial production of branched-chain fatty acids (BCFA).

Biological control of the root-knot nematode Meloidogyne incognita, one of the world's most destructive crop pathogens, presents a major opportunity for safely improving global agricultural yields. Its 86-Mb genome—the first to be sequenced for a strictly parthenogenetic species—provides a blueprint to design new strategies for plant protection.

It is commonly believed that graphene flakes form electrical percolation networks at low concentration, and thus can be used as conductive materials. Here, Yuan et al. show in graphene polymer composites that the transition to liquid crystals hinders the formation of percolated networks, resulting in high-kmaterials.