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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.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

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.

In 2022, mpox predominantly spread through sexual contact, necessitating updated prevention strategies. Here, the authors show that rectal challenge in male cynomolgus macaques with a 2022 clade IIb MPXV isolate mimics sexual transmission, and that vaccination with modified-vaccinia Ankara protects pre- but not post-exposure.

The JAK inhibitor ruxolitinib has been used for treatment of myeloproliferative neoplasms (MPN) and its association with clonal evolution requires further investigation. Here the authors report accumulation of RAS pathway mutations in ruxolitinib-treated myelofibrosis patients, stemming from RAS clonal selection induced by JAK2 inhibition.

Previous models of γ-tubulin ring complex (γTuRC) assembly implied that γ-tubulin complex proteins (GCPs) 4–6 serve as a scaffold for arranging multiple γ-tubulin small complexes (γTuSCs) into large γTuRCs. The crystal structure of human GCP4 represents a prototype for all GCPs and can be precisely positioned within γTuSC, providing a new framework for understanding γTuRC formation.

Here, the authors show that KDM2A regulates cell cycle progression, modulation of H3K36me2 and H3K27me3 chromatin states and gene repression which are critical for survival of differentiating spermatogonia. KDM2A regulates progression through meiosis as well.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Autophagy has a key protective role under nutrient stress. Here the authors unveil in yeast a specific mechanism of induction of autophagy upon sulfur deprivation that requires the transcription activator Met4 and involves SAM as signaling molecule.

Sepsis induces a period of immunosuppression which can be problematic in the face of subsequent infectious challenge. Here the authors show the presence of PD-L1 expressing regulatory plasma cells that can inhibit T cells in a murine model and in patients with sepsis.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

Here, Carvalho et al show that Listeria starved in water shed their cell wall to form osmotically stable viable but non-culturable cells, that can revert back to walled, culturable and virulent forms.

Liver fibrosis is a consequence of the sustained inflammatory processes underpinning chronic liver disease. Here authors show that autophagy in CD4 T cells is an important process in preventing the emergence of pathogenic Th17 cells, which are causal to the progression of liver fibrosis.

Different proteins localised at telomeres ensure chromosome end stability to prevent double strand-end break recognition. Here the authors provide new insight into how in S. cerevisiae the interaction between Rif2 and Rad50 inhibits MRX functions at telomeres.

This study uses ice sheet modeling experiments to show that thawing portions of the Antarctic ice sheet bed can increase century-scale mass loss, particularly in the Wilkes and Enderby Land regions of East Antarctica.

HIV remission has been seen in people living with HIV after the cessation of antiretroviral therapy and is termed post treatment control. Here Passaes and colleagues present an SIV model that shows early initiation of antiretroviral therapy after SIV infection is linked to improved post treatment control upon cessation of antiviral therapy and associates with the expansion of an enhanced memory pool of CD8 + T cells‘.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Marie-Paule Roth and colleagues report that targeted disruption of Bmp6 in mice leads to a rapid and massive accumulation of iron in several tissues, showing that it is critical for iron homeostasis.

The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.

EPAC1 is a cAMP-activated guanine nucleotide exchange factor (GEF) for Rap GTPases and a major transducer of cAMP signaling. Here, the authors show anionic membranes can activate EPAC1 independently of cAMP, increase its affinity for cAMP by two orders of magnitude, and synergize with cAMP to yield maximal GEF activity.

Fonio millet is a fast growing orphan cereal crop with a great potential for dryland agriculture. Here, the authors report chromosome-scale reference genome assembly and population genomic resources to shed light on genetic diversity, population structure and domestication of fonio millet.

Differences in virulence across the Listeria monocytogenes species are determined by the fine-tuning of SigB pathway responsiveness and reflect host adaptation.

Myotonic dystrophy type 1 (DM1) is characterized by debilitating neurological symptoms. Dinca et al. demonstrate the pronounced impact of DM1 on the morphology and RNA metabolism of astrocytes. Their findings suggest astroglial pathology in DM1 brain dysfunction.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

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.

Overall survival in metastatic non-small cell lung cancer is improved by immunotherapy but individual responses widely vary, and predictive biomarkers are urgently needed. Here authors show that multimodal markers, based on clinical, pathological, radiological, and transcriptomic data are more reliable at patient risk stratification than unimodal markers, considering one type of input data only.

Broomrape (Orobanche) is a parasitic plant that infects crops. Here, quantitative genetics and mapping in sunflower identify one resistance gene named HaOr7. It is a membrane receptor-like kinase that prevents attachment of the parasitic plant to the sunflower roots.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.