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Interleukin-10 promotes the formation of microcirculatory defects in the brain associated with cognitive impairment in a mouse model of type 1 diabetes.

New data show that the HMCES protein suppresses DNA double-strand break formation by cross-linking to and thereby stabilizing an abasic site generated during replication-coupled repair of a DNA interstrand cross-link, thus demonstrating a physiological role of HMCES in DNA repair.

It has been challenging to make long RNAs with site-specific modifications for NMR study. Here the authors present SegModTeX: a method for site-specific and segmental labeling of RNAs independent of their sequence or segment length, with applications for biological- and artificial NTP analogues at purity and scale sufficient for NMR.

Iron has been shown to be necessary for the activation and differentiation of CD8⁺ T cells. Here the authors investigate changes in CD8⁺ T cell metabolism in iron limiting conditions and find that aspartate is increased yet downstream nucleotide synthesis is suppressed and addition of exogenous aspartate partially rescues T cell function.

Newman et al. show that, upon mitochondrial DNA (mtDNA) replication stress, enlarged nucleoids are trafficked to endosomes. Endosomal rupture releases mtDNA into the cytoplasm, triggering cGAS–STING activation and innate immune signalling.

The Complement component 9 (C9) is the pore-forming component of the Membrane Attack Complex which targets pathogens. Here authors use structural biology to compare monomeric C9 to C9 within the polymeric assembly and identify the element which inhibits C9 self-assembly in the absence of the target membrane.

Lotto et al. delineate cell diversity and mechanisms during heart valve development using scRNA-seq. They identify distinct cell types and states, the emergence of epithelial-mesenchymal plasticity, and cell interactions that may govern this process.

SF3B1 mutations confer sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). Mechanistically, this is independent of homologous recombination repair and instead relies on a defective replication stress response due to a reduction of the cyclin-dependent kinase 2 interacting protein (CINP). PARPi treatment of SF3B1 mutant (SF3B1^MUT) tumors leads to replication stress induced by increased fork origin firing and culminates in cell cycle stalling.

The patriarch of the haematopoietic system, which generates all the various kinds of specialized blood cells, is a stem cell found in adult bone marrow. Studies of how it differentiates have revealed a remarkable finding -- if this cell is denied the transcription factor Pax5 at a particular stage, instead of becoming an antibody-producing B cell some six other options become available to it.

The most spectacular example of plate convergence on Earth was the motion of the Indian plate towards Eurasia, and the subsequent collision. Density estimates of the Greater Indian continent, after its upper crust is scraped off at the Himalayan front, suggest that this continental plate is readily subductable, potentially explaining why the convergence did not halt on collision.

Three-dimensional dynamic computer models show how accretionary tectonic margins evolve from the initial plate-collision state, through a period of plate margin instability, and then re-establish a stable convergent margin; the models illustrate how significant curvature of the orogenic system develops, as well as the mechanism for tectonic escape of the back-arc region.

In this work, researchers engineer HIV-1 immunogens using molecular dynamics simulations to enhance vaccine designs that select for specific antibody mutations. Their approach improved the selection of mutations crucial for broadly neutralizing antibody responses, offering a promising strategy for HIV vaccine development.

Efforts are ongoing to find which human or viral factors underpin whether a person with COVID-19 will develop severe symptoms. Clinical evidence linked to two viral lineages now provides key insights into this enigma.

In this Review, the authors provide an overview of the roles of individual histone variants in multiple processes, including gene regulation, DNA replication and DNA repair, and the cellular consequences of their dysfunction.

Computational simulations show that variations in the rate of fluvial erosion between tectonically active and inactive mountain ranges may relate to a bidirectional coupling between bedrock river incision and landslides.

In this study, Henderson and Zhou et al. visualize the development of a HIV-1 broadly neutralizing antibody (bnAb) from germline to maturity by determining cryo-EM structures of HIV-1 Envelope (Env) proteins bound to Fab fragments of antibodies at different stages of development of a Env V3-glcyan supersite targeting bnAb clone.

The SARS-CoV-2 spike ectodomain is destabilized by cold temperature storage, an effect that can be reversed by incubation at 37 °C or by stabilizing its conformation in the ‘down’ state.

The SARS-CoV-2 spike glycoprotein is flexible, and its receptor-binding domain (RBD) fluctuates between up or down conformations. Mutations engineered into the spike ectodomain either lock the RBD in the down state or make it adopt the up conformation more readily.

Interferons (IFNs) activate and regulate antitumour immune responses. This Review discusses lessons that can be learnt from using type I IFNs in oncology and our current understanding of the interferome in modifying antitumour immune responses.

Interstrand crosslinks (ICLs) are a type of DNA damage that is induced by various chemotherapeutics, such as cisplatin. This Review discusses how these lesions are repaired through multiple pathways, including the Fanconi anaemia pathway, and how ICL repair mediates sensitivity to these drugs.

Influenza is an infectious respiratory disease that, in humans, is caused by influenza A and influenza B viruses. This Primer discusses the biological features of influenza viruses, their effects on human and animal health and the mitigation strategies to reduce the burden of this disease.

The differentiation of αβ T cells is a complex process. Using data sets from the Immunological Genome Project, Benoist and colleagues identify candidate mediators of key transitions during thymocyte selection and maturation.

The functional and regulatory aspects of the ‘mitochondrial divisome’ are separated into core and accessory machinery, thus providing a mechanistic understanding of the process of mitochondrial fission.

The objective of the Paris climate agreement is to limit global-average temperature increase to well below 2 degrees Celsius above pre-industrial levels and to further pursue limiting it to 1.5 degrees Celsius; here, the adequacy of the national plans submitted in preparation for this agreement is assessed, and it is concluded that substantial enhancement or over-delivery on these plans is required to have a reasonable chance of achieving the Paris climate objective.