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Small molecule antagonists of CCR6 are potential drugs for autoimmune disorders. Here the authors present inactive structures of CCR6 bound by different allosteric antagonists from two series simultaneously, offering multiple approaches to inhibit CCR6.

Correlating aromatic carbons attached to fluorine with meta-position hydrogens in fluorine-labelled phenylalanines can yield two-dimensional correlations with narrow linewidths in large proteins. Adapting phenylalanine-tRNA synthetase increases the incorporation rate, while expanding the genetic code enables site-specific incorporation of fluorinated phenylalanine. The resulting HC_F-transverse relaxation-optimized spectroscopy can illuminate protein dynamics and drive multiplexed drug discovery campaigns.

RNA-based viruses can be engineered to express artificial microRNAs (amiRNAs). Here, the authors identify a candidate amiRNA that confers a replicative advantage to oncolytic viruses, enhancing their anticancer potency, and show that intercellular transfer of extracellular vesicles carrying the amiRNA promotes bystander killing of uninfected cancer cells.

Integrins regulate haematopoietic stem cell (HSC) homeostasis and engraftment into the bone marrow (BM) niche upon transplantation. Here, the authors show that HSC quiescence and function in the BM is regulated by the interaction of PERIOSTIN and INTEGRIN αv and subsequent increase in p27Kip1.

Targeting the integrin VLA-4 with natalizumab has shown efficacy in treating multiple sclerosis, but relapse still occurs in some patients. Here the authors use a high-content cell imaging (HCI) pipeline and machine learning to assess the morphology of T cells from MS patients prior to natalizumab regime for defining features associated with treatment responses.

Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.

P. falciparum and vivax are responsible for most cases of malaria but are not genetically closely related and differ in their clinical and epidemiological impacts. In this study, the authors investigate the genomic and epidemiological characteristics of the two parasites in a co-endemic setting of Guyana.

Dendritic cells experience cell shape changes while migrating within the complex physical environment of tissues. Sensing of these shape changes modifies their migratory properties and imprints these cells with immunoregulatory properties.

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.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

The integration of 1,024 independent silicon quantum dot devices with on-chip digital and analogue electronics, all of which operate below 1 K, allows characteristic data across the quantum dot array to be acquired and analysed in under 10 min.

An analysis of fish and macroinvertebrate communities in European rivers over 32 years shows that inland ship traffic is associated with declining taxonomic richness, diversity and trait richness and with increased taxonomic evenness.

Combining a large-scale dataset of 23 ungulate species (in which newborns follow contrasting tactics of predator avoidance) with continuous-time stochastic movement models, the authors reveal that there are multiple dimensions of maternal movement behaviour and space use.

The mechanisms by which pyruvate metabolism defects lead to neurological symptoms in Leigh syndrome patients remain unclear. Here, the authors show a link between pyruvate metabolism and translation fidelity that is important for brain development.

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 effect of global warming on Antarctic temperatures is difficult to quantify, due to short weather observations and large internal variability. Here the authors use ice cores to identify polar amplification that results in warming in Antarctica larger than the internal variability.

To fully understand the potential shortcomings of SARS-CoV-2 vaccination, it is necessary to delineate the properties of the antibodies elicited, during immunization, and also infection. Through investigation of the SARS-CoV-2 spike-reactive B cell repertoire, authors identify following infection, a subset of B cells enriched and almost exclusively target a non-neutralizing S2 epitope present in aberrant forms.

SARS-CoV-2 variants with mutations in spike have emerged during the pandemic. Magaret et al. show that in Latin America, efficacy of the Ad26.COV2.S vaccine against moderate to severe–critical COVID-19 varied by sequence features, antibody escape scores, and neutralization impacting features of the SARS-CoV-2 variant.

Pancreatic cancer is not caused by a specific series of genetic alterations that occur sequentially but by one, or few, catastrophic events that result in simultaneous oncogenic genetic rearrangements, giving rise to highly aggressive tumours.

Analyses of data from more than 200,000 individuals identify phenotypic features associated to carrying variants in autism-associated genes, in individuals with and without a diagnosis of autism.

Multiplexed error-robust fluorescence in situ hybridization (MERFISH) together with deep-learning-based nucleus segmentation enabled the construction of a highly detailed and informative spatially resolved single-cell atlas of human fetal cortical development.

Kinetic modeling of in vitro enzymatic reaction networks (ERNs) is severely hampered by the lack of training data. Here, authors introduce a methodology that combines an active learning-like approach and flow chemistry to create optimized datasets for an intricate ERN.

Loss of MEN1 affects tumor growth, varing with the components of the tumor microenvironment. These tumors show redistribution of MLL1 on chromatin and the activation of a viral mimicry response.

Whether invasive species must first establish in conditions within their native climatic niche before spreading remains largely untested. This study presents the Niche Margin Index for estimating climatic niche-matching of alien mammal species to a particular site, which could be used to help predict the success of invasions.

Spin–orbit coupling is implemented in an optical lattice clock using a narrow optical transition in fermionic 87Sr atoms, thus mitigating the heating problems of previous experiments with alkali atoms and offering new prospects for future investigations.

Here, the authors perform a genome-wide study and identify a genetic variant enriched in the Finnish population that is strongly associated with isolated cleft palate. This finding suggests a genetic basis for the high prevalence of cleft palate in Finland.

Multi-modal profiling reveals major alterations in colonic B cells in patients with ulcerative colitis, including reduced clonal diversity of plasma cells, and suggests that circulating gut-homing plasmablasts could serve as a biomarker for disease activity.

Individuals with SYK gain-of-function variants develop immunodeficiency and systemic inflammation, which are recapitulated in a knock-in mouse model. Treatment of these mice with bone marrow transplantation or with a SYK inhibitor ameliorates disease symptoms, highlighting potential therapeutic strategies for patients with SYK mutations.

The blood vessel wall is a complex multi-layered structure, yet upon injury or infection, neutrophil leukocytes are rapidly migrating from the blood stream to the affected tissues, by a process termed diapedesis. Authors here show that the final steps of diapedesis through the outer pericyte layer is regulated by perivascular mast cells via IL-17A production.

Improvements in European freshwater biodiversity occurred mainly before 2010 but have since plateaued, and communities downstream of dams, urban areas and cropland were less likely to experience recovery.

A multiproxy record of Gigantopithecus blacki provides insights into the ecological context of this species, which became extinct around 250,000 years ago, when increased seasonality led to a change in forest cover.

Here, Claireaux et al. show that people who naturally control HIV infection express lower levels of the viral co-receptor CCR5 in specific CD4⁺ T cells, and that this results from mutations or receptor internalization by CD4⁺ T cell-produced chemokines.

SARS-CoV-2 infection damages the airways. Here the authors show that SARS-CoV-2 infection induces the rapid loss of airway motile cilia, resulting in altered cilia clearance function. Cilia loss is preceded by reduced expression of the ciliogenesis regulator Foxj1.

Repeat expansions in the FGF14 gene can cause late-onset cerebellar ataxia (SCA27B), however the defining features of pathogenic expansions remain uncertain. Here, the authors compare the sequence and structure of FGF14 repeat expansions in patients and controls, leading them to suggest a lower pathogenic threshold and emphasizing the importance of sequencing the full expansion for accurate interpretation.

Oxide nanolites crystallisation in natural magma increases melt, and hence bulk magma viscosity mainly due to iron extraction. This increase can be sufficient to drive magma fragmentation depending on magma degassing and ascent dynamics.

The impact of bacteriophages in the human gut microbiome remains poorly understood. Here, the authors characterize coliphages isolated from a large cohort of 1-year-old infants and show that temperate coliphages dominate, while virulent ones have greater infectivity and broader host range.

Previous studies have shown that both rare pathogenic mutations and common genetic variants contribute to the familial risk of developing colorectal cancer. Here, the authors carry out a two-stage genome-wide association study and identify six new loci associated with colorectal cancer.

Alternative stable states in forests have implications for the biosphere. Here, the authors combine forest biodiversity observations and simulations revealing that leaf types across temperate regions of the NH follow a bimodal distribution suggesting signatures of alternative forest states.

Trained on 1.5 million whole-slide images from 100,000 patients, a pathology foundation model is shown to improve performance of specialized models in detection of rare cancers.

Analysis of 100 consecutive personalized bacteriophage therapy cases supports the use of personalized and sometimes pre-adapted, bacteriophage preparations, often in combination with antibiotics.

RAS-induced senescence is a safeguarding process against tumour development. Here, the authors show that RAS activation destabilises the transcription factor ZNF768, which blocks ZNF768- dependent repression of p53 activity and thus induces senescence.

Analysing 27 years of freshwater invertebrate biomonitoring data from European rivers, the authors show that although some commonly used biodiversity metrics can reflect anthropogenic impacts at broad spatial scales, there was little consistency among other metrics in accurately reflecting community responses.

Hofstadter’s butterfly is a fractal pattern which pictorially represents the behavior of electrons under an applied magnetic field in a 2D lattice as a pair of butterfly wings. Here, the authors recreate this pattern by measuring the acoustic density of states in a fine-tuned one-dimensional acoustic array.