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Computational modeling and design of G Protein-Coupled Receptor quaternary structures reveals a signaling bias switch at the receptor dimer interface that selectively controls G protein vs β-arrestin activation.

Post injury cytoskeletal modifications in neurons are not fully understood. Here the authors describe a pro-survival actin cytoskeletal reorganization in neurons triggered during a model of ischemic stroke.

How carvedilol, a β1-blocker, activates β2-adrenoceptors, is unclear. Here, the authors resolve this enigma and show that carvedilol drives all of its detectable cellular β2-adrenoceptor signals by slow and low efficacy G protein activation.

The influence of biodiversity on multiple ecosystem processes is not well understood. Analysing 94 biodiversity-ecosystem functioning experiments, Lefcheck et al. find that increased species richness maintains more ecological functions, across multiple taxa, trophic levels and habitats.

Skin inflammation is often accompanied by systemic disease, yet the pathways that regulate this escalation are little known. Here authors show that transgenic expression of human CD1a in mice leads to the escalation of experimental skin inflammation and systemic inflammatory disease, and the generalized symptoms could be alleviated by blocking antibodies developed against CD1a.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Dog vaccination is an effective rabies prevention measure, but widespread vaccination campaigns are challenging in settings like India with large free-roaming dog populations. Here, the authors describe a One Health campaign in Goa state which led to a large reduction of cases in dogs and elimination in humans.

The ventral hippocampal CA3 and CA1 subfields play a critical role in the resolution of approach-avoidance conflict. Here the authors show that the subfields contribute to the regulation of this behavior through topographically distinct projections to the lateral septum.

Four researchers offer tips for excelling in interdisciplinary training.

Breast cancer is most commonly diagnosed via a needle biopsy. In this study, the authors show that cervical samples from women with breast cancer have a methylation signature different to that of healthy controls.

Most of the archaeological record of the Middle to Later Stone Age transition comes from southern Africa. Here, Shipton et al. describe the new site Panga ya Saidi on the coast of Kenya that covers the last 78,000 years and shows gradual cultural and technological change in the Late Pleistocene.

How biodiversity is linked to multiple ecosystem functions is not fully understood. Here, the authors show that a new mechanism, which they term the 'jack-of-all-trades' effect, best explains patterns of tree diversity and ecosystem multifunctionality in European forests.

Analysing data from 39 grassland biodiversity experiments, the authors uncover the direct and indirect contributions to ecosystem stability of taxonomic, phylogenetic and functional trait diversity.

Solid oxide-ion conductors are crucial components in many energy and environment technologies. Here, the authors produce La₂Mo₂O₉nanowires with high ionic conductivity which is attributed to both the stabilization of the high-temperature phase and excess conduction in the disordered surface phases.

In vertebrate embryos, Wnt/β-catenin signaling induces an organizer area guiding the formation of body axes and inducing extra axes upon transplantation. Here, Kraus et al. show that Wnt ligands also induce an organizer in a sea anemone, indicating that the organizer dates back over 600 million years.

It is feared that reprogramming may introduce DNA mutations. Here Bhutani et al. take three different reprogramming methods and using comparative whole genome analyses do identify nucleotide variations that are different in reprogrammed cells from the original fibroblasts, but none convey oncogenic potential.

The combination of anti-GD2 and CD47 blockade mediates robust anti-tumor activity in mouse models of neuroblastoma, osteosarcoma and small-cell lung cancer by reorienting macrophage activity toward tumor cell phagocytosis.

Emerging variants of SARS-CoV-2 raise concerns about vaccine efficiency. Here, the authors present a post-hoc analysis for the ChAdOx1 nCoV-19 (AZD1222) vaccine trial in Brazil and provide efficacy against symptomatic COVID-19 caused by the Zeta (P.2) and other variants.

Investigations of an Icelandic volcanic eruption confirm that sulfate aerosols caused a discernible yet transient brightening effect, as predicted, but their effect on the liquid water path was unexpectedly negligible.

This work reveals the structural and biochemical basis for phosphorylation-dependent day/night signaling by KaiC in the cyanobacterial circadian clock.

An ensemble of climate model simulations, as well as hydrological modelling and flood risk mapping, are used to show the role of anthropogenic warming on the extreme rainfall that caused the 2013/14 floods in southern England.

Associations with mycorrhizal fungi can affect the outcome of plant competition in complex ways. Here the authors use a decade-long field survey and two hyphal exclusion experiments to reveal a critical role of underground fungal networks in facilitating seedling growth and fitness of ectomycorrhizal plants but not arbuscular mycorrhizal plants.

A novel gene expression classifier of AML heterogeneity captures patient-specific variation in leukemia cell composition and predicts clinical responses to treatment.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Deep-sea diving mammals routinely undergo extreme physiological challenges not experienced by their terrestrial counterparts. Using high-resolution electrocardiographic recorders fitted to seals and dolphins, Williams et al. report an increased frequency of cardiac arrhythmias at greater exercise intensity and dive depth.

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

Glacially-derived iron fertilizes the Southern Ocean ecosystem, but the quantities transported by runoff from Antarctica are unknown. Here, the authors show significant fluxes associated with surface meltwater runoff, and demonstrate that a marked increase in export can be expected in response to climate warming.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

Nature speaks to old hands and first timers about the work they did to make their reviews sing.

Quantifying Greenland's future contribution to sea level requires accurate portrayal of its outlet glaciers in ice sheet simulations. Here, the authors show that outlet glacier flow can be captured if ice thickness is well constrained and vertical shearing as well as membrane stresses are included in the model.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

Here the authors present improved intramolecular sensors for β-arrestin2 and 1, which enable assessment of conformational changes of both isoforms in living cells. These reveal that the same GPCR induces differential conformational rearrangements that determine the functional diversity between the two β-arrestins.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Protected areas are thought essential for biodiversity conservation, but few studies confirm that protection benefits species. Here, Gray and Hill et al. analyse a global, taxonomically broad database to show that local species richness and abundance are higher inside protected areas than outside.

Nature explores how better investment in science might help India’s economic development.

Ionizing radiation may induce irreparable DNA damage leading to cancer. Here, the authors identify a specific signature of mutations arising in patients exposed to ionizing radiation and suggest that radiation-induced tumorigenesis is associated with higher rates of genome-wide deletions and balanced inversions.

The immunosuppressive role of regulatory T (Treg) cells largely depends on their virtue of expressing the transcription factor FOXP3. Here the authors show that the E3 deubiquitinase USP21 stabilizes FOXP3 by mediating its deubiquitination and helps to maintain the expression of Treg signature genes and Treg lineage stability in mice.

It remains unclear whether exotic and native species are functionally different. Using a global grassland experiment, Seabloomet al. show that native and exotic species respond differently to two globally pervasive environmental changes, addition of mineral nutrients and alteration of herbivore density.

The anion channel TMEM16A is activated by intracellular Ca²⁺ in a highly cooperative process. Here authors combine electrophysiology and autocorrelation analysis to observe the sampling of intermediate conformations during gating.

A molecular mechanism involving CCR5 and CCL5 determines the temporal window in which a memory can be linked with subsequent memories, and in aged mice an increase in CCR5 is associated with defects in memory linking.

A low-dose, single-exposure electron diffraction approach is used to reveal the dislocation character and operative slip systems in beam-sensitive molecular crystals.

Achieving effective collaboration in bioengineering is an art and a science. Here we outline strategies for building and sustaining interdisciplinary partnerships, and outline challenges, opportunities and funding options for establishing and strengthening collaborative research.