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Cellular niches are highly heterogenous in triple negative breast cancer. Here, the authors utilise imaging mass cytometry and spatial transcriptomics to characterise the microenvironment in Black American and White American patients.

Selection drives divergence between species, contributing to speciation, while simultaneously favoring extensive diversity that is maintained across populations within a species. This study demonstrates how the selection landscape is complex and multidimensional across three species of Phlox flowers.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.

ATLAS is a tool for circuit tracing, demonstrated here in rodents. It allows anterograde transsynaptic tracing, starting from genetically defined neurons.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

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.

Majority of biologic drugs and vaccines require temperature-controlled conditions throughout the supply chain to minimize thermal inactivation and contamination, which is costly and impractical. Here, the authors report chemical dispersants that non-covalently solvate proteins within fluorous liquids, resulting in non-aqueous, fluorine-based liquid protein formulations that biochemically rigidify protein structure to yield thermally stable biologics that are also resistant to degradation.

During visual learning, neural plasticity is driven by unsupervised learning in mice.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Chen et al. show that in mice, extracellular matrix remodeling drives early migration of the anterior signaling center, establishing the body axis sooner than expected—a mechanism potentially conserved in humans.

Aggarwal et al. report a secondary analysis of the EMPACT-MI trial, which evaluates the effects of empagliflozin according to baseline kidney function in patients after myocardial infarction, showing that empagliflozin offers kidney protection, reduces heart failure events and was safe to initiate in patients with acute myocardial infarction, irrespective of baseline kidney function.

Extratropical feedbacks between climate and aerosols from landscape fire and biogenic secondary organic aerosols are significant, according to a global aerosol model that is constrained by observations.

‘The timing and ecological dynamics of extinction in the late Pleistocene are not well understood. Here, the authors use sediment ancient DNA from permafrost cores to reconstruct the paleoecology of the central Yukon, finding a substantial turnover in ecosystem composition between 13,500-10,000 years BP and persistence of some species past their supposed extinctions.’

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

It is unclear whether species’ responses to climate change tend to be adaptive or sufficient to keep up with climate change. Here, Radchuk et al. perform a meta-analysis showing that in birds phenology has advanced adaptively in some species, though not all the way to the new optima.

Massive tabular icebergs broke off of the UK during the last ice age. The widespread break-up of the ice shelves which produced these giant icebergs can be traced to around 18,000 years ago, and likely enhanced rates of ice retreat across the North Sea.

Kim et al. demonstrate neutrophil- and macrophage-enriched subtypes in triple-negative breast cancer and how these immune profiles affect therapeutic responses to immune checkpoint blockade.

FLVCR2 is expressed in the blood–brain barrier of mouse and human, and is the major mediator of choline uptake into the brain.

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.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Markov, Ren, Senkow and colleagues report that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterized patients who recovered, whereas responses against nonstructural proteins and activation of NF-κB were associated with poor outcomes.

The energetic costs of seasonal bird migration are challenging to measure. Here bio-loggers paired with radio telemetry and energetic modelling show that blackbirds offset the energetic cost of migration by decreasing heart rate and body temperature 28 days before departure but do not decrease total daily energy expenditure in warmer wintering areas.

Divergent transcription from promoters and enhancers occurs in many species, but it is unclear if it is a general feature of all eukaryotic cis regulatory elements. Here the authors define cis regulatory elements in worms, flies, and human; and identify several differences in regulatory architecture among metazoans.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Trachoma is targeted for global elimination as a public health problem by 2030. Here, the authors combine data from 14 African populations to show that IgG in children is a robust approach to monitor transmission as populations approach elimination.