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In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

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.

Many genetic loci have been identified to be associated with kidney disease, but the molecular mechanisms are not well understood. Here, the authors perform epigenome-wide association studies on kidney function measures to identify epigenetic marks and pathways involved in kidney function.

Serum urate concentration can be studied in large datasets to find genetic and epigenetic loci that may be related to cardiometabolic traits. Here the authors identify and replicate 100 urate-associated CpGs, which provide insights into urate GWAS loci and shared CpGs of urate and cardiometabolic traits.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

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.

Non-planar nanographenes are materials with promising prospects for chiroptical and optoelectronic applications. Now bilayer molecular nanographenes composed of two hexa-peri-haxabenzocoronene units linked by a spirocycle have been synthesized. Modulation of the electronic properties of one of the benzocoronene units enables an electron-transfer process between the donor and acceptor moieties, leading to the formation of zwitterionic open-shell bilayer spironanographenes.

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).

Hypomethylating agents, such as 5-Azacytidine (5-AZA), are standard of care for patients with myelodysplastic and myeloid malignancies, however response rates are limited and risk of relapses high. Here the authors show that inhibition of lysyl oxidases synergizes with 5-AZA to improve erythropoiesis and reduce disease burden in myelodysplastic neoplasms models.

Bone marrow-derived mesenchymal stroma cells (MSCs) in myeloid neoplasia have been hypothesized to carry somatic mutations and contribute to pathogenesis. Here the authors analyse ex-vivo cultures and primary MSCs derived from patients with myelodysplastic syndromes, finding functional alterations but no evidence of clonal mutations.

Germline biallelic pathogenic MUTYH variants predispose patients to colorectal cancer (CRC); however, approaches to identify MUTYH variant carriers are lacking. Here, the authors evaluated mutational signatures that could distinguish MUTYH carriers in large CRC cohorts, and found MUTYH-associated somatic mutations.

The authors report PROTAC ternary complex structures involving the E3 ligase cIAP1 and target protein BTK, showing that cooperativity is not always correlated with degradation efficiency.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region.

Andreev bound states in semiconductor–superconductor hybrid structures are studied using microwave spectroscopy — a tool that could be also used for investigating Majorana modes.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

The spectroscopic and photometric observations of a high-mass, transiting warm Jupiter, TIC 241249530 b, with an orbital eccentricity of 0.94, provide evidence that hot Jupiters may have formed by means of a high-eccentricity tidal-migration pathway.

This study uses Strand-seq to explore the landscape of mosaic structural variants (mSVs) in human hematopoietic stem and progenitor cells from people of different ages. The analysis highlights patterns of enrichment for mSVs in specific cell types, with associated phenotypes, and suggests that clonal expansions due to mSVs are generally restricted to older individuals.

The suppression of edge-localized modes in tokamak plasmas is crucial to prevent them from damaging the walls of the chamber. Now experiments confirm the role that magnetic islands play in suppressing these detrimental modes.

Highly active antiretroviral therapy is crucial to controlling the progression of HIV infection. Therapy failure is often—but not always—attributed to resistance mutations in the HIV-1–encoded protein targets. Here Rosenbloom et al. use mathematical modeling to explain the distinct patterns of resistance found with different classes of antiretroviral drugs and predict specific single-pill combination therapies that might prevent resistance even in the setting of poor patient adherence.

Seropositive samples of SARS-CoV-2 were detected as early as mid-February in patients at Mount Sinai Hospital in New York City, and antibody positivity increased during the first wave of the pandemic and remained stable afterwards.

Leukaemic stem cells drive acute myeloid leukaemia (AML) progression and relapse but they are incompletely characterized. Here, the authors combine single-cell transcriptomics and clonal tracking using nuclear and mitochondrial somatic variants to distinguish healthy, pre-leukaemic and leukaemic stem cells in AML.

Linking structural variants to gene expression information identifies aberrant signaling pathways.

Several parameters in the bone marrow (BM) niche regulate leukaemic stem cell status and disease progression. Here, the authors show that calcium-sensing receptor affects the ___location of acute myeloid leukaemia (AML) cells in the BM niche which influences self-renewal of leukaemic stem cells and AML development

Many island plant species share a syndrome of characteristic phenotype and life history. Cerca et al. find the genomic basis of the plant island syndrome in one of Darwin’s giant daisies, while separating ancestral genomes in a chromosome-resolved polyploid assembly.

Genome wide association studies in cancer are used to understand the heritable genetic contribution to disease risk. Here, the authors perform a genome wide association study in European patients with acute myeloid leukemia and identify loci associated with risk of developing the disease.

A diverse array of antigens can trigger allergic reactions. Here the authors present the ‘AllerScan’ programmable phage display library, which is an efficient and unbiased approach for profiling anti-allergen antibody reactivities at cohort scale, with which a key wheat epitope is found to distinguish between wheat allergy and tolerance.

Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.

The heart is formed from several spatiotemporally distinct progenitor pools during development. Here they show that modulation of retinoic acid signaling can instruct human pluripotent stems cells into heart progenitors that are useful for studying human development and disease.

Chlorine radicals function as a strong atmospheric oxidant, particularly in polar regions, where levels of hydroxyl radicals are low. Measurements in the Arctic reveal high levels of molecular chlorine during the day, consistent with a photochemical source.

Analysis of growth dynamics in a dataset from 107 patients with chronic lymphocytic leukaemia (CLL) reveals both exponential and logistic patterns of growth, which are associated with differences in genetic attributes and clinical outcomes.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

In this study, the authors show that MeCP2 interacts with the NCoR/SMRT co-repressor complex and that a discrete cluster of Rett syndrome–causing mutations in the C-terminal ___domain of MeCP2 disrupts this interaction, impairing transcriptional repression. Knock-in mice expressing one of these MeCP2 missense mutations exhibit severe motor phenotypes.

Niche crosstalk with Haematopoietic cells underlies normal haematopoiesis and myeloid disorders. Here the authors report a Stabilin2-Cre driver mouse with Cre-activity restricted to bone marrow sinusoidal endothelial cells, and that Stabilin2-Cre driven overactivation of b-catenin leads to erythroid differentiation defects and anaemia.