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Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

Metabolite extraction with organic solvents is assumed to remove/denature proteins. Here, the authors uncover a vast landscape of >1,000 proteins in metabolite extracts. These proteins can retain catalytic activity and drive post-extraction metabolite changes, obscuring biological interpretation.

Classifying groups is an important challenge in mathematics and has led to the identification of groups which do not belong to the main families. Here Duncan et al. introduce a type of moonshine which is a connection between these groups, number theory and potentially physics.

Increased atmospheric evaporative demand in recent years has increased drought severity by an average of 40% globally across both dry and wet regions, and the trend is likely to continue under future warming scenarios.

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.

DiNardo et al. perform a phase 1b/2 clinical trial of telaglenastat (CB-839) in combination with azacytidine in persons with advanced myelodysplastic syndromes and report on the treatment safety and efficacy, including a definition of clinical responders.

Activation of ESCRT prevents potentially lethal outcomes of minor perturbations in lysosomal integrity. Here authors show that Ca2 + -activated scrambling of sphingomyelin and its cytosolic turnover drives lysosomal repair independently of ESCRT.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Integrative analysis in patients with diffuse large B-cell lymphoma uncovers that biallelic mutations on TMEM30A are associated with a favorable outcome and enhanced sensitivity to CD47 blockade.

Retinoic acid is known to be effective against bone marrow metastatic neuroblastoma cells, but not primary tumors. Here, authors discover that bone morphogenetic protein signaling is responsible for determining neuroblastoma cell fate and sensitivity to retinoic acid.

Fossil lipid biomarkers previously thought to be diagnostic of sponges (and thus indicative of animal life) are found to be preserved in unicellular Rhizarian protists, questioning a pre-Cambrian origin of sponges.

Huntington’s disease (HD) is a neurodegenerative disease that shows selective regional vulnerability. Here, the authors show that postmortem brain HD astrocytes are regionally diverse, with a striatal disease-associated state and a cortical compensatory state that mitigated neural death.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

The function of de novo lipogenesis (DNL) in adipocytes has been a mystery as it contributes little to fat storage in these cells. Here, the authors show that DNL is a critical source of fatty acids for membrane-expanding processes like autophagy.

Over half the world’s rivers dry periodically, yet little is known about the biological communities in dry riverbeds. This study examines biodiversity across 84 non-perennial rivers in 19 countries using DNA metabarcoding. It finds that nutrient availability, climate and biotic interactions influence the biodiversity of these dry environments.

Delta-valerobetaine is a microbiome-derived metabolite that correlates with obesity-related phenotypes in humans, and exacerbates diet-induced obesity in mice.

Rich and colleagues identify that lymphatic endothelial-like cells in glioblastoma drive the growth of cancer stem cells via CCL21–CCR7 signaling, inducing KAT5 to acetylate HMGSC1, which enhances its protein stability and cholesterol synthesis.

Genomic analysis of neuroblastoma has revealed important disease etiology. In this study, the authors assembled whole genome, exome and transcriptome data from over 700 neuroblastomas and identified molecular signatures correlated with age, and rare, potentially targetable variants overlooked in smaller cohorts.

Triclosan is an antimicrobial additive in consumer products that has been detected in human breast milk. Here the authors report that exposure of pregnant mice to triclosan leads to lactational exposure to newborns and the development of liver steatosis.

In most cancers, mutations that lead to oncogene activation and tumor suppressor inactivation synergize to promote tumorigenesis. However, in neuroblastomas, MYCN amplification and ATRX mutations are mutually exclusive and incompatible.

Here the authors evaluate single cell gene expression from mouse and human Huntington’s disease brains, finding incomplete oligodendrocyte maturation and pathways involved. Treating mice with thiamine/biotin ameliorates molecular pathology.

Notch1 is frequently activated promoting T-cell acute lymphoblastic leukaemia (T-ALL). Here, the authors show that Notch1 induces oxidative phosphorylation dependency in T-ALL and synergism when inhibiting both mitochondrial complex I and glutaminolysis in preclinical murine and human xenograft models.

Phytoplankton are important primary producers. Here the authors investigate phytoplankton physiological changes associated with bloom phases and mixing regimes in the North Atlantic, finding that stratification and deep mixing shape accumulation rates by altering physiology and viral production.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

The understanding of altered lipid metabolism by isocitrate dehydrogenase 1 (IDH1) mutations in gliomas at a compartment-specific level is limited. Here, the authors use Raman spectroscopy to monitor organelle-specific metabolic changes and report that IDH1 mutations induce phospholipid imbalances which lead to ER and Golgi dilation.

An aged, senescent immune system has a causal role in driving systemic ageing, and the targeting of senescent immune cells with senolytic drugs has the potential to suppress morbidities associated with old age.

Super-enhancers are regions of genomic DNA comprised of multiple putative enhancers that contribute to dynamic gene expression patterns during development. Here the authors identify a modular super-enhancer in murine retinal development and show that distinct modules are responsible for retinal progenitor cell proliferation during early and bipolar neuron genesis during late retinal development.

Sustainable sources are needed to meet the demand for long-chain polyunsaturated fatty acids. Here the authors construct an artificial biosynthetic gene cluster in Y. lipolytica capable of producing a high concentration of PUFAs.

Cholesterol transport is tightly regulated in the cell and in lysosomes is regulated by NPC1/2. Here, Heybrock et al. use molecular modeling, knockout mice and cell based studies to show that LIMP-2 also mediates lysosomal cholesterol transport.