Search

SPI1 fusion genes in T-cell acute lymphoblastic leukemia (T-ALL) are commonly found with co-occurring NRAS mutations. Here, the authors show that the combination of these oncogenes is necessary to drive T-ALL in a murine model and that the oncogenic activity of the SPI1 fusion is dependent on β-catenin.

Recent advances have increased the dimensionality and complexity of immunological data. The authors developed a machine learning approach to incorporate prior immunological knowledge and applied it on clinical examples and a simulation study. The approach may be useful for high-dimensional datasets in clinical settings where the cohort size is limited.

A mouse model of Down syndrome (DS) highlights the importance of triplication of the IFNR gene cluster for a variety of DS-associated traits. Copy number correction resulted in amelioration of multiple phenotypes associated with the condition.

Here, 3D nanofabrication and elasticity programming of monolithic soft microrobots equipped with magnetic springs with strain response at piconewton forces capable of deformation on micrometre length scales is demonstrated for applications in cell force sensing, cell manipulation and soft actuation.

The nervous system utilizes adaptive strategies to mitigate trauma-induced neurodegeneration. Here, the authors report that a MAPK phosphatase VHP-1 is induced by trauma and regulates transcriptional responses to mechanical stress in a C. elegans model.

The mechanisms underlying the influence of aging on cancer are incompletely understood. Warde et al. establish a new model of age- and sex-dependent adrenal cancer. Their work uncovers a tumor-protective role for myeloid immune cells that is enhanced by androgens.

Peinado and colleagues show that small extracellular vesicles and secreted NGFR cargo induce lymphangiogenesis and develop the lymph node pre-metastatic niche to promote melanoma metastasis, which could be targeted pre-clinically with NGFR inhibition.

Singlet fission is an important process occurring in solar cells, however the mechanism is not well understood. Here the authors reveal intermediates during singlet fission of a non-conjugated pentacene dimer, developing a single kinetic model to describe the data over seven temporal orders of magnitude at room and cryogenic temperatures.

Slow-cycling melanoma persister cells are characterised by a high, reversible expression of H3K4 demethylase KDM5B. Here, the authors use genetic and chemical methods to enforce a permanent high expression of KDM5B and show that these cells transit to a melanocytic differentiated state and undergo cell cycle arrest.

Ramabadran et al. identify a DNA methylation-independent role for DNMT3A in stem cell activation, mediated through recruitment of SF3B1 and splicing regulation.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

PBRM1, encoding for a subunit of the SWI/SNF complex, is the second most frequently mutated gene in clear cell renal cell carcinoma (ccRCC). Here, the authors show that PBRM1 loss reduces IFNγ-mediated signalling resulting in a less immunogenic tumor microenvironment and that PBRM1 mutations correlate with lack of response to checkpoint inhibitor therapy in ccRCC patients..

Interdigitation between polymer brushes decorated on two sliding surfaces induces low friction, which needs to be minimized for bio-lubricant applications. Here the authors show that this friction can be substantially reduced in the systems where immiscible polymer brushes are in contact.

This Evidence-Based Guideline presents the first Pan American League of Associations for Rheumatology recommendations for the management of axial spondyloarthritis, addressing therapeutic targets, the use of pharmacological and non-pharmacological interventions and monitoring of patients.

In this Review, Minkoff and tenOever examine the relationship between SARS-CoV-2 biology and innate immunity, and they explore how antagonism and dysregulation of host innate immune defences contribute to COVID-19 disease severity.

Modulation of the unfolded protein response by targeting IRE1 has several potential therapeutic applications. Here, the authors provide a first structural view of inhibitors engaging the RNase-active site of IRE1 that suggests avenues towards the generation of analogues with increased potency and selectivity.

The rational design of out-of-equilibrium demixing transitions remains challenging. Active fluids are used to control the liquid–liquid phase separation of passive DNA nanostars and establish the activity-based control of the phase diagram.

Aberrant crosstalk between cancer stem cells and their microenvironment triggers angiogenesis and TGFβ signalling, creating conditions that are conducive for hijacking leptin and leptin receptor signalling, which in turn launches downstream PI3K–AKT–mTOR signalling during the benign-to-malignant transition.

Specificity in signaling activated by receptor tyrosine kinases is typically attributed to characteristics of their intracellular domains. Here, the authors demonstrate that an extracellular receptor sequence motif controls intracellular signaling as a result of extracellular glycan interactions.

Genomic and transcriptomic analyses of chronic lymphoproliferative disorder of natural killer cells identifies somatic gain-of-function mutations in the chemokine gene CCL22 with cell-extrinsic effects. Mutations caused biased signaling downstream of the G-protein-coupled receptor for CCL22 and deregulated interactions with the hematopoietic microenvironment.

Targeting the glycolytic PFKFB3 enzyme is being studied as a therapeutic strategy against cancer. Here the authors identify PFKFB3 as being involved in homologous recombination (HR) repair of DNA double strand breaks (DSBs) and present a PFKFB3 inhibitor.

SARS-CoV-2 is shown to infect and replicate in human pancreatic tissue, including in β-cells, which is associated with morphological, transcriptomic and functional changes.

The phosphatase Shp-2 was implicated in NK cell education due to its reported association with inhibitory receptors, but its function in this context is unclear. Here the authors show that Shp-2 is not required for NK cell function, but is necessary for IL-15-induced metabolic burst and expansion.

In this Review on cardiodermatology, Gelfand and colleagues discuss specific skin findings associated with cardiovascular diseases, important cutaneous adverse effects of common cardiovascular therapies, and the effects of dermatological diseases and dermatological treatment on cardiovascular risk.

Two conceptual strategies for encoding information into self-assembling building blocks highlight opportunities and challenges in the realization of programmable colloidal nanostructures.

Idiopathic pulmonary fibrosis is a disease caused by persistent micro-injuries to the lung ultimately resulting in death. Here, the authors describe the use of a small molecule OGG1 inhibitor, TH5487, as a potent and potentially clinically relevant treatment for IPF.

A ‘bottom-up’ approach for calculating the rate of organic carbon burial in the global ocean shows larger variability than has been previously estimated, suggesting that the organic carbon cycle acted as positive feedback of past global warming.

B cells are playing an active role in shaping the tumour immune microenvironment and the anti-tumour immune response in melanomas. Here authors show that intra-tumoral B cells are aberrantly activated and produce antibodies that are potentially autoreactive.

Auxin rapidly modulates root growth through simultaneous activation of two opposing mechanisms—TMK1-mediated apoplast acidification and TIR1/AFB-mediated apoplast alkalinization.

End-stage kidney disease confers a high risk for severe COVID-19 infection. Using an at-risk group (end-stage kidney disease patients with COVID-19), authors using RNA-sequencing of immune cells and plasma proteomic profiling to investigate the host response to viral infection.

A robust signature of circulating inflammatory proteins is causally associated with 10-year risk of progression to end-stage renal disease in diabetic patients

The Ebola virus glycoprotein is a target for cross-protective antibodies. Here, Janus et al. report the crystal structure of the antigen-binding fragment of a pan-reactive antibody bound to a conserved epitope of the glycoprotein, facilitating rational design of cross-protective vaccines and therapeutics.

Protein phosphorylation and dephosphorylation are essential aspects of biology. Wang et al., report that Toxoplasma gondiiprotein phosphatase 2A (PP2A) mediated dephosphorylation is critical for starch metabolism and bradyzoite differentiation.

Ting and colleagues use multi-omics to examine the alterations undergone by CD4⁺ T cells following HIV-1 infection. They describe mechanistic changes that lead to elevated oxidative phosphorylation, which, if inhibited, leads to suppression of HIV-1 infection.

At low concentration, uncharged amphiphilic block copolymers form discrete micelles. Here the authors show that triblock copolyelectrolytes can form phase separated gels at low concentrations, which can be useful in applications, such as, tissue engineering and water purification.

High-pressure experiments play a critical role in understanding planetary interiors, but are notoriously difficult to carry out. Here, the authors demonstrate a laboratory platform for the controlled exploration of deuterium, with results that challenge existing models of ionization under compression.