Search

Zhao et al. used single-cell and spatial multiomics data analysis of human and mouse lung adenocarcinoma tumors and cell lines to reveal TP53 mutation-associated changes in cancer cells and their microenvironment.

Increasing mitochondrial oxidative capacity and energy expenditure holds therapeutic potential for obesity and metabolic disorders. Here, the authors identify MTCH2 as a mitochondrial regulator of fatty acid oxidation via interaction with CPT1.

Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity drives proliferation of small lung cell cancer via paracrine interactions and through synapses formed with tumour cells.

This study reveals that brain aberrations after preterm birth are highly individual yet shaped by early injury and social environment, influencing long-term cognitive outcomes.

Current antimalarials often fail to target mature stage V gametocytes. To aid antimalarial drug discovery, the authors present a preclinical malaria transmission-blocking drug research platform, using engineered parasites, that facilitates the screening for gametocytocidal compounds in vitro and the evaluation of transmission-blocking drug activity in vivo.

Toxoplasma gondii RNA triphosphatase, the first enzyme in mRNA capping machinery, is essential and has a completely different structure and mechanism compared to the human RNA ortholog, making RNA triphosphatase a promising therapeutic target for toxoplasmosis.

Infection of mosquito immune cells by dengue and Zika virus enhances the spread of virus infection to mosquito tissues, such as the salivary glands, to promote virus transmission and highlights conserved roles of immune cells in virus dissemination.

Locked nucleic acids have high binding and utility but currently suffer from off target effects due to the high does needed. Here, the authors show lipid nanoparticles can safely and effectively deliver locked nucleic acids to inflamed tissue in the gut, reducing the required dose and improving therapeutic outcomes in IBD.

Here, the authors present and characterise a collection of human gut bacteria including novel taxa associated with health conditions and a large diversity of plasmids. All isolates, their genomes and metadata are publicly available, facilitating research by others (www.hibc.rwth-aachen.de).

Chou et al. demonstrate that activation of the thrombin receptor protease-activated receptor 1 in the lung lymphatic vasculature mediates morphological changes in lymphatic endothelial cell junctions to augment lung lymphatic drainage in models of lung injury.

Targeting proinflammatory/oxidative enzymes is a promising approach to treat inflammatory diseases. Here the authors present a dual-specificity inhibitor for the simultaneous targeting of Vascular Adhesion Protein-1 and Myeloperoxidase, two cooperative but functionally independent enzymes, and report potent anti-inflammatory effects of the dual inhibitor in multiple animal models of inflammatory disease.

Sleeping sickness caused by African trypanosome parasites induces a chronic, and potentially lethal, infection in humans. Here, the authors uncover a conserved protein, Q586B2, playing an important regulatory role in Trypanosomatid infection establishment.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Accumulation of advanced glycation end products such as carboxymethyllysine (CML) has been associated with aging but their molecular roles are largely unclear. Here, the authors use proteomics to identify CML sites and show that CML formation affects protein homeostasis and cell proliferation.

Lolo et al. show caveolin-1 functions in non-caveolae structures termed dolines. Whereas caveolae respond to high forces over a mechanical threshold, dolines transduce low and medium mechanical forces gradually in a complementary buffering system.

T cell exhaustion was thought to be strictly associated only with chronic infections and tumours, but it turns out that acute infections also generate a subset of precursor T cells with exhaustion-like phenotypes.

During each replication cycle of P. falciparum in the human bloodstream, a small proportion of parasites commits to sexual development and differentiates into transmission-relevant gametocytes. Applying CRISPR-based genome editing, Boltryk et al. engineer P. falciparum lines with sexual commitment rates of 75% to promote future studies on gametocyte biology.

The dramatic increase in survival of extremely premature infants has been associated with a growing population of individuals with neurodevelopmental disabilities. To date, clinical trials of neuroprotective agents in preterm infants have been limited, but new data suggest that erythropoietin might have important neuroprotective effects in these vulnerable infants.

The saw-scaled viper venom causes continued tissue damage that may cause death. Here the authors show that the venom attracts neutrophils to the bite site and induces neutrophil extracellular traps that capture venom components causing tissue damage, which can be prevented by enzymatic DNA degradation.

Single-nucleus and single-cell RNA sequencing plus spatial profiling with four methods of core biopsies from 60 patients with metastatic breast cancer reveal patient-specific gene expression programs of breast cancer metastases that are maintained across time, site of metastasis and spatial profiling method, with spatial phenotypes correlating with microenvironmental features.

Genome-wide and multitrait analyses identify novel loci associated with hypertrophic cardiomyopathy and relevant left ventricular traits. Gene-level burden analyses show that rare truncating SVIL variants are associated with high risk of hypertrophic cardiomyopathy.

High-quality multimodal single-cell, bulk and spatial genomics data are prepared from low-input, frozen needle biopsy specimens collected during routine clinical procedures.

Macrophages are pleiotropic and can have different functions and phenotypes. Here the authors show that a population of macrophages, previously described as pro-fibrotic, can be induced through Notch2 blockade and that in a mouse lung injury and fibrosis model this macrophage population does not promote inflammation or fibrosis.

Inspired by biology, great progress has been made in creating artificial molecular motors. Here the authors report the synthesis and characterization of the Lawnmower, an autonomous, protein-based artificial molecular motor and show their design is capable of track-guided motion.

Correct loading of the MCM2-7 helicase is crucial for DNA replication and cell cycle progression. Here, the authors used high-resolution genomics to demonstrate how ORC is displaced from origins, which serves as a mechanism for distributive MCM loading onto DNA.

Transition paths by which embryonic stem cells commit to different lineages are not well understood. Here, the authors use combined lineage plus 37-dimensional protein information to identify a developmental cell population co-expressing Sox1 and FoxA2.

Genetic exchange of Leishmania parasites in the sand fly host is mediated by natural IgM antibodies, providing insights that will help generate reproducible and increased recovery of backcrosses for research purposes.

Lifestyle interventions are promising tools for achieving healthy aging. Here, authors show how environmental enrichment can reverse multi-omic alterations associated with the aging process in the murine dorsal hippocampus.

Molecular mechanisms of macrophage-mediated regulation of artery growth in response to ischemia are poorly understood. Here the authors show that vascular endothelium controls macrophage maturation and differentiation via Notch signaling, which in turn promotes arteriogenesis and ischemic tissue recovery.

We know that nutrition and obesity can impact male fertility, but specific dietary guidelines for men trying to conceive don’t exist. Here the authors show that diet composition is likely more important than body fat in influencing reproductive traits and each macronutrient has different impacts.

Human iPSC-CMs are invaluable for cardiac disease modeling and regeneration. Here, authors developed an optimized suspension culture protocol to efficiently and reproducibly differentiate hiPSCs into cardiomyocytes and cardiac organoids.

Antibody production is the main effector function of B cells. Rawlings and colleagues show that Trypanosome cruzi induces rapid IL-17 production by B cells that is required for parasite control.

The search for antivirals against SARS-CoV-2 continue due to the emergence of variants of concerns, able to escape the vaccinal humoral response. In this work, authors pre-clinically explore the potential of kinetin against SARS-CoV-2, which could be used alone or in combination with other antivirals.

Natural killer T (NKT) cells include type I that express semi-invariant T cell receptor (TCR), and type II that cover a broader repertoire. Here the authors describe the crystal structure of a type II NKT TCR complexed with CD1d/antigen to propose that type II NKT TCRs may adapt multiple CD1d docking modes to maximise antigen recognition efficacy.

Protection against SARS-CoV-2 infection involves T cell and B cell responses but only studying one or the other has proved difficult. Here the authors immunise with a fusion protein construct of N and RBD proteins from SARS-CoV-2 and find that this promotes protection in animal models preferentially via T cells.

Single-cell RNA-sequencing technology gives access to cell cycle dynamics without externally perturbing the cell. Here the authors present DeepCycle,a robust deep learning method to infer the cell cycle state in single cells from scRNA-seq data.

Rolandelli et al. define how immune cells from the tick Ixodes scapularis are affected by infection and show that this cell population have distinct signatures and functions in immunity, metabolism and proliferation.

Natural Killer cells regulate foetal growth. Here the authors use a humanized transgenic mouse to demonstrate that specific HLA-C KIR2DL interactions promote changes in maternal and foetal cell transcriptomes, resulting in modifications to placental vasculature, intercellular communications and foetal growth restriction.