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Narcolepsy has genetic and environmental risk factors, but the specific genetic risk loci and interaction with environmental triggers are not well understood. Here, the authors identify genetic loci for narcolepsy, suggesting infection as a trigger and dendritic and helper T cell involvement.

Increasing the number of chromosome sets alters the physiology of cells. Here, the authors show that although the number of chromosome sets increases, the proteome does not scale linearly with the increasing ploidy.

25-Hydroxycholesterol induces expression of the microRNAs miR-130b and miR-185 in HCV-infected cells, and these inhibit viral fatty acid desaturation, lipid uptake and biosynthesis, thereby limiting infection. HCV counteracts this immunometabolic response by downregulating these microRNAs.

During malignant transformation, the ability of mammary epithelial cells to cope with oncogene-induced DNA damage and avoid chromosomal instability is determined by stemness-related expression of the canonical epithelial-to-mesenchymal transition transcription factor ZEB1 and its target MSRB3, a methionine sulfoxide reductase involved in antioxidant defense.

The authors show pro-inflammatory responses are needed for Marburg virus control in its natural bat reservoir, and that if reduced, humanlike disease and shedding results, suggesting that natural immunomodulatory stressors may increase spillover risk.

Global profiling of hyper-reactive tryptophan sites across whole proteomes using tryptophan chemical ligation by cyclization (Trp-CLiC) reveals a systematic map of tryptophan residues that participate in cation–π interactions, including functional sites that can regulate protein-mediated phase-separation processes.

A cascadable all-optical NOT gate is a requirement for full-logic in optical computing. By introducing the concept of non-ground-state polariton amplification in organic semiconductor microcavities, the authors realized the operation of an all-optical cascadable universal gate.

Using two complementary approaches to induce hypercholesterolemia in mice, Di Nunzio, Hellberg, Zhang, Ahmed et al. identified liver macrophages as key cells that organize the systemic responses to lipoproteins during the initial phases of atherosclerosis pathogenesis.

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Linda Holmfeldt, Lei Wei et al. report whole-genome and exome sequencing of 40 childhood hypodiploid acute lymphoblastic leukemias.

The molecular control of germinal center selection is still being determined. Dalla-Favera and colleagues show that the cell-cycle regulator c-Myc is essential for B cell selection and reentry into the germinal center.

Here, the relationship between unfolding and amyloid aggregation of glaucoma-associated myocilin is probed, showing that myocilin is not at equilibrium and pathogenic aggregation competes directly with unfolding.

Deep proteome sequencing achieves ~80% coverage of the human proteome.

Treatments to rescue vision are currently limited. Here, the authors identify a cone-driven gain control mechanism that reduces visual function beyond the atrophic area in humans. They also show that activating laterally projecting cells results improved vision in two mouse models of retinal degeneration.

Z-DNA anchors the AIRE-mediated transcriptional program by enhancing the generation of double-stranded breaks and promoter poising.

Supramolecular networks from telechelic polymers hold promise for advanced material design, yet tracking molecular scission-reaggregation kinetics in bulk materials remains challenging. Here, the authors use solid-state ¹H NMR spectroscopy to directly measure the aggregation-scission dynamics in poly(ε-caprolactone) modified with oligopeptide end groups that form one-dimensional hydrogen-bonded aggregates.

The involvement of cAMP-dependent regulation of HCN4 in the chronotropic heart rate response is a matter of debate. Here the authors use a knockin mouse model expressing cAMP-insensitive HCN4 channels to discover an inhibitory nonfiring cell pool in the sinoatrial node and a tonic and mutual interaction between firing and nonfiring pacemaker cells that is controlled by cAMP-dependent regulation of HCN4, with implications in chronotropic heart rate responses.

A high-salt diet in mice induces cognitive impairment through a signalling cascade that culminates in increased phosphorylation of tau.

In a preclinical study, the delivery of an AAV-based gene therapy encoding GDNF in the brain prevented the return to alcohol use behaviors in a non-human primate model.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

Although varicose veins are a common condition, the genetic basis is not well understood. Here, the authors find genetic variants associated with varicose veins and show that a higher polygenic risk score for varicose veins correlates with a greater likelihood of patients undergoing surgical treatment.

Subpopulations of cytokine-producing and myofibroblastic hepatic stellate cells, identified by single-cell RNA sequencing, protect against or promote the development of hepatocellular carcinoma via high expression of hepatocyte growth factor or type I collagen, respectively..

Adipocyte-expressed long non-coding RNAs (lncRNAs) have been shown to regulate the transcription of genes involved in lipid metabolism. Here the authors describe a human adipocyte-specific lncRNA, ADIPINT, which regulates lipid metabolism in white adipocytes in part through its interaction with the metabolic enzyme pyruvate carboxylase.

Endocannabinoids are bioactive lipid molecules produced in the body. Here, Geurts et al. create mice lacking the endocannabinoid-producing enzyme NAPE-PLD in adipocytes and report defects in adipose-induced browning, which are mediated by alterations in the gut microbiome.

It is well known that the pH of tumor tissue is lower than that of the corresponding normal adjacent tissue. Here, the authors report a clinical trial of a pH activatable nanoparticle for imaging tumours.

Analysis of signatures of hypoxia in more than 8,000 tumors from 19 cancer types identifies hypoxia-driven mutation signatures and dysregulation of microRNAs.

Despite the known role of telomere length in cancer, its association with genomic features remains unclear. Here, the authors integrate telomere length, genomics, transcriptomics and proteomics in localized prostate cancer and reveal links between telomere maintenance, disease drivers and clinical outcomes.

A first-in-man study of robotic-assisted intraocular surgery shows the feasibility and safety of the robotic device for the peeling of retinal membranes and for the injection of a therapeutic under the retina.

Nucleosome profiling from cell-free DNA (cfDNA) represents a potential approach for cancer detection and classification. Here, the authors develop Griffin, a computational framework for tumour subtype classification based on cfDNA nucleosome profiling that can work with ultra-low pass sequencing data.

High-grade gliomas functionally remodel neural circuits in the human brain, promoting tumour progression and impairing cognition.

Random mutagenesis can uncover novel genes involved in phenotypic traits. Here the authors perform a large-scale phenotypic screen on over 100 mouse strains generated by ENU mutagenesis to identify mice with age-related diseases, which they attribute to specific mutations revealed by whole-genome sequencing.

Magneto-fluorescent nanoparticles hold promise for bioimaging applications, but synthesizing uniform particles with tunable sizes remains challenging. Chen et al. propose an approach for co-assembling magnetic particles with fluorescent quantum dots, leading to well-defined core-shell structures.

Excessive glucose production by the liver contributes to poor blood glucose control in type 2 diabetes. Here the authors report that the liver kinase B1 (Lkb1) suppresses amino acid driven postprandial glucose production in the liver through the aminotransferase Agxt.

The development of anode-free batteries requires current collectors able to deposit and remove Li metal upon cycling efficiently. Here, the authors report the use of high dielectric porous BaTiO₃ to avoid the formation of inhomogeneous Li metal depositions during anode-free cell cycling.

Ludwig et al. map transcription and chromatin accessibility in single cells across the brainstem dorsal vagal complex, thereby identifying neuronal populations, including some that control feeding.

Enzymes in the cytidine diphosphate–ethanolamine metabolic pathway, which promotes de novo synthesis of phosphatidylethanolamine, are shown to act as post-transcriptional mediators of the differentiation of T follicular helper (T_FH) cells, by regulating the chemokine receptor CXCR5.

Boyer et al. created genetic mouse models of muscular dystrophy in which satellite cells were selectively depleted. The depletion of satellite cells at select times was protective. Myofibers no longer had plasma membrane instability leading to tissue wasting in the muscular dystrophies.

Drake and colleagues demonstrate that castration in prostate cancer models promotes IL-8 secretion and immunosuppressive myeloid-derived suppressor cell migration, and that inhibiting this axis in combination with checkpoint blockade can mitigate tumor progression.

The fusion of muscle progenitor cells to form syncytial myofibers is required for skeletal muscle development and regeneration. Here, the authors describe a novel and specific molecular regulation of muscle cell fusion driven by transforming growth factor beta (TGFβ) signaling.

IFNγ secretion by CD8⁺T cells is critical for immunotherapy efficacy. In this study, the authors show that melanoma patients can become resistant to immunotherapy by acquiring chromosomal alterations and subsequent inactivating mutations in genes of the IFNγ signalling cascade, most often JAK1 or JAK2.

Net gain of ~10 dB µm^–1 and sub-picosecond switching time are shown at room temperature for optical transistors using polymers in a microcavity.

Grant Stewart, Andrew Jackson, Christopher Mathew, Fowzan Alkuraya and colleagues identify a novel replication fork protein, DONSON, which is important for maintaining genome stability. Mutations in DONSON cause microcephalic dwarfism and lead to stalled replication forks and DNA damage.

The study of the pathophysiology and possible interventions for non-ST-segment elevation myocardial infarction is hindered by the lack of a reproducible pre-clinical model. Here, authors develop an ovine model to reproduce post-ischemic remodeling in non-ST myocardial infarction and reveal distinct complex sugar moieties in cellular membranes and extracellular matrix patterns in infarcted tissue.

Aß are extracellular deposits relevant in Alzheimer’s disease (AD). This study shows that Aß plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided by the microglia and unchained by reduced presenilin function, a trait of AD, in endothelial cells.

Analysis of genomic networks from 430 modern individuals across 21 Pacific island populations reveals the human settlement history of Polynesia.

To characterize molecular changes during cell type transitions, the authors develop a method to simultaneously measure protein expression and thermal stability changes. They apply this approach to study differences between human pluripotent stem cells, their progenies, parental and allogeneic cells.