Search

Taylor et al. show that tumor cells promote white adipose tissue (WAT) wasting and cachexia by overactivation of Notch1 signaling and retinoic acid production in distant WAT endothelium, which can be therapeutically targeted to inhibit wasting.

How we juggle morally conflicting outcomes during learning remains unknown. Here, by comparing variants of reinforcement learning models, the authors show that participants differ substantially in their preference, with some choosing actions that benefit themselves while others choose actions that prevent harm.

Lateral roots grow at specific angles with respect to gravity. Two auxin transporters, PIN3 and PIN7, in gravi-sensing cells establish hormone gradients that balance downward and upward growth to generate stable, non-vertical roots.

SKP2 is an oncogenic E3-ubiquitin ligase. Here the authors show that SKP2 is epigenetically regulated by the muscle lineage transcription factor MYOD, supports tumorigenesis in the Fusion Negative (FN) subtype of rhabdomyosarcoma (RMS) and impairs differentiation promoting degradation of p57^Kip2.

Dietary serine and glycine starvation has emerged as a potential therapy for cancer. Here, the authors show that inhibition of PHGDH, which mediates the first step in the serine synthesis pathway, improves the therapeutic efficacy of serine depletion diet in mouse xenograft models.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

Microbes in ancient groundwaters can be very diverse and productive. Some microbes seem to produce oxygen in the dark, which others use to consume the greenhouse gas methane. Their metabolisms are relevant for groundwater health and global change.

In this study, the authors show that host microbiota play a key role in modulating microglia homeostasis. Germ-free mice or mice with only limited microbiota complexity displayed defects in microglial cell proportions and maturation, leading to impaired innate immune responses. The authors find that short-chain fatty acid signaling regulates these effects in vivo.

Non-alcoholic steatohepatitis (NASH) is characterized by lipid accumulation within hepatocytes and fibrosis. Seitz et al. show that the GTPase protein Rab24 is increased in the livers of people who are obese or have NASH.

Sensing DNA bases by surface-enhanced Raman spectroscopy (SERS) in plasmonic nanopores has suffered from rapid flow through of molecules. Here, the authors attach DNA molecules to gold nanoparticles which, due to electro-plasmonic trapping, allow for controlled residence times and discrimination of single nucleotides.

Blockade of lymphotoxin β-receptor (LTβR) signalling restores WNT signalling and epithelial repair in a model of chronic obstructive pulmonary disease.

Damian Smedley and colleagues report the phenotypic characterization of the first 3,328 genes by the International Mouse Phenotyping Consortium. They develop new mouse models based on genes known to be associated with human mendelian diseases and identify potential disease-associated genes with little or no previous functional annotation.

Hyperammonemia occurs in liver diseases affecting ureagenesis, and is life-threatening. Here, the authors show that liver UDP-GlcNAc is increased during hyperammonemia, leading to O-GlcNAcylation of the rate-limiting ureagenesis enzyme CPS1, that enhanced ureagenesis and ammonia detoxification. They also showed that pharmacological increase of protein O-GlcNAcylation reduces hyperammonemia in mouse models of liver disease.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

The origin of blue ejecta around the fresh craters of dwarf planet Ceres is unknown. Here, the authors show that the blue color results from high porosity of the surface, induced by sublimation of ice-phyllosilicate mixture produced by impacts.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Insulin enhances mRNA translation via the translation initiation factor eIF6. Here, Brina et al. show that insulin-mediated activation of eIF6 is associated with the selective translation of genes involved in glycolysis and lipid synthesis with characteristic G/C-rich and uORF sequences in their mRNA.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

Greg Barsh and colleagues show that two loci for dark skin in mice result from mutations in Rps19 and Rps20, encoding the ribosomal proteins S19 and S20. They further show that the dark skin phenotype and other pleiotropic effects of these mutations, including reduced erythrocyte count and body size, are mediated through stabilization of p53.

Up-scaling represents a key challenge for photovoltaics based on metal halide perovskites. Using a composite of 2D and 3D perovskites in combination with a printable carbon black/graphite counter electrode; Granciniet al., report 11.2% efficient modules stable over 10,000 hours.

The regulatory role of calcitonin in bone homeostasis is well studied, yet its molecular activity is poorly understood. The authors show that calcitonin regulates bone cells function by inhibiting the osteoclast secretion of sphingosine 1-phosphate, a lipid mediator of osteoclast–osteoblast crosstalk.

HIV infection may affect the immune response to vaccination. Here the authors show that humoral response in persons living with HIV after the third dose of a SARS-CoV-2 vaccine is strong and higher than that achieved with the second dose, while cell-mediated immunity remains stable.

Nuclei with equal neutron (N) and proton (Z) numbers show enhanced correlations that have been predicted to favour an unusual type of pairing, distinct from normal nuclear superfluidity. Here, technically challenging observations are reported of excited states in the N = Z = 46 nucleus ⁹²Pd, from which evidence is inferred for a type of spin-aligned structure in the ground and low-lying excited states, not established in nuclei before and differing from previous predictions.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Identification and characterization, using a comprehensive embryonic phenotyping pipeline, of 410 lethal alleles during the generation of the first 1,751 of 5,000 unique gene knockouts produced by the International Mouse Phenotyping Consortium.

Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

Heart failure is a major public health issue but due to our poor disease understanding the current therapies are symptomatic. Here the authors identify Myoscape as a novel cardiac protein regulating membrane localization of the L-type calcium channel and heart's contractile force, thus promising new therapeutic avenues for heart failure.

During volcanic eruptions, solidifying magma ascends through the volcanic conduit, often accompanied by repetitive, drum-beat seismicity. Laboratory experiments on magma samples from Soufrière Hills Volcano, Montserrat, and Mount St Helens Volcano, USA, show that viscous melt formed at the surface between the rising magma and conduit walls can temporarily halt magma ascent, accentuating the cyclical seismicity.

Data from the Southern Ocean sea-ice extent, the biological productivity of the ocean, and atmospheric iron flux over the past eight glacial cycles indicate that during glacial terminations, changes in Patagonia apparently preceded Antarctic sea-ice reduction — showing that multiple mechanisms may be responsible for different phases of CO₂ increase during glacial terminations.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

Future tokamak nuclear fusion reactors depend on efficient current drive methods, but it is hard to penetrate the high-density plasma in these devices. In this paper the authors show that radio frequency waves coupled to lower hybrid plasma waves, when the peripheral temperature of the plasma is high, can penetrate the plasma core.