Search

The taurine–taurine transporter axis is a critical dependency of aggressive myeloid leukaemias.

In mice, prolonged consumption of a high-fat diet decreases interest in calorie-rich foods as a result of reduced neurotensin expression and signalling, which uncouples hedonic feeding behaviour linked to neurons projecting from lateral nucleus accumbens to ventral tegmental area.

The role of neutrophils is increasingly being recognized in chronic inflammation and metabolic disorders. Here the authors show that visceral adipose tissue from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community.

The molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, authors uncover a role for the EMC2- SLC25A46-Mic19 axis in mitochondrial lipid metabolism and liver disease

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.

ADAR1 is an adenosine deaminase that acts on double-stranded RNA. Orkin and colleagues show that ADAR1 protects hematopoietic stem cells from interferon-induced insult and is needed to maintain long-term hematopoiesis.

An adipocyte-selective product of the Clstn3 locus (CLSTN3β) facilitates the use of stored triglyceride by limiting lipid droplet (LD) expansion, defining a molecular mechanism that regulates LD form and function to facilitate lipid utilization in thermogenic adipocytes.

Non-alcoholic fatty liver disease (NAFLD) has become a prevalent chronic liver disease, however, drugs to treat this disease are still lacking. Here, the authors show that PPDPF inhibits the development of hepatic steatosis by negatively regulating mTORC1-S6K-SREBP1 signaling, which provides a potential therapeutic candidate for NAFLD treatment.

Beneficial and detrimental effects have been ascribed to the different Thrombospondin (Thbs) proteins in the adult mammalian heart. Here, the authors show that Thbs1-mediated activation of PERK-eIF2α-ATF4-induced autophagy regulates adult cardiomyocyte size in the stressed heart.

A high percentage of smooth muscle cells in atherosclerotic lesions lose expression of smooth muscle marker proteins and acquire the phenotype of other cell types, a process of functional importance in lesion pathogenesis that is controlled by the transcription factor KLF4.

The peripheral nervous system uses neuroimmune cardiovascular interfaces to assemble a structural artery–brain circuit, and therapeutic intervention in the artery–brain circuit attenuates atherosclerosis.

LncRNA loci potentially contain multiple modes that can exert function, including DNA regulatory elements. Here, the authors generated genetic models in mice to dissect the role of the syntenically conserved lncRNA Firre in the context of hematopoiesis.

Chen et al. show that the endoplasmic reticulum stress sensor IRE1α acts in white and beige adipocytes to restrain beige adipocyte activation, through regulation of lipolysis and Pgc1α messenger RNA levels, respectively.

Type 2 diabetes (T2D) is characterized by pancreatic beta-cell failure. Here, the authors show restoration of Phosphatidylinositol transfer protein alpha (PITPNA), a mediator of PtdIns-4-phosphate synthesis in the trans-Golgi network, in human T2D islets reverses impaired insulin granule maturation, exocytosis, and ER stress.

AKT inhibitors synergize with agents that suppress the histone methyltransferase EZH2 and promote robust tumour regression in multiple triple-negative breast cancer models in vivo by triggering an involution-like process.

Giafaglione et al. define metabolic regulation of prostate epithelial lineage identity and show that modulation of lactate metabolism alters response to antiandrogen therapy.

Aging-related Meibomian gland shrinkage is associated with dry eye disease. Here, the authors identify Meibomian gland stem cell populations and identify regulatory pathways altered in aging, suggesting new therapeutic targets for Meibomian gland dysfunction.

Here, authors screening mutant embryonic stem cells and identify a new gene termed ‘attenuated hematopoietic development (Ahed)’, which encodes a nuclear protein. Ahed is shown to be essential lifelong hematopoiesis.

The molecular target of the antidiabetic medicine metformin is identified as PEN2, a subunit of γ-secretases, and the PEN2–ATP6AP1 axis offers potential targets for screening for metformin substitutes.

Endothelial cell (EC) dysfunction and inflammation contribute to plaque destabilization in atherosclerosis, increasing the risk of thrombotic events. Here, the authors show that epsin promotes EC inflammation via a mechanism involving IP3R1 degradation, and that deletion of epsin in the endothelium prevents EC dysfunctoin and atherosclerosis in mice.

Fibrodysplasia ossificans progressiva is an ultra-rare genetic disorder with progressive heterotopic ossification. Yang et al develop different gene therapy approaches and show their efficacy in mouse models and in human induced pluripotent stem cells.

Aberrant EGFR expression is associated with triple-negative breast cancer (TNBC). Here the authors identify that TMEM25 interacts with EGFR and the loss of TMEM25 allows monomeric EGFR-mediated hyperactivation of STAT3 to promote TNBC progression.

Omicron BA.1 is attenuated in infection models though the precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging. Here the authors present pGLUE, a plasmid-based viral genome assembly and rescue strategy, to systematically characterize Omicron mutations and show that Omicron NSP6 has weakened lipid flow to replication organelles and reduced viral RNA replication.

Early lipid accumulation is thought to contribute to liver regeneration through unclear functional mechanisms. Here the authors identify an epigenetic regulator, MIER1, that bridges the acute lipid accumulation and cell cycle gene transcription during liver regeneration after surgical resection in male mice.

Superconductivity at temperatures approaching 40 K for a hole-doped nickel oxide that is isostructural with cuprate superconductors demonstrates the existence of a broader family of materials and potential for achieving higher-temperature superconductivity.

Therapeutic administration of IL-27—serum levels of which are decreased in individuals with obesity—improves thermogenesis, protects against diet-induced obesity and ameliorates insulin resistance in mouse models of obesity.

Tripe-negative breast cancers poorly respond to immune checkpoint inhibition therapy, due to their immune-hostile tumour microenvironment. Authors here show that the oncogene MYC plays a pivotal role in suppressing anti-tumour immunity via directly regulating the transcription of interferon signalling genes.

Benegiamo et al. identify genetic variants of the mitochondrial supercomplex assembly factor COX7A2L in the skeletal muscle of mice and humans that promote cardiorespiratory fitness.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

The anti-aging intervention calorie restriction (CR) is thought to act via the nutrient-sensing multiprotein complex mTORC1. Here the authors show that the mTORC1-inhibitor rapamycin and CR use largely distinct mechanisms to slow mouse muscle aging.

Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Here the authors show that obesity induces the expression of the mitochondrial form of arginase ARG2 in PDA and that ARG2 silencing or loss results in ammonia accumulation and suppression of obesity-driven PDA tumor growth.

The role of hydrogen in engendering superconductivity in layered nickelates is under intense debate. Here, the authors perform secondary ion mass spectroscopy and see no evidence for extensive hydrogen incorporation into superconducting nickelates.

Yang et al. show that neuronatin (NNAT) can explain part of the phenotypic variation of complex traits, independently of genetics or the environment. Such NNAT-dependent variations can stratify human cohorts into four metabolic sub-types, including two distinct types of obesity.

Xu et al. report that nuclear SIRT1 is recognized as an autophagy substrate during senescence and also observe ageing of the immune system.

Mutations in two previously unreported Plasmodium falciparum genes, acetyl-CoA transporter (pfact) and UDP-galactose transporter (pfugt), convey resistance to two imidazolopiperazine antimalarial compounds.