Search

Soft auditory brainstem implant in the cochlear nucleus of macaque evokes auditory-like perceptions with high resolution and tonotopic specificity.

Adipose tissue accommodates large volume changes upon expansion, but the molecular mechanisms involved are not fully understood. Here, Aboy et al. describe CAV1 Y14 phosphorylation as required for appropriate adipocyte caveolae flattening and homeostasis.

How adipose mitochondria activity is fine-tuned in response to obesity is an active area of study. Here, the authors show that mitochondrial protein MCJ can block thermogenesis and that silencing this gene can correct obesity-related comorbidities.

Targeting of diseased cells is key to the development of next-generation pharmaceuticals, but is often hindered by a lack of specific cell surface markers. Here the authors develop an RNA-based approach, which allows precise control of gene expression, with translation only occurring within preselected cell types of interest.

Magnetic resonance fingerprinting (MRF) requires a uniform B₁⁺ radiofrequency field. Here the authors present plug-n-play MRF, a technique that enables multiparametric imaging with heterogeneous B₁⁺fields, and demonstrate its utility in the presence of RF distortion caused by a metallic orthopaedic implant.

A flexible magnetic resonance imaging coil bearing an array of high-impedance detectors can be stitched onto a glove and used to image the biomechanics of the hand’s soft tissue.

Eberhard et al. show that SEMA3A regulates liver sinusoidal endothelial cell fenestrations by signaling through NRP1 and LIMK1, revealing a pathway that connects hyperlipidemia to the development of steatotic liver disease.

Understanding the regulatory mechanisms governing brown and beige adipose mediated thermogenesis is of interest in order to develop therapeutic strategies to treat obesity. Here, the authors show that adipocyte-expressed apoptosis signal-regulating kinase 1 (ASK1) inhibits browning in response to cold, β3 receptor activation, and LPS.

Schneeberger et al. show that glutamatergic neurons within the dorsal raphe nucleus of the brainstem are enriched with the orexin 1 receptor Hcrtr1, which can be pharmacologically targeted to treat obesity in mice.

Mast cells are shown to function as sensor cells linking antigen recognition in type 2 immunity to antigen-specific avoidance behaviour, preventing immune activation and inflammation.

Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.

Endothelial cells in white adipose tissue are shown to produce polyamines, which regulate adipocyte lipolysis, thus demonstrating how local angiocrine signals contribute to healthy adipose tissue homeostasis.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

The lactylation of lysine residues on histones in mammalian cells is stimulated by hypoxia and bacterial challenges, and increased histone lactylation induces genes involved in wound healing.

Brown adipose thermogenesis increases energy expenditure and relies on uncoupling protein 1 (UCP1), however, UCP1 knock-out mice show resistance to diet-induced obesity at room temperature. Here, the authors show that this resistance relies on FGF21-signaling, inducing the browning of white adipose tissue.

Glucocorticoids are associated with stress. Here, the authors show that high levels of glucocorticoid stress promote secretory autophagy of matrix metalloproteinase 9 via a stress responsive chaperone, increasing brain-derived neurotrophic factor processing and potentially altering adult synaptic plasticity.

Ramachandran et al. identify a previously unappreciated function for transcriptional repressor B cell lymphoma 6 (BCL6) in muscle proteostasis and strength, and provide mechanistic insight into the molecular underpinnings of this function.

GLP-1 is an incretin hormone and neuromodulator produced by gut enterocytes and CNS neurons. Brierley et al. find that GLP-1 from peripheral and central sources acts independently through distinct gut–brain circuits to suppress eating.

Skeletal muscle plays a key role in regulating systemic glucose and metabolic homeostasis. Here, the authors show that the catalytic activity of Vav2, an activator of Rho GTPases, modulates those processes by favoring the responsiveness of this tissue to insulin and related factors.

Blockade of intrahepatic accumulation and function of platelets represents a potential approach to treat non-alcoholic steatohepatitis (NASH) and prevent subsequent progression to hepatocellular carcinoma

Glucose-dependent insulinotropic polypeptide (GIP) is a gut incretin hormone released in response to nutrients. Here, the authors report an anti-inflammatory and antiobesogenic mechanism of GIP by showing that loss of GIP receptor signalling in myeloid cells promotes pro-inflammatory S100A8/A9 release in adipose tissue.

Defective insulin secretion is observed early in the development of diabetes. Here the authors report that β cell-specific deficiency of the insulin prohormone convertase 1/3 (PC1/3) leads not only to hyperglycemia, but also to hyperphagic obesity in mice.

Oestrogen has various metabolic and physiological effects. Here the authors show that oestrogen receptor alpha signalling determines lineage commitment of murine adipose progenitor cells, regulating their differentiation into white adipocytes, beige adipocytes or smooth muscle cells.

The histone demethylase Lsd1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Here, the authors show that the loss of Lsd1 in the trophectoderm of mouse embryos leads to premature differentiation of trophoblast stem cells, partially due to de-repression of the transcription factor Ovol2.

Emerging studies suggest that p53 is an important regulator of energy metabolism, yet there is little known about the metabolic function of this tumor suppressor in the hypothalamus. Here, authors illustrate that p53, specifically in AgRP neurons, is required for adaptation to diet-induced obesity.

Extended exposure to breastfeeding in rodent pups protects them from diet-induced obesity in adulthood by increasing thermogenesis and energy expenditure. This is mediated by liver-derived FGF21 signalling to the lateral hypothalamic area.

A rationally designed peptide agonist that targets three key hormone receptors reduces obesity and its complications in a manner superior to other agonists.

Four secreted bacterial serine hydrolases found by an ABPP approach in Vibrio cholerae–infected rabbits, and one in human infection, regulate the levels of intelectin, an intestinal lectin that binds V. cholerae during infection and may facilitate bacterial surveillance in the intestine.

Cryo-EM structures of the human mitochondrial chaperone Hsp60 reveal alternating apical domain conformations that enable simultaneous client and co-chaperone interactions. These results provide a structural mechanism for efficient client capture and chaperone cycling.

Hyper-insulinemia associated with excess calorie intake may cause metabolic dysfunction. Here the authors report that mice with partially reduced insulin receptor expression in peripheral tissues are protected from and experience reversal of fatty liver disease.

Transfer of senescent cells into naive, young mice can induce physical dysfunction, and a senolytic can reverse this dysfunction and potently increase lifespan in aged mice.

This protocol provides structure-guided capsid library approaches to evolve new adeno-associated viral vectors for enhanced CNS gene delivery with altered tissue tropism, higher transduction efficiency and the ability to evade pre-existing humoral immunity.

An analysis of POLE and POLD1 mutations distinguishes driver mutations from passengers and explores their functionality. Driver mutations are associated with specific mutational signatures and correlate with immune checkpoint blockage response.

Understanding the mode of small-molecule binding to amyloid filaments is critical for diagnosing and treating neurodegeneration. The authors use cryo-EM to reveal a stacked binding motif which may hasten design of diagnostics and therapeutics.

This study of 23,000 non-diabetic individuals highlights loci associated with fasting glucose and fasting insulin in diverse cohorts with whole genome sequence data.

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.