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The ventromedial hypothalamus (VMH) serves as a satiety center in the brain, however, the neural circuits involved are incompletely understood. Here, the authors decipher a neural circuit from VMH to the paraventricular thalamus that suppresses food intake.

Idiopathic pulmonary fibrosis has been associated with aberrant expansion of KRT5-expressing basal cells. Here the authors show how changes in the ECM glycoprotein SPARC restrict the movement of KRT5+ cells, affecting their retention within fibrotic tissue.

Nahrendorf and colleagues show that B cells in the bone marrow are an important source of the neurotransmitter acetylcholine, which limits hematopoiesis through modulating the signals produced by the bone marrow stromal niche during steady-state and emergency hematopoiesis.

The discrepancy between the short half-life of ketamine and its long-lasting effects is due to ketamine being trapped in NMDA receptors, and its release depends on neural activity in the lateral habenula.

The chimeric cytokine IC7Fc combines the beneficial effects of the cytokines IL-6 and CNTF on weight loss and metabolism in mice, with no obvious side effects in mice and non-human primates.

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.

A large-scale genome-wide meta-analysis conducted across different platforms identifies genetic loci regulating levels of circulating metabolites.

Microglia can help clear amyloid β plaques in the Alzheimer’s disease brain but may also become dysfunctional and can contribute to disease progression. March-Diaz et al. reveal that hypoxia, a potentially modifiable risk factor for Alzheimer’s disease, disrupts the metabolism and function of microglia near plaques, which may contribute to neuropathology.

Single-cell transcriptomics studies on human and mouse non-small cell lung cancer and conditional knockout mouse models show that IL-4 from bone marrow basophils drives the development of granulocyte-monocyte progenitors to myeloid cells that suppress antitumour immunity.

Antenatal glucocorticoid therapy is indicated for mothers at risk of preterm delivery. Here, the authors show that the circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders later in life in mice and in a retrospective observational study in human infants.

Tumor-associated myeloid cells directly support progression of T-cell acute lymphoblastic leukemia (TALL). Here, the authors show that T-ALL cells must contact myeloid cells and activate integrin signaling and downstream FAK/PYK2 kinases to survive.

Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations in the TSC1 or TSC2 genes, which negatively regulate mTORC1 signalling. Here the authors selectively delete Tsc1 from dopamine neurons in mice and find impairments in striatal dopamine release that are sufficient to reduce cognitive flexibility.

Although myeloid cell dysfunction has been observed in COVID-19, the underlying mechanisms remain incompletely understood. Here, the authors demonstrate that monocytes from patients with mild to moderate COVID-19 show a blunted innate immune response and a pro-thrombotic signature following secondary SARS-CoV-2 challenge.

Intravital imaging reveals macrophage-driven de novo induction of cancer stem cells in vivo, and their dramatic enrichment on dissemination through TMEM doorways. These findings provide a mechanism for the validated ability of TMEM doorway density to be prognostic for distant recurrence of metastatic tumors in breast cancer patients.

The mechanisms underlying epilepsy development are not well understood. Here the authors show that loss of a key component of the so called blood-brain barrier drives seizures in mice and is also lost in humans with treatment resistant epilepsy

Mirchandani and colleagues show that tissue hypoxia alters the number and phenotype of circulating monocytes and their differentiation into lung macrophages, with important implications for the resolution of inflammation in the lung.

Roesch and colleagues use clinical datasets and mouse models of BRAF-mutant melanoma to reveal a role for IL-17A in positive responses to anti-PD-1 and anti-CTLA-4 therapy, which they also link to infiltrating neutrophils.

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..

Natural selection may favor traits underlying aging-related diseases if they benefit the young. Wang et al. find that oxidative activation of CaMKII provides physiological benefits critical to the initial and continued success of vertebrates but at the cost of disease, frailty, and shortened lifespan.

It is traditionally believed that callosal and non-callosal fates are determined early after a neuron’s birth, and that cortical layer (L) 4 excitatory neurons of the primary somatosensory (S1) barrel cortex project only ipsilaterally. However, here authors demonstrate, using a novel axonal retrotracing strategy, that L4 neurons develop transient interhemispheric axons that are refined in an area- and layer-specific manner during postnatal development.

REV-ERB in GABAergic neurons orchestrates the rhythmic sensitivity of hepatic glucose production to insulin-mediated suppression that peaks at wakening, with implications in the extended dawn phenomenon.

Bharathan et al. discover that the endoplasmic reticulum associates with keratin intermediate filaments and desmosomal cell–cell junctions, and that desmosomes and the keratin cytoskeleton regulate the distribution, dynamics and function of the endoplasmic reticulum network.

The molecular mechanisms connecting Niemann Pick C1 cholesterol transporter (NPC1) loss to Niemann-Pick Type C neuropathology remain unknown. Here, the authors demonstrate that loss of NPC1 function alters the nanoscale distribution and function of ion channels to promote abnormal calcium entry, mitochondrial dysfunction, and neurotoxicity.

Mass spectrometric profiling of a glycan library reveals that sialylated glycans, especially sialic acid-containing gangliosides, interact with the RBD of the SARS-CoV-2 spike protein and are involved in ACE2-dependent viral infection.

Todd et al. show a daily rhythm in aggression propensity in male mice and reveal a novel polysynaptic circuit within the hypothalamus by which the central circadian clock (the suprachiasmatic nucleus) influences neurons that regulate attack behavior.

Enteric glial cells have tissue-wide immunoregulatory roles through the upregulation of IFNγ-dependent genes both at steady state and after parasite infection, promoting immune homeostasis and CXCL10-mediated tissue repair after pathogen-induced intestinal damage in mice.

Regulation of cell polarity is key to ensure directed cell migration. Here, Atkins et al. identify the primary cilium cAMP/cGMP ratio as a master regulator of the cell polarity of migrating cortical interneurons downstream of the CXCL12 chemokine.

A switch system is developed to control the expression of therapeutic genes, involving the administration of a small-molecule drug to induce splicing-mediated control of mRNA translation.

Hunger status in a fly is shown to drive either sleep-dependent or sleep-independent memory formation through different mushroom body circuits.

Severe COVID-19 is characterized by an accumulation of and functional changes in neutrophils. Using metabolomics, the authors demonstrate that neutrophils display a reduction in GAPDH activity in severe COVID-19 and that GAPDH inhibition promotes neutrophil extracellular trap formation.

Organ transplantation involving aged donors is often confounded by reduced post-transplantation organ survival. By studying both human organs and mouse transplantation models, here the authors show that pretreating the donors with senolytics to reduce mitochondria DNA and pro-inflammatory dendritic cells may help promote survival of aged organs.

Neutrophils employ several mechanisms to control the growth of fungi, including enzymes, reactive oxygen species, extracellular traps, and formation of “swarms”. Here, Hopke et al. study how the different mechanisms work together, using an in vitro assay with human neutrophils and clusters of live Candida cells.

A study demonstrates that specific interactions between the two committed enzymes for the synthesis of lipopolysaccharide and peptidoglycan enable coordinated assembly of the outer membrane and cell wall in the Gram-negative pathogen Pseudomonas aeruginosa.

Meacham et al. report that adiponectin receptors suppress chronic inflammatory signalling by immune effector cells to prevent haematopoietic stem cell exit from quiescence and, thus, protect them from exhaustion.

Analyses of layer 5 cortical pyramidal neurons in 10 mammalian species show that human neurons are distinct in that they do not follow the expected allometric relationship between neuron size and membrane conductance.

γδ T cells have potent effector functions through their production of IFN-γ or IL-17. Pennington and colleagues demonstrate that IFN-γ⁺ γδ T and IL-17⁺ γδ T cells have distinct metabolic requirements that can be independently targeted to elicit specific immune responses.

In fibrotic biliary disease, portal fibroblasts promote both biliary scarring and bile duct regeneration. Here, the authors report that the non-canonical Wnt-PCP signalling promotes bile duct scarring in mice, and inhibition of Wnt-ligands reduces the scarring without impairing regeneration.

Disruptions to the ER-Golgi network can lead to neurodevelopmental disorders, though our understanding of these Golgipathies remains incomplete. Here Lauri, Tartaglia and colleagues show that ARF3 mutations cause a rare pediatric neurological disorder and perform detailed molecular characterization in fish.

Arterial flow regulates artery diameter but other mechanisms may also affect this. Here, the authors show that the guanine nucleotide exchange factor Trio and GTPases Rac1 and RhoG, triggers F-actin remodeling in arterial endothelial cells, independent of flow, to enhance lumen diameter in zebrafish and cell models.

Silent nociceptors remained enigmatic ever since they were first described decades ago. Here, Nees. et al. show that inflammation-induced upregulation of TMEM100 unsilences silent nociceptors, which triggers secondary mechanical pain hypersensitivity.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Controlled human infection models (CHIMs) provide a pathway for accelerating vaccine development. Here, the authors describe the isolation, characterization, and GMP manufacture of a clinical Leishmania major strain to be used as a resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.

Persistent neural activity in the mouse hypothalamus encodes aversive emotional states related to specific threatening stimuli.

Nanoparticle albumin bound paclitaxel (nab-PTX) is widely used in the clinic to treat different cancers, but the effect of albumin on the distribution of the drug in tumours is not clear. Here the authors show that the accumulation of nab-PTX in tumours is affected by signalling molecules involved in nutrient uptake and processing, which could be reprogrammed to increase the drug’s efficacy.

Cell migration is essential for many physiological processes. Its deregulation causes cancer metastasis and it is not well understood how it is tightly controlled. We identify NHSL1 as a negative regulator of actin nucleating Scar/WAVE-Arp2/3 complexes, cell protrusion stability, and cell migration.

Catalytic gold nanoclusters that respond to protease activity in vivo and are excreted in urine can offer a quick colorimetric tool for disease detection in resource-limited settings.

This Review provides an overview of the main applications of single-port robotic surgery in urology, presenting emerging outcomes and discussing the transformative potential of this approach.

The pathogenic function of XBP1-expressing astrocytes in experimental autoimmune encephalomyelitis and multiple sclerosis have been studied using FIND-seq, a new method combining microfluidics cytometry, PCR-based detection of nucleic acids and cell sorting for in-depth single-cell transcriptomics analyses of rare cells.