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Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.

KCTD10 interacts with the DNA replication machinery and the RNA polymerase complex, inducing ubiquitination and removal of the transcription machinery in the event of co-directional transcription–replication conflicts.

In 1971, Günter Blobel and David Sabatini formulated the signal hypothesis, which proposed that proteins contain signal sequences that target them for secretion. Over the past 40 years this concept has expanded, and topogenic signals are now known to target proteins to many parts of the cell.

VCPIP1 is a deubiquitylase that binds the essential protein VCP/p97. Here, the authors present cryo-EM structures of VCPIP1 bound to VCP and the VCP-VCPIP1-p47 ternary complex along with biochemical and cellular data highlighting the functional importance of VCPIP1 domains in Golgi maintenance.

Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity drives proliferation of small lung cell cancer via paracrine interactions and through synapses formed with tumour cells.

The JAK inhibitor ruxolitinib has been used for treatment of myeloproliferative neoplasms (MPN) and its association with clonal evolution requires further investigation. Here the authors report accumulation of RAS pathway mutations in ruxolitinib-treated myelofibrosis patients, stemming from RAS clonal selection induced by JAK2 inhibition.

Genome-wide CRISPR/Cas9 screening reveals novel modulators of heparan sulfate proteoglycans that regulate cellular uptake of α-synuclein fibrils, including in human dopaminergic neurons.

Using viral barcode tracing to detect interactions between glioblastoma cells and non-malignant astrocytes in patient samples, investigators discovered a pathway that reduces tumour-specific immunity and identified potential therapeutic targets.

Functional roles of natural acetylcholine (ACh) dynamics are not fully understood. This study reveals dynamic changes in ACh release across the mouse striatum during learning and extinction, identifying how and where release dynamics shape brain plasticity to gate learning and promote extinction of cue-reward associations.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

In this study, Flickinger et al. uncover the essential role of cytosolic NADK and why the relative importance of this role further depends on folate availability.

A study of human and mouse models of pancreatic cancer finds that inhibiting the lipid kinase PIKfyve interferes with the cancer’s lipid homeostasis, making it a potential target for drug development.

Mammary morphogenesis is a complex process. Here the authors describe how stem cells build a three-dimensional self-organizing multi-lineage tissue by showing that positional signals from the extracellular matrix through the collagen receptor DDR1 lead stem cells to differentiate into multi-lineage committed multi-layered progeny.

A compilation of distribution, phylogenetic, trait and risk data for more than 10,000 species of terrestrial vertebrates finds that conservation plans that target species diversity are typically also representative of phylogenetic and functional diversity.

Szmyd et al. show that DNA repair pathways impact whether cells with DNA lesions arrest in mitosis. The formation of homologous recombination-driven double Holliday junctions elicits mitotic cell death and suppresses inflammatory signalling.

Gan et al. identify the GPCR-like protein GPR137B that interacts with Rag GTPases to recruit mTORC1 to lysosomes. They show that GPR137B controls dynamic Rag and mTORC1 activity as well as lysosome morphology.

Venetoclax monotherapy is effective in 40% of t(11:14) positive multiple myeloma (MM). Here, the authors show that electron transport chain complex I (CI) and complex II (CII) activity predict MM sensitivity to venetoclax, and inhibition of CI with IACS-010759 or CII with TTFA increase sensitivity.

VE-cadherin is a cell adhesion and signaling molecule that regulates lymphatic cell behaviors. Here the authors show how the VE-cadherin interactome changes in response to junctional remodeling by adrenomedullin and identify mechanisms of VE-cadherin recycling and reelin secretion.

The authors reveal a mechanism for regulation of behaviour during approach avoidance conflicts that relies on two specialized, parallel circuits that allow bidirectional hippocampal control of the prefrontal cortex.

Visual threat triggers contrasting freeze and escape defensive responses in two species of deer mice as a result of different activation thresholds downstream of the superior colliculus in the dorsal periaqueductal grey.

Goodman et al. found that Tau is critical for ROS-induced lipid droplet formation in glia from flies and mammals. Too much or too little glial Tau disrupts lipid droplets, leaving the glia susceptible to neuronal ROS-induced damage and causing phenotypes in tau^−/− flies.

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.

Studying changes in the metabolic properties of kidney cancer in patients reveals an increased need for mitochondrial metabolism as tumors metastasize from the kidney to distant organs.

Changes in the expression of the RNA-binding protein HuR are common in several cancers. Here, the authors show that HuR regulates glutaminase mRNA metabolism in the context of breast cancer. This work reveals that dual inhibition of HuR and glutaminase may have therapeutic potential.

Dysfunctional telomeres activate innate immune responses through mitochondrial TERRA–ZBP1 complexes to eliminate cells that are destined for neoplastic transformation.

Decreased brain coenzyme Q₁₀ levels cause encephalopathy and are associated with neurodegeneration; supplementation with 4-HMA or 4-HB restores coenzyme Q₁₀ synthesis in mice and humans with HPDL variants, improving survival and neurological symptoms in HPDL-driven mitochondrial encephalopathy.

Mutations in the RRAGD gene are causative of an autosomal dominant disorder characterized by kidney tubulopathy and cardiomyopathy. Here, the authors identify a new RRAGD P88L mutation, demonstrating that all the identified RRAGD mutations inhibit the nuclear translocation of MiT/TFE transcription factors, resulting in defective responses to lysosomal or mitochondrial damage.

How cells adapt to glucose starvation is still elusive. Here, Levy et al. show that the mTOR substrate 4EBP1 protects human, mouse, and yeast cells from glucose starvation and is exploited by cancer cells to promote tumorigenesis.

Biologist who decoded how proteins are sorted in cells.

An improved ligand-exchange process allows the realization of solution-deposited films of quantum dots with reduced energetic disorder and, as a result, solar cells with improved open-circuit voltage, charge-carrier transport and stability.

Tau aggregates are associated with several neurodegenerative disorders. In this work, I. Saha and colleagues show that valosin-containing protein (VCP) recruited to Tau fibrils disaggregates them. However, this process comes at a cost: it generates seeding-active Tau species as byproduct.

Dai et al. show that in response to low glucose levels, AMP-activated protein kinase-mediated phosphorylation of WDR24, a component of the GATOR2 complex, leads to suppression of mTORC1 activation.