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Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

The involvement of cell death pathways in the early stage of pancreatic ductal adenocarcinoma (PDAC) development, especially KRAS-dependent acinar-to-ductal metaplasia (ADM), remains to be investigated. Here, the authors find that TAK1 mediates cell survival during ADM transdifferentiation through suppression of apoptosis and necroptosis, which could be targeted for prevention and treatment of PDAC.

In glioblastoma (GBM), tumour microtubes (TM) connect tumour cells to a broader cellular network, with roles in tumour progression and therapy resistance. Here, the authors combine a dye uptake method in GBM xenograft models with subsequent scRNA-seq to infer a TM connectivity signature, finding CHI3L1 as a marker of connectivity.

Striatal neural circuits control reward-associated behaviors but the role of astrocytes is still unclear. Here, the authors show that chemogenetic manipulation of striatal astrocyte in mice restore obesity-associated cognitive defect and exert a control on whole-body metabolism.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Addition of an inexpensive, biocompatible polymer reduces spontaneous fusions of organoids in culture.

Most proteases have their own endogenous, specific inhibitors which protect living organisms from the deleterious effects of excessive proteolytic activity. Here, authors identify PCPE-2 as a potent and specific inhibitor of BMP-1/tolloid-like proteases.

Maintaining neural progenitor cell stemness has proven challenging in vitro, due to their propensity to form cell-dense neurospheres. Here, the authors developed a 3D hydrogel system that supports neural progenitor cell stemness maintenance and differentiation by tuning matrix mechanics and cell-binding cues, enabling long-term expansion and neuron formation without needing dense cell clusters.

How the larval environment influences the sensory characteristics of the future adult is largely unknown. Here, using Drosophila as a model, the authors show that the presence of certain bacterial species during the larval stage modify the gustatory capacities of the future adult flies.

Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

mTORC1 expression is increased during ageing of muscle, and on the other hand, its activation promotes muscle hypertrophy. Here, the authors assess whether mTORC1 has positive or negative effects on ageing, and show that its long-term inhibition preserves muscle mass and function and neuromuscular junction integrity, whereas muscle-specific activation is associated with sarcopenia.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Cortical GABAergic interneurons are highly diverse in their gene expression, electrophysiological properties, and connectivity. Here the authors reveal three distinct subtypes of Htr3a-GFP+ interneurons using the single-cell RNA-seq approach, and identify MEIS2 as a marker for one such subtype.

RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence.

RMC-7977, a compound that exhibits potent inhibition of the active states of mutant and wild-type KRAS, NRAS and HRAS variants has a strong anti-tumour effect on RAS-addicted tumours and is well tolerated in preclinical models.

Sheikh et al. show that deficiency in the lysine acetyltransferase MOF causes aberrant accumulation of fatty acids in neural cells, which in turn triggers inflammation in nearby pericytes, resulting in brain haemorrhaging.

Structural, spectroscopic and kinetic analyses suggest that class II benzoyl-CoA reductases from anaerobic bacteria use an unusual tungsten cofactor and a conserved histidine to perform a reduction akin to the widely used Birch reduction in organic chemistry.

In the developing heart, blood flow transmits mechanical signals to progenitor cells that ultimately leads to valve formation. Here, the authors identify the origin of the valve progenitor cells and fibronectin1bas a transcriptional target of the mechanotransduced signals responsible for valve formation.

A challenge in the semiconductor industry is to create integrated circuits that use new physical state variables — other than charge or voltage — to offer memory and logic functions. Memristive devices, which combine the electrical properties of a memory element and a resistor, use resistance instead, and here such 'memristors' are shown to perform logic operations as well.

Effective treatment options for mitochondrial diseases are scarce. Here, Aiyar et al. identify the TIM23 mitochondrial protein sorting machinery as a potential intervention point for mitochondrial ATP synthase disorders.

PdCO is a switchable optogenetic tool for inhibiting synaptic transmission in neuronal terminals in vivo, as demonstrated in a variety of contexts mainly in the mouse.

Bioprinting has potential in the biofabrication of three dimensional tissues, but is poorly suited to the manipulation of neural organoids. Here, the authors develop a bioprinting platform to allow the arrangement of organoids to form assembloids.

The development of robust and active anode materials for oxygen evolution reaction is challenging. Perovskite nanocatalysts with high mass activity towards water splitting and electronic structures changing drastically during operando conditions are reported.

The neuropeptide CRH is believed to induce aversive, stress-like behavioral responses. Here the authors describe a distinct population of CRH neurons in the extended amygdala that act to suppress anxiety by positively modulating dopamine release.

Lightning Pose is an efficient pose estimation approach that requires few labeled training data owing to its semi-supervised learning strategy and ensembling.

RaPID uses biotin ligases BirA* and the faster acting BASU to label proteins in the proximity of an RNA motif of interest in living cells.

Human pluripotent stem cell-derived in vitro models have potential as tools to study aspects of human brain development. Here, Heilshorn and colleagues review biomaterial-based approaches that may be integrated into these models in an effort to develop them further and better recapitulate neurodevelopmental processes.

CD98hc in macrophages attenuates the severity of colitis. This change in the macrophage development is associated with increased expression of apoptotic genes, suggesting that CD98hc maintains the gut homeostasis by ensuring the development of gut macrophages.

A modular architecture for managing and sharing electrophysiology, behavior, colony management and other data has been built to support individual laboratories or large consortia.

A small-size engineered enzyme, ultraID, is presented for proximity-dependent biotinylation, that shows efficient labeling in mammalian cell culture, E. coli and S. cerevisiae.

Integrating bioprinting with organoid technology can enhance tissue engineering by improving complexity, reproducibility and scalability. This Review discusses living materials in bioprinting, current organoid bioprinting methods, support baths and future innovations that could advance complex tissue development and applications.

Goblet cells through their production and secretion of mucins play an essential role in protecting the host against luminal insults, and contribute to the mutualism between host and gut microbiota. Loss of epithelial Gpr35 disrupts the goblet cell compartment by reducing their numbers and increasing pyroptosis levels. Dysregulation of goblet cells is correlated with changes in the mucosa-associated bacterial communities. As a result, Gpr35^f/fVil⁺ mice displayed increased susceptibility to C. rodentium-induced colitis. (Adapted from SERVIER MEDICAL ART (CC of license 3.0)).

The SRP Alu domain is involved in co-translational protein targeting. Soni et al. investigate the Alu domain of Plasmodium falciparum, the agent of malaria, and find that unlike any other it adopts an open conformation.