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Understanding the mechanisms of chemoresistance in multiple myeloma (MM) remains elusive. Here, the authors identify a long non-coding RNA termed as PLUM that is overexpressed in NF-ĸB mutant high-risk MM and interacts with EZH2 to mediate PRC2 complex formation promoting chemoresistance via the activation of the UPR pathway.

Self-assembled multidomain supramolecular peptide hydrogels that engage in dynamic covalent bonding with small-molecule drugs and biologics are shown to offer sustained release, extend the activity, and maintain safe and potent drug levels in vivo.

A workflow combining optogenetic perturbations with spatial transcriptomics to program spatiotemporal gene expression patterns in organoids.

Scalable platforms for non-invasive action potential recording are needed. Here, the authors present a reliable method to capture APs with patch-clamp-like fidelity from stem cell-derived cardiomyocytes using an Electrolyte-Gated Polymer Field-Effect Transistors.

Whether and how highly penetrant NDD (neurodevelopmental disorder) genes such as Syngap1 regulate sensorimotor integration are not fully understood. This study shows that Syngap1 expression in cortical projection neurons promotes cognitive abilities in mice through forming distributed networks that integrate sensory information with motor signals, a dynamic process required for perception and attention.

A combination of optogenetic, electrophysiological and neuroanatomical tracing methods defines midbrain periaqueductal grey circuits for specific defensive behaviours.

Engineering gene expression systems that can be programmed to respond to specific environmental conditions is challenging. Here, the authors develop a synthetic bow-tie circuit that is able to sense signals from microRNA molecules and affect a change in protein dynamics in mammalian cells.

The bidirectional loop circuit between layers 5/6 of the lateral entorhinal cortex and the medial prefrontal cortex encodes item–outcome associative memory in mice.

Analyses of consummatory reproductive behaviours in male mice uncover a brain mechanism whereby an internal state can attribute a social quality to a generic touch to initiate purposeful reproductive actions.

The N-acyl-cyclolysine system regulates the expression of co-localized operons encoding diverse secreted molecules in Bacteroidota.

Single-cell profiling of vagal sensory neurons from seven organs in mice and calcium-imaging-guided spatial transcriptomics reveal that interoceptive signals are coded through three distinct dimensions, allowing efficient processing of multiple signals in parallel using a combinatorial strategy.

Polyneuropathy causes are difficult to pinpoint. Here, authors used single-nucleus and spatial transcriptomics of 37 human peripheral nerves to identify focal perineurial hyperplasia and endoneurial lipid-associated macrophages in polyneuropathies.

The amygdala central nucleus (CeA) has been implicated in feeding regulation, but the underlying circuit mechanisms are incompletely understood. The authors show, in mice, that GABAergic serotonin receptor 2a–expressing CeA neurons are active during eating and promote positive reinforcement and food consumption, partly through long-range inhibition of the parabrachial nucleus.

Basal ganglia output neurons fire dynamically in bidirectional and movement-specific patterns to license forelimb movements. 

Sex pheromones that increase mating have been reported across a number of different species, yet there is little known about pheromones that suppress female mating drive. This study reports that juvenile female mice release a pheromone, ESP22, which suppresses sexual receptivity of adult female mice by evoking a robust rejection behavior upon male mounting.

Transcriptomic analysis following epidural electrical stimulation of the lumbar spinal cord during neurorehabilitation in mice identifies a population of neurons that orchestrates the restoration of walking following paralysis.

Breast cancer cells interact with neighbouring adipocytes, but the mechanisms are not fully understood. Here, the authors show that triple-negative breast cancer (TNBC) cells transfer cAMP through gap junctions, activating lipolysis in tumour-associated adipocytes to promote TNBC growth.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

The authors developed a computational approach to probe the stability of amyloid fibrils and discover networks of hotspot interactions. Understanding the mechanisms of amyloid folding will help identify novel methods to treat protein (mis)folding diseases.

The authors establish the claustrum-Cre transgenic mouse line and demonstrate that the claustrum orchestrates cortical slow-wave activity by synchronously driving the inhibitory interneurons in widespread cortical areas.

High-resolution, spatial transcriptomic analysis of colorectal cancers using matched sequencing- and imaging-based methods characterizes immune cells and their interactions with the tumor microenvironment.

The ASAP4 family of genetically encoded voltage indicators allows recording of action potentials and subthreshold activity with either one- or two-photon microscopy over extended periods of time.

Krabbe, Paradiso et al. show that amygdala VIP interneurons are activated by instructive cues for associative learning. These interneurons provide a mandatory disinhibitory signal permitting plasticity in response to unexpected salient events.

Haematopoietic stem cell numbers are restricted at both systemic and local levels.

iGluSnFR variants with improved signal-to-noise ratios and targeting to postsynaptic sites have been developed, enabling the analysis of glutamatergic neurotransmission in vivo as illustrated in the mouse visual and somatosensory cortex.

Targeting histone deacetylases (HDACs) alone has shown limited success in solid tumours. Here, authors report that the HDAC1/2 inhibitor romidepsin confers responsiveness to receptor tyrosine kinase inhibitors, with enhanced therapeutic effects in models of hepatocellular carcinoma, leading to tumour regression and an immune-stimulatory profile.

tRNAs are essential for translating genetic information into proteins. Here, the authors develop a method to synthesize all 21 essential tRNAs from a single DNA in vitro, enabling protein production and providing a foundation for artificial cells and genetic code reprogramming.

The authors identify thousands of genetic variants affecting RNA splicing in primary human chondrocytes and link several of them to osteoarthritis risk using genome editing and computational approaches.

The control of translation during mitosis has an important role in cancer cell biology. Here the authors report that in mitotically arrested cancer cells, redistribution of ribosomes towards upstream open reading frames results in enhanced presentation of immunogenic peptides on cancer cell surface.

Inflammatory bowel disease is characterised by epithelial dysfunction. Here the authors show that loss of the nuclear receptor LRH-1 leads to epithelial disruption by altering Notch signaling in mouse intestinal organoids, and that LRH-1 overexpression ameliorates immune-mediated colitis in a mouse model.

In the mouse caudal brainstem, functionally distinct neuronal subpopulations, which are distinguishable by neurotransmitter identity, connectivity and location, regulate locomotion parameters.

Virus-host competition drives evolution of diverse antiviral defences in bacteria and antidefense systems in their viruses (phages). Here, Silas et al. use a functional screen of phage accessory genes to show how bacterial cell-surface sugars can be major determinants of phage host-range, and how some phage proteins injected into bacterial cells inhibit host immunity.

Optogenetics is applied to the entire mouse spinal cord.

TDP-43 nuclear clearance and loss-of-function, a hallmark of ALS-FTD and other neurodegenerative diseases, causes widespread inclusion of harmful cryptic exons. Here, the authors developed SnapMine to analyze cryptic exon inclusion across public RNA-seq datasets and identified that the antifungal ciclopirox olamine (CPX) induces such inclusion via heavy metal toxicity and oxidative stress.

Soft objects challenge visual processing in unique ways, yet most models of vision focus on rigid bodies. Here, the authors use computational modeling to reveal that simulation-based intuitive physics underlies human soft object perception.

Using large-scale screening and structure-guided mutagenesis, fast and sensitive GCaMP sensors are developed and optimized with improved kinetics without compromising sensitivity or brightness.

A small population of prostaglandin E2-responsive glossopharyngeal sensory neurons provides a sensory pathway between airway and brainstem that mediates sickness responses to early-phase influenza virus infection.

Feeding and stress are deeply related to each other, yet neural circuits how they interact are not fully understood. Here, the authors show that the parabrachial-to-parasubthalamic nucleus pathway is involved in fear-induced feeding suppression.

Wastewater surveillance can help in pandemic or outbreak response. Here, the authors report an unsupervised learning approach to detect emerging SARS-CoV-2 variants from rural and urban wastewater showing it achieves earlier detection than existing methods and detects new variants without clinical testing data.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

By investigating the paradoxical retention of a photolyase gene in a light-deprived blind cavefish, the authors reveal a novel light-independent function for CPD photolyase in the repair of oxidative stress-induced DNA damage

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

Functional MRI studies across ages show that the classic homunculus of the motor cortex in humans is in fact discontinuous, alternating with action control-linked regions termed the somato-cognitive action network.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

Conventional adhesives stick poorly to wet tissue because water severely undermines the adhesive chemicals they rely on. To overcome this, Yang et al. develop a bio-inspired adhesive microneedle array whose tips swell on contact with water, forming a mechanical bond to living tissue.

Dengue virus transmission by Ae. aegypti mosquitoes poses a significant public health threat, necessitating innovative control strategies. Here, the authors demonstrate that, while successive blood feeding increases earlier dengue virus dissemination, the inhibitory effects of Wolbachia remain strong, highlighting Wolbachia’s potential to disrupt dengue transmission under natural feeding conditions.

Transcriptomic analysis of brain samples collected from dolphins found beached in the Indian River Lagoon during algal bloom seasons shows Alzheimer’s disease related molecular signatures.

GFP reporter lines are useful for labeling specific cell types. Here, the authors developed a method to convert GFP expression directly into Cre recombinase activity. GFP-dependent Cre was delivered via electroporation or AAV to neural tissues in the mouse, and could be used for optogenetic control of specific cell types.

In this work, authors utilise comparative transcriptomics to reveal lncRNAs that distinguish pathogen-specific from core macrophage responses. They identify a Q fever-specific AHR-regulated CYP1B1-AS1/CYP1B1 axis that modulates mitochondrial homeostasis and survival of Coxiella burnetii.