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Striatal hyperactivity has been linked to compulsive behavior, but cell-type and pathway specific mechanisms are unclear. Here, the authors show excessive grooming in Sapap3-KO mice is associated with indirect pathway hyperactivity and suppression of hyperactivity normalizes grooming.

Sivanandan, Leitmann, and colleagues present the CellPaint-POSH platform, which combines pooled CRISPR screening with Cell Painting. Using self-supervised deep learning on cell images, the method enables discovery of gene function and biological networks.

Cheng et al., use non-infectious stable viral replicon cell lines in genome-wide CRISPR KO screens across diverse viral pathogens to identify host factors specifically involved in the intracellular stages of viral replication.

A combination of genome-wide CRISPR screens in target cancer cells identifies pathways that regulate γδ T cell killing and BTN3A cell surface expression.

This study uses the rumen gut microbiome to show that core microbes exhibit attributes of ecological generalists with broad functional capacity and traits that enable them to be metabolically independent while also supporting non-core microbes and the host.

From metagenomic sequencing of coastal soils along a salinity gradient, this study shows contrasting eco-evolutionary strategies for relieving carbon limitation under salt stress in bacteria and archaea. The findings suggest that bacteria conserve energy through genome streamlining when facing salt stress, while archaea invest in carbon-acquisition pathways to broaden their resource usage.

Herpesviruses bind to heparan sulphate (HS) on the surface of cells before infecting them. Here, the authors show that heparanase, a host enzyme that degrades HS and is upregulated on viral infection, is required for the release of newly formed viruses from infected cells.

Research on plant root-associated microbial communities may help develop more efficient or sustainable crop production methods. Here the authors analyse the citrus rhizosphere microbiome, using both amplicon and deep shotgun metagenomic sequencing of samples collected across six continents.

Macrophages possess different G protein-coupled receptors such as the orphan receptor GPRC5B. Here the authors characterise the function of GPRC5B in macrophages in knockout mice showing that in the absence of GPRC5B there is increased inflammatory responses and macrophage activation because of reduced EP2-mediated anti-inflammatory effects.

The taxonomic and functional diversity of marine microbial communities are shaped by both environmental and biotic factors. Here, the authors investigate the functional biogeography of epipelagic prokaryotic communities along a 13,000-km transect in the Southern and Atlantic Oceans, showing finely tuned genetic adaptations to regional conditions.

Here, the authors present an update to a widely used curatedMetagenomicData (cMD) database and use it to create a catalog of microbiome-phenotype associations (age, sex, body mass index), and develop an oral enrichment score in the gut microbiome independently of age.

The microbiomes associated with reef corals are complex and diverse. Here, the authors investigate fire coral clones naturally occurring in distinct habitats as a model system to disentangle the contribution of host genotype and environment on their microbiome, and predict genomic functions based on taxonomic profiles.

Risk associated with genetically defined forms of autism spectrum disorder (ASD) can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing insight into the convergent impact of ASD genetic risk on human neurodevelopment.

The organization of gut microbes in lumen and mucosa and the microbial genes regulating this organization remain poorly understood. Here, using in vitro cultures incorporating a complex gut microbial community in mucin-hydrogel carriers, the authors show greater richness and strain-specific spatial organization, enabling discovery of associated genes.

Experiments in mouse models show that proper recovery of the intestinal microbiota following depletion, with or without faecal microbiota transplant therapy, is dependent on syntrophic interactions that occur only with specific dietary interventions.

Cryo-EM structures of the stabilized prefusion conformation of the glycoprotein B ectodomain—the HSV-1 entry machine—identify a prefusion-specific neutralizing antibody and reveal how prefusion glycoprotein B may evade antibody-mediated neutralization.

Plant male reproduction is controlled by gibberellin signalling via the transcription factor GAMYB. Here, deletion of GAMYB in a moss species lacking a gibberellin signalling pathway gives rise to abnormal spores, suggesting that primitive plants used GAMYB for the control of sexual organ development.

Brief ciprofloxacin exposure in humans drives antibiotic resistance evolution in gut bacteria through selective sweeps, particularly involving DNA gyrase mutations, which persist long after exposure and demonstrate the human gutʼs capacity to promote resistance evolution.

Activin receptor-like kinase 4 (ALK4) is frequently downregulated or mutated in cancers. Here the authors find that ALK4 loss promotes canonical TGF-β signaling and cancer progression through increasing TGF-β receptor N-linked glycosylation and subsequently stabilizing these receptors at the cell surface.

OsTCP19 is a modulator of the tillering response to nitrogen in rice, and introgression of an allele of OsTCP19 associated with a high tillering response into modern rice cultivars markedly improves their nitrogen-use efficiency.

Bacterial functional diversity does not necessarily correlate with taxonomic diversity because average genome size may vary by community. Here, Wang et al. investigate bacterial communities along a natural pH gradient in forest soils, and find that average genome size and functional diversity decrease, whereas taxonomic diversity increases, as soil pH rises from acid to neutral.

RNA Polymerase III (Pol III) transcribes non-coding RNA, including tRNAs. Applying different RNA-Seq techniques, Dremel et al. provide the Pol III transcriptional landscape of Herpes simplex virus 1 (HSV-1) infected cells. Infection leads to an increase in tRNA expression from host euchromatin and Pol II re-localization to tRNA loci. They also find that Pol III – associated factors bind to the viral genome.

This study maps out the diversity and evolution of the bacterial order Caulobacterales, including the model organism C. crescentus, which reveals widespread phototrophy and illuminates the evolution of bacterial cell shapes and lifecycle complexity.

Herold et al. present an integrated meta-omics framework to investigate how mixed microbial communities, such as oleaginous bacterial populations in biological wastewater treatment plants, respond with distinct adaptation strategies to disturbances. They show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity.

The timing and locations of aftershocks following the initial impact of an earthquake are key to mitigate potential further hazards. Here the authors use the seismic ground velocity as input parameter to provide accurate probabilities of post seismic occurrence within 30 min of the main shock.

Here, the authors develop a genome evolution model to investigate the origin of functional redundancy in the human microbiome by analyzing its genomic content network and illustrate potential ecological and evolutionary processes that may contribute to its resilience.

Multiplexed editing using Cas12a transgenic mice facilitates the study of disease models with complex genotypes.

Chronic lung diseases are characterized by molecular and cellular composition changes. Here the authors use single-cell RNA sequencing to map cell type-specific changes in human tracheal epithelium related to smoking, and to provide evidence for a tuft-like progenitor for pulmonary neuroendocrine cells and ionocytes.

Systems genetics reveals interactions between host and microbial phenotypes in the murine gut, including a role for Akkermansia muciniphila in the production of immunomodulatory ornithine lipids.

During plant innate immunity ROS is produced via the NADPH oxidase RBOHD. Here, Lee et al. show that RBOHD protein abundance is regulated through phosphorylation by the PBL13 receptor-like cytoplasmic kinase and via ubiquitination by PIRE, a newly identified E3 ubiquitin ligase.

Sustainable food production under climate change requires farming practices that support plant–soil–microbe interactions. This study suggests that conservation agriculture with warming enhances wheat nitrogen uptake by reducing microbial competition.

Inhibitor-induced kinase degradation is a common event that positions supercharging of endogenous degradation circuits as an alternative to classical proximity-inducing degraders.

Epigenetic regulators are potential therapeutic drug targets in leukemia. Here, the authors perform combinatorial CRISPR knockouts to test gene-gene pairings in leukemia cells to discover compensatory non-lethal or synergistic lethal combinations with therapeutic potential.

A study reports single-cell RNA-sequencing profiles for more than 1.6 million cell nuclei from 101 whole mouse embryos including 22 mutant and 4 wild-type genotypes, from one experiment.

Ulva macroalgal ecosystem is a highly efficient natural bioremediation system, reducing coastal triazine herbicides by up to 89% through pathways involving macroalga-microbiome synergistic functions, according to a field investigation combined with designed simulation conducted in Yellow Sea, China.

Protein-truncating variants (PTVs) are predicted to significantly affect a gene’s function and, thus, human traits. Here, DeBoever et al. systematically analyze PTVs in more than 300,000 individuals across 135 phenotypes and identify 27 associations between PTVs and medical conditions.

Direct interaction between the small GTPase Rab7a and the cation channel TPC2 has been reported but the functional regulation is less clear. Here, the authors show that Rab7a enhances the activity of TPC2 to promote melanoma progression through the GSK3β/β-Catenin/MITF axis.

Drosophila Microproteins Simba1/2 act in neural stem cells and blood-brain-barrier glia to promote reactivation of neural stem cells via activating WNT/Wingless signaling, while human ortholog ZNF706 is found to have a conserved role in activating WNT pathway.

The magnitude 7.6 Izmit earthquake that struck Turkey in 1999 was nucleated by an eastward-migrating cascade of foreshocks, according to high-resolution analyses of seismic data.

Intravenous infusion of ketamine rapidly reduces obsessive-compulsive disorder symptoms. Here, the authors show in mice that ketamine acts by increasing activity in a fronto-striatal circuit that causally controls compulsive grooming behaviour.