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l-cysteine is required for the growth of Lactobacillus iners, a vaginal microbiome species typically associated with adverse outcomes that lacks cysteine biosynthesis pathways and key uptake mechanisms present in other lactobacilli. Cystine uptake inhibitors can be used to suppress L. iners abundance in vitro in favour of L. crispatus, a species associated with favourable outcomes.

The PI3K–PANK4 axis regulates coenzyme A synthesis, the abundance of acetyl-CoA, and CoA-dependent processes such as lipid metabolism, and these regulatory mechanisms coordinate cellular CoA supplies with the demands of hormone and growth-factor-driven or oncogene-driven metabolism and growth.

The Peruvian Amazon is facing the highest known input of mercury pollution of any ecosystem globally. Intact forests located near artisanal gold mining are particularly at risk from this toxin.

This study reports endothelial leakiness in vitro, in silico and in vivo, where adherens junctions are disrupted by their exposure to the anionic oligomers and seeds of Alzheimer’s amyloid beta, preceding proinflammatory and pro-oxidative events.

Injectable bioelectronics face low conductivity due to poor polymer dispersibility. Here, authors engineer dopants in conductive polymers to boost their water dispersibility 5-fold and conductivity 20-fold, enabling biodegradable, 3D-printable hydrogels for wearables and implantable devices.

Isolating the neural mechanisms of consciousness is complicated by task report and other irrelevant signals. Here, the authors removed report and eye movement confounds to uncover large scale cortical-subcortical networks specific for human visual consciousness.

By integrating the serum concentration of a broadly neutralizing antibody (bNAb) with its in vitro 80% inhibitory concentration, the PT₈₀ biomarker may be used to guide target levels of bNAbs for effective prevention of HIV-1 acquisition.

Mucosal surfaces are a primary route of HIV entry, yet the compartmentalisation between mucosal and peripheral immune systems remain a challenge for HIV vaccine candidates. Authors utilise a combination of intranodal tonsil MALT and systemic vaccination in the rhesus macaque model to explore immune responses and protection from highly pathogenic simian homologue of HIV.

Cancer cells have been shown to be dependent upon glutamine for growth. Here, the authors show that intracellular asparagine, a glutamine-derived metabolite, is critical to cancer cell growth and can compensate glutamine deficiency by acting as an amino acid exchange factor.

New delivery platforms are needed to allow broader application of biotherapeutics for CNS diseases. Here, the authors show enhanced CNS delivery with a transport vehicle engineered to bind CD98hc, a highly expressed target at the blood-brain barrier.

Highly selective formation of C₂₊ alcohols is obtained using CO electroreduction with a trimetallic-copper-based catalyst incorporating gold nanoparticles and isolated silver atoms.

Previously, authors have identified GW461484A (GW) as an inhibitor of the kinase Yck2 in the fungal pathogen Candida albicans. Here, they report the synthesis of GW analogs with improved pharmacological properties and activity in mouse models of systemic candidiasis.

Wang et al show that the pathogen Pseudomonas aeruginosa employs two distinct acyl-CoA dehydrogenases for β-oxidation. They identify the substrate selectivity filter in each enzyme, and show that the enzymes are required for optimal virulence.

Dendritic cells concentrated in vivo within a hydrogel have been metabolically tagged with azido groups to enable tracking as well as delivery of antigens, adjuvants and cytokines, thereby facilitating targeted immunomodulation.

Off-target effects in CRISPR screens for essential regulatory elements have not been systematically evaluated. Here the authors find Cas9 nuclease, CRISPRi/a each have distinct off-target effects, and that these can be accurately identified and removed using the GuideScan sgRNA specificity score.

The default mode network (DMN) is a core brain network in humans. Here, the authors show that marmoset primates also possess a DMN-like network but, unlike in the human DMN, dlPFC is a more prominent node than mPFC, suggesting mPFC is more developed in humans than in other primates.

Theory predicts that organisms in varied environments should evolve to be more phenotypically flexible. Evidence combining genetic and physiological variation with thermal acclimation experiments shows that the thermogenic flexibility of wild juncos is greatest in populations where temperatures are most variable.

Design of a two-component protein array enables robust formation of complex large-scale ordered biologically active materials.

In this work, the authors study the immunological and virological effects of administering either wild-type anti-HIV-1 broadly neutralizing antibodies (bNAbs) or bNAbs with a mutation that increases binding to Fc-gamma receptors (FcγRs) to rhesus macaques in the acute phase of SHIV_AD8-EO infection.

Zhu et al. discover that in human brain there is widespread anatomic distribution of low-frequency somatic, mosaic L1 insertions, using deep whole-genome sequencing of neuronal and glial fractions and machine-learning analysis.

Kinetic modulatory profiling identifies regulators of ferroptosis, including the FDA-approved drug bazedoxifene, which acts in an off-target manner as a radical trapping antioxidant while mTOR inhibitors increased resistance to ferroptosis.

Kim and colleagues perform a phase 2 clinical trial (ELM-2) of odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma and report on the primary analyses of the efficacy and safety profile.

The emergence and spread of artemisinin resistance has compromised antimalarial efficacy. Here, Mok et al. apply quantitative transcriptomics, proteomics, and metabolomics to provide evidence that K13 mutations alter multiple aspects of the parasite’s intra-erythrocytic development to enhance survival following artemisinin treatment.

Getting synthetic biology circuit-based sensors into field applications is still a challenge. Here the authors combine a circuit sensor with a glucose meter for small analyte and nucleic acid detection.

A genomic barcoding scheme called two-layer DNA seqFISH+ enables the simultaneous mapping of more than 100,000 loci and has been used to identify cell-type-specific subnuclear compartments in the mouse brain.

The vast scale of emerging on-demand chemical collections presents a challenge for efficiently identifying promising drug candidates. Here, the authors develop a bottom-up computational strategy to first explore fragment space and then exploit the most promising scaffolds, successfully identifying diverse and potent BRD4 binders.

Splice sites must be correctly identified for introns to be removed from pre-mRNAs and for expression of the correct mRNA isoforms. Here, the authors elucidate how the human U1 snRNP splicing factor recognizes 5′ splice sites and how a splicing modulating drug can enhance splice site recognition.

Whole-genome sequencing of matched serial tumours from patients identifies two key mutagenic factors (APOBEC3 and chemotherapy) and extrachromosomal DNA-forming structural variants that drive treatment resistance in urothelial cancer.

Our genes ensure that our minds are never 'blank slates'.

Ultra-high resolution mass spectrometry revealed that plastic bags leach labile compounds. Bioassays performed in Scandinavian lakes indicated that these compounds are incorporated into biomass faster and more efficiently than natural organic matter.

Experimental evidence for charge coupling to ferroelectric soft mode is scarce. Here, the authors find a photogenerated coherent phonon coupling to the electronic transition above the bandgap in the van der Waals ferroelectric semiconductor NbOI2.

HIV vaccine development can be aided by knowledge of correlates of protection. Here the authors identify engagement and reprogramming of tolerogenic CD14⁺ myeloid cells mediating a spatiotemporal balance of pro- and anti-inflammatory responses, as correlates of efficacy in female macaques vaccinated with the DNA/ALVAC/gp120/Alum platform.

A consortium reports the tripling of the number of genetic markers in Phase II of the International HapMap Project. This map of human genetic variation will continue to revolutionize discovery of susceptibility loci in common genetic diseases, and study of genes under selection in humans.

How maternal factors influence a newborn’s microbiota remains unclear. Here, the authors examined the buccal, rectal, and stool microbiotas of newborns within three days of birth and explore the impact of over 200 maternal factors on the newborns’ microbiotas.

Elevated intraocular pressure (IOP) is a heritable risk factor for primary open angle glaucoma. Using forward mouse genetics, cell biology, pharmacology and human genetic data, the authors identify CACNA2D1 as an IOP risk gene that can be therapeutically targeted by the drug pregabalin in animal models.

7DW8-5 is a glycolipid that binds CD1d and stimulates invariant natural killer T (iNKT) cells. Here the authors show that 7DW8-5, when administered intranasally, provides prophylactic anti-viral effects against influenza, RSV, and SARS-CoV-2 in mice or hamsters, and that this effect is mediated by iNKT cells and IFN-γ.

Mutations in pre-mRNA processing factors cause autosomal dominant retinitis pigmentosa. Here the authors provide insights into the pathophysiological mechanisms underlying non-syndromic retinal disease caused by heterozygous mutations in genes encoding ubiquitously expressed splicing factors.

Although multiple reaction monitoring (MRM) mass spectrometry holds considerable promise for quantifying candidate protein biomarkers in blood, transferability of MRM assays between laboratories has never been shown. Addona et al. assess the reproducibility, dynamic range and limits of detection and quantification of MRM across multiple sites.

The Alx3 transcription factor, expressed in prenatal tooth development, is shown to revitalize adult progenitor cells in decellularized scaffolds, leading to enhanced parenchymal dental pulp and vascularized stroma regeneration in vivo.

Stress exposure shapes survival mechanisms in bacteria. Here, the authors show that individual pneumococcal cells react to stress by competence self-induction, which may propagate to non-competent cells, promoting multilevel heterogeneity and favouring survival.

Many phototransistors are multi-component systems with inorganic materials or involve faradaic processes that can be irreversible. Using a single photoactive polymer, Druet et al. report a reversible, water-compatible n-type photoelectrochemical transistor with potentiometric photodetection and current modulation.

ETS transcription factor ERG has been implicated in numerous cancers, including leukemia. Here, the authors show that ERG interaction with the NCoR-HDAC3 co-repressor complex is essential for its leukemogenic activity. Highlighting this interaction as a potential therapeutic target, HDAC3 inhibition led to reduced growth of ERG-dependent leukemia cells in vitro and in vivo.