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Here the authors show that Xist drives non-stoichiometric recruitment of SHARP/SPEN to the inactive X chromosome, including at regions not occupied by Xist, through concentration-dependent homotypic assemblies of SHARP, which is required for chromosome-wide silencing. This spatial amplification allows Xist to balance chromosome-wide silencing and specificity to the X thereby enabling Xist to silence the X, the whole X, and nothing but the X.

The calcium binding protein S100B is an abundantly expressed protein in the brain and has neuro-protective functions by inhibiting Aβ aggregation and metal ion toxicity. Here, the authors combine cell biology and biochemical experiments with chemical kinetics and NMR measurements and show that S100B protein is an extracellular Tau chaperone and further characterize the interactions between S100B and Tau.

Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

Bailleul et al. employ histology, histochemistry and Energy Dispersive Spectroscopy to confirm the presence of disputed ovarian follicles in a specimen of fossil Cretaceous bird. These findings have implications for the evolution of the avian breeding system seen in birds today.

A new multi-speleothem record from Guatemala demonstrates that Atlantic Ocean circulation and sea surface temperature controlled Central American monsoon convection during the last glacial cycle, with a limited role for orbital summer insolation.

Lack of muscle stem cell targeting limits the treatment of muscular dystrophies. Here, the authors describe a platform based on functionalized gold nanoparticles that allows selective delivery of therapeutic oligonucleotides and promotes skeletal muscle regeneration.

This study reveals that prion protein (PrP) promotes copper toxicity in Wilson disease by facilitating copper endocytosis. The authors demonstrate that suppressing PrP reduces copper overload and liver damage, offering a potential therapeutic strategy for this fatal inherited disorder.

Genome-wide ancient DNA data from 225 individuals who lived in southeastern Europe between 12000 and 500 bc reveals that the region acted as a genetic crossroads before and after the arrival of farming.

A Pitx1 enhancer shows activity in forelimbs and hindlimbs but only interacts with Pitx1 in hindlimbs because of its three-dimensional configuration. Structural variants that affect three-dimensional conformation induce Pitx1 expression in forelimbs and cause partial arm-to-leg transformation in mice and humans.

Bacteriorhodopsin (bR) is a light-driven proton pump. Here the authors combine time-resolved crystallography at a free-electron laser, ultrafast spectroscopy and quantum chemistry to study the structural changes following multiphoton photoexcitation of bR and find that they occur within 300 fs not only in the light-absorbing chromophore but also in the surrounding protein.

How the airway microbiome influences asthma pathophysiology remains unclear. Here, the authors analyse nasal samples of cohort of school-age children with persistent asthma and find that the microbiota’s patterns and composition at time of early loss of asthma control associate with severe asthma exacerbations.

Perro and colleagues develop a CD3⁺ T cell engager co-targeting BCMA and CD38 to improve immunotherapy for multiple myeloma, demonstrate cytotoxicity in patient-derived samples and murine models and develop a quantitative systems pharmacology model.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Providing detailed structural descriptions of the ultrafast photochemical events that occur in light-sensitive proteins is key to their understanding. Now, excited-state structures in the reversibly switchable fluorescent protein rsEGFP2 have been solved by time-resolved crystallography using an X-ray laser. These structures enabled the design of a mutant with improved photoswitching quantum yields.

Cosmological hydrodynamical simulations of the ΛCDM Universe show that isolated quenched ultra-diffuse galaxies are formed as backsplash galaxies that were once satellites of another galactic group or cluster halo but are today a few megaparsecs away from them.

Calorie burning is normally turned off in thermogenic brown fat at warm temperatures. Here the authors show that adipocyte oxygen sensing directly boosts brown fat calorie burning, even at warm temperatures.

How bacteria sense and respond to nitrogen is a key question in microbial physiology. This work unveils the mechanism by which the central nitrogen metabolic enzyme, glutamine synthetase, directly signals nitrogen availability to the GlnR regulator.

The human gut Bifidobacterium longum can use host N-glycans as carbon and energy sources via a specific and cooperative multienzymatic system.

Kumar and colleagues report cryo-EM structures of Arabidopsis O-fucosyltransferase SPINDLY in its apo and GDP-fucose bound states, revealing distinct active-site features enabling GDP-fucose recognition and surprisingly dynamic conformations that regulate its enzymatic activity.

The caudal ventrolateral medulla was thought to be involved in pain control, but its pathway was unknown. Here, Gu et al. identify the molecular components of a caudal ventrolateral medulla–locus coeruleus–spinal cord pathway and show it has a role in counter-stimulus pain control.

Pulmonary hypertension due to left heart disease is characterized by pulmonary arterial stiffening that results from extracellular matrix remodeling. Here, the authors show that elastin stabilization improves arterial biomechanics and attenuates pulmonary hypertension.

Mutations to the splicing machinery may have an important role in myelodysplasia. Here, the authors describe splicing factor gene mutations in myelodysplasia and report tumor suppressor, epigenetic, iron metabolism and heme biosynthesis genes as their targets.

Controlling the rotational dynamics of polyatomic molecules is a key to the quantum renaissance of molecular physics with applications such as information encoding, quantum sensing, and chiral sensitive spectroscopy. Here, the authors present a method for complete control of the rotational dynamics in chiral asymmetric top molecules through quantum control theory.

Here, Cabral et al., perform a multi-omics analysis of the gut microbiome of capybara, the largest living rodent, unveiling enzymatic mechanisms for the breakdown of lignocellulosic biomass, and report two undescribed families of carbohydrate-active enzymes.

A study reports europium molecular crystals with optically addressable spin states that exhibit ultra-narrow linewidths, demonstrating the use of rare-earth molecular crystals as a platform for photonic quantum technologies.

This study investigates the effectiveness of COVID-19 vaccine boosters following a primary series of CoronaVac vaccination. Using data from Brazil during the Omicron wave, the authors show that boosters provided protection against severe disease, with higher effectiveness from a BNT162b2 than CoronaVac booster.

Time-series observations from the JWST of the transiting exoplanet WASP-39b show gaseous water in the planet’s atmosphere and place an upper limit on the abundance of methane.

Many island plant species share a syndrome of characteristic phenotype and life history. Cerca et al. find the genomic basis of the plant island syndrome in one of Darwin’s giant daisies, while separating ancestral genomes in a chromosome-resolved polyploid assembly.

A study using calcium imaging in the mouse forepaw system identifies neurons in the posterior insular cortex that respond to cooling and/or warming with distinct response dynamics.

In battery research, the areas of the electrodes and cell dimensions affect the energy storage performance. Here the authors discuss the factors that influence the reliability of electrochemical measurements and battery performance in lithium-ion cells with different electrode areas.

Beas et al. show that stress exposure drives disinhibition of PVT projection neurons. This process involves an LC-mediated rise in extracellular DA in the midline thalamus, requires D2 receptors on PVT neurons, and increases stress sensitivity.

Genetic studies of eczema to date have mostly explored common genetic variation. Here, the authors perform a large meta-analysis for common and rare variants and discover 8 loci associated with eczema. Over 20% of the heritability of the condition is attributable to rare variants.

Multiple cryo-EM structures of rat TRPV1 at different temperatures illustrate steps in the heat-dependent gating of this important sensory receptor.

Vo’, Italy, is a unique setting for studying SARS-CoV-2 antibody dynamics because mass testing was conducted there early in the pandemic. Here, the authors perform two follow-up serological surveys and estimate seroprevalence, the extent of within-household transmission, and the impact of contact tracing.

In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.

Chris Garcia, David Baker and colleagues use a computational approach to develop designed repeat protein binders (DRPBs), which function as human Frizzled (Fz) subtype-selective antagonists and enable identification of Fz subtypes active in different organs.

Messenger RNAs transcribed from olfactory-receptor genes may have non-coding functions that include recruitment of transcriptional enhancers and inhibition of potentially thousands of competing alleles to ensure stable transcription of a single allele.

Here, authors report chemokine receptors structures obtained using coarse-grained metadynamics. CCR5 and CXCR4 homo- and heterodimers differ in the conformations of ligand binding sites and of the G protein interaction interface, suggesting structural basis for the rational design of biased ligands.

In myelinated fibres conduction and adhesion proteins aggregate at discrete foci, but it is unclear if this organization is present in other excitable cells. Using nanoscale visualization and in silico techniques, the authors show that adhesion/excitability nodes exist at the intercalated discs of adult cardiac muscle.

Modulation of the unfolded protein response by targeting IRE1 has several potential therapeutic applications. Here, the authors provide a first structural view of inhibitors engaging the RNase-active site of IRE1 that suggests avenues towards the generation of analogues with increased potency and selectivity.

Ruth Halaban and colleagues report exome sequences of 147 melanoma tumors. They identified a recurrent somatic activating alteration in the Rho GTPase RAC1 in sun-exposed melanomas.

A platform for systemic therapeutic transgene expression independent of patient mutations needs a safe and highly transcribed locus. Here the authors ex vivo edit HPSCs using CRISPR-Cas9 to integrate transgenes under the α-globin promoter to achieve erythroid specific expression.

Here, Bachmann et al. provide data on long-term dynamics of the HIV-1 reservoir in 1,057 individuals on suppressive antiretroviral therapy and show that in 26.6% of individuals the reservoir increases. Viral blips and low-level viremia are significantly associated with a slower reservoir decay.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Alx3-induced modulation of Mitf expression alters melanocyte differentiation and gives rise to the hair colour differences underlying the repeated evolution of dorsal stripes in rodents.

Nitrogen monoxide at low concentrations can promote the formation of highly oxygenated organic molecules, which are crucial precursors to secondary organic aerosol (SOA), rather than inhibit it as traditionally thought.

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.