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This study shows that high-molecular weight tau has enhanced seeding capacity, and seeding differences can define molecular subtypes of progressive supranuclear palsy, underpinning the disease’s heterogeneity.

Cross-species transcriptomics on vulnerable neuronal populations unravels the transcription factor CREB3 and its regulatory network as resilience markers of ALS. Genetics and epidemiology further identify the protective rare variant CREB3R119G.

Dbr1 exhibits debranching specificity and effect on splicing. Here the authors combine co-immunoprecipitation, RNA binding and lariat analysis and suggest a role for Dbr1 interactor AQR in intron recycling. Dbr1 depletion leads to increased dwell time of spliceosome on excised lariats.

The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

Advancements in sequencing technologies and assemblers have enabled us to generate a complete, haplotype-resolved X chromosome in cattle. This study discovers the cattle X centromere is a natural neocentromere and characterises its genetic and epigenetic structure.

Schrecker, Son and colleagues identify the accessory subunits transmembrane protein 9 (TMEM9) and TMEM9B for chloride transporters ClC-3, ClC-4 and ClC-5 and establish the roles of TMEM9 and phosphatidylinositol 3,5-bisphosphate in the regulation of ClC-3 activity and endosomal ion homeostasis.

Modelling magnetic data for lanthanide clusters is challenging due to spin–orbit coupling and crystal field effects. Here, the authors use multi-frequency electron paramagnetic resonance spectroscopy to measure directly the interaction between two dysprosium(III) ions in a dimeric system.

Palaeoenvironmental analysis reveals the ecological history of the Andean–Amazonian corridor, where European colonization resulted in depopulation, land-use decline and forest succession such that by the nineteenth century the region came to be seen as a pristine natural environment.

The histone variant H3.3 is phosphorylated at Ser31 in induced genes, and this selective mark stimulates the histone methyltransferase SETD2 and ejects the ZMYND11 repressor, thus revealing a role for histone phosphorylation in amplifying de novo transcription.

Endosomal function depends on luminal ion homeostasis. Here the authors identify TMEM9 and TMEM9B as inhibitory subunits of endosomal ClC-3 to ClC−5 that prevent endosomal swelling and disease by regulating their Cl⁻/H⁺ exchange and trafficking.

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.

The MuvB protein complex regulates genes that are differentially expressed through the cell cycle, yet its precise molecular function has remained unclear. Here the authors reveal MuvB associates with the nucleosome adjacent to the transcription start site of cell-cycle genes and that the tight positioning of this nucleosome correlates with MuvB-dependent gene repression.

DOT1A and DOT1B are African trypanosome homologues of the enzyme DOT1 methyltransferase, which is involved in the methylation of the histone H3K79. In this study, the authors identify specific residues that modulate the specificity of these enzymes for different forms of methylation.

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.

UNAGI deciphers cellular dynamics from human disease time-series single-cell data and facilitates in silico drug perturbations to discover drugs potentially active against complex human diseases.

Paramagnetic heterometallic rings have long been considered as possible qubits within a quantum information processing system. Here, the authors employ supramolecular chemistry to fabricate multiple rings around multi-armed threads, as an important step towards generating useful qubit arrays.

The detoxification pathway photorespiration has been thought to be photoprotective in dynamic light. The authors report that, instead, growth in dynamic light buffers plants against photorespiratory lesions by reducing photosynthesis and inducing metabolite re-routing.

The PRODIGITAL-D trial in adults aged 60+ years from socioeconomically deprived areas of Brazil showed that a 6-week self-help mobile messaging psychosocial intervention was effective in improving depression recovery at 3 months compared to a single message control intervention.

Magnetic fields can enhance electrocatalysis, yet its effect on mass transport has been overlooked. Here, the authors track the motion induced on the electrolyte ions, demonstrating that mass transport effects can double the catalyst activity with low reactant availability, as in oxygen reduction.

Zeziulia et al. identify the proton-activated Cl⁻ channel ASOR/TMEM206 as necessary for shrinkage of macropinosomes, which is needed for downstream sorting events.

The bicyclic disulfide–containing compound thiolutin has broad antimicrobial activity and targets the essential proteasomal deubiquitinase Rpn11 and other metalloproteases, leading to inhibition of enzymatic activity through a mechanism involving zinc chelation.

Analysis of diet and body size in terrestrial and aquatic vertebrates shows that a U-shaped relationship between body size and trophic guild prevails across extant vertebrates with the exception of marine mammals and seabirds. Analysis of fossil data shows that, for terrestrial mammals, this pattern has persisted for at least 66 million years, despite anthropogenic perturbance, which may have greater effects in the next centuries.

The red dwarf star YZ Ceti produced two observed bursts of radio waves that may have been caused by the star interacting magnetically with a nearby Earth-like planet, as the radio bursts occur at similar points in the planet’s two-day orbit.

Mass cytometry can be used to scale up multiplexed serology testing, as shown for the simultaneous detection of antibody levels against multiple SARS-CoV-2 proteins in hundreds of serum samples.

Tooth morphology has provided many insights into the tempo and mode of dietary evolution in mammals. A study of fossil and extant squamates shows that this group also repeatedly evolved increasingly complex teeth with more flexibility than mammals, and that higher tooth complexity and herbivory likely led to higher speciation rates.

A proteolytically derived fragment of the epigenetic regulator HDAC4 protects the heart through transcriptional repression of the hexosamine biosynthetic pathway, thereby inhibiting protein O-GlcNAcylation and maintaining normal calcium handling and contractility of cardiomyocytes.

TSC22D4 regulates hepatic lipoprotein production, but has so far mainly been studied in the context of cancer cachexia. Here, the authors show TSC22D4 inhibition improves insulin sensitivity in several mouse models of diabetes, which they attribute at least in part to the induction of secreted LCN13.

Bacterial symbionts are increasingly known to influence behaviour and fitness in insects. Here, Frago et al. show that plants fed on by aphids with symbionts have altered volatile chemical profiles, leading to reduced parasitoid attack of aphids.

Defects in the cell adhesion molecule GlialCAM, the membrane protein MLC1 and the chloride channel ClC-2 are implicated in leukodystrophy. Here, Hoegg-Beiler et al.show that these proteins form a functional complex to maintain homoeostatic chloride ion transport supporting normal glial function in mice.

Blood brain barrier (BBB) opening is being investigated as a therapeutic approach for neurodegenerative diseases. Here, the authors report the results of a phase I trial to evaluate the feasibility and safety of BBB opening of the right parieto-occipito-temporal cortex in Parkinson´s disease with dementia.

The chromosomal kinase JIL-1 is responsible for interphase histone H3S10 phosphorylation and has been proposed to protect active chromatin from heterochromatinisation. Here, the authors show that JIL-1 is stabilized and anchored to active genes and telomeric transposons by JASPer, which binds to H3K36me3 nucleosomes via its PWWP domain.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Muñoz-Gil and colleagues report the results of an open challenge where they benchmarked algorithms for the characterization of motion changes in single-particle tracking. By ranking methods on simulations, the competition revealed strengths and limitations of AI and classic approaches, guiding researchers toward optimal tools.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

Biological determinants for developing post-acute sequelae of SARS-CoV-2 infection are largely unclear. Here, by comparing markers during acute infection in individuals who developed PASC with those who recovered, the authors found that early viral dynamics and immune responses might play a role in PASC pathogenesis.

The identification of metabolic vulnerabilities of tumor cells constitutes a major topic in cancer research. Here, the authors introduce gmctool, a computational tool that enables to accomplish this task using genome-scale metabolic networks and RNA-sequencing data.

Biotic homogenization, which is increased similarity in the composition of species among communities, is rising due to human activities. Using North American mammal fossil records from the past 30,000 years, this study shows that this phenomenon is ancient, beginning between 12,000 and 10,000 years ago with the extinction of the mammal megafauna.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Calcium-activated chloride currents are thought to amplify the olfactory signal during the transduction process. Here the authors identify Ano2 as the critical channel in both main olfactory epithelium and in the vomeronasal organ. Surprisingly, disruption of Ano2 did not reduce performance in an olfactory behavioral task, suggesting that olfaction does not actually depend on these channels.