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A randomized phase 2 study recently showed that the addition of ATR inhibitor berzosertib to gemcitabine improved PFS compared to gemcitabine alone in patients with ovarian cancer. In this preplanned exploratory study, the authors demonstrate that a genomic biomarker of replication-stress is associated with outcome to gemcitabine alone and may predict which patients benefit from addition of the ATR inhibitor berzosertib.

The European X-ray free-electron laser (EuXFEL) in Hamburg is the first XFEL with a megahertz repetition rate. Here the authors present the 2.9 Å structure of the large membrane protein complex Photosystem I from T. elongatus that was determined at the EuXFEL.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

West and colleagues develop the Variant Database software tool for examination of changing Spike mutations in SARS-CoV-2 genomes. The authors use this to detect emerging lineages of SARS-CoV-2 in New York and report the rapid spread of the B.1.526 lineage in the city.

Protein targets that are affected by ROS and underly impaired inotropic effects in the heart are largely unknown. Here, the authors identify the γ-subunit of IDH3 as a redox switch linking oxidative stress to impaired metabolism and heart function.

An antimatter hypernucleus formed by an anti-lambda hadron, an antiproton and two antineutrons was observed through its two-body decay after production in ultrarelativistic heavy-ion collisions.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

A Phase I/II trial previously revealed variable anti-tumor efficacy of the PARP inhibitor niraparib in combination with the PD-1 inhibitor pembrolizumab in platinum-resistant ovarian cancer patients. Here, the authors perform an integrated genomic and immunomics analysis of tumor samples from the same patients and find potential predictive biomarkers of response to such combination therapy.

Analysis of genetic data and blood lipid measurements from over 300,000 participants in the Million Veteran Program identifies new associations for blood lipid traits.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Patricia Munroe, Joanna Howson and colleagues genotype ∼350,000 individuals and identify 30 new blood pressure– or hypertension-associated risk loci. Their analyses provide insights into the pathophysiology of hypertension and highlight new potential targets for clinical intervention.

Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

Emission from atomic hydrogen at a wavelength of 21 centimetres had been observed from galaxies at a maximum redshift of 0.4, but is now reported at a redshift of about 1.

A large scale approach for multifunctional smart display systems in traditional textiles has yet to be demonstrated. Here, authors present a foldable, rollable 46-inch smart textile lighting/display system for smart homes and internet of things applications via the systematic design and integration of versatile fibre devices into textile form factors.

The intrinsically disordered linker histone H1.0 and prothymosin α form a complex which exhibits slow exchange between bound and unbound populations at low protein concentrations and fast exchange at high concentrations. Here authors explain this observation by the formation of transient ternary complexes favored at high protein concentrations that accelerate the exchange.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Senescence degrades reward-based decision-making. Here the authors show that there are abnormalities in older adults in a functional magnetic resonance imaging measure of reward prediction error (RPE) signaling and changes in the structural connectivity of areas encoding reward value information. Administration of levodopa ameliorated behavioral deficits and restored RPE signaling in some older adults.

JmjC histone demethylases (KDMs) are cancer targets due to their links to cell proliferation, but selective inhibition remains a challenge. Here the authors identify potent inhibitors of KDM4A-C—viain vitroselection from a vast library of cyclic peptides—that show selectivity over other KDMs.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

Cooperative water wires formed by clustering of artificial water channels enhance membrane permselectivity.

Drake and colleagues demonstrate that castration in prostate cancer models promotes IL-8 secretion and immunosuppressive myeloid-derived suppressor cell migration, and that inhibiting this axis in combination with checkpoint blockade can mitigate tumor progression.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Kristal et al. find that rewriting a résumé so that previously held jobs are listed with the number of years worked (instead of employment dates) increases callbacks from real employers compared to résumés without employment gaps by approximately 8%.

mTORC1 blocks lysosomal nutrient generation. Here, the authors show that mTORC1 inactivation triggers V-ATPase assembly, which rapidly initiates lysosomal acidification and degradation of protein contents throughout the lysosomal population.

Blocking mitochondrial complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in vivo in an animal disease model.

Solar water splitting for hydrogen generation may be a future source of renewable energy. Here, the authors demonstrate that controlled p-type doping of metal-nitride nanowires can eradicate surface potential barriers and promotes stable stoichiometric dissociation of water under visible light.

Designing energy-efficient and scalable hardware capable of accelerating Monte Carlo algorithms is highly desirable for probabilistic computing. Here, Singh et al. combine stochastic magnetic tunnel junction-based probabilistic bits with versatile field programmable gate arrays to achieve this goa

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

Clairmont et al. find that the TRIP13 ATPase regulates REV7–Shieldin dissociation to promote homology-directed repair and suppress non-homologous end joining, and show the importance of PARPi resistance in BRCA1-deficient cancers.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

The direct transformation of crude oil to chemicals can become a game changer in refocusing the petroleum industry production, but remains technically challenging. Here, the authors introduce a multi-zone fluidized bed reactor in combination with an engineered cracking catalyst for the efficient one-pot production of light olefins from crude oil.

Valyl-tRNA synthetase (VARS) charges valyl-tRNA with the amino acid valine, required for translation. Here, the authors describe a progressive epileptic encephalopathy in individuals from five families carrying biallelic mutations in the VARS gene that leave the enzyme activity partially intact.

Electrostatic gating of 2D transistors with ionic liquids presents intrinsic limitations. Here, the authors demonstrate n-type MoS₂ and p-type WSe₂ transistors on a lithium-ion solid electrolyte substrate, displaying sub-threshold values approaching the ideal limit of 60 mV/dec and complementary amplifier gain of 34 with 1 V supply.

Correlations in momentum space between hadrons created by ultrarelativistic proton–proton collisions at the CERN Large Hadron Collider provide insights into the strong interaction, particularly the short-range dynamics of hyperons—baryons that contain strange quarks.

HD 74423 is an unusual binary star system containing two λ Boötis pulsators. TESS photometry reveals that one of the pair is pulsating along its tidal axis—but only in one hemisphere. Such an odd arrangement provides an interesting laboratory in which to study stellar pulsations and tidal distortion.

The identification of Escherichia coli ycfD and human MINA53 and NO66 as ribosomal amino acid hydroxylases defines a role for 2-oxoglutarate/iron-dependent oxygenases in translational regulation.