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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.

The processes regulating cardiomyocyte (CM) maturation are unclear. Here, the authors show that serum response factor regulates CM maturation only in neonatal CMs through stage-specific chromatin occupancy that affects cell size, sarcomere and transverse-tubule organization, and mitochondria

Anecdotal reports from patients prescribed semaglutide describe a reduced desire to drink. Here, the authors show that semaglutide is associated with a 50%-56% reduced risk for both the incidence and recurrence of alcohol use disorder in real-world populations.

Breeding has increased crop productivity, but whether it has also changed phenotypic plasticity is unclear. Here, the authors find maize genomic regions selected for high productivity show reduced contribution to genotype by environment variation and provide evidence for regulatory control of phenotypic stability.

Epigenomic profiling and massively parallel reporter assays identify 892 functional differentially-active single-nucleotide variants (daSNVs) linked to ten neuropsychiatric diseases. CRISPRi and gene editing approaches show magnesium transport dysfunction as a common genetic pathomechanism.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

The ambipolar field of Earth controls the structure of the polar ionosphere and boosts its scale height by 271%, physically driving  the polar wind and acting as the source of the magnetospheric cold H⁺ ion population.

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.

Evidence synthesized from 252 large-herbivore exclusion studies suggests that herbivore-induced change in dominance, independent of site productivity or precipitation, best predicts herbivore effects on biodiversity in grassland and savannah sites.

Coenzyme Q (CoQ) is a lipid made in the inner mitochondrial membrane with antioxidant roles throughout the cell, but regulation of its cellular distribution is unclear. Here the authors identify two proteins that have reciprocal CoQ trafficking functions to help coordinate CoQ localization in yeast.

The medium-resolution transmission spectrum of the exoplanet WASP-39b, described using observations from the Near Infrared Spectrograph G395H grating aboard JWST, shows significant absorption from CO₂ and H₂O and detection of SO₂.

Conventional smart windows with tunable transparency are based on electrochromic systems that consumes energy. Here Wheeler et al. demonstrate a halide perovskite based photo-switchable window that dynamically responds to sunlight and change colors via reversible phase transitions.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Very early observations of a type Ia supernova—from within one hour of explosion—show a red colour that develops and rapidly disappears. These data provide information on the initial explosion mechanism: surface nuclear burning on the white dwarf or extreme mixing of the nuclear burning process.

A possible kilonova associated with a nearby, long-duration gamma-ray burst suggests that gamma-ray bursts with long and complex light curves can be spawned from the merger of two compact objects, contrary to the established gamma-ray burst paradigm.

Peptide-centric chimeric antigen receptors (PC-CARs) provide a platform to address the challenges involved in targeting intracellular oncoproteins, and PC-CARs based on the neuroblastoma-dependency gene PHOX2B induce elimination of aggressive tumors.

Genomic analysis of Plasmodium DNA from 36 ancient individuals provides insight into the global distribution and spread of malaria-causing species during around 5,500 years of human history.

Minogue et al. show that glutarate, a metabolite derived from tryptophan catabolism, has the ability to shape anti-tumour T cell responses by modulating pyruvate handling and alpha-ketoglutarate-dependent dioxygenases.

Adaptation of Mycobacterium tuberculosis to the host environment is principally mediated through its transcription factors. Here, the authors report the DNA binding and transcriptional profile of ~80% of all predicted M. tuberculosistranscription factors, and find wide-spread dormant DNA binding.

By comparing neural responses to diverse visual stimuli measured with a standardized two-photon imaging pipeline, the authors reveal response specializations within the mouse visual cortex.

Variant detection in problematic genes is facilitated with a curated benchmark.

Antimicrobial peptide LL37 can bind nucleic acids and potentiate their sensing by endosomal TLRs. Here the authors show that LL37 binds to RNA from neutrophil extracellular traps (NETs), which amplifies inflammation and production of more LL37 and NETs via TLR8/13, suggesting that LL37 contribution to psoriasis may be fueled by NET-associated RNA.

Intravital imaging reveals macrophage-driven de novo induction of cancer stem cells in vivo, and their dramatic enrichment on dissemination through TMEM doorways. These findings provide a mechanism for the validated ability of TMEM doorway density to be prognostic for distant recurrence of metastatic tumors in breast cancer patients.

Despite the significance of mosquitos for human health, little research has focused on their phylogeny. Here, the authors present a resolved phylogenetic history of mosquitoes based on phylogenomics showing that these major disease vectors radiated coincidentally with geologic events and the diversification of their hosts.

Content-aware frame interpolation (CAFI) improves the temporal resolution in time-lapse imaging by accurately predicting images in between image pairs. By allowing fewer frames to be imaged, CAFI also enables gentler live-cell imaging.

A large-scale transcriptome analysis in Drosophila melanogaster, across tissues, cell types and conditions, provides insights into global patterns and diversity of transcription initiation, splicing, polyadenylation and non-coding RNA expression.

CTL responses are critical in protection against pathogens. Here, using mass spectrometry and flow cytometry, the authors characterize the kinetics of influenza A virus class I MHC epitopes cross-presented in professional antigen presenting cells and identify new epitopes that elicit T cell responses in infected mice.

Immune analyses against circulating SARS-CoV-2 variants show that mRNA vaccination induces robust neutralizing antibodies and boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection.

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.

Fibre snacks that target distinct features of the microbiomes of donors with obesity transplanted into gnotobiotic mice also lead to fibre-specific changes in the microbiome and physiology when used in controlled-diet human studies.

Microbial natural products represent a large reservoir of potential pharmaceutical agents. Here, Johnston et al. describe a computer-automated programme for connecting genome sequences with identified and isolated natural products.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

The ATR inhibitor ceralasertib has shown clinical activity in combination with immune-checkpoint inhibitors in several cancer types. Here the authors report the anti-tumor activity and the immunomodulatory changes, dependent on up-regulation of type I interferon pathway, following intermittent ATR inhibition in preclinical cancer models.

Metal carbenes are accessed using a metallaphotoredox platform that exploits iron carbene reactivity using readily available chemical feedstocks and α-elimination.

In this study, the authors compare the viral kinetics of first and second SARS-CoV-2 infections using data from an occupational surveillance scheme in the National Basketball League. They find that second infections tend to have a faster clearance time, and that clearance times in first and second infections were positively correlated.