Here, we introduce the Mariana Trench Environment and Ecology Research (MEER) project, which provides the first systematic view of the ecosystem in the hadal zone.
For microbiome research to be translated into clinical applications, the field needs to move beyond correlational studies; we suggest adopting a multi-phase iterative approach that leverages in vivo and ex vivo strategies, as well as a combination of traditional microbiology, with big-data approaches.
Cryo-EM structures provide a snapshot of subunit assembly and atomic architecture in endogenous NMDA receptors, shedding light on their in vivo function, which is highly associated with learning and memory.
Recordings from electrocorticography brain-computer interface (BCI) in tetraplegic participants find mesoscale representational stability and plasticity with neurofeedback that allows for long-term neuroprosthetic control of a robotic arm and hand.
Is it possible to restore the human gut microbiome in industrialized settings and reintroduce microbial species that have been lost? In healthy adults, Li et al. found that consuming a diet mimicking non-industrialized dietary patterns (restore diet) together with a bacterium rarely found in industrialized human gut microbiomes (Limosilactobacillus reuteri) enhanced persistence of the latter. The diet also redressed several microbiome features altered by industrialization, which was linked to considerable cardiometabolic benefits.
Schneider et al. identify guanylate kinase 1 (GUK1), a GDP-synthesizing enzyme, as a target of oncogenic signaling in lung cancer. Phosphorylation of GUK1 augments nucleotide pools and is important for G protein signaling and tumor proliferation.
Parturition timing in mice is controlled by locus-specific adjustment of histone H3 trimethyl lysine 27 (H3K27me3) levels within uterine fibroblasts in early gestation, with subsequent locus-specific H3K27me3 erosion associated with gene induction post-midgestation.
Correlative cryo-confocal and cryo-electron tomography is shown to robustly target a specific chromosomal locus. When applied to visualize human mitotic chromosomes, this approach reveals kinetochore complexes within chromatin clearings that distinguish the site for spindle microtubule attachment.
An early fusion intermediate conformation of the SARS-CoV-2 spike protein induced by ACE2 binding is uncovered. AL5E is an engineered protein that targets this structure, exhibits potent inactivation of ACE2-using coronaviruses, and inhibits their infection, thus revealing a new class of anti-coronavirus targets.
A natural variation in COOL1, a negative regulator of cold tolerance, leads to its gene suppression by upstream bZIP transcription factor, thereby improving cold tolerance for high-latitude adaptation in maize.
Most land plants form symbioses with microbes to acquire nutrients and restrict infection by pathogens. A single pair of LysM receptors mediates dosage-dependent perception of different chitin oligomers to precisely discern symbiotic and pathogenic microbes in M. paleacea, enabling terrestrialization.
iMARS was developed as a standardized framework to advance multienzyme spatial optimization from trial and error to a rational design paradigm, with demonstrated applications in biomanufacturing and PET plastic biodegradation.
Metagenomic sequencing of 1,648 sediment samples from 6–11 km water depths, including the Mariana Trench, highlights the hadal microbial ecosystem and its environmental driving forces.
Genomic analysis of the amphipod Hirondellea gigas revealed population homogeneity within the Mariana Trench but genetic differentiation between nearby hadal features. Multi-omics analysis showed that host-symbiotic interactions contribute to its adaptation to high-pressure and food-limited hadal environments.
Genome assemblies from 11 deep-sea fishes, representing key lineages, reveal a convergent rtf1 gene mutation that affects transcriptional efficiency. Additionally, biochemical measurements challenge the assumption that TMAO content consistently increases with depth, suggesting a more complex mechanism of adaptation.
High-throughput experimental validation of genetic variants linked to eight psychiatric disorders reveals the regulatory mechanisms underlying variants with pleiotropic and disorder-specific effects.
In a population-based cohort of 191 children with diverse solid tumors, systems-level analyses unravel immune variation with age and tumor type and provide a reference for future precision immunotherapies tailored for the evolving immune systems of children.
Combining affinity purification with precision mass spectrometry and AI-driven molecular docking defines the network of endogenous protein-metabolite interactions in Escherichia coli.
Khan et al. outline key challenges in studying solute carrier (SLC) proteins, critical gatekeepers of metabolism, and propose directions for understanding their functions in physiology and disease.
RNA plays a central role in protein biosynthesis and performs diverse regulatory and catalytic functions, making it essential for all processes of life. Like DNA, RNA is constantly subjected to damage from endogenous and environmental sources. However, while the DNA damage response has been extensively studied, it was long assumed that RNA lesions are relatively inconsequential due to the transient nature of most RNA molecules. Here, we review recent studies that challenge this view by revealing complex RNA damage responses that determine survival when cells are exposed to nucleic acid-damaging agents and promote the resolution of RNA lesions.
Research on the molecular genetic basis for cardiomyopathies, primary heart muscle disorders, has made significant progress in the past decades. This article reviews current understanding of the genetic underpinnings of inherited cardiomyopathies and discusses future therapeutic opportunities.
The ongoing circulation of 2.3.4.4b H5N1 avian influenza virus, highlighted by recent cattle outbreaks, poses a significant threat to both animal and public health. Structural insights uncover the molecular mechanisms behind the receptor-binding properties of bovine H5N1 to human and bovine tissues, providing critical insights into its transmission potential and public health risks.
Cone-shaped HIV-1 capsids with largely intact lattices accumulate at and pass through nuclear pores in primary human macrophages. The nuclear pores can crack open upon passage of the HIV-1 capsid, possibly to relieve a steric blockage of capsids inside pores.
High-resolution cryo-EM structures and biochemical data reveal the dynamic process by which the ABCH transporter binds and transports lipid substrates and insecticides across cell membranes while detoxifying insecticides, providing atomic-level insights for the development of arthropod pest control agents and strategies for managing pesticide resistance.
Plant intercellular communication is regulated via tubular ER-PM membrane contact through PI4P and MCTP protein tethers.
HNRNPK condensates change material properties when interacting with Xist RNA, thereby facilitating incorporation of silencing factors and spreading in cis of Xist ribonucleoprotein complexes across the X chromosome.
Beyond its role as RNA m6A writer, METTL3-METTL14 can mediate 5mC deposition on DNA by recruiting the DNA methyltransferase DNMT1 to chromatin. The two marks co-orchestrate the expression of key genes in differentiating ESC, allowing proper exit from pluripotency.
Lymph node swelling is a well-known symptom of infection. A shift in the chemoattractant code controls lymphocyte recruitment from blood into inflamed lymph nodes, allowing lymphocytes to accumulate so that even rare antigen-specific cells can encounter their activating antigen.
Computational methods were used to design mosaic nanoparticle vaccines displaying receptor-binding domains of SARS-CoV-2 variants and sarbecoviruses. Immunization of naive and pre-vaccinated mice elicited more potent cross-reactive antibody responses against SARS-CoV-2 variants and sarbecoviruses with spillover potential compared with previous nanoparticles.
By analyzing the cervicovaginal microbiome across the entire natural history of incident Chlamydia trachomatis (CT) infection among Black and Hispanic adolescent and young adult women in NYC, researchers can better understand associations between the cervicovaginal microbiome and CT infection risk, likelihood of reinfection, pelvic inflammatory disease, and miscarriage.
A metagenome-informed metaproteomics approach unravels the interplay between the host, gut microbiome, and diet in animal models as well as in human cohorts and identifies disease biomarkers of dysbiosis and gut disorders.
Valeros et al. identify rhodoquinone (RQ), an electron carrier present in mammalian mitochondria, that can deliver electrons to fumarate instead of O2 as the terminal electron acceptor. The authors develop tools to reprogram the ETC to the RQ/fumarate pathway, conferring resistance to hypoxia in vitro and in vivo.
The Human Microbiome Compendium is a unified database of publicly available human gut microbiome 16S samples, built with the integrated data from hundreds of independent projects. The compendium is used to quantify variation in gut microbiome composition across the globe.
A Newcastle disease virus engineered to enhance anti-tumor immune responses provided a 90% rate of disease control in a clinical trial of 20 patients with diverse refractory cancer types and with distant metastases.
Organelle proteomics defines the cellular landscape of protein localization and highlights the role of subcellular remodeling in driving responses to perturbations such as viral infections.
Mapping transcription start sites across five mammalian species before, during, and after embryonic genome activation unveils widespread transposable element-driven transcription and co-option of evolutionary old elements for genome regulation.
Jheannelle Johnson is a winner of the fifth annual Rising Black Scientists Awards for a scholar in the life and health sciences. We asked emerging Black scientists to tell us about their scientific vision and goals, experiences that sparked their interest in science, how they want to contribute to a more inclusive scientific community, and how these all fit together on their journey. This is her story.
Kenna Gloria Agbugba is a winner of the fifth annual Rising Black Scientists Awards for a scholar in the physical, data, earth, and environmental sciences. We asked emerging Black scientists to tell us about their scientific vision and goals, the experiences that sparked their interest in science, how they want to contribute to a more inclusive scientific community, and how these all fit together on their journey. This is her story.
Victor Ekuta is a winner of the fifth annual Rising Black Scientists Awards for a scholar in the life and health sciences. We asked emerging Black scientists to tell us about their scientific vision and goals, the experiences that sparked their interest in science, how they want to contribute to a more inclusive scientific community, and how these all fit together on their journey. This is his story.
Nyasha Milanzi is a winner of the fifth annual Rising Black Scientists Awards for a scholar in the physical, data, earth, and environmental sciences. We asked emerging Black scientists to tell us about their scientific vision and goals, experiences that sparked their interest in science, how they want to contribute to a more inclusive scientific community, and how these all fit together on their journey. This is her story.
The incidence of early-onset colorectal cancer (EO-CRC) is surging, and by 2030, one-third of all CRCs will occur before the commonly recommended screening age of 50 years. The time required for EO-CRC to reach the metastatic stage is unknown, yet this knowledge is critical to tailor early-diagnosis screening strategies. Here, Mauri, Patelli, et al. discuss how defining a key biological feature of EO-CRC may be central to protecting young adults from an alarming and probably unprecedented tumor epidemic.
Pathogen-derived cyanide in the environment is detected and detoxified by C. elegans parents, generating a byproduct that acts as an intergenerational signal to protect progeny from infection.
Norepinephrine oscillations during NREM sleep drive synchronized changes in cerebral blood volume and cerebrospinal fluid, promoting glymphatic clearance. Optogenetic and pharmacological manipulations confirm that vasomotion, regulated by norepinephrine, acts as a pump for brain fluid transport.
Single-cell measurement of the Huntington’s disease-causing CAG repeat reveals that somatic expansion of this repeat drives pathological changes in neurons, providing insights into disease progression, with implications for therapeutics in HD and potentially other DNA-repeat expansion disorders.
Trans-ancestry GWAS of major depression identifies 697 genetic variants and 308 genes, implicating neural and molecular mechanisms and drug repurposing opportunities.
Structures of GPR4 from Mus musculus and Xenopus under various pH conditions are solved to elucidate the common and distinct activation mechanisms of protonation-induced GPR4 from different species. Evolutionary analysis and functional study identify that the GPR4 receptor from Xenopus has a distinct optimal pH activation profile associated with its adaptation to aquatic life.
Howard et al. combine mechanistic deep mutational scanning, cryo-EM, and constant-pH molecular dynamics simulations to provide a holistic view of proton activation in human pH-sensitive GPCRs.
The cryo-EM structure and mutational analysis of the Nipah virus polymerase complex identify features critical for RNA replication and transcription with the potential to aid in the development of antivirals.
High-resolution imaging reveals that areas within the host cell cytoplasm, where viral proteins accumulate, undergo significant structural and physical transformations over the course of the Ebola virus life cycle. The changes to these “viral factories” drive the replication and spread of Ebola viruses in the host.
Shedu is a single-component prokaryotic defense system that provides immunity against bacteriophages, using the tetrameric protein SduA that recognizes and nicks free DNA ends. The DNA end-sensing mechanism of Shedu reinforces the principle of molecular pattern recognition that underpins innate immunity in all domains of life.
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