Search

The ratio between the levels of two synaptic proteins in cerebrospinal fluid predicts future cognitive resilience versus decline among presymptomatic individuals and individuals with early Alzheimer’s disease harboring amyloid and tau pathology.

Nature Biotechnology’s annual survey highlights university startups that are, among other things, rethinking how to deliver gene-editing therapy and tackling various metabolic conditions, immune disorders and cancer with microbiome treatments or immunotherapy. Michael Eisenstein, Ken Garber, Esther Landhuis, Caroline Seydel and Laura DeFrancesco report.

Authors report MagNet, a plasma extracellular vesicle (EV) enrichment strategy using magnetic beads. Proteomic interrogation of this plasma EV fraction enables the detection of proteins that are beyond the dynamic range of mass spectrometry of unfractionated plasma.

Surgical nerve injuries can cause significant morbidity, yet no approved fluorescent agents exist for visualization. Here, the authors show in a Phase I multi-site trial that bevonescein was safe, established optimal dosing and timing, and provided a fluorescence signal for intraoperative nerve identification.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Deep phenotyping of responses to carbohydrate meals and mitigators revealed interindividual differences in postprandial glycemic responses that reflect underlying metabolic physiology, such as insulin resistance and beta cell dysfunction.

Analysis combining multiple global tree databases reveals that whether a ___location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.

Neuropixels 1.0 NHP is a 45-mm, high-density silicon probe capable of recording large numbers of neurons with single-neuron resolution from most areas in a macaque’s brain.

Crystal structures of HIV Env trimer with native glycosylation in complex with neutralizing antibodies reveal a glycan shield of high-mannose and complex-type N-glycan and indicate a path for germline-targeting vaccine design.

Standard approaches for identifying pleiotropic genetic variants may lead to spurious results. Here the authors present a new statistical method and show that it uncovers five genes linked to metabolites in METSIM participants, which were previously undetected by existing methods.

A biomimetic multicomponent sensor design enables continuous analyte detection in the bloodstream.

Glycosylation of human IgG antibodies in bacterial hosts has proven challenging. Here, the authors identify a bacterial enzyme enabling E. coli to glycosylate IgGs at native sites, thereby advancing therapeutic antibody development in this host.

Human enhancers contain a high density of sequence features that are required for their normal in vivo function.

Two BCMA-targeted CAR T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have been approved for the treatment of multiple myeloma (MM). Here the authors report distinct expansion, phenotype, function, and toxicity of cilta-cel vs. ide-cel CAR T cells in a realworld cohort of patients with MM.

Nature Biotechnology’s annual survey highlights academic start ups that are, among other things, correcting misfolded or disordered proteins, creating second-generation GPCR agonists, building a new gene delivery platform and mining cancer genomes for novel targets.

A method, RARE-seq, for sensitive detection of cell-free RNAs in blood is demonstrated to have diverse clinical applications including diagnosing and characterizing human cancers, and tracking response to RNA therapeutics.

The discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing through cellular differentiation at scale.

Here the authors engineer a bispecific antibody (Ab) for HIV-1 by combining a gp41 N-heptad repeat targeting Ab with a CD4 binding Ab. Prepositioning via CD4 binding results in high neutralization breadth and potency, and experiments in HIV infected humanized male mice show reduction of viral load.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

Analysis of data on six stable crops, capturing two-thirds of global crop calories, allows estimation of agricultural impacts and the potential of global producer adaptations to reduce output losses owing to climate change.

Genetic and physical maps for the 16 chromosomes of Saccharomyces cerevisiae are presented. The genetic map is the result of 40 years of genetic analysis. The physical map was produced from the results of an international systematic sequencing effort. The data for the maps are accessible electronically from the Saccharomyces Genome Database (SGD: http://genome-www.stanford.edu/Saccharomyces/).

Hematopoietic stem cells (HSCs) differentiate into multiple lineages, with such capacity impacted by aging. Here the authors identify Kit^lo HSCs as a functionally distinct population that exhibits distinct lymphoid-primed chromatin landscapes, which drive enhanced lymphoid reconstitution capacity, and is altered in aged hosts.

Efficient sunlight-to-fuel conversion requires materials that produce long-lived charges, but increasing carrier lifetimes in visible-light-active photocatalysts has proven difficult. Now it has been shown that rapid charge deactivation via metal-centred states prevents long lifetimes and limits photocatalytic performance. These insights bridge solid-state and molecular photochemistry, informing strategies for improved photocatalyst design.

ACTA2 p.R179 variants cause pediatric strokes due to moyamoya disease (MMD)-like occlusions. Here, the authors show that Acta2^R179C/+ smooth muscle cells are immature, causing MMD-like lesions that are reversed by altering cellular metabolism.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Transcriptomic and proteomic analyses show that high levels of the extracellular-matrix protein osteopontin are associated with the attenuated foreign-body response elicited by breast silicone implants wrapped with acellular dermal matrix.

Neurodegenerative diseases are linked to changes in the immune system and inflammation. Here, the authors studied immune cells from healthy individuals and neurodegenerative diseases and identified sex-specific disease-associated changes.

Transcriptomic and proteomic analyses of cells and matrix along the fibrotic trajectory in mouse lung identified PI16 as an anti-fibrotic factor with potential for therapeutic application in humans.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Blood plasma protein data was combined with machine learning models for a simple method to determine differences in organ-specific aging; the study provides a basis for the prediction of diseases and aging effects using plasma proteomics.

Ark⁺, a fully open artificial intelligence foundation model, demonstrates exceptional capabilities in diagnosing common, rare and novel thoracic diseases.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Despite exhibiting ferroelectric features, SrTiO₃ fails to display long-range polar order at low temperatures due to quantum fluctuations. An ultrafast X-ray diffraction experiment now probes polar dynamics of this material at the nanometre scale.

Measuring pharmacodynamics (PD) is vital for drug development but traditional PD studies are labor and resource intensive. Wu et al. introduce a kinase-modulated bioluminescent indicator for noninvasive visualization of Akt-related drug PD in living animals.

Functional, tumour-promoting GABAergic neuron-to-glioma synapses in diffuse midline gliomas are identified.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Metal carbonyl complexes show photoreactivity interesting for catalytic and biological applications. Here the authors capture the structural dynamics of the photodissociation of iron pentacarbonyl in real space and time using ultrafast X-ray scattering.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Using deep sequencing of human carotid plaque cells from male and female patients with carotid stenosis, Sukhavasi et al. identify sex-biased cell-type-specific gene-regulatory networks and different phenotypes in smooth muscle cells, including an osteogenic phenotype in females and a chondrocytic phenotype in males.

Staphylococcus epidermidis induces a potent, durable and specific antibody response that is conserved in humans and non-human primates, and which could be redirected against pathogens as a new form of topical vaccination.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Circulating tumor DNA (ctDNA) allows genotyping of the tumor in multiple myeloma. Here, the authors show that minimal residual disease (MRD) by ctDNA can be detected after CAR-T therapy correlates with bone marrow-based MRD to track clonal evolution and inform treatment resistance mechanisms.

JAK inhibitors display very good clinical responses in patients with myeloproliferative neoplasms, irrespective of JAK2 mutational status. Here, the authors discover that JAK inhibitors exert their anti-tumorigenic effects by targeting the bone marrow stroma and non-malignant hematopoietic cells instead of the oncogenic signaling in myeloproliferative neoplasms.