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The first-in-human clinical trial of the LRRK2-targeting antisense oligonucleotide BIIB094 in Parkinson’s disease demonstrates that the treatment is well tolerated and produces dose-dependent reductions in cerebrospinal fluid levels of LRRK2 and phosphorylated Rab10, indicating successful target engagement.

Merlin, a vision–language foundation model trained on a large dataset of paired CT scans, patient record data and radiology reports, demonstrates strong performance across model architectures, diagnostic and prognostic tasks, and external sites.

Extensive measurements of the emissions of methane, nitrous oxide and ammonia from wastewater treatment facilities in the USA present higher values than are currently stated in national inventories. The results of this analysis show that greenhouse gas and nitrogenous emissions from the wastewater sector are often overlooked and that their impact on climate should be reassessed.

Here the authors describe a stabilization technology that engineers crosslinks between tyrosine sidechains into a natively folded vaccine immunogen and show that immunogenicity is improved in small animal models by locking the most potently neutralizing epitopes.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

Fast inactivation is characteristic of voltage-gated sodium channels. In this work, the authors show that this process occurs in two distinct, consecutive steps and propose a lock and key model for fast inactivation.

Engineering of local Anopheles gambiae under containment enables the generation of a transgenic strain equipped with non-autonomous gene drive capabilities that robustly inhibits genetically diverse Plasmodium falciparum isolates obtained from naturally infected children.

The underlying molecular mechanisms of neuroinflammation and axonal damage in progressive multiple sclerosis remains unclear. Here, authors show proteomics results of human progressive multiple sclerosis brain tissues and found extracellular matrix proteins (annexin, S100, AHNAK families) were enriched in lesions and white matter.

An artificial intelligence hardware approach that uses the adaptive reservoir computation of biological neural networks in a brain organoid can perform tasks such as speech recognition and nonlinear equation prediction.

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.

Insecticide resistance can limit the effectiveness of insecticide-treated nets for malaria prevention, but other factors such as access and durability also contribute. Here, the authors quantify impacts of this ‘cascade’ of factors using a mathematical model.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

Breugnathair elgolensis gen. et sp. nov., an early squamate identified from a newly discovered Middle Jurassic skeleton on the Isle of Skye, provides new evidence on the origins of snakes.

Oxidative catalytic depolymerization of polystyrene (PS) can produce benzoic acid, but the annual consumption of benzoic acid is ~40 times lower than PS, so benzoic acid should be converted to higher-volume chemicals for the process to be viable. Here, the authors report a hybrid chemical and biological process that uses PS as feedstock for production of adipic acid, a high-volume co-monomer for nylon 6,6, via benzoic acid.

Mathieu Lupien, Jason Moore and colleagues show that breast cancer risk–associated SNPs commonly disrupt the binding of FOXA1 to chromatin, thereby directly affecting gene expression.

Epichaperomics allow the study of protein-protein interactions and their alterations, but probes have been limited to capturing HSP90 epichaperomes. Here, the authors introduce and validate a toolset of HSP70 epichaperome ligands, and use them in epichaperomics to identify a mechanism with which cancer cells can enhance the fitness of mitotic protein networks.

Instabilities in chiral plasmas can amplify electromagnetic waves, raising the question of whether chiral solids behave similarly. Now a magneto-chiral instability is demonstrated in tellurium, observed as growing terahertz emission after photoexcitation.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

This study examines the emerging use of agentic artificial intelligence (AI) in biomedical research, highlighting the challenges and opportunities that may inform the design of agentic AI systems suitable for broad deployment.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

By studying cortical activity patterns during prey capture and spontaneous behavior in marmosets, the authors identify distinct subnetworks defined by reliable spike timing correlations. These subnetworks emerge during prey capture, with each potentially playing different roles in controlling reaching movements.

High entanglement fidelity between neutral atoms is achieved using highly excited Rydberg states. The unique electron structure provided by alkaline-earth atoms makes it a promising platform for various quantum-technology-based applications.

In a prospective study involving 92 physicians from multiple institutions, access to large language model assistance on top of conventional resources increased a score expressing the quality of their reasoning in addressing patient care while assessing five clinical vignettes.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Gut microbiota play a critical role in drug metabolism. Now, by exploring the human gut microbial metabolism of G-protein-coupled receptor (GPCR)-targeting drugs, uncommon pathways and biotransformations are elucidated, revealing how the activity of the metabolized drugs against target GPCRs is modulated.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Seven leading geneticists express their views about where the unidentified components of the heritability for complex human diseases might lie and how this could affect the underlying genetic architecture, as well as offering suggestions of how genomic research could be targeted to address this key issue.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A unified realization of the volt, ohm and ampere can be achieved by integrating a quantum anomalous Hall resistor and a programmable Josephson voltage standard in a single cryostat.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

A superconductor placed near a quantum Hall edge can show emergent excitations with a range of exotic features. For instance, such heterostructures are predicted to exhibit non-local signatures that are direct extensions of ‘Andreev reflection’.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

A critical goal in functional genomics is evaluating which non-coding elements contribute to gene expression, cellular function, and disease. Here the authors present a CRISPRi-based method using truncated guides disrupts transcription factor binding and enhancer activity across thousands of sites, expanding CRISPRi targeting scope for functional genomics and enabling efficient screening of repeated genomic elements

Allele-preferential transcription factor binding can influence pancreatic ductal adenocarcinoma risk loci function. Here, the authors show allele-specific JunB and JunD binding at chr1p36.33 and propose a role for KLHL17 in protein homeostasis by mitigating inflammation.

Oncolytic viruses create an inflamed tumour microenvironment allowing T cells to respond to immune checkpoint blockade therapy more efficiently. Authors here show that in a hepatocellular carcinoma model, a dominant anti-viral rather than anti-tumour T cell response is elicited by an oncolytic vesicular stomatitis virus, unless the virus is designed to express tumour antigens, which restores therapeutic benefit.

A scalable method for the growth of perovskite oxides thin films on silicon is desirable for integration of buffer layers in devices. Here the authors demonstrate the stoichiometric growth of thin SrTiO₃ layers on silicon at high growth rates by hybrid molecular beam epitaxy.

Unlike Amazonian forests, African forests have maintained their carbon sink until recently but by 2030 the African carbon sink will have shrunk by 14 per cent and the Amazonian sink will reach almost zero.

This Perspective highlights the existence of gaps between the computational complexity and energy efficiency required for the continued scaling of deep neural networks and the hardware capacity actually available with current CMOS technology scaling, in situations where edge inference is required; it then discusses various architecture and algorithm innovations that could help to bridge these gaps.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

An inverse design strategy is reported for the organization of nanoscale matter using DNA-programmable bonds and the fabrication of hierarchically ordered 3D assemblies.

Precolibactin 886 is a complex microbiome-derived metabolite implicated in colorectal cancer and produced by the clb gene cluster. A chemical synthesis and analysis of precolibactin 886 is reported which shows that its biosynthetic precursor degrades to other known clb metabolites. The data also provide insights into the structures and reactivity of advanced clb products.

The third variable (V3) loop on the HIV-1 Env glycoprotein is required for viral entry. Here, the authors applied DARPin technology to produce broadly neutralizing inhibitors targeting a region of V3 that becomes accessible after binding to the CD4 receptor.

The mechanisms by which noncoding genetic variation shapes tissue macrophage phenotypic diversity remain obscure. Glass and colleagues define cell-intrinsic and environmental effects contributing to genetic control of Kupffer cell transcription.