Browse Articles

Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Measurement of a strong nonlinear force between superconductors compatible with the Casimir force

U.S. researchers express outrage over proposed changes to managing federal grants

White House receives 340,000 comments on rules many fear would politicize science

Intermetallic Pt3In concave tetrahedra for oxygen reduction electrocatalysis in proton exchange membrane fuel cells

A transcriptional biosensor reveals mechanisms of α-ketoglutarate signaling to chromatin

The metabolite α-ketoglutarate (αKG) is required for chromatin demethylation, but mechanisms that control αKG abundance in the nucleus are poorly defined. We designed a biosensor to monitor this metabolite pool in human cells using an αKG-responsive cyanobacterial transcription factor, NtcA, and used it to identify genes that regulate αKG in the nucleus. We defined an interorganelle pathway in which sequential mitochondrial activities of glutamic-pyruvic transaminase 2 (GPT2) and the SLC25A11 transporter supply nuclear αKG. In a mouse model of GPT2 deficiency, an inborn error of metabolism, Gpt2 loss caused histone hypermethylation in the brain and dysregulated neurodevelopmental genes. Restoring αKG counteracted these changes and promoted mouse fitness. Our work provides a tool to directly monitor nuclear αKG and reveals nuclear αKG depletion as a key pathogenic mechanism underlying GPT2 deficiency.

Amine/ammonium buffering enables efficient anti-Markovnikov hydroamination of olefins with alkylamines

Deep-sea oddities and boatloads of other new species — June’s best science images

A cinnamyl alcohol dehydrogenase–like scaffold organizes monoterpenoid indole alkaloid biosynthesis

Biosynthesis of ~3,000 monoterpenoid indole alkaloids (MIAs), including the anticancer drug vinblastine, involves the highly unstable intermediate strictosidine aglycone. Its formation by strictosidine β-glucosidase (SGD) and subsequent conversion by geissoschizine synthase (GS) occur in spatially separated compartments, representing a major biosynthesis bottleneck. Here we discover VinBLAST, a cinnamyl alcohol dehydrogenase–like protein repurposed as a scaffold for efficient processing of this labile intermediate. VinBLAST physically mediates SGD and GS interaction in the nucleus and allosterically enhances GS catalytic efficiency. VinBLAST homologs from diverse plant families enhance biosynthesis of several representative MIAs, with the production of catharanthine increased to ~160 mg L −1 in yeast, nearly 1,000-fold higher than previous studies. Our discovery provides a missing link in organizing MIA biosynthesis and enables scalable bioproduction of geissoschizine-derived therapeutics.

Alginate foraging is conserved in geographically and taxonomically distinct ruminant microbiomes

Abstract Seaweed plays a crucial role in carbon cycling and is expected to be a valuable resource for sustainable biomass, with applications in biofuel production, human nutrition, and animal feed. Although seaweed has historically been used as a feed source for livestock grazing near coastlines, the process by which it is digested in the rumen remains unknown. Here, we show how the brown alga Saccharina latissima is catabolized within the rumen ecosystem of two different ruminant species using in vivo and in vitro experimental systems. Evidence of digestion was obtained using a combination of animal models, bacterial imaging, multilayered meta-omics, and enzyme biochemistry. Our results demonstrate that geographically distinct ruminants harbor conserved alginate utilization loci, of which essential enzymes were expressed in response to S. latissima in the diet. While core enzymes involved in alginate metabolism have been maintained throughout populations, ancillary enzymes appear to be gained or lost through gene duplication or loss events. The conservation of these systems indicates that the ruminant microbiome retains a latent capacity to metabolize marine polysaccharides.

As the Arctic warms, gray whale boom turns into a bust

Scientists point to changes that jeopardize the marine mammals’ critical feeding grounds

The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation

China boosts prestigious grants for young scientists — will it ease competition?

Lymph nodes now optional

A subset of dendritic cells orchestrates the formation of tertiary lymphoid structures in tumor tissues

A generalized Knudsen theory for gas transport in disordered porous materials

Abstract Gas transport through nanoporous materials is central to membrane separations, catalysis, and energy technologies. Predicting permeability in these materials is crucial for performance evaluation and material design, but their complex porous network poses significant challenges. Here, we develop a generalized theoretical framework for Knudsen flow in random porous materials. We further derive a concise permeability equation dependent solely on two measurable structural parameters: mean pore size and porosity. Monte Carlo simulations across 5000 random porous networks with porosities ranging from 0 to 0.8 validate the theory with R 2  = 0.985. Non-equilibrium molecular dynamics simulations confirm the applicability of the theory to porous membrane materials, including polymers of intrinsic microporosity, polyamide, and zeolitic imidazolate frameworks. By accounting for molecular size effects, we extend the framework to predict gas selectivity in materials with sub-nanometer pores, showing good agreement with experimental data for weakly adsorbing gases. This work extends Knudsen theory to random porous networks and molecular-sized pores, providing a practical and accessible tool for predicting gas permeability and selectivity in nanoporous materials.

Parallel independent voltage computing along dendrites of CA3 pyramidal neurons

Dendritic computation contributes to information processing in cortical circuits. Hippocampal CA3 plays a central role in navigation, but how the dendrites of CA3 pyramidal neurons process information in vivo remains largely unknown. Using voltage imaging across dendrites and somata of CA3 pyramidal neurons during virtual reality–guided navigation in mice, we found that the dendritic arbor comprises multiple independent computational units that can dynamically couple to or dissociate from somatic activity, depending on behavioral conditions. Dendritic activity shapes subcellular representations of space, reward, and context through conditional coupling to the somatic output. Furthermore, spatially cotuned dendrites retain their coordination during sharp-wave ripples. These findings demonstrate that past, present, and future representations coexist within the dendritic arbor of CA3 pyramidal neurons, collectively shaping behaviorally relevant neuronal coding.

Structural and spectral adaptation of the seagrass Posidonia oceanica photosystem I to seabed light

Cyclic sealing and drainage on an oceanic transform fault

Oceanic transform faults have been considered conservative, shear-dominated boundaries, yet their proximity to magmatic systems implies fluid involvement. In this work, we discovered tidally modulated tremor at the Gofar transform fault along the East Pacific Rise. Tremor amplitude correlates with semidiurnal tides during periods of sparse seismicity and low in situ compressional to shear wave velocity ratio ( V p/ V s), but this correlation weakens following earthquake swarms accompanied by high V p/ V s. We propose a valve-like sealing-drainage dynamic process where sealing traps volatiles and boosts tidal sensitivity, sustaining tremor activity until rupture opens high porosity and permeability pathways, which silences tremors, triggers microseismicity, and resets the system through hydrothermal resealing. Thus, transform faults are likely permeable and tide critical, with energy release oscillating between tremors and rupture, paced by magmatic volatile supply and healing.

Mechanistic insight into signal bias by the agonist-dependent conformational dynamics of GPR84

Drying of the Aral Sea reshapes the anthropogenic carbon inventory of Central Asia

Lakes store large quantities of carbon in their sediments, contributing to climate regulation. Yet the fate of this carbon after lake desiccation remains unclear. Using a space-for-time substitution approach, combining sediment cores, carbon dioxide flux measurements, and remote sensing, we quantified organic carbon losses from the world’s largest desiccated lake, the Aral Sea. Since 1960, exposed lake bed sediments have released 204 ± 53 teragrams of carbon (Tg C), with vegetation growth offsetting less than 1%. Incorporating these emissions alters the regional carbon budget, transforming the Aral Sea basin from a presumed land-use-change carbon sink into a net source. Reflooding the sea could prevent an additional 165 ± 13 Tg C release, reframing restoration not only as an ecological and humanitarian imperative but also as a climate mitigation opportunity.

Slab stagnation sustained by wet harzburgite and dry basaltic slab assemblages