Browse Articles

A highly active Burkholderia polyketoacyl-CoA thiolase for production of triacetic acid lactone

Abstract Triacetic acid lactone (TAL) is a versatile platform chemical traditionally biosynthesized via decarboxylative Claisen condensation by 2-pyrone synthase. However, this route is limited by poor efficiency and dependence on malonyl-CoA. Here, we show that non-decarboxylative Claisen condensation by polyketoacyl-CoA thiolases offers a more efficient alternative. Through mining homologs of a previously reported enzyme from Cupriavidus necator , we identify five thiolases with TAL production activity. One candidate, BktBbr from Burkholderia sp. RF2-non_BP3, exhibits approximately 30-fold higher activity in vitro and supports 30-fold higher TAL titers in Escherichia coli compared to the original enzyme. Fed-batch fermentation achieves titers up to 2.8 g L⁻¹. Structural analysis of BktBbr co-crystallized with CoA esters guides rational engineering to further enhance performance. Our discovery of a highly active thiolase establishes an alternative enzymatic route to produce TAL efficiently, providing a scalable foundation for sustainable biomanufacturing.

Interoception vs. Exteroception: Cardiac interoception competes with tactile perception, yet also facilitates self-relevance encoding

Internal bodily signals, notably the heartbeat, influence our perception of the external world—but the nature of this influence remains unclear. Different frameworks, originating in opposing views of the function of interoception, have developed largely in parallel. One line of evidence (Internal/External Competition) indicates that interoceptive and exteroceptive inputs compete for neural resources. Another line (Self-related Facilitation) shows a link between interoceptive and self-related processing, which might include computing the self-relevance of exteroceptive inputs. We contrasted these accounts within a single experimental task for which they yielded distinct predictions. We measured heartbeat-evoked potentials (HEPs, a measure of cardiac interoception) with electroencephalogram and manipulated the self-relevance of an audio-tactile stimulus by placing the audio source either inside or outside the peripersonal space immediately around the body. On the one hand, prestimulus HEP amplitudes over the somatosensory cortex were linked to slower reaction times and affected audio-tactile stimulus-evoked responses in the same area, indicating competition for shared neural resources. On the other hand, prestimulus HEPs over integrative sensorimotor and default-mode network regions facilitated stimulus self-relevance encoding, both in reaction times and audio-tactile evoked responses. Importantly, Competition and Facilitation effects were spatially and statistically independent from each other. We therefore reconcile the two views by showing the coexistence of two independent mechanisms: one that allocates neural resources to either internal bodily signals or the external world, and another by which interoception and exteroception are combined to determine the self-relevance of external signals. Our results highlight the multidimensionality of HEPs and of internal states more generally.

A hybrid BiLSTM-CNN approach for intrusion detection for IoT applications

Chemical reprogramming of fibroblasts into retinal pigment epithelium cells for vision restoration

LUMINIDEPENDENS orchestrates global transcriptional repression in <i>Arabidopsis</i>

Genomic integrity is constantly challenged by transcription/replication conflicts, a major source of replication stress and instability across all life forms. While extensive studies have elucidated mechanisms for resolving transcription/replication conflicts in animals, yeast, and prokaryotes, their counterparts in plants remain largely unexplored. Through a forward genetic screen, we identified LUMINIDEPENDENS (LD), previously known for its role in regulating the flowering repressor FLC , as a key factor in mitigating replication stress in plants. Notably, transcriptomic analyses reveal that LD loss results in the upregulation of over half of the Arabidopsis genes, placing LD as a global transcriptional repressor. Consistent with this role, LD directly binds a substantial portion of the Arabidopsis genome and interacts with the MED18 subunit of the Mediator complex to modulate RNA polymerase II phosphorylation. These findings uncover a fundamental function of LD in fine-tuning transcription at a genome-wide scale, with potentially an additional role in suppressing transcription–replication conflicts by locally dampening transcription and promoting replication fork progression. Our work highlights an intriguing genome-protective strategy in plants, that could shed light on mechanisms involved in transcription–replication conflict management in eukaryotic systems.

UIGen: a hybrid framework for underwater image encryption based on evolutionary chaotic system and multi-domain transformation

Quantum-inspired superposition and nonseparable states of reconfigurable metasurfaces in classical systems

Glycoside hydrolase–mediated glucomannan catabolism in <i>Segatella copri</i> , a target of microbiota-directed foods for malnourished children

Evidence is emerging that perturbed postnatal gut microbiota development is causally related to childhood undernutrition. Clinical trials in undernourished Bangladeshi children found that a polysaccharide-rich, microbiota-directed complementary food (MDCF-2) designed to repair this perturbation produced superior ponderal and linear growth compared to a standard ready-to-use supplementary food. Subsequent analyses disclosed several candidate bioactive polysaccharides in the MDCF and their bacterial targets, notably strains of Segatella copri that possess carbohydrate-active enzymes (CAZymes) organized into polysaccharide utilization loci (PULs) targeting these glycans. A Bangladeshi S. copri isolate (BgF5_2) containing these PULs metabolized MDCF-2 glycans and promoted MDCF-dependent weight gain in a gnotobiotic mouse model emulating the clinical trials. Identifying prebiotic mixtures that mimic the effects of MDCF-2 would offer new options for treatment and prevention. Here, we describe a CAZyme-based approach to characterize the effects of glucomannan, a component of MDCF obtainable from sustainable sources, on growth and gene expression in S. copri BgF5_2 in vitro and in gnotobiotic mice. Biochemical characterization of purified CAZymes expressed by two of its MDCF-2 and glucomannan-targeted PULs disclosed a multifunctional GH26|GH5_4 CAZyme, inducible by glucomannan, that degrades several bioactive MDCF-2 glycans; glucomannan, arabinoxylan, xyloglucan, and mixed-linkage β-glucan. Our data suggest that this CAZyme functions as a multisubstrate “sentinel” that can produce diverse oligosaccharides from a variety of β-linked glycans, with each oligosaccharide able to induce corresponding PULs and non-PUL enzymes. This observation, plus the restricted distribution of the multifunctional CAZyme among S. copri strains, may partially explain strain responsiveness to MDCF-2.

Social inequities in the transition to environmentally optimized commuting

Self-driving lab discovers principles for steering spontaneous emission beyond conventional Fourier optics

Abstract We develop an autonomous experimentation platform to accelerate interpretable scientific discovery in ultrafast nanophotonics, targeting a novel method to steer spontaneous emission from reconfigurable semiconductor metasurfaces. Despite the potential of reconfigurable semiconductor metasurfaces with embedded sources for spatiotemporal control, achieving arbitrary far-field control remains challenging. Here, we present a self-driving lab (SDL) platform that addresses this challenge by discovering the governing equations for predicting the far-field emission profile from light-emitting metasurfaces. We discover that both the spatial gradient (grating-like) and the curvature (lens-like) of the local refractive index are key factors in steering spontaneous emission. The SDL employs a machine-learning framework comprising: (1) a variational autoencoder for generating complex spatial refractive index profiles, (2) an active learning agent for guiding experiments with real-time closed-loop feedback, and (3) a neural network-based equation learner to uncover structure-property relationships. The SDL demonstrates up to a four-fold enhancement in peak emission directivity (up to 77%) over a 74° field of view within ~300 experiments. Our findings reveal that combinations of positive gratings and lenses are as effective as negative lenses and gratings for all emission angles, offering a novel strategy for controlling spontaneous emission beyond conventional Fourier optics.

RETRACTED: A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest cancer survival rates. Recent studies using RAS inhibitors have opened the door to more efficacious therapies, although their beneficial effect is still limited mainly due to the rapid appearance of tumor resistance. Here, we demonstrate that genetic ablation of three independent nodes involved in downstream (RAF1), upstream (EGFR), and orthogonal (STAT3) KRAS signaling pathways leads to complete and permanent regression of orthotopic PDACs induced by KRAS/TP53 mutations. Likewise, a combination of selective inhibitors of KRAS (RMC-6236/daraxonrasib), EGFR family (afatinib), and STAT3 (SD36) induced the complete regression of orthotopic PDAC tumors with no evidence of tumor resistance for over 200 d posttreatment. This combination therapy also led to significant regression of genetically engineered mouse tumors as well as patient-derived tumor xenografts (PDX) in the absence of tumor relapses. Of importance, this combination therapy was well tolerated. In sum, these results should guide the development of new clinical trials that may benefit PDAC patients.

Association of HLA class I allele and tuberculosis susceptibility: a systematic review and meta-analysis

A Pseudomonas aeruginosa quorum-sensing inducer controls lung permeability in establishing chronic infection via EGFR

Intercellular diffusion of cyclic nucleotides followed by gap junction closure restarts meiosis in mouse preovulatory follicles

Signaling by luteinizing hormone (LH) in the outer granulosa cells of mammalian ovarian follicles causes meiosis to resume in the oocyte, located ~10 cell layers away, preparing the oocyte for ovulation and fertilization. This long-distance communication is accomplished by cAMP and cGMP diffusion through gap junctions, but knowledge of cAMP dynamics in the oocyte is based on static measurements, and information about cAMP changes in the granulosa cells has not been integrated with information about cAMP changes in the oocyte. By simultaneous multihour imaging of both compartments of live ovarian follicles, using mice expressing an improved cAMP sensor, we elucidate how the meiosis-activating signal is transmitted. In response to LH, cAMP generated in the granulosa cells diffuses within ~10 min to the oocyte. cAMP in the granulosa cells then remains high for at least 5 h, but over a 3-h period, cAMP in the oocyte decreases to a new plateau level below the original baseline. We show that the cAMP decrease in the oocyte depends not only on the established mechanism of LH lowering cGMP in the oocyte, which relieves inhibition of the PDE3A phosphodiesterase in the oocyte, but also on the subsequent LH-induced closure of gap junctions between the granulosa cells. This closure prevents cAMP from diffusing into the oocyte from the granulosa cells, a concept that has been proposed but not previously tested. We conclude that LH coordinates changes in both cGMP and gap junctions to lower cAMP in the oocyte, reinitiating meiotic progression.

Highly transparent dye-sensitized solar cells with UV-absorbing fluorene dyes and tetramethylthiourea electrolytes

Inherent instability of simple DNA repeats shapes an evolutionarily stable distribution of repeat lengths

Abstract Using the Telomere-to-Telomere reference, we assemble the distribution of simple tandem repeat lengths present in the human genome. Analyzing over three hundred mammalian genomes, we find remarkable consistency in the shape of the distribution across evolutionary epochs. All observed genomes harbor an excess of long repeats, which are potentially prone to developing into repeat expansion disorders. We measure mutation rates for repeat length instability, quantitatively model the per-generation action of mutations, and observe the corresponding long-term behavior shaping the repeat tract length distribution. We find that short repetitive sequences appear to be a straightforward consequence of random substitution. Evolving largely independently, longer repeats (above roughly 10 nt) emerge and persist in a rapidly mutating dynamic balance between expansion, contraction, and interruption. These mutational processes, collectively, are sufficient to explain the abundance of long repeats, without invoking natural selection. Our analysis constrains properties of molecular mechanisms responsible for maintaining genome fidelity that underlie repeat instability.

Hot electron–driven tandem CO ₂ reduction and propane dehydrogenation over plasmonic black gold nanoreactors

Catalytic CO 2 reduction into value-added products is an energy-intensive process and typically relies on molecular hydrogen as reductant. Coupling CO 2 reduction with propane dehydrogenation for in situ hydrogen generation presents a sustainable alternative but conventionally demands high temperatures, causing undesirable side reactions such as cracking and coke formation. Here, we demonstrate a nonthermal catalytic pathway driven by hot electrons generated via localized surface plasmon resonance. Using a plasmonic catalyst comprising Ga–Ni–Mn active sites anchored on broadband plasmonic “black gold,” we achieve tandem CO 2 reduction and propane dehydrogenation under visible-light irradiation. The catalyst consistently produces equimolar amounts (~1,600 µmol g −1 h −1 ) of CO and propene under flow conditions, maintaining exceptional stability even after 500 h. Notably, light illumination suppresses undesired side reactions, such as dry reforming of propane, cracking, and coking, preserving a stable stoichiometric ratio of CO and propene. Mechanistic studies, including controlled thermal experiments, Arrhenius analysis, and finite-difference time-domain simulations, confirm that catalytic selectivity and stability originate specifically from plasmon-induced hot electrons rather than photothermal effects. Comprehensive structural characterization using X-ray absorption near-edge structure and extended X-ray absorption fine structure, in situ diffuse reflectance infrared Fourier transform spectroscopy, ultrafast transient absorption spectroscopy, and density functional theory calculations elucidate that plasmonic excitation promotes advantageous charge-transfer states within Ga–Ni–Mn ensembles, facilitating selective activation of CO 2 and propane. This study establishes hot electron–driven plasmonic catalysis as a distinctive strategy for tandem propane dehydrogenation and circular CO 2 utilization under mild conditions.

Barriers to assistive technology uptake among persons with disabilities in selected urban districts in Ghana

Comparing pedestrian safety between electric and internal combustion engine vehicles

Abstract Vehicle electrification has become a major strategy for mitigating transport carbon emissions. Concerns have been raised about electric vehicle’s safety impacts due to their quieter driving and heavier weight compared to conventional internal combustion engine vehicles. This research utilizes Great Britain’s STATS19 road safety database to understand the pedestrian safety implications of electric vehicles. We show that the pedestrians are no more likely to collide with a fully (battery) electric vehicle compared to a conventional vehicle. In case of a collision, pedestrians are no more likely to be severely injured by an electric vehicle either. Hybrid electric vehicles have a higher pedestrian casualty rate – possibly related to their driving pattern – but the associated pedestrian injuries are less severe than those with internal combustion engine vehicles.

Structure of human green cone opsin yields insights into mechanisms underlying the rapid decay of its active, signaling state

Cone opsins enable daylight vision and color discrimination. Like their dim-light cousin rhodopsin (Rho) found in rod cells, they use a covalently attached retinal ligand to sense light and initiate visual phototransduction by activating G proteins. Unfortunately, we know less about their structural properties, in part because their activated state is unstable—cone opsins release their retinal agonist within seconds after light activation, ~100× faster than Rho. To determine what causes this rapid release and how it affects G protein activation, we solved the structure of active-state, wild-type human green cone opsin (GCO WT ) stabilized with a mini-G protein and then compared its structural and biophysical properties to Rho. Our results reveal unique features in the active-state GCO WT structure. These include i) a larger water channel connected to a larger retinal binding cavity, ii) a larger “hole” near the retinal Schiff base that could facilitate both retinal escape and water access; and iii) a potential anionic residue, E102, that lies within ~3.6 Å of the Schiff base. Our biophysical assays show that neutralizing E102 (mutant GCO E102Q ) slows retinal release (~8×) from the receptor and increases G protein activation. Surprisingly, our kinetic studies suggest that entropic factors are the main cause for the faster retinal release from activated GCO WT . These unique attributes in GCO WT likely facilitate its function in bright daylight. These results support the proposal that rapid retinal release from an active-state cone opsin helps prevent signal saturation and enables rapid resetting of the receptor.