Browse Articles

Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans

Abstract Protection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. We addressed this knowledge gap with the nematode Caenorhabditis elegans and its microbiota isolate Pseudomonas fluorescens MYb115 that is known to protect against Bacillus thuringiensis (Bt) infection. We find that MYb115-mediated protection depends on sphingolipids (SLs) that are derived from an iterative type I polyketide synthase (PKS) cluster Pf SgaAB, thereby revealing a non-canonical pathway for the production of bacterial SLs as secondary metabolites. SL production is common in eukaryotes but was thought to be limited to a few bacterial phyla that encode the serine palmitoyltransferase (SPT) enzyme, which catalyses the initial step in SL synthesis. We demonstrate that Pf SgaB encodes a pyridoxal 5’-phosphate-dependent alpha-oxoamine synthase with SPT activity, and find homologous putative PKS clusters present across host-associated bacteria that are so far unknown SL producers. Moreover, we provide evidence that MYb115-derived SLs affect C. elegans defence against Bt infection by altering SL metabolism in the nematode host. This work establishes SLs as structural outputs of bacterial PKS and highlights the role of microbiota-derived SLs in host protection against pathogens.

Caloric restriction mimetic 2-deoxyglucose alters metabolic and transcriptomic phenotype in association with changes in chromatin accessibility in human astrocytes

Abstract Caloric restriction and ketogenic diets may modify the progression of neurological disorders, including HIV-associated neurological disorders and Alzheimer’s disease, in part by influencing astrocyte function. This study examines how metabolic substrate availability affects metabolic processes and gene expression in human astrocytes. We exposed astrocytes to the glycolysis inhibitor 2-deoxyglucose (2-DG), to mimic caloric restriction, prior to stimulation with interleukin-1β and measured extracellular flux using the Seahorse ® platform. We next analyzed gene expression and chromatin accessibility changes using RNA-sequencing and ATAC-sequencing, respectively. Finally, we tested the effects of glucose deprivation and the ketone body β-hydroxybutyrate (BHB) on inflammatory gene expression. 2-DG reduced oxygen consumption rate and extracellular acidification rate in the presence of IL-1β, while concomitantly decreasing expression of pro-inflammatory cytokines TNF, IL-6, and C3. These changes were linked to altered chromatin structure. The metabolic substrate β-hydroxybutyrate was associated with reduced cytokine expression compared to glucose. Inhibition of glycolysis attenuated IL-1β-induced inflammation and gene expression changes and altered chromatin architecture. Both glucose deprivation and BHB treatment reduced inflammatory cytokine expression, with additive effects when combined with 2-DG. These results suggest that targeting glycolysis could provide therapeutic strategies for treating neurological diseases through modulation of astrocyte-driven inflammation.

Himalayan “S-type” granite generated from I-type sources

Partial melting of metasedimentary rocks is generally accepted as the source of peraluminous Himalayan leucogranites—they are commonly considered as pure “S-type” (sedimentary source) granites. Here, a uniquely comprehensive geochronological and geochemical dataset shows that partial melting of metaigneous rocks in the eastern Himalaya produced peraluminous leucogranites—these supposed S-type leucogranites have I-type (igneous) sources. Inherited magmatic zircons from leucogranites and metaigneous rocks have indistinguishable ages, trace element compositions, and Hf isotope compositions, distinct from zircons in metasedimentary rocks. Experimentally, partial melting of metagranitic rocks rather than metapelites predicts alkali major element chemistry of these leucogranites better. High δ 18 O, high 87 Sr/ 86 Sr, and low ε Nd (t) for Himalayan leucogranites have been used to argue for a metasedimentary rock source, but overlapping values occur in metaigneous rocks. Although sediment-sourced leucogranites also occur, igneous-sourced leucogranites are likely common in large hot orogens. A survey of leucogranite geochemistry across the Himalaya suggests that ~20% might be I-type, with no apparent spatial or temporal bias. I-type leucogranites appear to be rare-metal poor, however. Unlike prior assertions that I-type granites represent juvenile additions to orogens, metaigneous-sourced Himalayan granites more likely represent crustal reworking.

Modeling potential of halophytes in the production of biofuel and edible oil using linear regression and an adaptive neuro-fuzzy inference system

Can increasing the size and flexibility of a molecule reduce decoherence and prolong charge migration?

Coherent superposition of electronic states, created by ionizing a molecule, can initiate ultrafast dynamics of the electron density. Correlation between nuclear and electron motions, however, typically dissipates the electronic coherence in only a few femtoseconds, especially in larger and more flexible molecules. We, therefore, use ab initio semiclassical dynamics to study decoherence in a sequence of analogous organic molecules of increasing size and find, surprisingly, that extending the carbon skeleton in propynal analogs slows down decoherence and prolongs charge migration. To elucidate this observation, we decompose the overall decoherence into contributions from individual vibrational modes and show that: 1) The initial decay of electronic coherence is caused by high- and intermediate-frequency vibrations via momentum separation of nuclear wavepackets evolving on different electronic surfaces. 2) At later times, the coherence disappears completely due to the increasing position separation in the low-frequency modes. 3) In agreement with another study, we observe that only normal modes that preserve the symmetry of the molecule induce decoherence. All together, we justify the enhanced charge migration by a combination of increased hole-mixing and the disappearance of decoherence contributions from specific vibrational modes—CO stretching in butynal and various H rockings in pentynal.

Exhaustive analysis and simple model of an angular displacement optical fiber sensor

Abstract Accurate tilt-angle measurement is vital in applications ranging from aerospace to civil infrastructure monitoring, especially under harsh conditions where conventional inclinometers may fail. Here, we present a comprehensive analytical model for multi-axis tilt sensing based on intensity-modulated optical fiber sensors (OFDSs). By capturing how a Gaussian beam, reflected from a tilted target, couples into arrays of receiving fibers, our model bridges geometric fiber parameters, numerical aperture, and target distance to predict the measured power for various tilt angles and axes. We validate its performance experimentally using multiple fiber-bundle configurations: bifurcated, trifurcated, differential, symmetrical, and quasi–random 19-fiber arrangements, demonstrating accurate operation up to $$\pm 20^\circ$$ tilt over distances of up to 15 mm. In each case, the theoretical predictions match well with measured data, showing that differential or concentric fiber layouts suppress noise and eliminate ambiguities in tilt-direction detection. A $$\pm 5\%$$ parametric sweep shows that NA drift contributes $$\le 6\%$$ signal change, while core- and spacing-tolerances each add $$< 4\%$$ , confirming that the sensor retains its specified accuracy when fabricated with standard-spec fibers. Compared to existing fiber-optic and mechanical inclinometers, our approach is simpler to fabricate, can be tailored to specific operational ranges, and remains reasonably resilient under the tested $$\pm 5\%$$ variations. Moreover, we show how multi-fiber geometries enable axis-wise tilt discrimination and improved sensitivity through differential measurements. These findings highlight the potential for cost-effective, real-time, multi-axis tilt sensors that can address Industry 5.0 and advanced physics lab instrumentation needs. Future work will extend the sensor to larger angular spans and complex reflective surfaces, aiming to further broaden its applicability and reach.

Randomized cross-over trial comparing stress responses amongst undergraduates and surgeons with and without background music during simulated surgery

Modular arrangement of synaptic and intrinsic homeostatic plasticity within visual cortical circuits

Neocortical circuits use synaptic and intrinsic forms of homeostatic plasticity to stabilize key features of network activity, but whether these different homeostatic mechanisms act redundantly or can be independently recruited to stabilize different network features is unknown. Here, we used pharmacological and genetic perturbations both in vitro and in vivo to determine whether synaptic scaling and intrinsic homeostatic plasticity (IHP) are arranged and recruited in a hierarchical or modular manner within layer 2/3 (L2/3) pyramidal neurons in the rodent primary visual cortex (V1). Surprisingly, although the expression of synaptic scaling and IHP was dependent on overlapping signaling pathways, they could be independently recruited by manipulating spiking activity or NMDA receptor (NMDAR) signaling, respectively. Further, we found that changes in visual experience that affect NMDAR activation but not mean firing selectively trigger IHP, without recruiting synaptic scaling. These findings support a modular model in which synaptic and IHP respond to and stabilize distinct aspects of network activity.

Lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndrome

Exploring diverse supramolecular tessellation through hierarchical assemblies of nonalternant nanographene

Tessellation, as an ancient and fascinating mathematical pursuit, has not only captivated mathematicians but also has attracted chemists’ increasing attention at the molecular level in recent years. Exploring tessellation at the molecular scale is pivotal for gaining profound insights into the effects of tessellation on materials and elucidating the essential design principles for supramolecular tessellation. In this study, we develop a dynamic fullerene host ( 1 ) with three consecutive heptagons, which promotes diverse supramolecular tessellation via hierarchical assembly. In the solid state, molecule 1 arranges itself into a layered square-shaped tessellation in the crystal superstructure. Interestingly, the co-crystal structures of 1 with C 60 and C 70 exhibit highly ordered triangular and rhombic tessellation patterns, respectively, due to the adaptive regulation of heptagons with different curved guests, demonstrating the first series of layered tessellated framework in supramolecular fullerene chemistry. This work not only enriches the development of in-solution supramolecular tessellation but also facilitates the rational design of tessellated 2D layered molecular materials

Energy consumption analysis and prediction in exercise training based on accelerometer sensors and deep learning

CRISPR screen reveals a simultaneous targeted mechanism to reduce cancer cell selenium and increase lipid oxidation to induce ferroptosis

Ferroptosis is a cell death mechanism distinguished by its dependence on iron-mediated lipid oxidation. Cancer cells highly resistant to conventional therapies often demonstrate lipid metabolic and redox vulnerabilities that sensitize them to cell death by ferroptosis. These include a unique dependency on the lipid antioxidant selenoenzyme, glutathione peroxidase 4 (GPx4), that acts as a ferroptosis inhibitor. Synthetic high-density lipoprotein-like nanoparticle (HDL NP) targets the high-affinity HDL receptor scavenger receptor class B type 1 (SR-B1) and regulates cell and cell membrane lipid metabolism. Recently, we reported that targeting cancer cell SR-B1 with HDL NP depleted cell GPx4, which is accompanied by increased cell membrane lipid peroxidation and cancer cell death. These data suggest that HDL NP may induce ferroptosis. Thus, we conducted an unbiased CRISPR-based positive selection screen and target validation studies in ovarian clear cell carcinoma (OCCC) cell lines to ascertain the mechanism through which HDL NP regulates GPx4 and kills cancer cells. The screen revealed two genes, acyl-CoA synthetase long chain family member 4 (ACSL4) and thioredoxin reductase 1 (TXNRD1), whose loss conferred resistance to HDL NP. Validation of ACSL4 supports that HDL NP induces ferroptosis as the predominant mechanism of cell death, while validation of TXNRD1 revealed that HDL NP reduces cellular selenium and selenoprotein production, most notably, GPx4. Accordingly, we define cancer cell metabolic targets that can be simultaneously actuated by a multifunctional, synthetic HDL NP ligand of SR-B1 to kill cancer cells by ferroptosis.

Explainable artificial intelligence with temporal convolutional networks for adverse weather condition detection in driverless vehicles

Genomic analyses identify 15 risk loci and reveal <i>HDAC2</i> , <i>SOX2-OT</i> , and <i>IGF2BP2</i> in a naturally occurring canine model of gastric cancer

Gastric cancer ranks as the fifth most common human cancer worldwide and has a poor survival rate and limited treatment options. Despite the high prevalence and mortality rate, the genetic etiology is largely unknown. In dogs, a clinically and histologically similar disease disproportionately affects two breeds, the Belgian Tervuren and Belgian Sheepdog, which develop the intestinal and diffuse tumor subtypes observed in humans. We performed a Bayesian genome-wide association study and selection analyses in this naturally occurring canine model to elucidate underlying genetic risk factors for gastric cancer and identified 15 associated loci. Variant filtering revealed germline putative regulatory variants for the EPAS1 ( HIF2A ) and PTEN genes and a coding variant in CD101 . Two loci are overrepresented among cases of intestinal tumor subtype. Although closely related to Tervuren and Sheepdogs, Belgian Malinois rarely develop gastric cancer. Across-breed analyses uncovered haplotypes enriched in Malinois at SOX2-OT and IGF2BP2 that are at significantly higher frequency among genome-wide association study controls. Among Tervuren and Sheepdogs, HDAC2 putative regulatory variants were present at comparatively high frequency and were associated with risk of gastric cancer. Here, we describe a complex genetic architecture governing gastric cancer in a dog model, including genes such as PDZRN3 and KLHL29 , that have not been associated with human gastric cancer.

Loading of a porous rock with constant micro-seismic event rate suppresses seismicity and promotes subcritical failure

Abstract Catastrophic failure is the end result of progressive localisation of damage creating brittle failure on a variety of system scales in the Earth. However, the factors controlling this evolution, and the relationship between deformation and the resulting earthquake hazard, are not well constrained. Here we address the question of how to adapt operational controls in a strain-inducing laboratory experiment so as to minimize associated microseismicity. We simultaneously image the induced damage using x-rays at a synchrotron, and detect acoustic emissions which can be fed back to change operational controls on the experiment. We confirm that using continuous servo-control based on acoustic emission event rate not only slows down deformation compared to standard constant strain rate loading, but also suppresses events of all sizes, including extreme events. We develop a new model that explains this observation, based on the observed evolution of microstructural damage and the fracture mechanics of subcritical crack growth. The model is independently consistent with the observed stress history and acoustic emission statistics. Our results imply that including seismic event rate control may improve risk management of induced seismicity over a range of event magnitudes, if similar processes are relevant at larger scales.

Daily briefing: NIH foreign-grant cuts could leave thousands without care worldwide

Environmental DNA adsorption to chitin can promote horizontal gene transfer by natural transformation

Horizontal gene transfer by natural transformation (NT) is induced in Vibrio cholerae upon attachment to chitin surfaces in the aquatic environment. Here, we show that free environmental DNA adsorbs to chitin surfaces under physiologically realistic conditions. Using live-cell imaging and a fluorescent NT reporter, we demonstrate with cellular resolution microscopy that V. cholerae utilizes chitin-bound DNA as a reservoir for genetic exchange. Additionally, we demonstrate that uptake of DNA from this chitin-bound reservoir requires the forceful retraction of competence type IV pili. These findings uncover a role for retraction force in driving pilus-dependent NT and suggest that chitin particle surfaces can act as hotspots for horizontal gene transfer.

Modelling of an imprecise sustainable production control problem with interval valued demand via improved centre-radius technique and sparrow search algorithm

Independent transitions to fully planktonic life cycles shaped the global distribution of medusozoans in the epipelagic zone

Life history traits influence marine species dispersal and habitat colonization. Medusozoans (jellyfish and siphonophores) exhibit diverse life cycles, evolved from an ancestral cycle alternating between a benthic polyp and a pelagic medusa. Despite their ecological importance, factors shaping medusozoan distribution remain poorly understood. By integrating metabarcoding and environmental data from the Tara Oceans expedition with life history traits, we provide global evidence supporting the longstanding hypothesis that benthic polyp presence/absence is a key factor influencing the distribution and abundance of planktonic medusozoans in the surface ocean. We inferred on a time-calibrated phylogeny of Medusozoa multiple transitions to a fully planktonic (holoplanktonic) life cycle, either through polyp loss, acquisition of drifting polyps, or development of polyps parasitizing pelagic organisms. We could associate each transition with a shift toward offshore habitats and the emergence of globally dominant Operational Taxonomic Units (OTUs), whose abundance far exceeds that of any nonholoplanktonic medusozoans in the planktonic realm. The prevalence of holoplanktonic medusozoans in terms of abundance and diversity is broadly observed in coastal and offshore environments, peaking over greater bathymetric depths in tropical and subtropical regions. We show that holoplanktonic and nonholoplanktonic groups interact with distinct yet compositionally similar planktonic communities. Holoplanktonic OTUs occupy more peripheral positions in a plankton interactome, suggesting greater flexibility in biotic interactions, an adaptive trait in rapidly changing planktonic ecosystems. These findings highlight how life cycle evolution shaped the global distribution of medusozoans and suggest that variations in life history may significantly influence how medusozoans respond to global environmental changes.

Predicting drug-target interactions using machine learning with improved data balancing and feature engineering