Browse Articles

Efficient detection of intrusions in TON-IoT dataset using hybrid feature selection approach

Assessing conformation validity and rationality of deep learning-generated 3D molecules

Design and implementation of an open-access arsenic biosensor

Local PI(4,5)P2 synthesis by septin-associated PIPKIγ isoforms controls centralspindlin association with the midbody during cytokinesis

Abstract Cytokinesis critically depends on phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ]. Synthesis of PI(4,5)P 2 is crucial for several stages of cytokinesis, including actomyosin ring assembly and constriction, membrane tethering of spindle microtubules, and midbody organization. How these activities of PI(4,5)P 2 are spatiotemporally controlled is unknown. Here we unravel a crucial function for local PI(4,5)P 2 synthesis at the ingressed cleavage furrow by septin-binding isoforms of PIPKIγ to control midbody formation. We demonstrate that loss of PIPKIγ isoforms perturbs cytokinesis by impairing septin association with microtubules, and anillin and septin deposition at the intercellular bridge and at the midbody. This mechanism requires the ability of PIPKIγ isoforms to synthesize PI(4,5)P 2 and to associate with septins. Septins and PIPKIγ further synergize to promote centralspindlin recruitment to the midbody. Our findings establish septin-associated PIPKIγ isoforms as spatiotemporal controllers of midbody organization during cytokinesis that act through generating a local pool of PI4,5P 2 at the ingressed cleavage furrow.

Integrin αv contributes to the regulation of vascular smooth muscle cell stiffness

Abstract Arterial stiffening is influenced by the organization of focal adhesions in vascular smooth muscle cells (VSMCs). We investigated the contribution of α v integrins to both arterial wall stiffness (Young’s modulus measured by echography) and VSMC stiffness (assessed by atomic force microscopy). Mice with VSMC-specific deletion of α v integrins (α v SMKO ) were compared with controls at baseline and following angiotensin II infusion. Unstimulated cultured α v -deficient (α v -KD) VSMCs exhibited higher stiffness than controls, with a further increase after angiotensin II. To interpret AFM measurements performed at shallow indentation depths, we developed a computational model of VSMC nanoindentation. Simulations showed that higher apparent Young’s moduli at shallow indentation fall within the experimental range of α v -KD cells. These cells also displayed enhanced actin polymerization, further amplified by angiotensin II through the formation of cortical F-actin. In vivo, arterial pressure and wall elastic modulus were similar between α v SMKO and control mice at baseline and after angiotensin II, despite α v SMKO mice exhibiting lower elastin and higher collagen content under angiotensin II. Together, these findings indicate that the comparable increase in arterial stiffness observed in α v SMKO mice under angiotensin II is driven primarily by elevated VSMC stiffness resulting from cortical actin redistribution, which outweighs extracellular matrix changes.

Synthesis of 2D amorphous carbons via energy-autonomous carbonization of polyaniline upon decomposition of HClO₄

Abstract Despite centuries of advancement, the synthesis of carbon materials remains heavily reliant on energy-intensive thermal processes. Conventional methods require external heating for prolonged periods to overcome high energy barriers, posing challenges for sustainable large-scale production. Here we show an energy-autonomous synthesis pathway that utilizes the intrinsic chemical energy stored within a polyaniline-HClO 4 composite. Triggered by mild thermal, microwave, or mechanical stimulation, the precursor undergoes a rapid exothermic self-propagation driven by the explosive decomposition of perchlorate species. This single-step process, completed in ≈0.4 s, simultaneously generates intense localized heat and a massive volume of gas, which forcibly exfoliates and carbonizes the polymer into interconnected 2D amorphous carbon nanosheets. We demonstrate that this energy-efficient method achieves carbon conversion efficiencies comparable to traditional pyrolysis. Furthermore, the reaction intensity is precisely tunable via the precursor water content, ensuring potential for safe industrial scale-up. This approach also enables the atomic-level incorporation of transition metals, creating a versatile platform for the design of catalysts for oxygen and carbon dioxide reduction reactions. This work provides a scalable, energy-autonomous pathway for carbon synthesis and offers a platform for the precise construction of catalytic architectures.

Microbiome by transcriptome interactions triggered by a switch to an alternative diet in Nellore cattle

Adgrg6/Gpr126 is required for compact wall integrity and establishing trabecular identity during cardiac trabeculation

Abstract How adhesion G protein-coupled receptors (aGPCRs) control development remains unclear. aGPCR Adgrg6/Gpr126 has been associated with heart trabeculation. Defects in this process cause cardiomyopathies and cardiac dysfunction. How cardiomyocytes attain trabecular identity is poorly understood. Here, we show that different domains of Gpr126 distinctly regulate compact wall integrity and trabecular identity. Maternal zygotic (MZ) gpr126 stl47 early truncation mutants exhibit hypotrabeculation, whereby N-cadherin distributes randomly along apical/basal/lateral membranes of compact layer cardiomyocytes. In contrast, zygotic and MZ gpr126 st49 mutants, expressing a N-terminal fragment lacking the GPS motif (NTF ΔGPS ), exhibit a multilayered ventricular wall containing polarized cardiomyocytes with normal N-cadherin localization and increased Notch activity. Notably, endocardially expressed gpr126 C-terminal fragment (CTF) reinstates trabeculation in gpr126 st49 mutants. Collectively, our data reveal domain-specific roles of Gpr126 during trabeculation, whereby the NTF is required for maintaining cell-cell adhesion and compact wall integrity, whereas the CTF is essential to provide trabecular identity.

Zero electromagnetic coupling of closely spaced identical helical resonators

Abstract The interaction between closely spaced elements in an electromagnetic array typically leads to significant inter-element coupling, altering the resonance properties of each element. This coupling influences, often limiting the performance of metamaterials, filters, and phased arrays. In this study using both numerical simulations and experimental validation, we explore the electromagnetic coupling between identical helical microwave resonators and demonstrate how, under specific geometric conditions, near-zero coupling can be achieved even at highly sub-wavelength separations ( $$<\frac{\lambda }{10}$$ ). Experimental samples are produced using 3D-printed molds subsequently filled with low-melting-point Field’s metal, enabling precise and repeatable resonator construction. The numerical analysis is further extended to infinite periodic chains of identical helices, revealing that similar geometric conditions enable control over propagating mode dispersion, including near-zero group velocity.

Interleukin-10 expressing B lineage cells in visceral adipose tissue protect against aging-related insulin resistance and extend lifespan

The antioxidant capacity and in-vitro anticancer effects of Artocarpus lakoocha Roxb. against laryngeal cancer cells

Trifunctional flavoenzyme-catalyzed asymmetric 4-alkyl-butenolide assembly in avenolide biosynthesis

G-quadruplexes self-assembled from nucleotide monomers as stable prepolymer scaffolds in aqueous environments

Abstract Life is composed of genetic and functional polymers, such as nucleic acids. For life to have emerged, a prebiotic mechanism for assembling these polymers is essential. In a prebiotic environment teeming with diverse organic molecules, selecting, concentrating and bringing together only relevant building blocks poses a significant challenge. G-quadruplexes, a secondary structure of DNA and RNA, are known to self-assemble from nucleotide monomers, creating an ideal preassembly for nucleotide polymerization. We investigate the detailed structure of self-assembled G-quadruplexes using high-resolution atomic force microscopy (AFM) measurements in solution. We show that G-quadruplexes of nucleotide monomers are stable on surfaces in aqueous solution at concentrations orders of magnitude below their solubility limit. When subjected to cycles of evaporation and rehydration at elevated temperatures, the G-quadruplexes partially transform into extended, RNA-like structures, also stable on surfaces in solution, consistent with a polymeric nature. G-quadruplexes self-assembled from nucleotide monomers could have served as persistent prepolymer scaffolds, providing genuine molecular selectivity in prebiotic environments.

Pan-RAF inhibitor exarafenib targets BRAF class II/III NSCLC and reveals ARAF-KSR1 resistance and combination strategies

Abstract Oncogenic BRAF mutations, including those in non-small cell lung cancer (NSCLC), are classified as Class I, II, or III. While approved therapies exist for BRAF Class I mutants, no approved therapies exist for Class II and III BRAF-mutated NSCLC. Analysis of a circulating tumor DNA database reveals Class II and III mutations comprise ~65% of BRAF-mutant NSCLC cases, with Class II patients showing worse outcomes than Class I. Exarafenib, a distinct pan-RAF inhibitor, demonstrates potent activity against BRAF Class II and III mutant preclinical models and initial clinical activity. Resistance studies reveal rewiring to an ARAF-mediated bypass pathway, characterized by RAS-mediated ARAF-KSR1 complexes maintaining MAPK signaling despite pan-RAF inhibitor treatment. RAS or MEK inhibition co-targeting is effective against this resistance mechanism. This study provides preclinical rationale for clinical testing of exarafenib in BRAF Class II/III cancers and unveils RAS-mediated ARAF-KSR1 complex formation as a resistance mechanism and rational co-therapy strategies.

In silico discovery of natural compound-derived multi-target inhibitor for Huntington’s disease therapy

FANCD2 restrains fork progression and prevents fragility at early origins upon re-replication

An aquaculture simulator for rainbow trout (Oncorhynchus mykiss) based on a fish schooling behavioral model and a dynamic energy budget

Abstract Aquaculture is increasingly important for meeting the rising global demand for seafood. To improve the sustainability of the aquaculture industry, there have been increasing efforts to develop smart aquaculture technologies, including simulation methods, to optimize growth and feeding strategies. This study developed a simulation model, which incorporates a fish behavior model based on the Boids model and a dynamic energy budget, for the purpose of improving the efficiency of rainbow trout ( Oncorhynchus mykiss ) aquaculture. The proposed simulation method predicts the growth trajectories of individual fish and evaluates the effects of different feeding levels on fish growth and feed efficiency. The simulation results were compared with those of a live rearing experiment to evaluate its accuracy. Rainbow trout growth trajectories were accurately predicted. However, longer-term simulations showed increasing divergence between the simulated and experimental data. The proposed simulation method allows the optimization of growth and feeding efficiency under various feeding strategies. Further refinements of the simulation model, including considering density effects and parameter adjustments, may lead to more accurate long-term predictions. The simulation-based approach developed in this study will contribute to a better understanding of rainbow trout growth, with potential applications for other aquaculture species and contexts.

Cross ionization mode chemical similarity prediction between tandem mass spectra in metabolomics

Abstract Mass spectrometry is a cornerstone of untargeted metabolomics, enabling the characterization of metabolites in both positive and negative ionization modes. However, comparisons across ionization modes have remained a substantial challenge due to the distinct fragmentation patterns produced by each polarity. To overcome this barrier, we present MS2DeepScore 2.0, a machine learning-based model to predict chemical similarity between mass fragmentation spectra, which works both between different and the same ionization modes. We demonstrate the utility of MS2DeepScore 2.0 in three case studies, where MS2DeepScore enabled cross-ionization mode molecular networking, enhancing data exploration and metabolite annotation. To ensure robustness, we have implemented a quality estimation method that flags spectra with low information content or those dissimilar to the training data, thereby minimizing false predictions. Altogether, MS2DeepScore 2.0 extends our current capabilities in organizing, exploring, and annotating untargeted metabolomics profiles.

Systematic review and meta-analysis of the spatio-temporal changes in apparent tsetse fly density in Uganda from 1980 to 2022

Convergent extreme reductive evolution in ancient planthopper symbioses

Abstract Strictly heritable endosymbiotic bacteria that provide limiting nutrients to sap-sucking hemipteran insects are known for their highly reduced genomes conserved in organization and function. Here, we show how in ancestral endosymbionts of planthoppers, Sulcia and Vidania , which have been gradually losing genes during ~263 my of co-diversification with hosts, co-infections by additional microbes and host ecological switches coincided with more dramatic genomic changes. At its extremes, this has resulted in the smallest non-organellar bacterial genomes known, at barely 50-52 kb. Such minuscule Vidania genomes evolved convergently in two planthopper superfamilies, and are strikingly similar in gene contents, including the ability to produce a single amino acid (phenylalanine) for the host. Losing many additional cell-function genes places them very close to organelles of symbiotic origin in the level of host dependence, further blurring the bacteria-organelle boundary.