Browse Articles

Experimental and numerical investigation on mechanical properties and fracture mechanisms of deep marble under triaxial compression

Differential effects of sole and phosphorus based nitrogen fertilizer sources on wheat growth and nutrient use efficiency

Suturing fragmented landscapes: Mosaic hybrid zones in plants may facilitate ecosystem resiliency

Many widespread plant taxa of western North America have diversified into phenotypically and genetically divergent lineages due to complex biogeographic histories across heterogeneous landscapes. Mosaic hybrid zones can form when geographically co-occurring, yet environmentally distinct, lineages cross-pollinate and form hybrids that occupy unique environmental niches absent of a geographic cline. This expands the total environmental space across which parental and hybrid individuals grow, resulting in larger, less fragmented geographic distributions. Here, we highlight hybridization mosaics across three study systems containing taxa critical to widespread plant communities in western North America: Ericameria nauseosa , Artemisia tridentata , and Sphaeralcea fendleri . The systems contain diverged taxa that co-occur across the landscape and hybridize readily. Hybridization among taxa has facilitated niche expansion into intermediate environments consistent with unique combinations of adaptive genetic variation, creating more continuity within each study system—study systems occupy ~820 to 270,000 km 2 more geographic area by virtue of hybridization. Furthermore, hybrids are predicted to play important roles in future climates, as they may occupy 8 to 475% larger distributions compared to present. Convergent patterns signal mosaic hybridization as an underappreciated mechanism with broad ecological and evolutionary ramifications. Leveraging mosaic hybridization may assist the creation of restoration management plans that aim to mitigate the deleterious effects of habitat fragmentation on ecosystems in the context of climate change.

Comparative proteomics analysis of MRSA under different experimental conditions

Micro magnetic resonance spectroscopy for noninvasive metabolic screening of mammalian embryos and oocytes

Analyzing cellular health and metabolism without compromising cell integrity is a major challenge. We present a noninvasive technique using micro magnetic resonance spectroscopy (micro MRS) for nondestructive metabolic fingerprinting at the single-cell scale. This is an application of micro MRS to bovine preimplantation embryos (~8 cells) and oocytes (single cell), with measurements performed on a total of over 150 samples. Among various applications, this method holds significant potential for assisted reproductive technologies (ART), where metabolic assessments of preimplantation embryos could improve treatment outcomes. Early results indicate that classification models using micro MRS data effectively distinguish embryos with high developmental potential and show correlation with oocytes maturity. Furthermore, a multigenerational safety study in a mouse model revealed no adverse effects from embryo exposure to static magnetic field. These findings indicate that micro MRS is a promising, safe tool for assessing embryo metabolism, potentially improving the efficiency and outcomes of ART.

A note on the analysis of Herrmann–May lattices for small exponent RSA

Early-life human CD8 ⁺ T cells exhibit rapid, short-lived effector responses and a unique transcription factor landscape

Neonates and infants are distinct in their clinical and cellular responses to viral infections, with neonatal CD8 + T cells displaying innate-like characteristics and a low threshold for T cell receptor activation. However, specific molecular programs that drive these unique responses are incompletely understood, particularly in humans, and targetable pathways to modulate viral illness in this vulnerable population remain to be elucidated. Early-life immune responses may be developmentally programmed to prioritize avoidance of tissue immunopathology, especially while maternal immunoglobulin provides passive immunity. We set out to define the unique response characteristics and transcription factor landscape of neonatal human CD8 + T cells. Here, we report evidence that naïve neonatal human CD8 + T cells are poised for an accelerated effector switch, with elevations of killer cell lectin-like receptor G1 (KLRG1), killer cell lectin-like receptor B1 (KLRB1/CD161), Fc epsilon receptor I-gamma ( FCER1G ), DNAX accessory molecule-1 (DNAM1/CD226), granzymes, tumor necrosis factor alpha (TNFα), interleukin 2 (IL-2), and glycolysis compared to naïve adult CD8 + T cells. Further, rapid proliferation and cell death occur upon activation of neonatal CD8 + T cells, with cell viability largely rescued by IL-2 or IL-7. These features are coupled with a unique transcription factor landscape, including high expression of thymocyte selection associated high mobility group box (TOX) and HELIOS ( IKZF2 ), and these signatures continue in postnatal life until at least 2 mo of age. We conclude that early-life human CD8 + T cells maintain a unique transcriptional state associated with an accelerated effector switch and short-lived effector program, revealing key nodes of regulation relevant for the unique immunobiology of neonatal humans.

Improvement of osteogenic differentiation in umbilical cord-derived human mesenchymal stem cells through specific MiRNA inhibition

A trans-species cytoplasmic polymorphism is associated with seed shape and aridity across multiple species of sunflowers

The cytoplasmic genomes of plants and animals often fail to track species boundaries. However, the mechanisms responsible for such patterns are poorly understood, in part because few studies have linked cytoplasmic variation to phenotypic traits or environmental differences. Here, we use 1,554 previously published and 185 new whole genome sequences representing 14 taxa from the sunflower genus Helianthus , 91 phenotypic traits measured in common gardens, and 39 environmental variables to test for environmental and phenotypic effects of cytoplasmic genome variation. In agreement with previous work, two distinct chloroplast clades were found across multiple species and the sharing of chloroplast clades between species was mainly due to repeated introgression rather than incomplete lineage sorting. Two mitochondrial clades were also found that matched the chloroplast clades for 98% of individuals, implying predominantly maternal inheritance of both genomes. Cytoplasmic clade was associated with differences in seed shape across several species, and likely with aridity, suggestive of a role in local adaptation. Conversely, we failed to find any credible cytonuclear interactions based on associations between chloroplast and nuclear variation. Taken together, this work suggests that cytoplasmic genomes in annual sunflowers represent a trans-species balanced polymorphism that is likely maintained by adaptation to different environments. More broadly, our results corroborate the syngameon concept, showing how introgression across even very strong reproductive barriers can facilitate environmental adaptation across a species complex.

A preliminary assessment of a stool-based microRNA profile for early colorectal cancer screening

Abstract Colorectal cancer screening methods are well established worldwide as a fundamental pilar in CRC management, namely through non-invasive faecal occult blood testing. However, the limited sensitivity of faecal occult blood test for detecting precancerous lesions highlights the need to search for alternative tools, such as microRNAs (miRs). The main aim of this study was to identify stool-based miR profiles for early colorectal cancer detection. A panel with miR-21-5p, miR-199a-5p, and age showed a moderate performance for colorectal cancer detection (sensitivity: 88%). Additionally, miR-451a, miR-21-5p, miR-199a-5p, age, and gender showed high performance for discriminating high-grade dysplasia lesions (sensitivity: 91%). Moreover, when we obtained a positive result in either panel, we achieved a sensitivity of 96% for high-grade dysplasia lesions identification. Finally, when a negative result was obtained in these panels after a positive faecal occult blood test result, we accurately identified individuals without lesions. These findings demonstrate the potential of miR panels as non-invasive biomarkers for colorectal cancer and high-grade dysplasia lesions detection and could constitute a secondary screening method following a positive faecal occult blood test.

Rare variants in <i>BMAL1</i> are associated with a neurodevelopmental syndrome

Through international gene-matching efforts, we identified 10 individuals with ultrarare heterozygous variants, including 5 de novo variants, in BMAL1 , a core component of the molecular clock. Instead of an isolated circadian phenotype seen with disease-causing variants in other molecular clock genes, all individuals carrying BMAL1 variants surprisingly share a clinical syndrome manifest as developmental delay and autism spectrum disorder, with variably penetrant sleep disturbances, seizures, and marfanoid habitus. Variants were functionally tested in cultured cells using a Per2 -promoter driven luciferase reporter and revealed both loss-of-function and gain-of-function changes in circadian rhythms. The tested BMAL1 variants disrupted PER2 mRNA cycling, but did not cause significant shifts in cellular localization or binding with CLOCK. Conserved variants were further tested in Drosophila , which confirmed variant-dependent effects on behavioral rhythms. Remarkably, flies expressing variant cycle , the ortholog of BMAL1 , also demonstrated deficits in short- and long-term memory, reminiscent of the highly prevalent developmental delay observed in our cohort. We suggest that ultrarare variants in the BMAL1 core clock gene contribute to a neurodevelopmental disorder.

Influence of aging on dermal elastin fiber architecture and skin firmness assessed by finite element modeling

Abstract Skin firmness and elasticity are largely determined by the dermal extracellular matrix, particularly the elastin fiber network. Age-related degradation of elastin alters its architecture, contributing to diminished skin resilience. However, the quantitative relationship between elastin fiber geometry and macroscopic skin firmness remains incompletely understood. In this study, we developed a novel computational framework integrating realistic 3D elastin fiber geometries–extracted from confocal microscopy images of human abdominal skin samples (Caucasian females, aged 38–78 years)–into a finite element (FE) model of the dermal matrix. The elastin networks were explicitly represented as beam elements within the FE domain. Unconfined compression simulations were conducted to evaluate skin’s elastic resistance force and correlate it with quantified geometric parameters of the elastin networks. The results revealed a significant age-dependent decline in skin firmness, strongly associated with reductions in fiber diameter, fiber count, volume fraction, network connectivity (as indicated by increased fragmentation and reduced maximum cluster size), and the proportion of vertically oriented fibers. Among these, fiber count and maximum cluster size were the most important predictors of skin firmness. This study provides quantitative, mechanistic insights into how specific architectural alterations in elastin fibers directly impact the mechanical properties of aging skin. These findings emphasize the critical role of elastin network integrity and structural organization in maintaining skin function and offer a compelling rationale for therapeutic or cosmetic strategies aimed at preserving or restoring the elastin framework to maintain skin firmness.

Structural basis of auxin binding and transport by <i>Arabidopsis thaliana</i> AUX1

Indole-3-acetic acid (IAA), the major form of auxin, is essential for plant growth. Auxin resistant 1 (AUX1), the first identified auxin importer, plays a crucial role in polar auxin transport (PAT). Here, we present cryo-EM structures of Arabidopsis thaliana AUX1 in the IAA-free and IAA-bound states. AUX1 exists as a monomer that contains 11 transmembrane helices (TMs). TMs 1 to 5 and 6 to 10 constitute the two halves of a classic LeuT-fold, and TM11 interacts with both halves at the interface. In the IAA-bound state, IAA is specifically recognized in a central pocket formed by TM1, TM3, TM6, and TM8. In the presence of IAA, TM1 and TM6 undergo marked conformational changes that are critical for IAA transport. His249 stands out to be a key residue for substrate uptake and release. Our structures reveal the molecular basis for AUX1-mediated IAA binding and transport.

Investigation of ribociclib, abemaciclib and palbociclib resistance in ER+ breast cancer cells reveal potential therapeutic opportunities

Abstract The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) ribociclib, abemaciclib, and palbociclib have transformed outcomes in patients with ER+ /HER2 − advanced breast cancer (BC). However, most patients eventually progress, and therapeutic options beyond CDK4/6i are an area of ongoing investigation. Here, we generated and evaluated ribociclib, abemaciclib, and palbociclib-resistant BCs. MCF7 and T47D (ER+ /HER2−) cells were chronically treated with increasing doses of ribociclib (R), abemaciclib (A), or palbociclib (P) over 8 months (0-600 nM). CDK4/6i-resistant cell lines (MCF7rR, MCF7rA, MCF7rP, T47DrR, T47DrA, and T47DrP) were isolated and evaluated for their aggressive phenotypes, cross-resistance, transcriptomic changes, and sensitivity to volasertib (PLK1 inhibitor) and barasertib (AukB inhibitor). Immunohistochemical evaluation of CDK4, CDK6, and p53 (n = 1005) and transcriptomic evaluation of AukB and PLK1 were performed in 5031 clinical breast cancers. MCF7rR, MCF7rA, MCF7rP, T47DrR, T47DrA, and T47DrP cells manifested aggressive phenotypes such as increased spheroid formation, invasion, proliferation, and progression through the G1/S phase of the cell cycle despite CDK4/6i treatment, increased resistance to apoptosis, and cross-resistance to other CDK4/6i. Transcriptomic analysis revealed the enrichment of distinct pathways in resistant cells, particularly the upregulation of cell cycle regulatory genes such as PLK1, AukB, CDKN2B and TGFβ. PLK1 or AukB overexpressing resistant cells were sensitive to volasertib (PLK1 inhibitor) and barasertib (AukB inhibitor) therapy, which was associated with G2/M cell cycle arrest and increased apoptosis. We conclude that cell cycle upregulation leading to G2/M progression is a key route for CDK4/6i resistance. AukB or PLK1 inhibitors that block G2/M phase could be a promising strategy.

Genomic origins and evolution of neo-sex chromosomes in Pacific Island birds

The standard model of sex chromosome evolution is based on ancient XY or ZW systems. Young neo-sex chromosomes that form via the translocation of autosomal material to preexisting sex chromosomes provide materials to study early events in sex chromosome evolution. Neo-sex chromosomes are taxonomically widespread but, until recently, appeared to be rare in female-heterogametic taxa, including birds. Here, we report on the comparative evolutionary genomics of newly discovered neo-Z and neo-W sex chromosomes in two Pacific Island birds, the honeyeater species, Myzomela tristrami and M. cardinalis . Our results show that 19 to 21 Mya, ~85% of chr5 , an autosome, translocated to the pseudoautosomal region (PAR) of an ancestral sex chromosome (Z or W) and rapidly recombined onto its heterolog, leaving the remainder of chr5 to segregate as a remnant autosome. A large inversion then established a nonrecombining (NR) neo-W region and a neo-PAR. The accumulation of at least seven additional inversions created interspersed blocks of ancestral and neo-W sequence, without expanding the NR region. The neo-W experienced mass invasion by endogenous retrovirus repeats, a reduced efficacy of selection, and functional degeneration. Many of our observations are consistent with predictions of the standard model, whereas others highlight idiosyncrasies of neo-sex chromosomes that arise via translocation of autosomal sequence to ancestral sex chromosomes. We speculate, in particular, that the repository of retrotransposons on the ancestral W may have been an accelerant in the evolution of neo-W structure, content, and functional degeneration.

Gut microbiota distinguishes aging hispanics with Alzheimer’s disease: associations with cognitive impairment and severity

Larval diapause slows adult epigenetic aging in an insect model, <i>Nasonia vitripennis</i>

Epigenetic clocks based on DNA methylation provide robust biomarkers of biological age, yet the mechanistic basis and functional significance of slowing these clocks remain unclear. Progress has been limited by the lack of short-lived, genetically tractable model organisms with functional DNA methylation systems. The jewel wasp, Nasonia vitripennis , offers a unique solution. It combines a functional DNA methylation system with a short lifespan and established tools for experimental manipulation. We previously developed an epigenetic clock in Nasonia , but whether this clock reflects plastic, environmentally driven aging processes was unknown. Here, we test this directly by experimentally inducing larval diapause, a naturally occurring developmental arrest triggered by environmental cues. Diapause extended median adult lifespan by 36% and significantly slowed the rate of epigenetic aging. Using whole-genome bisulfite sequencing across multiple adult timepoints, we show that while adults that have passed through diapause as larvae initially emerge epigenetically older, their subsequent epigenetic aging proceeds 29% more slowly than adults that have not passed through diapause as larvae. Clock CpGs were enriched for gene ontology terms related to conserved nutrient-sensing and developmental pathways, including insulin/IGF signaling and mTOR, supporting the established mechanistic link between development and epigenetic aging. These findings demonstrate that epigenetic aging is plastic in Nasonia and can be experimentally modulated by early-life environment, establishing this animal model as a tractable system for dissecting the causal mechanisms of epigenetic aging.

Positive lymph node ratio as a nodal staging system to avoid stage migration between remnant and primary proximal gastric cancers

PDCSA: A parallel discrete crow search algorithm for influence maximization in social networks

The essence of the influence maximization (IM) problem is how to identify the set of seed nodes so that the node numbers ultimately affected in the network reach the maximum under a certain spreading model. In the field of influence maximization research, the investigation of seed nodes identifying algorithms is a hot yet challenging work. Although conventional greedy algorithms and heuristic algorithms have high performance, their efficiency remains a challenge when applied to large-scale social networks. In recent years, swarm intelligence-based optimization algorithms have seen increasing application in addressing this problem, with notable improvements in performance. However, the efficiency of these swarm intelligence-based algorithms still needs to be improved in large-scale social networks. Based on this issue, a parallel discrete crow search algorithm (PDCSA) designed for parallel computing is proposed. Based on the evolution characteristics, PDCSA makes full use of the efficiency advantage of parallel computing to improve the time efficiency of solving IM problems.The results of experiments conducted on six datasets show that PDCSA achieves performance comparable to state-of-the-art algorithms, with the added advantages of high efficiency and robustness.

Hardware-in-loop implementation of an adaptive MPPT controlled PV-assisted EV charging system with vehicle-to-grid integration

Abstract The penetration of electric vehicles (EVs) into society needs extensive charging infrastructure. The existing charging system solely depends on the grid supply, which is essentially fossil fuel-dependent and leads to carbon emissions and environmental pollution. This can be minimized by incorporating renewable energy into the charging grid. This article presents a charging scheme combining photovoltaic (PV) and grid, offering a clean and dependable charging plan to sustain green transport. The proposed work presents the modelling and controlling a 10 kW EV charging/discharging framework integrating PV and grid. This work has multi-fold objectives: i) the development of an intelligent hybrid maximum power point tracking (MPPT) strategy, ii) the design of a fuzzy logic controlled bidirectional charger, iii) the setup of a PV-grid integrated charging system, and iv) the implementation of vehicle-to-grid (V2G) operation. The proposed charging system utilizes PV power and seamlessly switches to grid power whenever required. Since the performance of the PV source is affected by varying temperatures and irradiance, MPPT methods are needed to extract maximum power from the PV source. This paper developed and compared perturb and observe (P&amp;O), Particle swarm optimization (PSO), and hybrid PSO + Adaptive neuro-fuzzy inference system (ANFIS) based algorithm for MPPT. The findings indicate that the PSO + ANFIS-driven method offers the highest tracking efficiency of 99.5%. This algorithm is also tested under dynamic partial shading conditions (PSC) to ensure robustness, and it led to achieving fast convergence and high efficiency despite multiple power peaks. In addition, the designed bidirectional charging system maximizes solar energy collection, minimizes the charging cost, and improves grid stability through demand balancing. The overall system is validated in a hardware-in-loop real-time environment through FPGA-based OPAL-RT.