Search Results (115)

The Elk Herd Optimiser (EHO) is a novel metaheuristic algorithm inspired by the reproductive behaviour of elk herds. However, it suffers from insufficient convergence accuracy and population diversity. To address these issues, this study proposes an improved EHO (IEHO). A novel individual update strategy for the breeding phase is introduced to meet the requirements of convergence speed and diversity during evolution. A new population grouping strategy is also developed to achieve a dual balance between elite guidance and spatial distribution. Cauchy distribution sampling is used to generate learning weights, and population diversity is adopted to control the step size of movement, allowing real-time monitoring and supplementation of population diversity. A differentiated learning strategy based on fitness ranking divides individuals into high-quality and ordinary categories, implementing elite guidance and swarm intelligence learning, respectively. A hybrid evolutionary mechanism, integrating reverse learning driven by generalised opposition and perturbation based on the Cauchy distribution, substantially strengthens the algorithm’s resistance to entrapment in local optima. Moreover, dimension-masked crossover operations are introduced to greatly optimise the efficiency of population information sharing. Finally, through comparative experiments to verify the overall performance of IEHO on the CEC2017 test suite, compared with other competing algorithms, IEHO achieves the highest number of optimal solutions across multiple test functions. Full article

Voltage-gated potassium channels (Kv) are a large family of potassium channels composed of 40 members across 12 subtypes. The KCNH genes encode three subfamilies of voltage-gated potassium channels: Kv10 (EAG, ether à go go), Kv11 (ERG, EAG-related gene), and Kv12 (ELK, EAG-like K). Kv channels play prominent roles in neuronal and cardiovascular systems. Mutations in Kv channels have been linked to many human diseases, such as epilepsy, heart arrhythmias, and cancers. Significant progress has been made in understanding protein structures, physiological functions, and pharmacological modifiers. However, the evolutionary history and gene expression of vertebrate KCNH genes during embryonic development remain largely unknown. We systematically identified and cloned 14 kcnh genes in zebrafish. Then, we examined the vertebrate KCNH channel evolution by phylogenetic and syntenic analyses. Our data reveal that the three subtypes of the KCNH gene family had already evolved in invertebrates, long before the emergence of vertebrates. The number of vertebrate KCNH genes increased, most likely due to whole-genome duplications (WGDs). In addition, we examined zebrafish kcnh gene expression during early embryogenesis by in situ hybridization. Each subgroup’s genes showed similar but distinct gene expression domains with some exceptions. Most of them were expressed in neural tissues. Notably, kcnh6a showed robust expression in the developing heart, consistent with its conserved role in cardiac repolarization. Additionally, a few kcnh genes were transiently expressed in non-neural tissues, such as somites and the notochord, suggesting they may have a unique role in embryonic development. Our phylogenetic and developmental analyses of KCNH channels shed light on their evolutionary history and potential roles during embryogenesis, in line with their physiological functions and human channelopathies. Full article

Reintroductions of extirpated species are an important tool in wildlife conservation. Understanding how reintroduced populations acclimatize to novel environments can lend insight into social learning that in turn is valuable for assessing reintroduction success and maximizing efficacy of subsequent efforts. During 2012, 2013, and 2014, the Virginia Department of Wildlife Resources implemented soft releases of elk (Cervus canadensis) translocated to southwestern Virginia from eastern Kentucky. We investigated home range establishment and post-release movements of these reintroduced elk (n = 60). We found adults moved farther from the release site than either yearlings or calves (F = 6.93, p = 0.001). Elk released in 2012 and 2013 took similar amounts of time to establish home ranges (median 181 days, range 108–214 days; and median 189 days, range 147–209 days, respectively), but individuals released in 2013 remained closer to the release site ($\overline{x}$ = 605.5 m, SD = 335.7 m, closer) presumably by joining established social groups. However, the 2014 cohort generally took longer to establish home ranges (median: 231 days; range: 56–258 days) and moved farthest from the release site ($\overline{x}$ = 1360.2 m, SD = 293.9 m, farther than 2012 individuals) possibly due to the larger cohort size and resulting intraspecific competition, or the earlier release date that year. Our findings suggest the number of consecutively released cohorts, the timing of the release, and the composition of age classes for released individuals are important considerations for reintroductions. Full article

In this study, we systematically analyzed the dynamic changes in chromatin accessibility and the transcriptional responses in the spleen of largemouth bass (Micropterus salmoides) following infection with iridovirus (LMBV) using the assay for transposase-accessible chromatin with sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq). Based on post-infection survival status, largemouth bass were classified into a resistant group (SR) and a susceptible group (SS). A total of 11,317 differentially accessible regions were identified between the two groups, among which the chromatin accessibility of core promoter regions was entirely increased in the SR group, suggesting that chromatin remodeling in these regions may directly participate in the transcriptional regulation of immune-related genes. Functional enrichment analysis revealed that genes associated with differentially accessible regions were significantly enriched in immune-related pathways such as autophagy, apoptosis, Toll-like receptor signaling, and NOD-like receptor signaling. Motif analysis further identified that transcription factors significantly enriched in the SR group included CTCF and heterodimers composed of multiple members of the ETS and FOX transcription factor families. Through integrative analysis, seven transcription factors (CTCF, Spi1, ETV2::FOXI1, FOXJ2::ELF1, FOXO1::ELK1, SPIC, and FOXO1::ELF1) were found to be significantly enriched in core promoter regions. To further screen for differentially expressed genes directly regulated by chromatin accessibility changes, an overlapping analysis was performed between 629 predicted target genes and 2656 differentially expressed genes (DEGs), resulting in the identification of 71 candidate genes. Among these, three immune-related genes (irf4a, btk, and nfil3-2) belonging to the ETS and FOX families were identified. This study reveals the dynamic chromatin accessibility landscape of largemouth bass in response to LMBV infection and demonstrates that increased chromatin accessibility in core promoter regions is closely associated with the resistant phenotype. Heterodimers of ETS and FOX family transcription factors may participate in antiviral immune responses by regulating the expression of key immune genes such as irf4a, btk, and nfil3-2, providing potential epigenetic molecular markers for disease resistance breeding in fish. Full article

Fetal skeletal muscle development involves coordinated interactions among myogenic, stromal, vascular, and immune compartments, yet the cellular and molecular programs guiding tissue maturation remain incompletely understood. To address this, we generated a high-resolution single-cell atlas of fetal female goat skeletal muscle and performed trajectory analysis, transcription factor activity profiling, and intercellular communication mapping. Unsupervised clustering identified RUNX2 mesenchymal progenitors, fibro-adipogenic progenitors (FAPs), myofibroblasts, endothelial cells, macrophages, differentiating myocytes, and mature skeletal muscle fibers, revealing a heterogeneous ecosystem in which stromal populations support myogenic progression and vascular and immune cells contribute to tissue organization. Pseudotime analysis traced a maturation continuum from differentiation-competent myocytes to contractile fibers, marked by sequential activation of extracellular matrix remodeling, cytoskeletal stabilization, and sarcomere assembly. KEGG and GO enrichment highlighted stage-specific engagement of ErbB, Hedgehog, and Hippo signaling, as well as cell cycle and ubiquitin-mediated proteolysis pathways, linking proliferation, differentiation, and structural maturation. Transcription factor profiling revealed early-stage proliferative and morphogenetically permissive states driven by E2F4/5, HMGA2, and HAND2, transitioning to late-stage differentiation, ECM remodeling, and tissue stabilization orchestrated by CEBPB, CREB3L1, ELK1, and E2F2. Cell–cell communication analysis showed a developmental redistribution of signaling authority, from ECM-driven, progenitor-centered networks to modular, structurally stabilized interactions. These findings define the cellular, transcriptional, and signaling framework orchestrating fetal skeletal muscle maturation. Full article

(1) Different classes of antidepressant drugs have been shown to activate lysophosphatidic acid (LPA) receptors, but their effects on the receptor signaling stimulated by LPA have not been fully investigated. In the present study, we examined the effect of the tricyclic antidepressant amitriptyline on the LPA-induced activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Rho signaling in C6 glioma cells and cultured rat astrocytes. (2) LPA receptor signaling was investigated by using Western blot and microscopic immunofluorescence assays. Rho activation was determined by a pull-down assay. (3) Amitriptyline potentiated the LPA-induced activation of ERK1/2 signaling, as indicated by the more than additive increases in the phosphorylation/activation of key components of this pathway including fibroblast growth factor 1 receptor, MEK1/2, ERK1/2, Elk-1, and cyclic AMP response element binding protein (CREB). Amitriptyline also enhanced the expression of brain-derived neurotrophic factor (BDNF) elicited by LPA. In contrast, the antidepressant failed to mimic the LPA-induced activation of Rho and Rho-dependent responses, such as the reversal of astrocyte stellation, accumulation of stress fibers, and the phosphorylation of focal adhesion kinase and myosin target subunit of myosin phosphatase isoform 1. Moreover, when combined with LPA, amitriptyline curtailed Rho activation and the Rho-mediated cellular responses. (4) These results demonstrate that in astroglial cells, amitriptyline exerts a balanced action on LPA-activated receptors by enhancing the neuroprotective ERK1/2-CREB-BDNF signaling and dampening the potentially detrimental Rho–ROCK pathway, and suggest that this unique property may contribute to the antidepressant activity of the drug. Full article

Background: A major technical challenge in single-cell transcriptomics is the absence of an integrative analytic pipeline that can simultaneously leverage gene regulatory network (GRN) architecture, AI-assisted gene panel discovery, and functional relevance analyses to generate coherent biological insights. Existing approaches often treat these components independently, focusing on clusters, marker genes, or predictive features without integrating them into a mechanistically grounded framework. Consequently, comprehensive screening that links regulatory association, gene signature screening, and functional interpretation within single-cell datasets remains limited, underscoring the need for an integrated strategy. Methods: We developed an integrative bioinformatics pipeline based on Gene regulatory network–AI–Functional Analysis (GAFA), combining latent-space integration, unsupervised clustering, diffusion pseudotime analysis, lineage-resolved generalized additive modeling, GRN inference, and machine learning-based gene panel discovery. This framework enables systematic mapping of cell-state structure, reconstruction of differentiation and effector trajectories, and identification of transcriptional and regulatory features strongly associated with clinical outcomes. As a case study, we applied the pipeline to NK cell transcriptomes from six CML patients (two early relapse, two late relapse, two durable treatment-free remission—TFR; 15 samples) collected at TKI discontinuation and 6–12 months after therapy cessation. Results: We reanalyzed publicly available scRNA-seq data from a previously published CML cohort to evaluate NK-cell transcriptional programs associated with treatment-free remission and relapse. We resolved six transcriptionally distinct NK cell states spanning CD56^bright-like cytokine-responsive, early activated, terminally mature, cytotoxic, lymphoid trafficking, and HLA-DR⁺ immunoregulatory populations, each exhibiting outcome-specific compositional differences. Pseudotime analysis revealed two major NK cell lineages—a maturation trajectory and a cytotoxic effector trajectory. TFR samples displayed balanced occupancy of both lineages, whereas early relapse samples showed marked depletion of the maturation branch and preferential accumulation in cytotoxic end states. AI-guided feature selection and random forest modeling identified an 18-gene panel that distinguished NK cells from TFR and relapse samples in an exploratory manner. Among them, CST7, FCER1G, GNLY, GZMA, and HLA-C were conventional NK-associated genes, whereas ACTB, CYBA, IFITM2, IFITM3, LYZ, MALAT1, MT2A, MYOM2, NFKBIA, PIM1, S100A8, S100B, and TSC22D3 were novel. The GRN inference further uncovered outcome-specific regulatory modules, with RUNX3, EOMES, ELK4, and REL regulons enriched in TFR, whereas FOSL2 and MAF regulons were enriched in relapse, and their downstream targets linked to IFN-γ signaling, metabolic reprogramming, and immunoregulatory feedback circuits. Conclusions: This AI-enabled single-cell analysis demonstrates how NK cell state composition, differentiation trajectories, and regulatory network rewiring collectively shape TFR versus relapse following TKI discontinuation in CML. The integrative pipeline provides a modular framework that could be extended to additional datasets for data-driven biomarker discovery and mechanistic stratification, and highlights candidate transcriptional regulators and NK cell programs that may be leveraged to improve remission durability, pending validation in larger patient cohorts. Full article

Patterns of resource selection are driven by the decision-making processes of animals occurring at multiple scales from where to establish a home range (i.e., second order selection) to which resource patches to use within the home range (i.e., third order selection). Elk (Cervus canadensis) were reintroduced to southwestern Virginia, USA, from 2012 to 2014 following successful translocations onto reclaimed surface coal mines in the region. We sought to understand how elk have acclimated following their translocation using location data from GPS-collared adult female elk (n = 33) collected from 2019 to 2022 along with remotely sensed terrain and land cover data. We utilized continuous-time movement models paired with generalized linear mixed-effects modeling to describe seasonal resource selection at second and third orders. At both scales of selection and throughout the year, female elk selected reclaimed surface mines, conifer forests, ridgetops, and areas with lower terrain roughness, while avoiding mixed hardwood and oak (Quercus spp.) forests. Unmined open land was only selected at the third order during periods of forage scarcity (i.e., winter) and increased metabolic requirements (i.e., late gestation). Although surface coal mining leaves legacy environmental impacts on the landscape, management of these sites provides benefits to elk and maintains open habitat that is otherwise limited. Full article

Oropouche virus (OROV) is an emerging zoonotic arthropod-borne virus of public health importance. The host range of OROV is largely unknown, but antibody evidence suggests that wildlife and livestock species could be susceptible hosts. To identify potential North American mammalian reservoir hosts, OROV replication curves were generated using eight cell lines derived from livestock, wildlife, and domestic animal species (cow, sheep, bison, white-tailed deer, elk, pig, horse, and dog). The virus replicated in all cell lines by 48 h post infection, except for the horse cells. OROV replication success was greatest in the bison cells followed by pig and dog cells. Moderate replication was achieved in the deer, elk, sheep, and cow cells. These results indicate that numerous animal species may be susceptible hosts for OROV, including important agricultural and wildlife species, but pathogenesis studies are required to confirm this finding. Identifying the reservoir hosts for OROV will allow livestock producers, veterinarians, and public health officials to prepare appropriate vector and disease control measures should the virus initiate an outbreak in the United States. Full article

Proton Exchange Membrane (PEM) fuel cells represent a promising clean energy technology due to their high efficiency, environmental sustainability, and wide applicability in transportation and stationary power systems. Accurate parameter extraction from PEM fuel cell models is critical for reliable performance prediction, control, and optimization. However, this task is challenging because of the nonlinear, multimodal, and highly coupled characteristics of fuel cell models. To address this challenge, this paper proposes an Enhanced Elk Herd Optimizer (EEHO), incorporating a novel best-bull–guided differential reproduction mechanism to improve search accuracy, convergence speed, and robustness. The proposed enhancement enables a portion of offspring solutions to be generated by perturbing the global best solution using scaled differences between randomly selected herd members. This mechanism strengthens exploitation around promising regions while maintaining population diversity and preventing premature convergence. The EEHO is applied to extract seven unknown parameters of PEM fuel cell models by minimizing the sum of squared errors between experimental and simulated voltage data. The effectiveness of the proposed method is validated using two commercial PEM fuel cell stacks, namely a 250 W stack and a BCS 500 W stack. Extensive comparative evaluations against the conventional Elk Herd Optimizer and several well-established methods demonstrate that the EEHO achieves superior performance in terms of accuracy, convergence speed, robustness, and statistical consistency. The proposed algorithm attains lower error values, faster convergence, and more stable performance across multiple independent runs. Furthermore, the extracted parameters produce highly accurate voltage and power characteristics, closely matching experimental observations. The results confirm that the proposed EEHO provides an efficient, reliable, and robust optimization framework for PEM fuel cell parameter extraction and offers strong potential for broader applications in energy system modeling, intelligent optimization, and renewable energy optimization problems. Quantitatively, the proposed EEHO achieved a significant reduction in the averages of the Sum of Squared Errors (SSE) of up to 24.96% and 23.29% compared with the conventional EHO for the 250 W stack and a BCS 500 W stack, respectively, demonstrating its superior accuracy in parameter estimation. To further validate the robustness and generalization capability of the proposed EEHO, two additional commercial PEM fuel cell datasets, of Ballard Mark V and Modular SR-12, are investigated and compared against several state-of-the-art optimization algorithms. The results, supported by Wilcoxon and Friedman statistical tests and boxplot analyses, confirm that EEHO consistently achieves superior accuracy, stability, and convergence reliability across different operating conditions. Full article

Treponeme-associated hoof disease (TAHD) is an emerging disease of free-ranging elk (Cervus canadensis) in the northwestern United States. Affected elk develop chronic foot lesions, lameness, debilitation, and an apparent increase in mortality, but the onset of lameness and associated changes in activity are not fully understood. We evaluated the accuracy of a newly developed leg-mounted tri-axial accelerometer monitor (Advanced Telemetry Systems) on captive elk and collected monitor-derived data to assess activity before and during an experimental TAHD challenge. Monitors provided reliable data with 85% overall accuracy of the continuous onboard classification of activity as standing, moving, or bedded against direct visual observation using seven healthy elk. Further, following TAHD challenge, monitor-derived data were able to detect that treatment elk exhibiting abnormal locomotion spent more time bedded and less time moving or standing. During the challenge period, treatment elk spent roughly 10% more of the day bedded than control elk. These findings suggest that leg-mounted activity monitors can detect changes in elk activity and may serve as a useful tool for future wildlife disease monitoring efforts. Full article

Background/Objectives: Surfactin is a biosurfactant with various biological activities, including antibacterial and anti-inflammatory properties; however, its effects on bone metabolism remain poorly understood. This study aimed to investigate the effects of surfactin on osteoclast differentiation and elucidate its underlying molecular mechanisms. Methods: RAW264.7 cells were treated with receptor activator of nuclear factor-kappa B ligand (RANKL) and surfactin, and osteoclast differentiation and maturation were evaluated by tartrate-resistant acid phosphatase and F-actin staining, respectively. Gene expression of differentiation markers was assessed using real-time reverse transcription-quantitative polymerase chain reaction, while the kinetics of intracellular signaling molecules and transcription factors were analyzed using Western blot analysis. Results: Surfactin treatment significantly inhibited osteoclast differentiation and maturation, as well as the mRNA expression of Nfatc1, Acp5, and Cathepsin K. Although surfactin did not markedly affect RANKL-induced activation of the NF-κB or MAPK-mediated signaling, it significantly suppressed the expression of c-Fos at both the mRNA and protein levels. Furthermore, surfactin attenuated the phosphorylation of Elk1, a transcription factor involved in c-Fos induction. Conclusions: Surfactin inhibits RANKL-induced osteoclast differentiation by negatively regulating the Elk1-AP-1-NFATc1 axis. Surfactin may thus be a promising therapeutic candidate for the treatment of metabolic bone disorders and inflammatory bone destruction. Full article

Data exfiltration poses a major cybersecurity challenge because it involves the unauthorized transfer of sensitive information. Intrusion Detection Systems (IDSs) are vital security controls in identifying such attacks; however, their effectiveness in cloud computing environments remains limited, particularly against covert channels such as Internet Control Message Protocol (ICMP) and Domain Name System (DNS) tunneling. This study compares two widely used IDSs, Snort and Suricata, in a controlled cloud computing environment. The assessment focuses on their ability to detect data exfiltration techniques implemented via ICMP and DNS tunneling, using DNSCat2 and Iodine. We evaluate detection performance using standard classification metrics, including Recall, Precision, Accuracy, and F1-Score. Our experiments were conducted on Amazon Web Services (AWS) Elastic Compute Cloud (EC2) instances, where IDS instances monitored simulated exfiltration traffic generated by DNSCat2, Iodine, and Metasploit. Network traffic was mirrored via AWS Virtual Private Cloud (VPC) Traffic Mirroring, with the ELK Stack integrated for centralized logging and visual analysis. The findings indicate that Suricata outperformed Snort in detecting DNS-based exfiltration, underscoring the advantages of multi-threaded architectures for managing high-volume cloud traffic. For DNS tunneling, Suricata achieved 100% detection (recall) for both DNSCat2 and Iodine, whereas Snort achieved 85.7% and 66.7%, respectively. Neither IDS detected ICMP tunneling using Metasploit, with both recording 0% recall. It is worth noting that both IDSs failed to detect ICMP tunneling under default configurations, highlighting the limitations of signature-based detection in isolation. These results emphasize the need to combine signature-based and behavior-based analytics, supported by centralized logging frameworks, to strengthen cloud-based intrusion detection and enhance forensic visibility. Full article

Background: Individual differences in immune responses to African swine fever virus (ASFV), whether induced by vaccination or natural infection, may be linked to genetic variation in the genes involved in antigen presentation. Methods: A total of nine pigs from the 112-population were selected for RNA-seq analysis. To pinpoint key transcription factors (TFs) regulating gene expression in the lymph nodes, weighted Kendall’s Tau rank correlation analysis was performed to link the TF binding potential with the extent of differential expression of target genes. Results: CD8⁺ T cells expressing a specific epitope of the ASFV p72 protein (ACD8⁺) accounted for 41% of the total CD8⁺ T cells in peripheral blood. A total of 2062 transcripts were identified as differentially expressed across the nine pigs (q-value < 1 × 10⁻⁸). Differential expression levels of the target genes for MECP2, ETS1, ZBTB33, ELK4, and E2F4 were significantly correlated with their TF binding potential (p < 0.05). Six SNPs were identified in the promoter region of ELK4. Analysis of the 112-pig population revealed that SNPs at S.-404A>G and S.-668C>T loci were significantly associated with ACD8⁺ levels (q-value < 0.01). Individuals with the AA genotype at S.-404A>G had significantly higher ACD8⁺ counts compared to those with AG and GG genotypes (q-value < 0.05). At the S.-668C>T locus, ACD8⁺ levels were highest in the CC genotype, followed by CT and TT genotypes, with CC showing notably higher ACD8⁺ counts (q-value < 0.05). Notably, the S.-404A>G site overlaps with potential binding sites for TFs FOXA2, GATAs, and TRPS1, while the S.-668C>T site lies within the binding regions for NR1H3, RARA, VDR, and NR1I3. Conclusion: These mutations may disrupt TFs binding to the ELK4 promoter, potentially reducing ELK4 expression and impairing antigen processing and presentation. Full article

Background/Objectives: GPA is a PR3-ANCA–predominant small vessel vasculitis with organ involvement. Real-world, single-centre data are needed to interpret evolving therapies and phenotype patterns in national conditions. Material and Methods: Retrospective cohort study of consecutive GPA patients managed at the National Institute of Geriatrics, Rheumatology and Rehabilitation (Warsaw, Poland) from 1 September 2010 to 1 September 2025. Data included demographics, phenotype, BVAS, organ involvement, PR3/MPO-ANCA serology, and induction/maintenance therapies. Results: Fifty patients were included (54.0% men). Mean age was 52.5 years; mean BMI was 26.15 kg/m². Ear-nose-throat (ENT) disease was frequent: rhinosinusitis 76.0%, nasal cartilage destruction 64.0%, subglottic stenosis 34.0%. Pulmonary nodules occurred in 52.0%, cavitation in 28.0%, and diffuse alveolar haemorrhage in 34.0%. Renal involvement included haematuria in 42.0%, chronic kidney disease (CKD) in 32.0%, and rapidly progressive kidney disease in 22.0%. Orbital inflammation was 36.0%, and PR3-ANCA was positive in 70.0%. All patients received glucocorticoids for induction; cyclophosphamide 28/50 (56.0%), rituximab 6/50 (12.0%), and mycophenolate with methotrexate 6/50 (32%). Maintenance therapy included methotrexate (78.0%), mycophenolate (64.0%), rituximab (52.0%), and azathioprine (12.0%). Conclusions: This Polish single-centre cohort shows an ear-nose-throat-lung-kidney (ELK)-dominant, PR3-predominant GPA phenotype and frequent but variable kidney involvement. Over 2010–2025, practice changed toward rituximab-based strategies, steroid minimisation, selective use of plasma exchange, and early avacopan uptake, with tofacitinib for maintenance therapy as a possible new therapeutic option. Full article