Search Results (147)

Background: Centromeric alpha satellite DNA is organized into higher-order repeats (HORs), whose precise structure is often difficult to resolve in standard genome assemblies. The recent telomere-to-telomere (T2T) assembly of the human genome enables complete analysis of centromeric regions, including the full structure of HOR arrays. Methods: We applied the novel high-precision GRMhor algorithm to the complete T2T-CHM13 assembly of human chromosome 21. GRMhor integrates global repeat map (GRM) and monomer distance (MD) diagrams to accurately identify, classify, and visualize HORs and their subfragments. Results: The analysis revealed a novel Cascading 11mer HOR array, in which each canonical HOR copy comprises 11 monomers belonging to 10 different monomer types. Subfragments with periodicities of 4, 7, 9, and 20 were identified within the array. A second, complex 23/25mer HOR array of mixed Willard’s/Cascading type was also detected. In contrast to the hg38 assembly, where a dominant 8mer and 33mer HOR were previously annotated, these structures were absent in the T2T-CHM13 assembly, highlighting the limitations of hg38. Notably, we discovered a novel 52mer HOR—the longest alpha satellite HOR unit reported in the human genome to date. Several subfragment repeats correspond to alphoid subfamilies previously identified using restriction enzyme digestion, but are here resolved with higher structural precision. Conclusions: Our findings demonstrate the power of GRMhor in resolving complex and previously undetected alpha satellite architectures, including the longest canonical HOR unit identified in the human genome. The precise delineation of superHORs, Cascading structures, and HOR subfragments provides unprecedented insight into the fine-scale organization of the centromeric region of chromosome 21. These results highlight both the inadequacy of earlier assemblies, such as hg38, and the critical importance of complete telomere-to-telomere assemblies for accurately characterizing centromeric DNA. Full article

Kernicterus spectrum disorder is the permanent and highly disabling neurologic sequel of neonatal exposure to hyperbilirubinemia, presenting, among other symptoms, variable and untreatable motor disabilities. To search for potential biomolecular explanations, we used a Gunn rat colony exhibiting spontaneous hyperbilirubinemia and a large variability of motor deficits on a beam-walking test. Histological and microscopic analyses confirmed worsening damage in the cerebellum (Cll; hypoplasia, increased death of neurons, and disrupted astroglial structures) and parietal motor cortex (hCtx; increased cell sufferance and astrogliosis). Clustering and network analyses of transcriptomic data reveal rearrangement of the physiological expression patterns and signaling pathways associated with bilirubin neurotoxicity. Bilirubin content among hyperbilirubinemic (jj) animals is overlapped, which suggests that the amount of bilirubin challenge does not fully explain the tissue, transcriptomic, proteomic, and neurobehavioral alterations. The expression of nine genes involved in key postnatal brain development processes is permanently altered in a phenotype-dependent manner. Among them, Grm1, a metabotropic glutamatergic receptor involved in glutamate neurotoxicity, is consistently downregulated in both brain regions both at the transcriptomic and proteomic levels. Our results support the role of Grm1 and glutamate as biomolecular markers of ongoing bilirubin neurotoxicity, suggesting the possibility to improve diagnosis by ¹H-MR spectroscopy. Full article

The foot deformation approach (FDA) estimates the ground reaction force (GRF) and moment (GRM) from kinematic data with practical accuracy, low computational cost, and no requirement for training data. Our previous study demonstrated practical estimation accuracy of the FDA under barefoot conditions. However, since the FDA estimates GRFs and GRMs based on foot deformation under body weight, there are concerns about its applicability to footwear conditions, where the foot deformation characteristics differ from those of bare feet. Following the issue, this study conducted a walking experiment at three different speeds with running shoes and sneakers to investigate the impact of footwear on GRF prediction using the FDA. The results showed that the FDA successfully provided practical accuracy when shoes were worn, comparable to that for a barefoot participant. The FDA offers advantages for estimating GRFs and GRMs for the footwear condition, while eliminating the need for collecting training data and enabling rapid analysis and feedback in clinical settings. Although the FDA cannot fully eliminate the effects of footwear and movement speed on prediction accuracy, it has the potential to serve as a convenient biomechanical-based method for estimating GRFs and GRMs during sports and daily activities with footwear. Full article

Background: The Montreal Cognitive Assessment (MoCA) is widely used to evaluate global cognitive function; however, its precision in measurement in heterogeneous populations—especially among patients with Parkinson’s disease (PD)—remains underexplored. Methods: In this multicenter cross-sectional study, we examined the psychometric properties of the Brazilian Portuguese MoCA in 484 PD patients (age range, 26–90 years; mean ± SD, 59.9 ± 11.1 years; disease duration range, 1–35 years; mean ± SD, 8.7 ± 5.4 years) using Item Response Theory (IRT). The Graded Response Model (GRM) was employed to estimate item difficulty and discrimination parameters, and differential item functioning (DIF) concerning age and education was investigated via a Multiple Indicators Multiple Causes (MIMIC) model. Results: The MoCA demonstrated essential unidimensionality and robust model fit. GRM analyses revealed that items within the Attention and Naming domains had high discrimination, indicating sensitivity to subtle cognitive deficits, while Memory items exhibited lower discrimination. Orientation items showed low difficulty thresholds, suggesting a propensity for ceiling effects. The MIMIC model further indicated that age and education significantly influenced overall scores: increasing age was associated with lower performance, whereas higher educational attainment correlated with better outcomes, particularly in Memory Recall and Executive/Visuospatial domains, even after accounting for their modest inverse relationship. Conclusions: Our findings support the validity of the Brazilian Portuguese MoCA for cognitive screening in PD while highlighting item-level biases linked to age and education. These results advocate for using education-adjusted norms and computerized scoring algorithms that incorporate item parameters, ultimately enhancing the reliability and fairness of cognitive assessments in diverse clinical populations. Full article

From a geotechnical engineering viewpoint, recycling and reuse of crushed glass and tire rubber can significantly help reduce the demand for natural resources (i.e., sand and gravel aggregates). Following an earlier study by the authors aimed at characterizing gravel–rubber mixtures (GRM), this paper focuses on the geotechnical assessment of gravel–glass–rubber mixtures (GGRM) made of recycled crushed green glass bottles and recycled granulated tire rubber. Specifically, the compaction, one-dimensional compressibility, and shear strength characteristics of GGRM prepared at 40% and 55% rubber content by volume (R_B) with varying glass content by volume (G_L) are investigated. It is found that compacted GGRM possesses high strength (i.e., friction angle ≥ 30°) and adequate compressibility, making it a suitable general and structural fill material for use in eco-friendly geotechnical applications. Full article

The human genome is widely transcribed, with part of these transcribed regions producing stably expressed protein-coding or non-coding RNAs. Long intergenic non-coding RNAs (lincRNAs) are significantly differentially expressed in various cell lines and tissues. However, the influence of their transcription events remains unclear. In this study, we constructed a human genomic interaction network and found frequent interactions between lincRNA genes and protein-coding genes that are highly related to the occupancy of RNA polymerase II on the lincRNA gene. Interestingly, in the human genome interaction networks, the degree of lincRNA genes was significantly higher than that of protein-coding genes. The promoter regions of the protein-coding genes interacting with the lincRNA genes are enriched with R-loop structures, indicating that lincRNA may influence the target genes through R-loop structures. These promoters were enriched in more transcription factor binding sites. Furthermore, the whole network and sub-network could be utilized to explore potential biomarkers of leukemia. We found that zinc finger protein 668 (ZNF668), eosinophil granule ontogeny transcript (EGOT), and glutamate metabotropic receptor 7 (GRM7) could serve as novel biomarkers for acute myeloid leukemia (LMAL). Pasireotide acetate (CAS No. 396091-76-2) represents a potential drug for LMAL patients. These results suggested that potential biomarkers and corresponding drugs for cancer could be identified based on lincRNA–promoter network/sub-network topological parameters. Full article

Social relationship recognition (SRR) holds significant value in fields such as behavior analysis and intelligent social systems. However, existing methods primarily focus on modeling individual visual traits, interaction patterns, and scene-level contextual cues, often failing to capture the complex dependencies among these features and the hierarchical structure of social groups, which are crucial for effective reasoning. In order to overcome these restrictions, this essay suggests a SRR model that integrates Gated Graph Neural Network (GGNN) and Transformer. The task for SRR in this model is image-based. Specifically, the purpose of a novel and robust hybrid feature extraction module is to capture individual characteristics, relative positional information, and group-level cues, which are used to construct relation nodes and group nodes. A modified GGNN is then employed to model the logical dependencies between features. Nevertheless, GGNN alone lacks the capacity to dynamically adjust feature importance, which may result in ambiguous relationship representations. The Transformer’s multi-head self-attention (MSA) mechanism is integrated to improve feature interaction modeling, allowing the model to capture global context and higher-order dependencies effectively. By fusing pairwise features, graph-structured features, and group-level information. Experimental results on public datasets such as PISC demonstrate that the proposed approach outperforms comparison models including Dual-Glance, GRM, GRRN, Graph-BERT, and SRT in terms of accuracy and mean average precision (mAP), validating its effectiveness in multi-feature representation learning and global reasoning. Full article

Background: The reproductive performance of water buffalo significantly impacts the economic aspects of production. Traditional breeding methods are constrained by low heritability and numerous influencing factors, making it difficult to effectively improve reproductive efficiency. Genome-wide association studies (GWAS) offer new possibilities for exploring reproductive traits in water buffalo, opening up new avenues for efficient breeding. Methods: Using whole-genome resequencing, we identified quantitative trait loci (QTLs) associated with four suggestive reproductive traits: calving interval (CI), calf birth weight (CBW), dam birth weight (BW), and age at first calving (FCA). The study focused on identifying genetic variants that influence these reproductive traits. Results: Our research identified 52 suggestive regulatory loci associated with reproductive traits in water buffalo. Based on a 50 kb interval, we annotated these loci to 58 candidate genes. These loci involve genes such as AGBL4, GRM1, NCKAP5, and NRXN1, which are primarily enriched in pathways including the FOXO signaling pathway, calcium ion pathways, estrogen signaling pathway, and phospholipase D signaling pathway. These pathways directly or indirectly regulate the reproductive efficiency of water buffalo. Conclusions: This study has revealed suggestive regulatory genes (AGBL4, GRM1, NCKAP5, NRXN1) associated with reproductive traits in water buffalo. This not only enhances our understanding of the molecular mechanisms underlying complex traits but also points towards strategies for improving the reproductive capacity of water buffalo. These findings provide a solid foundation for future breeding programs aimed at enhancing water buffalo productivity. Full article

Phenomenological models are highly effective tools for forecasting disease dynamics using real-world data, particularly in scenarios where detailed knowledge of disease mechanisms is limited. However, their reliability depends on the model parameters’ structural and practical identifiability. In this study, we systematically analyze the identifiability of six commonly used growth models in epidemiology: the generalized growth model (GGM), the generalized logistic model (GLM), the Richards model, the generalized Richards model (GRM), the Gompertz model, and a modified SEIR model with inhomogeneous mixing. To address challenges posed by non-integer power exponents in these models, we reformulate them by introducing additional state variables. This enables rigorous structural identifiability analysis using the StructuralIdentifiability.jl package in JULIA. We validated the structural identifiability results by performing parameter estimation and forecasting using the GrowthPredict MATLAB Toolbox. This toolbox is designed to fit and forecast time series trajectories based on phenomenological growth models. We applied it to three epidemiological datasets: weekly incidence data for monkeypox, COVID-19, and Ebola. Additionally, we assessed practical identifiability through Monte Carlo simulations to evaluate parameter estimation robustness under varying levels of observational noise. Our results confirm that all six models are structurally identifiable under the proposed reformulation. Furthermore, practical identifiability analyses demonstrate that parameter estimates remain robust across different noise levels, though sensitivity varies by model and dataset. These findings provide critical insights into the strengths and limitations of phenomenological models to characterize epidemic trajectories, emphasizing their adaptability to real-world challenges and their role in informing public health interventions. Full article

Adversarial attacks on visual object tracking aim to degrade tracking accuracy by introducing imperceptible perturbations into video frames, exploiting vulnerabilities in neural networks. In real-world symmetrical double-blind engagements, both attackers and defenders operate with mutual unawareness of strategic parameters or initiation timing. Black-box attacks based on iterative optimization show excellent applicability in this scenario. However, existing state-of-the-art adversarial attacks based on iterative optimization suffer from high computational costs and limited effectiveness. To address these challenges, this paper proposes the Universal Low-frequency Noise black-box attack method (ULN), which generates perturbations through discrete cosine transform to disrupt structural features critical for tracking while mimicking compression artifacts. Extensive experimentation on four state-of-the-art trackers, including transformer-based models, demonstrates the method’s severe degradation effects. GRM’s expected average overlap drops by $97.77\%$ on VOT2018, while SiamRPN++’s AUC and Precision on OTB100 decline by $76.55\%$ and $78.9\%$, respectively. The attack achieves real-time performance with a computational cost reduction of over $50\%$ compared to iterative methods, operating efficiently on embedded devices such as Raspberry Pi 4B. By maintaining a structural similarity index measure above $0.84$, the perturbations blend seamlessly with common compression artifacts, evading traditional spatial filtering defenses. Cross-platform experiments validate its consistent threat across diverse hardware environments, with attack success rates exceeding $40\%$ even under resource constraints. These results underscore the dual capability of ULN as both a stealthy and practical attack vector, and emphasize the urgent need for robust defenses in safety-critical applications such as autonomous driving and aerial surveillance. The efficiency of the method, when combined with its ability to exploit low-frequency vulnerabilities across architectures, establishes a new benchmark for adversarial robustness in visual tracking systems. Full article

The paper presents studies on the use of waste from wind turbine blades (WTBs) in the production of thermoplastic composites and regranulate-based products of acrylonitrile-butadiene-styrene (ABS) copolymers. Composites containing two types of WTB fractions (finely milled fraction—GRm and dust fraction—GRd) were produced using a co-rotating twin-screw extruder. During extrusion, different screw configurations of the plasticizing system as well as different material formulations were investigated. The studied composites contained from 10 to 70 wt% of shredded WTB, as well as up to 15 wt% of additional components, mainly those improving impact strength and processing properties. It was found that the individual WTB fractions generally deteriorate the mechanical properties of ABS. However, a composite containing 30 wt% GRm and modified with an additional 7 wt% ACM-G2 (impact modifier type) can be hot-pressed into good quality panels. It can also be successfully used to produce profiles in the extrusion process, mainly due to its significantly reduced viscosity. The studies presented in this article showed one of the possible ways of using WTB waste. It is advantageous because it uses WTB waste in a thermoplastic ABS matrix, which is also a secondary raw material. As a consequence of this, a completely new composite material based wholly on secondary raw materials can be obtained, which can be subjected to multiple processing. Full article

Natural gene variants of metabotropic glutamate receptor subtype 7 (Grm7), coding for mGluR7, affect individuals’ alcohol-drinking preference. Psychopharmacological investigations have suggested that mGluR7 is also involved in responses to cocaine, morphine, and nicotine exposures. We review the pleiotropic effects of Grm7 and the principle of recombinant quantitative trait locus introgression (RQI), which led to the discovery of the first mammalian quantitative gene accounting for alcohol-drinking preference. Grm7/GRM7 can play important roles in mammalian ontogenesis, brain development, and predisposition to addiction. It is also involved in other behavioral phenotypes, including emotion, stress, motivated cognition, defensive behavior, and pain-related symptoms. This review identified pleiotropy and the modulation of neurobehavioral processes by variations in the gene Grm7/GRM7. Patterns of pleiotropic genes can form oligogenic architectures whosecombined additive and interaction effects can significantly predispose individuals to the expressions of disorders. Identifying and characterizing pleiotropic genes are necessary for understanding the expressions of complex traits. This requires tasks, such as discovering and identifying novel genetic elements of the genetic architecture, which are unsuitable for AI but require classical experimental genetics. Full article

Background: Water buffaloes represent a crucial genetic resource for the global dairy industry, yet enhancements in their production performance remain relatively constrained. The advent of advanced sequencing technologies, coupled with genome-wide association studies (GWASs), has significantly boosted the potential for breeding superior-quality water buffalo. Methods: An integrated genomic analysis was performed on sequencing data from 100 water buffaloes, utilizing the high-quality UOA_WB_1 genome assembly as a reference. This study particularly emphasized reproduction-related traits, with a focus on age at first calving (AFC). Results: Our analysis revealed two significant single-nucleotide polymorphisms (SNPs). Based on these genetic markers, the GRM1 gene was identified as a candidate gene. This gene shows substantial involvement in various reproduction-associated pathways, including the FOXO signaling pathway, calcium signaling pathway, and estrogen signaling pathway. Conclusions: The identification of GRM1 as a candidate gene provides a robust theoretical basis for molecular breeding strategies aimed at enhancing fertility in water buffaloes. These findings offer critical scientific support for optimizing breeding programs, thereby improving overall production efficiency. Full article

Background/Objectives: The ~1.6 kb NBPF repeat units in neuroblastoma breakpoint family (NBPF) genes are specific to humans and are associated with cognitive capacity in higher primates. While the number of NBPF monomers/Olduvai sequences in humans is approximately 2–3 times greater than in great apes, the difference in copy number values of canonical NBPF 3mer Higher-order repeats (HORs)/Olduvai triplets between humans and great apes is substantially larger. This study aims to analyze the organization and evolutionary significance of NBPF 3mer HORs/Olduvai triplets in fully sequenced primate genomes. Methods: We applied the global repeat map (GRM) algorithm to identify canonical and variant NBPF 3mer HORs/Olduvai triplets in the complete genomes of humans, chimpanzees, gorillas, and orangutans. The resulting monomer arrays were analyzed using the GRMhor algorithm to generate detailed schematic representations of NBPF HOR organization. Results: The analysis reveals a distinct difference in NBPF-related patterns among these primates, particularly in the number of tandemly organized canonical 3mer HORs/Olduvai triplets: 61 tandemly organized canonical NBPF 3mer HORs/Olduvai triplets in humans, compared to 0 in chimpanzees and orangutans, and 9 in gorillas. When considering only tandemly organized 3mer HORs/Olduvai triplets with more than three copies, the numbers adjust to 36 in humans and 0 in great apes. Furthermore, the divergence between individual NBPF monomers in humans and great apes is twice as high as that observed within great apes. Conclusions: These findings support the hypothesis that the tandem organization of NBPF 3mer HORs/Olduvai triplets plays a crucial role in enhancing cognitive capacity in humans compared to great apes, potentially providing a significant evolutionary advantage. This effect complements the impact of the increased number of individual NBPF monomers/Olduvai sequences, together contributing to a synergistic amplification effect. Full article

Background/Objectives: Research on pharmacogenetic variability in response to prescribed drugs and across ethnic groups is essential for personalized medicine, particularly in admixed and unstudied populations. For the first time, this study examines CYP2D6, CYP2C9, and CYP2C19 alleles and genotypes in 197 healthy volunteers from the Dominican Republic, as part of the RIBEF-CEIBA collaborative network. Methods: The analysis focuses on the participants’ tri-hybrid genomic ancestry, with CYP alleles determined by real-time PCR and molecular ancestry inferred using 90 AIMs. Linear regression was used to associate ancestry components with CYP frequencies. Results: The average ancestry was 23.8% European, 42.6% Native American, and 33.6% African, the latter being higher than in most Latin American populations. Native American ancestry was also higher than expected. Predicted phenotype frequencies based on genotypes were 4.2% poor metabolizers (gPMs) and 3.6% ultrarapid metabolizers (gUMs) for CYP2D6, as well as 3% gPMs, 22.8% rapid metabolizers (gRMs), and 1.5% gUMs for CYP2C19. No gPM individuals were observed for CYP2C9. Certain alleles associated with decreased CYP2D6 activity (*17 and *29) and increased CYP2C19 activity (*17 and gUMs) were positively linked with African ancestry and negatively with Native American ancestry. Rare CYP2C9 alleles (*5 and *6) with clinical relevance were additionally found. Conclusions: These findings build on previous results from the RIBEF-CEIBA collaborative network, demonstrating differences in allele frequencies of CYP2D6, CYP2C9, and CYP2C19 in relation to genomic ancestry. In summary, ethnicity must be considered in the development of pharmacogenetic guidelines for clinical application, research, and regulation to avoid widening the biotechnology gap and to allow Personalized Medicine to reach the entire world population. Full article