Search Results (8,270)

Chicken (Gallus gallus domesticus) domestication, likely associated with dry-rice farming in central Thailand, has led to substantial loss of ancestral immune-related genetic diversity in commercial chicken lineages. This study addresses allelic loss by providing the first comprehensive analysis of the highly polymorphic BG1 gene, an MHC-linked marker across the wild–domestic interface in Thailand and Vietnam, using high-depth Illumina amplicon sequencing. Genomic DNA from 47 Thai and Vietnamese chicken populations was extracted using a salting-out protocol following ethical sampling. Allelic variation was examined by targeting the BG1 intron 15–exon 16 region using triplicate PCR and Salus Pro NGS sequencing. Evolutionary dynamics and selection pressures were analyzed using AmpliSAS, MrBayes, and Datamonkey, while AlphaFold 3 was used to predict and validate 3D protein structures. We identified 98 novel alleles and 172 polymorphic sites within the BG1 intron 15–exon 16 region encoding an Ig-like domain. Extensive allele sharing between indigenous chickens and red junglefowl indicated strong balancing selection and trans-species polymorphism. Selection analyses showed that purifying selection conserved structural integrity at codons 9, 13, and 18, while variation at other sites enhanced immune recognition. AlphaFold 3 modeling confirmed conservation of the β-sandwich fold across variants, maintaining stability of the Immunoreceptor Tyrosine-based Inhibition Motif (ITIM). Thus, despite the regional gene flow, geographic isolation has shaped distinct signatures, as evidenced by the presence of 38 unique Thai and 9 unique Vietnamese alleles in addition to breed-specific private markers in the Betong (BG1*TH88), Decoy (BG1*TH91), and Tre (BG1*VN54) populations. A notable adaptive outlier under positive selection (ω = 1.357) was detected in the Dong Tao population, suggesting a recent selective sweep. These findings support the mission of the Siam Chicken Bioresource Project (SCBP) to utilize indigenous breeds as genetic reservoirs and provide a molecular basis for restoring resilience traits in domestic poultry to enhance global food security. Full article

Background/Objectives: tRNAs, tRNAomes, aminoacyl-tRNA synthetases (AARSs), the first proteins, ribosomes and the genetic code coevolved. We utilize sequence data to reconstruct key steps in establishing the first code on Earth. Methods: Networks were constructed to describe initial tRNAome and AARSome evolution. Results: tRNA-34 wobble and tRNA-37 modifications were necessary to evolve the code, as were additional tRNA modifications, so diverse tRNA modification enzymes (i.e., histidyl-tRNA -1 GTP synthase) are among the first proteins. tRNA-linked chemistry brought asparagine, glutamine, cysteine and possibly additional amino acids into the code. tRNA, tRNA modifications and tRNA-linked chemistry were core founding innovations for code evolution. Coevolution of AARSomes was also essential. Class II and class I AARSs have distinct folds but are nonetheless homologs by sequence. Early AARS enzymes folded around Zn motifs. Networks were generated for tRNAomes and AARSomes in ancient Archaea, because Archaea are the closest living organisms to the last universal common ancestor. Conclusions: The first code on Earth was surprisingly ordered, and the few apparent deviations from the regular order can yet be explained. Early in the evolution of the code, innovation was more strongly selected than accuracy. The code froze, however, because of evolving fidelity mechanisms. A historical record was documented in tRNA and in the genetic code structure and has been preserved in living organism sequences. AARSome structure describes the first code evolution more adequately than tRNAomes. Full article

Cardiovascular diseases have high mortality rates and present a high burden on society and the global healthcare system. A large quantity of drugs have been developed, such as aspirin, ACE inhibitors, beta-blockers, and statins. Although these traditional drugs have decreased the morbidity and mortality of cardiovascular diseases, they still have multiple limitations. Due to their shortcomings, researchers have continued to search for novel targets for drug treatment. The tripartite motif (TRIM) protein family is a superfamily with E3 ubiquitin ligase activity and involves diversified processes including proliferation, development, signal transduction, and immune regulation. The latest research has shown that TRIM proteins participate in the progression of cardiovascular diseases, such as cardiac hypertrophy, cardiac ischemia–reperfusion injury, heart failure, hypertension, atherosclerosis, and so on. In this review, we summarize the structure and function of TRIM proteins, as well as the mechanisms of their involvement in various cardiovascular diseases, aiming to raise awareness of the importance of TRIM proteins in cardiovascular disease research and treatment. Advancing our understanding of mechanisms mediated by TRIM proteins may emphasize their contributions to cardiovascular diseases and provide the opportunity to develop novel and targeted therapeutic strategies to combat cardiovascular diseases. Full article

Repeat breeder (RB) cows fail to conceive after three or more breeding attempts, yet the uterine factors contributing to this condition remain unclear. Here, we compared uterine fluid composition, endometrial cell responses to uterine fluid, and uterine microbiota between normal pregnant (Normal) and RB cows. Uterine fluid was collected from multiparous Holstein cows classified as Normal (n = 5; conception within three breeding attempts) or RB (no conception after four attempts); RB cows were classified as RB-Rec (n = 4; conceived after uterine lavage) or RB-NoRec (n = 3; did not conceive after uterine lavage). Uterine fluids were applied to bovine endometrial cells, and microbiota composition was analyzed. Concentrations of lipopolysaccharide in the uterine fluid did not differ between the three groups, and uterine fluid from both RB groups significantly increased C-X-C motif chemokine ligand 8 secretion relative to the Normal group. RNA-seq revealed distinct endometrial cell responses to RB-NoRec uterine fluid, with enrichment of immune-related pathways including phagosome, ferroptosis, and cellular senescence. Uterine microbiota profiles differed among groups, with short-chain fatty acid-producing genera (e.g., Fusicatenibacter and Dorea) predominant in Normal cows and inflammation-associated genera (e.g., Trueperella and Helicobacter) predominant in RB-NoRec cows. These data indicate that uterine fluid properties and microbiota composition vary with reproductive status and may modulate endometrial immune activation associated with fertility outcomes. Full article

IGF1 plays a critical role in cell proliferation and survival. Previous studies show that IGF1 binds to integrin αvβ3 and induces αvβ3-IGF1-IGF1R ternary complex formation. However, how IGF1 binding to αvβ3 leads to IGF1R activation is unclear. Previous studies showed that Gα13, a guanine nucleotide-binding protein of the G12 class of Gα proteins, binds to the integrin β3 tail through the EEE motif upon fibrinogen binding to integrin αIIbβ3 and induces RhoA activation. We discovered that the EEE/AAA mutation of the β3 tail inhibited IGF1-induced cell survival, suggesting that Gα13 binding to the β3 tail is required for IGF1 signaling. Since RhoA activation may not be directly involved in IGF1R activation, we studied if Gα13 binds to molecules other than RhoA. Since Gα13 binds to several cytoplasmic tyrosine kinases, we studied if Gα13 binds to the IGF1R kinase by a docking simulation. The simulation predicted that Gα13 binds to the IGF1R kinase through a new binding site. Mutating the predicted Gα13 binding site in the IGF1R kinase (residues 1020-1022) or the predicted IGF1R kinase binding site in Gα13 (residues 260-279) inhibited Gα13 binding to the IGF1R kinase, which is consistent with the docking model. Notably, the Gα13(260-279A) mutant inhibited IGF1-induced cell survival. We propose that IGF1 binding to αvβ3 induces Gα13 binding to the β3 tail and subsequent Gα13 binding to the IGF1R kinase, leading to IGF1R activation. Interestingly, Gα13(260-279A) mutation inhibited cell survival due to a constitutively active Gα13(Q226L) mutant. We propose that Gα13(Q226L) induces its effect by binding to the IGF1R kinase. We propose that the Gα13 binding site of the IGF1R kinase or the IGF1R binding site in Gα13 may be a novel therapeutic target. Full article

Chlamydia trachomatis has evolved sophisticated mechanisms to manipulate key host cell signaling pathways to facilitate its intracellular reproduction. N6-methyladenosine (m6A) in RNA is known to regulate various physiological and disease processes, and is also involved in the regulation of pathogenic and developmental processes in many pathogens. However, the specific impact of m6A modification on the intracellular growth of C. trachomatis remains poorly understood. In this study, our analysis of the m6A methylation profiles of host cell mRNAs following C. trachomatis infection revealed significant alterations in the distribution of m6A modifications, methylation motifs, and m6A-modified host target genes. We further demonstrate that chlamydial intracellular reproduction is mediated by the host methyltransferase-like (METTL) enzyme METTL14. Silencing METTL14 significantly reduced the reproduction efficiency of C. trachomatis. Mechanistically, C. trachomatis activates the Mitogen-Activated Protein Kinase (MAPK) and Phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/AKT) signaling pathways through METTL14, thereby inhibiting host cell apoptosis and promoting intracellular bacterial reproduction. Collectively, these findings identify METTL14 as a key host factor for chlamydial intracellular reproduction, providing new mechanistic insights and potential targets for therapeutic intervention. Full article

Banana productivity is severely limited by drought, yet the molecular basis of drought adaptation and endophyte-mediated stress alleviation remains poorly understood. Here, we performed a genome-wide analysis of the SQUAMOSA promoter-binding protein-like (SPL) transcription factor family in Musa acuminata and examined their transcriptional responses to drought stress and Serendipita indica inoculation. We identified 38 MaSPL genes, all encoding proteins with the conserved SBP domain and predicted nuclear localization. Phylogenetic, motif, gene structure, and collinearity analyses indicated that MaSPL genes are evolutionarily conserved, unevenly distributed across chromosomes, and expanded primarily through segmental duplication under purifying selection. Promoter analysis showed several cis-acting elements and transcription factor binding sites related to light, phytohormone, and stress signaling. Ten MaSPL genes were predicted as putative targets of miR156. qRT-PCR analysis showed that drought stress markedly downregulated the tested MaSPL genes, whereas miR156a expression increased, supporting an inverse regulatory relationship. Under drought, S. indica inoculation enhanced expression of most tested MaSPLs, restoring transcript accumulation while reducing miR156a to near-basal levels. Notable responses were observed in members of the MaSPL2, MaSPL9, and MaSPL13, respectively. S. indica improves drought tolerance by enhancing antioxidant defenses, reducing oxidative stress, and preserving photosynthetic and osmotic stability. Taken together, our results demonstrate that S. indica confers drought resilience in banana by counteracting drought-induced repression of MaSPL genes via the miR156–SPL module and by strengthening key physiological defense mechanisms. Full article

As a key figure among Japanese American artists, Yasuo Kuniyoshi attracted scholarly attention for his melancholic paintings produced during and shortly after the Second World War. Many of his works from this period portrayed somber figures in masks painted in muted color palettes. Kuniyoshi also placed his figures in bleak circus or carnival settings, imbuing these traditionally festive settings with an air of sadness. As many scholars argued, Yasuo’s solemn postwar paintings reflected the artist’s disillusionment with American society after he was labeled an “enemy alien” as a Japanese artist living in the U.S. during the Pacific War. While his postwar paintings have been extensively studied, his lithographic works remained overlooked due to their scarcity. This paper examines Kuniyoshi’s two postwar lithographs, Carnival and Mask, which follow the same carnival motifs as his late-life works, but represent a departure from his earlier artistic principles. Through the close analysis of the artist’s two lithographs and comparison to contemporary paintings, this paper argues that Kuniyoshi’s lithographs function as reflexive records of his paintings, serving as platforms for him to experiment with new artistic techniques and themes. Furthermore, examining the lithographs in the context of the artist’s full oeuvre, this paper will highlight how Kuniyoshi blurred the boundaries between artistic mediums, mirroring his broader efforts to navigate the challenges of postwar identity and artistic expression. Full article

Bovine adenovirus (BAdV) is associated with respiratory and enteric diseases in cattle. In this study, the complete genomic sequence of a novel BAdV strain (named BAdV/LN/CHN/2023) was sequenced and annotated using the next-generation sequencing (NGS) technology. The viral genome comprises 32,391 base pairs with a GC content of 44.93%, encoding 33 predicted open reading frames (ORFs), consistent with the genomic organization of mastadenoviruses. Comparative genomic analysis confirmed that BAdV/LN/CHN/2023 contains conserved structural and functional motifs characteristic of the genus Mastadenovirus. Phylogenetic analysis revealed that BAdV/LN/CHN/2023 shares low similarity with all currently recognized bovine mastadenoviruses classified by the International Committee on Taxonomy of Viruses (ICTV). In addition, an open reading frame (ORF) encoding the 146R protein was annotated in this strain; this feature has not been identified in any previously recognized bovine mastadenoviruses. This study presents the first full-length genomic sequence of a putative BAdV-11 strain, and based on ICTV criteria, we propose that this strain represents a novel mastadenovirus species, supported by phylogenetic distance and genomic divergence. Our findings expand the known genetic diversity of BAdVs and contribute to a better understanding of their evolutionary relationships. Full article

This study examines the hypothetical issue of the impact of ancient Egyptian beliefs on Africa as a whole. Several focal points are explored. These include (1). The situation of the discipline of folklore within allied academic specializations. (2). Culture diffusion within Africa, and (3). Spoken folk stories as the only field that integrates, in the space and time continuum, culture on the one hand, with its bearers/(society), on the other. (4). [Beside the] colonial past, the problem, is a result of a number of academic factors that include: (a). The establishment at universities of African studies departments that confine the continent to the sub-Saharan tier excluding Africa of the North; thus, folklore is isolated without a proper stage for studying it academically (see Dorson 1972); (b). The stereotyping concerning the capacity of scholars with unfamiliar names or recognized departmental membership as capable of dealing with theory or innovation, though some of their ideas are adopted by the famous without accrediting the source; (c). Ignoring the unfamiliarity for the family (especially under conditions of secrecy; cf. bias, ethnocentrism); and (d). Inadequacy of academic classroom pedagogy on the basics of verbal lore. Folklore in its original, mainly verbal branches, as represented by Stith Thompson’s monumental works on motif (1955–1958), and its predecessor by Antti Aarne on Type, (1910, 1928, 1961/1964), whose coverage, especially on Africa of the North, is seriously lacking in both the Type and Motif Indexes. The tracking of this line begins with recent calls for need for morphological studies of a South African tale (Dseagu [²⁰⁰¹] 2021). An association among various regions of Africa with ancient Egypt concerning mythological contacts merits this investigation. Full article

Background/Objectives: Selective inhibition of JAK1 remains a major challenge in cytokine-signaling therapeutics due to the high structural similarity of the JAK family. Here, we present an integrated computational framework that combines large-scale binding-site conformational analysis, ensemble docking, and protein–ligand interaction fingerprinting (PLIF) to elucidate the structural determinants of JAK1 selectivity and prioritize JAK1-biased scaffolds. Methods: A curated set of JAK1 and JAK2 catalytic-domain structures was clustered to capture binding-site diversity, and representative conformers were evaluated using >2300 annotated ligands. Docking performance was assessed via AUC, early enrichment metrics, and structural pose validation against experimentally resolved complexes. The workflow was subsequently applied to a library of ~6000 drug-like compounds to prioritize candidates with predicted JAK1 preference. Results: Across the ensemble, the most predictive features reliably separated active from inactive ligands (AUC = 0.78–0.82) and captured subtle, systematic rank shifts supporting the reported JAK1 bias. Interaction fingerprint analysis revealed a conserved hinge-binding motif required for potency, alongside a JAK1-enriched hotspot adjacent to Glu aD.55 that contributes to isoform discrimination. Applied to a library of ~6000 drug-like molecules, the workflow yielded 174 candidates predicted to exhibit preferential JAK1 recognition and reduced JAK2 engagement. Conclusions: These findings define the structural and physicochemical features underlying JAK1 selectivity and illustrate how ensemble-based modeling can guide the discovery of next-generation selective kinase inhibitors. Full article

Developing Pt-free electrocatalysts is the main solution for reducing the intolerable cost of hydrogen production through the hydrogen evolution reaction (HER), while sustaining rare-earth elements. Thus, we have synthesized carbon nanoflakes derived from carbon cloth doped with controllable boron atoms (Bx/C), where x refers to boron atomic contents (x = 3.42, 5.04, 9.79, and 14.64 wt.%), driven by the impregnation of carbon cloth containing polyester (CC) in an aqueous solution of boric acid, followed by drying at 80 °C for 1 h and then calcination at 500 °C for 2 h under nitrogen. The method allows the conversion of one-dimensional CC to a two-dimensional flake-like structure, in situ enriched with B-C motifs as active sites for HER. The HER performance depends on interfacial interaction of boron with carbon, but B₁/C (B = 3.42 wt %) was the optimum with a HER current of 370 mA/cm² at −0.78 V, overpotential at 10 mA/cm² (ƞ_HER@10) of 372 mV, Tafel slope of 166 mV/dec, and stability for 60 h, besides a hydrogen production rate of 1.57 mol·g⁻¹·h⁻¹ of catalyst, due to endowing surface area, intermolecular charge transfer, and electrical conductivity. The data obtained may pave the way for designing heteroatom-integrated carbon from biomass for promoting low-cost HER. Full article

The BONZAI/BON (copine) gene family encodes evolutionarily conserved proteins that modulate the balance between plant defense responses and growth. However, comprehensive identification and functional exploration of BON members have remained largely lacking in wheat. In this study, we identified 10 Triticum aestivum BON (TaBON) members, which are unevenly distributed across seven wheat chromosomes. Phylogenetic analysis clustered these TaBON proteins into two distinct groups. Gene structure and conserved motif analyses revealed high evolutionary conservation within the TaBON family. Cis-acting element analysis revealed that the promoter regions of TaBON genes are enriched with elements responsive to hormones, abiotic stress, and biotic defense signals. Expression profiling further demonstrated distinct transcriptional patterns of TaBON genes in response to infections by Puccinia striiformis f. sp. tritici (stripe rust), Blumeria graminis f. sp. tritici (powdery mildew), Fusarium graminearum, and Zymoseptoria tritici. Overall, this study presents a comprehensive analysis of the TaBON members and provides valuable molecular information for understanding its role in disease resistance. Full article

Tau is a protein associated with microtubules principally expressed in neuronal cells, where it plays a fundamental role in cytoskeleton stabilization and axonal transport. Several diseases collectively named tauopathies, such as Alzheimer’s disease, have been associated with an imbalance in the expression of alternative spliced Tau transcripts and the accumulation of hyperphosphorylated Tau, causing dysfunction and death of neuronal cells. Therefore, understanding the Tau exon splicing mechanisms may contribute to elucidating molecular factors that could underlie the development of neurodegenerative disorders. The aim of this study was to define the role of selected splicing factors in regulating Tau exon expression in cell lines and neuronal organoids. We demonstrated the role of the RNA-binding motif protein 20 (RBM20) splicing factor in regulating Tau exon 6 and exon 10, applying RNA-binding assay and qPCR analyses. Furthermore, we demonstrated that Tau expression was regulated during cerebral organoid differentiation, recapitulating in vivo Tau expression. These results suggest the feasibility of using brain organoid technology to study Tau alternative splicing during neural development, confirming that 3D cellular models could be used to study and characterize pathological processes taking place in Tau-related pathologies. Full article

The town of Guano, located in the province of Chimborazo, Ecuador, is a canton renowned for its concentration of cultural expressions related to traditional artisanal techniques, such as the production of garments and leather goods, tanning, textile weaving, products made from cabuya or totora reeds, and knotted rugs. These artisanal practices are embedded in a long-standing historical and symbolic framework, linked to processes of cultural transmission and identity reinterpretation. Furthermore, Guano has been a pivotal site in Ecuadorian archaeological history thanks to the studies of Jacinto Jijón y Caamaño (1927), who identified six cultural phases of the Puruhá culture through ceramic and stratigraphic analysis. The province has earned recognition as the “Cradle of Ecuadorian Nationality” due to its valuable archaeological heritage. However, much of the interpretation of this legacy has been constructed from colonial-era archaeological approaches, which have limited the understanding of the Puruhá worldview and generated interpretive shifts in the cultural attribution of its iconography. This research analyzes, from a semiotic and decolonial perspective, the semiotic codes present in the iconography of the Puruhá culture, observable in archaeological ceramic pieces and their reinterpretation in the Guano rugs, understood as living cultural artifacts. The analysis of the denotative and connotative levels of the graphic motifs integrates the iconographic study, Andean fractal design, and the examination of contemporary artisanal discourses. The results demonstrate the existence of a structured symbolic system, based on principles of duality, complementarity, cyclicality, and the tripartite division of the cosmos, as well as the persistence of patterns such as spirals and zoomorphic figures in current textile production. The study identifies that, despite this symbolic continuity, those who possess this knowledge often attribute these symbols to external cultural frameworks, primarily the Inca culture, which limits their potential as a resource for identity, culture, and tourism. In this sense, the research provides a situated and non-hegemonic interpretive framework that contributes to the cultural reinterpretation of the Guano knotted carpets, offering input for safeguarding intangible cultural heritage, strengthening local identity, and designing sustainable cultural interpretation strategies. Full article