Search Results (384)

Plants have evolved a complex, multilayered immune system that integrates molecular recognition, signaling pathways, epigenetic regulation, and small RNA-mediated control. Recent studies have shown that DNA-level regulatory mechanisms, such as RNA-directed DNA methylation (RdDM), histone modifications, and chromatin remodeling, are critical for modulating immune gene expression, allowing for rapid and accurate pathogen-defense responses. The epigenetic landscape not only maintains immunological homeostasis but also promotes stress-responsive transcription via stable chromatin modifications. These changes contribute to immunological priming, a process in which earlier exposure to pathogens or abiotic stress causes a heightened state of preparedness for future encounters. Small RNAs, including siRNAs, miRNAs, and phasiRNAs, are essential for gene silencing before and after transcription, fine-tuning immune responses, and inhibiting negative regulators. These RNA molecules interact closely with chromatin features, influencing histone acetylation/methylation (e.g., H3K4me3, H3K27me3) and guiding DNA methylation patterns. Epigenetically encoded immune memory can be stable across multiple generations, resulting in the transgenerational inheritance of stress resilience. Such memory effects have been observed in rice, tomato, maize, and Arabidopsis. This review summarizes new findings on short RNA biology, chromatin-level immunological control, and epigenetic memory in plant defense. Emerging technologies, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using Sequencing), ChIP-seq (Chromatin Immunoprecipitation followed by Sequencing), bisulfite sequencing, and CRISPR/dCas9-based epigenome editing, are helping researchers comprehend these pathways. These developments hold an opportunity for establishing epigenetic breeding strategies that target the production of non-GMO, stress-resistant crops for sustainable agriculture. Full article

Background: Mongolia is experiencing a rapid epidemiologic transition in which high burdens of micronutrient malnutrition, infection, and cardiometabolic disease are simultaneously prevalent. This cross-sectional study sought to understand how nutritional, lifestyle, and cardiometabolic risk factors are distributed among a population at high-risk for tuberculosis (TB), comprising household contacts (HHCs) and healthcare workers, (HCWs) in Ulaanbaatar, Mongolia, and how these factors are associated with TB infection. Methods: A total of 196 HHCs and 241 HCWs were assessed for latent TB infection (LTBI) using the QuantiFERON-TB Gold Plus (QFT-Plus) assay and for diabetes using fingerprick samples for fasting blood glucose. Participants also underwent assessments of their diet and physical activity, nicotine dependence, body mass index, and serum 25(OH)D concentration. We examined associations between assessed risk factors and LTBI using multivariate logistic regression. Results: The prevalence of LTBI was 47% for both HHCs and HCWs. A total of 54% percent of HHCs and 68% of HCWs had low physical activity levels; 63% of HHCs and 95% of HCWs were overweight or obese; 7% of HHCs and 4% of HCWs had impaired or diabetic fasting blood glucose [FBG]; and 49% of HHCs and 70% of HCWs were vitamin D deficient. In a multivariable analysis of HHCs, LTBI was independently associated with lower serum [25(OH)D], and the odds ratio (OR) was 3.18 (95% CI 1.38–7.79; p = 0.009). In contrast, the probability of LTBI did not differ significantly between vitamin D-deficient and non-deficient HCWs, and the OR was 0.89 (95% CI 0.59–1.37; p = 0.42). In a pooled analysis of HHCs and HCWs, the probability of LTBI did not significantly differ between vitamin D-deficient vs. non-deficient participants. The association between serum [25(OH)D] and LTBI among HHCs and HCWs was significantly modified by fasting blood glucose (FBG), such that a lower vitamin D status was significantly more common among those in the highest tertile of FBG than among those in the lowest tertile of FBG. Conclusions: Nutritional, lifestyle, and cardiometabolic risk factors are highly prevalent among HHCs and HCWs with TB in Ulaanbaatar, Mongolia. These findings underscore the importance of simultaneously controlling TB infection, malnutrition, and cardiometabolic risks among HHCs and HCWs to reduce the disease burden in Mongolia. Full article

According to a clever but rarely quoted or acknowledged work of E. Vessiot that won the prize of the Académie des Sciences in 1904, “Differential Galois Theory” (DGT) has mainly to do with the study of “Principal Homogeneous Spaces” (PHSs) for finite groups (classical Galois theory), algebraic groups (Picard–Vessiot theory) and algebraic pseudogroups (Drach–Vessiot theory). The corresponding automorphic differential extensions are such that $di{m}_K\left(L\right)=\mid L/K\mid <\infty$, the transcendence degree $trd(L/K)<\infty$ and $trd(L/K)=\infty$ with $difftrd(L/K)<\infty$, respectively. The purpose of this paper is to mix differential algebra, differential geometry and algebraic geometry to revisit DGT, pointing out the deep confusion between prime differential ideals (defined by J.-F. Ritt in 1930) and maximal ideals that has been spoiling the works of Vessiot, Drach, Kolchin and all followers. In particular, we utilize Hopf algebras to investigate the structure of the algebraic Lie pseudogroups involved, specifically those defined by systems of algebraic OD or PD equations. Many explicit examples are presented for the first time to illustrate these results, particularly through the study of the Hamilton–Jacobi equation in analytical mechanics. This paper also pays tribute to Prof. A. Bialynicki-Birula (BB) on the occasion of his recent death in April 2021 at the age of 90 years old. His main idea has been to notice that an algebraic group G acting on itself is the simplest example of a PHS. If G is connected and defined over a field K, we may introduce the algebraic extension $L=K\left(G\right)$; then, there is a Galois correspondence between the intermediate fields $K\subset K^{\prime }\subset L$ and the subgroups $e\subset G^{\prime }\subset G$, provided that $K^{\prime }$ is stable under a Lie algebra $\Delta$ of invariant derivations of $L/K$. Our purpose is to extend this result from algebraic groups to algebraic pseudogroups without using group parameters in any way. To the best of the author’s knowledge, algebraic Lie pseudogroups have never been introduced by people dealing with DGT in the spirit of Kolchin; that is, they have only been considered with systems of ordinary differential (OD) equations, but never with systems of partial differential (PD) equations. Full article

This contribution provides new data on Italian first language acquisition and phonological development in preschool children. In total, 104 3- to 6;4-year-old typically developing Italian children were tested with two novel nonword tasks tackling the Italian consonantal system: one for repetition (NWR) and one for discrimination (NWD). NWR data were analyzed in terms of repetition accuracy, featural characteristics, and phonological processes, while NWD was analyzed according to signal detection theory (i.e., A-prime and d-prime) and in terms of discrimination accuracy. The results show the significant role of age on children’s repetition and discrimination abilities: as the children grow older, all the scores improve and the number of errors declines. No complete overlap is found between what children can produce and what they can discriminate, which is in line with what has already been documented in other languages. The findings contribute to the state of the art on the Italian language and provide new perspectives on some methodological issues specific to this language. Full article

The endocannabinoid system regulates key biological functions such as neuroprotection, pain modulation, inflammation, and immunomodulation. Cannabis-based therapies have gained attention due to the therapeutic potential of their bioactive compounds, particularly phytocannabinoids like cannabidiol (CBD), which exhibit anti-inflammatory, neuroprotective, and immunomodulatory properties. Mesenchymal stem cells (MSCs) are widely studied for their regenerative and immunomodulatory potential. This study evaluated the effects of priming canine adipose tissue-derived MSCs (cAT-MSCs) with a CBD-rich cannabis extract on cell morphology, viability, neurotrophic factor gene expression, and cytokine gene and protein expression. cAT-MSCs (n = 5) were primed for 24 h and divided into three groups: Control (C, unprimed), D1 (2.25 µM CBD), and D2 (225 nM CBD). No morphological or viability changes were observed. Gene expression analysis showed that groups D1 and D2 exhibited increased HGF expression. D1 also showed increased IDO and decreased BDNF expression. In contrast, no significant changes were observed in GDNF, IL-10, TNF-α, IFN-γ, or PTGES2. Regarding the cytokine profile, GM-CSF, IL-2, and IL-10 were undetectable. Notably, IL-8 and MCP-1 levels were significantly reduced in D1 compared to the control. These findings suggest that CBD priming modulates key regenerative and inflammatory mediators in cAT-MSCs, supporting its potential application in enhancing the efficacy of cell-based therapies. Full article

Metabolic engineering of mesenchymal stem/stromal cells (MSCs) represents a compelling frontier for advanced cellular therapies, enabling the precise tuning of their biological outputs. This feature paper examines the critical role of engineered culture microenvironments, specifically 3D platforms, hypoxic preconditioning, and other priming approaches, which are synthetic biology strategies used to guide and optimize MSC metabolic states for desired functional outcomes. We show that these non-genetic approaches can significantly enhance MSC survival, immunomodulatory capacity, and regenerative potential by shifting their metabolism toward a more glycolytic phenotype. Furthermore, we propose a new paradigm of “designer” MSCs, which are programmed with synthetic circuits to sense and respond to the physiological cues of an injured microenvironment. This approach promises to transform regenerative medicine from an inconsistent field into a precise, predictable, and highly effective therapeutic discipline. Full article

This paper investigates functional identities in superalgebras, building on Wang’s foundational work. We study d-superfree subsets and k-supercommuting maps in prime superalgebras, both with and without superinvolution, introducing new results on symmetric and skew elements. Using SageMath, we computationally verify key properties in the finite-dimensional superalgebra $M_2\left(\mathbb{Q}\right)$, including supercommutators, superinvolutions, and k-supercommuting maps, thereby providing concrete illustrations of the abstract theory. These computations underscore the practical applicability of functional identities in finite-dimensional settings and offer fresh insights into superalgebra structures. Full article

Background: Accurate and stable instrument positioning is critical in dental implant procedures, particularly in anatomically constrained regions. Conventional navigation systems assume a static patient head, limiting adaptability in dynamic surgical conditions. This study proposes and validates a real-time motion compensation framework that integrates optical motion tracking with a collaborative robot to maintain tool alignment despite patient head movement. Methods: A six-camera OptiTrack Prime 13 system tracked rigid markers affixed to a 3D-printed human head model. Real-time head pose data were streamed to a Kuka LBR iiwa robot, which guided the implant handpiece to maintain alignment with a predefined target. Motion compensation was achieved through inverse trajectory computation and second-order Butterworth filtering to approximate realistic robotic response. Controlled experiments were performed using the MAiRA Pro M robot to impose precise motion patterns, including pure rotations (±30° at 10–40°/s), pure translations (±50 mm at 5–30 mm/s), and combined sinusoidal motions. Each motion profile was repeated ten times to evaluate intra-trial repeatability and dynamic response. Results: The system achieved consistent pose tracking errors below 0.2 mm, tool center point (TCP) deviations under 1.5 mm across all motion domains, and an average latency of ~25 ms. Overshoot remained minimal, with effective damping during motion reversal phases. The robot demonstrated stable and repeatable compensation behavior across all experimental conditions. Conclusions: The proposed framework provides reliable real-time motion compensation for dental implant procedures, maintaining high positional accuracy and stability in the presence of head movement. These results support its potential for enhancing surgical safety and precision in dynamic clinical environments. Full article

The Long Interspersed Element-1 (L1) retrotransposon is an ancient genetic parasite that comprises a significant part of the human genome. ORF2p is a multifunctional enzyme with endonuclease (EN) and reverse transcriptase (RT) activities that mediate target-primed reverse transcription of RNA into DNA. Structural studies of LINE-1 ORF2p consistently show a single Mg²⁺ cation in the reverse transcriptase active site, conflicting with the common DNA polymerase mechanism which involves two divalent cations. We explored a reaction pathway of the DNA elongation based on the recent high-resolution ternary complex structure of the ORF2p. The combined quantum and molecular mechanics approach at the QM (PBE0-D3/6-31G**)/MM (CHARMM) level is employed for biased umbrella sampling molecular dynamics simulations followed by umbrella integration utilized to obtain the free energy profile. The nucleotidyl transfer reaction proceeds in a single step with a free energy barrier of 15.1 ± 0.8 kcal/mol, and 7.8 ± 1.2 kcal/mol product stabilization relative to reagents. Concerted nucleophilic attack by DNA O3′ and proton transfer to Asp703 occur without a second catalytic metal ion. Estimated rate constant ∼60 s⁻¹ aligns with RT kinetics, while analysis of the Laplacian of the electron density along the cleaving P-O bond identifies a dissociative mechanism. Full article

Retinoic acid (RA) plays a key role in mucosal immune regulation and tolerance, with implications for inflammatory bowel disease (IBD). However, its effects have not been extensively studied in humanized in vitro models that recapitulate epithelial–immune interactions. We established a 3D in vitro small intestinal model composed of three epithelial cell types, naïve CD4⁺ T cells, and monocyte/dendritic cell (M/DC) precursors derived from CD34⁺ umbilical cord blood hematopoietic stem/progenitor cells. The epithelial microenvironment strongly suppressed monocyte/DC differentiation and T cell activation, indicating a regulatory role of epithelial-derived signals. Retinoic acid (RA) priming of M/DC precursors induced CD103⁺CD11b⁺Sirp1α⁻ regulatory DCs and promoted a shift from naive to memory-type T cells. Upon addition of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β), the model mimicked an inflamed intestinal state, resulting in CD14⁺CD16⁺ inflammatory monocytes and increased T cell activation (CD25⁺CD69⁺). RA-primed DCs modestly counterbalanced T cell activation and IBD-like responses, even under inflammatory conditions. Flow cytometry and clustering analysis revealed distinct immune cell phenotypes depending on RA exposure and cytokine context. This model provides a reproducible and physiologically relevant human system to study RA-mediated immune programming in the intestinal mucosa and may support the development of novel therapeutic strategies for IBD and related inflammatory conditions. Statistical differences were evaluated using ANOVA with Tukey’s post-hoc test (n = 4; p < 0.05). Full article

The molecular basis for the distinct intestinal tropism of infectious bronchitis virus (IBV) strains remains poorly understood. This study identifies the S2 subunit of the spike glycoprotein as the critical determinant conferring duodenal tropism to the IBV CSL strain. Comparative pathogenesis in specific-pathogen-free (SPF) chicks revealed that the CSL strain achieved significantly higher viral titers in the duodenum compared to strains D90, PYG QX1, and XXX QX5. This duodenal replication was associated with severe epithelial inflammation, characterized by upregulation of pro-inflammatory cytokines (IL-6, IL-17A, IL-22, TNF-α, IFN-β, IFN-γ) and disruption of barrier integrity via downregulation of tight junction proteins (Occludin, Claudin-1, ZO-1). Crucially, reverse genetics using the non-enterotropic D90 backbone demonstrated that recombinant viruses carrying the CSL-S2 gene (rD90-ΔS/CSL and rD90-ΔS2/CSL), but not those carrying CSL-S1 (rD90-ΔS1/CSL), replicated efficiently and induced inflammation in the duodenum, phenocopying wild-type CSL. In contrast, renal tropism was independent of the S2 subunit. These findings establish the S2 subunit as both necessary and sufficient for IBV duodenal tropism, uncoupling it from renal pathogenicity. This identifies S2 as a prime molecular target for developing next-generation vaccines against intestinal IBV pathotypes. Full article

Natural killer (NK) cells are promising candidates for adoptive immunotherapy, but their clinical application requires standardized expansion protocols that yield functional cells in sufficient numbers. This study examined how initial seeding density and donor-intrinsic variability affect NK cell proliferation and receptor phenotype during in vitro expansion in a G-Rex^® 24-well plate under IL-2 stimulation. NK cells from healthy donors were analyzed longitudinally by flow cytometry, and targeted SNP sequencing of selected receptor genes (IL2RA, IL2RB, FCGR3A, NCR1, KLRK1, and ICAM-1) was performed to assess potential genetic contributions. A seeding density of 2.0 × 10⁶ cells/cm² promoted high expansion rates and favorable expression of activating receptors including CD16a, NKp46, and NKG2D. Nonetheless, marked inter-donor differences were observed. Some donors exhibited impaired proliferation and aberrant receptor expression, possibly associated with high-priority SNPs and distinct haplotype structures. Others showed robust proliferation despite the absence of identifiable genetic drivers, suggesting the involvement of variants in other genes or non-genetic mechanisms such as epigenetic priming or adaptive NK-cell differentiation. These results highlight the influence of both culture conditions and donor-intrinsic factors on NK-cell expansion outcomes. Integrating phenotypic and genetic analyses may improve the reproducibility and personalization of NK-cell-based manufacturing protocols for therapeutic use. Full article

Grapevine (Vitis vinifera L.) cultivation is an important agricultural sector worldwide. Its expansion into new areas, like Kazakhstan, brings significant phytosanitary risks. Viroids, such as grapevine yellow speckle viroid 1 (GYSVd-1) and hop stunt viroid (HSVd), are RNA pathogens that threaten vineyard productivity. They can cause a progressive decline through latent infections. Traditional diagnostic methods are usually targeted and therefore not suitable for thorough surveillance. In contrast, modern high-throughput sequencing (HTS) methods often face challenges due to their high costs and complicated sample preparation, such as ribosomal RNA (rRNA) depletion. This study introduces a simplified diagnostic workflow that overcomes these barriers. We utilized the latest Oxford Nanopore V14 cDNA chemistry, which is designed to prevent internal priming, by substituting a targeted oligo(dT)VN priming strategy to facilitate the sequencing of non-polyadenylated viroids from total RNA extracts, completely bypassing the rRNA depletion step and use of random oligonucleotides for c DNA synthesis. This method effectively detects and identifies both GYSVd-1 and HSVd. This workflow significantly reduces the time, cost, and complexity of HTS-based diagnostics. It provides a powerful and scalable tool for establishing strong genomic surveillance and phytosanitary certification programs, which are essential for supporting the growing viticulture industry in Kazakhstan. Full article

Let us consider the finite commutative ring R, whose unity is $1\ne 0.$ Its weakly zero-divisor graph, represented as $W\Gamma \left(R\right)$, is a basic undirected graph with two distinct vertices, $c_1$ and $c_2$, that are adjacent if and only if there exist $r\in$ $\mathrm{ann}\left(c_1\right)$ and $s\in$ $\mathrm{ann}\left(c_2\right)$ that satisfy the condition $rs=0$. Let $D\left(G\right)$ be the distance matrix and $Tr\left(G\right)$ be the diagonal matrix of the vertex transmissions in basic undirected connected graph G. The $D_{\alpha }$ matrix of graph G is defined as $D_{\alpha }\left(G\right)=\alpha Tr\left(G\right)+(1-\alpha )D\left(G\right)$ for $\alpha \in [0,1]$. This article finds the $D_{\alpha }$ spectrum for the graph $W\Gamma \left({\mathbb{Z}}_n\right)$ for various values of n and also shows that $W\Gamma \left({\mathbb{Z}}_n\right)$ for $n={\vartheta }_1{\vartheta }_2{\vartheta }_3\dots {\vartheta }_t{\eta }_1^{d_1}{\eta }_2^{d_2}\dots {\eta }_s^{d_s}(d_i\ge 2,t\ge 1,s\ge 0)$, where ${\vartheta }_i$’s and ${\eta }_i$’s are the distinct primes, is $D_{\alpha }$ integral. Full article

To investigate the sintering shrinkage behavior of multigeneration, multilayer zirconia materials using geometrical measurements. Seven zirconia CAD/CAM materials were analyzed, comprising two mono-generation zirconia (HTML: Katana Zr, HTML Plus, 3Y-TZP; UTML: Katana Zr, UTML, 5Y-TZP) and five strength-gradient multilayer zirconia (AIDI: optimill 3D PRO Zir; PRIT: Priti multidisc ZrO₂ multicolor; UPCE: Explore Esthetic; ZCPC: IPS e.max ZirCAD Prime; ZYML: Katana YML) materials. Cubes (10 × 10 × 10 mm³) were milled in varying positions within the disks. Geometrical measurements were applied before and after dense sintering using a micrometer screw gauge, light microscopy, as well as surface scans and shrinkages were calculated. Data were analyzed using Kolmogorov–Smirnov, five-way ANOVA followed by the Scheffé post hoc test, and partial eta squared, as well as the Kruskal–Wallis test, including Bonferroni correction (p < 0.05). The highest influence on the shrinkage was exerted by the zirconia material (^η_P² = 0.893, p < 0.001), followed by the test method (^η_P² = 0.175, p < 0.001), while the vertical and horizontal position and measurement point showed no impact on the shrinkage results (p = 0.195–0.763) in the global analysis. Depending on the test method, the pooled shrinkage values of all tested zirconia materials varied between 17.7 and 20.2% for micrometer screw gauge, 17.7 and 20.1% for light microscopy, and 17.8 and 21.1% for surface scan measurements. The shrinkage values measured in the upper, middle, and lower multilayered vertical direction did not differ significantly in the global analysis for the multilayer materials. Therefore, a uniform shrinkage of these strength-gradient multilayer zirconia materials within clinically relevant restorations can be assumed. Full article