Search Results (5,224)

Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with dysfunction, with or without a structural substrate. They are frequently genetically determined. The dysfunction may be mechanical, both of the systole and diastole, or electrical, including arrhythmias or conduction disorders. Originally, only dilated, hypertrophic, restrictive–obliterative and arrhythmogenic dysfunctions were considered cardiomyopathies. Nowadays, since dysfunction can also be electric, disorders affected by electrical dysfunction without a structural substrate can be regarded as cardiomyopathies as well. This is the case of channellopathies and ryanodine receptors. This paper is a review of the history of cardiomyopathies, including the issues of their classification and nomination, genetic background and gene therapy. Full article

The original purpose of this study was to compare human and pig scRNA-seq data to determine why pigs do not have brown adipocytes. However, during the experiment, we identified brown adipocytes in pigs. Therefore, we aimed to confirm that these adipocytes were brown adipocytes via a comparative analysis using typical mouse brown adipose tissue sections. We found that swine brown adipocytes were distributed in an island-like pattern, with three typical characteristics: (1) numerous mitochondria and small lipid droplets, (2) a cellular volume smaller than that of white adipocytes, and (3) expression of specific marker genes (EBF2 and ATP2B4). The expression levels of the thermogenesis-related genes UCP2/3 were not significantly increased. Thus, we conducted ceRNA network analysis, revealing that high expression of the key microRNA miR-10383 increased the thermogenic efficiency of UCP3 in the cold exposure group. In addition, the epigenetic memory of UCP3 was disrupted. Chromatin accessibility and Whole-Transcriptome Sequencing of Groin Adiposesibility results revealed peaks in the promoter regions of the UCP2/3 genes. In our discussion of the study’s limitations, we explain how to repeat the experiment to significantly increase the UCP2/3 protein content. This study fills a research gap regarding brown fat in pigs and can provide a reference for future studies on fat metabolism. Full article

The tubulin polymerization promoting proteins (TPPPs) are a small family of conserved proteins originally characterized as microtubule binding proteins. TPPP1, the first identified member, both binds to and bundles microtubules. Its homologs, TPPP2 and TPPP3, are encoded by separate genes on distinct chromosomes but both lack the N-terminal tail present in TPPP1. Functional studies revealed that TPPP3 retains comparable microtubule binding and bundling capacity to TPPP1, whereas TPPP2 displays markedly reduced binding and no bundling activity. Intriguingly, TPPP3 has been implicated in many different diseases. In this review, we summarize the current findings on TPPP3 and its dysregulation in various diseases including cancer, reproductive dysfunction, musculoskeletal conditions, endothelial dysfunction, and neurodegenerative diseases. Full article

Leaf rust, a devastating fungal disease caused by Puccinia triticina (Pt), severely impacts wheat quality and yield. Identifying genetic loci for wheat leaf rust resistance, developing molecular markers, and breeding resistant varieties is the most environmentally friendly and economical strategy for disease control. This study utilized a recombinant inbred line (RIL) population of Doumai and Shi4185, combined with the wheat 90 K single nucleotide polymorphisms (SNPs) chip data and maximum disease severity (MDS) of leaf rust from four environments, to identify adult plant resistance (APR) loci through linkage mapping. Additionally, kompetitive allele-specific PCR (KASP) markers suitable for breeding were developed, and genetic effects were validated in a natural population. In this study, 5 quantitative trait loci (QTL) on chromosomes 1B (2), 2A and 7B (2) were identified through inclusive composite interval mapping, and named as QLr.lfnu-1BL1, QLr.lfnu-1BL2, QLr.lfnu-2AL, QLr.lfnu-7BL1 and QLr.lfnu-7BL2, respectively, explaining 4.54–8.91% of the phenotypic variances. The resistance alleles of QLr.lfnu-1BL1 and QLr.lfnu-1BL2 originated from Doumai, while the resistance alleles of QLr.lfnu-2AL, QLr.lfnu-7BL1 and QLr.lfnu-7BL2 came from Shi4185. Among these, QLr.lfnu-1BL2, QLr.lfnu-7BL1 and QLr.lfnu-7BL2 overlapped with previously reported loci, whereas QLr.lfnu-1BL1 and QLr.lfnu-2AL are likely to be novel. Two KASP markers, QLr.lfnu-2AL and QLr.lfnu-7BL, were significantly associated with leaf rust resistance in a diverse panel of 150 wheat varieties mainly from China. Totally, 34 potential candidate genes encoded the NLR proteins, receptor-like kinases, signaling kinases and transcription factors were selected as candidate genes for the resistance loci. These findings will provide stable QTL, available breeding KASP markers and candidate genes, and will accelerate the progresses of wheat leaf rust resistance improvement through marker-assisted selection breeding. Full article

Background: Tumor-associated macrophages (TAMs) are essential regulators of the glioblastoma (GBM) microenvironment; their functional heterogeneity and interaction networks are not fully elucidated. We identify RNF135 as a novel TAM-enriched gene associated with immune activation and adverse prognosis in GBM. Methods: To evaluate RNF135’s expression profile, prognostic significance, and functional pathways, extensive transcriptome analyses from TCGA and CGGA cohorts were conducted. The immunological landscape and cellular origin of RNF135 were outlined using single-cell RNA-seq analyses and bulk RNA-seq immune deconvolution (MCP-counter, xCell and ssGSEA). Cell–cell communication networks between tumor cells and RNF135-positive and -negative tumor-associated macrophage subsets were mapped using CellChat. Results: RNF135 predicted a poor overall survival and was markedly upregulated in GBM tissues. Functional enrichment analyses showed that increased cytokine signaling, interferon response, and innate immune activation were characteristics of RNF135-high samples. Immune infiltration profiling showed a strong correlation between the abundance of T cells and macrophages and RNF135 expression. According to the single-cell analyses, RNF135 was primarily expressed in TAMs, specifically in proliferation, phagocytic, and transitional subtypes. RNF135-positive TAMs demonstrated significantly improved intercellular communication with aggressive tumor subtypes in comparison to RNF135-negative TAMs. This was facilitated by upregulated signaling pathways such as MHC-II, CD39, ApoE, and most notably, the CCL signaling axis. The CCL3/CCL3L3–CCR1 ligand–receptor pair was identified as a major mechanistic driver of TAM–TAM crosstalk. High RNF135 expression was also linked to greater sensitivity to Selumetinib, a selective MEK1/2 inhibitor that targets the MAPK/ERK pathway, according to drug sensitivity analysis. Conclusions: RNF135 defines a TAM phenotype in GBM that is both immunologically active and immunosuppressive. This phenotype promotes inflammatory signaling and communication between cells in the tumor microenvironment. Targeting the CCL–CCR1 axis or combining RNF135-guided immunomodulation with certain inhibitors could be a promising therapeutic strategies for GBM. Full article

Collagen VI is an extracellular matrix component encoded by COL6A1, COL6A2 and COL6A3 genes. Causative variants in these genes are associated with the following collagen VI-related myopathies: severe Ullrich congenital muscular dystrophy (UCMD), milder Bethlem myopathy (BM) and intermediate phenotypes (INT). We report the mutation landscape of COL6A genes in 138 Italian patients affected with a collagen VI-related phenotype. The patient cohort included 44 (32%) UCMD, 9 (7%) INT, 61 (44%) BM and 21 (15%) INT/BM patients; 3 patients (2%) with a myosclerosis myopathy (MM) phenotype were also considered. We identified 104 different variants: 26 in COL6A1 (25%), 52 in COL6A2 (50%) and 26 in COL6A3 (25%). The variant spectrum includes missense, splicing, small indel, frameshifting and nonsense variants. Glycine substitutions in the triple helical domain of the collagen VI protein are the commonest variants and occur in all phenotypes. Our genetic profiling disclosed a unique mutation scenario and phenotypic association of the COL6A2 gene with respect to COL6A1 and COL6A3, which may be related to a different evolutive history. Landscape mutation analysis of variants occurring in ultrarare conditions, such as collagen VI-related myopathies, is crucial to better understand the variations’ profile and to gain insight into fundamental knowledge about gene structure and its evolutive origin. Full article

A rapid targeted screening method for 22 compounds, including flavonoids, glycosides, and phenolics, in Dendrobium officinale was developed using UHPLC–MS/MS, demonstrating good linear correlation coefficients, precision, repeatability, and stability. D. officinale from the Guangnan and Maguan regions can be effectively classified into two distinct categories using PCA. In addition, OPLS-DA discriminant analysis enables clear separation between groups, with samples forming well-defined clusters. The 22 chemical components provide valuable origin-related information for D. officinale. The compounds with VIP values of >1 included eriodictyol, vanillic acid, protocatechuic acid, gentisic acid, and naringenin. The difference in naringenin content between D. officinale from the two production areas was minimal. By contrast, eriodictyol and vanillic acid were relatively abundant in D. officinale from Guangnan, while gentisic acid and protocatechuic acid were more prevalent in D. officinale from Maguan. The pathways with higher Kyoto Encyclopedia of Genes and Genomes enrichment were primarily associated with lipid metabolism and atherosclerosis, fluid shear stress and atherosclerosis, and nonalcoholic fatty liver disease. These findings suggest that D. officinale exhibits promising lipid-balancing properties and potential cardiovascular health benefits. Seven machine learning algorithms—Random Forest, XGBoost, Support Vector Machine, k-Nearest Neighbor, Backpropagation Neural Network, Random Tree, and CatBoost—demonstrated superior accuracy and precision in distinguishing D. officinale from the Guangnan and Maguan regions. The key compounds with higher weights—vanillic acid, chrysoeriol, trigonelline, isoquercitrin, gallic acid, 4-hydroxybenzaldehyde, eriodictyol, sweroside, apigenin, and homoeriodictyol—play a crucial role in model construction and the identification of D. officinale from the Guangnan and Maguan regions. The quantification of 22 compounds using UHPLC–MS/MS, combined with PCA, OPLS-DA, and machine learning, enables effective discrimination of D. officinale from these two Yunnan production areas. Full article

Recent developments in next-generation sequencing technology have led to the creation of extensive, open-source protein databases consisting of hundreds of millions of sequences. To render these sequences applicable in biomedical applications, they must be meticulously annotated by wet lab testing or extracting them from existing literature. Over the last few years, researchers have developed numerous automatic annotation systems, particularly deep learning models based on machine learning and artificial intelligence, to address this issue. In this work, we propose a transformer-based fusion model capable of predicting Gene Ontology (GO) terms from full-scale protein sequences, achieving state-of-the-art accuracy compared to other contemporary machine learning annotation systems. The approach performs particularly well on clustered split datasets, which comprise training and testing samples originating from distinct distributions that are structurally diverse. This demonstrates that the model is able to understand both short and long term dependencies within the protein’s structure and can capture sequence features that are predictive of the various GO terms. Furthermore, the technique is lightweight and less computationally expensive compared to the benchmark methods, while at the same time unaffected by sequence length, rendering it appropriate for diverse applications with varying sequence lengths. Full article

Yield components are the most important breeding objectives, directly determining maize high-yield breeding. It is well known that these traits are controlled by a large number of quantitative trait loci (QTL). Therefore, deeply understanding the genetic basis of yield components and identifying key regulatory candidate genes can lay the foundation for maize marker-assisted selection (MAS) breeding. In this study, our aim was to identify the key genomic regions that regulate maize yield component formation through bioinformatic methods. Herein, 554 original QTLs related to 11 yield components, including ear length (EL), hundred-kernel weight (HKW), ear weight (EW), cob weight (CW), ear diameter (ED), cob diameter (CD), kernel row number (KRN), kernel number per row (KNR), kernel length (KL), grain weight per plant (GW), and kernel width (KW) in maize, were collected from the MaizeGDB, national center for biotechnology information (NCBI), and China national knowledge infrastructure (CNKI) databases. The consensus map was then constructed with a total length of 7154.30 cM. Approximately 80.32% of original QTLs were successfully projected on the consensus map, and they were unevenly distributed on the 10 chromosomes (Chr.). Moreover, 44 meta-QTLs (MQTLs) were identified by the meta-analysis. Among them, 39 MQTLs controlled two or more yield components, except for the MQTL4 in Chr. 1, which was associated with HKW; MQTL11 in Chr. 2, which was responsible for EL; MQTL19 in Chr. 3, which was related to KRN; MQTL26 in Chr. 5, which was involved in HKW; and MQTL36 in Chr. 7, which regulated EL. These findings were consistent with the Pearson correlation results, indicating that these traits exhibited co-linked heredity phenomena. Meanwhile, 159 candidate genes were found in all of the above MQTLs intervals, of which, 29 genes encoded E3 ubiquitin protein ligase, which was related with kernel size and weight. Other genes were involved in multiple metabolic processes, including plant hormones signaling transduction, plant growth and development, sucrose–starch synthesis and metabolism, and reproductive growth. Overall, the results will provide reliable genetic resources for high-yield molecular breeding in maize. Full article

Autosomal-dominant sleep-related hypermotor epilepsy (ADSHE) was the first distinct genetic epilepsy proven to be caused by mutation of the CHRNA4 gene, originally reported in 1994. In the past three decades, pathomechanisms of ADSHE associated with mutant nicotinic acetylcholine receptors (nAChRs) have been explored via various studies, including in vitro experiments and genetic rodent models. However, findings emphasize that functional abnormalities of ADSHE-mutant nAChRs alone cannot generate ictogenesis; rather, development of abnormalities in various other transmission systems induced by ADSHE-mutant nAChRs during the neurodevelopmental process before the ADSHE onset is involved in development of epileptogenesis/ictogenesis. Intra-thalamic GABAergic disinhibition induced by loss-of-function of S284L-mutant nAChRs (S286L-mutant nAChRs in rat ADSHE models) contributes to enhancing propagation of physiological ripple-burst high-frequency oscillation (HFO) and Erk signaling during sleep, leading to enhancement of the trafficking of pannexin1, connexin43, and P2X7 purinergic receptor to the astroglial plasma membrane. The combination of activation of physiological ripple-HFO and upregulation of astroglial hemichannels under the GABAergic disinhibition plays an important role in generation of epileptogenic fast-ripple-HFO during sleep. Therefore, loss-of-function of the S284L-mutation alone cannot drive ictogenesis but contributes to the development of epileptogenesis as an initial abnormality. Based on these recent findings using genetic rat ADSHE models, harboring the rat S286L-mutant Chrna4 corresponding to the human S284L-mutant CHRNA4, this report proposes hypothetical pathomechanisms of ADSHE. Full article

Background and Objectives: Changes in the environment and physiology may be associated with an increased or decreased risk of cancer. Our study aims to evaluate the strength and the direction of the selection acting on oncosuppressor genes in association with phenotypic changes. Methods: We calculated the relative evolutionary rate (RER) using the converge method and linear regression on branches of phylogenetic trees. The association between changes in the evolutionary rate of oncosuppressors (DNA repair and cell cycle control genes) and trait selection was studied. The evolutionary rates of single oncosuppressor genes and pathways were evaluated. We studied two types of traits: those that are characteristic of vertebrates, such as homeothermy (the ability to maintain a constant body temperature), flight, and amnions; and those that are characteristic of mammals, such as high body mass and lifespan, an underground lifestyle, and hibernation. The analysis included 19,445 genes; 100 vertebrates and 46 mammalian species. We studied ancestral branches individually and all the clades having a trait. Results: Oncosuppressor genes accelerated in association with the ability to fly; p-value = 0.03 (positive or relaxed negative selection) and decelerated in homeothermic species; p-value = 0.04 (stabilizing selection). DNA repair genes were significantly accelerated in ancestral branches and in all clades of amniotic, homeothermic, and high-body-mass mammals (p-value < 0.05, FDR correction). Cell cycle control genes were under stabilizing selection in homeothermic animals, high-body-mass, long-lived, and underground mammals (p-value < 0.05, FDR correction). Data on the evolution of oncosuppressors are crucial for understanding the origin of cancer and will be important for future studies of tumor pathogenesis, pathomorphosis, and microevolution. Conclusions: The selection of traits associated with changes in cancer risk leads to positive/relaxed negative and stabilizing selection of oncosuppressor genes. Full article

Brucellosis remains an underreported zoonotic disease in Ecuador. Its control program in cattle integrates diagnostic testing, vaccination, and eradication incentives, although participation is largely voluntary. Since 2025, vaccination has become compulsory nationwide. Human surveillance remains largely passive, and strain-level data are very limited. This study applied an integrated approach, combining serology (Rose Bengal and SAT-EDTA), microbiological culture, and molecular diagnostics, to assess the presence and diversity of Brucella spp. in cattle and pigs from six slaughterhouses in the northern Andean highlands. A total of 2054 cattle and 1050 pigs from Carchi, Imbabura, and Pichincha were sampled. Among cattle, 133 (6.5%; 95% CI: 5.5–7.6) were seropositive, and viable B. abortus strains were isolated from 17 (12.8%). Genus identification was confirmed by IS711-PCR, while species- and biovar-level differentiation was achieved with AMOS-PCR; additional assays targeting the ery gene and RB51 marker were used to distinguish field from vaccine strains. Biotyping and molecular analysis revealed a predominance of B. abortus biovar 4 (13/17 isolates) over biovar 1, all confirmed as field strains. In pigs, 10 animals (0.95%) tested seropositive, but no isolates were recovered, highlighting limitations of serology in swine. Most livestock, including the positives, originated locally, reinforcing the representativeness of our findings. The successful isolation and molecular characterization of B. abortus demonstrates the value of combining diagnostic strategies beyond serology. These results underscore the utility of active surveillance when supported by traceability systems; this approach may also contribute to guide interventions to reduce infection risk in livestock and humans. Full article

Strawberry (Fragaria × ananassa Duch.) is a widely cultivated and economically important fruit crop with increasing consumer demand worldwide. Nowadays, in Uzbekistan, strawberry cultivation surpasses that of many other fruits and vegetables in terms of production volume. However, most genetic studies have focused on a limited set of cultivars, leaving a substantial portion of varietal diversity unexplored. This study aimed to evaluate the genetic variability and heritability among selected strawberry cultivars, as well as correlations between certain valuable agronomic traits, using molecular and statistical approaches. Polymorphism analysis was performed, using 67 gene-specific SSR markers, through PCR, and allele variations were observed in 46.3% of the markers analyzed. Among them, 31 markers displayed polymorphic bands, identifying fifty alleles, with one to four alleles per marker. Phylogenetic analysis was performed using MEGA 11 software, while statistical evaluations included AMOVA (GenAIEx), correlation (OriginPro), and descriptive statistics based on standard agronomic methods. Additionally, the degree of cross-compatibility and pollen viability among the cultivars were studied, and their significance for cultivar hybridization was analyzed. The highest fruit weight was observed in the Cinderella cultivar (26.2 g), and a moderate negative correlation (r = −0.688) was found between fruit number and fruit weight. These findings demonstrate the potential of molecular tools for assessing genetic diversity and provide valuable insights for breeding programs aimed at developing improved strawberry cultivars with desirable agronomic traits. Full article

Guava (Psidium guajava L.), a perennial species native to tropical regions of the Americas, holds significant economic value and plays an important role in the global fruit industry. Although several reference genomes have been published, population-level genomic studies remain limited, hindering genetic improvement efforts. In this study, we conducted whole genome re-sequencing of 62 guava accessions, primarily from Southern China and Brazil. A total of 4,887,006 high-quality SNPs and 731,469 InDels were identified for population genomic analyses. Phylogenetic and population structure analyses revealed subgroupings that largely corresponded to geographic origins. The data indicated that extensive hybridization between accessions from Brazil and or within China has contributed to the development of many dominant commercial varieties. Genetic diversity analyses showed that Brazilian accessions exhibited higher nucleotide diversity and more rapid linkage disequilibrium decay than those from China. Environmental factors and artificial selection likely imposed selective pressures that shaped guava’s adaptability and agronomic traits. A preliminary genome-wide association study (GWAS) identified PgMYB4 as a candidate gene potentially associated with fruit flesh color. These findings provide novel insights into the genetic diversity, population history, and domestication of guava, and lay a valuable foundation for future breeding and improvement strategies. Full article

Background: Skin diseases of inflammatory origin, such as atopic dermatitis, psoriasis and acne, have a substantial prevalence in the world population. Natural products are particularly important at a topical level. Essential oils are examples of natural products and thyme in particular has been used for medicinal purposes due to its biological properties. Objectives: The aim of present work was to study the anti-inflammatory potential of Thymus mastichina essential oil, focusing on purified terpene-rich fractions. whose major compounds were thymol and linalool, eucalyptol and α-terpineol, and γ-terpinene and terpinolene, respectively. Additionally, a phytocannabinoid formulation containing cannabidiol (CBD) and cannabigerol (CBG) was evaluated to explore potential synergistic effects. Methods: Thymus mastichina essential oil was extracted and purified to obtain terpene-enriched fractions, which were used to develop three distinct formulations. These were screened for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and assessed for cytotoxicity in HaCaT human keratinocytes. Anti-inflammatory potential was evaluated via gene expression. Selected thyme formulations—alone or in combination with CBD/CBG—were also tested in vivo using a mouse model of acute skin inflammation. Results: The antioxidant activity of the three formulations showed a reduction in DPPH radicals. In addition, the formulations demonstrated to be safe in vitro in the human keratinocyte cell model HaCaT. Under PMA-induced inflammatory stress, the fractions modulated-inflammatory gene expression to varying degrees While terpene fractions alone showed moderate activity, their combination with CBD/CBG enhanced the anti-inflammatory response. In vivo, the gel formulations reduced oedema in a mouse model of acute inflammation. Conclusions: The data support the safe and effective use of Thymus mastichina-derived terpene fractions for topical anti-inflammatory applications. The synergistic effect observed with CBD and CBG suggests that combining essential oil terpenes with phytocannabinoids may offer a novel therapeutic strategy for managing inflammatory skin disorders. Full article