Search Results (148)

In this study we searched for correlations between polymorphic variants that determine sex hormone-binding globulin concentration (SHBG_con) and uterine fibroids (UFs). The work was performed on a sample of 1542 women (569 with UFs and 973 without UFs [control]), from whom we obtained experimental data on the distribution of nine single-nucleotide polymorphisms (SNPs) affecting the SHBG_con (data confirmed in genome-wide association studies [GWASs]). When searching for associations with UFs, both the independent effects of SNPs and the effects of their SNP–SNP interactions (SNP-SNP_ints) were taken into account during the “deep study” of the functionality of seven important UF loci and 115 strongly linked [r² ≥ 0.80] variants (an in silico methodology was used). As the results show, two SHBG_con-related SNPs correlated with UF risk: rs3779195 [T/A] BAIAP2L1 (OR_AA = 0.38; 95%CI_AA = 0.20–0.91; p_perm(AA) = 0.023) and rs440837 [A/G] ZBTB10 (OR_GG = 1.93; 95%CI_GG = 1.17–3.14; p_perm(GG) = 0.010). At the same time, seven SHBG_con-related SNPs interacting with each other (four models of such SNP-SNP_ints [p_perm ≤ 0.01)] were found to influence UF risk. These SHBG_con-related SNPs, determining susceptibility to UF, showed strong functional relevance and were involved in pathways of gene transcription regulation, interactions with hormone ligand-binding receptors, the content control of SHBG, testosterone, liver enzymes, lipids, etc. This study’s results demonstrate the effect of significant SHBG_con-related genetic determinants of UF risk. Full article

Basal cell carcinoma (BCC), the most common skin cancer, is primarily driven by Hedgehog (Hh) and TP53 pathway alterations. Although additional pathways were implicated, the mutational landscape in Asian populations, particularly Koreans, remains underexplored. We performed whole-exome sequencing of BCC tumor tissues from Korean patients and analyzed mutations in 11 established BCC driver genes (PTCH1, SMO, GLI1, TP53, CSMD1/2, NOTCH1/2, ITIH2, DPP10, and STEAP4). Mutational profiles were compared with Caucasian cohort profiles to identify ethnicity-specific variants. Ultraviolet (UV)-exposed and non-UV-exposed tumor sites were compared; genes unique to non-UV-exposed tumors were further analyzed with protein–protein interaction analysis. BCCs in Koreans exhibited distinct features, including fewer truncating and more intronic variants compared to Caucasians. Korean-specific mutations in SMO, PTCH1, TP53, and NOTCH2 overlapped with oncogenic gain-of-function/loss-of-function (GOF/LOF) variants annotated in OncoKB, with some occurring at hotspot sites. BCCs in non-exposed areas showed recurrent mutations in CSMD1, PTCH1, and NOTCH1, suggesting a UV-independent mechanism. Novel mutations in TAS1R2 and ADCY10 were exclusive to non-exposed BCCs, with protein–protein interaction analysis linking them to TP53 and NOTCH2. We found unique ethnic-specific and UV-independent mutational profiles of BCCs in Koreans. TAS1R2 and ADCY10 may contribute to tumorigenesis of BCC in non-exposed areas, supporting the need for population-specific precision oncology. Full article

Microcystins (MCs) are the most toxic and abundant cyanotoxins found in natural waters during harmful cyanobacterial blooms. These toxins pose a significant threat to plant, animal, and human health due to their toxicity. Degradation of MCs by MC-degrading bacteria is a promising method for controlling these toxins, demonstrating safety, high efficiency, and cost-effectiveness. In this study, we isolated potential MC-degrading bacteria (strains TA13, TA14, and TA19) from Lake Kasumigaura in Japan and found that they possess a high capacity for MC degradation. Based on 16S rRNA gene sequencing, all three isolated strains were identified as belonging to the Klebsiella species. These bacteria effectively degraded MC-RR, MC-YR, and MC-LR under various temperature and pH conditions within 10 h, with the highest degrading activity and degradation rate observed at 40 °C. Furthermore, the isolated strains efficiently degraded MCs not only under neutral pH conditions, but also in alkaline environments. Additionally, we detected the MC-degrading gene (mlrA) in all three isolated strains, marking the first report of the mlrA gene in Klebsiella species. The copy number of the mlrA gene in the strains increased after exposure to MCs. These findings indicate that strains TA13, TA14, and TA19 significantly contribute of MC bioremediation in Lake Kasumigaura during cyanobacterial blooms. Full article

Background/Objectives: Sweet taste receptor TAS1R2 is expressed in skeletal muscle, yet its role in muscle metabolism remains poorly understood. Methods: Here, we leverage the BXD recombinant inbred mouse panel and Tas1r2 whole-body knockout (bKO) models to investigate the transcriptional impact of Tas1r2 deficiency on skeletal muscle function. Results: A gene network analysis revealed significant overlap in transcriptomic signatures between BXD strains with low Tas1r2 expression (BXD L_Tas1r2) and bKO muscle, particularly in pathways regulating oxidative phosphorylation, cytoplasmic ribosome function, and proteostasis. Notably, Tas1r2 expression negatively correlated with genes involved in fatty acid metabolism, suggesting its role in lipid utilization. Under high-fat diet (HFD) conditions, BXD_HFD L_Tas1r2 mice exhibited further enrichment in pathways linked to proteasome degradation, oxidative stress, and interleukin signaling, amplifying the transcriptomic convergence with bKO models. Key transcription factors (Mlxipl, Nfic, Rxrb) exhibited altered regulatory patterns under dietary stress, indicating that TAS1R2 influences metabolic adaptability through transcriptional reprogramming. Conclusions: Given that human TAS1R2 variants rarely result in complete loss of function (LOF), the BXD panel provides an effective dose-dependent model to bridge the gap between knockout phenotypes and human SNP carriers. Our findings establish TAS1R2 as a metabolic regulator in skeletal muscle and highlight the utility of genetically diverse mouse populations in dissecting gene-diet interactions relevant to human metabolic diseases. Full article

Scomberomorus guttatus and Scomberomorus commerson are both important marine economic fish species worldwide, with high scientific and ecological value. In this study, the complete mitochondrial genome sequences of these two species of mackerel were obtained by using next-generation sequencing technology, with total lengths of 16,562 bp and 16,594 bp, respectively. Like most teleosts, both species possess 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 non-coding region D-loop. The base composition showed significant AT bias (55.1%, 53.4%) and anti-G bias (16.0%, 16.2%). In their control area, the terminal-associated sequence (TAS) was identified, and a total of three core sequences with repeated “---TACAT---ATGTA---” were found. There are typical CSB-E structures and CSB-D-like structures in the central conserved domain (CD), but no CSB-F structures have been found. Meanwhile, the CSB-2 and CSB-3 structures were identified in the conserved sequence block (CSB), but the CSB-1 structure was missing. To further investigate the phylogenetic relationships within the Scombridae family, this study conducted a comparative analysis of mitochondrial genomes from 30 Scombridae species. Phylogenetic trees encompassing 60% of the documented Scombridae species were constructed using the Neighbor-Joining (NJ) and Maximum Likelihood (ML) methods. The results revealed a close evolutionary relationship between the genus Scomber and Rastrelliger, while the genus Scomberomorus exhibited closer affinities to Thunnus, Euthynnus, and Katsuwonus. At the species level, Scomberomorus guttatus diverged earlier from Scomberomorus commerson. These findings refine and update the phylogenetic relationships among Scombridae species, providing critical molecular evidence and insights for deeper exploration of their evolutionary history and genetic affinities. Full article

Crohn’s disease (CD) is a chronic inflammatory disorder with potential progression to stricturing (B2) or penetrating (B3) phenotypes, leading to significant complications. Early identification of patients at risk for these complications is critical for personalized management. This study aimed to develop a predictive model using clinical data and a Korean-specific transcriptome-wide association study (TWAS) to forecast early progression in CD patients. A retrospective analysis of 430 Korean CD patients from 15 hospitals was conducted. Genotyping was performed using the Korea Biobank Array, and gene expression predictions were derived from a TWAS model based on terminal ileum data. Logistic regression models incorporating clinical and gene expression data predicted progression to B2 or B3 within 24 months of diagnosis. Among the cohort, 13.9% (60 patients) progressed to B2 and 16.9% (73 patients) to B3. The combined model achieved mean area under the curve (AUC) values of 0.788 for B2 and 0.785 for B3 progression. Key predictive genes for B2 included CCDC154, FAM189A2, and TAS2R19, while PUS7, CCDC146, and MLXIP were linked to B3 progression. This integrative model provides a robust approach for identifying high-risk CD patients, potentially enabling early, targeted interventions to reduce disease progression and associated complications. Full article

Background/Objectives: Studies have hypothesised that single-nucleotide polymorphisms (SNPs) in the TAS1R2 and TAS1R3 genes may alter sweet compound detection and eating habits, thereby increasing the risk of obesity. This in vitro study aims to measure the impact of human TAS1R2/TAS1R3 polymorphisms, some of which are thought to be involved in obesity, on the response of the sweet taste receptor to various sweeteners. It also aims to identify new SNPs in an obese population associated with a decrease in or loss of TAS1R2/TAS1R3 function. Methods: First, the effects of 12 human TAS1R2-SNPs and 16 human TAS1R3-SNPs, previously identified in the literature, on the response of the sweet taste receptor stimulated by 12 sweeteners were investigated using functional cellular assays. Second, a total of 162 blood samples were collected from an obese population (BMI between 25 and 35 kg/m²) involved in the SWEET project. The TaqMan method for SNP genotyping was carried out using DNA extracted from blood samples to identify new SNPs and predict possible/probable TAS1R2/TAS1R3 loss of function. Results: Although certain human TAS1R2/TAS1R3 SNPs showed reduced receptor response, they were not associated with particular phenotypes. Seven SNPs were predicted to severely impair the human TAS1R2/TAS1R3 response to sweeteners. Conclusions: Although some TAS1R2- and TAS1R3-SNPs have previously been associated with obesity, our cellular results do not confirm this association and reinforce the hypothesis, put forward by other researchers, that sweet taste perception and sugar consumption are governed by factors other than the TAS1R2 and TAS1R3 genes. Full article

Reactive oxygen species (ROS), as signaling molecules, play a crucial role in the plant immune response. However, the mechanism(s) by which viruses affect ROS metabolism remain largely unexplored. Here, we found that wheat yellow mosaic virus (WYMV)-encoded P1 is a pathogenic protein. Transcriptomic and proteomic integrative analyses were performed on WYMV-infected overexpressing-P1 wheat and wild-type plants. A total of 9245 differentially expressed genes (DEGs) and 1383 differentially expressed proteins (DEPs) were identified in the transcriptome and proteome, respectively. At their intersection, 373 DEGs/Ps were identified. Enrichment analysis revealed that the expression of genes related to the ROS metabolism pathway in overexpressed P1 transgenic wheat (OE-P1) plants significantly increased during WYMV infection. We screened peroxidase (TaPOD) and thioredoxin reductase (TaTrxR) as they showed the most significant differences in expression. The silencing of TaPOD and TaTrxR revealed that they positively regulate WYMV infection by reducing ROS accumulation. Furthermore, hydrogen peroxide treatment induced WYMV resistance in wild-type wheat plants and OE-P1 transgenic plants. This study provides a theoretical basis for the role of P1 in plant viral infection. Full article

Sarcopenia corresponds to a decrease in muscle mass and strength. CCL5 is a new myokine whose expression, along with the CCR5 receptor, is increased in sarcopenic muscle. Therefore, we evaluated whether CCL5 and CCR5 induce a sarcopenic-like effect on skeletal muscle tissue and cultured muscle cells. Electroporation in the tibialis anterior (TA) muscle of mice was used to overexpress CCL5. The TA muscles were analyzed by measuring the fiber diameter, the content of sarcomeric proteins, and the gene expression of E3-ligases. C₂C₁₂ myotubes and single-isolated flexor digitorum brevis (FDB) fibers were also treated with recombinant CCL5 (rCCL5). The participation of CCR5 was evaluated using the antagonist maraviroc (MVC). Protein and structural analyses were performed. The results showed that TA overexpression of CCL5 led to sarcopenia by reducing muscle strength and mass, muscle-fiber diameter, and sarcomeric protein content, and by upregulating E3-ligases. The same sarcopenic phenotype was observed in myotubes and FDB fibers. We showed increased reactive oxygen species (ROS) production and carbonylated proteins, denoting oxidative stress induced by CCL5. When the CCR5 was antagonized, the effects produced by rCCL5 were prevented. In conclusion, we report for the first time that CCL5 is a novel myokine that exerts a sarcopenic-like effect through the CCR5 receptor. Full article

Species of the family Echeneidae are renowned for their capacity to adhere to various hosts using a sucking disc. This study aimed to examine the mitochondrial genome characteristics of three fish species (Echeneis naucrates, Remora albescens, and Remora remora) within the family Echeneidae and determine their phylogenetic relationships. The findings revealed that the mitochondrial genome lengths of the three species were 16,611 bp, 16,648 bp, and 16,623 bp, respectively, containing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a D-loop region. Most PCGs utilized ATG as the initiation codon, while only cox I used the GTG as the initiation codon. Additionally, seven genes employed incomplete termination codons (T and TA). The majority of PCGs in the three species displayed negative AT-skew and GC-skew values, with the GC-skew amplitude being greater than the AT-skew. The Ka/Ks ratios of the 13 PCGs did not exceed 1, demonstrating these species had been subjected to purification selection. Furthermore, only tRNA-Ser (GCT) lacked the D arm, while other tRNAs exhibited a typical cloverleaf secondary structure. Bayesian inference (BI) and maximum likelihood (ML) methods were utilized to construct a phylogenetic tree of the three species based on the 13 PCGs. Remora remora was identified as a distinct group, while R. osteochir and R. brachyptera were classified as sister taxa. This study contributes to the mitochondrial genome database of the family Echeneidae and provides a solid foundation for further systematic classification research in this fish group. Full article

Background: Bladder cancer (BC) is one of the ten most common cancers worldwide, with a high recurrence rate and significant variation in clinical outcomes based on tumor grade and stage. This study aimed to investigate the gene expression profiles at different cancer stages to assess their potential prognostic value. Methods: RNA was extracted from paraffin-embedded BC tissues and the gene expression levels of CDC20 and CCNB1 were analyzed using qRT-PCR. A total of 54 BC patient samples were included in the analysis and categorized into low-grade (LG) (n = 23) and high-grade (HG) (n = 31) tumors, as well as stages pTa, pT1, and pT2. Results: CDC20 gene expression was significantly higher in the HG group (mean fold-change: 16.1) compared to the LG group (mean fold-change: 10.54), indicating a significant association with tumor grade (p = 0.039). However, no significant differences were observed in CDC20 expression across the cancer stages. For CCNB1, while gene expression was significantly elevated in higher-stage tumors (pT2 vs. pTa; p = 0.038), no significant association was found between CCNB1 expression and tumor grade. Survival analysis revealed that increased CCNB1 expression and advanced cancer stage were associated with poorer overall survival, whereas no significant impact of CDC20 expression or tumor grade on survival was observed. Correlation analysis indicated a positive relationship between CDC20 expression and tumor grade (r = 0.284, p = 0.038) and between CCNB1 expression and tumor stage (r = 0.301, p = 0.027). Conclusions: Our findings suggest that CDC20 overexpression is linked to higher tumor grades, while CCNB1 overexpression is associated with more advanced cancer stages in BC. These results underscore the potential utility of CDC20 and CCNB1 as biomarkers for tumor prognosis and as therapeutic targets. Further studies with larger cohorts are needed to validate these findings and better understand the molecular mechanisms driving BC progression. Full article

The root is an important organ by which plants directly sense variation in soil moisture. The discovery of drought stress-responsive genes in roots is very important for the improvement of drought tolerance in wheat varieties via molecular approaches. In this study, transcriptome sequencing was conducted on the roots of drought-tolerant wheat cultivar YH1818 seedlings at 0, 2, and 7 days after treatment (DAT). Based on a weighted gene correlation network analysis of differentially expressed genes (DEGs), 14 coexpression modules were identified, of which five modules comprising 3107 DEGs were related to 2 or 7 DAT under drought stress conditions. A total of 223,357 single-nucleotide polymorphisms (SNPs) of these DEGs were retrieved from public databases. Using the R language package and GAPIT program, association analysis was performed between the 223,357 SNPs and the drought tolerance coefficient (DTC) values of six drought resistance-related traits in 114 wheat germplasms. The results revealed that 18 high-confidence SNPs of 10 DEGs, including TaPK, TaRFP, TaMCO, TaPOD, TaC3H-ZF, TaGRP, TaDHODH, TaPPDK, TaLectin, and TaARF7-A, were associated with drought tolerance. The RT–qPCR results confirmed that these genes were significantly upregulated by drought stress at 7 DAT. Among them, TaARF7-A contained three DTC-related SNPs, which presented two haplotypes in the tested wheat germplasms. YH1818 belongs to the Hap1 allele, which is involved in increased drought tolerance. This study revealed key modules and candidate genes for understanding the drought-stress response mechanism in wheat roots. Full article

The Chinese Tan sheep is a unique breed of sheep that is typical throughout China, mainly used for fur and meat production. They are widely distributed in northwestern China and are famous for their lambskin and shiny white curly wool. In this study, the phenotypic traits of wool length, birth weight, and head coat color were evaluated in 256 Chinese Tan sheep breeds. Whole genome sequencing generated 23.67 million high-quality SNPs for genome-wide association studies (GWAS). We identified 208 significant SNPs associated with birth wool length, implicating RAD50, MACROD2, SAMD5, SASH1, and SPTLC3 as potential candidate genes for this trait. For birth weight, 1056 significant SNPs, with 76.89% of them located on chromosome 2, were identified by GWAS, and XPA, INVS, LOC121818504, GABBR2, LOC101114941, and LOC106990096 were identified as potential candidate genes for birth weight. The GWAS for head coat color identified 1424 significant SNPs across three chromosomes, with 99.65% on chromosome 14, and SPIRE2, TCF25, and MC1R as candidate genes were found to be possibly involved in the development of the black-headed coat color in sheep. Furthermore, we selected head coat color as a representative trait and performed an independent test of our GWAS findings through multiplex PCR SNP genotyping. The findings validated five mutation sites in chromosome 14 (14,251,947 T>A, 14,252,090 G>A, 14,252,158 C>T, 14,252,329 T>G, and 14,252,464 C>T) within the exon1 of the MC1R gene (517 bp), as identified by GWAS in an additional 102 Tan sheep individuals, and revealed that black-headed sheep predominantly exhibited heterozygous genotypes, possibly contributing to their color change. Our results provide a valuable foundation for further study of these three economically important traits, and enhance our understanding of genetic structure and variation in Chinese Tan sheep. Full article

A transcription-aided selection (TAS) strategy is proposed in this paper, which utilizes the positive regulatory roles of genes involved in the plant immunity pathways to screen crops with high disease resistance. Increased evidence has demonstrated that upon pathogen attack, the expression of diverse genes involved in salicylic acid (SA)-mediated SAR are differentially expressed and transcriptionally regulated. The paper discusses the molecular mechanisms of the SA signaling pathway, which plays a central role in plant immunity, and identifies differentially expressed genes (DEGs) that could be targeted for transcriptional detection. We have conducted a series of experiments to test the TAS strategy and found that the level of GmSAGT1 expression is highly correlated with soybean downy mildew (SDM) resistance with a correlation coefficient R² = 0.7981. Using RT-PCR, we screened 2501 soybean germplasms and selected 26 collections with higher levels of both GmSAGT1 and GmPR1 (Pathogenesis-related proteins1) gene expression. Twenty-three out of the twenty-six lines were inoculated with Peronospora manshurica (Pm) in a greenhouse. Eight showed HR (highly resistant), four were R (resistant), five were MR (moderately resistant), three were S (susceptible), and three were HS (highly susceptible). The correlation coefficient R² between the TAS result and Pm inoculation results was 0.7035, indicating a satisfactory consistency. The authors anticipate that TAS provides an effective strategy for screening crops with broad-spectrum and long-lasting resistance. Full article

Background/Objective: The Bale monkey (Chlorocebus djamdjamensis) is a threatened primate species endemic to Ethiopia and, in contrast to other members of the genus Chlorocebus, lives at high altitudes and feeds mainly on bamboo. Two populations of the species are present, one in continuous bamboo forest (CF) in the eastern part of the species’ range, and the other in fragmented forest (FF) in the western part. Based on mitochondrial DNA and phenotypic characteristics, previous studies have suggested introgression by parapatric congeners into the FF population but not into the CF population. The objective of this study was to gain insights into the evolutionary history of Bale monkeys and their potential genetic adaptations to high altitudes and for bamboo consumption. Methods: We sequenced the whole genomes of individuals from both populations and compared their genomes with those of the other five Chlorocebus species. We applied phylogenetic methods and conducted population demographic simulations to elucidate their evolutionary history. A genome-wide analysis was conducted to assess gene flow and identify mutations potentially associated with adaptations to high altitudes and for bamboo metabolism. Results: Our analyses revealed Bale monkeys as the sister clade to Chlorocebus aethiops and showed that gene flow occurred between C. aethiops and FF but not between C. aethiops and CF. In addition, we detected non-synonymous mutations in genes potentially associated with the adaptation to high altitudes (EPAS1) in both populations and with the adaptation for bamboo metabolism (TAS2R16, MPST, and TST) mainly in the CF population. Conclusions: Our study provides insights into the evolutionary history of a threatened primate species and reveals the genetic basis for its adaptions to unique environments and for diet specialization. Full article