Search Results (27)

Primary ciliary dyskinesia (PCD) is a rare hereditary disorder belonging to the group of ciliopathies, with autosomal recessive, autosomal dominant, and, less frequently, X-linked inheritance patterns. The aim of this study was to investigate the genetic heterogeneity of the Russian population of PCD patients based on national registry data. The study included patients with PCD confirmed by molecular genetic testing. Quantitative data were analyzed using non-parametric statistical methods. Differences were considered statistically significant at p < 0.05. The study included 109 patients with PCD. Molecular genetic testing identified pathogenic variants in 29 autosomal recessive genes. The analysis of pathogenic variant distribution in the Russian PCD cohort revealed the highest number of changes in the DNAH5 and DNAH11 genes. 26 genetic variants in 13 genes were identified for the first time in the Russian population. Variants in the DNAH5 gene were significantly more frequent in Kartagener’s syndrome (KS) patients (32/55%) compared to those without KS (11/21.5%) (χ² = 12.8; p = 0.0004; OR = 4.48). Preliminary data indicate that the frequency spectrum of DNAH5 and DNAH11 genes in Russian patients is similar to international trends. Additionally, there is an accumulation of pathogenic variants in the DNAH5, DNAH11, CCDC39, and CFAP300 genes. Full article

Inherited retinal dystrophies (IRDs) are a diverse group of monogenic disorders associated with dysfunction of the retina. High myopia, commonly defined as a spherical equivalent ≤ −6.00 D or axial length ≥ 26.5 mm, is a recurring clinical feature across several IRDs, and could serve as an early diagnostic clue. This review provides a summary of IRDs associated with high myopia to guide the clinician in establishing a molecular diagnosis for patients. We performed a comprehensive literature review of articles in PubMed, ScienceDirect, and JAMA Network to identify associations between monogenic IRDs and high myopia. Genes associated with IRDs and high myopia clustered into functional categories that included collagen/structural integrity (COL2A1, COL9A1, COL11A1, COL18A1, P3H2), phototransduction and visual cycle (PDE6C, PDE6H, GUCY2D, ARR3, RBP3), ciliary trafficking and microtubule-associated genes (RPGR, RP2, IFT140, CFAP418, FAM161A), synaptic ribbon and bipolar cell signaling (NYX, CACNA1F, TRPM1, GRM6, LRIT3, GPR179), opsin-related genes (OPN1LW, OPN1MW), and miscellaneous categories (VPS13B, ADAMTS18, LAMA1). Associations between IRDs and high myopia spanned stationary and progressive retinal disorders and included both cone-dominant and rod-dominant diseases. High myopia accompanied by other visual symptoms and signs such as nyctalopia, photophobia, or reduced best-corrected visual acuity should heighten suspicion for an underlying IRD. Earlier diagnosis of IRDs for patients could facilitate timely genetic counseling, participation in clinical trials, and interventions for patients to preserve vision.: Full article

The wild yak (Bos mutus) is a flagship species on the Qinghai–Tibet Plateau, possessing significant ecological functions and conservation value. Using single-nucleotide polymorphism markers from whole-genome resequencing, we systematically analyzed golden wild yak (n = 37), common wild yak (n = 106), and domestic yak (Bos grunniens) (n = 20) to characterize the population genetic structure and adaptive selection signals in the golden wild yak. Genetic diversity analyses revealed that the golden wild yak had the lowest nucleotide diversity (π = 0.00148) and the highest inbreeding coefficient (F_Hom = 0.043). Population structure analyses integrating principal component analysis, phylogenetic tree, and ancestral component clustering indicated that the golden wild yak formed a relatively independent evolutionary lineage. However, its genetic differentiation from sympatric common wild yak population was limited (fixation index = 0.031). Selective sweep analysis identified a set of candidate positively selected genes in the golden wild yak genome associated with key traits and physiological functions, including coat color (TYRP1), hypoxia adaptation (MYH11, POLQ), reproductive function (SLC9C1, SPAG16, CFAP97D1), and immune response (CASP8, PGGT1B, BIRC6). Overall, our study reveals a distinct genetic background and selection signatures in the golden wild yak and provides genomic insights to inform the conservation and management of the wild yak. Full article

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired mucociliary clearance due to defects in motile cilia. This study investigates the impact of loss-of-function mutations in the CFAP300 gene on the ciliary structure and function in three PCD patients. Using a multimodal approach, we integrated molecular genetic testing, transmission electron microscopy, the high-speed video microscopy assay and immunofluorescence staining to analyze ciliary motility and protein expression in both ex vivo and in vitro-obtained ciliary cells. Our results revealed that the pathogenic variant c.198_200delinsCC (p.Phe67ProfsTer10) in CFAP300 led to the absence of the functional CFAP300 protein, the complete loss of outer and inner dynein arms and immotile cilia. Air–liquid interface (ALI)-cultured cells from patients exhibited no ciliary beating, contrasting with healthy controls. Immunostaining confirmed the absence of CFAP300 in patient-derived cilia, underscoring its critical role in dynein arm assembly. These findings highlight the diagnostic utility of ALI cultures combined with functional and protein analyses for PCD, offering a clinically actionable framework that can be readily incorporated into standard diagnostic workflows. Full article

Lesch–Nyhan disease (LND) is associated with a complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity due to mutations in the HPRT1 gene. Although the physiopathology of LND-related neurological manifestations remains unknown, a defective neuronal developmental process is the most widely accepted hypothesis. We generated an HPRT-deficient line from the pluripotent human embryonic cell line NT2/D1 by CRISPR-Cas9 and induced its differentiation along neuroectodermal lineages by retinoic acid treatment. As levels of folic acid in the culture media may affect results in LND models, we employed physiological levels of folate. The effect of HPRT deficiency on neural development-related gene expression was evaluated using two methodological approaches: a directed qPCR array of genes related to neuronal differentiation, and global gene expression by RNAseq. HPRT-deficient pluripotent cells presented altered expression of genes related to pluripotency in human embryonic stem cells, such as DPPA3 and CFAP95, along with genes of the homeobox gene family. HPRT-deficient pluripotent cells were able to differentiate along neuro-ectodermal lineages but presented consistent dysregulation of several genes from the homeobox gene family, including EN1 and LMX1A. GO enrichment analysis of up- and downregulated genes in HPRT-deficient cells showed that the most significant biological processes affected are related to development and nervous system development. Full article

Continuous flight auger piles (CFAPs) are highly versatile and productive deep foundation elements. Known for their execution speed, low noise, and minimal vibration, they are extensively used in Brazil, particularly for urban projects or environmentally sensitive areas. Technologically, they employ a Real-Time Operation System (RTOS) to control the execution energy for each drilled pile. When used effectively, this energy-based monitoring system can provide information that replaces or correlates with other challenging-to-measure variables, accommodating the impact of various exogenous variables on a pile’s execution and performance. Foundation designers often define one or more characteristic lengths for different pile groups, considered representative for each group despite uncertainties and morphological changes along the terrain. Hence, considering an energy-based control, which enables an individual assessment for each pile, is beneficial given soil’s complexity, which can vary significantly even within a small area. By determining the optimal execution energy, individualized stopping criteria for piles can be established, directly influencing costs and productivity and enhancing reliability. The present paper proposes a methodological workflow to automate the necessary calculations for execution energies, correlate them with bearing capacities measured by load tests or estimated from standard soil surveys, and predict the execution energy and corresponding stopping criteria for the drilling depth of each pile. This study presents a case study to illustrate the methodology proposed, accounting for a real construction site with multiple piles. It shows that considering fixed-length piles may not favor safety, as the energy-based analysis revealed that some piles needed longer shafts. This study also shows that for the 316 CFAPs analyzed with depths ranging from 8 to 14 m, a total of 564 m of pile shafts was unnecessary (which accounted for more than 110 m³ of concrete), indicating that cost optimization is possible. Overall, these analyses improve design safety and reliability while reducing execution costs. The results demonstrate that execution energy can serve as a proxy for subsurface resistance, correlating well with NSPT values and bearing capacity estimations. The methodology enables the individualized assessment of pile performance and reveal the potential for improving the reliability and cost-effectiveness of the geotechnical design process. Full article

Xinjiang Brown cattle is an elite dual-purpose breed (raised for dairy and beef) developed in China. To elucidate its genomic architecture, we conducted whole-genome resequencing of 169 Xinjiang Brown cattle, followed by structural variation (SV) detection and a genome-wide association study (GWAS). We identified 71,668 SVs, among which deletions were the most prevalent, followed by translocations, inversions, duplications, and insertions. We further identified 1286 high-frequency SVs involving 2016 protein-coding genes. Through functional enrichment analysis of these genes, we revealed associations of genetic variation at genomic positions near genes implicated in immune response and disease resistance (NFKBIZ and PTPRT), growth and development (HDAC4 and MEF2A), and milk production (TP63, FABP4, and MEF2A). GWAS analysis of 31 body conformation traits revealed 58 SVs significantly associated with five traits (chest width, rear udder width, udder depth, rump width, and heel depth) at the genome-wide level. Additionally, nine candidate genes (CLINT1, EBF1, PAM16, GRIP1, CFAP54, SLC22A16, DOK5, ETAA1, and IPMK) were identified as potentially involved in the genetic regulation of body conformation traits. These findings provide novel insights for genetic improvement strategies and indicate that precision breeding could further enhance the production performance of this breed in the future. Full article

Background: The testis, a critical reproductive organ in male animals, is responsible for sperm production and androgen secretion. Testis weight often correlates with reproductive performance, yet the genetic factors influencing testicular traits in chickens remain unclear. Methods: Previous genome-wide association studies (GWAS) have identified key genes affecting testicular traits in Kangle Yellow chickens, along with the associated regulatory pathways and Gene Ontology (GO) terms, through bioinformatic analyses. In this study, we utilized the existing literature, full-length transcriptome data, and proteome analyses to select key candidate genes. Results: We identified 13 associated markers for chicken testicular traits with 262 candidate genes. Nine candidate genes were found to regulate chicken testicular traits referred to integrated analysis, including CDH3, ZFPM1, CFAP52, ST6GAL1, IGF2BP2, SPG7, CDT1, NFAT5, and OPRK1. Physical interactions among these genes were also observed, implicating mechanisms such as cell adhesion molecules and neuroactive ligand–receptor interaction. Conclusions: These findings provide a genetic basis for improving testicular traits in Chinese native chicken breeds. Full article

Seasonal outbreaks and occasional pandemics triggered by influenza viruses annually impose considerable burdens on public health and finances. The continual evolution of viral strains with drug resistance emphasizes the urgency of discovering novel agents for influenza viruses. This study investigated a set of innovative substances derived from Morinda officinalis with antiviral potential against influenza virus strains. The top candidate, anthraquinone-2-carboxylic acid (A2CA), presented antiviral activity against diverse influenza virus strains, including those resistant to oseltamivir. In an influenza mouse model, the pre-administration of A2CA dose-dependently ameliorated influenza A virus (IAV)-mediated weight loss as well as protected mice from a lethal IAV infection. In addition, lung injury and cytokine dysregulation were mitigated. Further investigation revealed that IAV-induced activation of the RIG-I/STAT1 signaling pathway did not occur after A2CA treatment. A time-of-addition assay revealed that A2CA targeted the final phase of intracellular replication, which was further determined by molecular docking between A2CA and the IAV RdRp protein. Finally, transcriptome analysis revealed that the TP53TG3C, CFAP57 and SNX30-DT genes may be involved in the antiviral effects of A2CA. These results play a part in achieving a thorough comprehension of the capacity of A2CA to inhibit influenza virus infection. Full article

Background: Food insecurity is a major global problem, with over 2.8 billion people reported as unable to afford a healthy diet in 2022. While charitable food assistance programs (CFAPs) play an important role in improving food access, ensuring the quality and safety of donated foods is crucial for safeguarding needy communities from food-related illnesses. This study evaluated the safety and quality of food donations at a food bank warehouse in the eThekwini District using a novel methodology. Methods: In March 2024, a five-day audit was conducted at a food bank warehouse in the eThekwini District, KwaZulu-Natal, South Africa. A mobile device was utilized to document comprehensive information on all incoming deliveries, including the type of food, product details (such as brand, name, and variety), donor information, weight, and date markings. The audit assessed 1037 items, totaling 64,818 kg of donated food, against established food safety standards. Each item was visually inspected upon arrival and classified as ‘unsuitable’, ‘potentially unsafe’, or ‘unsafe’ for human consumption. Results: Out of the 64,818 kg of donated food, 95.5% (61,886 kg) was deemed satisfactory. However, 4.5% of the total, which amounts to 2932 kg, was categorized as either unsafe (355 kg), potentially unsafe (1182 kg), or unsuitable (1395 kg) for consumption. Retail supermarkets donated the largest weight of food, and also of the food classified as unsafe or unsuitable. Conclusions: The study highlights an urgent need for improved quality control and safety measures in food donations to CFAPs. Stricter handling and inspection guidelines are essential to ensure the quality of charitable food, reduce health risks, and build public trust in donation programs. Full article

Background: Reproductive performance is critical in the pig industry, and improved sow performance could lead to increased economic benefits. GWAS and ROH analyses based on SNP array data were conducted to identify the breed-specific genetic architecture underlying the variation in NBA and TNB. Methods: A total of 7488 breeding pigs with phenotypic data from 1586 Duroc, 2256 Landrace, and 3646 Yorkshire breeds, along with 76,756 SNP markers from Korean grand-grand-parent (GGP) breeding farms, were used. Results: In the Duroc breeds, SNPs on SSC 9 and 17 were found to be associated with the SIDT2 and TGM2 genes, respectively. In the Landrace breed, PPP1R9A, LMTK2, and GTF2H3 on SSCs 9, 3, and 14, respectively, were associated with both TNB and NBA. With the Yorkshire breed genome, GRID1, DLGAP2, ZZEF1, PARG, RNF17, and NDUFAF5 in SSCs 14, 15, 12, 14, 11, and 17, respectively, were associated with NBA and TNB traits. These genes have distinct functions, ranging from synaptic transmission and cytoskeletal organization to DNA repair and cellular energy production. In the Duroc breed, six genes identified in the ROH islands were associated with various biological pathways, molecular functions, and cellular components. NT5DC1 was associated with metaphyseal chondrodysplasia, CRTAC1 with ion binding, CFAP43 with spermatogenic failure, CASC3 with intracellular mRNA localization, ERC2 with cellular component organization, and FOCAD with Focadhesin. In the Landrace and Yorkshire breeds, PDE6D was associated with GTPase inhibitor activity. Conclusions: Through GWAS and ROH analyses, we identified breed-specific SNP markers associated with NBA and TNB in three breed genotypes, providing insights for improving reproductive performance efficiency and contributing to future breeding strategies. Full article

Proteasome 26S Subunit, Non-ATPase 9 (psmd9) plays an important role in the balance of protamine and the stability of the nucleolar structure during spermatogenesis. In this study, we cloned the psmd9 of Cynoglossus semilaevis and analyzed its expression pattern. psmd9 was identified on the Z chromosome of C. semilaevis, which is considered an interesting candidate gene for spermatogenesis. qRT-PCR and FISH experiments showed that the psmd9 gene was significantly highly expressed in the testes. It is worth noting that the expression level of psmd9 in male fish testes is significantly higher than that in pseudomales. In order to further explore the role of psmd9 in spermatogenesis, a male testicular cell line was used as the experimental material. The results of the psmd9-RNAi and overexpression experiments showed that psmd9 had a synergistic effect with spermatogenesis-related genes dnd1, cfap69, dnah3 and dnajb13, but had an antagonistic effect with ccne2. Our findings offer a scientific foundation for comprehending the role of psmd9 in the spermatogenesis regulatory network of C. semilaevis. Full article

The hybrid yellow catfish exhibits advantages over pure yellow catfish in terms of fast growth, fast development, a high feeding rate, and strong immunity; additionally, it is almost sterile, thus ensuring the conservation of the genetic stock of fish populations. To investigate the sterility mechanism in hybrid yellow catfish (P. fulvidraco (♀) × P. vachelli (♂)), the mRNA and miRNA of the gonads of P. fulvidraco, P. vachelli, and a hybrid yellow catfish were analyzed to characterize the differentially expressed genes; this was carried out to help establish gene expression datasets to assist in the further determination of the mechanisms of genetic sterility in hybrid yellow catfish. In total, 1709 DEGs were identified between the hybrid and two pure yellow catfishes. A KEGG pathway analysis indicated that several genes related to reproductive functions were upregulated, including those involved in the cell cycle, progesterone-mediated oocyte maturation, and oocyte meiosis, and genes associated with ECM–receptor interaction were downregulated. The spermatogenesis-related GO genes CFAP70, RSPH6A, and TSGA10 were identified as being downregulated DEGs in the hybrid yellow catfish. Sixty-three DEmiRNAs were identified between the hybrid and the two pure yellow catfish species. The upregulated DEmiRNAs ipu-miR-194a and ipu-miR-499 were found to target the spermatogenesis-related genes CFAP70 and RSPH6A, respectively, playing a negative regulatory role, which may underscore the miRNA–mRNA regulatory mechanism of sterility in hybrid yellow catfish. The differential expression of ipu-miR-196d, ipu-miR-125b, and ipu-miR-150 and their target genes spidr, cep85, and kcnn4, implicated in reproductive processes, was verified via qRT-PCR, consistent with the transcriptome sequencing expression trends. This study provides deep insights into the mechanism of hybrid sterility in vertebrate groups, thereby contributing to achieving a better understanding and management of fish conservation related to hybrid sterility. Full article

Canine osteosarcoma (OSA) is an aggressive bone neoplasia with high metastatic potential. Metastasis is the main cause of death associated with OSA, and there is no current treatment available for metastatic disease. Proteomic analyses, including matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI TOF/TOF MS), are widely used to select molecular targets and identify proteins that may play a key role in primary tumours and at various steps of the metastatic cascade. The main aim of this study was to identify proteins differently expressed in canine OSA cell lines with different malignancy phenotypes (OSCA-8 and OSCA-32) compared to canine osteoblasts (CnOb). The intermediate aim of the study was to compare canine OSA cell migration capacity and assess its correlation with the malignancy phenotypes of each cell line. Using MALDI-TOF/TOF MS analyses, we identified eight proteins that were significantly differentially expressed (p ≤ 0.05) in canine OSA cell lines compared to CnOb: cilia- and flagella-associated protein 298 (CFAP298), general transcription factor II-I (GTF2I), mirror-image polydactyly gene 1 protein (MIPOL1), alpha-2 macroglobulin (A2M), phosphoglycerate mutase 1 (PGAM1), ubiquitin (UB2L6), ectodysplasin-A receptor-associated adapter protein (EDARADD), and leucine-rich-repeat-containing protein 72 (LRRC72). Using the Simple Western technique, we confirmed high A2M expression in CnOb compared to OSCA-8 and OSCA-32 cell lines (with intermediate and low A2M expression, respectively). Then, we confirmed the role of A2M in cancer cell migration by demonstrating significantly inhibited OSA cell migration by treatment with A2M (both at 10 and 30 mM concentrations after 12 and 24 h) in a wound-healing assay. This study may be the first report indicating A2M’s role in OSA cell metastasis; however, further in vitro and in vivo studies are needed to confirm its possible role as an anti-metastatic agent in this malignancy. Full article

DNA methylation (DNAm) is associated with the reproductive system. However, the genetic mechanism through which DNAm regulates gene expression and thus affects litter size in goats is unclear. Therefore, in the present work, genome-wide DNAm profiles of HP and LP Jining Grey goat ovary tissues were comprehensively analyzed via WGBS, and RNA-Seq data were combined to identify candidate genes associated with litter size traits in the Jining Grey goat. Finally, BSP and RT-qPCR were used to verify the sequencing results of the key genes. Notably, the DNMT genes were downregulated at the expression level in the HP group. Both groups exhibited comparable levels of methylation. A total of 976 differentially methylated regions (DMRs) (973 DMRs for CG and 3 DMRs for CHG) and 310 differentially methylated genes (DMGs) were identified in this study. Through integration of WGBS and RNA-Seq data, we identified 59 differentially methylated and differentially expressed genes (DEGs) and ultimately screened 8 key DMGs (9 DMRS) associated with litter size traits in Jining Grey goats (SERPINB2: chr24_62258801_62259000, NDRG4: chr18_27599201_27599400, CFAP43: chr26_27046601_27046800, LRP1B. chr2_79720201_79720400, EPHA6: chr1_40088601_40088800, TTC29: chr17_59385801_59386000, PDE11A: chr2_117418601_117418800 and PGF: chr10_ 16913801_16914000 and chr10_16916401_16916600). In summary, our research comprehensively analyzed the genome-wide DNAm profiles of HP and LP Jining Grey goat ovary tissues. The data findings suggest that DNAm in goat ovaries may play an important role in determining litter size. Full article