Genes最新文献

Background: Mycetia, a subshrub genus within the subfamily Rubioideae (Rubiaceae), is predominantly distributed in tropical Asia, lacking comprehensive plastid genomic resources. This study aimed to characterize the complete plastid genomes of two Mycetia species and explore their structural features and evolutionary relationships.

Methods: The plastid genomes of Mycetia hirta and Mycetia sinensis were sequenced and assembled. We analyzed genome structure, simple sequence repeats (SSRs), long repeats, codon usage, nucleotide diversity (π), and Ka/Ks and conducted phylogenetic analysis.

Results: Both genomes exhibited a typical quadripartite structure (153,989-154,588 bp; GC content 37.7-37.8%), encoding 126 genes (86 protein-coding, 8 rRNA, and 32 tRNA). Both chloroplast genomes contained 52-60 SSRs and three repeat types with minor interspecific differences. Junction regions and codon usage were highly conserved, with slight variations in RSCU values. The average π was 0.0096, and the non-coding trnE-trnT (π = 0.0817) emerged as a potential DNA barcode. The average Ka/Ks was 0.2900, indicating purifying selection. Phylogenetic analysis confirmed the monophyly of Mycetia within Argostemmateae.

Conclusions: This study provides the first comparative plastid genomic analysis for Mycetia, enhancing our understanding of its genetic diversity and supporting future phylogenetic and taxonomic research on the genus.

Background/objectives: Mammary gland traits (milk quality and lactation performance) are economically critical for B. taurus and O. aries, but core regulatory hub genes remain unclear due to high false positives in single-method transcriptomic analyses. This study aimed to identify robust hub genes linked to species-specific differences in mammary gland tissue via an integrated bioinformatics strategy.

Methods: Raw transcriptomic data (77 B. taurus and 77 O. aries mammary gland samples) were retrieved from the European Nucleotide Archive (ENA); after quality control, differential expression gene (DEG) screening, weighted gene co-expression network analysis (WGCNA), and SHapley Additive exPlanations (SHAP)-assisted machine learning were performed, with core genes defined as the intersection of the three gene sets, and functional enrichment and protein-protein interaction (PPI) network analyses were used to prioritize hub genes.

Results: A total of 13,138 high-quality genes were retained, including 6148 DEGs, 4698 WGCNA core module genes, and 500 SHAP-high-contribution genes, yielding 178 core genes that were significantly enriched in the "translation" (p < 0.001) pathways; hub genes were identified via PPI network analysis.

Conclusions: These findings indicate that RPS15 and RPL7A are core species-difference signals in mammary gland tissue of B. taurus and O. aries, providing insights into inter-species molecular differences, and this integrated strategy enhances the robustness of hub gene identification in pure bioinformatics studies.

Background/Objectives: The RET (Rearranged during Transfection) gene encodes a receptor tyrosine kinase. RET plays a critical role in embryonic development and postnatal physiology. This review provides a comprehensive overview of RET-associated disorders, focusing on the molecular mechanisms of RET activation, associated clinical phenotypes and therapeutic implications. In addition, we present an updated RET mutation database. Methods:RET mutation database is built through the integration and curation of data from two major RET mutation repositories: the Leiden Open Variation Database (LOVD) and the Cancer Knowledge Base (CKB) as well as information derived from the ClinVar database. Results: To date, 78 pathogenic RET mutations have been identified, among these, 71 (91.0%) are single nucleotide substitutions (missense variants), 2 (2.6%) are deletions, 1 (1.3%) are indels, 2 (2.6%) are nonsense mutations and 1 (1.3%) mutation affecting the introns. A pronounced clustering was observed in exons 10-11, accounting for ~60% of cases, suggesting a potential mutational hotspot with structural or functional relevance. Conclusions: Aberrant RET activation, resulting from activating missense variants, gene fusions, or overexpression, underlies a wide spectrum of human diseases. These include multiple endocrine neoplasia type 2A (MEN2A), medullary thyroid carcinoma (MTC), Hirschsprung disease, and pheochromocytoma. The existence and use of a database classifying variants in the RET gene plays a fundamental role in molecular diagnostics and personalized medicine.

Background: ATP-binding cassette (ABC) transporters regulate xenobiotic efflux, oxidative stress responses, and blood-brain barrier (BBB) homeostasis. Dysregulation of transporters such as ABCC1, ABCB1, and ABCA2 has been linked to neuropsychiatric disorders, yet their expression patterns in schizophrenia and their modulation by antipsychotic treatment remain unclear. This study investigated longitudinal changes in the expression of these genes in schizophrenia patients before and after antipsychotic therapy, compared with healthy controls.

Methods: Sixty individuals with schizophrenia and sixty matched healthy controls were included. Serum samples were obtained from patients during the acute pre-treatment phase and after clinical improvement following antipsychotic therapy. Gene expression of ABCC1, ABCB1, and ABCA2 was measured by RT-qPCR (normalized to ACTB). Log2 fold-change (log2FC) values relative to controls were calculated. Group differences were assessed with Mann-Whitney U and Wilcoxon signed-rank tests, and associations with clinical severity were analyzed using correlations with Positive and Negative Syndrome Scale (PANSS) scores.

Results: In the acute phase, ABCC1 and ABCB1 expression were significantly downregulated in schizophrenia compared with controls (both p < 0.001). Antipsychotic treatment produced significant increases in both genes, though expression remained below control levels. ABCA2 showed no baseline differences but exhibited marked upregulation after treatment (p < 0.001). Higher baseline ABCC1 expression was associated with greater pre-treatment symptom severity, whereas higher baseline ABCB1 expression was associated with, rather than predicted, poorer clinical improvement. No significant correlations were found for ABCA2.

Conclusions: These findings demonstrate distinct, gene-specific alterations in ABC transporter expression in schizophrenia. ABCC1 and ABCB1 appear suppressed during acute illness and partially restored with antipsychotic therapy, while ABCA2 shows a strong treatment-related upregulation. ABC transporter expression-particularly ABCB1-may provide preliminary molecular insight into treatment-related variability, although biomarker utility cannot be established from the present data. Longitudinal pharmacogenomic studies are needed to clarify their clinical relevance.

Background/Objectives: In digenic populations, all females produce males and females in their offspring. Monogenic populations are composed of gynogenic (female-producing) and androgenic (male-producing) females. A theoretical population genetic model for evolution of digenic to monogenic populations is presented here. Methods: A controlling gene was associated with each of the four processes that characterise monogenic populations: (1) oogenesis is conventional, whereas spermatogenesis is unusual and it is characterised by the exclusive formation of X-bearing sperm (gene (s)), i.e., the paternal chromosomes are eliminated so that only the maternal ones are transmitted to the next generation; (2) the X chromosome that is eliminated in the zygote is the one inherited from the father (gene r); (3) an imprinting process occurs in the mother (gene g), which protects the maternally inherited X chromosome from elimination in the zygote and the whole maternal chromosome complement in spermatogenesis; (4) a maternal factor is produced during oogenesis (gene e), which inactivates the elimination factor [r] in the zygote, thus controlling the elimination of the paternal X chromosome. The sequences of emergence of the genes (e s r g) that transform a digenic population into a monogenic one were analysed. Results: The following evolutionary sequences were found: (1) the sequence (r s e) under dominant conditions of gene (s) and recessive conditions of gene (r); and (2) the sequences (s r e), (r s e), and (e s r) under recessive conditions of gene (s) and gene (r). It was also found that the process of genomic imprinting is a necessary condition for the generation of a monogenic population. Furthermore, a quantitative change in the interaction between the elimination factor and its maternal inhibitor modifies the genotypic formula of the monogenic state. Conclusions: The number and types of evolutionary transitions of a digenic to a monogenic population depends on the dominant or recessive characteristic of the newly emerging genes. The imprinting process must already be present in the digenic population from which the monogenic one evolves; otherwise, the population cannot reach the monogenic state.

Background/Objectives: Pharmacogenetic (PGx) testing is gaining importance in optimizing psychiatric pharmacotherapy, yet routine use remains limited due to cost and unclear patient selection criteria. The CYP Pharmacogenetic Risk Score (CYPRI) is a clinical tool designed to identify psychiatric patients most likely to benefit from PGx testing, based on medication profile, adverse drug reactions (ADRs), and therapeutic drug monitoring (TDM) results. This study aimed to evaluate the clinical relevance of the CYPRI by identifying its weaknesses and gaps in a clinical setting, propose targeted modifications to address those limitations, and assess the applicability of the improved version in a routine clinical setting. Methods: In a retrospective analysis, data from 92 patients with depression at Frankfurt University Hospital were evaluated using the CYPRI score. Its association with the clinical impact of PGx testing, measured by the IMPACT score, was analyzed using ordinal regression and Receiver Operating Characteristic (ROC) analysis. Based on the findings, a revised version of CYPRI was developed and applied to the retrospective cohorts of Frankfurt and Prague. Results: The original CYPRI score was significantly associated with increased IMPACT score, suggesting its clinical value in detecting non-normal CYP2D6 and/or CYP2C19 metabolizers. However, the corrected version (hereafter referred to as CYPRI_cor), which emphasized clinically relevant pharmacokinetic factors, showed improved clinical specificity while maintaining similar discriminative performance. In the Frankfurt cohort, the area under the curve (AUC) for CYPRI_cor was 0.68 (95% CI 0.56-0.79), and in the Prague cohort, the AUC for CYPRI_cor was 0.71 (95% CI 0.60-0.81). While the overall discriminative ability in Frankfurt was slightly lower, CYPRI_cor achieved a specificity of 0.69, enabling more precise identification of patients most likely to benefit from PGx testing. A CYPRI Cut-off of ≥4 was determined to indicate clinical impact. Conclusions: The CYPRI_cor score was designed to optimize and to rule out potential limitations of the original score, particularly regarding the attribution of ADRs and the weighting of TDM results. Although the modifications did not improve discriminative performance in the Frankfurt dataset, the proposed changes remain meaningful. Prospective clinical studies need to verify the clinical utility of the CYPRI_cor.

Background/objectives: Identifying archaeobotanical wheat remains is central to reconstructing the evolutionary history of cereal crops. Beyond documenting agricultural practices, such analyses provide critical evidence of phylogenetic diversity, lineage persistence, and local extinction events within the genus Triticum L. This study applies advanced computational morphometrics to reveal deep-time changes in wheat species distribution, including the disappearance of taxa now phylogeographically confined to central Asia.

Methods: We developed a machine learning framework integrating Random Forest compared with logistic regression to classify morphometric data from 848 dry and 340 experimentally carbonized modern grains representing multiple wheat taxa (genus Triticum), alongside 15 archaeobotanical T. turgidum subsp. parvicoccum and 38 T. aestivum var. antiquorum. This probabilistic classifier was then applied to 2463 archeological wheat grains, including 48 from Punta de los Gavilanes and 517 from Almizaraque (southeastern Spain, 3rd-2nd millennium BC).

Results: The analysis identified Triticum sphaerococcum and other phylogenetically distinct wheat taxa-today restricted to central and south Asia-among western European Bronze Age assemblages. These findings indicate that lineages now regionally extinct once formed part of a broader cultivated gene pool spanning into the western Mediterranean. Morphometric evidence highlights that past wheat diversity encompassed multiple clades and morphotypes absent from modern European germplasm.

Conclusions: Our results demonstrate substantial phylogenetic turnover in wheat over the past 4000 years, marked by regional extirpations and contraction of once-widespread lineages to central Asia. This provides rare archeological evidence for the tempo and mode of cereal phylogeography, illustrating how domesticated lineages underwent extinction and range restriction akin to wild taxa. By integrating computational morphometrics with archaeobotanical evidence, this study establishes a scalable framework for tracing cryptic phylogenetic diversity, refining models of wheat domestication and assessing long-term genetic erosion in cultivated plants.

Background: Secondary pathogenic/likely pathogenic germline variants (P/LPGVs) identified on solid tumor genomic profiling (TGP) are a commonly encountered clinical issue. A proportion of oncology patients that undergo TGP will have a secondary P/LPGV identified that may not have been otherwise discovered based on clinical and family history criteria for hereditary cancer syndrome screening. The confirmation of P/LPGVs on germline sequencing has potential treatment implications for patients.

Methods: The study design was a retrospective review for secondary data analysis. The inclusion criteria for this study were adult patients with solid tumor malignancy who underwent TGP and germline sequencing. The objective of this study is to evaluate the concordance rate of secondary P/LPGVs on TGP of adult patients with solid tumor malignancy at Hoag Presbyterian Hospital and Tower Health-Reading Hospital. The second and third aims are to analyze if the confirmed P/LPGVs are concordant with the patient's tumor type and to analyze the variant allele frequencies (VAFs) of the identified secondary P/LPGVs on the tumor genomic profiling.

Results: The data included 75 patients who underwent both TGP and germline sequencing, with a median age of 62.5 years. The most represented genes with P/LPGVs in the combined data included BRCA1 and BRCA2, both with 14, and MSH2, with 9. The overall germline concordance rate for the combined population was 64.1%, with 59 out of 92 P/LPGVs identified on both germline and somatic tumor testing.

Conclusions: The overall germline concordance rate of 64% for the combined population is in accordance with the reported literature. Possible reasons for the variability in rates could be related to reporting guidelines for secondary germline variants, which can vary by company, and differences between somatic and germline variant curation. The study of P/LPGVs in populations from community cancer centers has the potential to increase the data of underrepresented minority groups regarding this important clinical issue and help expand understanding of hereditary cancer syndrome phenotypes.

Background/Objectives: Arnica montana L. is widely recognized for its diverse biological activities, including antimicrobial effects. This study aimed to evaluate the antimicrobial and antibiofilm activity of A. montana L. extracts against Acinetobacter baumannii, a pathogen of urgent public health concern due to its increasing antibiotic resistance and capacity for biofilm formation. Methods: The antimicrobial activity of ethanolic (EtE) and aqueous (AqE) extracts of A. montana flowers was evaluated via the broth microdilution method. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), and the MBC/MIC ratio were used. The effects of EtE on A. baumannii biofilm formation were assessed via a crystal violet assay. Additionally, transcriptional profiling of biofilm-associated genes following exposure to sub-MIC levels of the extract was conducted via RT-qPCR. Results: The anti-Acinetobacter activity of EtE was demonstrated (MIC = 234.4 and 468.75 µg/mL for A. baumannii ATCC BAA-3252 and ATCC 19606, respectively). The EtE exhibited bactericidal activity against both strains, whereas the AqE showed no activity. Additionally, EtE inhibited biofilm formation and significantly downregulated the expression of key biofilm-associated genes, including those of the csu operon and ompA. Conclusions: Arnica montana EtE demonstrated antimicrobial and antibiofilm activities against A. baumannii and inhibited biofilm development by suppressing the transcription of genes involved in pilus assembly and surface adherence, highlighting their essential role in biofilm formation.

Hypophosphatasia (HPP) is an exceptional genetic bone disorder of metabolic character caused by a deficit of the tissue-nonspecific alkaline phosphatase isoenzyme (TNSALP). This protein is encoded by the ALPL (alkaline phosphatase liver/bone/kidney) gene. In the medical literature, HPP is also known as Rathbun's syndrome, named after the Canadian physician who first identified this disorder. Patients exhibit persistently low serum alkaline phosphatase (ALP) levels. In fact, ALP renders this measure a reliable indicator of the condition. Adult HPP is varied, with some patients exhibiting only moderate, non-pathognomonic symptoms. They include arthropathy, arthrodynia, chondrocalcinosis, osteopenia, osteomalacia, and generic musculoskeletal discomfort. Healthcare may require coordinating several services to manage a patient with HPP. This comprehensive review will highlight the genetic knowledge, pathology data, and patient management approaches, including Medicare's coverage. In addition, this paper aims to address specific themes related to HPP, including its significance, current challenges, and controversies.