Region Of Gene Research Articles

Clinical and genetic analysis of a patient with Neuronal intranuclear inclusion body disease characterized by cortical enhancement in the posterior brain region

To explore the clinical, imaging, and genetic characteristics of an adult patient with sporadic Neuronal intranuclear inclusion disease (NIID). A patient who had visited the First People's Hospital of Chenzhou on August 6, 2023 was selected as the study subject. Results of clinical examination, neuroimaging, and genetic testing were retrospectively analyzed along with a literature review. The number of GGC trinucleotide repeats in the 5'-untranslated region of the NOTCH2NLC gene was determined by GC-PCR. The patient had presented with episodic encephalopathy, with enhanced magnetic resonance imaging showing enhancement features of the posterior cerebral cortex during the period of acute episode. Genetic testing revealed an increased number of GGC repeats (n = 97) in the 5'- untranslated region of the NOTCH2NLC gene, which confirmed the diagnosis of NIID. Clinical attention should be paid to the enhanced MRI findings of patients with adult-onset NIID, for whom posterior cortical enhancement may be characteristic manifestation during the acute phase of encephalopathy-like episode.

Epidemiological and molecular characteristics of Infectious bursal disease virus naturally infected in the broiler flocks in the Mekong Delta of Vietnam during 2015 and 2018

Infectious bursal disease is a highly contagious and economically devastating disease in the poultry industry worldwide caused by Infectious bursal disease virus (IBDV). However, the data on epidemiological and molecular characteristics of the IBDV outbreak in broiler flocks in the Mekong Delta of Vietnam is unclear. Herein, the epidemiological data of IBDV–positive flocks over a period of 2015–2018 were recorded and the hypervariable region of the VP2 gene of IBDV was amplified to analyze the local phylogeny. The current investigation showed that the overall morbidity and mortality rates of IBDV–positive flocks were 45% and 4.81%, respectively. The IBDV–positive birds occurred clinical signs and macroscopic findings involved with the very virulent (vv) IBDV outbreak. Epidemiological results revealed that IBDV was frequently infected in broiler flocks at 12–42 days, and birds belonging to Tau Vang and Binh Dinh breeds were more sensitive to IBDV. Also, the morbidity rate of IBDV was dramatically decreased in the open farming system. Flocks with complete vaccination significantly dropped morbidity in comparison with other groups. Regarding phylogenetic analysis, all identified IBDV sequences clustered in the same branch of vv phenotype and closely homology with prior strains circulated in Vietnam and other countries. These findings first indicated the epidemiological characteristics of the IBDV–positive broiler flocks in the Mekong Delta and highlighted the IBDV strain circulating in this region.

Two new species of Dulcicalothrix (Nostocales, Cyanobacteria) from India and erection of Brunnivagina gen. nov., with observations on the problem of using multiple ribosomal operons in cyanobacterial taxonomy.

Two new species of Dulcicalothrix, D. adhikaryi sp. nov. and D. iyengarii sp. nov., were discovered in India and are characterized and described in accordance with the rules of the International Code of Nomenclature for algae, fungi, and plants (ICN). As a result of phylogenetic analysis, Calothrix elsteri is reassigned to Brunnivagina gen. nov. During comparison with all Dulcicalothrix for which sequence data were available, we observed that the genus has six ribosomal operons in three orthologous types. Each of the three orthologs could be identified based upon indels occurring in the D1-D1' helix sequence in the ITS rRNA region between the 16S and 23S rRNA genes, and in these three types, there were operons containing ITS rRNA regions with and without tRNA genes. Examination of complete genomes in Dulcicalothrix revealed that, at least in the three strains for which complete genomes are available, there are five ribosomal operons, two with tRNA genes and three with no tRNA genes in the ITS rRNA region. Internal transcribed spacer rRNA regions have been consistently used to differentiate species, both on the basis of secondary structure and percent dissimilarity. Our findings call into question the use of ITS rRNA regions to differentiate species in the absence of efforts to obtain multiple operons of the ITS rRNA region through cloning or targeted PCR amplicons. The ITS rRNA region data for Dulcicalothrix is woefully incomplete, but we provide herein a means for dealing with incomplete data using the polyphasic approach to analyze diverse molecular character sets. Caution is urged in using ITS rRNA data, but a way forward through the complexity is also proposed.

Epigenetic repression of de novo cysteine synthetases induces intra-cellular accumulation of cysteine in hepatocarcinoma by up-regulating the cystine uptake transporter xCT

BackgroundThe metabolic reprogramming of amino acids is critical for cancer cell growth and survival. Notably, intracellular accumulation of cysteine is often observed in various cancers, suggesting its potential role in alleviating the oxidative stress associated with rapid proliferation. The liver is the primary organ for cysteine biosynthesis, but much remains unknown about the metabolic alterations of cysteine and their mechanisms in hepatocellular carcinoma cells.MethodsRNA-seq data from patients with hepatocarcinoma were analyzed using the TNMplot database. The underlying mechanism of the oncogenic alteration of cysteine metabolism was studied in mice implanted with BNL 1ME A.7 R.1 hepatocarcinoma.ResultsDatabase analysis of patients with hepatocellular carcinoma revealed that the expression of enzymes involved in de novo cysteine synthesis was down-regulated accompanying with increased expression of the cystine uptake transporter xCT. Similar alterations in gene expression have also been observed in a syngeneic mouse model of hepatocarcinoma. The enhanced expression of DNA methyltransferase in murine hepatocarcinoma cells caused methylation of the upstream regions of cysteine synthesis genes, thereby repressing their expression. Conversely, suppression of de novo cysteine synthesis in healthy liver cells induced xCT expression by up-regulating the oxidative-stress response factor NRF2, indicating that reduced de novo cysteine synthesis repulsively increases cystine uptake via enhanced xCT expression, leading to intracellular cysteine accumulation. Furthermore, the pharmacological inhibition of xCT activity decreased intracellular cysteine levels and suppressed hepatocarcinoma tumor growth in mice.ConclusionsOur findings indicate an underlying mechanism of the oncogenic alteration of cysteine metabolism in hepatocarcinoma and highlight the efficacy of alteration of cysteine metabolism as a viable therapeutic target in cancer.

Targeted Reprogramming of Pathogenic Fibroblast Genes at the 3'-Untranslated Regions by DNA Nanorobots for Periodontitis.

Periodontitis, with its persistent nature, causes significant distress for most sufferers. Current treatments, such as mechanical cleaning and surgery, often fail to fully address the underlying overactivation of fibroblasts that drives this degradation. Targeting the post-transcriptional regulation of fibroblasts, particularly at the 3'-untranslated regions (3'UTR) of pathogenic genes, offers a therapeutic strategy for periodontitis. Herein, we developed a DNA nanorobot for this purpose. This system uses a dynamic DNA nanoframework to incorporate therapeutic microRNAs through molecular recognition and covalent bonds, facilitated by DNA monomers modified with disulfide bonds. The assembled-DNA nanoframework is encapsulated in a cell membrane embedded with a fibroblast-targeting peptide. By analyzing the 3'UTR regions of pathogenic fibroblast genes FOSB and JUND, we identified the therapeutic microRNA as miR-1-3p and integrated it into this system. As expected, the DNA nanorobot delivered the internal components to fibroblasts by the targeting peptide and outer membrane that responsively releases miR-1-3p under intracellular glutathione. It resulted in a precise reduction of mRNA and suppression of protein function in pathogenic genes, effectively reprogramming fibroblast behavior. Our results confirm that this approach not only mitigates the inflammation but also promotes tissue regeneration in periodontal models, offering a promising therapeutic avenue for periodontitis.

Microbiological and molecular profile of furcation defects in a population with untreated periodontitis.

To describe the microbiological composition of subgingival dental plaque and molecular profile of gingival crevicular fluid (GCF) of periodontal furcation-involved defects. Fifty-seven participants with periodontitis contributed with a degree II-III furcation involvement (FI), a non-furcation (NF) periodontal defect and a periodontally healthy site (HS). Subgingival plaque was analysed by sequencing the V3-V4 region of the 16S rRNA gene, and a multiplex bead immunoassay was carried out to estimate the GCF levels of 18 GCF biomarkers. Aiming to explore inherent patterns and the intrinsic structure of data, an AI-clustering method was also applied. In total, 171 subgingival plaque and 84 GCF samples were analysed. Four microbiome clusters were identified and associated with FI, NF and HS. A reduced aerobic microbiota (p = .01) was detected in FI compared with NF; IL-6, MMP-3, MMP-8, BMP-2, SOST, EGF and TIMP-1 levels were increased in the GCF of FI compared with NF. This is the first study to profile periodontal furcation defects from a microbiological and inflammatory standpoint using conventional and AI-based analyses. A reduced aerobic microbial biofilm and an increase of several inflammatory, connective tissue degradation and repair markers were detected compared with other periodontal defects.

Regulation of the expression of MHETase and TPA degradation genes involved in the degradation of PET in Ideonella sakaiensis.

Ideonella sakaiensis is a bacterium that can degrade and consume polyethylene terephthalate (PET), a plastic material that was previously considered non-biodegradable. The degradation of PET requires two enzymes, namely poly (ethylene terephthalate) hydrolase (PETase) and mono (2-hydroxyethyl) terephthalate hydrolase (MHETase), which break down PET into terephthalate (TPA) and ethylene glycol (EG), which serve as carbon sources for the bacterium. Previous studies have focused on the enzymatic properties, structure, and mechanism of action of PETase and MHETase. However, the regulation of PETase and MHETase gene expression has not been investigated. This study identified a protein that binds to the MHETase promoter DNA, MHETase gene-regulating protein (MRP) in I. sakaiensis. PET or TPA induced the expression of PETase and MHETase genes. Furthermore, the induction of the MHETase gene was abolished by the deletion of the mrp gene, while the expression of the PETase gene was maintained. In addition, the genes involved in TPA metabolism were not induced in the mrp mutant. Furthermore, the growth of the PET and TPA deteriorated due to mrp mutation. Also, MRP binds to the promoter regions of the MHETase gene and TPA metabolizing genes, but not to the PETase gene promoter. These results suggest that MRP is a transcription factor that activates MHETase and TPA-metabolizing genes.

Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype

Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Molecular and cellular role of variants of the promoter region of HAND1 gene in sporadic and isolated ventricular septal defect.

Ventricular septal defect (VSD) is the most common type of congenital heart disease. HAND1 gene plays a crucial role in the development of the heart, but the role of the variants in the HAND1 gene promoter region in patients with VSD has not been explored yet. From 588 participants (300 with isolated and sporadic VSD and 288 healthy controls), DNA was extracted from blood samples. Variants at the HAND1 gene promoter region were analyzed through Sanger sequencing. Subsequently, cell functional validation was conducted through cell experiments, including dual-luciferase reporter gene analysis, electrophoretic mobility shift analysis, and bioinformatics analysis was also conducted. The promoter region of HAND1 gene had a total of 9 identified variant sites. Among them, 4 variants were exclusively found in VSD patients, and 1 variant (g.3631A>C) was newly discovered. Cell functional experiments indicated that all four variants decreased the transcriptional activity of HAND1 gene promoter with three of them reached statistical significance (p < 0.05). Subsequent analysis using JASPAR (a transcription factor binding profile database) suggests that these variants may alter the binding sites of transcription factors, potentially contributing to the formation of VSD. Our study for the first time identified variants in the promoter region of HAND1 gene in Chinese patients with isolated and sporadic VSD. These variants significantly decreased the expression of HAND1 gene, impacting transcription factor binding sites, and thereby demonstrating pathogenicity. This study offers new insights into the role of HAND1 gene promoter region, contributing to a better understanding of the genetic basis of VSD formation.

The comparison of gut microbiota between wild and captive Asian badgers (Meles leucurus) under different seasons

The gut microbiota plays an important role in the immunology, physiology and growth and development of animals. However, currently, there is a lack of available sequencing data on the gut microbiota of Asian badgers. Studying the gut microbiota of Asian badgers could provide fundamental data for enhancing productivity and immunity of badgers’ breeding, as well as for the protection of wild animals. In this study, we first characterized the composition and structure of the gut microbiota in the large intestines of wild and captive Asian badgers during summer and winter by sequencing the V3-V4 region of the 16S ribosomal RNA gene. A total of 9 dominant phyla and 12 genera among the bacterial communities of the large intestines exhibited significant differences. Our results showed that Firmicutes and Proteobacteria were the most predominant in both wild and captive badgers, regardless of the season. Romboutsia, Streptococcus and Enterococcus may represent potential sources of zoonoses, warranting further attention and study. Our findings indicated that the diversity and availability of food resources were the most important influencing factors on the gut microbiota of Asian badgers, providing fundamental data for the protection and conservation of wild animals. Variation in the gut microbiota due to season, age and sex in both wild and captive Asian badgers should be considered in future research directions. Furthermore, combined multi-omics studies could provide more information for wild animal conservation, and enhancing our understanding of the molecular mechanism between the microbiota and host.

Analysis of histomorphology and SERNINA5 gene expression in different regions of epididymis of cattleyak.

The molecular mechanism of sterility in cattleyak is still unresolved. The related factors of infertility in cattleyak were studied by tissue section, SERPINA5 gene cloning and bioinformatics technology. Tissue sections of the epididymis showed poorly structured and disorganized epithelial cells in the corpus of the epididymis compared to the caput of the epididymis, while in the cauda part of the epididymis, the extra basal smooth muscle was thinner, the surface of the epithelial lumen was discontinuous and the epithelium was markedly degenerated. The results of gene cloning showed that the coding sequence (CDS) region of the SERPINA5 gene in cattleyak was 1215bp in length, encoding a total of 404 amino acids, of which the isoleucine content was the highest, accounting for a total of 49 amino acids (12.1%). The results of real-time fluorescence quantitative PCR (qPCR) showed that the expression of the SERPINA5 gene in the epididymis caput in cattleyak was significantly higher than that in the corpus and cauda (P < 0.05), but there were no significant differences between the corpus and cauda. In the current study, histological and bioinformatics analysis, physicochemical properties, and the expression analysis of the SERPINA5 gene in different regions of the epididymis in cattleyak were carried out to explore the biological complications of cattleyak infertility.

Joint GWAS and WGCNA Identify Genes Regulating the Isoflavone Content in Soybean Seeds.

Isoflavone is a secondary metabolite of the soybean phenylpropyl biosynthesis pathway with physiological activity and is beneficial to human health. In this study, the isoflavone content of 205 soybean germplasm resources from 3 locations in 2020 showed wide phenotypic variation. A joint genome-wide association study (GWAS) and weighted gene coexpression network analysis (WGCNA) identified 33 single-nucleotide polymorphisms and 11 key genes associated with soybean isoflavone content. Gene ontology enrichment analysis, gene coexpression, and haplotype analysis revealed natural variations in the Glyma.12G109800 (GmOMT7) gene and promoter region, with Hap1 being the elite haplotype. Transient overexpression and knockout of GmOMT7 increased and decreased the isoflavone content, respectively, in hairy roots. The combination of GWAS and WGCNA effectively revealed the genetic basis of soybean isoflavone and identified potential genes affecting isoflavone synthesis and accumulation in soybean, providing a valuable basis for the functional study of soybean isoflavone.

A First Approach for the In Vitro Cultivation, Storage, and DNA Barcoding of the Endangered Endemic Species Euonymus koopmannii

Euonymus koopmannii is a rare and protected species in Kazakhstan, valued for its ecological role in soil stabilization and its ornamental properties. This study presents the first use of micropropagation and phylogenetic analysis for the endemic plant E. koopmannii. Seedlings of E. koopmannii proved to be more effective than internodes as primary explants for plant micropropagation of in vitro culture, with a multiplication coefficient of 28.5 from seedlings and 6.1 from internodes. On MSR I medium supplemented with 0.5 mg/L IBA and 0.05 mg/L IAA, a higher success rate of 67% was achieved for root formation of test tube-grown E. koopmannii plants. Using mannitol as an osmotic agent at a concentration of 8 mg/L prolonged the storage time of E. koopmannii under slow growth conditions when compared to CCC and abscisic acid. Phylogenetic relationships and species identification were analyzed using four DNA-barcoding markers, comparing E. koopmannii with species from NCBI. All candidate barcoding markers showed sufficient levels of interspecific genetic variation among Euonymus species. In addition, ITS region and rbcL gene sequences effectively distinguished E. koopmannii from other species. These results provide fundamental information that will be valuable for future biotechnological and molecular studies.

Gene body methylation evolves during the sustained loss of parental care in the burying beetle

Epigenetic modifications, such as 5-methylcytosine (5mC), can sometimes be transmitted between generations, provoking speculation that epigenetic changes could play a role in adaptation and evolution. Here, we use experimental evolution to investigate how 5mC levels evolve in populations of biparental insect (Nicrophorus vespilloides) derived from a wild source population and maintained independently under different regimes of parental care in the lab. We show that 5mC levels in the transcribed regions of genes (gene bodies) diverge between populations that have been exposed to different levels of care for 30 generations. These changes in 5mC do not reflect changes in the levels of gene expression. However, the accumulation of 5mC within genes between populations is associated with reduced variability in gene expression within populations. Our results suggest that evolved change in 5mC could contribute to phenotypic evolution by influencing variability in gene expression in invertebrates.

Overexpression of Toxic Poly(Glycine-Alanine) Aggregates in Primary Neuronal Cultures Induces Time-Dependent Autophagic and Synaptic Alterations but Subtle Activity Impairments

The pathogenic expansion of the intronic GGGGCC hexanucleotide located in the non-coding region of the C9orf72 gene represents the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation leads to the accumulation of toxic RNA foci and dipeptide repeats (DPRs), as well as reduced levels of the C9orf72 protein. Thus, both gain and loss of function are coexisting pathogenic aspects linked to C9orf72-ALS/FTD. Synaptic alterations have been largely described in C9orf72 models, but it is still not clear which aspect of the pathology mostly contributes to these impairments. To address this question, we investigated the dynamic changes occurring over time at the synapse upon accumulation of poly(GA), the most abundant DPR. Overexpression of this toxic form induced a drastic loss of synaptic proteins in primary neuron cultures, anticipating autophagic defects. Surprisingly, the dramatic impairment characterizing the synaptic proteome was not fully matched by changes in network properties. In fact, high-density multi-electrode array analysis highlighted only minor reductions in the spike number and firing rate of poly(GA) neurons. Our data show that the toxic gain of function linked to C9orf72 affects the synaptic proteome but exerts only minor effects on the network activity.

Optical genome mapping identifies a homozygous deletion in the non-coding region of the SCN9A gene in individuals from the same family with congenital insensitivity to pain

Optical genome mapping identifies a homozygous deletion in the non-coding region of the SCN9A gene in individuals from the same family with congenital insensitivity to pain

Evolution of Virus-like Features and Intrinsically Disordered Regions in Retrotransposon-derived Mammalian Genes.

Several mammalian genes have originated from the domestication of retrotransposons, selfish mobile elements related to retroviruses. Some of the proteins encoded by these genes have maintained virus-like features; including self-processing, capsid structure formation, and the generation of different isoforms through -1 programmed ribosomal frameshifting. Using quantitative approaches in molecular evolution and biophysical analyses, we studied 28 retrotransposon-derived genes, with a focus on the evolution of virus-like features. By analyzing the rate of synonymous substitutions, we show that the -1 programmed ribosomal frameshifting mechanism in three of these genes (PEG10, PNMA3, and PNMA5) is conserved across mammals and originates alternative proteins. These genes were targets of positive selection in primates, and one of the positively selected sites affects a B-cell epitope on the spike domain of the PNMA5 capsid, a finding reminiscent of observations in infectious viruses. More generally, we found that retrotransposon-derived proteins vary in their intrinsically disordered region content and this is directly associated with their evolutionary rates. Most positively selected sites in these proteins are located in intrinsically disordered regions and some of them impact protein posttranslational modifications, such as autocleavage and phosphorylation. Detailed analyses of the biophysical properties of intrinsically disordered regions showed that positive selection preferentially targeted regions with lower conformational entropy. Furthermore, positive selection introduces variation in binary sequence patterns across orthologues, as well as in chain compaction. Our results shed light on the evolutionary trajectories of a unique class of mammalian genes and suggest a novel approach to study how intrinsically disordered region biophysical characteristics are affected by evolution.

Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an annual incidence of two cases/100 000. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. CML is characterized by a balanced genetic translocation, t(9;22) (q34;q11.2), involving a fusion of the Abelson murine leukemia (ABL1) gene from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein. Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib, are approved by the United States Food and Drug Administration (FDA) for first-line treatment of newly diagnosed CML in the chronic phase (CML-CP). Clinical trials with second and third-generation TKIs in frontline CML-CP therapy reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of their potent efficacy and the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. All four TKIs are equivalent if the aim of therapy is to improve survival. In younger patients with high-risk disease and in whom the aim of therapy is to induce a treatment-free remission status, second-generation TKIs may be favored. For CML post-failure on frontline therapy, second-line options include second and third-generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities and financial status, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP and failure (due to resistance) of at least two TKIs and for all patients in advanced-phase disease. Older patients who have a cytogenetic relapse post-failure on all TKIs can maintain long-term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non-TKI anti-CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, and others).

Blood Leukocyte DNA Methylation Markers of Periodontal Disease and Risk of Lung Cancer in a Case-Control Study Nested in the CLUE II Cohort.

Periodontal disease and DNA methylation markers have separately been associated with lung cancer risk. Examining methylation levels at genomic regions previously linked to periodontal disease may provide insight on the link between periodontal disease and lung cancer. In a nested case-control study drawn from the CLUE II cohort, we measured DNA methylation levels in 208 lung cancer cases and 208 controls. We examined the association between 37 DNA methylated CpG sites at three genomic regions, Homeobox 4 (HOXA4), Zinc finger protein (ZFP57) and a lcRNA gene region located in Chr10 (ENSG00000231601), and lung cancer risk. Statistically significant associations with lung cancer risk were observed for all 14 CpG sites from HOXA4 (odds ratio [OR] ranging 1.41-1.62 for 1 SD increase in methylation level, especially within 15 years) and one CpG site on gene ENSG00000231601 (OR=1.34 for 1 SD increase in DNA methylation level). While CpG sites on gene ZFP57 were not associated with lung cancer risk overall, statistically significant inverse associations were noted for six CpGs when restricting follow-up to 15 years (OR=0.73-0.77 for 1 SD increase in methylation level). Key methylation changes associated with periodontal disease are also associated with lung cancer risk. For both HOXA4 and ZFP57, that these associations were stronger within 15 years of follow up suggests that they act late in the natural history of lung cancer. Identifying biological pathways that link periodontal disease and lung cancer could provide new opportunities for lung cancer detection and prevention.

Trypanosoma infection and bloodmeal analysis in post-feeding sand flies across Thailand

Phlebotomine sand flies are recognized as a primary vector of Leishmania and are also suspected vectors of Trypanosoma. The transmission cycle of these parasites relies on the distribution of sand fly vectors, parasites, and reservoir animals. This study aimed to detect Leishmania and Trypanosoma DNA and identify the sources of bloodmeals in post-feeding sand flies captured across Thailand. A total of 42,911 field female sand flies were collected from 11 provinces across Thailand using CDC light traps. Among these, 253 post-feeding sand flies were selected for analysis. The predominant species in this study was Sergentomyia khawi (33.60 %). The DNA was extracted from individual female sand flies. Polymerase chain reaction (PCR), specific to the internal transcribed spacer 1 (ITS1) and the small subunit ribosomal RNA (SSU rRNA) gene regions were used to detect the presence of Leishmania and Trypanosoma DNA, respectively. Additionally, cytochrome c oxidase subunit I (COI) gene region was utilized to identify the sources of host bloodmeals. Leishmania DNA was not detected in any specimens. The analysis of SSU rRNA sequences revealed the presence of Trypanosoma DNA (11.46 %, 29/253) in sand fly samples. Among these samples, T. noyesi (1.58 %, 4/253) was identified in Idiophlebotomus longiforceps and Phlebotomus asperulus, Trypanosoma Anura01+02/Frog2 (1.18 %, 3/253) in Se. khawi, and Trypanosoma Anura04/Frog1 (8.70 %, 22/253) in Se. khawi, Se. hivernus and Grossomyia indica. Bloodmeal analysis utilizing the COI gene revealed a diverse range of vertebrate hosts’ blood, including bird, bat, frog and sun skink. Our findings confirm the presence of Trypanosoma DNA and identify the sources of bloodmeals from vertebrate hosts in various sand fly species, suggesting their potential as possible vectors for Trypanosoma in Thailand. Furthermore, our study is the first to provide molecular evidence using the COI gene to identify frogs as a host blood source for sand flies in Thailand. Further studies focusing on the isolation of live parasites in sand flies to confirm vector potential and examining the role of animal reservoirs will enhance our understanding of the host-parasite relationship and enable more efficient control for disease transmission.