Nuclear Polymorphism Research Articles

A Case of a Clinically Proliferating Trichilemmal Cyst Following the Take of Febuxostat and Calcium Carbonate

Trichilemmal cysts or pilar cysts are keratin-filled cysts that originate in the outer root sheath. They are typically found on the scalp of middle-aged women. They are inherited as an autosomal dominant trait. Trichilemmal cysts range from simple trichilemmal cysts to benign and malignant proliferative trichilemmal cysts. Proliferation can be clinical or histological. Clinically, it may present as an increase in size with the onset of an ulceration. Histologically, it translates as the acquisition of certain features which are the dermal proliferation of a squamous epithelium that arranges in a lobular fashion with clear cells containing glycogen in some areas surrounded by a somewhat cellular and glassy stroma; and especially the trichilemmal keratinization in the centre of lobules. There are also certain histopathological criteria to distinguish benign from malignant proliferating trichilemmal cysts. A malignant trichilemmal cyst is characterized by a high mitotic index, atypical mitoses, significant nuclear polymorphism, and tumor invasion of adjacent tissues. Immunohistochemistry can also confirm the benign character by expression of cytokeratin 10 and involucrin. We report here a case of a clinically proliferating trichilemmal cyst following the introduction of calcium carbonate and febuxostat in a patient undergoing treatment for hypertension and renal failure, but retaining a typically simple and benign character on histology.

Genetic QT score as a predictor of sudden cardiac death in participants with sleep-disordered breathing in the UK Biobank.

The goal of this study was to evaluate the association between a polygenic risk score (PRS) for QT prolongation (QTc-PRS), QTc intervals and sudden cardiac death (SCD) in participants enrolled in the UK Biobank with and without sleep-disordered breathing (SDB). The QTc-PRS was calculated using allele copy number and previously reported effect estimates for each single nuclear polymorphism SNP. Competing-risk regression models adjusting for age, sex, BMI, QT prolonging medication, race, and comorbid cardiovascular conditions were used for SCD analyses. 500,584 participants were evaluated (56.5 ±8 years, 54% women, 1.4% diagnosed with sleep apnea). A higher QTc-PRS was independently associated with the increased QTc interval duration (p<0.0001). The mean QTc for the top QTc-PRS quintile was 15 msec longer than the bottom quintile (p<0.001). SDB was found to be an effect modifier in the relationship between QTc-PRS and SCD. The adjusted HR per 5-unit change in QTc-PRS for SCD was 1.64 (95% CI 1.16 - 2.31, p=0.005) among those with SDB and 1.04 (95% CI 0.95 - 1.14, p=0.44) among those without SDB (p for interaction =0.01). Black participants with SDB had significantly elevated adjusted risk of SCD (HR=9.6, 95% CI 1.24 - 74, p=0.03). In the UK Biobank population, the QTc-PRS was associated with SCD among participants with SDB but not among those without SDB, indicating that SDB is a significant modifier of the genetic risk. Black participants with SDB had a particularly high risk of SCD.

Breeding success of the interspecies hybrids: Reduced fertility in the hybridogeneous magpie population (&lt;i&gt;Pica pica&lt;/i&gt; × &lt;i&gt;Pica serica&lt;/i&gt;, Aves)

Data on the breeding success of hybrids, collected during direct field observations, are principally important for understanding nature of the species isolating factors and future fate of the hybridogeneous populations. In the zone of secondary contact between Eurasian magpie Pica pica and Oriental magpie Pica serica, emerging right now, limited hybridization occurs, what has been shown in our reported data on nuclear single nucleotide polymorphisms (SNP). In the present work, we have analyzed composition of 119 nesting pairs and content of 89 nests in the hybridogeneous population of P. pica leucoptera × P. serica jankowskii in Eastern Mongolia, then in the recent contact zone in Eastern Transbaikalia (South Siberia) and the relatively pure populations of P. p. leucoptera in Central Transbaikalia and P. s. jankowskii in Northeast China. In the hybridogeneous population of Mongolia, significantly increased portion of nonviable clutches with all dead eggs was recorded, as well as a portion of partly dead clutches, compared with the data on the pure population of Central Transbaikalia. The egg mortality was found to be much less dramatic in the population of the Eastern Transbaikalia, where hybridization is less pronounced than in Mongolia. Several possible mechanisms of genetic incompatibilities breaking the reproductive barriers are discussed. The future fate of this magpie contact zone is considered, taking in account selection against hybridization which was revealed in this study. Among possible scenarios, reinforcement of prezygotic isolation may occur, i. e., in the species-specific calls. It is possible that a kind of mosaic hybrid zone with some features of tension zone will appear. Monitoring of the unique situation with the emerging zone of contact and hybridization of two young magpie species is needed, as a necessary addition to genomic studies.

Strong Small-Scale Differentiation but No Cryptic Species Within the Two Isopod Species Asellus aquaticus and Proasellus coxalis in a Restored Urban River System (Emscher, Germany).

Worldwide, humans have strongly altered river networks. Key changes resulted in modified hydromorphology, poor habitat quality and availability, migration barriers, and pollution. Restoration measures aim at mitigating anthropogenic stressors and at restoring connectivity, but the biological success of these measures is not guaranteed. Analyzing genetic diversity and metapopulation structure of target species in the river network with genetic markers can help to understand recolonization processes and to identify persisting gene flow barriers. Here, we studied the population genetic structure of the two pollution-tolerant detritivorous isopod species, Asellus aquaticus and Proasellus coxalis, in the former heavily degraded and polluted, but now mostly restored Emscher catchment in Germany. For both species, we analyzed mitochondrial cytochrome c oxidase I (COI) gene sequences and nuclear genome-wide single nucleotide polymorphism (SNP) data. Surprisingly, we found a strong metapopulation structure for both species with several isolated populations on a small-scale of few kilometers, but a still high genetic diversity, especially in the COI gene. For both taxa, potentially cryptic species are known, but our SNP data showed that the mitochondrial lineages represent only one species, each, in the study area. This highlights the importance of integrating high-resolution nuclear markers into species identification because species diversity may otherwise be overestimated. While we could identify some migration barriers and find indications for passive dispersal by birds or humans, these factors could not fully explain the local metapopulation structure, suggesting that also other drivers, such as isolation by adaptation, priority effects, or biotic interactions, play a role in shaping the population genetic structure.

Genome-wide species delimitation and quantification of the extent of introgression in eriophyoid mite Epitrimerus sabinae complex (Acariformes: Eriophyoidea)

Species complex hinders the exploration of terrestrial species diversity, particularly in small arthropod lineages that are morphologically indistinguishable from each other. The Epitrimerus sabinae complex in the Eriophyoidea provides a valuable case study in species complex delimitation, as they exhibit limited morphological variations. In this study, we obtained thousands of nuclear genomic single-nucleotide polymorphisms via whole-genome sequencing from 55 E. sabinae complex specimens, covering their potential all known distribution ranges. We implemented a framework to infer cryptic speciation, which involved phylogenetic and genetic clustering to identify potential species, followed by population demographic assessment to confirm lineage independence (and thus species status). Our results demonstrate that the E. sabinae complex comprises ten distinct species. These species range from highly divergent, genetically isolated lineages, to differentiated populations involving gene flow. This gene flow is widespread across species boundaries, indicating potential genetic introgression among them. Additionally, demographic analyses revealed that the ten species have followed unique trajectories in size change during the Quaternary period. Time-calibrated phylogenies further showed that speciation in the E. sabinae complex occurred rapidly, resulting in a rapid radiation during the Neogene period. Collectively, parallelism/convergence and recent divergence involving multiple gene flows may explain the homoplasy of E. sabinae complex. Our results highlight the integrated approach in species complex delimitation.

Association of nuclear factor-kappa B1 (NF-κB1) Ins/Del gene polymorphism with Hepatitis C virus outcomes.

To explore the association of nuclear factor-kappa B1 polymorphism in the promotor area of the gene with hepatitis C virus infection outcomes. The case-control study was conducted at the Hepatology and Gastroenterology Teaching Hospital, Baghdad, Iraq, from Dec 1, 2020, to Aug 30, 2021, and comprised individuals ages 20-68 years. Group 1 had patients with persistent hepatitis C virus infection, group 2 had subjects with spontaneous hepatitis C virus clearance, group 3 had subjects treated with direct-acting antiviral drugs, and group 4 had healthy controls. Venous blood was collected for polymorphism genetic analysis of nuclear factor-kappa B1 insertion/deletion ATTG (Adenine-Thymine- Thymine-Guanine) at rs28362491 using a high-resolution melting technique. Data was analysed using SPSS 27. Of the 88 subjects, there were 22(25%) in each of the 4 groups. Overall, there were 55(62.5%) females and 33(37.5%) males, and 40(45.45%) were aged 20-39 years while 48(54.54%) were aged 40-68 years (p>0.05). The Ins allele of rs28362491 was significantly more frequent in the patients than in controls (p=0.0053). The carriage of rs28362491 insertion/insertion and insertion/deletion genotypes, compared to wild-type homozygous deletion/deletion, had a significantly higher risk of developing hepatitis C virus infection (p=0.0013). No association was found between rs28362491 and spontaneous hepatitis C virus clearance (p>0.05). The insertion allele of rs28362491 was found to be associated with increased susceptibility to developing hepatitis C virus infection.

Possible effects of ancestry-related oxysterol-binding protein-like 10 genetic polymorphisms on dengue virus replication and anti-dengue immune response

PurposeOxysterol-binding protein-like 10 (OSBPL10) gene has been associated with reduced susceptibility to severe dengue in individuals of African descent. The aim of this study was to determine the possible effect of OSBPL10 on dengue virus (DENV) replication as well as the impact of African and European haplotypes of six OSBPL10 small nuclear polymorphisms (SNPs) on dengue multiplication and innate immune response. MethodsWe conducted gene knockdown experiments targeting OSBPL10 in THP-1 and Huh-7D12 cell lines, followed by a DENV-2 replication assay. Extracellular viral load was determined using qRT-PCR. To investigate the impact of SNPs haplotypes on viral replication and gene expression we cultured peripheral blood mononuclear cells (PBMC) from individuals with homozygous African and European haplotypes of OSBPL10 with DENV-2. Individual genotyping was performed using High Resolution Melt (HRM) analysis. The level of viral replication was assessed through plaque assay, while RT-PCR was employed to determine the expression levels of RXR-α, IFN-γ, IL-10 and IL-8 genes. ResultsIn vitro OSBPL10 knockdown significantly reduced DENV-2 replication. Individuals carrying European haplotypes showed higher DENV titers along with elevated levels of RXR-α and IL-8 mRNA compared to those carrying African haplotypes, who exhibited lower viral loads alongside increased IFN-γ and IL-10 expression. ConclusionsOur findings further explore the role of OSBPL10 in DENV multiplication, immune response to infection. The European haplotypes of OSBPL10 appear to increase DENV replication and promote RXR-α and IL-8 mRNA expression which correlates with the suppressive effect of these mediators on type I IFN, promoting viral replication and a deficient antiviral response. In contrast, the African haplotype showed a reduction in DENV replication and enhanced IFN-γ and IL-10 mRNA expression, which could be related to the better management of dengue infection and the low frequency of severe disease in this ethnic groupe.

Assessing the association between common functional Nuclear Factor Kappa-b gene polymorphisms (NFKB1, NFKBIZ, NFKBIA) and Alzheimer´s disease

The Nuclear Factor Kappa-b (NF-Κb) pathway has been implicated in the pathogenesis of Alzheimer´s disease (AD). We determined whether common variants in the NF-Κb genes were associated with the risk of developing late-onset AD (LOAD). A total of 639 Spanish LOAD and 500 controls were genotyped for the NFKB1 rs28362491/rs7667496, NFKBIA rs696, NFKBIZ rs3217713 and APOE-Ɛ2/3/4 polymorphisms. Rs7667496 C was increased in the patients (p<0.001) with the CC genotype showing a significant risk (CC vs T+, OR= 1.58, 95 %CI=1.25–2.01). The CC genotype was significantly associated with LOAD after correction by APOE-4+ genotypes, age and sex (p=0.0003, OR=1.88, 95 %CI=1.28–2.78). The NFKB1 rs28362491 I - rs7667496 C haplotype was significantly increased in the patients (p=0.02). NFKBIA and NFKBIZ variants were not associated with the risk of LOAD in our population. In conclusion, NFKB1 variants were associated with the risk of LOAD in our population. This finding encourages further studies to determine the involvement of the NF-kB components in LOAD.

Advancing livestock and poultry disease diagnosis with high-resolution melt curve analysis

High-Resolution Melting (HRM) is a sensitive polymerase chain reaction-based molecular assay used to detect, single nuclear polymorphisms, mutations, and variations in genotypes of pathogens. HRM analysis is more convenient than other detection and discrimination approaches since it is a closed-tube method, that is the polymerase chain reaction amplification and subsequent analysis are carried out sequentially in the well. It finds application in various veterinary diagnoses and discrimination of genotypes of the microorganisms. Numerous public health organizations have recommended increased monitoring activities to support current surveillance programs in response to the threat of bioterrorism and emerging infectious diseases. HRM assay will be an efficient, cost-effective disease diagnostic and genotype of circulating pathogen identification method thereby aiding in disease surveillance which is important for monitoring the spread of infectious diseases. This review emphasizes the application of HRM in livestock, poultry, and companion animals in recent times carried out all over the world for determining the genotype, strain, and breed differentiation including pathogens classification.

The 3'UTR Polymorphisms in the NLRP3 Gene Associated with the Risk of COPD and Their Putative Effects on the microRNA Mechanism.

Aims: Evaluating the association between a single nucleotide polymorphism in the 3' untranslated region (3'UTR) of the miRNA binding site of the NLRP3 gene and the occurrence and development of chronic obstructive pulmonary disease (COPD) and providing information to aid in the early detection and treatment of COPD. Materials and Methods: The regulatory single nuclear polymorphisms (SNPs) located in NLRP3 3'UTR were searched by using the dbSNP database and miRNA binding site prediction database. Meanwhile, samples from COPD patients and healthy controls in the same period were used for verification. The clinical baseline information of all subjects was collected, and the transcription level and protein expression level of NLRP3 and the expression level of inflammatory factors downstream of NLRP3 were detected. The effects of SNPs' single nucleotide changes on the transcription and expression of inflammatory factors were analyzed. Results: The study included 418 participants (249 in the COPD group and 169 in the control group). NLRP3 SNPs with miRNA binding sites include rs10754558 (G > C), rs1664774076 (ATAT > del), and rs1664775106 (C > G). Furthermore, two genotypes, GCG and GCA, were discovered to have a linkage mutation at 3'UTR 459-461. COPD susceptibility is tightly associated with the expression of the rs1664774076 del/del genotype, and the risk of COPD increased by 2.770 times (p = 0.003). Type 459-461 GCA was substantially related to the likelihood of developing COPD at various stages (p < 0.05). Except for rs10754558, all homozygous mutants increased NLRP3 mRNA and protein levels. NLRP3 had the greatest area under the receiver operating characteristic (ROC) curve for predicting the development and diagnosis of COPD when compared with its downstream inflammatory variables (AUC = 0.9291). Conclusions: The NLRP3 rs1664774076 del/del genotype is a COPD susceptibility gene, and the GCA genotype at 459-461 can be used as an early predictor of COPD exacerbation. The NLRP3 3'UTR polymorphism may alter the loss of miRNA binding sites, leading to an increase in NLRP3 expression. In the development of COPD, NLRP3 has a better diagnostic value than traditional inflammatory factors. The Clinical Trials Registration number Z: protocol KY01-2020-11-06.

Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21

BackgroundSingle nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear.MethodsA case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC.ResultsTCF21 rs2327430 (OR = 0.78, P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39, P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47, P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells.ConclusionOur findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.

Circular genetic structure of the Abies nephrolepis species complex shaped by the circular landform of Northeast Asia

AbstractAimPinaceae have been noted for their tendency towards reticulation as a result of interspecific hybridization. Here, we demonstrated the phylogeographic dynamics of the native Northeast Asian sub‐alpine conifer, Abies nephrolepis species complex (ANSC), evolving in circular overlaps along the Northeast Asian landform, which functions as a corridor with the sea, thus acting as a geographic barrier.LocationNortheast Asia: the Korean Peninsula, Japanese Archipelago, Russian Far East and northeastern China.TaxonAbies nephrolepis species complex (Family Pinaceae, Genus Abies, Section Balsamea, Abies nephrolepis, A. koreana, A. veitchii and A. sachalinensis).MethodsA total of 728 individuals from 38 ANSC populations were analysed using multiplexed inter‐simple sequence repeat genotyping by sequencing to capture variations in biparental nuclear genomes. Eight mitochondrial regions and eight chloroplast regions of each individual were sequenced using the MiSeq platform and Sanger sequencing. Species distribution models were generated.ResultsBayesian clustering with 507 nuclear single nucleotide polymorphisms and the discrepancy between cytoplasmic and nuclear genome lineages implied contemporary and ancient connections between neighbouring species in the form of circular overlap. This genetic connectivity was supported by principal component analysis. Strong correlations between genetic distance and geographic distance were observed, suggesting that gene flow occurs through a continuous chain around the sea. We also found that gene flow direction and intensity changed over time, with support from palaeodistribution modelling.ConclusionPast hybridization events were captured in cytoplasmic genomes, generating heterogeneity across maternal ancestries. This intensive phylogeographic study demonstrates speciation with incomplete reproductive isolation (continuous gene flow) among neighbouring species with an alteration of the direction and intensity of gene flow due to climate change. The divergence of ANSC due to repeated isolation and reconnection caused by heterogenous physiological environments and climate fluctuation provides a model to solve evolutionary scenarios for reticulate evolution in Pinaceae and other plants.

Both nuclear and cytoplasmic polymorphisms are involved in genetic conflicts over male fertility in the gynodioecious snail, Physa acuta.

Gynodioecy, the coexistence of hermaphrodites with females, often reflects conflicts between cytoplasmic male sterility (CMS) genes and nuclear genes restoring male fertility. CMS is frequent in plants and has been recently discovered in one animal: the freshwater snail, Physa acuta. In this system, CMS was linked to a single divergent mitochondrial genome (D), devoid of apparent nuclear restoration. Our study uncovers a second, novel CMS-associated mitogenome (K) in Physa acuta, demonstrating an extraordinary acceleration of molecular evolution throughout the entire K mitochondrial genome, akin to the previously observed pattern in D. This suggests a pervasive occurrence of accelerated evolution in both CMS-associated lineages. Through a 17-generation introgression experiment, we further show that nuclear polymorphisms in K-mitogenome individuals contribute to the restoration of male function in natural populations. Our results underscore shared characteristics in gynodioecy between plants and animals, emphasizing the presence of multiple CMS mitotypes and cytonuclear conflicts. This reaffirms the pivotal role of mitochondria in influencing male function and in generating genomic conflicts that impact reproductive processes in animals.

DNA Repair Genetics and the Risk of Radiation Pneumonitis in Patients With Lung Cancer: A Systematic Review and Meta-analysis

AimsERCC1 rs11615 and ERCC2 rs238406 single nuclear polymorphism (SNPs) are known for their association with treatment outcome, likely related to radiosensitivity of both tumor and normal tissue in patients with non-small-cell lung cancer. This study aimed to review the effect of 1) these ERCC1/2 SNPs and 2) other SNPs of DNA repair genes on radiation pneumonitis (RP) in patients with lung cancer. Materials and methodsSNPs of our interest included ERCC1 rs11615 and ERCC2 rs238406 and other genes of DNA repair pathways that are functional and biologically active. DNA repair SNPs reported by at least two independent studies were pooled for meta-analysis. The study endpoint was radiation pneumonitis (RP) after radiotherapy. Recessive, dominant, homozygous, heterozygous, and allelic genotype models were used where appropriate. ResultsA total of 16 studies (3080 patients) were identified from the systematic review and 12 studies (2090 patients) on 11 SNPs were included in the meta-analysis. The SNPs were ATM rs189037, ATM rs373759, NEIL1 rs4462560, NEIL1 rs7402844, APE1 rs1130409, XRCC3 rs861539, ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs238406, ERCC2 rs13181, and XRCC1 rs25487. ERCC1 rs11615 (236 patients) and ERCC2 rs238406 (254 patients) were not significantly associated with RP. Using the allelic model, the G allele for NEIL1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the C allele for rs7402844 (OR 0.70, 95% CI: 0.49, 0.99, P = 0.04). Similarly, the T allele for APE1 gene was significantly associated with a reduced odds of developing symptomatic (grade ≥2) RP compared to the G allele for rs1130409 (OR 0.59, 95% CI: 0.43, 0.81, P = 0.001). ConclusionGenetic variation in the DNA repair pathway genes may play a significant role in the risk of developing radiation pneumonitis in patients with lung cancer. Further studies are needed on genotypic features of DNA repair pathway genes and their association with treatment sensitivity, as such knowledge may guide personalized radiation dose prescription.

Geomorphic impacts within Red River Fault and island shifting as witnessed by the phylogeography of the largest water strider

Palaeogeological events and climate oscillations profoundly impact the demographics and distributions of small-range species, increasing the extinction risk. The largest water strider worldwide, Gigantometra gigas (Hemiptera: Gerridae), exhibits restricted distributions in Vietnam and southern China. Herein, we generated three genomic datasets (mitogenomes, 146 nuclear protein-coding genes and single nucleotide polymorphisms) with ecological niche modelling (ENM) to explicitly test whether the present-day distribution of G. gigas actually resulted from geographical and climatic effects. We found that the origin of this largest water strider reached the divergence time of the genus within Gerridae, providing a greater opportunity to explore its response to geographic movements. The right-lateral motion of the Red River Fault facilitated the divergence of two phylogeographic lineages, resulting in the “north–south component” genetic pattern in G. gigas. The Hainan and southeast Vietnam populations of the southern linage were completely separated by the Beibu Gulf but exhibited similar genetic compositions, confirming that Hainan had a continental origin and that Hainan Island joined with the Indo-China Peninsula to promote gene exchange among populations. Additionally, we noticed the low genetic diversity but long demographic history of the northern lineage, which displayed population dynamics opposite to those of other organisms. Integrating the demographic changes and ENM findings revealed that suitable habitat contraction and rapid demographic decline during the Last Glacial Maximum (LGM) triggered the low genetic diversity of the northern lineage. Overall, the demographic history of the largest water strider was mainly shaped by geographical features, and first provided evidence from the phylogeographic perspective of aquatic insects to support the hypothesis of Hainan Island shifting.

Genomic diversity and structure of a Neotropical microendemic fig tree.

Genetic diversity is a key component of evolution, and unraveling factors that promote genetic differentiation in space and time is a central question in evolutionary biology. One of the most diverse and ecologically important tree genera in tropical forests worldwide is Ficus (Moraceae). It has been suggested that, given the great dispersal capacity of pollinating fig wasps (Chalcidoidea; Agaonidae), the spatial genetic structure, particularly in monoecious fig species, should be weak. However, no studies have addressed the factors that determine the genetic structure of Ficus species in regions of high geological, geographic, and climatic complexity, such as the Mexican Transition Zone. Using nuclear single nucleotide polymorphisms (5311 SNPs) derived from low-coverage whole genomes and 17 populations, we analyzed the population genomics of Ficus pringlei to characterize neutral and adaptive genetic variation and structure and its association with geographic barriers such as the Trans-Mexican Volcanic Belt, environmental heterogeneity, and wind connectivity. From genomic data of 71 individuals, high genetic diversity, and the identification of three genomic lineages were recorded (North, South, and Churumuco). The results suggest that genetic variation is primarily determined by climatic heterogeneity. Ficus pringlei populations from the north and south of the Trans-Mexican Volcanic Belt also exhibited minimal genetic differentiation (F ST = 0.021), indicating that this mountain range may not act as an insurmountable barrier to gene flow. Wind connectivity is also highlighted in structuring putative adaptive genetic variation, underscoring the intricate complexity of the various factors influencing genetic variation in the species. This study provides information on the possible mechanisms underlying the genetic variation of endemic species of the tropical dry forest of Western Mexico, such as F. pringlei.

Association Analysis Provides Insights into Plant Mitonuclear Interactions.

Cytonuclear interaction refers to the complex and ongoing process of coevolution between nuclear and organelle genomes, which are responsible for cellular respiration, photosynthesis, lipid metabolism, etc. and play a significant role in adaptation and speciation. There have been a large number of studies to detect signatures of cytonuclear interactions. However, identification of the specific nuclear and organelle genetic polymorphisms that are involved in these interactions within a species remains relatively rare. The recent surge in whole genome sequencing has provided us an opportunity to explore cytonuclear interaction from a population perspective. In this study, we analyzed a total of 3,439 genomes from 7 species to identify signals of cytonuclear interactions by association (linkage disequilibrium) analysis of variants in both the mitochondrial and nuclear genomes across flowering plants. We also investigated examples of nuclear loci identified based on these association signals using subcellular localization assays, gene editing, and transcriptome sequencing. Our study provides a novel perspective on the investigation of cytonuclear coevolution, thereby enriching our understanding of plant fitness and offspring sterility.

Mitonuclear epistasis involving TP63 and haplogroup Uk: Risk of rapid progression of knee OA in patients from the OAI

To investigate genetic interactions between mitochondrial deoxyribonucleic acid (mtDNA) haplogroups and nuclear single nucleotide polymorphisms (nSNPs) to analyze their impact on the development of the rapid progression of knee osteoarthritis (OA). A total of 1095 subjects from the Osteoarthritis Initiative, with a follow-up time of at least 48-months, were included. Appropriate statistical approaches were performed, including generalized estimating equations adjusting for age, gender, body mass index, contralateral knee OA, Western Ontario and McMaster Universities Osteoarthritis Index pain, previous injury in target knee and the presence of the mtDNA variant m.16519C. Additional genomic data consisted in the genotyping of Caucasian mtDNA haplogroups and eight nSNPs previously associated with the risk of knee OA in robust genome-wide association studies. The simultaneous presence of the G allele of rs12107036 at TP63 and the haplogroup Uk significantly increases the risk of a rapid progression of knee OA (odds ratio=1.670; 95% confidence interval [CI]: 1.031-2.706; adjusted p-value=0.027). The assessment of the population attributable fraction showed that the highest proportion of rapid progressors was under the simultaneous presence of the G allele of rs12107036 and the haplogroup Uk (23.4%) (95%CI: 7.89-38.9; p-value<0.05). The area under the curve of the cross-validation model (0.730) was very similar to the obtained for the predictive model (0.735). A nomogram was constructed to help clinicians to perform clinical trials or epidemiologic studies. This study demonstrates the existence of a mitonuclear epistasis in OA, providing new mechanisms by which nuclear and mitochondrial variation influence the susceptibility to develop different OA phenotypes.

Patients with long-term survival in malignant gliomas after photodynamic therapy

Analysis of long-lived patients from the group of patients with glioblastomas after using photodynamic therapy in the structure of their complex treatment in order to assess the influence of various factors on their life expectancy. In total, a single-center, retrospective categorical study analyzed the long-term results of treatment of 63 patients with glioblastoma in the structure of complex treatment including photodynamic therapy. Clinical factors (age, sex, number of cases, preoperative Karnofsky index, location and size of the tumor, radicality of the operation), histological (nuclear polymorphism, mitosis, vascular proliferation, necrosis), immunohistochemical (Ki-67, p53 index) molecular-genetic factors (expression of VEGF, MGMT, IDH, CD34), amount of radiation and chemotherapy were analyzed. In the entire group of patients, there was a direct correlation of life expectancy with MGMT status, IDH status, the number of courses of chemotherapy, the age of the patient, and the severity of the first surgical intervention. Clinical features such as age at diagnosis and extent of surgical resection and amount of chemotherapy have predictive value in assessing their effect on life expectancy. Mutations in IDH and MGMT promoter methylation were the most important molecular factors determining long-term patient survival.

Discovery of a new population of the endangered giant water bug Kirkaldyia deyrolli (Heteroptera: Belostomatidae) in Kyushu and evaluation of their genetic structure

AbstractThe giant water bug Kirkaldyia deyrolli is one of the most well‐known endangered aquatic insects in Japan. The population of this species in Kyushu, one of the four major islands of the Japanese Archipelago, is extremely limited. In the present study, we identified a new population of K. deyrolli and undertook population genetic structure analyses based on genome‐wide nuclear DNA single nucleotide polymorphisms (SNPs). We collected samples using a nonlethal sampling method and obtained 59,279 SNPs. The results of our study confirm that sufficient SNP data for population genetic structure analysis can be obtained through nonlethal sampling. We determined that the newly identified population is genetically differentiated from a previously identified population on Kyushu. Therefore, this population is considered highly important for the conservation of K. deyrolli in Kyushu.