Genotypic Differences Research Articles

Aggressiveness in Italian Children with ADHD: MAOA Gene Polymorphism Involvement.

ADHD is a neurodevelopmental disorder that children and adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls. We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p = 0.02 and p = 0.03, respectively), whereas the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p = 0.0002 and p = 0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highlighted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness, suggesting that these genotypes may be protective towards specific changes in behavior (p = 0.05). Interestingly, an increase in the GG genotype of rs6323 (p = 0.01) and a decrease in GT genotype (p = 0.0005) was also found in patients without aggressive behavior compared to controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help in the early detection of patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

Association study of the Taq1D rs1800498 polymorphism of the DRD2 gene with personality traits in a group of athletes

Introduction: This study investigates an association between the human dopamine receptor 2 gene DRD2 Taq1D rs1800498 polymorphism and personality traits among athletes, exploring the genetic underpinnings of sports performance and psychological characteristics. It aims to understand how genetic factors related to dopamine reception influence athletic predispositions and behaviors. Materials and Methods: An association study was conducted with 391 male participants, comparing 159 sports subjects with 232 non-trained controls. Personality traits were assessed using the NEO Five-Factor Inventory, while the DRD2 Taq1D rs1800498 polymorphism was genotyped through real-time PCR. Results: Significant differences in the DRD2 Taq1D rs1800498 genotype and allele frequencies were found between athletes and controls, with athletes displaying higher scores in extraversion and conscientiousness on the NEO-FFI scales. These findings suggest a genetic influence on certain personality traits relevant to sports performance. Conclusions: The study supports the notion that genetic factors, specifically the DRD2 Taq1D rs1800498 polymorphism, are associated with personality traits that may influence athletic performance. This insight contributes to the field of psychogenetics in sports, offering a deeper understanding of how genetics and personality interact to shape athletic capabilities.

Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles

Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality rate, 0.5–40 %, depending on the virus species, and no vaccine or effective treatment for severe Orthohantavirus infections exists. In Europe, the Puumala virus (PUUV), carried by the bank vole Myodes glareolus, causes a milder form of HFRS. Despite the reliance on serology and PCR for diagnosis, the three genomic segments of Swedish wild-type PUUV have yet to be completely sequenced.We have developed a targeted hybrid-capture method aimed at comprehensive genomic sequencing of wild-type PUUV isolates and the identification of other Orthohantaviruses. Our custom-designed panel includes >11,200 probes covering the entire Orthohantavirus genus. Using this panel, we sequenced complete viral genomes from bank vole lung tissue, human plasma samples, and cell-cultured reference strains. Analysis revealed that Swedish PUUV isolates belong to the Northern Scandinavian lineage, with nucleotide diversity ranging from 2.8 % to 3.7 % among them. Notably, no significant genotypic differences were observed between the viral sequences from reservoirs and human cases except in the nonstructural protein.Despite the high endemicity of PUUV in Northern Sweden, these are the first complete Swedish wild-type PUUV genomes and substantially increase our understanding of PUUV evolution and epidemiology. The panel's sensitivity enables genomic sequencing of human samples with viral RNA levels reflecting the natural progression of infection and underscores our panel's diagnostic value, and could help to uncover novel Orthohantavirus transmission routes.

Association of TGFBR2 gene polymorphisms (rs6785358 and rs764522) with congenital heart disease susceptibility in Egyptians

Aim: Transforming growth factor beta (TGF-β) receptor II (TGFBR2) is a basic constituent of TGF-β signalling pathway and is important in heart development. This study investigates the relationship between TGFBR2 gene variance and congenital heart defects (CHD) among Egyptians. Methods: The study involved 75 CHD-affected subjects and 100 healthy controls. Genotyping of two selected tag single nucleotide polymorphisms (tagSNPs, rs6785358, rs764522) within the TGFBR2 gene was conducted using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) assays. Results: Significant genotype differences were found for rs764522 and rs6785358 (P < 0.05). In the case of rs6785358, the G/G genotype was more prevalent in cases than controls (18.7% vs. 4.0%). This significance was observed in both the codominant model [A/A vs. A/G vs. G/G; odds ratio (OR) = 0.20, 95% confidence interval (CI) = 0.06–0.66, P = 0.0073] and the recessive model (A/A + A/G vs. G/G; OR = 0.19, 95% CI = 0.06–0.60, P = 0.0018). For rs764522, the G/G genotype was more prevalent in cases than controls (21.3% vs. 0.0%). Significant associations were observed in the codominant model (C/C vs. C/G vs. G/G; OR = 0.43, 95% CI = 0.02–0.90, P < 0.0001), as well as in the dominant model (C/C vs. C/G + G/G) and recessive model (C/C + C/G vs. G/G; P < 0.0001). Gender-specific analysis indicated that the C/G genotype was less common in male cases compared to females and controls (OR = 0.24, 95% CI = 0.07–0.84). For rs6785358, the G/G genotype frequency was higher in male cases compared to females and controls (OR = 0.10, 95% CI = 0.01–0.88 and OR = 0.22, 95% CI = 0.05–0.94, respectively). Conclusions: These findings indicate that TGFBR2 gene SNPs (rs6785358 and rs764522) may be risk factors for CHD in Egyptians.

Integrative annotation scores of variants for impact on RNA binding protein activities.

The ENCODE project generated a large collection of eCLIP-seq RNA binding protein (RBP) profiling data with accompanying RNA-seq transcriptomes of shRNA knockdown of RBPs. These data could have utility in understanding the functional impact of genetic variants, however their potential has not been fully exploited. We implement INCA (Integrative annotation scores of variants for impact on RBP activities) as a multi-step genetic variant scoring approach that leverages the ENCODE RBP data together with ClinVar and integrates multiple computational approaches to aggregate evidence. INCA evaluates variant impacts on RBP activities by leveraging genotypic differences in cell lines used for eCLIP-seq. We show that INCA provides critical specificity, beyond generic scoring for RBP binding disruption, for candidate variants and their linkage-disequilibrium partners. As a result, it can, on average, augment scoring of 46.2% of the candidate variants beyond generic scoring for RBP binding disruption and aid in variant prioritization for follow-up analysis. INCA is implemented in R and is available at https://github.com/keleslab/INCA.

Physiological responses, ion accumulation and yield performance of wheat (Triticum aestivum L.) to salt stress

Wheat is affected by various biotic and abiotic stresses, especially salinity, which reduces the growth and yield drastically. High salinity is a major constraint for wheat productivity in many countries, including Bangladesh. With this view, here, an experiment was conducted to observe genotypic differences in physiological, ion accumulation, agro-morphological and yield performance of wheat against different levels of salinity. Experimental variables consisted of five salt tolerant genotypes (G 20–2–2, G 20–1–2, G 13–2, G 22–2, G 9–2), one susceptible genotype (G 24–2) and one standard check variety (BARI ghom 25), which assigned to four levels of salinity with electrical conductivities control (0.3), 4, 8 and 12 dS m−1. Irrespective of genotypes, salinity stress significantly decreased the yield and yield attributes. Results of analyses based on salt tolerance indices of plant growth related and yield contributing parameters, ionic balance (Na+, K+ and Na+ /K+ ratio), and stress indicators such as chlorophyll content, photosynthetic rate (Pn), stomatal conductance (gs) and transpiration rate (Tr) revealed genotypes G 20–2–2, G 13–2 and G 20–1–2 as salt tolerant, genotype G 9–2 as moderately salt-tolerant and G 24–2 and G 22–2 as salt-sensitive genotypes. Additionally, lower accumulations of hydrogen peroxide and malondialdehyde, and higher activities of antioxidant enzymes in the salt-tolerant genotypes G 20–2–2 and G 13–2 than in the salt-sensitive genotype G 24–2 indicated reduced oxidative damage in genotypes G 20–2–2 and G 13–2 relative to that in genotype G 24–2. Collectively, our findings suggest that the optimum growth and yield of salt tolerant genotypes are associated with decreased Na+/K+ ratio, increased antioxidant enzymes activity and reduced oxidative stress.

Добив и качество на тютюн Виржиния в зависимост от генотипа и агротехничски практики

The effects of three N rates (0, 20 and 40 kg N ha-1) and time of topping (topping at early flowering and topping at full flowering) on yield and quality (percentage of first, second and third grade dried tobacco, and chemical composition) of Virginia tobacco genotypes (Virginia 0514, Hybrid 33, Hybrid 27) were studied in field experiment in 2015-2016. The experimental design was a randomized complete block replicated three times. The most important factor that affects leaf yield was N rate. Genotype differences and time of topping also had a significant effect on the yield. The application of 20 and 40 kg N ha-1 improved the leaf yield by 12.6%, and 17.8%, respectively, in comparison with unfertilized plants. When tobacco was topped at early flowering stage, the yields of the different genotypes increased by 4.3%-10.1% compared to the topping at full flowering. Nitrogen fertilization and topping had almost the same effect on the quality of the tobacco (as determined by the percentage of first grade dried tobacco). The genotype effect was weaker but also statistically significant. The quantity of the first class was also determined by the interaction of topping and nitrogen rate. Topping at early flowering increased the concentrations of nicotine and total nitrogen in tobacco. The reducing sugars/nicotine ratio was higher, and in this case more favorable, when tobacco plants were topped at full flowering stage. Nicotine content (2.33%-3.53%) increased when the rate of nitrogen increased. There was a negative relationship between increasing N levels and reducing sugars content.

Oral Microbiota and Porphyromonas gingivalis Kgp Genotypes Altered in Parkinson's Disease with Mild Cognitive Impairment.

Cognitive impairment (CI) is a common complication of the non-motor symptoms in Parkinson's disease (PD), including PD with mild cognitive impairment (PD-MCI) and PD dementia. Recent studies reported the oral dysbiosis in PD and CI, respectively. Porphyromonas gingivalis (P. gingivalis), a pathogen of oral dysbiosis, plays an important role in PD, whose lysine-gingipain (Kgp) could lead to AD-type pathologies. No previous study investigated the composition of oral microbiota and role of P. gingivalis in PD-MCI. This study aimed to investigate the differences of oral microbiota composition, P. gingivalis copy number, and Kgp genotypes among PD-MCI, PD with normal cognition (PD-NC) and periodontal status-matched control (PC) groups. The oral bacteria composition, the copy number of P. gingivalis, and the Kgp genotypes in gingival crevicular fluid from PD-MCI, PD-NC, and PC were analyzed using 16S ribosomal RNA sequencing, quantitative real-time PCR, and MseI restriction. We found that the structures of oral microbiota in PD-MCI group were significantly different compared to that in PD-NC and PC group. The relative abundances of Prevotella, Lactobacillus, Megasphaera, Atopobium, and Howardella were negatively correlated with cognitive score. Moreover, there was a significant difference of Kgp genotypes among the three groups. The predominant Kgp genotypes of P. gingivalis in the PD-MCI group were primarily Kgp II, whereas in the PD-NC group, it was mainly Kgp I. The Kgp II correlated with lower MMSE and MoCA scores, which suggested that Kgp genotypes II is related to cognitive impairment in PD.

Negative effects of water deficit on cocoa tree yield are partially mitigated by irrigation and potassium application

Yields of most tropical crops are strongly reduced by drought, but this may be partially mitigated by irrigation and potassium application. Understanding the mechanisms regulating these relationships is essential to select crop varieties reaching high yield under environmental stress. We conducted a 2-year field experiment (2020–2022) to investigate the effects of seasonal irrigation, potassium application and their interaction on cocoa reproduction and yield, using six genotypes in Côte d’Ivoire. Potassium application increased pod number and size, contributing significantly to annual yield, but this effect was conditional to soil water availability. Similarly, irrigation when combined with potassium application almost doubled yield from 1.5 to 3.0 kg/tree (2000 kg ha−1 yr−1 to 4000 kg ha−1 yr−1, respectively). This yield effect was mostly the result of positive effects of irrigation on pod number per tree and, to a lesser extent, due to its positive effects on bean number per pod and bean mass. Irrigation effects on pod number were associated with an increased number of cherelles whereas the larger pod number during the major harvest compared to the minor harvest was associated with lower cherelle wilt. We also found a more than two-fold genotypic difference in yield, with the genotypes CI02 and CI03 and to a lesser extent hybrid M having lower yields having lower yields than the genotype CI01. These genotypic yield differences were associated with differences in both cherelle wilt and initial cherelle production rates. The effects of withholding irrigation on yield were significantly dependent on the genotype, reflecting a potential genotypic difference in drought tolerance. The development of climate adaptive strategies for cocoa production requires integrating effects of irrigation, potassium application and cocoa genotype on yields. Future research should focus on unraveling the underlying genotypic and ecophysiological mechanisms of the results presented here, and identifying other potential approaches to enhance the resilience of cocoa to increasing water deficit under climate change.

Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

High-throughput homogenous assay for the direct detection of Listeria monocytogenes DNA

The Amplified Luminescent Proximity Homogenous Assay-linked Immunosorbent Assay (AlphaLISA) is known for detecting various protein targets; however, its ability to detect nucleic acid sequences is not well established. Here, the capabilities of the AlphaLISA technology were expanded to include direct detection of DNA (aka: oligo-Alpha) and was applied to the detection of Listeria monocytogenes. Parameters were defined that allowed the newly developed oligo-Alpha to differentiate L. monocytogenes from other Listeria species through the use of only a single nucleotide polymorphism within the 16S rDNA region. Investigations into the applicability of this assay with different matrices demonstrated its utility in both milk and juice. One remarkable feature of the oligo-Alpha is that greater sensitivity could be achieved through the use of multiple acceptor oligos compared to only a single acceptor oligo, even when only a single donor oligo was employed. Additional acceptor oligos were easily incorporated into the assay and a tenfold change in the detection limit was readily achieved, with detection limits of 250 attomole of target being recorded. In summary, replacement of antibodies with oligonucleotides allows us to take advantage of genotypic difference(s), which both expands its repertoire of biological markers and furthers its use as a diagnostic tool.

Global change impacts on mineral nutritional quality of cereal grains: Coordinated datasets and analyses to advance a systems-based understanding

ContextGlobal nutritional health outcomes are directly reliant on agroecosystem nutrient outputs. Appropriately, there is concern surrounding the impacts of a changing climate not only on crop yields, but also on crop nutritional quality (e.g., mineral nutrient concentrations). Quantifying the impacts of elevated CO2 concentrations, elevated temperature, drought stress, edaphic factors, and agronomic management on crop yields and mineral nutrition is critical, yet a systems-level understanding of these interactive factors is poorly developed, limiting our ability to effectively target solutions. Empirical data for climate impacts on crop nutritional quality remain scarce, with much of the research emerging from valuable, but geographically limited, Free-air CO2 Enrichment (FACE) experiments, several of which suggest that human nutrition will be adversely impacted by e[CO2]. Specific concerns center on observed declines in grain protein, iron, and zinc concentrations due to already wide-spread human nutritional deficiencies in these nutrients. ObjectivesAs global change experiments expand to pursue questions regarding interactive climate impacts on crop yields and nutritional quality, it is imperative to interrogate the measurements, data standardization, and metadata needed for unifying synthesis. The data reported for shifts in crop nutritional quality are often incomplete, precluding the generalizability and comparability of results. MethodsWe frame this review around six inter-reliant methods, tools, and practices to support maximally useful experimental datasets to inform questions of global change impacts on crop nutrition and aid in detecting genotypic differences in mineral nutrient density. The bulk of the data and discussion centers on wheat (Triticum aestivum L.) due to the central role this crop plays in human nutrition and sustained biofortification efforts. ResultsTo permit experimental comparability and synthesis, datasets should (1) clearly delineate analytical methods and standards and (2) link mean nutrient concentrations with the covariate of yield. (3) Multi-year, multi-location data is required to identify genotypes with significant deviations in nutrient concentrations, with (4) data normalized for yield within appropriate analytical frameworks. (5) Inclusion of data on soil properties, weather, and abiotic and biotic stresses as well as (6) agronomic practices and nutrient management is essential for understanding global change impacts on nutritional outcomes. ConclusionsCoordinated, multi-dimensional data will permit the syntheses and meta-analyses needed to identify and quantify climate impacts on nutrition. ImplicationsThis work is essential to effectively target nutritional solutions, to develop modeling tools to support nutritional planning, and to identify areas where agronomic management and breeding can minimize climate impacts on nutritional outcomes.

Abstract 5671: Profiling intra-tumor heterogeneity and chromosomal instability in malignant peripheral nerve sheath tumors

Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft-tissue sarcomas that manifest on peripheral nerves, constituting 2% of all sarcomas. While previous genomic analyses of MPNSTs have been conducted on small cohorts, often limited to single samples per patient and lacking comprehensive resolution, the extent of intra-tumor heterogeneity and the contribution of chromosomal instability to MPNST development remains unclear. To address these limitations, we developed a multi-omics integration pipeline and applied it to bulk Whole Genome Sequencing (WGS), single-cell RNA sequencing(scRNA-seq), single-cell DNA sequencing (scDNA-seq), spatial transcriptomics (ST), and Laser Capture Microsection (LCM) sequencing data. 60 tumor samples were collected from 17 patients with MPNST, and the above five techniques were applied to each sample. Overall, tumors harbor a high degree of chromosomal instability and evidence of whole-genome doubling (WGD). We reconstructed tumor phylogenetic trees from WGS data using Dirichlet Process-based methods. Intriguingly, our findings indicated that for patient 2.3, primary tumor samples PT_1 and PT_2 displayed a close phylogenetic relationship, while local recurrences LR_2 and LR_3 represented a different branch of the phylogenetic tree. Moreover, scRNA-seq analysis of patient 2.16 highlighted an enrichment of immune cells, including macrophages, B cells, and T cells. To infer copy number alterations (CNA) of tumor cells from scRNA-seq data, we leveraged inferCNV, with normal cells identified within the same sample as controls. Significant copy number gains were identified on chromosomes 5, 7, 8, and 15 in patient 2.16. The inferred copy number changes derived from scRNA-seq were validated against copy number profiles obtained through WGS using Battenberg, revealing a remarkable congruence. In the scDNA analysis of patient 2.12, we observed that all tumor cells exhibited biallelic loss of CDKN2A, with a majority showcasing WGD and chromosome 7 amplification. This finding underscored the potential significance of CDKN2A in the pathogenesis of this tumor, in keeping with the observation that CDKN2A is recurrently mutated and lost in MPNSTs. Our research profiled the tumors' evolutionary histories and intra-tumor heterogeneity down to single-cell resolution, highlighting the genotype and phenotype differences between tumor subclones. By shedding light on the genomic landscape of MPNSTs, we aspire to make profound contributions to the field of sarcoma research, ultimately improving patient outcomes. Citation Format: Yixiao Cheng, Haixi Yan, Maxime Tarabichi, Zhihui Zhang, Chunxu Gao, Tom Lesluyes, Adrienne Flanagan, Peter Van Loo. Profiling intra-tumor heterogeneity and chromosomal instability in malignant peripheral nerve sheath tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5671.

Maize emergence rate and leaf emergence speed estimation via image detection under field rail-based phenotyping platform

Accurate and efficient acquisition of maize emergence rate and leaf emergence speed in the field is essential for detecting seed quality, evaluating crop field management plans, and yield assessment. This study constructs a system solution to obtain the maize seedling emergence rate and leaf emergence speed based on the field rail-based phenotyping platform and convolutional neural network. Firstly, we use the field rail-based phenotyping platform to collect a high-temporal sequence visible light images of maize plant during the seedling stage. In the first stage, an improved Faster R-CNN is used to detect maize seedlings in the plot images, and the plant ROI area is cropped as the input for the second stage network. In the second stage, the best performing ResNeSt network out of four backbone networks is chosen, using the Mask R-CNN model to segment the leaves of the input plant image, which is then used to calculate the number of leaves. We propose a quantification index for leaf emergence speed based on a weighted average combination of leaf numbers. Using the method described in this paper, we analyzed the plant images from 52 inbred lines plots of over seven consecutive days. The experimental results show that when the Intersection Over Union (IOU) is 0.50, the bbox_mAP of the maize seedling detection model is 0.969, with an accuracy rate of 99.53%. Compared with manual counting, the calculated R2 is 0.997 and RMSE is 43.382. The segm_mAP of the plant leaf segmentation model is 0.942. The differences in emergence rate and leaf emergence speed across 52 inbred lines were compared, providing new phenotyping reference indices for further exploring the genotypic differences affecting seed emergence and leafing.

Varietal responses to a soil amendment: Balancing cadmium mitigation and mineral biofortification in wheat production

The application of soil amendment (SA) and the cultivation of low Cd-accumulating varieties have been a widely favored strategy to enable the safe utilization of Cd-contaminated arable land. However, little has been reported on the reciprocal effects of SA on the Cd mitigation and nutritional quality of different wheat varieties. In this study, we evaluated the impact of an SA on agronomic traits, Cd accumulation, translocation and mineral nutrition of 12 wheat varieties in an acidic field with a Cd concentration of 0.46 mg/kg. The results showed that the SA significantly reduced soil DTPA Cd (42.3 %) and resulted in a slight decrease in wheat grain yield (4.24–9.72 %, average 7.62 %). Similarly, the SA significantly reduced grain Cd concentrations (average 61.65 %) while increased the concentrations of beneficial elements such as Mo and Se in all wheat varieties. However, this intervention also led to a reduction in the concentration of essential mineral elements (such as Ca, Fe, and Mn) in whole wheat grain and starchy endosperm, as well as a reduction in their proportion in the bran. Based on genotypic differences, Huaimai 33, Zhenmai 168, Sumai 188 and Yangmai 28 were considered to be the relatively most promising wheat varieties for achieving a balance among food safety, nutritional quality, and economic yield in this region. Taken together, this study highlights the varietal differences in Cd mitigation and mineral accumulation in different wheat varieties in response to the SA, offering new perspectives for phytoremediation and biofortification strategies for Cd-contaminated farmland.

Apolipoprotein E E3/E4 genotype is associated with an increased risk of type 2 diabetes mellitus complicated with coronary artery disease

ObjectiveDyslipidemia is a co-existing problem in patients with diabetes mellitus (DM) and coronary artery disease (CAD), and apolipoprotein E (APOE) plays an important role in lipid metabolism. However, the relationship between the APOE gene polymorphisms and the risk of developing CAD in type 2 DM (T2DM) patients remains controversial. The aim of this study was to assess this relationship and provide a reference for further risk assessment of CAD in T2DM patients.MethodsThe study included 378 patients with T2DM complicated with CAD (T2DM + CAD) and 431 patients with T2DM alone in the case group, and 351 individuals without DM and CAD were set as controls. The APOE rs429358 and rs7412 polymorphisms were genotyped by polymerase chain reaction (PCR) - microarray. Differences in APOE genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for age, gender, body mass index (BMI), history of smoking, and history of drinking to access the relationship between APOE genotypes and T2DM + CAD risk.ResultsThe frequencies of the APOE ɛ3/ɛ4 genotype and ε4 allele were higher in the T2DM + CAD patients, and the frequencies of the APOE ɛ3/ɛ3 genotype and ε3 allele were lower than those in the controls (all p < 0.05). The T2DM + CAD patients with ɛ4 allele had higher level in low-density lipoprotein cholesterol (LDL-C) than those in patients with ɛ2 and ɛ3 allele (p < 0.05). The results of logistic regression analysis showed that age ≥ 60 years old, and BMI ≥ 24.0 kg/m2 were independent risk factors for T2DM and T2DM + CAD, and APOE ɛ3/ɛ4 genotype (adjusted odds ratio (OR) = 1.93, 95% confidence interval (CI) = 1.18–3.14, p = 0.008) and ɛ4 allele (adjusted OR = 1.97, 95% CI = 1.23–3.17) were independent risk factors for T2DM + CAD. However, the APOE genotypes and alleles were not found to have relationship with the risk of T2DM.ConclusionsAPOE ε3/ε4 genotype and ε4 allele were independent risk factors for T2DM complicated with CAD, but not for T2DM.

Genetic Divergence of Ashwagandha (Withania somnifera (L.) Dunal) for Growth and Yield Traits

Genetic divergence among 32 Ashwagandha (Withania somnifera (L.) Dunal) accessions of different geographic origins was assessed using Mahalanobis D2 statistics. Observations revealed significant genotypic differences, and accordingly, genotypes were classified into six clusters. Cluster I was the largest, with twenty genotypes, followed by the cluster II, which has eight, and clusters III, IV, V, and VI contained only one most divergent genotype. The maximum divergence was observed between clusters II and III (D2 = 47.90), followed by clusters V and VI (D2 = 43.95), and clusters III and VI (D2 = 42.29). Cluster IV had the least inter-cluster distance (D2 = 22.82) with cluster VI. Clusters III, IV, V, and VI had only one genotype each, and hence, the intra-cluster distance was zero. The genotype of cluster V was unique as it had the highest values for fresh and dry root weight per plant, diameter and length of the main root, number of secondary roots per plant, number of berries per plant, and girth of stem with a high seed yield per plant. Cluster VI was desirable in respect of days to 50 per cent flowering and days to root harvest. Cluster II exhibited the highest value for height of plant and branches per plant. Cluster IV had the highest mean values for the number of seeds per berry. Thus, hybridization among these genotypes can generate desirable transgressive segregants. Aim of Studies: To assess the genetic divergen of Withania somnifera. Place and Duration of Study: Department of Horticulture, College of Agriculture, UAS, GKVK, Bengaluru from 2020-21 to 2021-22. Methodology: The genetic divergence between the genotypes in the population was estimated using formula D2= p (Yit - Yjt) and genetic divergence among 32 Ashwagandha (Withania somnifera (L.) Dunal) accessions of different geographic origins was assessed using Mahalanobis D2 statistics. Observations revealed significant genotypic differences, and accordingly. Results: Observations revealed significant genotypic differences, and accordingly, genotypes were classified into six clusters. Cluster I was the largest, with twenty genotypes, followed by the cluster II, which has eight, and clusters III, IV, V, and VI contained only one most divergent genotype. The maximum divergence was observed between clusters II and III (D2 = 47.90), followed by clusters V and VI (D2 = 43.95), and clusters III and VI (D2 = 42.29). Cluster IV had the least inter-cluster distance (D2 = 22.82) with cluster VI. Clusters III, IV, V, and VI had only one genotype each, and hence, the intra-cluster distance was zero. The genotype of cluster V was unique as it had the highest values for fresh and dry root weight per plant, diameter and length of the main root, number of secondary roots per plant, number of berries per plant, and girth of stem with a high seed yield per plant. Cluster VI was desirable in respect of days to 50 per cent flowering and days to root harvest. Cluster II exhibited the highest value for height of plant and branches per plant. Cluster IV had the highest mean values for the number of seeds per berry Conclusion of finding: Significant genetic divergence and complementarity for most features has been shown by the genotypes of clusters II and III and clusters V and VI. This could lead to significant genetic improvement for particular characters and their selection for new varieties.

Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan.

The genetic pathways that modulate ageing in multicellular organisms are typically highly conserved across wide evolutionary distances. Recently RNA polymerase III (Pol III) was shown to promote ageing in yeast, C. elegans and D. melanogaster. In this study we investigated the role of Pol III in mammalian ageing using C57BL/6N mice heterozygous for Pol III (Polr3b+/-). We identified sexually dimorphic, organ-specific beneficial as well as detrimental effects of the Polr3b+/- mutation on health. Female Polr3b+/- mice displayed improved bone health during ageing, but their ability to maintain an effective gut barrier function was compromised and they were susceptible to idiopathic dermatitis (ID). In contrast, male Polr3b+/- mice were lighter than wild-type (WT) males and had a significantly improved gut barrier function in old age. Several metabolic parameters were affected by both age and sex, but no genotype differences were detected. Neither male nor female Polr3b+/- mice were long-lived compared to WT controls. Overall, we find no evidence that a reduced Pol III activity extends mouse lifespan but we do find some potential organ- and sex-specific benefits for old-age health.

Distribution patterns of molecular markers of antimalarial drug resistance in Plasmodium falciparum isolates on the Thai-Myanmar border during the periods of 1993–1998 and 2002–2008

BackgroundPolymorphisms of Plasmodium falciparum chloroquine resistance transporter (pfcrt), Plasmodium falciparum multi-drug resistance 1 (pfmdr1) and Plasmodium falciparum kelch 13-propeller (pfk13) genes are accepted as valid molecular markers of quinoline antimalarials and artemisinins. This study investigated the distribution patterns of these genes in P. falciparum isolates from the areas along the Thai-Myanmar border during the two different periods of antimalarial usage in Thailand.ResultsPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect pfcrt mutations at codons 76, 220, 271, 326, 356, and 371 as well as pfmdr1 mutation at codon 86. The prevalence of pfcrt mutations was markedly high (96.4–99.7%) in samples collected during both periods. The proportions of mutant genotypes (number of mutant/total isolate) at codons 76, 220, 271, 326, 356 and 371 in the isolates collected during 1993–1998 (period 1) compared with 2002–2008 (period 2) were 97.9% (137/140) vs. 97.1% (401/413), 97.9% (140/143) vs. 98.8% (171/173), 97.2% (139/143) vs. 97.1% (333/343), 98.6% (140/142) vs. 99.7% (385/386), 96.4% (134/139) vs. 98.2% (378/385) and 97.8% (136/139) vs. 98.9% (375/379), respectively. Most isolates carried pfmdr1 wild-type at codon 86, with a significant difference in proportions genotypes (number of wild type/total sample) in samples collected during period 1 [92.9% (130/140)] compared with period 2 [96.9% (379/391)]. Investigation of pfmdr1 copy number was performed by real-time PCR. The proportions of isolates carried 1, 2, 3 and 4 or more than 4 copies of pfmdr1 (number of isolates carried correspondent copy number/total isolate) were significantly different between the two sample collecting periods (65.7% (90/137) vs. 87.8% (390/444), 18.2% (25/137) vs. 6.3%(28/444), 5.1% (7/137) vs. 1.4% (6/444) and 11.0% (15/137) vs. 4.5% (20/444), for period 1 vs. period 2, respectively). No pfk13 mutation was detected by nested PCR and nucleotide sequencing in all samples with successful analysis (n = 68).ConclusionsThe persistence of pfcrt mutations and pfmdr1 wild-types at codon 86, along with gene amplification in P. falciparum, contributes to the continued resistance of chloroquine and mefloquine in P. falciparum isolates in the study area. Regular surveillance of antimalarial drug resistance in P. falciparum, incorporating relevant molecular markers and treatment efficacy assessments, should be conducted.

Effect of nitrogen fixation enhancing type SEN1 gene on soybean growth

ABSTRACT It is well known that the growth of legumes is greatly affected not only by fertilizer nitrogen but also by fixed nitrogen by symbiosis with rhizobia. We have reported that a polymorphism in SEN1, which is essential for nitrogen fixation in Lotus japonicus, could be used to enhance nitrogen fixation and plant growth. In this study, we examined whether the same strategy could be applied to Glycine max. Sequencing of orthologs of the LjSEN1 gene in 38 soybean cultivars revealed that the polymorphism occurred at Glyma.08g076300. We defined the standard sequence that most of the cultivars retained as Peking type SEN1, and the mutated sequence found in Enrei as Enrei type SEN1. To investigate the effect of genotype differences, we generated near-isogenic lines by crossing Enrei with Fukuyutaka, which has Peking type SEN1, and analyzed their characteristics. The results showed that Enrei type enhanced nitrogen fixation activity and promoted plant growth. Since soybean SEN1 has been reported to be a homolog of vacuolar iron transporter-like protein, we investigated the iron content in the nodules. In the result, the iron content in the nodules of Enrei type was significantly higher than that of Peking type. Iron is known to be present in the active center of nitrogenase, and the high iron content may have contributed to the increased nitrogen fixation activity. These results suggest that Enrei type SEN1 is a nitrogen fixation enhancing gene and that introduction of Enrei type SEN1 may reduce nitrogen fertilizer application and increase yield.