Resistance of bmr energy sorghum hybrids to sugarcane borer and fall armyworm

The lower lignin content in plants species with energy potential results in easier cellulose breakdown, making glucose available for ethanol generation. However, higher lignin levels can increase resistance to insect attack. The objective of this work was to evaluate the susceptibility of a bmr-6 biomass sorghum (a mutant genotype with a lower concentration of lignin) to important pests of energy sorghum, Diatraea saccharalis and Spodoptera frugiperda. Experiments were performed in the laboratory and greenhouse to evaluate the development of these pests on the biomass sorghum bmr hybrids BR007, BR008, and TX635 and their respective conventional near-isogenic genotypes (without the bmr gene). The lignin content was higher in non-bmr hybrids, but the evaluated insect variables varied between treatments, not being consistent in just one hybrid or because it is bmr or not. The lowest survival of S. frugiperda was observed in the BR008 hybrid, both bmr and non-bmr. The S. frugiperda injury scores on plants in the greenhouse were high (>7) in all treatments. For D. saccharalis, there was no difference in larval survival in the laboratory, but in the greenhouse, the BR007 hybrid, both bmr and non-bmr, provided greater survival. Due the need to diversify the energy matrix and the fact that greater susceptibility of the bmr hybrids to either pests was not found in this study, these results hold promise for cultivation of these biomass sorghum hybrids for the production of biofuels.

Association of NAT-2 gene polymorphisms toward lung cancer susceptibility and prognosis in North Indian patients treated with platinum-based chemotherapy

Aim: The present study has been carried out to evaluate the association of the N-acetyl transferase 2 ( NAT2) variants in North Indian lung cancer patients and healthy controls. Furthermore, we have also determined the effect of the polymorphic variants of the NAT2 gene on the clinical outcomes and overall survival among lung cancer (LC) subjects treated with platinum-based doublet chemotherapy. Methods: This case-control study comprised a total of 550 cases and 550 healthy controls. The genotyping was carried out using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and the statistical analysis was carried out using MedCalc. Results: There was a lack of any significant association for both 590G>A and 803A>G polymorphisms toward risk for LC, but 857G>A polymorphism exhibited a risk toward LC (p = 0.005). Whereas, variant alleles for the 481C>T polymorphism had a decreased risk for LC (p = 0.0003). Further, 857G>A polymorphism conferred a positive association between genotype and ADCC (p = 0.001) and 481C>T polymorphism had a decreased risk for SQCC (OR = 0.39, p = 0.0006) and SCLC (p = 0.001) subjects. The smokers carrying mutant genotype for the 481C>T polymorphism had a decreased risk toward LC (p < 0.0001) even in light (p = 0.002) as well as heavy smokers (p = 0.001). In case of females, 2.59-fold and 3.66-fold increased risk of LC development was observed in subjects with intermediate and slow acetylator for the 857G>A polymorphism. Whereas, in case of males this polymorphism depicts a reduced risk for LC. On the other hand, 803A>G depicted a 2.82-fold risk of LC in case of female subjects who were slow acetylators. Our study exhibits a significant difference in the overall haplotype distribution between cases and controls. In our study overall, (857G>A, 481C>T, 803A>G) was found to be best model, but was not significant using MDR. Considering the CART results 481C>T polymorphism came out to be the most significant factor in determining the LC risk. For the 803A>G polymorphism, a threefold odds of lymph node invasion were observed for mutant genotype, the recessive model exhibited an odd of 2.8. 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy as the survival time for such patients was better. Conclusion: These results suggest that NAT2 variant genotype for 590G>A and 803A>G was not found to modulate risk toward LC, but 857G>A polymorphism exhibited a risk toward LC and 481C>T polymorphism had a decreased risk for LC. NAT2 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy and 481C>T came out to be significant factor using CART.

GSTP1 Ile105Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy

Background Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile 105 Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy. Methods The polymorphism of GSTP1 Ile 105 Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles ( Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02). Conclusions Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia

GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients

Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p < 0.001), while the dominant CC was a protective factor (p = 0.004). Regarding miR-137 rs1625579, the mutant genotype TT was reported as a risk factor for CHBV (p < 0.001) and the normal GG genotype was a protective factor, p < 0.001. The serum GAS5 was significantly higher in the mutant TT genotype of GAS5 SNP as compared to the other genotypes (p = 0.007). Concerning miR-137 rs1625579, the mutant TT genotype was significantly associated with a lower serum expression level of miR-137 (p = 0.018). We revealed the dysregulated expression levels of GAS5 and miR-137 linked to their functioning SNPs were associated with CHBV risk and might act as potential therapeutic targets.

Molecular profile of the D. melanogaster mutant genotype w1118 in the presence of variable amount of deuterium (D)

The Drosophila melanogaster w1118 mutant line was used to identify the effect of deuterium (D) on DNA synthesis. D concentrations ranged from 30ppm to 96.89% (low and very high amount respec-tively). Five generations of flies were bred on culture media prepared with 6 concentrations of D. For each generation the DNA was analyzed, and its variability was established. The results showed a small involvement of D in the successive synthesis of nuclear DNA.

Do MTHFR C677T Genetic Polymorphism Influence in the Pathogenesis of Amyotrophic Lateral Sclerosis?

Amyotrophic Lateral Sclerosis (ALS) is a progressive and lethal neurodegenerative disease without a definitive diagnostic test and effective treatment. A plethora of studies suggest that genetic factors play an important role in ALS development, and potentially link folate pathway dysregulation to disease pathogenesis. This study aims to evaluate folate dysregulation due to MTHFR C677T polymorphism and other factors such as sociodemographic and clinical, to better elucidate the involvement of these factors in ALS pathogenesis, and to investigate possible biomarkers for use as disease diagnostics or prognostics. This hospital-based case-control study analyzed 101 patients diagnosed with ALS and 119 considered healthy, with no suspicion or diagnosis of neurodegenerative disease. Blood samples were collected, stored, and underwent DNA extraction. Clinical and sociodemographic data from patients were collected through a questionnaire, as well as consultation of medical records. Genotypic analyses were performed using PCR-RFLP, and statistical analysis of clinical and genotypic data was conducted with SPSS software, version 23. The results show a higher presence of the mutant genotype (p = 0.02) in the case group, and suggest that mutant allele (T) is a risk factor for ALS susceptibility (OR = 1.54; 95% CI = 1.05–2.29; p = 0.03). Mutant genotype (T/T) interacts with both demographics (White p = 0.005 / Brown p = 0,001) and clinical factors (Physical activity p = 0.006) as risk factors for ALS. Also, a significant difference in alcohol consumption (p = 0.001) between the case and control group was observed. Moreover, a statistical trend towards faster disease progression and death was observed for patients with the mutant allele (T) (p = 0.06). Thus, the results of this study suggest that folate deficiency due to MTHFR C677T polymorphism is implicated in ALS through pathogenic mechanisms and interaction with other risk factors, resulting in faster disease progression and early death.

Case Report: Recurrent Variant c.298 TA in CCN6 Gene Found in Progressive Pseudorheumatoid Dysplasia Patients From Patni Community of Gujarat: A Report of Three Cases

Biallelic mutations in the CCN6 gene are known to cause a rare genetic disorder—progressive pseudorheumatoid dysplasia (PPD). PPD is characterized by distinct joint deformities of interphalangeal joints, stiffness, gait disturbance, abnormal posture, and absence of inflammation, resulting in significant morbidity. The largest case series of PPD from India suggests c.233G&gt;A and c.1010G&gt;A to be the most common mutations in the CCN6 gene, although the distribution of these variants among endogamous communities in India has not been carried out. We here report three cases of PPD from three independent families belonging to the Patni community of Gujarat, a community known to practice endogamy. All three cases had short stature, gait disturbance, scoliosis, and interphalangeal joint deformities. Analysis by whole-exome sequencing in the first case showed the presence of a previously known, homozygous, missense variant c.298T&gt;A (p.Cys100Ser) in exon 3 of the CCN6 gene in all cases. Due to all three families belonging to the same community, analysis by Sanger sequencing in the remaining two cases for the variant mentioned earlier showed both cases to be of homozygous mutant genotype. Unaffected family members, i.e., parents and siblings, were either heterozygous carriers or wildtype for the said variant. The present case series is the first report of a recurrent variant occurring across multiple PPD-affected individuals from unrelated families belonging to the same community from India.

Pharmacological rescue of tumor intrinsic STING expression and immune response in LKB1-mutant lung cancer via the IAP-JAK regulatory axis

Harnessing the power of the immune system to treat cancer has become a core clinical approach. However, rewiring of intrinsic circuitry enables tumor cells to escape immune attacks, leading to therapeutic failure. Pharmacological strategies to reverse tumor genotype-dictated therapeutic resistance are urgently needed to advance precision immunotherapy. Here, we identify antagonists of Inhibitor of Apoptosis Protein (IAP) as potent sensitizers that restore immune-dependent killing of LKB1-mutant lung cancer cells. Mechanistic studies reveal an LKB1-IAP-JAK trimolecular complex that bridges the LKB1-mutant genotype with IAP-dependency and a STING-deficiency-mediated immune resistance phenotype. Ultimately, inhibition of IAP re-establishes JAK-regulated STING expression and DNA sensing pathway as well as enhanced cytotoxic immune cell infiltration and selective immune-dependent anti-tumor activity in an LKB1-mutant immune-competent mouse model. Thus, IAP-JAK-modulatory strategies, like IAP inhibitors, offer promising immunotherapy adjuvants to re-establish the responsiveness of "immunologically-cold" LKB1-mutant tumors to immune checkpoint inhibitors or STING-directed therapies.

Low molecular weight heparin prophylaxis for placenta-mediated complications in women with F2G20210A mutation

Introduction. A prothrombin-mutant genotype is a known risk factor in gestational complications.Aim — efficacy assessment in pregravid heparin prevention of pre-eclampsia (PE) and foetal growth retardation (FGR) in females with F2G20210A genotype and suprathreshold prothrombin activity.Patients and methods. A single-centre randomised controlled study enrolled 80 pregnant women carrying prothrombin F2G20210A. The inclusion criterion was a pregravid plasma prothrombin activity > 171 %. The study cohort consisted of 50 women (mean age 31.2 ± 3.7 years) receiving low molecular-weight heparin (LMWH) in menstrual cycle at weight-based elevated prevention doses. A comparison group comprised 30 pregnant women (mean age 31.3 ± 2.9 years) not receiving LMWH prophylaxis.Results. A pregravid start of LMWH treatment at high prophylactic doses in F2G20210A genotype carriers with prothrombin activity > 171 % allowed an absolute risk reduction (ARR) of PE by 46.7 % [p = 0.0001; number needed to treat (NNT): 2.1; 95 % confidence interval (CI) 3.4–1.56], severe PE by 30.7 % [p = 0.0001; NTT: 3.3; 95 % CI (6.7–2.2)] and FGR by 30.7 % [p = 0.0001; NTT: 3.3; 95 % CI (6.7–2.2)].Conclusion. Use of LMWH is justified in prevention of placenta-mediated complications in F2G20210A genotype carriers with a suprathreshold-high prothrombin activity.

Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes

The spread of Plasmodium falciparum resistant parasites remains one of the major challenges for malaria control and elimination in Sub Saharan Africa. Monitoring of molecular markers conferring resistance to different antimalarials is important to track the spread of resistant parasites and to optimize the therapeutic lifespan of current drugs. This study aimed to evaluate the prevalence of known mutations in the drug resistance genes Pfcrt, Pfmdr1, Pfdhfr and Pfdhps in two different epidemiological settings in Cameroon. Dried blood spots collected in 2018 and 2019 from asymptomatic individuals were used for DNA extraction and then the Plasmodium infection status was determined byPCR. Detection of SNPs was performed by nested PCR followed by allele-specific restriction analysis (ASRA). The prevalence of each genotype was compared between sites using the Chi square and Fisher’s exact tests. A high prevalence of the Pfcrt K76 wild type allele was found in both sites (88.5 and 62.29% respectively; P< 0,0001). The prevalence of Pfmdr1 mutations 86Y and 1246Y was respectively 55.83 and 1.45% in Mfou and 45.87 and 5.97% in Tibati, with significant difference between the studied areas (P<0.0001). Overall, the Pfdhfr triple-mutant genotype (51I/59R/108N) was highly prevalent (> 96%), however no SNP was detected at codon 164. In Pfdhps, the prevalence of the 437G mutation reached (90%) and was at higher frequency in Mfou (P< 0.0001). Overall, the Pfdhps mutations 540E and 581G were less common (0.33 and 3.26%, respectively). The quadruple resistant genotype (Pfdhfr 51I/59R/108N+Pfdhp437G) was found almost 90% of the samples. The wild-type genotype (Pfdhfr N51/C59/S108/164I+Pfdhps A437/K540/A581) was never identified and the sextuple mutant (Pfdhfr 51I/59R/108N+Pfdhp437G/540E/581G), kwon as super resistant appeared in two samples from Tibati. These findings demonstrate declining trends in the prevalence of mutations conferring resistance to 4-aminoquinolines, especially to chloroquine. However, a high level of mutations in P. falciparum genes related to SP resistance was detected and this raises concerns about the future efficacy of IPTp-SP and SMC in Cameroon.