Genetic variation in histidine rich proteins among Indian Plasmodium falciparum population: possible cause of variable sensitivity of malaria rapid diagnostic tests

BACKGROUND: Rapid diagnostic tests (RDTs) have revolutionized the diagnosis of malaria. Among the various factors affecting RDTs sensitivity is genetic variation of the antigen used. The genetic variation in PfHRP2 and PfHRP3 proteins was studied among the Indian Plasmodium falciparum isolates. METHODS: One hundred and forty isolates of P. falciparum were collected from six geographical regions of India. Target genes encoding PfHRP2 and PfHRP3 antigens were sequenced to study genetic polymorphism. Minimum detection limit giving a positive rapid diagnostic test was also determined. RESULTS: Extensive variations were observed in amino acid repeat types of PfHRP2 and PfHRP3. PfHRP2 exhibited more polymorphism than PfHRP3. Significant relation was observed between type 2 and type 7 repeats and RDT detection rate as higher number of these repeats showed better sensitivity with RDTs. CONCLUSION: The results provide insights into the genetic diversity of Pfhrp2 and Pfhrp3 genes among Indian P. falciparum population and its relation to RDT sensitivity

Human Cataract Mutations in EPHA2 SAM Domain Alter Receptor Stability and Function

The cellular and molecular mechanisms underlying the pathogenesis of cataracts leading to visual impairment remain poorly understood. In recent studies, several mutations in the cytoplasmic sterile-α-motif (SAM) domain of human EPHA2 on chromosome 1p36 have been associated with hereditary cataracts in several families. Here, we have investigated how these SAM domain mutations affect EPHA2 activity. We showed that the SAM domain mutations dramatically destabilized the EPHA2 protein in a proteasome-dependent pathway, as evidenced by the increase of EPHA2 receptor levels in the presence of the proteasome inhibitor MG132. In addition, the expression of wild-type EPHA2 promoted the migration of the mouse lens epithelial αTN4-1 cells in the absence of ligand stimulation, whereas the mutants exhibited significantly reduced activity. In contrast, stimulation of EPHA2 with its ligand ephrin-A5 eradicates the enhancement of cell migration accompanied by Akt activation. Taken together, our studies suggest that the SAM domain of the EPHA2 protein plays critical roles in enhancing the stability of EPHA2 by modulating the proteasome-dependent process. Furthermore, activation of Akt switches EPHA2 from promoting to inhibiting cell migration upon ephrin-A5 binding. Our results provide the first report of multiple EPHA2 cataract mutations contributing to the destabilization of the receptor and causing the loss of cell migration activity

Chickpea

The narrow genetic base of cultivated chickpea warrants systematic collection, documentation and evaluation of chickpea germplasm and particularly wild Cicer species for effective and efficient use in chickpea breeding programmes. Limiting factors to crop production, possible solutions and ways to overcome them, importance of wild relatives and barriers to alien gene introgression and strategies to overcome them and traits for base broadening have been discussed. It has been clearly demonstrated that resistance to major biotic and abiotic stresses can be successfully introgressed from the primary gene pool comprising progenitor species. However, many desirable traits including high degree of resistance to multiple stresses that are present in the species belonging to secondary and tertiary gene pools can also be introgressed by using special techniques to overcome pre- and post-fertilization barriers. Besides resistance to various biotic and abiotic stresses, the yield QTLs have also been introgressed from wild Cicer species to cultivated varieties. Status and importance of molecular markers, genome mapping and genomic tools for chickpea improvement are elaborated. Because of major genes for various biotic and abiotic stresses, the transfer of agronomically important traits into elite cultivars has been made easy and practical through marker-assisted selection and marker-assisted backcross. The usefulness of molecular markers such as SSR and SNP for the construction of high-density genetic maps of chickpea and for the identification of genes/QTLs for stress resistance, quality and yield contributing traits has also been discussed

An in vivo P-31 NMR study of the phosphorus metabolites in developing seeds of wheat, soybean and mustard

In vivo 31P NMR spectra of wheat, soybean and mustard seeds were recorded during ripening. Signals were detected from phosphomonoesters, cytoplasmic and vacuolar inorganic phosphate (P1), phytate, nucleoside triphosphate (NTP) and nucleoside diphosphosugars. The spectra of extracts showed an accumulation of phytate during development, accompanied by a decrease in inorganic phosphate, and this was reflected in the in vivo spectra. The intrinsic width of the resonances was a significant obstacle to the interpretation of the in vivo spectra in all three cases, and the problem became more severe with increasing maturity. However, it was still possible to use the chemical shift of the cytoplasmic P1 signal to monitor cytoplasmic pH in both soybean and mustard, and the results provide evidence for the existence of a hypoxic state in developing seeds during the active biosynthetic phase. © 1997 John Wiley and Sons, Ltd

Genetic variation in histidine rich proteins among Indian <it>Plasmodium falciparum</it> population: possible cause of variable sensitivity of malaria rapid diagnostic tests

Abstract Background Rapid diagnostic tests (RDTs) have revolutionized the diagnosis of malaria. Among the various factors affecting RDTs sensitivity is genetic variation of the antigen used. The genetic variation in PfHRP2 and PfHRP3 proteins was studied among the Indian Plasmodium falciparum isolates. Methods One hundred and forty isolates of P. falciparum were collected from six geographical regions of India. Target genes encoding PfHRP2 and PfHRP3 antigens were sequenced to study genetic polymorphism. Minimum detection limit giving a positive rapid diagnostic test was also determined. Results Extensive variations were observed in amino acid repeat types of PfHRP2 and PfHRP3. PfHRP2 exhibited more polymorphism than PfHRP3. Significant relation was observed between type 2 and type 7 repeats and RDT detection rate as higher number of these repeats showed better sensitivity with RDTs. Conclusion The results provide insights into the genetic diversity of Pfhrp2 and Pfhrp3 genes among Indian P. falciparum population and its relation to RDT sensitivity.</p

Intentional pesticide poisoning and pesticide suicides in Nepal

Introduction Intentional pesticide poisoning is a major clinical and public health problem in agricultural communities in low and middle income countries like Nepal. Bans of highly hazardous pesticides (HHP) reduce the number of suicides. We aimed to identify these pesticides by reviewing data from major hospitals across the country and from forensic toxicology laboratories. Methods We retrospectively reviewed medical records of 10 hospitals for pesticide poisoned patients and two forensic laboratories of Nepal from April 2017 to February 2020. The poison was identified from the history, referral note, and clinical toxidrome in the hospitals and from gas chromatography analysis in the laboratories. Data on demographics, poison, and patient outcome were recorded on a data collection sheet. Simple descriptive analysis was performed. Results Among hospital cases (n = 4148), the commonest form of poisoning was self-poisoning (95.8%) while occupation poisoning was rare (0.03%). Case fatality was 5.3% (n = 62). Aluminum phosphide (n = 38/62, 61.3%) was the most commonly identified lethal pesticide for deaths. Forensic toxicology laboratories reported 2535 deaths positive for pesticides, with the compounds most commonly identified being organophosphorus (OP) insecticides (n = 1463/2535; 57.7%), phosphine gas (n = 653/2535; 25.7%; both aluminum [11.8%] and zinc [0.4%] phosphide) and organochlorine insecticides (n = 241/2535; 9.5%). The OP insecticide most commonly identified was dichlorvos (n = 273/450, 60.6%). Conclusion The data held in the routine hospital medical records were incomplete but suggested that case fatality in hospitals was relatively low. The pesticides identified as causing most deaths were dichlorvos and aluminum phosphide. Since this study was completed, dichlorvos has been banned and the most toxic formulation of aluminum phosphide removed from sale. Improving the medical record system and working with forensic toxicology laboratories will allow problematic HHPs to be identified and the effects of the bans in reducing deaths monitored