Browsing by Author "Kumari, Renu"

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Agronomic characteristics of autumn and winter seeded photoperiod insensitive spring wheat in agro-climate of north-west India
(Indian National Science Academy, 2012) Kumar, Sushil; Sharma, Vishakha; Chaudhary, Swati; Kumar, Arvind; Kumari, Renu
AI & ethics: charting a responsible future
(NATL INST SCIENCE COMMUNICATION-NISCAIR, 2024) Yadav, Gitanjali; Munshi, Angad; Kumari, Renu; Singh, Dhananjay; Kumari, Neeraj; Munshi, Usha Mujoo
Artificial intelligence (AI) is rapidly transforming the world, but its development and deployment raise critical ethical questions. This paper explores the key themes that emerged from a national conclave on AI and Ethics in India, bringing together industry and academic leaders. We examine the potential of AI for various sectors, with a thematic case study for the Genome Biology sector, alongside concerns about bias, privacy, and accountability. AI development and use, while underscoring the need for an ethical framework to guide its evolution, emphasizes the need for collaboration between academia and industry to develop ethical frameworks and translate principles into practical applications. In summary, ethical AI may serve as a moral framework of AI technologies to ensure that our technological capability aligns with fundamental societal values and human dignity on the road to progress. This framework by definition would not be a static set of commandments but a dynamic constantly evolving idea about the use of technologies like AI.
Coevolution mechanisms that adapt viruses to genetic code variations implemented in their hosts
(Indian Academy of Sciences, 2016) Kumar, Sushil; Kumari, Renu; Sharma, Vishakha
Viruses, the preponderant species, are the agents of horizontal gene transfer between cellular organisms, a major means for generation of genetic variability that drives evolution in varying environments. Recent work on virus × host interaction has led to revision of the conventional idea that the genetic code of the virus and host must be same so that the host translational system facilitates efficient, accurate and complete expression of the infecting viral genome. There is evidence now that differences between the genetic codes of viruses and their hosts are not an absolute barrier to virus multiplication. The recent work on mechanisms by which viruses overcome the mismatch in codon usage of host versus theirs is discussed here contextually. Examples of coevolution of viruses and their hosts, in terms of genetic code usage, discussed here agree with the concept that their evolution is reciprocally driven and therefore suggestive of a kind of long-term interdependent symbiotic relationship between them.
Common and distinguishing characteristics of genes and genomes and their evolution in the genome sequenced legumes
(Indian National Science Academy, 2013) Kumar, Sushil; Kumari, Renu; Sharma, Vishakha; Yadav, Gitanjali
By March 2013, genome sequences have been published for five legume species- Cicer arietinum (pulse crop chickpea), Cajanus cajan (pulse crop pigeonpea), Glycine max (pulse-cum-oil seed crop soybean), Lotus japonicus and Medicago truncatula (both model plants). The genome sequenced legumes belong to the subfamily papilionoideae of the angiosperm family leguminoseae, C. arietinum, L. japonicus and M. truncatula to the galegoid clade and C. cajan and G. max to millettioid clade. These diploid species have 2n number varying from 12 in L. japonicus, 16 in M. truncatula and C. arietinum, 22 in C. cajan and 40 in G. max. Comparisons among their genome sequences have revealed several important properties about structure and evolution of their genomes. Thirty five to 60% of genome is in the form of repititive elements, mainly transposons. Genome carries less than 50,000 protein-coding genes, 56 to 87% in two or more copies. All the five species arose from a common pre-papilionoid parent produced by inter-species hybridization accompanied by whole genome duplication (WGD or allotetraploidy) about 58 million years ago (Mya). Separation of clades and speciation occurred via sequence changes, over a period of > 40 million years. Individual genes underwent substitution and frameshift mutations. Chromosomal level rearrangements involved deletions, inversions, translocations, fission and fusions. There was spread of individual genes or blocks of genes followed by their tandem duplication. Deletion of orthologues was also involved in lineage specific changes. Ancestors of Glycine underwent an allotetraploid event after separation of C. cajan in the millettioid clade about 13 Mya. Developments relating to the applications of legume genome sequence knowledge are also discussed.
Cytosine hypomethylation at CHG and CHH sites in the pleiotropic mutants of Mendelian inheritance in Catharanthus roseus
(Indian Academy of Sciences, 2013) Kumari, Renu; Yadav, Gitanjali; Sharma, Vishakha; Sharma, Vinay; Kumar, Sushil
The 5S and 18S rDNA sequences of Catharanthus roseus cv 'Nirmal' (wild type) and its leafless inflorescence (lli), evergreen dwarf (egd) and irregular leaf lamina (ill) single mutants and lli egd, lli ill and egd ill double mutants were characterized. The lli, egd and ill mutants of Mendelian inheritance bore the names after their most conspicuous morphological feature(s). They had been chemically induced and isolated for their salt tolerance. The double mutants were isolated as morphological segregants from crosses between single mutants. The morphological features of the two parents accompanied salt tolerance in the double mutants. All the six mutants were hypomethylated at repeat sequences, upregulated and downregulated for many genes and carried pleiotropic alterations for several traits. Here the 5S and 18S rDNAs of C. roseus were found to be relatively low in cytosine content. Cytosines were preponderantly in CG context (53%) and almost all of them were methylated (97%). The cytosines in CHH and CHG (where H = A, T or C) contexts were largely demethylated (92%) in mutants. The demethylation was attributable to reduced expression of RDR2 and DRM2 led RNA dependant DNA methylation and CMT3 led maintenance methylation pathways. Mutants had gained some cytosines by substitution of C at T sites. These perhaps arose on account of errors in DNA replication, mediated by widespread cytosine demethylation at CHG and CHH sites. It was concluded that the regulation of cytosine ethylation mechanisms was disturbed in the mutants. ILL, EGD and LLI genes were identified as the positive regulators of other genes mediating the RdDM and CMT3 pathways, for establishment and maintenance of cytosine methylation in C. roseus.
Development of improved horticultural genotypes characterized by novel over-flowering inflorescence trait in periwinkle Catharanthus roseus
(Springer Science, 2012) Kumar, Sushil; Chaudhary, Swati; Kumari, Renu; Sharma, Vishakha; Kumar, Arvind
Floricultural genotypes with new plant architecture were developed in the seasonal/perennial garden plant Catharanthus roseus. The new genotypes were developed by crossing the double mutant line lli egd of C. roseus with two horticultural lines of C. roseus and a line of Catharanthus trichophyllus. As compared to the normal LLI inflorescence architecture in which racemose inflorescence had pairs of flowers subtended by one of the two leaves per node, the lli inflorescence of the new lines was excessively branched and each branch had two flowers per node which were bereft of subtending leaves. The new lines are novel in displaying several fold increased number of flowers on inflorescence unhindered by leaves. In the new floricultural lines the over-flowering lli trait was combined with variation in plant height, petal and eye colors and tolerance to the common fungal diseases.
Ebola virus disease: Biology, diagnosis, treatment and prevention of epidemics
(Indian National Science Academy, 2017) Kumar, Sushil; Kumari, Renu; Pandey, Richa; Sharma, Vishakha
Ebola virus disease (EVD) is a highly lethal contagious disease caused by the negative RNA strand Ebola virus. Reservoired in wild forest animals of Africa, Ebola virus infects humans that come in direct contact of diseased animals and outbreaks of EVD result from person to person spread of infection. A recent EVD outbreak in West Africa has killed several thousand persons. Since Ebola infection will persist in animals, EVD epidemics are expected to continue to occur in future. Infected travellers from Africa can initiate/import outbreaks in countries of other continents. This review describes the properties of the Ebola virus and EVD, the ongoing attempts to develop diagnostics, vaccines and medicines for prevention and cure of EVD and the supportive care that saves some EVD patients. Also discussed are measures that can stop and prevent EVD outbreaks. Need for inclusion of EVD in the education, research, drug and medical equipment manufacturing programmes, of the densly populated countries such as India, is emphasised.
Genetic control of leaf-blade morphogenesis by the Insecatus gene in Pisum sativum
(Indian Academy of Sciences, 2010) Kumar, Sushil; Chaudhary, Swati; Sharma, Vishakha; Kumari, Renu; Mishra, Raghvendra Kumar; Kumar, Arvind; Choudhury, Debjani Roy; Jha, Ruchi; Priyadarshini, Anupama; Kumar, Arun
To understand the role of INSECATUS (INS) gene in pea, the leaf blades of wild-type, ins mutant and seven other genotypes, constructed by recombining ins with uni-tac, af, tl and mfp gene mutations, were quantitatively compared. The ins was inherited as a recessive mutant allele and expressed its phenotype in proximal leaflets of full size leaf blades. In ins leaflets, the midvein development was arrested in distal domain and a cleft was formed in lamina above this point. There was change in the identity of ins leaflets such that the intercalary interrupted midvein bore a leaf blade. Such adventitious blades in ins, ins tl and ins tl mfp were like the distal segment of respective main leaf blade. The ins phenotype was not seen in ins af and ins af uni-tac genotypes. There was epistasis of uni-tac over ins. The ins, tl and mfp mutations interacted synergistically to produce highly pronounced ins phenotype in the ins tl mfp triple mutant. The role(s) of INS in leaf-blade organogenesis are: positive regulation of vascular patterning in leaflets, repression of UNI activity in leaflet primordia for ectopic growth and in leaf-blade primordium for indeterminate growth of rachis, delimitation of proximal leaflet domain and together with TL and MFP homeostasis for meristematic activity in leaflet primordia. The variant apically bifid shape of the affected ins leaflets demonstrated that the leaflet shape is dependent on the venation pattern.
Genetic interaction and mapping studies on the leaflet development (lld) mutant in Pisum sativum
(Indian Academy of Sciences, 2012) Kumar, Sushil; Mishra, Raghvendra Kumar; Kumar, Arvind; Chaudhary, Swati; Sharma, Vishakha; Kumari, Renu
In Pisum sativum, the completely penetrant leaflet development (lld) mutation is known to sporadically abort pinnae suborgans in the unipinnate compound leaf. Here, the frequency and morphology of abortion was studied in each of the leaf suborgans in 36 genotypes and in presence of auxin and gibberellin, and their antagonists. Various lld genotypes were constructed by multifariously recombining lld with a coch homeotic stipule mutation and with af, ins, mare, mfp, tl and uni-tac leaf morphology mutations. It was observed that the suborgans at all levels of pinna subdivisions underwent lld-led abortion events at different stages of development. As in leafblades, lld aborted the pinnae in leaf-like compound coch stipules. The lld mutation interacted with mfp synergistically and with other leaf mutations additively. The rod-shaped and trumpet-shaped aborted pea leaf suborgans mimicked the phenotype of aborted leaves in HD-ZIP-III-deficient Arabidopsis thaliana mutants. Suborganwise aborted morphologies in lld gnotypes were in agreement with basipetal differentiation of leaflets and acropetal differentiation in tendrils. Altogether, the observations suggested that LLD was the master regulator of pinna development. On the basis of molecular markers found linked to lld, its locus was positioned on the linkage group III of the P. sativum genetic map.
Genetics of dioecy and causal sex chromosomes in plants
(Indian Academy of Sciences, 2014) Kumar, Sushil; Kumari, Renu; Sharma, Vishakha
Dioecy (separate male and female individuals) ensures outcrossing and is more prevalent in animals than in plants. Although it is common in bryophytes and gymnosperms, only 5% of angiosperms are dioecious. In dioecious higher plants, flowers borne on male and female individuals are, respectively deficient in functional gynoecium and androecium. Dioecy is inherited via three sex chromosome systems: XX/XY, XX/X0 and WZ/ZZ, such that XX or WZ is female and XY, X0 or ZZ are males. The XX/XY system generates the rarer XX/X0 and WZ/ZZ systems. An autosome pair begets XY chromosomes. A recessive loss-of-androecium mutation (ana) creates X chromosome and a dominant gynoecium-suppressing (GYS) mutation creates Y chromosome. The ana/ANA and gys/GYS loci are in the sex-determining region (SDR) of the XY pair. Accumulation of inversions, deleterious mutations and repeat elements, especially transposons, in the SDR of Y suppresses recombination between X and Y in SDR, making Y labile and increasingly degenerate and heteromorphic from X. Continued recombination between X and Y in their pseudoautosomal region located at the ends of chromosomal arms allows survival of the degenerated Y and of the species. Dioecy is presumably a component of the evolutionary cycle for the origin of new species. Inbred hermaphrodite species assume dioecy. Later they suffer degenerate-Y-led population regression. Cross-hybridization between such extinguishing species and heterologous species, followed by genome duplication of segregants from hybrids, give rise to new species.
Identification and downstream analyses of domains amplified in plant genomes: The case of StAR-related lipid transfer (START) domains in rice
(Springer Nature Publishing AG, 2021) Mahtha, Sanjeet Kumar; Purama, Ravi Kiran; Kumari, Renu; Yadav, Gitanjali
Plant genomes can withstand small- and large-scale duplications, at a far greater success than any other kingdom in the tree of life, resulting in the existence and evolution of gene families, often with over a hundred members! The gene families, in turn, go through subfunctionalization or neofunctionalization, to form protein domains performing unique or grouped functions in context of the original activity. Due to the large number of such cases in the plant kingdom, it has become a routine task for plant biologists to investigate their specific gene family of interest. In this chapter, we provide a simple and standard pipeline for this effort, taking the example of steroidogenic acute regulatory protein (StAR) related lipid transfer (START) domains in rice, as reference. We describe the extraction, processing, and downstream analysis of Oryza sativa var. japonica proteome towards identification and comparative exploration of START domains. This was done by training profile Hidden Markov Models (HMM) of 35 reported START domains in Arabidopsis, which were then used to search potential homologs in rice. Downstream investigations included domain structure analysis, visualization of exon–intron patterns, chromosomal localization of START genes, and phylogenetic studies, followed by identification of cis-regulatory elements and gene regulatory network construction. Additionally, we have also highlighted various alternative tools and techniques that can be used to perform similar analyses, along with salient features.
Interaction between COCHLEATA and UNIFOLIATA genes enables normal flower morphogenesis in the garden pea, Pisum sativum
(Indian Academy of Sciences, 2011) Kumar, Sushil; Sharma, Vishakha; Chaudhary, Swati; Kumari, Renu; Kumari, Nisha; Mishra, Poonam
The simple stipules, leaflet and tendril bearing imparipinnately compound leaf blades and zygomorphic flowers, produced on stems of the diploid (2n = 14; ≥ 5000 Mbp nuclear genome) papilionoid Fabaceae plant Pisum sativum, are serving as unique and highly informative models for the dis- section of plant developmental programmes. The growing information has revealed that the processes of stipule, leaf and flower morphogeneses are genetically interconnected in P. sativum (Hofer et al. 1997; Yaxley et al. 2001; Wang et al.2008; Kumar et al. 2009).
Lychee-associated hypoglycaemic encephalopathy: A new disease of children described in India
(The National Academy of Sciences, India, 2020) Kumar, Sushil; Kumari, Renu; Pandey, Richa
Fruits of lychee tree (Litchi sinensis), extensively horticultured in India, China and many other countries, are delicious and possess many nutritious and medicinal properties. In India and other Asian countries, in lychee harvest season, outbreaks have been occurring of rapidly developing hypoglycaemia, encephalopathy, seizures and cerebral oedema in young children when they ingest lychee fruit arils in large numbers on empty stomach. It has been shown that the acute neurological illness is hypoglycaemic encephalopathy, caused by the actions of hypoglycin A (HGA) and methylenecyclopropylglycine (MCPG), the non-protein L-amino acids present in the edible arils of lychee fruits. Both HGA and MCPG phytotoxins are known to disrupt the pathways of β-fatty acid oxidation and gluconeogenesis in human body cells, result in accumulation of many undesirable metabolites of the blocked energy generating pathways, and altogether produced the often fatal hypoglycaemic illness. Here, the related work is summarized and commented upon and prospective genetical interventions in Litchi sinensis to eradicate the problem are outlined. Toxin-deficient lychee genotypes need to be developed by screening of germplasm accessions, and use of conventional and new site-directed mutagenesis technique of plant breeding. Lychee trees that produce super-toxin-rich (× 10 average toxin concentration) fruits are required to be identified and tagged to stop consumption of their fruits. New plantings must use toxin-deficient (low-toxin) lychee genotypes.
Metabolomics and molecular physiology perspective for drought and salinity stress tolerance
(Taylor & Francis Group, 2022) Jadhav, Sagar Sudam; Kumari, Renu; Mahtha, Sanjeet Kumar; Purama, Ravi Kiran; Lamba, Vinita; Yadav, Gitanjali
Among abiotic stresses, drought and salinity are mainly affecting crop production. Reactive oxygen species are produced during most of abiotic stresses and can damage cellular components. Therefore, plants produce specific antioxidants (e.g. carotenoids, xanthophylls), metabolites (e.g. flavonoids, phenols), osmoregulatory solutes (e.g. proline, sucrose) and thylakoid stabilizing isoprenes. Plant metabolic networks are complex, and excessive demand for these stress-responsive metabolites during abiotic stress is met only by reconfiguring the metabolic network. This chapter mainly discusses drought and salt stress-specific plant metabolomic and molecular responses and gives insights into signaling network involved thereof. Metabolomics combined with conventional breeding approaches (using introgression lines) has proven to be able to map abiotic stress-responsive loci and key candidates. The role of kinases and argonautes and the prospecting of stress-responsive metabolic quantitative trait loci and alleles are also discussed. The importance of amino acid and hormone metabolism and its connection with epigenetics is reviewed.
Musashi-2 causes cardiac hypertrophy and heart failure by inducing mitochondrial dysfunction through destabilizing Cluh and Smyd1 mRNA
(Springer Nature Publishing AG, 2023) Singh, Sandhya; Gaur, Aakash; Sharma, Rakesh Kumar; Kumari, Renu; Prakash, Shakti; Kumari, Sunaina; Chaudhary, Ayushi Devendrasingh; Prasun, Pankaj; Pant, Priyanka; Hunkler, Hannah; Thum, Thomas; Jagavelu, Kumaravelu; Bharati, Pragya; Hanif, Kashif; Chitkara, Pragya; Kumar, Shailesh; Mitra, Kalyan; Gupta, Shashi Kumar
Regulation of RNA stability and translation by RNA-binding proteins (RBPs) is a crucial process altering gene expression. Musashi family of RBPs comprising Msi1 and Msi2 is known to control RNA stability and translation. However, despite the presence of MSI2 in the heart, its function remains largely unknown. Here, we aim to explore the cardiac functions of MSI2. We confirmed the presence of MSI2 in the adult mouse, rat heart, and neonatal rat cardiomyocytes. Furthermore, Msi2 was significantly enriched in the heart cardiomyocyte fraction. Next, using RNA-seq data and isoform-specific PCR primers, we identified Msi2 isoforms 1, 4, and 5, and two novel putative isoforms labeled as Msi2 6 and 7 to be expressed in the heart. Overexpression of Msi2 isoforms led to cardiac hypertrophy in cultured cardiomyocytes. Additionally, Msi2 exhibited a significant increase in a pressure-overload model of cardiac hypertrophy. We selected isoforms 4 and 7 to validate the hypertrophic effects due to their unique alternative splicing patterns. AAV9-mediated overexpression of Msi2 isoforms 4 and 7 in murine hearts led to cardiac hypertrophy, dilation, heart failure, and eventually early death, confirming a pathological function for Msi2. Using global proteomics, gene ontology, transmission electron microscopy, seahorse, and transmembrane potential measurement assays, increased MSI2 was found to cause mitochondrial dysfunction in the heart. Mechanistically, we identified Cluh and Smyd1 as direct downstream targets of Msi2. Overexpression of Cluh and Smyd1 inhibited Msi2-induced cardiac malfunction and mitochondrial dysfunction. Collectively, we show that Msi2 induces hypertrophy, mitochondrial dysfunction, and heart failure.
New insight-guided approaches to detect, cure, prevent and eliminate malaria
(Springer, 2015) Kumar, Sushil; Kumari, Renu; Pandey, Richa
New challenges posed by the development of resistance against artemisinin-based combination therapies (ACTs) as well as previous first-line therapies, and the continuing absence of vaccine, have given impetus to research in all areas of malaria control. This review portrays the ongoing progress in several directions of malaria research. The variants of RTS,S and apical membrane antigen 1 (AMA1) are being developed and test adapted as multicomponent and multistage malaria control vaccines, while many other vaccine candidates and methodologies to produce antigens are under experimentation. To track and prevent the spread of artemisinin resistance from Southeast Asia to other parts of the world, rolling circle-enhanced enzyme activity detection (REEAD), a time- and cost-effective malaria diagnosis in field conditions, and a DNA marker associated with artemisinin resistance have become available. Novel mosquito repellents and mosquito trapping and killing techniques much more effective than the prevalent ones are undergoing field testing. Mosquito lines stably infected with their symbiotic wild-type or genetically engineered bacteria that kill sympatric malaria parasites are being constructed and field tested for stopping malaria transmission. A complementary approach being pursued is the addition of ivermectin-like drug molecules to ACTs to cure malaria and kill mosquitoes. Experiments are in progress to eradicate malaria mosquito by making it genetically male sterile. High-throughput screening procedures are being developed and used to discover molecules that possess long in vivo half life and are active against liver and blood stages for the fast cure of malaria symptoms caused by simple or relapsing and drug-sensitive and drug-resistant types of varied malaria parasites, can stop gametocytogenesis and sporogony and could be given in one dose. Target-based antimalarial drug designing has begun. Some of the putative next-generation antimalarials that possess in their scaffold structure several of the desired properties of malaria cure and control are exemplified by OZ439, NITD609, ELQ300 and tafenoquine that are already undergoing clinical trials, and decoquinate, usnic acid, torin-2, ferroquine, WEHI-916, MMV396749 and benzothi
Occurrence of molecularly diverse Bt Cry toxin-resistant mutations in insect pests of Bt+ corn and cotton crops and remedial approaches
(Indian Academy of Sciences, 2015) Kumar, Sushil; Kumari, Renu
Cultivation of Bt + genotypes has dispensed with insecticidal sprays and thereby corn and cotton farmers have hugely benefited worldwide. Recent recordings of genetically diverse Cry-resistance in insect pests of Bt + corn and cotton fields have raised grave concern. Curiously, bulk of Cry-resistant pink bollworms found in certain Bt + cotton fields in India proved homozygous for multiple linked mutations. Besides, dominantly inheritable Cry-resistance and cross resistance between different Cry-proteins have also been noted. To stem evolution of resistance against anti- insect protein-toxins, new nematology research on IPM procedures, complementary to refuge and Cry stacking technologies is imminently needed.
Origin, structure and function of millions of chromosomes present in the macronucleus of unicellular eukaryotic ciliate, Oxytricha trifallax: a model organism for transgenerationally programmed genome rearrangements
(Indian Academy of Sciences, 2015) Kumar, Sushil; Kumari, Renu
The unicellular eukaryotic ciliate protists characteristically contain a germline micronucleus (MIC) and a somatic macronucleus (MAC) in their cytoplasm. The MAC, which is crucial for the pursuit of cellular growth and mitotic divisions, is derived from a postzygotic MIC. The transition from MIC to MAC involves extensive editing of the MIC genome, followed by massive amplification of the residual MAC genome. The spirotrichous ciliate, Oxytricha trifallax, has been most extensively deployed as the model system to reveal the mechanism(s) of origin of the architectural complexities of MAC. This has been possible by the application of genome sequencing, synthetic RNA transgenesis and a variety of other genetic techniques. Here, we summarize and discuss the current observations of MAC genome derived from MIC genome, properties of MAC genome structure, function and significance of the novel features described in O. trifallax. The differences in the genome organization of O. trifallax and its relative alveolate species Paramecium tetraurelia and Plasmodium falciparum have been described. Aspects of programmed genome rearrangements, MAC genome structure and function requiring further analyses in different ciliate protest have been pointed out.
Perspectives of the Artemisia annua dry leaf therapy (ALT) for malaria and of its re-purposement as an affordable cure for artemisinin-treatable illnesses
(Indian National Science Academy, 2018) Goel, Richa; Kumari, Raj; Singh, Vijender; Kumari, Renu; Srivastava, Suchi; Kumar, Sushil
Malarial diseases continue to risk the lives of more than 3 billion people in 97 countries in the world, causing sickness in several million people and death to half a million patients. The preponderate malaria causing apicomplexan protozoan parasite species Plasmodium falciparum and Plasmodium vivax have become genetically resistant to most of the approved antimalarial drugs, including the artemisinin-based combination therapies (ACTs). At this time, there is a vigorous need to make enough efforts to meet the challenge of combating multi-drug resistant malaria by (a) speeding up the trials in progress on relatively more effective, new and mechanistically different antimalarial pharmaceuticals, (b) production of effective vaccines against falciparum and vivax malaria, (c) devising of new ways to use the presently available anti-malarials such as by using three-drugs ACTs and by using the different two-drug and three-drug ACTs sequentially, and (d) induction of Artemisia annua dry leaf therapy (ALT) of recent origin, but of ancient precedent, as an effective treatment for acute and complicated malaria. Here, a perspective type review is presented of the: pre-ALT antimalarial drugs, methodology of their usage and consequences of resistance development; safety, efficacy, affordability, quality maintenance and resilience to resistance development aspects of ALT; and possibilities of ALT re-purposement for treating many infectious-metabolic disorder related- and cancerous-diseases. In conclusion, an urgent need is emphasized for pilot studies and clinical trials on ALT to attest its deployment as anti-malarial and cure for diseases beyond malaria.
Pleiotropic phenotypes of the salt-tolerant and cytosine hypomethylated leafless inflorescence, evergreen dwarf and irregular leaf lamina mutants of Catharanthus roseus possessing Mendelian inheritance
(Indian Academy of Sciences, 2013) Kumari, Renu; Sharma, Vishakha; Sharma, Vinay; Kumar, Sushil
In Catharanthus roseus, three morphological cum salt-tolerant chemically induced mutants of Mendelian inheritance and their wild-type parent cv Nirmal were characterized for overall cytosine methylation at DNA repeats, expression of 119 protein coding and seven miRNA-coding genes and 50 quantitative traits. The mutants, named after their principal morphological feature(s), were leafless inflorescence (lli), evergreen dwarf (egd) and irregular leaf lamina (ill). The Southern-blot analysis of MspI digested DNAs of mutants probed with centromeric and 5S and 18S rDNA probes indicated that, in comparison to wild type, the mutants were extensively demethylated at cytosine sites. Among the 126 genes investigated for transcriptional expression, 85 were upregulated and 41 were downregulated in mutants. All of the five genes known to be stress responsive had increased expression in mutants. Several miRNA genes showed either increased or decreased expression in mutants. The C. roseus counterparts of CMT3, DRM2 and RDR2 were downregulated in mutants. Among the cell, organ and plant size, photosynthesis and metabolism related traits studied, 28 traits were similarly affected in mutants as compared to wild type. Each of the mutants also expressed some traits distinctively. The egd mutant possessed superior photosynthesis and water retention abilities. Biomass was hyperaccumulated in roots, stems, leaves and seeds of the lli mutant. The ill mutant was richest in the pharmaceutical alkaloids catharanthine, vindoline, vincristine and vinblastine. The nature of mutations, origins of mutant phenotypes and evolutionary importance of these mutants are discussed.