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Plasmodium Falciparum Life Cycle

Malaria is one of the world leading causes of death, especially among people living in sub-Sahara Africa and other tropical regions. Of the five species of the genus Plasmodium, the malaria protozoan parasite, known to infect Man, Plasmodium falciparum is responsible for the most virulent, severe and dangerous form of human malaria. Over the years, chemotherapy has played central role in the strategies towards the eradication of this disease. However, ability of P. falciparum to develop resistance to effective and affordable drugs and to pyrathroids, the active principle of the insecticides treated nets (ITNs) has made constant search for new pharmacotherapy imperative. This review presents an overview of the life cycle of the causative organism (P. falciparum), the efforts at controlling the disease and the molecular and cellular basis of the infection, with special emphasis on molecular chaperones of the heat shock proteins family as critical components of the parasite intra-erythrocytic development and survival. The motivation for the present work is also presented.

1.1 Introduction Malaria, whose pathogen is transmitted by female Anopheles mosquitoes, is both preventable and curable, but yet still impacting negatively on the health of millions of people and account for high rate of mortality, especially among children in sub-Sahara Africa (Breman, 2001; Greenwood et al., 2008; Hay et al., 2004; Rowe et al., 2006; Snow et al., 2005). Five species of the genus Plasmodium, the protozoan parasites, responsible for malaria infection are known to infect humans. They are P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi. It has been proposed that P. ovale consist of two species (Cox-Singh, 2010) and that zoonosis is the medium through which P. knowlesi infect humans (White, 2008). Of these, P. falciparum and P. vivax are numerically most important, with the former responsible for the most virulent, severe and dangerous form of human malaria (Greenwood et al., 2008).
The World Health Organization (WHO) 2011 Malaria reports (‘WHO | World Malaria Report 2011, 2012) estimated a total of 216 million episodes of malaria in 2010 with at least 655 000 deaths, mostly in Africa and among children under the age of 5 years. Malaria was reported to be prevalent in 99 countries with an estimated 3.3 billion people at risk. Though, supports by international donors has led to rapid decrease in malaria mortality, especially among adults in Africa, Murray et al., (2012) contended that the malaria mortality burden may actually be larger than previously estimated and that for the necessary elimination and eradication to be achieved at larger scale, there is an urgent need for more supports. Factors, such as lack of’sanitation, malnutrition, lack or reduced access to medications, poverty and the location of many of the poor countries affected by malaria in the tropical zones, all combined together to create an enabling environment for the disease to thrive. Though preventive approaches such as good sanitation and distribution of insecticide treated nets (ITNs) (Curtis et al., 2006), have been employed as strategy towards the eradication of this disease, chemotherapy remains the most widely used approach. The ability of P. falciparum to develop resistance to effective and affordable drugs (Cheeseman et al., 2012; Jambou et al., 2005; M’ller

Master Genes in Cotton Fiber Development

Cotton fibers are seed trichomes, which are single celled and arose from the epidermal layers of ovules. Fibre formation in cotton has divided into four distinct stages viz; fibre initiation, elongation, secondary cell wall accumulation and maturation. In fiber initiation stage up to 15-25% of epidermal cells of cotton ovules are differentiated into lint fibers which generally occurs between 0 to 1 DPA, then these fibre initials are begin to elongate until 5-20 DPA by diffusion growth mechanism followed by it secondary cell wall accumulation will take place with cellulose. Whereas, primary cell wall accumulation will done with variety of carbohydrate polymers in the elongation phase. This secondary cell wall biosynthesis will last up to 40-45 DPA, then the bolls will turn to open and maturation of lint fibre will take place by exposing to air (Seagull et al. 2000; Lee et al. 2007).
Despite knowing clear cut physiology of cotton fiber development there was not much improvement in fiber development with respect to yield and quality. Therefore, one should clearly understand the molecular mechanism underlying the process of fiber development and investigate master regulatory genes involved in fiber development will certainly helps to improve the yield and quality of fiber through breeding or genetic engineering technology. In view of this several researchers has worked extensively to find out the specific genes involved in the fiber initiation, elongation process through advanced molecular techniques. Based on the cDNA microarray technology, wu et al. (2006) identified 11 genes which are differentially expressed between fiber and fiberless mutant ovules in the early phases of fiber initiation out of 10,000 cDNA microarrays. Among these 11 differentially expressed genes, regulatory genes like GhMyb25, GhHD1 and GhCycD3 and structural genes like expansions, sucrose synthase, transporter genes, and fatty acid elongase genes were identified. Yang et al. (2006) also reported regulatory genes like WRKY and MYB transcription factors along with genes of auxin, brasinosteroid, GA3, ABA, ethylene signaling pathways during fiber cell initiation in wild type ovules compared to N1N1 mutants of the same genotype. Lee et al. (2006) also analyzed gene expression analysis using spotted oligo gene microarray technology between the TM 1 and its naked seed mutant lines (N1N1) and identified ~23 differentially expressed genes which were again regulatory and structural genes involved in early stage of fiber development.
In all these experiments transcription factors like HD and MYBs are well noticed and functions of these genes were already well determined in leaf trichome development of Arabidopsis thaliana and therefore these genes might be has the same role in seed trichome development of cotton. Furthermore, role of different phytohormones were well determined in in vitro development of lint fibers from ovules are agreeable with the results of cDNA microarray analysis data of Yang et al. (2006). Moreover, functions of many of these reported genes were not known but some of the important regulatory and structural genes were functionally characterized either by over expressing or silencing in model crops as well as in cotton crop. For example over expression of potato sucrose synthase (Sus) under S7 viral promoter resulted in an average 18% increase of seed number, 22% increases of fiber weight and 20-33% increase of fiber length per boll has reported compared to null plants by Xu et al. (2012). In the similar way Haigler et al. (2007); Jiang et al. (2012) also proved in the improvement of fiber quality and yield in terms of micronaire, maturity ration and fiber length compared to wild types by over expression of spinach sucrose phosphate synthase (Sps) gene and GhSusA1 gene respectively. Further Ruan et al. (2003) was reported repression of fiber initiation, elongation and seed development by suppression of sucrose synthase gene, which clearly indicates the key role of sucrose synthase related genes in the fiber development especially in the initiation and cell wall depositions. Apart from the structural genes regulatory genes like MYBs were also functionally characterized. In cotton more than 200 MYBs are reported, among them GhMYB25 a homologue of Am MIXTA was functionally characterized by developing over expressed and silenced lines of the GhMYB25 (Machado et al. 2009). They reported the crucial role of GhMYB25 in trichome development in various organs including ovules of cotton especially in the time of cell expansion and elongation stages.
An increased 15-35% number of fiber initials were observed relative to wild types in over expressed lines, where as 10-20% lesser fiber initials were reported in silenced lines which ultimately results in short mature fiber. Similarly R2R3 MYB gene GhMYB109 function was evaluated in cotton by suppressing native gene through RNAi technology, the silenced lines showed reduced bolls with short fibers having ~2.3 cm in length compared to ~3.4 cm length of wild types. Further they also examined the regulatory effect of this transcription factor on other key genes involved in fiber development through RT PCR and found that substantial decrease in expressions of phytohormonal genes like GhACO1, GhACO2 and cytoskeletal genes like GhACT1, GhTUB1. Similarly improved fibre quality was reported through RNAi approach also by Ibrokhim et al. (2014). Furthermore, over expression of a steroidal gene GhDET2 lead to increase in fiber number by 22.6% and fiber length by 10.7% in T2 generation over the controls. Apart from genes involved in fiber initiation, the genes which are involved in fiber elongation were also functionally characterized in cotton such as GhTUB1 (Li et al. 2002), GhACT1 (Li et al. 2005) and xyloglucan endotransglycosylase/hydrolase (Lee et al. 2010). Recently Zhang et al. (2011) reported an increase of >15% of lint yield after conducting three years of field experiments in transgenic cotton expressing iaaM gene a IAA biosynthetic gene. Apart from the plant origin genes, transgenic cotton was also reported with animal origin genes for fiber development with acsA and acsB genes of A.xylinum (Li et al. 2004) and silk warm fibroin gene (fbn) with increased fiber length and strength by ~28% and ~18%, respectively (Li et al. 2009).
To summarize, there is a much scope to find out master genes involved in cotton fiber development and functional characterization of already known differentially expressed genes especially the roles transcription factors how they are regulating other network of genes and whether this regulation is directly or indirectly influence the cotton fiber development. Further, the reported cotton transgenics has to undergone the critical quality and yield evaluations under field conditions, because most of the times the transgenics plants developed for fiber yield might be associated with trichome development in other parts or throughout plant which may not be accepted by farmers some times and also to translate the benefits of transgenics to the farmers. In addition to these, reports are also available for cotton seed oil improvement by reducing gossypol a hepato toxic terpinoid compound (Sunilkumar et al. 2006). Apart from insect,