Structural modeling identifies Plasmodium vivax 4-diphosphocytidyl-2C-methyl-d-erythritol kinase (IspE) as a plausible new antimalarial drug target

Malaria parasites utilize Methylerythritol phosphate (MEP) pathway for synthesis of isoprenoid precursors which are essential for maturation and survival of parasites during erythrocytic and gametocytic stages. The absence of MEP pathway in the human host establishes MEP pathway enzymes as a repertoire of essential drug targets. The fourth enzyme, 4-diphosphocytidyl-2C-methyl-d-erythritol kinase (IspE) has been proved essential in pathogenic bacteria, however; it has not yet been studied in any Plasmodium species. This study was undertaken to investigate genetic polymorphism and concomitant structural implications of the Plasmodium vivax IspE (PvIspE) by employing sequencing, modeling and bioinformatics approach. We report that PvIspE gene displayed six non-synonymous mutations which were restricted to non-conserved regions within the gene from seven topographically distinct malaria-endemic regions of India. Phylogenetic studies reflected that PvIspE occupies unique status within Plasmodia genus and reflects that Plasmodium vivax IspE gene has a distant and non-conserved relation with human ortholog Mevalonate Kinase (MAVK). Structural modeling analysis revealed that all PvIspE Indian isolates have critically conserved canonical galacto-homoserine-mevalonate-phosphomevalonate kinase (GHMP) domain within the active site lying in a deep cleft sandwiched between ATP and CDPME-binding domains. The active core region was highly conserved among all clinical isolates, may be due to >60% β-pleated rigid architecture. The mapped structural analysis revealed the critically conserved active site of PvIspE, both sequence, and spacially among all Indian isolates; showing no significant changes in the active site. Our study strengthens the candidature of Plasmodium vivax IspE enzyme as a future target for novel antimalarials.     

Myocardial phospholipid metabolism in alloxan diabetic rats

Alloxan diabetes in rats was found to decrease the level of phospholipids in the heart. Measurement of specific phosphatides showed that the decrease was restricted only to phosphatidylethanolamine and lysophosphatidylcholine. Study of $\text{in}$$\text{vivo}$ incorporation of ³²Pi indicated an impairment of phosphatidylethanolamine synthesis and conversion of phosphatidylcholine into lysophosphatidyl choline in the heart of diabetic rats. Treatment of diabetic rats with insulin restored the levels of phosphatidylethanolamine and lysophosphatidylcholine and incorporation of ³²Pi into these phosphatides to almost normal.     

Haloferax sp. D1227, a halophilic Archaeon capable of growth on aromatic compounds

A pink-pigmented halophilic Archaeon, Strain D1227, was isolated from soil contaminated with oil brine and shown to be a member of the genus Haloferax, based on: (1) its hybridization with a 16S rRNA probe universal for the Archaea; (2) its resistance to a broad spectrum of antibiotics that affect Bacteria; (3) its requirement for at least 0.86 M NaCl and 25 mM Mg²⁺ for growth; (4) its possession of C₅₀-carotenoids characteristic of the halophilic Arachaea; (5) the thin layer chromatographic pattern of its polar lipids, which was identical to that of other species of Haloferax; and (6) its pleomorphic cell morphology. However, in contrast to the known species of Archaea, Haloferax strain D1227 was able to use aromatic substrates (e.g., benzoate, cinnamate, and phenylpropanoate) as sole carbon and energy sources for growth. Physiologically similar organisms, such as Haloferax volcanii, Haloferax mediterrani, Haloarcula vallismortis, and Haloarcula hispanica, could not grow on these aromatic substrates. When grown on ¹⁴C-benzoate, strain D1227 mineralized 70% of the substrate and assimilated 19% of the ¹⁴C-label into cell biomass. In addition to growth on aromatic substrates, D1227 was also capable of growth on a variety of carbohydrates and organic acids. Optimum growth of strain D1227 occurred at 45°C in media containing 1.7–2.6 M NaCl and 100 mM Mg²⁺. Under optimum growth conditions, the cell shape varied from that of an oblate spheroid on mineral salts medium alone, to discshaped, irregular or triangular cells on the same medium amended with yeast extract and tryptone. To our knowledge, this is the first unequivocal demonstration of the ability of an Archacon to grow by mineralization of aromatic substrates, and it adds a new dimension to our appreciation of the physiological diversity of this group of prokaryotes.Abbreviations Ha. Haloarcula - Hf. Haloferax     

Human immunodeficiency virus type 1 Vif inhibits packaging and antiviral activity of a degradation-resistant APOBEC3G variant

Human immunodeficiency virus type 1 (HIV-1) Vif counteracts the antiviral activity of the human cytidine deaminase APOBEC3G (APO3G) by inhibiting its incorporation into virions. This has been attributed to the Vif-induced degradation of APO3G by cytoplasmic proteasomes. We recently demonstrated that although APO3G has a natural tendency to form RNA-dependent homo-multimers, multimerization was not essential for encapsidation into HIV-1 virions or antiviral activity. We now demonstrate that a multimerization-defective APO3G variant (APO3G C97A) is able to assemble into RNase-sensitive high-molecular-mass (HMM) complexes, suggesting that homo-multimerization of APO3G and assembly into HMM complexes are unrelated RNA-dependent processes. Interestingly, APO3G C97A was highly resistant to Vif-induced degradation even though the two proteins were found to interact in coimmunoprecipitation experiments and exhibited partial colocalization in transfected HeLa cells. Surprisingly, encapsidation and antiviral activity of APO3G C97A were both inhibited by Vif despite resistance to degradation. These results demonstrate that targeting of APO3G to proteasome degradation and interference with viral encapsidation are distinct functional properties of Vif.     

Interactive Effect of Silicon (Si) and Salicylic Acid (SA) in Maize Seedlings and Their Mechanisms of Cadmium (Cd) Toxicity Alleviation

Journal of Plant Growth Regulation - The present study has been conducted to evaluate the impact of silicon (Si) and salicylic acid (SA) in the regulation of Cd-induced toxicity in maize seedlings....     

Pseudomonas putida modulates the expression of miRNAs and their target genes in response to drought and salt stresses in chickpea (Cicer arietinum L.)

MicroRNAs are small non-coding regulatory RNA molecules that play an important role in the modulation of gene expression during various environmental stresses. Pseudomonas putida RA, a plant growth promoting rhizobacteria (PGPR) colonizes the root surface of plants improving their growth and development during abiotic stresses modulating the expression of stress-responsive genes; however, the impact of RA on stress responsive-miRNA remains elusive. The present study was an attempt to delineate the role of PGPR in modulating stress responsive-miRNAs in a tolerant desi chickpea genotype exposed to drought and salt stresses. The existence of variable expression patterns of individual miRNAs and their target genes under these stresses at different time points indicate a distinct miRNA-mediated perception and response mechanisms operating under these stresses in the presence or absence of RA in chickpea.     

Detection of nucleotide variants in FCGRT (Fc fragment of IgG,receptor, transporter,alpha) gene and their influence on colostral IgG concentration in Indian water buffalo (Bubalus bubalis)

Molecular Biology Reports - The neonatal Fc receptors (FcRn) mediate the transfer of immunoglobulin G (IgG) molecules from a dam’s circulation to the colostrum produced by it immediately...     

Paenibacillus lentimorbus Enhanced Abiotic Stress Tolerance Through Lateral Root Formation and Phytohormone Regulation

Under the stressed conditions plant growth-promoting rhizobacteria (PGPR) are able to stimulate plant growth through several mechanisms, including antioxidants alleviation, regulation of stress responsive genes and phytohormones etc. Present study is conducted to investigate the impact of Paenibacillus lentimorbus B-30488 inoculation on salinity and drought stress mitigation in Arabidopsis thaliana through modulation in defense enzymes, phyto-hormones and root system architecture associated gene expression profiling. In vitro experiments clearly demonstrated the role of B-30488 in stimulating the root length, branches, lateral root formation and biomass under salinity and drought stress. The inoculation of B-30488 modulated the phytohormones levels to protect the plants from salinity and drought stress. Similarly, defence enzymes were also activated under the stressed conditions, but B-30488 inoculation reduced the antioxidants content during salinity and drought stress as compared to their respective controls. Microscopy results showed decrease in lateral roots hair formation under both stresses and B-30488 inoculation not only mitigate but also enhanced the lateral root formation. Gene expression analysis through real time polymerase chain reaction (RT-PCR) showed modulated expression of several genes related to root development, stress and lateral root formation in B-30488 inoculated seedlings. Results based on the present study, B-30488 is also involved in alteration root architecture, its growth regulation via modulation in phytohormones and genes expression and overall significant improvement in plant growth under stress conditions.

     

Surfactant pollution,an emerging threat to ecosystem: Approaches for effective bacterial degradation

The use of surfactants in households and industries is inevitable and so is their discharge into the environment, especially into the water bodies as effluents. Being surface-active agents, their utilization is mostly seen in soaps, detergents, personal care products, emulsifiers, wetting agents, etc. Anionic surfactants are the most used class. These surfactants are responsible for the foam and froth in the water bodies and cause potential adverse effects to both biotic and abiotic components of the ecosystem. Surfactants are capable of penetrating the cell membrane and thus cause toxicity to living organisms. Accumulation of these compounds has been known to cause significant gill damage and loss of sight in fish. Alteration of physiological and biochemical parameters of water decreases the amount of dissolved oxygen and thus affecting the entire ecosystem. Microbes utilizing surfactants as substrates for energy form the basis of the biodegradation of these compounds. The main organisms for surfactant biodegradation, both in sewage and natural waters, are bacteria. Several Pseudomonas and Bacillus spp. have shown efficient degradation of anionic surfactants namely: sodium dodecyl sulphate (SDS), linear alkylbenzene sulphonate (LAS), sodium dodecylbenzenesulphonate (SDBS). Also, several microbial consortia constituting Alcaligenes spp., Citrobacter spp., etc. have shown efficacy in the degradation of surfactants. The biodegradation efficiency studies of these microbes/microbial consortia would be of immense help in formulating better solutions for the bioremediation of surfactants and help to reduce their potential environmental hazards.