The Dynamics of Stress p53-Mdm2 Network Regulated by p300 and HDAC1

We construct a stress p53-Mdm2-p300-HDAC1 regulatory network that is activated and stabilised by two regulatory proteins, p300 and HDAC1. Different activation levels of observed due to these regulators during stress condition have been investigated using a deterministic as well as a stochastic approach to understand how the cell responds during stress conditions. We found that these regulators help in adjusting p53 to different conditions as identified by various oscillatory states, namely fixed point oscillations, damped oscillations and sustain oscillations. On assessing the impact of p300 on p53-Mdm2 network we identified three states: first stabilised or normal condition where the impact of p300 is negligible, second an interim region where p53 is activated due to interaction between p53 and p300, and finally the third regime where excess of p300 leads to cell stress condition. Similarly evaluation of HDAC1 on our model led to identification of the above three distinct states. Also we observe that noise in stochastic cellular system helps to reach each oscillatory state quicker than those in deterministic case. The constructed model validated different experimental findings qualitatively.     

Analysis of a Borrelia burgdorferi phosphodiesterase demonstrates a role for cyclic‐di‐guanosine monophosphate in motility and virulence

The genome of Borrelia burgdorferi encodes a set of genes putatively involved in cyclic‐dimeric guanosine monophosphate (cyclic‐di‐GMP) metabolism. Although BB0419 was shown to be a diguanylate cyclase, the extent to which bb0419 or any of the putative cyclic‐di‐GMP metabolizing genes impact B. burgdorferi motility and pathogenesis has not yet been reported. Here we identify and characterize a phosphodiesterase (BB0363). BB0363 specifically hydrolyzed cyclic‐di‐GMP with a K_m of 0.054 µM, confirming it is a functional cyclic‐di‐GMP phosphodiesterase. A targeted mutation in bb0363 was constructed using a newly developed promoterless antibiotic cassette that does not affect downstream gene expression. The mutant cells exhibited an altered swimming pattern, indicating a function for cyclic‐di‐GMP in regulating B. burgdorferi motility. Furthermore, the bb0363 mutant cells were not infectious in mice, demonstrating an important role for cyclic‐di‐GMP in B. burgdorferi infection. The mutant cells were able to survive within Ixodes scapularis ticks after a blood meal from naïve mice; however, ticks infected with the mutant cells were not able to infect naïve mice. Both motility and infection phenotypes were restored upon genetic complementation. These results reveal an important connection between cyclic‐di‐GMP, B. burgdorferi motility and Lyme disease pathogenesis. A mechanism by which cyclic‐di‐GMP influences motility and infection is proposed.     

Structure,function and applications of carbonic anhydrase isozymes

The carbonic anhydrases enzymes (CAs, EC 4.2.1.1) are zinc containing metalloproteins, which efficiently catalyse the reversible conversion of carbon dioxide to bicarbonate and release proton. These enzymes are essentially important for biological system and play several important physiological and patho-physiological functions. There are 16 different alpha-carbonic anhydrase isoforms studied, differing widely in their cellular localization and biophysical properties. The catalytic domains of all CAs possess a conserved tertiary structure fold, with predominately β-strands. We performed an extensive analysis of all 16 mammalian CAs for its structure and function in order to establish a structure–function relationship. CAs have been a potential therapeutic target for many diseases. Sulfonamides are considered as a strong and specific inhibitor of CA, and are being used as diuretics, anti-glaucoma, anti-epileptic, anti-ulcer agents. Currently CA inhibitors are widely used as a drug for the treatment of neurological disorders, anti-glaucoma drugs, anti-cancer, or anti-obesity agents. Here we tried to emphasize how CAs can be used for drug discovery, design and screening. Furthermore, we discussed the role of CA in carbon capture, carbon sensor and metabolon. We hope this review provide many useful information on structure, function, mechanism, and applications of CAs in various discipline.     

Accurate Phylogenetic Tree Reconstruction from Quartets: A Heuristic Approach

Supertree methods construct trees on a set of taxa (species) combining many smaller trees on the overlapping subsets of the entire set of taxa. A ‘quartet’ is an unrooted tree over taxa, hence the quartet-based supertree methods combine many -taxon unrooted trees into a single and coherent tree over the complete set of taxa. Quartet-based phylogeny reconstruction methods have been receiving considerable attentions in the recent years. An accurate and efficient quartet-based method might be competitive with the current best phylogenetic tree reconstruction methods (such as maximum likelihood or Bayesian MCMC analyses), without being as computationally intensive. In this paper, we present a novel and highly accurate quartet-based phylogenetic tree reconstruction method. We performed an extensive experimental study to evaluate the accuracy and scalability of our approach on both simulated and biological datasets.     

An updated and comprehensive review on the ethnomedicinal uses,phytochemistry, pharmacological activity and toxicological profile of Tinospora crispa (L.) Hook. f. & Thomson

Phytochemistry Reviews - Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae) is a plant indigenous to Africa and South-East Asia. It is widely used in ethnomedicine to alleviate...     

Estimation of Genetic Divergence and Character Association Studies in Local and Exotic Diversity Panels of Soybean (<i>Glycine max</i> L.) Genotypes

The availability of favorable genetic diversity is a thriving vitality for the success of a breeding program. It provides a firm basis of selecting superior breeding lines for the development of high yielding crop genotypes. In this context, present investigation aimed to generate information on genetic divergence and character association in a diversity panel of 123 local and exotic soybean genotypes. Analysis of variance revealed significant response of the evaluated genotypes based on studied attributes. It depicted the probability of selecting desirable soybean genotypes by focusing on character association studies and genetic diversity analysis. Correlation analysis revealed that seed yield per plant showed high positive correlation with 100-seed weight followed by pods per plant and plant height. Furthermore, path coefficient analysis exposed that pods per plant had maximum direct contribution in seed yield per plant followed by 100-seed weight, days to flowering and SPAD measurement. Genotype named “G-10” showed maximum yield per plant followed by 24607, G-52, 24593, Arisoy, 24566, 17426, A-3127, 24570 and 24567. Genetic diversity analysis grouped the evaluated germplasm into 17 clusters. All clusters showed zero intra-cluster variability; while inter-cluster divergence ranged from 9.00 to 91.11. Cluster V showed maximum inter-cluster distance with cluster XII followed by that of between V and VIII. Moreover, cluster IV with superior genotypes (G-10, 24607, 24593 and 24566), VI (17426 and 24567), XIII (24570) and X (Arisoy and G-52) showed above mean values for most of the studied characters. Overall, the results of hybridization between the superior genotypes of these cluster pairs might be useful for soybean breeding with improving agronomic traits and adaptability.     

Genetic variability and advance under four selection procedures in wheat pedigree breeding programme

Summary Four methods of generation advance (SPS, SSD, BP and MMS) were compared in F₃ and F₄ generations. In the F₃ generation, the SPS and SSD methods of generation advance proved superior to the BP and MMS methods for grain yield per plant and for at least one of the yield component traits. The F₃ SSD population did not differ significantly from the F₃ SPS for any of the traits. However, the F₃ SSD population retained more range and cv for different traits than with other methods of generation advance. F₄ progenies derived from F₃ SSD population were significantly superior for grain yield than lines derived from the other three F₃ populations. The MMS method of generation advance proved useful for increasing the 1,000-grain weight for which initial selection was made.Part of Ph.D. Thesis submitted by senior author to Haryana Agricultural University, Hisar     

A new subgenus ofLathromeromyia [Hym.: Trichogrammatidae] an egg parasite ofTingidae [Het.] from India

SubgenusLathromeromina nov. of the genusLathromeromyia with a type speciesLathromeromyia (Lathromeromina) tingiphaga sp. nov. has been described and illustrated. Four species of Tingid hosts and their host plants are recorded.     

Molecular properties and enhancement of thermostability by random mutagenesis of glutamate dehydrogenase from Bacillus subtilis

The rocG gene encoding glutamate dehydrogenase from Bacillus subtilis (Bs-GluDH) was cloned, and expressed at considerable magnitude in Escherichia coli. The recombinant Bs-GluDH was purified to homogeneity and has been determined to have a hexameric structure (M(r) 270 kDa) with strict specificity for 2-oxoglutarate and L-glutamate, requiring NADH and NAD+ as cofactors respectively. The enzyme showed low thermostability with T(m) = 41 degrees C due to dissociation of the hexamer. To improve the thermostability of this enzyme, we performed error-prone PCR, introducing random mutagenesis on cloned GluDH. Two single mutant enzymes, Q144R and E27F, were isolated from the final mutant library. Their T(m) values were 61 degrees C and 49 degrees C respectively. Furthermore, Q144R had a remarkably high k(cat) value (435 s(-1)) for amination reaction at 37 degrees C, 1.3 times higher than that of the wild-type. Thus, Q144R can be used as a template gene to modify the substrate specificity of Bs-GluDH for industrial use.     

Crystallization and X-ray diffraction of spray-dried and freeze-dried amorphous lactose

Crystallization of spray-dried and freeze-dried amorphous lactose over different relative vapor pressures (RVP) and storage times was studied. Crystallization was observed from increasing peak intensities in X-ray diffraction patterns. Lactose was crystallized in the samples stored at RVP of 44.1% and above in both types of dehydrated powders. The rate of crystallization increased with increasing RVP and storage time. Similar crystallization behavior of both spray-dried and freeze-dried lactose was observed. Lactose crystallized as alpha-lactose monohydrate, anhydrous beta-lactose, and the anhydrous form of alpha- and beta-lactose in a molar ratio of 5:3 and 4:1 in both spray-dried and freeze-dried forms. Peak intensities of X-ray diffraction patterns for anhydrous beta-lactose were decreased, and for alpha-lactose monohydrate increased with increasing storage RVP and time. The crystallization data were successfully modeled using Avrami equation at RVP of 54.5% and above. The crystallization data obtained is helpful in understanding and predicting storage stability of lactose-containing food and pharmaceutical products.