Neuroprotective Effects of Bacopa monnieri in Experimental Model of Dementia

Alzheimer disease (AD) is characterized by dementia that begins as mild short term memory deficit and culminates in total loss of cognitive and executive functions. The present study was conducted to evaluate the neuroprotective potential of Bacopa monnieri (BM), an Indian traditional medicinal plant effective against cognitive impairment, in colchicine-induced dementia. Intracerebroventricular administration of colchicine (15?μg/5?μl) induced cognitive impairment in rats as assessed by elevated plus maze. This was accompanied by a significant increase in oxidative stress in term of enhanced levels of lipid peroxidation and protein carbonyls. Concomitantly, decrease in activity of antioxidant enzymes was observed in colchicine treated animals. BM (50?mg/kg body weight) supplementation reversed memory impairment observed in the colchicine treated rats. BM administration attenuated oxidative damage, as evident by decreased LPO and protein carbonyl levels and restoration in activities of the antioxidant enzymes. The activity of membrane bound enzymes (Na(+)K(+) ATPase and AChE) was altered in colchicine treated brain regions and BM supplementation was able to restore the activity of enzymes to comparable values observed in controls. The results suggest therapeutic potential of BM in the treatment of AD associated cognitive decline.     

Crystal structure of glutamyl-queuosine tRNAAsp synthetase complexed with L-glutamate: structural elements mediating tRNA-independent activation of glutamate and glutamylation of tRNAAsp anticodon

Glutamyl-queuosine tRNA^Asp synthetase (Glu-Q-RS) from Escherichia coli is a paralog of the catalytic core of glutamyl-tRNA synthetase (GluRS) that catalyzes glutamylation of queuosine in the wobble position of tRNA^Asp. Despite important structural similarities, Glu-Q-RS and GluRS diverge strongly by their functional properties. The only feature common to both enzymes consists in the activation of Glu to form Glu-AMP, the intermediate of transfer RNA (tRNA) aminoacylation. However, both enzymes differ by the mechanism of selection of the cognate amino acid and by the mechanism of its activation. Whereas GluRS selects l-Glu and activates it only in the presence of the cognate tRNA^Glu, Glu-Q-RS forms Glu-AMP in the absence of tRNA. Moreover, while GluRS transfers the activated Glu to the 3′ accepting end of the cognate tRNA^Glu, Glu-Q-RS transfers the activated Glu to Q34 located in the anticodon loop of the noncognate tRNA^Asp. In order to gain insight into the structural elements leading to distinct mechanisms of amino acid activation, we solved the three-dimensional structure of Glu-Q-RS complexed to Glu and compared it to the structure of the GluRS·Glu complex. Comparison of the catalytic site of Glu-Q-RS with that of GluRS, combined with binding experiments of amino acids, shows that a restricted number of residues determine distinct catalytic properties of amino acid recognition and activation by the two enzymes. Furthermore, to explore the structural basis of the distinct aminoacylation properties of the two enzymes and to understand why Glu-Q-RS glutamylates only tRNA^Asp among the tRNAs possessing queuosine in position 34, we performed a tRNA mutational analysis to search for the elements of tRNA^Asp that determine recognition by Glu-Q-RS. The analyses made on tRNA^Asp and tRNA^Asn show that the presence of a C in position 38 is crucial for glutamylation of Q34. The results are discussed in the context of the evolution and adaptation of the tRNA glutamylation system.     

Protective effects of vitamin E against atrazine-induced genotoxicity in rats

Atrazine (2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine) is one of the most commonly used herbicides to control grasses and weeds. The widespread contamination and persistence of atrazine residues in the environment has resulted in human exposure. Vitamin E is a primary antioxidant that plays an important role in protecting cells against toxicity by inactivating free radicals generated following pesticides exposure. The present study was undertaken to investigate the protective effect of vitamin E against atrazine-induced genotoxicity. Three different methods: gel electrophoresis, comet assay and micronucleus test were used to assess the atrazine-induced genotoxicity and to evaluate the protective effects of vitamin E. Atrazine was administered to male rats at a dose of 300 mg/kg body weight for a period of 7, 14 and 21 days. There was a significant increase (P<0.001) in tail length of comets from blood and liver cells treated with atrazine as compared to controls. Co-administration of vitamin E (100 mg/kg body weight) along with atrazine resulted in decrease in tail length of comets as compared to the group treated with atrazine alone. Micronucleus assay revealed a significant increase (P<0.001) in the frequency of micronucleated cells (MNCs) following atrazine administration. In the animals administrated vitamin E along with atrazine there was a significant decrease in percentage of micronuclei as compared to atrazine treated rats. The increase in frequency of micronuclei in liver cells and tail length of comets confirm genotoxicity induced by atrazine in blood and liver cells. In addition, the findings clearly demonstrate protective effect of vitamin E in attenuating atrazine-induced DNA damage.     

Quantitative proliferation dynamics and random chromosome segregation of hair follicle stem cells

Regulation of stem cell (SC) proliferation is central to tissue homoeostasis, injury repair, and cancer development. Accumulation of replication errors in SCs is limited by either infrequent division and/or by chromosome sorting to retain preferentially the oldest 'immortal' DNA strand. The frequency of SC divisions and the chromosome-sorting phenomenon are difficult to examine accurately with existing methods. To address this question, we developed a strategy to count divisions of hair follicle (HF) SCs over time, and provide the first quantitative proliferation history of a tissue SC during its normal homoeostasis. We uncovered an unexpectedly high cellular turnover in the SC compartment in one round of activation. Our study provides quantitative data in support of the long-standing infrequent SC division model, and shows that HF SCs do not retain the older DNA strands or sort their chromosome. This new ability to count divisions in vivo has relevance for obtaining basic knowledge of tissue kinetics.     

A computational study of the aerodynamic performance of a dragonfly wing section in gliding flight

A comprehensive computational fluid-dynamics-based study of a pleated wing section based on the wing of Aeshna cyanea has been performed at ultra-low Reynolds numbers corresponding to the gliding flight of these dragonflies. In addition to the pleated wing, simulations have also been carried out for its smoothed counterpart (called the 'profiled' airfoil) and a flat plate in order to better understand the aerodynamic performance of the pleated wing. The simulations employ a sharp interface Cartesian-grid-based immersed boundary method, and a detailed critical assessment of the computed results was performed giving a high measure of confidence in the fidelity of the current simulations. The simulations demonstrate that the pleated airfoil produces comparable and at times higher lift than the profiled airfoil, with a drag comparable to that of its profiled counterpart. The higher lift and moderate drag associated with the pleated airfoil lead to an aerodynamic performance that is at least equivalent to and sometimes better than the profiled airfoil. The primary cause for the reduction in the overall drag of the pleated airfoil is the negative shear drag produced by the recirculation zones which form within the pleats. The current numerical simulations therefore clearly demonstrate that the pleated wing is an ingenious design of nature, which at times surpasses the aerodynamic performance of a more conventional smooth airfoil as well as that of a flat plate. For this reason, the pleated airfoil is an excellent candidate for a fixed wing micro-aerial vehicle design.     

Phosphorus starvation response dynamics and management in plants for sustainable agriculture

Phosphorus (P) is an essential macronutrient required for the survival and reproduction of all living organisms. Its inorganic form (Pi) is taken up by the roots to support plant growth and development, and its availability directly determines agricultural productivity. The primary source of P replenishment in agriculture is chemical phosphate (Pi) fertilizers. While application of Pi-fertilizers to croplands ensures high yield agriculture, its intensive use leads to several environmental implications, including loss of soil fertility and pollution of water bodies with runoff fertilizer. Global non-renewable P-reserves are finite and would last for only a few hundred years. Therefore, a holistic approach is needed to combine Pi-use efficient germplasm with the targeted fertilization, agronomically superior fertilizer formulations for better P-management. The latest technologies to reclaim Pi from alternative sources need to be explored. In the present review, we first outline the challenges and environmental consequences of Pi-intensive fertilization, followed by plants' response and adaptive strategies to Pi starvation. Next, we discuss the role of microbes and Pi-nanofertilizer to plant Pi nutrition. Finally, a few cutting-edge technologies and innovative solutions available for reclaiming Pi from waste are argued.

     

Engineered Silybin Nanoparticles Educe Efficient Control in Experimental Diabetes

Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostrate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17±0.01 µg/lit to 0.57±0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status.     

Computational neuroscience and neuroinformatics: Recent progress and resources

The human brain and its temporal behavior correlated with development, structure, and function is a complex natural system even for its own kind. Coding and automation are necessary for modeling, analyzing and understanding the 86.1 ± 8.1 billion neurons, an almost equal number of non-neuronal glial cells, and the neuronal networks of the human brain comprising about 100 trillion connections. ‘Computational neuroscience’ which is heavily dependent on biology, physics, mathematics and computation addresses such problems while the archival, retrieval and merging of the huge amount of generated data in the form of clinical records, scientific literature, and specialized databases are carried out by ‘neuroinformatics’ approaches. Neuroinformatics is thus an interface between computer science and experimental neuroscience. This article provides an introduction to computational neuroscience and neuroinformatics fields along with their state-of-the-art tools, software, and resources. Furthermore, it describes a few innovative applications of these fields in predicting and detecting brain network organization, complex brain disorder diagnosis, large-scale 3D simulation of the brain, brain–computer, and brain-to-brain interfaces. It provides an integrated overview of the fields in a non-technical way, appropriate for broad general readership. Moreover, the article is an updated unified resource of the existing knowledge and sources for researchers stepping into these fields.     

An analysis of the interactions between folic acid and aromatic guest molecules

The formation of complexes between folate and therapeutic drug molecules is well known. In this work, we attempted to elucidate the role of the aromatic rings of folate and drug molecules in interactions between both of these molecules. A detailed molecular simulation study was carried out to explore the associative behavior of folic acid with phenylalanine and tyrosine, which show fluorescence emission following the excitation of these molecules at 257 nm and 274 nm, respectively. Therefore, studies of fluorescence emission from phenylalanine and tyrosine were performed in this work. The results of these studies indicated that folic acid associates with phenylalanine and tyrosine with binding constants ranging from 1.46 × 10⁴ to 2.66 × 10⁴ M^?1. X-ray diffraction studies suggested that folic acid self-assembly is maintained in the presence of associative interactions of the folic acid with guest molecules. These results demonstrate that the aromatic rings in the structures of the folic acid and the therapeutic drug play an important role in the encapsulation of guest molecules through folate self-assembly.     

Extracting proteins involved in disease progression using temporally connected networks

Background

Metabolic disorders such as obesity and diabetes are diseases which develop gradually over time in an individual and through the perturbations of genes. Systematic experiments tracking disease progression at gene level are usually conducted giving a temporal microarray data. There is a need for developing methods to analyze such complex data and extract important proteins which could be involved in temporal progression of the data and hence progression of the disease.

Results

In the present study, we have considered a temporal microarray data from an experiment conducted to study development of obesity and diabetes in mice. We have used this data along with an available Protein-Protein Interaction network to find a network of interactions between proteins which reproduces the next time point data from previous time point data. We show that the resulting network can be mined to identify critical nodes involved in the temporal progression of perturbations. We further show that published algorithms can be applied on such connected network to mine important proteins and show an overlap between outputs from published and our algorithms. The importance of set of proteins identified was supported by literature as well as was further validated by comparing them with the positive genes dataset from OMIM database which shows significant overlap.

Conclusions

The critical proteins identified from algorithms can be hypothesized to play important role in temporal progression of the data.