Modelling Cross Talk in the Spatiotemporal System Dynamics of Calcium, IP3 and Nitric Oxide in Neuron Cells.

The bioenergetic system of calcium ([Ca2+]), inositol 1, 4, 5-trisphophate (IP3) and nitric oxide (NO) regulate the diverse mechanisms in neurons. The dysregulation in any or all of the calcium, IP3 and nitric oxide dynamics may cause neurotoxicity and cell death. Few studies are noted in the literature on the interactions of two systems like [Ca2+] with IP3 and [Ca2+] with nitric oxide in neuron cells, which gives limited insights into regulatory and dysregulatory processes in neuron cells. But, no study is available on the cross talk in dynamics of three systems [Ca2+], IP3 and NO in neurons. Thus, the cross talk in the system dynamics of [Ca2+], IP3 and NO regulation processes in neurons have been studied using mathematical model. The two-way feedback process between [Ca2+] and IP3 and two-way feedback process between [Ca2+] and NO through cyclic guanosine monophosphate (cGMP) with plasmalemmal [Ca2+]-ATPase (PMCA) have been incorporated in the proposed model. This coupling handles the indirect two-way feedback process between IP3 and nitric oxide in neuronal cells automatically. The numerical outcomes were acquired by employing the finite element method (FEM) with the Crank-Nicholson scheme (CNS). The present model incorporating the sodium-calcium exchanger (NCX) and voltage-gated calcium channel (VGCC) provides novel insights into the various regulatory and dysregulatory processes due to buffer, IP3-receptor, ryanodine receptor, cGMP kinetics through PMCA channel, etc. and their impacts on the interactive spatiotemporal system dynamics of [Ca2+], IP3 and NO in neurons. It is concluded that the behavior of different crucial mechanisms is quite different for interactions of two systems of [Ca2+] and NO and the interactions of three systems of [Ca2+], IP3 and nitric oxide in neuronal cell due to mutual regulatory adjustments. The association of several neurological disorders with the alterations in calcium, IP3 and NO has been explored in neurons.

Study of disorders in regulatory spatiotemporal neurodynamics of calcium and nitric oxide.

Experimental studies have reported the dependence of nitric oxide (NO) on the regulation of neuronal calcium ([Ca2+]) dynamics in neurons. But, there is no model available to estimate the disorders caused by various parameters in their regulatory dynamics leading to various neuronal disorders. A mathematical model to analyze the impacts due to alterations in various parameters like buffer, ryanodine receptor, serca pump, source influx, etc. leading to regulation and dysregulation of the spatiotemporal calcium and NO dynamics in neuron cells is constructed using a system of reaction-diffusion equations. The numerical simulation is performed with the finite element approach. The disturbances in the different constitutive processes of [Ca2+] and nitric oxide including source influx, buffer mechanism, ryanodine receptor, serca pump, IP3 receptor, etc. can be responsible for the dysregulation in the [Ca2+] and NO dynamics in neurons. Also, the results reveal novel information about the magnitude and intensity of disorders in response to a range of alterations in various parameters of this neuronal dynamics, which can cause dysregulation leading to neuronal diseases like Parkinson's, cerebral ischemia, trauma, etc.

Mechanistic insights of neuronal calcium and IP3 signaling system regulating ATP release during ischemia in progression of Alzheimer's disease.

The mechanisms of calcium ([Ca2+]) signaling in various human cells have been widely analyzed by scientists due to its crucial role in human organs like the heartbeat, muscle contractions, bone activity, brain functionality, etc. No study is reported for interdependent [Ca2+] and IP3 mechanics regulating the release of ATP in neuron cells during Ischemia in Alzheimer's disease advancement. In the present investigation, a finite element method (FEM) is framed to explore the interdependence of spatiotemporal [Ca2+] and IP3 signaling mechanics and its role in ATP release during Ischemia as well as in the advancement of Alzheimer's disorder in neuron cells. The results provide us insights of the mutual spatiotemporal impacts of [Ca2+] and IP3 mechanics as well as their contributions to ATP release during Ischemia in neuron cells. The results obtained for the mechanics of interdependent systems differ significantly from the results of simple independent system mechanics and provide new information about the processes of the two systems. From this study, it is concluded that neuronal disorders cannot only be simply attributed to the disturbance caused directly in the processes of calcium signaling mechanics, but also to the disturbances caused in IP3 regulation mechanisms impacting the calcium regulation in the neuron cell and ATP release.

Effect of disturbances in neuronal calcium and IP3 dynamics on ß-amyloid production and degradation.

Overproduction and accumulation of ß-amyloid and its improper clearance can cause neurotoxicity leading to Alzheimer's disease. The production and degradation of ß-amyloid depend on the calcium ([Ca2+]) and IP3 dynamics in the nerve cells. Thus, there is a need to understand the impacts of disturbances in the processes of [Ca2+] and IP3 dynamics on ß-amyloid production and its degradation. Here, a model is proposed to investigate the role of [Ca2+] and IP3 dynamics on ß-amyloid production and degradation. The problem is formulated in terms of the initial boundary value problem involving the system of two reaction-diffusion equations respectively for [Ca2+] and IP3 in the nerve cell. The solution is obtained by employing the Finite element approach. The numerical results are used to analyze the impact of various mechanisms of calcium and IP3 dynamics on ß-amyloid production and degradation in a neuron cell. The results indicate that disturbances in any of the constitutive processes of interdependent calcium and IP3 dynamics like source influx, buffering, serca pump, and IP3 dynamics, etc. can cause dynamic changes in ß-amyloid production and degradation, which in turn can be the cause of neurotoxicity and neuronal disorders like Alzheimer's disease. Thus, the relationships obtained by the proposed model among various mechanisms can be useful in addressing the challenges of identifying specific constitutive processes causing neuronal disorders like Alzheimer's disease, etc., and developing the framework for their diagnosis and treatment.

Mining amino acid association patterns in class B GPCRs.

Class B GPCR family is a small group of receptors which are activated by peptides of intermediate length that range from 30 to 40 amino acid residues including hormones, neuropeptides and autocrine factors that mediate diverse physiological functions. They are involved in physiological processes like glucose homeostasis (glucagon and glucagon-like peptide-1), calcium homeostasis and bone turnover (parathyroid hormone and calcitonin), and control of the stress axis (corticotropin-releasing factor). Most of the GPCR structures and their functions are still unknown. Thus, the study of amino acid association patterns can be useful in prediction of their structure and functions. In view of above, in this paper, an attempt has been made to explore amino acid association patterns in class B GPCRs and their relationships with secondary structures and physiochemical properties. The fuzzy association rule mining is employed to take care of uncertainty due to variation in length of sequences. The association rules have been generated with the help of patterns discovered in the sequences.

Insilico model for prediction of lateral gene transfer in Rhodopseudomonas paulistris.

Study of evolutionary phenomenon is of great interest to biologists in discovering the secrets of life. The presence of reticulation events due to lateral gene transfer (LGT) among species poses new challenges for such evolutionary studies. In this paper an attempt has been made to develop an insilico model to predict LGT in the Rhodopseudomonas paulistris. Neighbour Joining method is employed to generate phylogenetic tree of 26 sequences of Alphaproteobacteria and one sequence of Cyanobacteria used as an out group. Then Least Squares approach is employed to predict the reticulation branches. Three reticulation branches were detected among these 27 sequences. The lateral gene transfer was predicted between Rhodopseudomonas paulistris 99 D and Rhodobacter sphaeroides, Rhodopseudomonas paulistris HMD 88 and Bradyrhizobium japonicum USDA and Bradyrhizobium japonicum USDA and Rhodobacter blasticus. The results obtained are in agreement with the results obtained by earlier research workers.

ProCoS: Protein composition server.

ProCoS is a free online tool for computing different combinations of peptide compositions. It is developed as an applet and a server with a capability to handle multiple FASTA sequences. The generalized algorithm for computing poly-amino acid composition forms the core of ProCoS. It produces output in different formats for easy visualization of results. It also allows composition analysis of sequences in full or in specific parts. Thus, ProCoS is user-friendly, flexible and unique.

In silico analysis of evolutionary patterns in restriction endonucleases.

Restriction endonucleases represent one of the best studied examples of DNA binding proteins. Type II restriction endonucleases recognize short sequences of foreign DNA and cleave the target on both strands with remarkable sequence specificity. Type II restriction endonucleases are part of restriction modification systems. Restriction modification systems occur ubiquitously among bacteria and archaea. Restriction endonucleases are indispensable tools in molecular biology and biotechnology. They are important model system for specific protein-nucleic acid interactions and also serve as good example for investigating structural, functional and evolutionary relationships among various biomolecules. The interaction between restriction endonucleases and their recognition sequences plays a crucial role in biochemical activities like catalytic site/metal binding, DNA repair and recombination etc. We study various patterns in restriction endonucleases type II and analyzed their structural, functional and evolutionary role. Our studies support X-ray crystallographic studies, arguing for divergence and molecular evolution. Conservation patterns of the nuclease superfamily have also been analyzed by estimating site-specific evolutionary rates for the analyzed structures related to respective chains in this study.

Ambush hypothesis revisited: Evidences for phylogenetic trends.

Recoding events occur in competition with standard readout of the transcript, and are site-specific. Recoding is the reprogramming of mRNA translation by localized alterations in the standard translational rules. Frame-shifting is one class of recoding and defined as protein translations that start not at the first, but either at the second (+1 frame-shift) or the third (-1 frame-shift) nucleotide of the codon. Coding sequences lack stop codons, but frame-shifted sequences contain many stop codons, termed off-frame stops or hidden stops. These hidden stops terminate frame-shifted translation, potentially decreasing energy, and resource waste on non-functional proteins. Our results support this putative ancient adaptive event for the selection of codons that can be part of hidden stop codons. All taxonomic groups represent positive correlation between codon usage frequencies and contribution of codons to hidden stops in off-frame context. Our analysis on nuclear and mitochondrial genomic data revealed phylogenomic selection of ambush mechanism. Strongest impact of this event was found in viruses and bacteria. It has been suggested that this mechanism has occurred and been utilized in the early stages of evolution.