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.

"If a woman has even one daughter, I refuse to perform the abortion": Sex determination and safe abortion in India.

In India, safe abortion services are sought mainly in the private sector for reasons of privacy, confidentiality, and the absence of delays and coercion to use contraception. In recent years, the declining sex ratio has received much attention, and implementation of the Pre-Conception and Pre-Natal Diagnostic Techniques (PCPNDT) Act (2003) has become stringent. However, rather than targeting sex determination, many inspection visits target abortion services. This has led to many private medical practitioners facing negative media publicity, defamation and criminal charges. As a result, they have started turning women away not only in the second trimester but also in the first. Samyak, a Pune-based, non-governmental organization, came across a number of cases of refusal of abortion services during its work and decided to explore the experiences of private medical practitioners with the regulatory mechanisms and what happened to the women. The study showed that as a fallout from the manner of implementation of the PCPNDT Act, safe abortion services were either difficult for women to access or outright denied to them. There is an urgent need to recognize this impact of the current regulatory environment, which is forcing women towards illegal and unsafe abortions.