The continuum of saffron secularism

The Sikh Riots in 1984, the Mumbai Riots in 1993, the Godhra Riots in 2002... all these events mark important milestones in the history of India. The memory of these days fills the common and the 'uncommon' man's heart with memories so dark that they are better not prodded. And the question is, what is the common factor that can be taken as the cause of the pogroms and their aggravating factors? Partisan Political Leaders, Spineless Bureaucracy, Aficionado Police and a Helpless Judiciary? The limbs of the largest democracy in the world have displayed nothing more than mere tokenism in either combating causes of communal tension or in helping people overcome the aftermath of the tension, let alone taking efforts to remove the causes. People of various communities live in India. Now in the religious spheres the environment is charged with religious fanaticism and religious conflicts. Gradually this religious fanaticism has manifested itself in a dreadful way, disturbing the peace and tranquillity of the social order. The assigned task of the various state players is not to get swayed by their communal passions and derive as much benefit as possible from this disease but to put a stop to the endless requiems that still remain to be sung at the loss of the many more lives if the communal ardour is not dampened. However, as far as communal passions are concerned, one has nothing to offer as a solution...peer-reviewe

An Overview of Computational Approaches in Structure Based Drug Design

Drug design is a costly and difficult process. Drug must fulfill several criteria of being active, nontoxic and bioavailable. The conventional way of synthesizing drugs is a monotonous process. But computer aided drug design is a proficient way to overcome the tedious process of conventional method. Drugs can be designed computationally by structure or target based drug designing (SBDD). This review summarizes the methods of structure based drug design, usage of related softwares and a case study that explores to find a suitable drug (lead) molecule for the mutated state of H-Ras protein in order to prevent complex formation with Raf protein.Keywords: computer aided drug design; structure based drug design; Ras-proteinDOI: http://dx.doi.org/10.3126/njb.v2i1.5680Nepal Journal of Biotechnology Jan.2012, Vol.2(1): 53-6

<span style="font-size:11.0pt;font-family: "Times New Roman","serif";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">Role of tetracycline and cAMP analogues in pancreatic β stem cell differentiation/proliferation process <i>via</i> modulation of epac2 protein</span>

172-178<span style="font-size:11.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-GB">For effective treatment of diabetes, appropriate pancreatic β stem cell proliferation enhancers and differentiation deactivators have to be designed and developed. The aim of the present work was to understand the nature and affinity of epac2 protein against analogues of tetracycline as deactivators and cAMP as activator for the pancreatic β cells. The peculiarity of this epac2 protein lies in the activation of proliferating activity of pancreatic β cells via stimulating glucagon like peptide1 (GLP1). This in turns induces Ca2+ signalling and insulin secretion. In the present work, docking simulation and pharmacophore study was carried out on cAMP and tetracycline analogues to predict the potential activator as well as deactivator of the proliferation and differentiation of pancreatic β stem cells. It was observed that some analogues of cAMP better contribute to the proliferative activities in comparison with cAMP itself. Moreover, some tetracycline analogues are likely to be more effective for the deactivation of proliferation and differentiation process of pancreatic β stem cells. The present study is likely to lead to the discovery of significant potential therapy for diabetes.</span

Axonal branching patterns of nucleus accumbens neurons in the rat

ABSTRACT The patterns of axonal collateralization of nucleus accumbens (Acb) projection neurons were investigated in the rat by means of single-axon tracing techniques using the anterograde tracer biotinylated dextran amine. Seventy-three axons were fully traced, originating from either the core (AcbC) or shell (AcbSh) compartment, as assessed by differential calbindin D28kimmunoreactivity. Axons from AcbC and AcbSh showed a substantial segregation in their targets; target areas were either exclusively or preferentially innervated from AcbC or AcbSh. Axon collaterals in the subthalamic nucleus were found at higher than expected frequencies; moreover, these originated exclusively in the dorsal AcbC. Intercompartmental collaterals were observed from ventral AcbC axons into AcbSh, and likewise, interconnections at pallidal and mesencephalic levels were also observed, although mostly from AcbC axons toward AcbSh targets, possibly supporting crosstalk between the two subcircuits at several levels. Cell somata giving rise to short-range accumbal axons, projecting to the ventral pallidum (VP), were spatially intermingled with others, giving rise to long-range axons that innervated VP and more caudal targets. This anatomical organization parallels that of the dorsal striatum and provides the basis for possible dual direct and indirect actions from a single axon on either individual or small sets of neurons. J. Comp. Neurol. 518:4649– 4673, 2010

In vivo spontaneous activity and coital-evoked inhibition of mouse accessory olfactory bulb output neurons

Little is known about estrous effects on brain microcircuits. We examined the accessory olfactory bulb (AOB) in vivo, in anesthetized naturally cycling females, as model microcircuit receiving coital somatosensory information. Whole-cell recordings demonstrate that output neurons are relatively hyperpolarized in estrus and unexpectedly fire high frequency bursts of action potentials. To mimic coitus, a calibrated artificial vagino-cervical stimulation (aVCS) protocol was devised. aVCS evoked stimulus-locked local field responses in the interneuron layer independent of estrous stage. The response is sensitive to α1-adrenergic receptor blockade, as expected since aVCS increases norepinephrine release in AOB. Intriguingly, only in estrus does aVCS inhibit AOB spike output. Estrus-specific output reduction coincides with prolonged aVCS activation of inhibitory interneurons. Accordingly, in estrus the AOB microcircuit sets the stage for coital stimulation to inhibit the output neurons, possibly via high frequency bursting-dependent enhancement of reciprocal synapse efficacy between inter- and output neurons

Cognition- and circuit-based dysfunction in a mouse model of 22q11.2 microdeletion syndrome : effects of stress

Genetic microdeletion at the 22q11 locus is associated with very high risk for schizophrenia. The 22q11.2 microdeletion (Df(h22q11)/+) mouse model shows cognitive deficits observed in this disorder, some of which can be linked to dysfunction of the prefrontal cortex (PFC). We used behavioral (n = 10 per genotype), electrophysiological (n = 7 per genotype per group), and neuroanatomical (n = 5 per genotype) techniques to investigate schizophrenia-related pathology of Df(h22q11)/+ mice, which showed a significant decrease in the total number of parvalbumin positive interneurons in the medial PFC. The Df(h22q11)/+ mice when tested on PFC-dependent behavioral tasks, including gambling tasks, perform significantly worse than control animals while exhibiting normal behavior on hippocampus-dependent tasks. They also show a significant decrease in hippocampus-medial Prefrontal cortex (H-PFC) synaptic plasticity (long-term potentiation, LTP). Acute platform stress almost abolished H-PFC LTP in both wild-type and Df(h22q11)/+ mice. H-PFC LTP was restored to prestress levels by clozapine (3 mg/kg i.p.) in stressed Df(h22q11)/+ mice, but the restoration of stress-induced LTP, while significant, was similar between wild-type and Df(h22q11)/+ mice. A medial PFC dysfunction may underlie the negative and cognitive symptoms in human 22q11 deletion carriers, and these results are relevant to the current debate on the utility of clozapine in such subjects