16 research outputs found
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