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21.
Suman Gupta Rakesh kumar Singh Kamna Nanda Mou Chatterjee Sindhuja Sundaram Dikshi Gupta 《Journal of receptor and signal transduction research》2013,33(2):100-106
In modern drug discovery, numerous assay formats are available to screen and quantitate receptor-ligand interactions. Radioactive assays are “gold standard” because they are fast, easy, and reproducible; however, they are hazardous, produce radioactive waste, require special lab conditions, and are expensive on a large scale. Thus, it provides a lot of importance to the “mix & measure” assays that have an optical readout. Fluorescence techniques are likely to be among the most important detection approaches used for high throughput screening due to their high sensitivity and amenability to automation. The aim of the present study was to determine the functional antagonistic affinities of standard muscarinic antagonists in CHO cells over expressing m1, m3, and m5 receptors and to compare them with the respective binding affinities. This study was further extended to elucidate that Ca+2 measurement assays can serve as a functional screening tool for GPCRs. For this purpose, standard muscarinic receptor antagonists, namely, tolterodine, oxybutynin, and atropine were used. We determined and compard the IC50 values of these three standard inhibitors in fura 2 AM loaded m1, m3, and m5 overexpressing CHO cells and in radioligand binding assay. Both the assays exhibited comparable rank order potencies of the standard inhibitors. This study suggests that Ca+2 mobilization assays can be an alternate to radioligand binding assays. 相似文献
22.
Cong Cao Mengia S. Rioult-Pedotti Paolo Migani Crystal J. Yu Rakesh Tiwari Keykavous Parang Mark R. Spaller Dennis J. Goebel John Marshall 《PLoS biology》2013,11(2)
Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) TrkB receptor signaling, which is known to be essential for both the induction and maintenance of LTP. We report that TrkB signaling in the AS mouse is defective, and show that reduction of Arc expression to control levels rescues the signaling deficits. Moreover, the association of the postsynaptic density protein PSD-95 with TrkB is critical for intact BDNF signaling, and elevated levels of Arc were found to impede PSD-95/TrkB association. In Ube3A deficient mice, the BDNF-induced recruitment of PSD-95, as well as PLCγ and Grb2-associated binder 1 (Gab1) with TrkB receptors was attenuated, resulting in reduced activation of PLCγ-α-calcium/calmodulin-dependent protein kinase II (CaMKII) and PI3K-Akt, but leaving the extracellular signal-regulated kinase (Erk) pathway intact. A bridged cyclic peptide (CN2097), shown by nuclear magnetic resonance (NMR) studies to uniquely bind the PDZ1 domain of PSD-95 with high affinity, decreased the interaction of Arc with PSD-95 to restore BDNF-induced TrkB/PSD-95 complex formation, signaling, and facilitate the induction of LTP in AS mice. We propose that the failure of TrkB receptor signaling at synapses in AS is directly linked to elevated levels of Arc associated with PSD-95 and PSD-95 PDZ-ligands may represent a promising approach to reverse cognitive dysfunction. 相似文献
23.
Stephen L. Hicks Rakesh Sharma Amad N. Khan Claire M. Berna Andrea Waldecker Kevin Talbot Chris Kennard Martin R. Turner 《PloS one》2013,8(12)
The neurodegenerative disorder amyotrophic lateral sclerosis may render patients unable to speak or write, so that objective assessment of cognitive impairment, which is commonly of a dysexecutive nature, is challenging. There is therefore a need to develop other methods of assessment that utilize other relatively unaffected motor systems. In this proof-of-principle study a novel eye-tracking version of the trail-making test was compared with performance on the standard written version in a group of healthy volunteers. There was good correlation for speed between both versions of Part B (R2=0.73), suggesting that this is a viable method to objectively assess cognitive impairment in disorders where patients are unable to speak or write. 相似文献
24.
Mayank Singh Clayton R. Hunt Raj K. Pandita Rakesh Kumar Chin-Rang Yang Nobuo Horikoshi Robert Bachoo Sara Serag Michael D. Story Jerry W. Shay Simon N. Powell Arun Gupta Jessie Jeffery Shruti Pandita Benjamin P. C. Chen Dorothee Deckbar Markus L?brich Qin Yang Kum Kum Khanna Howard J. Worman Tej K. Pandita 《Molecular and cellular biology》2013,33(16):3390
25.
26.
Muttaiya Sundaralingam Tuli P. Haromy 《Journal of biomolecular structure & dynamics》2013,31(1):55-61
Abstract The octahedral complex tetraammine(chloroaquo)cobalt(III) dichloride is shown to be the HCl hydrolysis product of both P1,2-bidentate tetraammine(pyrophosphato)cobalt(III) [CO(NH3)4HP207 or CoPP] and bidentate tetraammine(phosphato)cobalt(III) [Co(NH3)4P04or CoP]. The complex crystallizes in the orthorhombic space group Pna21 with cell dimensions α=13.033(2)Å, b=6.710(1) Å, and c=10.318(2)Å; the crystal structure was refined to a final disagreement index of 0.033. The average of the four Co-N distances is 1.944±6Å. The Co-Cl distance is 2.257(2)Å and the Co-O(W) distance is 1.971(4)Å. Both protons of the coordinated water molecule are engaged in strong hydrogen bonds to the two nonbonded chloride counterions with 0(W)-C1 distances of 3.087(6)Å and 3.123(6)Å. Each nonbonded chloride is engaged in seven hydrogen bonding interactions resulting from the high ratio of hydrogen bond donors to acceptors in the CoP structure. Cobalt bisphosphate (CoP2) is the final enzyme hydrolysis product when CoPP is used as substrate in the yeast inorganic pyrophosphatase reaction. The bridge oxygen atom is the site of initial CoPP cleavage both, for HCl catalyzed hydrolysis as well as for enzyme catalyzed hydrolysis. 相似文献
27.
Yelena Katsenovich Denny Carvajal Rakesh Guduru Leonel Lagos Chen-Zhong Li 《Geomicrobiology journal》2013,30(2):120-130
Production of nuclear fuel has resulted in hazardous waste streams that have contaminated the soil and groundwater. Arthrobacter strains, G975, G968, and G954 were used in the prescreening tests to evaluate their tolerance to UO2 2+ and investigate bacteria-U(VI) interactions under oxidizing pH-neutral conditions. Experiments have shown G975 is the fastest growing and the most uranium tolerant strain that removed about 90% of uranium from growth media. Atomic Force Microscopy images exhibited an irregular surface structure, which perhaps provided a larger surface area for uranium precipitation. The data indicate that aerobic heterotrophic bacteria may offer a solution to sequestering uranium in oxic conditions, which prevail in the vadose zone. 相似文献
28.
Stephen GS Vreden Jeetendra K Jitan Rakesh D Bansie Malti R Adhin 《Memórias do Instituto Oswaldo Cruz》2013,108(8):968-973
The emerging resistance to artemisinin derivatives that has been reported in
South-East Asia led us to assess the efficacy of artemether-lumefantrine as the first
line therapy for uncomplicated Plasmodium falciparum infections in
Suriname. This drug assessment was performed according to the recommendations of the
World Health Organization in 2011. The decreasing number of malaria cases in
Suriname, which are currently limited to migrating populations and gold miners,
precludes any conclusions on artemether efficacy because adequate numbers of patients
with 28-day follow-up data are difficult to obtain. Therefore, a comparison of day 3
parasitaemia in a 2011 study and in a 2005/2006 study was used to detect the
emergence of resistance to artemether. The prevalence of day 3 parasitaemia was
assessed in a study in 2011 and was compared to that in a study in 2005/2006. The
same protocol was used in both studies and artemether-lumefantrine was the study
drug. Of 48 evaluable patients in 2011, 15 (31%) still had parasitaemia on day 3
compared to one (2%) out of 45 evaluable patients in 2005/2006. Overall, 11 evaluable
patients in the 2011 study who were followed up until day 28 had negative slides and
similar findings were obtained in all 38 evaluable patients in the 2005/2006 study.
The significantly increased incidence of parasite persistence on day 3 may be an
indication of emerging resistance to artemether. 相似文献
29.
Rakesh Santhanam Xiaoying Rong Ying Huang Barbara A. Andrews Juan A. Asenjo Michael Goodfellow 《Antonie van Leeuwenhoek》2013,103(2):367-373
A Streptomyces strain isolated from a hyper-arid Atacama Desert soil was characterised using a polyphasic taxonomic approach. The strain, designated C2T, had chemical and morphological properties typical of the genus Streptomyces. The isolate formed a branch in the Streptomyces 16S rRNA gene tree together with the type strain of Streptomyces chromofuscus and was also loosely related to Streptomyces fragilis NRRL 2424T. DNA:DNA relatedness values between the isolate and its two phylogenetic neighbours showed that it formed a distinct genomic species. The strain was readily distinguished from these organisms using a combination of morphological and phenotypic data. Based on the genotypic and phenotypic results, isolate C2T represents a novel species in the genus Streptomyces, for which the name Streptomyces bullii sp. nov. is proposed. The type strain is C2T (=CGMCC 4.7019T = KACC 15426T). 相似文献
30.
Manasi Mishra Rakesh S. Joshi Sushama Gaikwad Vidya S. Gupta Ashok P. Giri 《Biochemical and biophysical research communications》2013,430(3):1060-1065
Pin-II protease inhibitors (PIs) are the focus of research interest because of their large structural–functional diversity and relevance in plant defense. Two representative Capsicum annuum PI genes (CanPI-15 and -7) comprising one and four inhibitory repeat domains, respectively, were expressed and recombinant proteins were characterized. β-Sheet and unordered structure was found predominant in CanPI-15 while -7 also displayed the signatures of polyproline fold, as revealed by circular dichroism studies. Inhibition kinetics against bovine trypsin indicated three times higher potency of CanPI-7 (Ki ~ 57 μM) than -15 (~184 μM). Activity and structural stability of these CanPIs were revealed under various conditions of pH, temperature and denaturing agent. Structure prediction, docking studies with proteases and mass spectroscopy revealed the organization of multiple reactive site loops of multi domain PIs in space as well as the steric hindrances imposed while binding to proteases due to their close proximity. 相似文献