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141.
Atom-based three dimensional-quantitative structure–activity relationship (3D-QSAR) model was developed on the basis of 5-point pharmacophore hypothesis (AARRR) with two hydrogen bond acceptors (A) and three aromatic rings for the derivatives of thieno[2,3-b]pyridine, which modulates the activity to inhibit the mGluR5 receptor. Generation of a highly predictive 3D-QSAR model was performed using the alignment of predicted pharmacophore hypothesis for the training set (R2?=?0.84, SD?=?0.26, F?=?45.8, N?=?29) and test set (Q2?=?0.74, RMSE?=?0.235, Pearson-R?=?0.94, N?=?9). The best pharmacophore hypothesis AARRR was selected, and developed three dimensional-quantitative structure activity relationship (3D-QSAR) model also supported the outcome of this study by means of favorable and unfavorable electron withdrawing group and hydrophobic regions of most active compound 42d and least active compound 18b. Following, induced fit docking and binding free energy calculations reveals the reliable binding orientation of the compounds. Finally, molecular dynamics simulations for 100?ns were performed to depict the protein–ligand stability. We anticipate that the resulted outcome could be supportive to discover potent negative allosteric modulators for metabotropic glutamate receptor 5 (mGluR5). 相似文献
142.
T. R. Mahalingam S. Vijayalakshmi R. Krishna Prabhu A. Thiruvengadasami Ann Wilber C. K. Mathews K. Radha Shanmugasundaram 《Biological trace element research》1997,57(3):191-206
Blood is one of the widely used specimens for biological trace element research because of its biological significance and
ease of sampling. We have conducted a study of the blood of the Kalpakkam township population for trace and minor elements.
For this purpose, analytical methods have been developed and standardized in our laboratory for the elemental analysis of
blood plasma and red cells. Inductively coupled plasma-mass spectrometry (ICP-MS), a relatively new technique, has been applied
for the analysis of trace elements. Details regarding spectral interference and matrix interference encountered in the analysis
of blood and the methods of correcting them have been discussed. Flame atomic absorption spectrometry (AAS)/atomic emission
spectrometry (AES) has been applied for the determination of minor elements. Precision and accuracy of these methods have
also been discussed. 相似文献
143.
144.
Antiserum to flight-muscle proteins was developed by injecting flight-muscle extract into rabbits. Immunodiffusion tests showed the presence of at least 4 antibodies formed against 4 proteins in the flight-muscle extract. During the 4th day of adult life, while vitellogenesis was under way, 4 proteins antigenically identical to those of flight-muscle extract were found in the blood. These four proteins were found in the first batch of laid eggs under immunodiffusion. The possibility of entry of muscle proteins into oöcytes by way of the blood is discussed. 相似文献
145.
A new soil isolate of Lactobacillus sp. grown in Yamanaka medium under submerged conditions showed the presence of d-glucose, d-xylose and d-ribose isomerases in washed cell suspension and cell free extracts. d-Xylose isomerase (d-xylose ketol-isomerase, EC 5.3.1.5) and d-ribose isomerase (d-ribose ketol-isomerase, EC 5.3.1.20) activities reached a maximum in 48 h of growth and then declined. d-Glucose isomerase (d-glucose 6-phosphate isomerase, d-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9) activity was maximum after 72 h and remained constant for ~120 h of growth. d-Glucose isomerase activity increased with the increase in number of generations of culture and reached a maximum in 5–6 generations, whereas d-xylose and d-ribose isomerase activities decreased. The washed and starved whole cells could be heat treated and immobilized on the rough surface of glass rods or glass slides using acetone treatment. The heat treated immobilized cells showed only the presence of d-glucose isomerase activity and showed no d-xylose and d-ribose isomerase activities. d-Glucose isomerase activity of heat treated immobilized cells was inhibited less by sorbitol, mannitol, sodium arsenate, cysteine and calcium ions than the free d-glucose isomerase activity in fresh untreated washed whole cells and cell free extracts. EDTA inhibition had the same effect for both forms. Ca2+inhibition could be reversed by adding Mg2+ions. 相似文献
146.
Ross G. Johnson Hung C. Le Kristen Evenson Shelby W. Loberg Tori M. Myslajek Andrea Prabhu Ann-Marie Manley Colette O’Shea Haiying Grunenwald Madelaine Haddican Patrick M. Fitzgerald Timothy Robinson Bruno A. Cisterna Juan C. Sáez Tai-Feng Liu Dale W. Laird Judson D. Sheridan 《The Journal of membrane biology》2016,249(6):713-741
147.
Tao Wu Sripriya Ramamoorthy Teresa Wilson Fangyi Chen Edward Porsov Hrebesh Subhash Sarah Foster Yuan Zhang Irina Omelchenko Michael Bateschell Lingyan Wang John?V. Brigande Zhi-Gen Jiang Tianyi Mao Alfred?L. Nuttall 《Biophysical journal》2016,110(2):493-502
Normal hearing in mammals depends on sound amplification by outer hair cells (OHCs) presumably by their somatic motility and force production. However, the role of OHC force production in cochlear amplification and frequency tuning are not yet fully understood. Currently, available OHC manipulation techniques for physiological or clinical studies are limited by their invasive nature, lack of precision, and poor temporal-spatial resolution. To overcome these limitations, we explored an optogenetic approach based on channelrhodopsin 2 (ChR-2), a direct light-activated nonselective cation channel originally discovered in Chlamydomonas reinhardtii. Three approaches were compared: 1) adeno-associated virus-mediated in utero transfer of the ChR-2 gene into the developing murine otocyst, 2) expression of ChR-2(H134R) in an auditory cell line (HEI-OC1), and 3) expression of ChR-2 in the OHCs of a mouse line carrying a ChR-2 conditional allele. Whole cell recording showed that blue light (470 nm) elicited the typical nonselective cation current of ChR-2 with reversal potential around zero in both mouse OHCs and HEI-OC1 cells and generated depolarization in both cell types. In addition, pulsed light stimulation (10 Hz) elicited a 1:1 repetitive depolarization and ChR-2 currents in mouse OHCs and HEI-OC1 cells, respectively. The time constant of depolarization in OHCs, 1.45 ms, is 10 times faster than HEI-OC1 cells, which allowed light stimulation up to rates of 10/s to elicit corresponding membrane potential changes. Our study demonstrates that ChR-2 can successfully be expressed in mouse OHCs and HEI-OC1 cells and that these present a typical light-sensitive current and depolarization. However, the amount of ChR-2 current induced in our in vivo experiments was insufficient to result in measurable cochlear effects. 相似文献
148.
Chandrasekhar Bhaskaran Nair Jagannath Manjula Pradeep Annamalai Subramani Prakash B. Nagendrappa Mulakkapurath Narayanan Manoj Sukriti Malpani Phani Kumar Pullela Pillarisetti Venkata Subbarao Siva Ramamoorthy Susanta K. Ghosh 《PloS one》2016,11(1)
Background
Sensitive and specific detection of malarial parasites is crucial in controlling the significant malaria burden in the developing world. Also important is being able to identify life threatening Plasmodium falciparum malaria quickly and accurately to reduce malaria related mortality. Existing methods such as microscopy and rapid diagnostic tests (RDTs) have major shortcomings. Here, we describe a new real-time PCR-based diagnostic test device at point-of-care service for resource-limited settings.Methods
Truenat® Malaria, a chip-based microPCR test, was developed by bigtec Labs, Bangalore, India, for differential identification of Plasmodium falciparum and Plasmodium vivax parasites. The Truenat Malaria tests runs on bigtec’s Truelab Uno® microPCR device, a handheld, battery operated, and easy-to-use real-time microPCR device. The performance of Truenat® Malaria was evaluated versus the WHO nested PCR protocol. The Truenat® Malaria was further evaluated in a triple-blinded study design using a sample panel of 281 specimens created from the clinical samples characterized by expert microscopy and a rapid diagnostic test kit by the National Institute of Malaria Research (NIMR). A comparative evaluation was done on the Truelab Uno® and a commercial real-time PCR system.Results
The limit of detection of the Truenat Malaria assay was found to be <5 parasites/μl for both P. falciparum and P. vivax. The Truenat® Malaria test was found to have sensitivity and specificity of 100% each, compared to the WHO nested PCR protocol based on the evaluation of 100 samples. The sensitivity using expert microscopy as the reference standard was determined to be around 99.3% (95% CI: 95.5–99.9) at the species level. Mixed infections were identified more accurately by Truenat Malaria (32 samples identified as mixed) versus expert microscopy and RDTs which detected 4 and 5 mixed samples, respectively.Conclusion
The Truenat® Malaria microPCR test is a valuable diagnostic tool and implementation should be considered not only for malaria diagnosis but also for active surveillance and epidemiological intervention. 相似文献149.
Sandeep R. Varma Thiyagarajan O. Sivaprakasam Abheepsa Mishra L. M. Sharath Kumar N. S. Prakash Sunil Prabhu Shyam Ramakrishnan 《PloS one》2016,11(1)
Human skin is body’s vital organ constantly exposed to abiotic oxidative stress. This can have deleterious effects on skin such as darkening, skin damage, and aging. Plant-derived products having skin-protective effects are well-known traditionally. Triphala, a formulation of three fruit products, is one of the most important rasayana drugs used in Ayurveda. Several skin care products based on Triphala are available that claim its protective effects on facial skin. However, the skin protective effects of Triphala extract (TE) and its mechanistic action on skin cells have not been elucidated in vitro. Gallic acid, ellagic acid, and chebulinic acid were deduced by LC-MS as the major constituents of TE. The identified key compounds were docked with skin-related proteins to predict their binding affinity. The IC50 values for TE on human dermal fibroblasts (HDF) and human keratinocytes (HaCaT) were 204.90 ± 7.6 and 239.13 ± 4.3 μg/mL respectively. The antioxidant capacity of TE was 481.33 ± 1.5 mM Trolox equivalents in HaCaT cells. Triphala extract inhibited hydrogen peroxide (H2O2) induced RBC haemolysis (IC50 64.95 μg/mL), nitric oxide production by 48.62 ± 2.2%, and showed high reducing power activity. TE also rescued HDF from H2O2-induced damage; inhibited H2O2 induced cellular senescence and protected HDF from DNA damage. TE increased collagen-I, involucrin and filaggrin synthesis by 70.72 ± 2.3%, 67.61 ± 2.1% and 51.91 ± 3.5% in HDF or HaCaT cells respectively. TE also exhibited anti-tyrosinase and melanin inhibition properties in a dose-dependent manner. TE increased the mRNA expression of collagen-I, elastin, superoxide dismutase (SOD-2), aquaporin-3 (AQP-3), filaggrin, involucrin, transglutaminase in HDF or HaCaT cells, and decreased the mRNA levels of tyrosinase in B16F10 cells. Thus, Triphala exhibits protective benefits on skin cells in vitro and can be used as a potential ingredient in skin care formulations. 相似文献
150.
Thennilapuram P. Ramamoorthy 《Brittonia》1984,36(3):297-299
Salvia raveniana Ramamoorthy, resemblingS. purpurea Cav. [S. sect.Purpureae (Epling) Epling], but differing in deeply sulcate stem, long unbranched terminal racemes, many-flowered verticils, the nature and color of pubescence (very white) of calyx contrasting with a red corolla that dries purple, the reflexed, revolute lower lip of corolla, the number of papillae in the corolla tube (2), and the slightly exserted stamens, is described from the State of Guerrero, Mexico. 相似文献