300 results on '"Sanjay K Singh"'
Search Results
252. Interaction of calcium-bound C-reactive protein with fibronectin is controlled by pH: in vivo implications
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Madathilparambil V, Suresh, Sanjay K, Singh, and Alok, Agrawal
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Models, Molecular ,Binding Sites ,DNA, Complementary ,Base Sequence ,Protein Conformation ,Hydrogen-Ion Concentration ,In Vitro Techniques ,Recombinant Proteins ,Article ,Extracellular Matrix ,Fibronectins ,Kinetics ,C-Reactive Protein ,Neoplasms ,Mutagenesis, Site-Directed ,Humans ,Calcium ,Protein Binding - Abstract
C-reactive protein (CRP) binds with high affinity to fibronectin (Fn), a major component of the extracellular matrix (ECM), but at physiological pH the binding is inhibited by calcium ions (Ca2+). Because CRP circulates in the blood in Ca2+ -bound form, the occurrence of CRP-Fn interactions in vivo has been doubtful. To define the basis of inhibition of CRP-Fn interaction by Ca2+ at pH 7.0, we hypothesized that Fn-binding site on CRP consisted of amino acids co-ordinating Ca2+. Site-directed mutagenesis of amino acids co-ordinating Ca2+ drastically decreased the binding of CRP to Fn, indicating that the Ca2+ -binding site indeed formed the Fn-binding site. To determine the requirements for possible interaction between Ca2+ -bound CRP and Fn, we investigated inhibition of CRP-Fn interaction by Ca2+ as a function of pH. Ca2+ did not inhibit binding of CRP to Fn at pH 6.5 and lower. The contrasting Fn binding properties of CRP at physiological and mildly acidic pH indicated that the interaction of Ca2+ -bound CRP with Fn was controlled by pH. We conclude that the inhibition of binding of CRP to Fn by Ca2+ at pH 7.0 is a mechanism to prevent CRP-Fn interactions under normal conditions. CRP, in its Ca2+ -bound state, is capable of binding Fn but only at the inflammatory sites and tumors with low pH. CRP, Fn, and the ECM all have been implicated in cancer. Taken together our data raise the possibility that CRP-Fn interactions may change the architecture of ECM to modify the development of tumors.
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- 2004
253. Sequential 2'-O-methylation of archaeal pre-tRNATrp nucleotides is guided by the intron-encoded but trans-acting box C/D ribonucleoprotein of pre-tRNA
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Elizabeth J. Tran, Sanjay K. Singh, E. Stuart Maxwell, Priyatansh Gurha, and Ramesh Gupta
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Archaeal Proteins ,RNA, Archaeal ,Biochemistry ,Methylation ,RNA Precursors ,Guide RNA ,Molecular Biology ,Haloferax volcanii ,Ribonucleoprotein ,biology ,Intron ,RNA ,Cell Biology ,biology.organism_classification ,RNA, Transfer, Trp ,Ribonucleoproteins, Small Nuclear ,Molecular biology ,Introns ,Cell biology ,Transfer RNA ,RNA splicing ,Mutagenesis, Site-Directed ,Nucleic Acid Conformation ,Gene Expression Regulation, Archaeal - Abstract
Haloferax volcanii pre-tRNA(Trp) processing requires box C/D ribonucleoprotein (RNP)-guided 2'-O-methylation of nucleotides C34 and U39 followed by intron excision. Positioning of the box C/D guide RNA within the intron of this pre-tRNA led to the assumption that nucleotide methylation is guided by the cis-positioned box C/D RNPs. We have now investigated the mechanism of 2'-O-methylation for the H. volcanii pre-tRNA(Trp) in vitro by assembling methylation-competent box C/D RNPs on both the pre-tRNA and the excised intron (both linear and circular forms) using Methanocaldococcus jannaschii box C/D RNP core proteins. With both kinetic studies and single nucleotide substitutions of target and guide nucleotides, we now demonstrate that pre-tRNA methylation is guided in trans by the intron-encoded box C/D RNPs positioned in either another pre-tRNA(Trp) or in the excised intron. Methylation by in vitro assembled RNPs prefers but does not absolutely require Watson-Crick pairing between the guide and target nucleotides. We also demonstrate for the first time that methylation of two nucleotides guided by a single box C/D RNA is sequential, that is, box C'/D' RNP-guided U39 methylation first requires box C/D RNP-guided methylation of C34. Methylation of the two nucleotides of exogenous pre-tRNA(Trp) added to an H. volcanii cell extract also occurs sequentially and is also accomplished in trans using RNPs that pre-exist in the extract. Thus, this trans mechanism is analogous to eukaryal pre-rRNA 2'-O-methylation guided by intron-encoded but trans-acting box C/D small nucleolar RNPs. This trans mechanism could explain the observed accumulation of the excised H. volcanii pre-tRNA(Trp) intron in vivo. A trans mechanism would also eliminate the obligatory refolding of the pre-tRNA that would be required to carry out two cis-methylation reactions before pre-tRNA splicing.
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- 2004
254. Earthquake Engineering Problems in Parallel Neuro Environment
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Sudhirkumar V. Barai and Sanjay K. Singh
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Earthquake engineering ,Polynomial ,Artificial neural network ,Computer science ,business.industry ,Computer Science::Neural and Evolutionary Computation ,Message Passing Interface ,Model-based reasoning ,ComputingMethodologies_PATTERNRECOGNITION ,Polynomial and rational function modeling ,Autoregressive model ,Autoregressive–moving-average model ,Artificial intelligence ,business ,Algorithm - Abstract
The aim of the paper is to explore the application of Parallel Neuro Simulator for the generation of artificial earthquake Parallel Neuro Simulator is a neural network code developed on PARAM 10000 using ‘C' language and MPI library subroutines In this study, two artificial neural network (ANN) models have been proposed to replace the auto-regressive moving average (ARMA) model First ANN model substitutes the polynomial model that represents the relation of initial site information and coefficients of polynomial and the second ANN based model substitutes the estimated parameters of the ARMA model Several Indian earthquake records have been used for present study on PARAM 10000 The variation in computational time with increasing number of processors has also been studied.
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- 2004
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255. Three new species of Pseudocercospora from the Nepal Himalaya
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Sanjay K. Singh and Usha Budathoki
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Pseudocercospora ,biology ,Triumfetta pilosa ,Botany ,Genetics ,Smilax ,Taxonomy (biology) ,Plant Science ,biology.organism_classification ,Ecology, Evolution, Behavior and Systematics ,Smilax aspera ,Biotechnology - Abstract
Pseudocercospora heterospermi sp. nov. on Heterospermum pedunculosum Linn., P. himalayana sp. nov. on Triumfetta pilosa Roth. and P. smilacis sp. nov. on Smilax aspera Linn., collected from Kathmandu Valley in Nepal Himalaya, are described, illustrated and compared with allied taxa.
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- 1995
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256. Method for efficient fast spin echo Dixon imaging
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Lyle D. Broemeling, Norman E. Leeds, Jingfei Ma, Ashok Kumar, and Sanjay K. Singh
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Image quality ,Phase (waves) ,Image processing ,Breast Neoplasms ,Iterative reconstruction ,Sensitivity and Specificity ,Imaging phantom ,Data acquisition ,Optics ,Nuclear magnetic resonance ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,Physics ,Fourier Analysis ,business.industry ,Echo-Planar Imaging ,Phantoms, Imaging ,Echo (computing) ,Brain ,Image Enhancement ,Models, Structural ,Adipose Tissue ,Spin echo ,Female ,business - Abstract
In order to satisfy the Carr-Purcell-Meiboom-Gill (CPMG) condition, echo shift as dictated in fast-spin-echo (FSE)-based Dixon imaging was previously achieved by applying a time shift to the readout gradient and the data acquisition window. Accordingly, interecho spacing is increased, which entails increased image blurring and, in multislice imaging, a significant reduction in the slice coverage for a given imaging time. In this work, a new method is developed by which the echo shift is induced by "sandwiching" in time the readout gradient with a pair of small gradients of equal area and of opposite polarity. While data with non-zero phase shifts between water and fat signals are collected as fractional echoes, no increase in echo spacing is necessary with the modified acquisition strategy, and increased time efficiency is therefore achieved. In order to generate separate water-only and fat-only images in data processing, a set of low-resolution images are first reconstructed from the central symmetric portion (either 128 x 128 or 64 x 64) of the acquired multipoint Dixon data. High-resolution images using all the acquired data, including some partial Fourier-reconstructed images, are then phase demodulated using the phase errors determined from the low-resolution images. The feasibility of the technique is demonstrated using a water and fat phantom as well as in clinical patient imaging.
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- 2002
257. MR-04 * DICER REGULATES GLIOMA STEM CELL STATE
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Sanjay K. Singh, Sameer Agnihotri, Frederick Lang, Erik P. Sulman, Joy Gumin, Alenoush Vartanian, Kelly Burrell, Amir Alamhabspour, Shahrzad Jalali, and Gelareh Zadeh
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Cancer Research ,Gene knockdown ,biology ,fungi ,Stem cell marker ,Gene expression profiling ,Abstracts ,Oncology ,SOX2 ,Cancer stem cell ,microRNA ,biology.protein ,Cancer research ,Neurology (clinical) ,Stem cell ,Dicer - Abstract
The role of cancer stem cells in tumor formation and tumor heterogeneity is currently one of the most researched topics in cancer biology, and microRNAs likely have functional relevance in regulation of critical genes and parameters implicated in glioma stem cell (GSC) behavior and differentiation. To address this, we investigated global role of microRNA in GSCs, focusing on DICER, which regulates double-stranded RNA processing for microRNA biogenesis. Analysis of data from the Cancer Genome Atlas (TCGA) database suggests that high Dicer expression level is correlated with better prognosis of GBM patients. Gene signatures correlated with DICER expression levels suggest DICER/miRNA mediated mechanisms potentially regulate a multitude of cellular pathways in GBMs. Immunohistochemistry analysis of GBM tissue microarray reveals that of 54 tumor samples, 26 (48%) of GBM patients have low or undetectable levels of DICER1 protein, indicating frequent inactivation in high grade glioma. To characterize this functionally, we utilized various in vitro approaches, including exposure to hypoxia, to characterize the GSC properties after knockdown of DICER (GSCs did not have significant variation in endogenous DICER levels). Using three different GSC lines, we found in all cases with Dicer knockdown resulted in increased proliferation of three independent GSC lines with concomitant decrease in levels of stem cell markers (Sox2, Bmi1 etc.), a phenotype observed even upon exposure to hypoxia, a state that is known to preserve and promote the stem-like cell phenotype. Results from self-renewal assays as well as expression profiling show that GSCs with depleted levels of Dicer lose stem cell characteristics and acquire a progenitor-cell like state. Our results highlight the role of DICER as potential regulators of GSC stem-like versus progenitor-like state.
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- 2014
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258. Abstract 212: Withaferin A in combination with cisplatin targets CD44 and Oct4 positive cancer stem cells in ovarian cancer
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J C. States, Sham S. Kakar, and Sanjay K. Singh
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Cisplatin ,Cancer Research ,biology ,business.industry ,CD44 ,Cancer ,medicine.disease ,Carboplatin ,Metastasis ,Ovarian tumor ,chemistry.chemical_compound ,Oncology ,chemistry ,Cancer stem cell ,Immunology ,biology.protein ,Cancer research ,Medicine ,business ,Ovarian cancer ,medicine.drug - Abstract
Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly, carboplatin coupled with paclitaxel. Although this treatment regimen is initially effective in a high percentage of cases, it is associated with severe side effects and within 6 to 24 months of initial treatment, tumor relapse occurs, which is attributed to the carcinomas having become platinum-resistant. Due to the poor survival of women with platinum-resistant carcinomas, and the severe side effects an alternative treatment strategy is warranted. We developed a novel strategy that combines cisplatin with withaferin A (WFA). WFA, a bioactive compound isolated from the plant Withania somnifera, is used in the US as an over-the-counter dietary supplement. More recently, it has been shown to prevent tumor growth, angiogenesis, and metastasis. In addition, WFA has been reported to inhibit Notch 1 signaling an important signaling pathway for the self-renewal and maintenance of cancer stem cell population. Based on this information, we hypothesize that a novel combination of withaferin A and cisplatin can target ovarian cancer cells and also ovarian cancer stem cells, which can reduce the cisplatin side effects and recurrence of ovarian cancer. Our hypothesis is supported by our preliminary studies in which epithelial ovarian cancer cell lines (A2780 and CaOV3 and A2780/CP70) when co-treated with low doses of the WFA (1.5 µM) and cisplatin (20 µM), resulted in inhibiting 80 to 90% cell proliferation within 48 h of treatment. In contrast, same concentration of each drug when used alone exhibited only 15% to 20% inhibition, respectively. In addition, treatment of nude mice bearing orthotopic ovarian tumors with WFA/cisplatin combination resulted in 80 to 90% reduction in tumor growth and complete inhibition of metastasis to other organs. In addition, treatment of mice bearing ovarian tumors with WFA/cisplatin combination showed a significant reduction in CD44 positive cancer stem cells analyzed by immuno-staining and western blot analysis of the CD44 protein. Tumors collected from mice treated with cisplatin alone revealed enrichment of CD44 positive cancer stem cells and expression of CD44 protein. Analysis of Notch1 signaling gene and its downstream signaling gene Hes1 showed a significant down regulation of expression. Notch1 plays an important role in renewal and maintenance of cancer stem cells which are reported to be chemo-resistance and play critical role in recurrence of cancer. Based on our results, we conclude that WFA/cisplatin combination therapy not only suppresses ovarian tumor growth but minimizes/eliminates cancer stem cell population, hence reduces the drug resistance and recurrence of cancer. This work was support by funds from James Graham Brown Cancer Center. Presenting author is a post-doctoral fellow. Citation Format: Sanjay K. Singh, J C. States, Sham S. Kakar. Withaferin A in combination with cisplatin targets CD44 and Oct4 positive cancer stem cells in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 212. doi:10.1158/1538-7445.AM2014-212
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- 2014
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259. Withaferin A Alone and in Combination with Cisplatin Suppresses Growth and Metastasis of Ovarian Cancer by Targeting Putative Cancer Stem Cells
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Mana Moghadamfalahi, Donald M. Miller, Surinder K. Batra, Sham S. Kakar, Mariusz Z. Ratajczak, Karen S. Powell, and Sanjay K. Singh
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medicine.medical_specialty ,lcsh:Medicine ,Mice, Nude ,Carcinoma, Ovarian Epithelial ,Metastasis ,Mice ,chemistry.chemical_compound ,Cancer stem cell ,Cell Line, Tumor ,Internal medicine ,Medicine and Health Sciences ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Neoplasms, Glandular and Epithelial ,Neoplasm Metastasis ,lcsh:Science ,Withanolides ,Ovarian Neoplasms ,Cisplatin ,Multidisciplinary ,biology ,lcsh:R ,CD44 ,Biology and Life Sciences ,Cancer ,Cell Biology ,medicine.disease ,Carboplatin ,3. Good health ,Endocrinology ,Oncology ,chemistry ,Withaferin A ,Neoplastic Stem Cells ,Cancer research ,biology.protein ,Women's Health ,lcsh:Q ,Female ,Ovarian cancer ,Cell Division ,Research Article ,Signal Transduction ,medicine.drug - Abstract
Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly, carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately within few months of initial treatment, tumor relapse occurs because of platinum-resistance. This is attributed to chemo-resistance of cancer stem cells (CSCs). Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs. Treatment of nude mice bearing orthotopic ovarian tumors generated by injecting human ovarian epithelial cancer cell line (A2780) with WFA and cisplatin (WFA) alone or in combination resulted in a 70 to 80% reduction in tumor growth and complete inhibition of metastasis to other organs compared to untreated controls. Histochemical and Western blot analysis of the tumors revealed that inclusion of WFA (2 mg/kg) resulted in a highly significant elimination of cells expressing CSC markers - CD44, CD24, CD34, CD117 and Oct4 and downregulation of Notch1, Hes1 and Hey1 genes. In contrast treatment of mice with CIS alone (6 mg/kg) had opposite effect on those cells. Increase in cells expressing CSC markers and Notch1 signaling pathway in tumors exposed to CIS may explain recurrence of cancer in patients treated with carboplatin and paclitaxel. Since, WFA alone or in combination with CIS eliminates putative CSCs, we conclude that WFA in combination with CIS may present more efficacious therapy for ovarian cancer.
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- 2014
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260. A new phorbol diester from Aleurites moluccana
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P. Satyanarayana, Sanjay K. Singh, G.N. Rao, and K.A. Kumar
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Pharmacology ,Hentriacontane ,Plants, Medicinal ,Traditional medicine ,biology ,Stereochemistry ,Plant Extracts ,Euphorbiaceae ,Esters ,General Medicine ,Pharmacognosy ,biology.organism_classification ,Aleurites ,Aleurites moluccana ,Phorbols ,Terpenoid ,chemistry.chemical_compound ,chemistry ,Coumarins ,Drug Discovery ,Phorbol ,Humans ,Diterpene ,Diterpenes - Abstract
A new phorbol diester, 13-O-myristyl-20-O-acetyl-12-deoxyphorbol (1), has been isolated from the benzene extract of the heartwood of Aleurites moluccana. In addition, hentriacontane, 6,7-dimethoxycoumarin, 5,6,7-trimethoxycoumarin and beta-sitostenone are being reported for the first time from this species.
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- 2001
261. The first analogues of LNA (locked nucleic acids): phosphorothioate-LNA and 2'-thio-LNA
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Alexei A. Koshkin, Ravindra Kumar, Jesper Wengel, Michael Meldgaard, Vivek K. Rajwanshi, and Sanjay K. Singh
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DNA, Complementary ,Base pair ,Stereochemistry ,Clinical Biochemistry ,Molecular Conformation ,Pharmaceutical Science ,Thio ,Biochemistry ,RNA, Complementary ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,Locked nucleic acid ,Molecular Biology ,Base Sequence ,Oligonucleotide ,Organic Chemistry ,RNA ,Thionucleotides ,Thymine ,chemistry ,Oligodeoxyribonucleotides ,Nucleic acid ,Molecular Medicine ,Nucleic Acid Conformation ,Thermodynamics ,Indicators and Reagents ,DNA - Abstract
LNA (Locked Nucleic Acids, 1, X = O, Y = O) is a novel oligonucleotide analogue capable of recognizing complementary DNA and RNA with unprecedented thermal affinities. Synthesis of the first chemically modified LNA analogues is reported. A 9-mer phosphorothioate-LNA containing three LNA thymine monomers (1, X = O, Y = S, Base = thymin-1-yl) and 9-mer LNAs containing one, three or five 2'-thio-LNA monomers (1, X = S, Y = O, Base = uracil-1-yl) were able to recognize both complementary DNA and RNA with thermal affinities comparable to those of parent LNA.
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- 1999
262. LNA (Locked Nucleic Acids): An RNA Mimic Forming Exceedingly Stable LNA:LNA Duplexes
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Alexei A. Koshkin, Sanjay K. Singh, Michael Meldgaard, Jesper Wengel, Vivek K. Rajwanshi, and Poul Nielsen
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Colloid and Surface Chemistry ,Chemistry ,Stereochemistry ,RNA ,General Chemistry ,Locked nucleic acid ,Biochemistry ,Catalysis - Published
- 1998
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263. Efficient synthesis of 1,3-benzodioxin-4-one and benzoxazine-2,4-diones
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Alan R. Katritzky, Alan R. Katritzky, Sanjay K. Singh, Rena Akhmedova, Chunming Cai, Sergey Bobrov, Alan R. Katritzky, Alan R. Katritzky, Sanjay K. Singh, Rena Akhmedova, Chunming Cai, and Sergey Bobrov
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ARKIVOC: vol. 2007, no. 6, (issn) 1551-7012, (dlps) 5550190.0008.602, This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 License. Please contact mpub-help@umich.edu to use this work in a way not covered by the license.
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- 2006
264. Characterization of chest masses by FDG positron emission tomography
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Daniel W. Cotten, Howard R. Gould, E. Buonocore, Karl F. Hubner, and Sanjay K. Singh
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medicine.medical_specialty ,Fluorine Radioisotopes ,Lung Neoplasms ,FDG-Positron Emission Tomography ,Deoxyglucose ,Patlak plot ,Sensitivity and Specificity ,Diagnosis, Differential ,Fluorodeoxyglucose F18 ,medicine ,Carcinoma ,Humans ,Radiology, Nuclear Medicine and imaging ,Lung cancer ,Thoracic Neoplasm ,Retrospective Studies ,Lung ,business.industry ,General Medicine ,Thoracic Neoplasms ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,Radiology ,Differential diagnosis ,Neoplasm Recurrence, Local ,business ,Nuclear medicine ,Tomography, X-Ray Computed ,Tomography, Emission-Computed - Abstract
Radiographic imaging techniques have proved to be of limited value in characterizing chest masses. Likewise, scintigraphic techniques with tumor-seeking single photon emitting agents have shown marginal practical benefit. In contrast, high resolution PET with [F-18]-2-fluoro-2-D-deoxyglucose (FDG) offers a unique opportunity to distinguish benign from malignant processes by determining metabolic characteristics. PET scan results, including graphical analysis of tumor transfer constants (Patlak plot) in 21 patients with primary lung cancer, were compared to clinical outcome (histologic proof or clinical follow-up of longer than 1 year) in 54 patients who had chest masses identified by CT and/or plain film. The patients were categorized into three groups. The first group (N = 23) had primary, unknown, lung masses. Differentiation of benign from malignant tumors by PET had a sensitivity of 100% and a specificity of 67%. The second group (N = 13) had proven lung carcinoma or lymphoma and post-therapy PET scanning for recurrent tumor. In this setting, PET had a sensitivity of 83% and a specificity of 80%. The third group (N = 18) had extrathoracic malignancies and suspected pulmonary metastases. Metastatic lesions were identified with a sensitivity of 87% and specificity of 83%. Glucose uptake by normal tissue is variable and inflammatory/infectious processes can have high FDG uptake and overlap with the glucose uptake of malignant tissue. FDG PET is useful in characterizing chest tumors based on the level of their metabolic activity. Malignant tissue has a high glucose uptake. Elevated FDG uptake by an active inflammatory process may produce overlapping results.(ABSTRACT TRUNCATED AT 250 WORDS)
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- 1995
265. Radiogenomic Mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma Multiforme
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Ferenc A. Jolesz, Sadhan Majumder, Bhanu Majadan, Sanjay K. Singh, Rivka R. Colen, Pascal O. Zinn, and Pratheesh Sathyan
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Male ,Pathology ,Cancer Treatment ,Gene Expression ,Diagnostic Radiology ,0302 clinical medicine ,Basic Cancer Research ,Gene expression ,Image Processing, Computer-Assisted ,Edema ,Neurological Tumors ,Regulation of gene expression ,Multidisciplinary ,Brain Neoplasms ,Genomics ,Middle Aged ,Magnetic Resonance Imaging ,Phenotype ,3. Good health ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,Female ,Radiology ,Research Article ,Adult ,medicine.medical_specialty ,Science ,Radiogenomics ,Periostin ,Biology ,03 medical and health sciences ,microRNA ,Genetics ,Cancer Genetics ,medicine ,Humans ,Neoplasm Invasiveness ,Survival analysis ,Aged ,Gene Expression Profiling ,Cancers and Neoplasms ,Survival Analysis ,Gene expression profiling ,MicroRNAs ,Cancer research ,Glioblastoma ,Glioblastoma Multiforme ,Software ,030217 neurology & neurosurgery - Abstract
BackgroundDespite recent discoveries of new molecular targets and pathways, the search for an effective therapy for Glioblastoma Multiforme (GBM) continues. A newly emerged field, radiogenomics, links gene expression profiles with MRI phenotypes. MRI-FLAIR is a noninvasive diagnostic modality and was previously found to correlate with cellular invasion in GBM. Thus, our radiogenomic screen has the potential to reveal novel molecular determinants of invasion. Here, we present the first comprehensive radiogenomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM.MethodsBased on The Cancer Genome Atlas (TCGA), discovery and validation sets with gene, microRNA, and quantitative MR-imaging data were created. Top concordant genes and microRNAs correlated with high FLAIR volumes from both sets were further characterized by Kaplan Meier survival statistics, microRNA-gene correlation analyses, and GBM molecular subtype-specific distribution.ResultsThe top upregulated gene in both the discovery (4 fold) and validation (11 fold) sets was PERIOSTIN (POSTN). The top downregulated microRNA in both sets was miR-219, which is predicted to bind to POSTN. Kaplan Meier analysis demonstrated that above median expression of POSTN resulted in significantly decreased survival and shorter time to disease progression (PConclusionHere, we propose a novel diagnostic method to screen for molecular cancer subtypes and genomic correlates of cellular invasion. Our findings also have potential therapeutic significance since successful molecular inhibition of invasion will improve therapy and patient survival in GBM.
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- 2011
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266. Purification of recombinant C-reactive protein mutants
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Avinash Thirumalai, Alok Agrawal, Asmita Pathak, Donald N. Ngwa, Toh B. Gang, David J. Hammond, and Sanjay K. Singh
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0301 basic medicine ,Protein Conformation ,Mutant ,Chromatography, Affinity ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,law ,Immunology and Allergy ,Cloning, Molecular ,Phosphocholine ,biology ,Acute-phase protein ,Chromatography, Ion Exchange ,Ligand (biochemistry) ,Recombinant Proteins ,C-Reactive Protein ,Biochemistry ,Liver ,Ethanolamines ,Recombinant DNA ,Chromatography, Gel ,Protein Binding ,Phosphorylcholine ,Immunology ,Blotting, Western ,Molecular Sequence Data ,Mutagenesis (molecular biology technique) ,Transfection ,Article ,Cell Line ,Structure-Activity Relationship ,03 medical and health sciences ,Animals ,Humans ,Amino Acid Sequence ,Anion Exchange Resins ,Innate immune system ,Binding Sites ,Base Sequence ,Sequence Homology, Amino Acid ,C-reactive protein ,DNA ,030104 developmental biology ,chemistry ,Mutation ,biology.protein ,Mutagenesis, Site-Directed ,Calcium ,030215 immunology - Abstract
C-reactive protein (CRP) is an evolutionarily conserved protein, a component of the innate immune system, and an acute phase protein in humans. In addition to its raised level in blood in inflammatory states, CRP is also localized at sites of inflammation including atherosclerotic lesions, arthritic joints and amyloid plaque deposits. Results of in vivo experiments in animal models of inflammatory diseases indicate that CRP is an anti-pneumococcal, anti-atherosclerotic, anti-arthritic and an anti-amyloidogenic molecule. The mechanisms through which CRP functions in inflammatory diseases are not fully defined; however, the ligand recognition function of CRP in its native and non-native pentameric structural conformations and the complement-activating ability of ligand-complexed CRP have been suggested to play a role. One tool to understand the structure-function relationships of CRP and determine the contributions of the recognition and effector functions of CRP in host defense is to employ site-directed mutagenesis to create mutants for experimentation. For example, CRP mutants incapable of binding to phosphocholine are generated to investigate the importance of the phosphocholine-binding property of CRP in mediating host defense. Recombinant CRP mutants can be expressed in mammalian cells and, if expressed, can be purified from the cell culture media. While the methods to purify wild-type CRP are well established, different purification strategies are needed to purify various mutant forms of CRP if the mutant does not bind to either calcium or phosphocholine. In this article, we report the methods used to purify pentameric recombinant wild-type and mutant CRP expressed in and secreted by mammalian cells.
- Published
- 1992
267. Activation of mouse complement C3 by human C-reactive protein (134.59)
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Sanjay K Singh, Madathilparambil V Suresh, David J Hammond, Kazue Takahashi, and Alok Agrawal
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Immunology ,Immunology and Allergy - Abstract
Human C-reactive protein (CRP), once bound to pneumococcal C-polysaccharide (PnC), interacts with C1q and activates the classical pathway of complement in human serum. In mouse serum also, PnC-bound CRP activates complement, but not through the classical pathway because human CRP does not interact with mouse C1q. This study was undertaken to determine the pathway through which human CRP activates mouse complement and to generate a CRP mutant incapable of activating mouse complement. We found that human CRP could bind to mouse mannose-binding lectins, indicating that human CRP might activate the lectin pathway of complement in mouse serum. Further experiments to investigate whether human serum activates the lectin pathway of complement in mouse serum are ongoing. We next determined the complement C3-activating potential of two CRP mutants, Y175A and L176Q, which do not bind to human C1q. As expected, both CRP mutants did not activate C3 in human seum. However, in mouse serum, the C3-activating potential of the L176Q CRP, but not of Y175A CRP, was drastically reduced compared to that of wild-type CRP. It has been shown previously that human CRP protects mice from lethality following infection with Streptococcus pneumoniae. The L176Q CRP is a useful mutant of CRP to define the contribution of CRP-mediated complement activation in the anti-pneumococcal function of human CRP in mouse models of infection. NIH R01HL071233
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- 2009
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268. Selective and Irreversible Inhibitors of Aphid Acetylcholinesterases: Steps Toward Human-Safe Insecticides
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Rajesh K. Mishra, T. Leon Lassiter, Stephen Brimijoin, Yuan Ping Pang, Sanjay K. Singh, Kun Yan Zhu, and Yang Gao
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Insecticides ,media_common.quotation_subject ,Pneumonia, Viral ,lcsh:Medicine ,Insect ,Chemistry/Applied Chemistry ,Viral Nonstructural Proteins ,Antiviral Agents ,Serine ,Betacoronavirus ,chemistry.chemical_compound ,Enzyme activator ,Botany ,Animals ,Humans ,Protease Inhibitors ,lcsh:Science ,Biochemistry/Biomacromolecule-Ligand Interactions ,Biotechnology/Small Molecule Chemistry ,Chemistry/Organic Chemistry ,Pandemics ,Cholinesterase ,media_common ,chemistry.chemical_classification ,Aphid ,Multidisciplinary ,biology ,SARS-CoV-2 ,lcsh:R ,COVID-19 ,food and beverages ,biology.organism_classification ,Acetylcholinesterase ,Molecular Docking Simulation ,Cysteine Endopeptidases ,Enzyme ,Biochemistry ,chemistry ,Biochemistry/Small Molecule Chemistry ,Aphids ,biology.protein ,lcsh:Q ,Biochemistry/Drug Discovery ,Coronavirus Infections ,Research Article ,Cysteine - Abstract
Aphids, among the most destructive insects to world agriculture, are mainly controlled by organophosphate insecticides that disable the catalytic serine residue of acetylcholinesterase (AChE). Because these agents also affect vertebrate AChEs, they are toxic to non-target species including humans and birds. We previously reported that a cysteine residue (Cys), found at the AChE active site in aphids and other insects but not mammals, might serve as a target for insect-selective pesticides. However, aphids have two different AChEs (termed AP and AO), and only AP-AChE carries the unique Cys. The absence of the active-site Cys in AO-AChE might raise concerns about the utility of targeting that residue. Herein we report the development of a methanethiosulfonate-containing small molecule that, at 6.0 microM, irreversibly inhibits 99% of all AChE activity extracted from the greenbug aphid (Schizaphis graminum) without any measurable inhibition of the human AChE. Reactivation studies using beta-mercaptoethanol confirm that the irreversible inhibition resulted from the conjugation of the inhibitor to the unique Cys. These results suggest that AO-AChE does not contribute significantly to the overall AChE activity in aphids, thus offering new insight into the relative functional importance of the two insect AChEs. More importantly, by demonstrating that the Cys-targeting inhibitor can abolish AChE activity in aphids, we can conclude that the unique Cys may be a viable target for species-selective agents to control aphids without causing human toxicity and resistance problems.
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- 2009
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269. Singh et al. reply
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Sanjay K. Singh, Mohamedi N. Kagalwala, Jan Parker-Thornburg, Henry Adams, and Sadhan Majumder
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Multidisciplinary - Published
- 2009
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270. Synthesis of Novel Bicyclo[2.2.1] Ribonucleosides: 2‘-Amino- and 2‘-Thio-LNA Monomeric Nucleosides
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Jesper Wengel, Ravindra Kumar, and Sanjay K. Singh
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chemistry.chemical_compound ,Monomer ,chemistry ,Bicyclic molecule ,Stereochemistry ,Organic Chemistry ,Thio - Published
- 1998
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271. (Z)-N-Formylnornuciferin Isolated from Piper argyrophylum
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Sanjay K. Singh, Virinder S. Parmar, Jesper Wengel, and O. Simonsen
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Piper ,biology ,medicine.drug_class ,Carboxamide ,General Medicine ,Crystal structure ,Ring (chemistry) ,biology.organism_classification ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Crystallography ,chemistry ,Group (periodic table) ,medicine ,Molecule ,Methanol ,Benzene - Abstract
The title compound (systematic name: 4,5,6a,7-tetrahydro-1,2-dimethoxy-6H-dibenzo[de,g]quinoline-6-carboxaldehyde), C 19 H 19 NO 3 , was isolated as a minor component from the methanol extract of stems of P. argyrophylum Miq. The molecules are non-planar and the two benzene ring planes are at an angle of 21.9 (1)°. The N-formyl group and the two neighbouring C atoms constitute a planar fragment. The C-O-C planes of the two methoxy groups are nearly perpendicular to each other.
- Published
- 1996
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272. Orbital Mass Secondary to Precursor T-Cell Acute Lymphoblastic Leukemia
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L. Jeffrey Medeiros, Jeffrey L. Myers, Richard E. Champlin, Lawrence E. Ginsberg, Bita Esmaeli, and Sanjay K. Singh
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Adult ,Pathology ,medicine.medical_specialty ,Myeloid ,Biopsy ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Ethmoid Sinus ,Leukemic Infiltration ,Ethmoid sinus ,hemic and lymphatic diseases ,Precursor cell ,Acute lymphocytic leukemia ,Biomarkers, Tumor ,medicine ,Humans ,medicine.diagnostic_test ,business.industry ,Myeloid leukemia ,medicine.disease ,eye diseases ,Ophthalmology ,medicine.anatomical_structure ,Paranasal sinuses ,Female ,Sarcoma ,Tomography, X-Ray Computed ,business ,Orbit - Abstract
We describe a 40-year-old woman with a history of precursor T-cell acute lymphoblastic leukemia who developed an orbital mass associated with diffuse infiltration of the paranasal sinuses. The clinical and radiologic findings suggested an orbital abscess. Examination of orbital and ethmoid sinus biopsy specimens revealed relapse of precursor T-cell acute lymphoblastic leukemia. Although orbital involvement by granulocytic sarcoma (also known as extramedullary myeloid cell tumor and chloroma) with or without concurrent acute myeloid leukemia is well described in the literature, similar presence of acute lymphoblastic leukemia of either precursor T-cell or B-cell lineage is rare.
- Published
- 2001
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273. A Synthetic gagp24 Epitope Chemically Coupled to BSA Through a Decaalanine Peptide Enhances HIV Type 1 Serodiagnostic Ability by Several Folds.
- Author
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Sanjay K. Singh, Nand K. Shah, and Prakash S. Bisen
- Abstract
p24 is an immunodominant gagcore protein of HIV-1. The synthetic immunodominant epitope of p24 and the recombinant p24 show poor immunoreactivity and specificity, respectively. Their application is, therefore, severely limited in the serodiagnosis of HIV-1, although it is an important marker for early diagnosis. These limitations have been overcome by conjugating the synthetic p24 to BSA through a decaalanine peptide spacer. The engineered p24 shows about 5-fold more efficient immunoreactivity than the synthetic p24, and, at the same time, shows a several fold reduction in nonspecific cross-reactivity as compared to recombinant p24. Our strategy to conjugate the p24 peptide epitope to BSA worked well as a consistent and reliable immunodiagnostic marker. This strategy may also prove useful for the diagnosis of other diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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274. Tuned Helical Array of RhIII/IrIII Cp* Complexes with Polypyridyl Ligands.
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Sanjay K. Singh, Manish Chandra, Santosh K. Dubey, and Daya S. Pandey
- Published
- 2006
275. Solid Phase Synthesis of Quinoxalines1.
- Author
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Sanjay K. Singh
- Published
- 2003
276. Nerve injury inhibits Oprd1 and Cnr1 transcription through REST in primary sensory neurons
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Ashok Subedi, Asieh Etemad, Aadhya Tiwari, Yuying Huang, Biji Chatterjee, Samantha M. McLeod, Yungang Lu, DiAngelo Gonzalez, Krishna Ghosh, Mario Sirito, Sanjay K. Singh, Elisa Ruiz, Sandra L. Grimm, Cristian Coarfa, Hui-Lin Pan, and Sadhan Majumder
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REST ,Dorsal root ganglion ,Chronic pain ,Opioid receptors ,Cannabinoid CB1 receptor ,Therapeutic target ,Medicine ,Science - Abstract
Abstract The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of four opioid receptor genes (Oprm1, Oprd1, Oprl1 and Oprk1) and the cannabinoid CB1 receptor (Cnr1) gene in the DRG regulate nociception. In this study, we determined the role of REST in controlling their expression in the DRG induced by spared nerve injury (SNI). SNI induced chronic pain hypersensitivity in wild-type mice and was accompanied by increased levels of Rest transcript and protein. Transcriptomic analyses of wild-type mouse DRGs suggested that SNI upregulates the expression of Rest transcripts and downregulates the transcripts of all four opioid receptor genes and the Cnr1 gene. Quantitative reverse transcription polymerase chain reaction analyses of these tissues validated these results. Analysis of publicly available bioinformatic data suggested that REST binds to the promoter regions of Oprm1 and Cnr1. Chromatin immunoprecipitation analyses indicated the presence of REST at these promoters. Full-length Rest conditional knockout in primary sensory neurons reduced SNI-induced pain hypersensitivity and rescued the SNI-induced reduction in the expression of Oprd1 and Cnr1 in mouse DRG. Our results suggest that nerve injury represses the transcription of at least the Oprd1 and Cnr1 genes via REST in primary sensory neurons and that REST is a potential therapeutic target for neuropathic pain. Thus, inhibiting REST activity could potentially reduce chronic neuropathic pain and augment opioid/cannabinoid analgesic actions by increasing the transcription of Oprd1 and Cnr1 genes in DRG neurons.
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- 2024
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277. An analysis of the cultural motivations for transborder data flow legislation.
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Rita M. Walczuch, Sanjay K. Singh, and Todd S. Palmer
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POLITICAL planning ,TRANSBORDER data flow - Abstract
Transborder data flow legislation (TDFL) has recently emerged as an important issue for IS professionals. Transborder data flow (TDF) is the movement of computer readable data across national boundaries. Many countries have enacted legislation barring this free flow of information, citing a concern for the privacy of citizens as the primary motivation. The need for privacy is the reflection of a society's cultural attributes. A framework is developed for exploratory analysis of the cultural motivations for data protection legislation. Based on Hofstede's research, establishes a relationship between certain attributes of culture and nations that have adopted/proposed TDFL. Using this relationship, discusses the reasons for which other nations have not adopted/ proposed TDFL. [ABSTRACT FROM AUTHOR]
- Published
- 1995
278. Role of traditional healers in the management of microbial keratitis in eastern Nepal [version 2; peer review: 2 approved]
- Author
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Simon Arunga, Abhishek Roshan, Abeer H. A. Mohamed Ahmed, Reena Yadav, Astrid Leck, Sailesh K. Mishra, Sanjay K. Singh, Matthew J. Burton, Tara Mtuy, Sandip Das Sanyam, Jeremy J. Hoffman, and David Macleod
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microbial keratitis (MK) ,traditional healers ,eye care ,treatment ,practices ,traditional eye medicine (TEM) ,eng ,Medicine ,Science - Abstract
Background Microbial Keratitis (MK) is a leading cause of corneal blindness due to infection and its consequences, with a higher incidence in resource-limited nations. Hospital-based patient records from different parts of Nepal suggest patients often use traditional eye medicine to treat MK. Traditional healers (TH) within the community are often the first point of care for MK management. Little is known of their practice, perceptions, and knowledge around MK management. We aimed to understand the role of traditional healers in the management of MK in south-eastern Nepal. Methods A cross-sectional, mixed method, descriptive study was conducted in the Siraha district of Nepal. A total of 109 traditional healers consented to participate in a survey of knowledge, attitude, and practices. Some participants were also invited to participate in in-depth interviews and focus group discussions. Interviews and focus groups were conducted and recorded in the Maithili language by a native speaking interviewer and transcribed into English. Descriptive analysis was performed for the survey. Data saturation was considered the endpoint for qualitative data collection, and a thematic was analysis applied. Results Traditional healers believe that infection of the eye can be caused by trauma, conjunctivitis, or evil spirits. They were unclear about differentiating MK from other eye conditions. They provided various types of treatment. Some were confident that they could treat severe ulcers that had not responded to medical therapy, while others thought treating larger diameter ulcers would be difficult. Although there were mixed responses in referring patients with MK, the majority of TH were willing to refer. Conclusion In a weak health system, traditional healers may help address barriers to healthcare access and reduce delays to definitive care, upon integration into the formal health system and referral pathway.
- Published
- 2024
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279. Tardive dystonia in patients with Tourette's syndrome
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Sanjay K. Singh and Joseph Jankovic
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Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Pediatrics ,Tetrabenazine ,Tourette's syndrome ,Behavior disorder ,otorhinolaryngologic diseases ,medicine ,Humans ,In patient ,Tardive Dystonia ,Psychiatry ,Dystonia ,medicine.disease ,nervous system diseases ,Neurology ,Neurology (clinical) ,Psychology ,Dystonic movements ,After treatment ,medicine.drug ,Antipsychotic Agents ,Tourette Syndrome - Abstract
We describe two patients with Gilles de la Tourette's syndrome (TS) who developed tardive dystonia after treatment with neuroleptics. The dystonic movements persisted after the offending drugs were stopped and improved with tetrabenazine. Tardive dystonia in TS has not been documented previously.
- Published
- 1988
280. An evolutionarily conserved function of C-reactive protein is to prevent the formation of amyloid fibrils
- Author
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Alok Agrawal, Asmita Pathak, Donald N. Ngwa, Avinash Thirumalai, Peter B. Armstrong, and Sanjay K. Singh
- Subjects
C-reactive protein ,Limulus polyphemus ,American horseshoe crab ,amyloidosis ,protein toxicity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
C-reactive protein (CRP) binds to phosphocholine (PCh)-containing substances and subsequently activates the complement system to eliminate the ligand. The PCh-binding function of CRP has been conserved throughout evolution from arthropods to humans. Human CRP, in its structurally altered conformation at acidic pH, also binds to amyloid-β (Aβ) and prevents the formation of Aβ fibrils. It is unknown whether the Aβ-binding function of CRP has also been evolutionarily conserved. The aim of this study was to determine whether CRP isolated from American horseshoe crab Limulus polyphemus was also anti-amyloidogenic and whether this function required structural alteration of Limulus CRP (Li-CRP). Two CRP species Li-CRP-I and Li-CRP-II were purified from hemolymph by employing PCh-affinity chromatography and phosphoethanolamine-affinity chromatography, respectively. Both Li-CRP-I and Li-CRP-II bound to immobilized Aβ at physiological pH. Unlike human CRP, Li-CRP did not require any changes in its overall structure to bind to Aβ. Both Li-CRP-I and Li-CRP-II bound to Aβ in the fluid phase also and prevented the fibrillation of Aβ. Additionally, ion-exchange chromatography of purified Li-CRP indicated that a variety of Li-CRP molecules of different subunit compositions were present in Limulus hemolymph, raising the possibility that the presence of various Li-CRP species in hemolymph facilitates the recognition of a range of proteins with differing amyloidogenicity. We conclude that the binding of CRP to Aβ is an ancient function of CRP. In invertebrates, the Aβ-binding function of CRP can protect the host from toxicity caused by amyloidogenic and pathogenic proteins. In humans, the Aβ-binding function of CRP can protect against inflammatory diseases in which the host proteins are ectopically deposited on either host cells or foreign cells in an inflammatory milieu since immobilized proteins may expose Aβ-like structures after deposition at places where they are not supposed to be.
- Published
- 2024
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281. C-reactive protein lowers the serum level of IL-17, but not TNF-α, and decreases the incidence of collagen-induced arthritis in mice
- Author
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Sanjay K. Singh, Amanda Prislovsky, Donald N. Ngwa, Undral Munkhsaikhan, Ammaar H. Abidi, David D. Brand, and Alok Agrawal
- Subjects
C-reactive protein ,collagen-induced arthritis ,IL-17 ,immune complex ,TNF-α ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The biosynthesis of C-reactive protein (CRP) in the liver is increased in inflammatory diseases including rheumatoid arthritis. Previously published data suggest a protective function of CRP in arthritis; however, the mechanism of action of CRP remains undefined. The aim of this study was to evaluate the effects of human CRP on the development of collagen-induced arthritis (CIA) in mice which is an animal model of autoimmune inflammatory arthritis. Two CRP species were employed: wild-type CRP which binds to aggregated IgG at acidic pH and a CRP mutant which binds to aggregated IgG at physiological pH. Ten CRP injections were given on alternate days during the development of CIA. Both wild-type and mutant CRP reduced the incidence of CIA, that is, reduced the number of mice developing CIA; however, CRP did not affect the severity of the disease in arthritic mice. The serum levels of IL-17, IL-6, TNF-α, IL-10, IL-2 and IL-1β were measured: both wild-type and mutant CRP decreased the level of IL-17 and IL-6 but not of TNF-α, IL-10, IL-2 and IL-1β. These data suggest that CRP recognizes and binds to immune complexes, although it was not clear whether CRP functioned in its native pentameric or in its structurally altered pentameric form in the CIA model. Consequently, ligand-complexed CRP, through an as-yet undefined mechanism, directly or indirectly, inhibits the production of IL-17 and eventually protects against the initiation of the development of arthritis. The data also suggest that IL-17, not TNF-α, is critical for the development of autoimmune inflammatory arthritis.
- Published
- 2024
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282. Elucidating the effects on polyphenol oxidase activity and allelic variation of polyphenol oxidase genes on dough and whole wheat-derived product color parameters
- Author
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Rajappa Harisha, Sumit Kumar Singh, Arvind Kumar Ahlawat, Sneh Narwal, J. P. Jaiswal, J. B. Singh, Rajeev Ranjan Kumar, Shaily Singhal, Adithya P. Balakrishnan, Priyanka Shukla, Beera Bhavya, Arpita Agrawal, Sanjay K. Singh, and Anju Mahendru-Singh
- Subjects
PPO activity ,dough and chapati color ,color analyzer ,phenol color test ,PPO genes ,Nutrition. Foods and food supply ,TX341-641 ,Food processing and manufacture ,TP368-456 - Abstract
ABSTRACTPolyphenol oxidase (PPO) activity is a primary cause of the development of unattractive dark brown discoloration of wheat-based end products. The present study aims to evaluate a set of 41 diverse wheat genotypes grown at three different locations in India for grain phenol color reaction, PPO activity and molecular marker-based characterization of alleles of PPO genes. Relationships among these parameters were analyzed along with the effects of grain PPO activity on dough and chapati color at different time intervals. The mean PPO activity ranged from 7.42 to 27.57 min−1 g−1 10−3 among the genotypes and it showed a significant negative correlation with color brightness (L*) of dough rested for 0 min (r = -0.406), 15 min (r = -0.406), 2 h (r = -0.502) and 4 h (r = -0.551) and whole wheat flour-derived chapati rested for 2 h (r = -0.267) and 4 h (r = -0.424). The overall quality color score was negatively correlated with PPO activity (r = -0.863) and showed a positive correlation with both dough and chapati visual color measured at different time intervals. PPO activity in the genotypes carrying different alleles was found to be Ppo-A1a>Ppo-A1b; Ppo-B2d>Ppo-B2a; and Ppo-D1b>Ppo-D1a. The allelic constitution Ppo-A1bPpo-B2aPpo-D1a and Ppo-A1bPpo-B2dPpo-D1 was found to produce the lowest PPO activity, and thus these alleles are recommended to be used in marker assisted breeding for low PPO activity genotypes to minimize the discoloration of wheat-based end-products.
- Published
- 2023
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283. Light regulation of the biosynthesis of phenolics, terpenoids, and alkaloids in plants
- Author
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Yongliang Liu, Sanjay K. Singh, Sitakanta Pattanaik, Hongxia Wang, and Ling Yuan
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Abstract Biosynthesis of specialized metabolites (SM), including phenolics, terpenoids, and alkaloids, is stimulated by many environmental factors including light. In recent years, significant progress has been made in understanding the regulatory mechanisms involved in light-stimulated SM biosynthesis at the transcriptional, posttranscriptional, and posttranslational levels of regulation. While several excellent recent reviews have primarily focused on the impacts of general environmental factors, including light, on biosynthesis of an individual class of SM, here we highlight the regulation of three major SM biosynthesis pathways by light-responsive gene expression, microRNA regulation, and posttranslational modification of regulatory proteins. In addition, we present our future perspectives on this topic.
- Published
- 2023
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284. Insights into the genomic architecture of a newly discovered endophytic Fusarium species belonging to the Fusarium concolor complex from India
- Author
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Shiwali Rana and Sanjay K. Singh
- Subjects
asexual morph ,novel taxon ,Fusarium ,genome mining ,antiSMASH ,secondary metabolites ,Microbiology ,QR1-502 - Abstract
In this study, a new species Fusarium indicum belonging to the Fusarium concolor species complex is established to accommodate an endophytic fungus isolated from Bambusa sp. and collected from Himachal Pradesh. The identity of this isolate was confirmed based on the asexual morphs, its cultural characteristics, and phylogenetic analyses. This isolate revealed out to be distinct by showing less similarity with described species in the genus Fusarium based on molecular sequence data, approximately 93.9% similarity based on translation elongation factor 1-alpha, and 94.2% similarity based on RNA polymerase II subunit. Furthermore, to increase knowledge about this novel species, whole-genome sequencing was carried out. The results displayed that Fusarium indicum NFCCI 5145 possesses a 40.2 Mb genome and 48.39% of GC content. Approximately 12,963 functional protein-coding genes were carefully predicted and annotated using different BLAST databases, such as Uniprot, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Pathogen Host Interactions (PHI), Clusters of Orthologous Groups (COG), and Carbohydrate-Active enzymes (CAZy). The orthologous proteins were identified using OrthoFinder and used for the phylogenetic analysis. ANIb confirmed that the isolate is closely related to the F. concolor species complex. It is known that Fusarium strains can produce a wide range of bioactive secondary metabolites. Therefore, in-depth mining for biosynthetic gene clusters for secondary metabolite biosynthesis of Fusarium indicum NFCCI 5145 was investigated using Antibiotics and Secondary Metabolites Analysis Shell (AntiSMASH) annotation. AntiSMASH results displayed that this isolate possesses 45 secondary metabolites of biosynthetic gene clusters (BGCs). These findings significantly improved our understanding of the strain Fusarium indicum NFCCI 5145 and its possible applications in different sectors including industry for the secondary metabolites and enzymes it can produce.
- Published
- 2023
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285. TP53-PTEN-NF1 depletion in human brain organoids produces a glioma phenotype in vitro
- Author
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Sanjay K. Singh, Yan Wang, Ahmed Habib, Mamindla Priyadarshini, Chowdari V. Kodavali, Apeng Chen, Wencai Ma, Jing Wang, N. U. Farrukh Hameed, Baoli Hu, Gregory N. Fuller, Scott M. Kulich, Nduka Amankulor, Rivka R. Colen, Lincoln A. Edwards, and Pascal O. Zinn
- Subjects
organoid ,nestin ,glioblastoma ,TP53 ,PTEN ,and NF1 tumor suppressors ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Glioblastoma (GBM) is fatal and the study of therapeutic resistance, disease progression, and drug discovery in GBM or glioma stem cells is often hindered by limited resources. This limitation slows down progress in both drug discovery and patient survival. Here we present a genetically engineered human cerebral organoid model with a cancer-like phenotype that could provide a basis for GBM-like models. Specifically, we engineered a doxycycline-inducible vector encoding shRNAs enabling depletion of the TP53, PTEN, and NF1 tumor suppressors in human cerebral organoids. Designated as inducible short hairpin-TP53-PTEN-NF1 (ish-TPN), doxycycline treatment resulted in human cancer-like cerebral organoids that effaced the entire organoid cytoarchitecture, while uninduced ish-TPN cerebral organoids recapitulated the normal cytoarchitecture of the brain. Transcriptomic analysis revealed a proneural GBM subtype. This proof-of-concept study offers a valuable resource for directly investigating the emergence and progression of gliomas within the context of specific genetic alterations in normal cerebral organoids.
- Published
- 2023
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286. The Enigmatic World of Fungal Melanin: A Comprehensive Review
- Author
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Malika Suthar, Laurent Dufossé, and Sanjay K. Singh
- Subjects
melanin ,bioactive pigment ,biotechnological potential ,fungi ,Biology (General) ,QH301-705.5 - Abstract
Synthetic dyes are generally not safe for human health or the environment, leading to the continuous search and growing demand for natural pigments that are considered safer, biodegrade more easily, and are environmentally beneficial. Among micro-organisms, fungi represent an emerging source of pigments due to their many benefits; therefore, they are readily viable on an industrial scale. Among all the bioactive pigments produced by fungi, melanin is an enigmatic, multifunctional pigment that has been studied for more than 150 years. This dark pigment, which is produced via the oxidative polymerization of phenolic compounds, has been investigated for its potential to protect life from all kingdoms, including fungi, from biotic and abiotic stresses. Over time, the research on fungal melanin has attracted a significant amount of scientific interest due to melanin’s distinct biological activities and multifarious functionality, which is well-documented in the literature and could possibly be utilized. This review surveys the literature and summarizes the current discourse, presenting an up-to-date account of the research performed on fungal melanin that encompasses its types, the factors influencing its bioactivity, the optimization of fermentation conditions to enhance its sustainable production, its biosynthetic pathways, and its extraction, as well as biochemical characterization techniques and the potential uses of melanin in a wide range of applications in various industries. A massive scope of work remains to circumvent the obstacles to obtaining melanin from fungi and exploring its future prospects in a diverse range of applications.
- Published
- 2023
- Full Text
- View/download PDF
287. Differentiating biological and chemical factors of top and deep soil carbon sequestration in semi-arid tropical Inceptisol: an outcome of structural equation modeling
- Author
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Avijit Ghosh, Amit K. Singh, Sunil Kumar, M. C. Manna, Ranjan Bhattacharyya, Rajesh Agnihortri, Sanjay K. Singh Gahlaud, Manjanagouda S. Sannagoudar, Kamini Gautam, R. V. Kumar, and Suresh K. Chaudhari
- Subjects
carbon stock ,land-use systems ,soil enzymes ,microbial biomass c ,silt + clay ,Environmental sciences ,GE1-350 - Abstract
Though soils sequester large amounts of carbon (C), variations in physical and chemical characteristics of top and deep layers necessitate the study of factors governing topsoil and deep soil C sequestration to predict land-use changes to alleviate climate change. Land-use systems involving pasture, trees, trees pasture and fallow were considered. The upper soil (0–15 cm) had ∼12, 34 and 59% higher microbial biomass C than the 15–30, 30–45 and 45–60 cm layers, respectively. Fluorescein diacetate (FDA) and dehydrogenase activities had similar trends. Across the land uses, topsoil layers had ∼17% lower silt + clay (s + c) content than deep layers. Amorphous iron content significantly increased with soil depth. In the top two soil layers, s + c accounted for ∼19–30% of total soil organic carbon (SOC); in the next two layers s + c could store >30% of total SOC. Stepwise regression analysis revealed FDA to be the most significant biological driver for SOC sequestration. Structural equation modeling showed that biological factors controlled C sequestration in topsoil layers, while s + c and amorphous iron were the major factors of C sequestration in deep layers. Current land uses are largely deficient of SOC and have the potential to store an additional22 Mg CO2e per ha.
- Published
- 2020
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288. Bilateral viral keratitis following corneal collagen crosslinking for progressive keratoconus
- Author
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Sanjeeta Sitaula, Sanjay K. Singh, and Anil Gurung
- Subjects
Corneal collagen crosslinking ,Herpetic keratitis ,Keratoconus ,Ophthalmology ,RE1-994 - Abstract
Abstract Purpose Corneal collagen crosslinking has been proven to be a useful technique to slow the progression of keratoconus. With its increasing use, we are encountering rare complications. We describe a case that developed bilateral viral keratitis after corneal collagen crosslinking with riboflavin and ultraviolet A for progressive keratoconus. Case report An 18-year-old boy underwent corneal collagen crosslinking in both the eyes at the same setting for bilateral progressive keratoconus. He was discharged with a soft bandage contact lens and asked to follow up in 5 days. Seven days later, the patient returned with severe pain, redness, and photophobia for the last 2 days. The bandage contact lens was removed. There was a central corneal lesion in a branching dendritic pattern in both the eyes and the corneal sensation was reduced. Based on the findings, a clinical diagnosis of bilateral viral keratitis was made. The dendrite healed completely in 10 days with oral and topical acyclovir treatment, and the cornea had a faint scar at 1 month follow-up with best-corrected visual acuity of 6/9 in both eyes with a rigid gas permeable lens. Discussion and conclusion Ultraviolet A light could be a stimulus to trigger reactivation of latent HSV infections even in patients with no history of clinically evident herpes virus ocular infections. Early diagnosis and timely treatment can have good visual outcome. Prophylactic antiviral medication may be useful to prevent this complication in individuals with prior history of viral keratitis.
- Published
- 2019
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289. Statistical Analysis for Generalized Progressive Hybrid Censored Data from Lindley Distribution under Step-Stress Partially Accelerated Life Test Model
- Author
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Aakriti Pandey, Arun Kaushik, Sanjay K. Singh, and Umesh Singh
- Subjects
Probabilities. Mathematical statistics ,QA273-280 ,Statistics ,HA1-4737 - Abstract
The aim of this paper is to present the estimation procedure for the step-stress partially accelerated life test model under the generalized progressive hybrid censoring scheme. The uncertainties are assumed to be governed by Lindley distribution. The problem with point and interval estimation of the parameters as well as the acceleration factor using maximum likelihood approach for the step-stress partially accelerated life test model has been considered. A simulation study is conducted to monitor the performance of the estimators on the basis of the mean squared error under the considered censoring scheme. The expected total time of the test under an accelerated condition is computed to examine the effects of the parameters on the duration of the test. In addition, a graph of the expected total time of the test under accelerated and un-accelerated conditions is provided to highlight the effect due to acceleration. One real data set has been analyzed for illustrative purposes.
- Published
- 2021
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290. C-Reactive Protein-Based Strategy to Reduce Antibiotic Dosing for the Treatment of Pneumococcal Infection
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Donald N. Ngwa, Sanjay K. Singh, and Alok Agrawal
- Subjects
C-reactive protein ,clarithromycin ,pneumococcal infection ,Streptococcus pneumoniae ,combination therapy ,Immunologic diseases. Allergy ,RC581-607 - Abstract
C-reactive protein (CRP) is a component of innate immunity. The concentration of CRP in serum increases in microbial infections including Streptococcus pneumoniae infection. Employing a mouse model of pneumococcal infection, it has been shown that passively administered human wild-type CRP protects mice against infection, provided that CRP is injected into mice within two hours of administering pneumococci. Engineered CRP (E-CRP) molecules have been reported recently; unlike wild-type CRP, passively administered E-CRP protected mice against infection even when E-CRP was injected into mice after twelve hours of administering pneumococci. The current study was aimed at comparing the protective capacity of E-CRP with that of an antibiotic clarithromycin. We established a mouse model of pneumococcal infection in which both E-CRP and clarithromycin, when used alone, provided minimal but equal protection against infection. In this model, the combination of E-CRP and clarithromycin drastically reduced bacteremia and increased survival of mice when compared to the protective effects of either E-CRP or clarithromycin alone. E-CRP was more effective in reducing bacteremia in mice treated with clarithromycin than in untreated mice. Also, there was 90% reduction in antibiotic dosing by including E-CRP in the antibiotic-treatment for maximal protection of infected mice. These findings provide an example of cooperation between the innate immune system and molecules that prevent multiplication of bacteria, and that should be exploited to develop novel combination therapies for infections against multidrug-resistant pneumococci. The reduction in antibiotic dosing by including E-CRP in the combination therapy might also resolve the problem of developing antibiotic resistance.
- Published
- 2021
- Full Text
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291. Treatment of Pneumococcal Infection by Using Engineered Human C-Reactive Protein in a Mouse Model
- Author
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Donald N. Ngwa, Sanjay K. Singh, Toh B. Gang, and Alok Agrawal
- Subjects
C-reactive protein ,complement ,factor H ,pneumococcal infection ,Streptococcus pneumoniae ,Immunologic diseases. Allergy ,RC581-607 - Abstract
C-reactive protein (CRP) binds to several species of bacterial pathogens including Streptococcus pneumoniae. Experiments in mice have revealed that one of the functions of CRP is to protect against pneumococcal infection by binding to pneumococci and activating the complement system. For protection, however, CRP must be injected into mice within a few hours of administering pneumococci, that is, CRP is protective against early-stage infection but not against late-stage infection. It is assumed that CRP cannot protect if pneumococci got time to recruit complement inhibitor factor H on their surface to become complement attack-resistant. Since the conformation of CRP is altered under inflammatory conditions and altered CRP binds to immobilized factor H also, we hypothesized that in order to protect against late-stage infection, CRP needed to change its structure and that was not happening in mice. Accordingly, we engineered CRP molecules (E-CRP) which bind to factor H on pneumococci but do not bind to factor H on any host cell in the blood. We found that E-CRP, in cooperation with wild-type CRP, was protective regardless of the timing of administering E-CRP into mice. We conclude that CRP acts via two different conformations to execute its anti-pneumococcal function and a model for the mechanism of action of CRP is proposed. These results suggest that pre-modified CRP, such as E-CRP, is therapeutically beneficial to decrease bacteremia in pneumococcal infection. Our findings may also have implications for infections with antibiotic-resistant pneumococcal strains and for infections with other bacterial species that use host proteins to evade complement-mediated killing.
- Published
- 2020
- Full Text
- View/download PDF
292. Conformationally Altered C-Reactive Protein Capable of Binding to Atherogenic Lipoproteins Reduces Atherosclerosis
- Author
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Asmita Pathak, Sanjay K. Singh, Douglas P. Thewke, and Alok Agrawal
- Subjects
atherosclerosis ,C-reactive protein ,inflammation ,low-density lipoprotein ,phosphocholine ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The aim of this study was to test the hypothesis that C-reactive protein (CRP) protects against the development of atherosclerosis and that a conformational alteration of wild-type CRP is necessary for CRP to do so. Atherosclerosis is an inflammatory cardiovascular disease and CRP is a plasma protein produced by the liver in inflammatory states. The co-localization of CRP and low-density lipoproteins (LDL) at atherosclerotic lesions suggests a possible role of CRP in atherosclerosis. CRP binds to phosphocholine-containing molecules but does not interact with LDL unless the phosphocholine groups in LDL are exposed. However, CRP can bind to LDL, without the exposure of phosphocholine groups, if the native conformation of CRP is altered. Previously, we reported a CRP mutant, F66A/T76Y/E81A, generated by site-directed mutagenesis, that did not bind to phosphocholine. Unexpectedly, this mutant CRP, without any more conformational alteration, was found to bind to atherogenic LDL. We hypothesized that this CRP mutant, unlike wild-type CRP, could be anti-atherosclerotic and, accordingly, the effects of mutant CRP on atherosclerosis in atherosclerosis-prone LDL receptor-deficient mice were evaluated. Administration of mutant CRP into mice every other day for a few weeks slowed the progression of atherosclerosis. The size of atherosclerotic lesions in the aorta of mice treated with mutant CRP for 9 weeks was ~40% smaller than the lesions in the aorta of untreated mice. Thus, mutant CRP conferred protection against atherosclerosis, providing a proof of concept that a local inflammation-induced structural change in wild-type CRP is a prerequisite for CRP to control the development of atherosclerosis.
- Published
- 2020
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293. Complement Activation by C-Reactive Protein Is Critical for Protection of Mice Against Pneumococcal Infection
- Author
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Sanjay K. Singh, Donald N. Ngwa, and Alok Agrawal
- Subjects
C-reactive protein ,acute phase response ,complement ,inflammation ,pneumococcal infection ,Immunologic diseases. Allergy ,RC581-607 - Abstract
C-reactive protein (CRP), a component of the innate immune system, is an antipneumococcal plasma protein. Human CRP has been shown to protect mice against infection with lethal doses of Streptococcus pneumoniae by decreasing bacteremia. in vitro, CRP binds to phosphocholine-containing substances, such as pneumococcal C-polysaccharide, in a Ca2+-dependent manner. Phosphocholine-complexed human CRP activates the complement system in both human and murine sera. The mechanism of antipneumococcal action of CRP in vivo, however, has not been defined yet. In this study, we tested a decades-old hypothesis that the complement-activating property of phosphocholine-complexed CRP contributes to protection of mice against pneumococcal infection. Our approach was to investigate a CRP mutant, incapable of activating murine complement, in mouse protection experiments. We employed site-directed mutagenesis of CRP, guided by its three-dimensional structure, and identified a mutant H38R which, unlike wild-type CRP, did not activate complement in murine serum. Substitution of His38 with Arg in CRP did not affect the pentameric structure of CRP, did not affect the binding of CRP to pneumococci, and did not decrease the stability of CRP in mouse circulation. Employing a murine model of pneumococcal infection, we found that passively administered H38R CRP failed to protect mice against infection. Infected mice injected with H38R CRP showed no reduction in bacteremia and did not survive longer, as opposed to infected mice treated with wild-type CRP. Thus, the hypothesis that complement activation by phosphocholine-complexed CRP is an antipneumococcal effector function was supported. We can conclude now that complement activation by phosphocholine-complexed CRP is indeed essential for CRP-mediated protection of mice against pneumococcal infection.
- Published
- 2020
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294. Visual Outcome of Descemet Membrane Endothelial Keratoplasty during the Learning Curve in Initial Fifty Cases
- Author
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Sanjay K. Singh and Sanjeeta Sitaula
- Subjects
Ophthalmology ,RE1-994 - Abstract
This study was performed to evaluate the clinical outcomes of the first fifty patients who underwent Descemet membrane endothelial keratoplasty (DMEK) during the 3-month postoperative period and to describe the challenges encountered during the learning curve. In this retrospective study, we reviewed the charts of patients who underwent DMEK. All information regarding patient demographics, indication for surgery, preoperative and postoperative visual acuity at 3 months, donor age, and complications encountered intraoperatively and postoperatively was recorded. Donor endothelial cell count at the time of surgery and during the 3-month follow-up was noted. Data were analyzed using SPSS version 17. Fifty eyes of 49 patients were included in the study with majority being female patients (male : female = 2 : 3). Mean age of patients was 56.8 ± 11.4 years with the age range of 22–78 years. The common indications for DMEK were pseudophakic bullous keratopathy –57.1%, Fuchs endothelial dystrophy-34.7%, failed grafts-6.1% (Descemet stripping endothelial keratoplasty (DSEK) and failed penetrating keratoplasty), and others. Preoperative best spectacle-corrected visual acuity was 20/63 in 41.8% of the cases, and 93% had visual acuity of 20/200 or better. Donor size was 8 mm, and average donor endothelial cell count (ECC) was 2919 ± 253 cells/mm2. Average ECC at 3 months postoperatively was 1750 ± 664 cells/mm2, which showed a 40% decrease in ECC. The most common encountered complication was graft detachment, which occurred in 16% cases for which rebubbling was done. Regular follow-up and timely identification of graft detachment may prevent the need for retransplantation.
- Published
- 2019
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295. Rediscovery of Penicillium paradoxum (Ascomycete: Aspergillaceae) from Maharashtra, India
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Kunhiraman C. Rajeshkumar, Sayali D. Marathe, Sneha S. Lad, Deepak K. Mayura, Sanjay K. Singh, and Santosh V. Swami
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Anamorphic ascomycete ,Phylogeny ,Taxonomy ,Western Ghats ,Ecology ,QH540-549.5 ,General. Including nature conservation, geographical distribution ,QH1-199.5 - Abstract
Penicillium paradoxum has an enigmatic Aspergillus-like anamorphic state; earlier named as Aspergillus paradoxus with a teleomorph state Hemicarpenteles paradoxus. The present paper describes the rediscovery of this species from India after five decades and includes a phylogenetic study of this strain. This is the first record of this strain from peninsular India including the Western Ghats.
- Published
- 2016
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296. REST–miR-21–SOX2 axis maintains pluripotency in E14Tg2a.4 embryonic stem cells
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Sanjay K. Singh, Anantha Marisetty, Pratheesh Sathyan, Mohamedi Kagalwala, Zhaoyang Zhao, and Sadhan Majumder
- Subjects
REST-miR-21-Sox2 axis in mESC pluripotency ,Biology (General) ,QH301-705.5 - Abstract
Our previous studies have shown that the regulatory network that maintains pluripotency in mouse embryonic stem cells (mESCs) is regulated in a context-dependent manner and can be modulated, at least in part, by re-calibration of an intracellular network of pluripotency factors as well as cues arising from the extracellular matrix. The transcriptional repressor REST represses miR-21 and, thus, regulates self-renewal in E14Tg2a.4 mESCs cultured in the absence of mouse embryonic fibroblast feeder cell effects. However, how miR-21 connects to the nuclear regulatory network has not been clear. Here, we show that miR-21, a direct target of REST-mediated repression, directly targets Sox2. Exogenously added miR-21 to mESCs decreases the expression of Sox2, decreasing mESC self-renewal, and this effect of miR-21 on mESC self-renewal can be blocked by expression of exogenous Sox2. Conversely, destabilization of Sox2 by miR-21 can be blocked by anti-miR-21. Thus, the REST–miR-21–Sox2 axis connects REST to the core nuclear pluripotency regulators in E14Tg2a.4 mESCs cultured in the absence of feeder cells.
- Published
- 2015
- Full Text
- View/download PDF
297. Fungal Pigments and Their Prospects in Different Industries
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Ajay C. Lagashetti, Laurent Dufossé, Sanjay K. Singh, and Paras N. Singh
- Subjects
color ,natural pigments ,fungal pigments ,dyeing ,textile fabrics ,Biology (General) ,QH301-705.5 - Abstract
The public’s demand for natural, eco-friendly, and safe pigments is significantly increasing in the current era. Natural pigments, especially fungal pigments, are receiving more attention and seem to be in high demand worldwide. The immense advantages of fungal pigments over other natural or synthetic pigments have opened new avenues in the market for a wide range of applications in different industries. In addition to coloring properties, other beneficial attributes of fungal pigments, such as antimicrobial, anticancer, antioxidant, and cytotoxic activity, have expanded their use in different sectors. This review deals with the study of fungal pigments and their applications and sheds light on future prospects and challenges in the field of fungal pigments. Furthermore, the possible application of fungal pigments in the textile industry is also addressed.
- Published
- 2019
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298. Correction: Radiogenomic Mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma Multiforme.
- Author
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Pascal O. Zinn, Bhanu Mahajan, Pratheesh Sathyan, Sanjay K. Singh, Sadhan Majumder, Ferenc A. Jolesz, and Rivka R. Colen
- Subjects
Medicine ,Science - Published
- 2012
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299. Social Work Professionals’ Emotional Intelligence, Locus Of Control And Role Efficacy: An Exploratory Study
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Sanjay K. Singh
- Subjects
social work professionals ,emotional intelligence ,locus of control ,role efficacy ,Personnel management. Employment management ,HF5549-5549.5 - Abstract
The principal objective of the study was to study social work professionals psychologically. This study was conducted on a sample of 178 participants. The findings depict role efficacy to be associated positively with emotional intelligence and internal locus of control, but negatively with external locus of control. Similarly, emotional intelligence was found to be associated positively with internality, but negatively related to externality. The findings also indicated that emotional intelligence alone accounts for 43% of the variance on role efficacy of social work professionals. The findings of the study have major implications for non-governmental organizations and are discussed.
- Published
- 2006
- Full Text
- View/download PDF
300. Newspaper reporters' role effectiveness: A comparative study of two levels of hierarchy
- Author
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Sanjay K. Singh and Paramjeet K. Dhillon
- Subjects
Newspaper reporters' role effectiveness ,Levels of hierarchy ,Industrial psychology ,HF5548.7-5548.85 - Abstract
Hardly any behavioural scientist ever thought of empirically studying newspaper reporters from a psychological perspective. Realising the dearth of study from psychological viewpoints this investigation was designed to examine the relationships as well as relative impact of the antecedent variables of Background information, organisational climate, organisational role stress, and journalistic writing attitude on to the role effectiveness of the lower level reporters and the higher level reporters. The results obtained were discussed in the light of the past researches in the area of effectiveness in-a-role in-an-organisation. Opsomming Bykans geen gedragswetenskaplike het al aan die idee gedink om koerant-verslaggewers vanuit ’n sielkundige perspektief te bestudeer nie. Gegewe die skaarste aan navorsing vanuit ’n sielkundige gesigshoek, is hierdie ondersoek ontwerp om die verhouding sowel as die relatiewe impak van oorsaaklike veranderlikes van agtergrondinligting, organisasieklimaat, organisatoriese rolstres en die joernalistieke skryfhouding op die roldoeltreffendheid van die laevlak verslaggewers en die hoëvlak verslaggewers te ondersoek. Die verkreë resultate word bespreek in die lig van die vorige navorsing ten opsigte van roldoeltreffenheid in ’n organisasie.
- Published
- 2004
- Full Text
- View/download PDF
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