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101.
Oh PS Patel VB Sanders MA Kanwar SS Yu Y Nautiyal J Patel BB Majumdar AP 《American journal of physiology. Gastrointestinal and liver physiology》2011,301(2):G347-G355
We have previously demonstrated that expression of the novel gene schlafen-3 (Slfn-3) correlates with intestinal epithelial cell differentiation (Patel VB, Yu Y, Das JK, Patel BB, Majumdar AP. Biochem Biophys Res Commun 388: 752-756, 2009). The present investigation was undertaken to examine whether Slfn-3 plays a role in regulating differentiation of FOLFOX-resistant (5-fluorouracil + oxaliplatin) colon cancer cells that are highly enriched in cancer stem cells (CSCs). Transfection of Slfn-3 in FOLFOX-resistant colon cancer HCT-116 cells resulted in increase of alkaline phosphatase activity, a marker of intestinal differentiation. Additionally, Slfn-3 transfection resulted in reduction of mRNA and protein levels of the CSC markers CD44, CD133, CD166, and aldehyde dehydrogenase 1 in both FOLFOX-resistant HCT-116 and HT-29 cells. This was accompanied by decreased formation of tumorosphere/colonosphere (an in vitro model of tumor growth) in stem cell medium and inhibition of expression of the chemotherapeutic drug transporter protein ABCG2. Additionally, Slfn-3 transfection of FOLFOX-resistant HCT-116 and HT-29 cells reduced Hoechst 33342 dye exclusion. Finally, Slfn-3 transfection inhibited the expression of transforming growth factor-α in both FOLFOX-resistant colon cancer cells, but stimulated apoptosis in response to additional FOLFOX treatment. In summary, our data demonstrate that Slfn-3 expression inhibits multiple characteristics of CSC-enriched, FOLFOX-resistant colon cancer cells, including induction of differentiation and reduction in tumorosphere/colonosphere formation, drug transporter activity, and autocrine stimulation of proliferation. Thus Slfn-3 expression may render colon CSCs more susceptible to cancer chemotherapeutics. 相似文献
102.
Determination of osteoporotic status is based primarily on areal bone mineral density (aBMD) obtained through dual X-ray absorptiometry (DXA). However, many fractures occur in patients with T-scores above the WHO threshold of osteoporosis, in part because DXA measures are insensitive to biomechanically important alterations in bone quality. The goal of this study was to determine--within groups of subjects with identical radius aBMD values--the extant variation in densitometric, geometric, microstructural, and biomechanical parameters. High resolution peripheral quantitative computed tomography (HR-pQCT) and DXA radius data from males and females spanning large ranges in age, osteoporotic status, and anthropometrics were compiled. 262 distal radius datasets were processed for this study. HR-pQCT scans were analyzed according to the manufacturer's standard clinical protocol to quantify densitometric, geometric, and microstructural indices. Micro-finite element analysis was performed to calculate biomechanical indices. Factor of risk of wrist fracture was calculated. Simulated aBMD calculated from HR-pQCT data was used to group scans for evaluation of variation in quantified indices. Indices reflecting the greatest variation within aBMD level were BMD in the central portion of the trabecular compartment (max CV 142), trabecular heterogeneity (max CV 90), and intra-cortical porosity (max CV 151). Of the biomechanical indices, cortical load fraction had the greatest variation (max CV 38). Substantial variations in indices reflecting density, structure, and biomechanical competence exist among subjects with identical aBMD levels. Overlap of these indices among osteoporotic status groups reflects the reported incidence of osteoporotic fracture in subjects classified as osteopenic or normal. 相似文献
103.
Proton binding equilibria (pKa values) of ionizable groups in proteins are exquisitely sensitive to their microenvironments. Apparent pKa values measured for individual ionizable residues with NMR spectroscopy are actually population‐weighted averages of the pKa in different conformational microstates. NMR spectroscopy experiments with staphylococcal nuclease were used to test the hypothesis that pKa values of surface Glu and Asp residues are affected by pH‐sensitive fluctuations of the backbone between folded and locally unfolded conformations. 15N spin relaxation studies showed that as the pH decreases from the neutral into the acidic range the amplitudes of backbone fluctuations in the ps‐ns timescale increase near carboxylic residues. Hydrogen exchange experiments suggested that backbone conformational fluctuations promoted by decreasing pH also reflect slower local or sub‐global unfolding near carboxylic groups. This study has implications for structure‐based pKa calculations: (1) The timescale of the backbone's response to ionization events in proteins can range from ps to ms, and even longer; (2) pH‐sensitive fluctuations of the backbone can be localized to both the segment the ionizable residue is attached to or the one that occludes the ionizable group; (3) Structural perturbations are not necessarily propagated through Coulomb interactions; instead, local fluctuations appear to be coupled through the co‐operativity inherent to elements of secondary structure and to networks of hydrogen bonds. These results are consistent with the idea that local conformational fluctuations and stabilities are important determinants of apparent pKa values of ionizable residues in proteins. Proteins 2014; 82:3132–3143. © 2014 Wiley Periodicals, Inc. 相似文献
104.
Lin Shao Pratiksha Bhatnagar Rajtilak Majumdar Rakesh Minocha Subhash C. Minocha 《Amino acids》2014,46(3):743-757
The effect of up-regulation of putrescine (Put) production by genetic manipulation on the turnover of spermidine (Spd) and spermine (Spm) was investigated in transgenic cells of poplar (Populus nigra × maximowiczii) and seedlings of Arabidopsis thaliana. Several-fold increase in Put production was achieved by expressing a mouse ornithine decarboxylase cDNA either under the control of a constitutive (in poplar) or an inducible (in Arabidopsis) promoter. The transgenic poplar cells produced and accumulated 8–10 times higher amounts of Put than the non-transgenic cells, whereas the Arabidopsis seedlings accumulated up to 40-fold higher amounts of Put; however, in neither case the cellular Spd or Spm increased consistently. The rate of Spd and Spm catabolism and the half-life of cellular Spd and Spm were measured by pulse-chase experiments using [14C]Spd or [14C]Spm. Spermidine half-life was calculated to be about 22–32 h in poplar and 52–56 h in Arabidopsis. The half-life of cellular Spm was calculated to be approximately 24 h in Arabidopsis and 36–48 h in poplar. Both species were able to convert Spd to Spm and Put, and Spm to Spd and Put. The rates of Spd and Spm catabolism in both species were several-fold slower than those of Put, and the overproduction of Put had only a small effect on the overall rates of turnover of Spd or Spm. There was little effect on the rates of Spd to Spm conversion as well as the conversion of Spm into lower polyamines. While Spm was mainly converted back to Spd and not terminally degraded, Spd was removed from the cells largely through terminal catabolism in both species. 相似文献
105.
106.
Nivedita Roy Supriya Chakraborty Bidisha Paul Chowdhury Sayantan Banerjee Kuntal Halder Saikat Majumder Subrata Majumdar Parimal C. Sen 《PloS one》2014,9(10)
Calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various Ca2+ pumps and channels. Two such fundamental calcium pumps are plasma membrane calcium ATPase (PMCA) and Sarco/endoplasmic reticulum calcium ATPase (SERCA) which play a pivotal role in maintaining intracellular calcium homeostasis. This intracellular Ca2+ homeostasis is often disturbed by the protozoan parasite Leishmania donovani, the causative organism of visceral leishmaniasis. In the present study we have dileneated the involvement of PMCA4 and SERCA3 during leishmaniasis. We have observed that during leishmaniasis, intracellular Ca2+ concentration was up-regulated and was further controlled by both PMCA4 and SERCA3. Inhibition of these two Ca2+-ATPases resulted in decreased parasite burden within the host macrophages due to enhanced intracellular Ca2+. Contrastingly, on the other hand, activation of PMCA4 was found to enhance the parasite burden. Our findings also highlighted the importance of Ca2+ in the modulation of cytokine balance during leishmaniasis. These results thus cumulatively suggests that these two Ca2+-ATPases play prominent roles during visceral leishmaniasis. 相似文献
107.
Diego A. Miranda Ji-Hyun Kim Long N. Nguyen Wang Cheng Bryan C. Tan Vera J. Goh Jolene S. Y. Tan Jadegoud Yaligar Bhanu Prakash KN S. Sendhil Velan Hongyan Wang David L. Silver 《The Journal of biological chemistry》2014,289(14):9560-9572
Triglycerides within the cytosol of cells are stored in a phylogenetically conserved organelle called the lipid droplet (LD). LDs can be formed at the endoplasmic reticulum, but mechanisms that regulate the formation of LDs are incompletely understood. Adipose tissue has a high capacity to form lipid droplets and store triglycerides. Fat storage-inducing transmembrane protein 2 (FITM2/FIT2) is highly expressed in adipocytes, and data indicate that FIT2 has an important role in the formation of LDs in cells, but whether FIT2 has a physiological role in triglyceride storage in adipose tissue remains unproven. Here we show that adipose-specific deficiency of FIT2 (AF2KO) in mice results in progressive lipodystrophy of white adipose depots and metabolic dysfunction. In contrast, interscapular brown adipose tissue of AF2KO mice accumulated few but large LDs without changes in cellular triglyceride levels. High fat feeding of AF2KO mice or AF2KO mice on the genetically obese ob/ob background accelerated the onset of lipodystrophy. At the cellular level, primary adipocyte precursors of white and brown adipose tissue differentiated in vitro produced fewer but larger LDs without changes in total cellular triglyceride or triglyceride biosynthesis. These data support the conclusion that FIT2 plays an essential, physiological role in fat storage in vivo. 相似文献
108.
Chuck R. Smallwood Lorne Jordan Vy Trinh Daniel W. Schuerch Amparo Gala Mathew Hanson Yan Shipelskiy Aritri Majumdar Salete M.C. Newton Phillip E. Klebba 《The Journal of general physiology》2014,144(1):71-80
Spectroscopic analyses of fluorophore-labeled Escherichia coli FepA described dynamic actions of its surface loops during binding and transport of ferric enterobactin (FeEnt). When FeEnt bound to fluoresceinated FepA, in living cells or outer membrane fragments, quenching of fluorophore emissions reflected conformational motion of the external vestibular loops. We reacted Cys sulfhydryls in seven surface loops (L2, L3, L4, L5, L7 L8, and L11) with fluorophore maleimides. The target residues had different accessibilities, and the labeled loops themselves showed variable extents of quenching and rates of motion during ligand binding. The vestibular loops closed around FeEnt in about a second, in the order L3 > L11 > L7 > L2 > L5 > L8 > L4. This sequence suggested that the loops bind the metal complex like the fingers of two hands closing on an object, by individually adsorbing to the iron chelate. Fluorescence from L3 followed a biphasic exponential decay as FeEnt bound, but fluorescence from all the other loops followed single exponential decay processes. After binding, the restoration of fluorescence intensity (from any of the labeled loops) mirrored cellular uptake that depleted FeEnt from solution. Fluorescence microscopic images also showed FeEnt transport, and demonstrated that ferric siderophore uptake uniformly occurs throughout outer membrane, including at the poles of the cells, despite the fact that TonB, its inner membrane transport partner, was not detectable at the poles. 相似文献
109.
D. T. Mourya P. D. Yadav A. Basu A. Shete D. Y. Patil D. Zawar T. D. Majumdar P. Kokate P. Sarkale C. G. Raut S. M. Jadhav 《Journal of virology》2014,88(6):3605-3609
During a survey in the year 2010, a novel phlebovirus was isolated from the Rousettus leschenaultii species of bats in western India. The virus was identified by electron microscopy from infected Vero E6 cells. Phylogenic analysis of the complete genome showed its close relation to severe fever with thrombocytopenia syndrome (SFTS) and Heartland viruses, which makes it imperative to further study its natural ecology and potential as a novel emerging zoonotic virus. 相似文献
110.