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131.
Jen C. Wang Hemant Sindhu Chi Chen Ajay Kundra Muhammad I. Kafeel Ching Wong Stephen Lichter 《PloS one》2015,10(3)
Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis. 相似文献
132.
Procedures are described for the solubilization of adenosine uptake sites in guinea pig and rat brain tissue. Using [3H]nitrobenzylthioinosine [( 3H]NBI) the solubilized site is characterized both kinetically and pharmacologically. The binding is dependent on protein concentration and is saturable, reversible, specific, and high affinity in nature. The KD and Bmax of guinea pig extracts are 0.13 +/- 0.02 nM and 133 +/- 18 fmol/mg protein, respectively, with linear Scatchard plots obtained routinely. Similar kinetic parameters are observed in rat brain. Adenosine uptake inhibitors are the most potent inhibitors of [3H]NBI binding with the following order of potency, dilazep greater than hexobendine greater than dipyridamole. Adenosine receptor ligands are much less potent inhibitors of binding, and caffeine is without effect. The solubilized adenosine uptake site is, therefore, shown to have virtually identical properties to the native membrane site. The binding of the adenosine A1 receptor agonist [3H]cyclohexyladenosine [( 3H]CHA) to the solubilized brain extract was also studied and compared with that of [3H]NBI. In contrast to the [3H]NBI binding site [3H]CHA binds to two apparent populations of adenosine receptor, a high-affinity site with a KD of 0.32 +/- 0.06 nM and a Bmax of 105 +/- 30 fmol/mg protein and a lower-affinity site with a KD of 5.50 +/- 0.52 nM and Bmax of 300 +/- 55 fmol/mg protein. The pharmacology of the [3H]CHA binding site is consistent with that of the adenosine receptor and quite distinct from that of the uptake [( 3H]NBI binding) site. Therefore, we show that the adenosine uptake site can be solubilized and that it retains both its binding and pharmacologic properties in the solubilized state. 相似文献
133.
The cheese whey, a by-product of dairy industry proved to be an attractive substrate for production of β-carotene. The β-carotene production from Mucor azygosporus MTCC 414 by using deproteinized waste whey filtrate under submerged fermentation was investigated. Various fermentation variables, such as lactose content in whey, initial pH, production temperature, incubation time, and carbon and nitrogen sources played significant role on β-carotene production. Maximum β-carotene production (385 μg/g dcw) was obtained with the whey (pH 5.5) containing 3.5% (w/v) lactose supplemented with soluble starch at (1.0%, w/v) at 30°C after a 5 days incubation. Moreover, unlike other microorganisms which utilize pre-hydrolyzed lactose, this Mucor azygosporus MTCC 414 was found to be capable of utilizing unhydrolyzed lactose present in the whey. 相似文献
134.
Ajay Pradhan Hazem Khalaf Scott A. Ochsner Rajini Sreenivasan Jarno Koskinen Marie Karlsson Jesper Karlsson Neil J. McKenna L��szl�� Orb��n Per-Erik Olsson 《The Journal of biological chemistry》2012,287(45):37926-37938
Testis differentiation in zebrafish involves juvenile ovary to testis transformation initiated by an apoptotic wave. The molecular regulation of this transformation process is not fully understood. NF-κB is activated at an early stage of development and has been shown to interact with steroidogenic factor-1 in mammals, leading to the suppression of anti-Müllerian hormone (Amh) gene expression. Because steroidogenic factor-1 and Amh are important for proper testis development, NF-κB-mediated induction of anti-apoptotic genes could, therefore, also play a role in zebrafish gonad differentiation. The aim of this study was to examine the potential role of NF-κB in zebrafish gonad differentiation. Exposure of juvenile zebrafish to heat-killed Escherichia coli activated the NF-κB pathways and resulted in an increased ratio of females from 30 to 85%. Microarray and quantitative real-time-PCR analysis of gonads showed elevated expression of NF-κB-regulated genes. To confirm the involvement of NF-κB-induced anti-apoptotic effects, zebrafish were treated with sodium deoxycholate, a known inducer of NF-κB or NF-κB activation inhibitor (NAI). Sodium deoxycholate treatment mimicked the effect of heat-killed bacteria and resulted in an increased proportion of females from 25 to 45%, whereas the inhibition of NF-κB using NAI resulted in a decrease in females from 45 to 20%. This study provides proof for an essential role of NF-κB in gonadal differentiation of zebrafish and represents an important step toward the complete understanding of the complicated process of sex differentiation in this species and possibly other cyprinid teleosts as well. 相似文献
135.
Enrico Munari Alcides Chaux Ajay M. Vaghasia Diana Taheri Sarah Karram Stephania M. Bezerra Nilda Gonzalez Roibon William G. Nelson Srinivasan Yegnasubramanian George J. Netto Michael C. Haffner 《PloS one》2016,11(1)
Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment. 相似文献
136.
137.
Sivakoti Ramana Ashis K. Biswas Amar B. Singh Ajay Narendra K. Ahirwar Ravulapalli D. Prasad 《International journal of phytoremediation》2015,17(7):709-715
The present study was conducted to evaluate the ability of a high biomass producing, drought tolerant succulent plant Mauritius hemp (Furcraea gigantea Vent.) for its tolerance to different levels of Cr (0, 25, 50, 100 and 200 mg Cr kg soil?1) and its potential for phytoremediation purposes. Based on the data on inhibition of the growth of plants with Cr, tolerance index and grade of growth inhibition, it was observed that the plant could tolerate up to 50 mg Cr kg ?1 soil. Absorption of Cr from soil to plant and its translocation into plant tissues were discussed in terms of bio concentration factor (BCF), transfer factor (TF), and translocation efficiency (TE%). Cr was mainly accumulated in the roots and exclusion of Cr was found to be the principal physiological tolerance mechanism followed by a marked increase in proline, ascorbic acid, total free amino acids in the leaf tissue and malic acid in the rhizosphere samples to counter Cr stress. Based on the tissue concentration of Cr (< 300 μg g?1 in the leaves and TF<1), it was concluded that, Furcraea gigantea could not be considered a hyperaccumulator and therefore unsuitable for phytoextraction of Cr. Nevertheless, Furcraea gigantea could be a suitable candidate for phytostablization of Cr contaminated soils. 相似文献
138.
Active compound oleandrin extracted from Nerium indicum (Lal Kaner) leaf has potent piscicidal activity. The piscicidal activity of oleandrin on freshwater fish C. punctatus was both time and dose dependent. Exposure to sub-lethal doses of oleandrin for 24hr and 96hr to fish caused significant alteration in the level of total protein, total free amino acid, nucleic acid, glycogen, pyruvate, lactate and enzyme protease, phosphatases, alanine aminotransferase, aspartate aminotransferase and acetylcholinesterase activity in liver and muscle tissues. The alterations in all the above biochemical parameters were also significantly time and dose dependent. The results show a significant recovery in all the above biochemical parameters, in both liver and muscle tissues of fish after the 7th day of the withdrawal of treatment. Toxicity persistence test of oleandrin on juvenile Labeo rohita shows that fish seed of common culturing carp can be released into rearing ponds after three days of oleandrin treatment. It supports the view that the oleandrin is safer and may be useful substitute of other piscicides for removing the unwanted freshwater fishes from aquaculture ponds. 相似文献
139.
Olivia Twu Natalia de Miguel Gila Lustig Grant C. Stevens Ajay A. Vashisht James A. Wohlschlegel Patricia J. Johnson 《PLoS pathogens》2013,9(7)
Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Here, we use a combination of methodologies including cell fractionation, immunofluorescence and electron microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to examine pathogenic properties of T. vaginalis. We have found that T.vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-specific proteins. We demonstrate that T. vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. In addition to establishing that parasite exosomes act to modulate host∶parasite interactions, these studies are the first to reveal a potential role for exosomes in promoting parasite∶parasite communication and host cell colonization. 相似文献
140.
K. B. Hebbar J. Rane S. Ramana N. R. Panwar S. Ajay A. Subba Rao P. V. V. Prasad 《Plant and Soil》2014,378(1-2):99-112