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21.
Manju Shri Arti Rai Pankaj Kumar Verma Prashant Misra Sonali Dubey Smita Kumar Sikha Verma Neelam Gautam Rudra Deo Tripathi Prabodh Kumar Trivedi Debasis Chakrabarty 《Protoplasma》2013,250(2):631-636
Agrobacterium-mediated transformation of indica rice varieties has been quite difficult as these are recalcitrant to in vitro responses. In the present study, we established a high-efficiency Agrobacterium tumefaciens-mediated transformation system of rice (Oryza sativa L. ssp. indica) cv. IR-64, Lalat, and IET-4786. Agrobacterium strain EHA-101 harboring binary vector pIG121-Hm, containing a gene encoding for β-glucuronidase (GUS) and hygromycin resistance, was used in the transformation experiments. Manipulation of different concentrations of acetosyringone, days of co-culture period, bacterial suspension of different optical densities (ODs), and the concentrations of l-cysteine in liquid followed by solid co-culture medium was done for establishing the protocol. Among the different co-culture periods, 5 days of co-culture with bacterial cells (OD600 nm?=?0.5–0.8) promoted the highest frequency of transformation (83.04 %) in medium containing l-cysteine (400 mg l?1). Putative transformed plants were analyzed for the presence of a transgene through genomic PCR and GUS histochemical analyses. Our results also suggest that different cultural conditions and the addition of l-cysteine in the co-culture medium improve the Agrobacterium-mediated transformation frequencies from an average of 12.82 % to 33.33 % in different indica rice cultivars. 相似文献
22.
Anamitra Ghosh Hariharan Saminathan Arthi Kanthasamy Vellareddy Anantharam Huajun Jin Gautam Sondarva Dilshan S. Harischandra Ziqing Qian Ajay Rana Anumantha G. Kanthasamy 《The Journal of biological chemistry》2013,288(30):21955-21971
Parkinson disease (PD) is a chronic neurodegenerative disease characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra. The pathophysiological mechanisms underlying PD remain unclear. Pin1, a major peptidyl-prolyl isomerase, has recently been associated with certain diseases. Notably, Ryo et al. (Ryo, A., Togo, T., Nakai, T., Hirai, A., Nishi, M., Yamaguchi, A., Suzuki, K., Hirayasu, Y., Kobayashi, H., Perrem, K., Liou, Y. C., and Aoki, I. (2006) J. Biol. Chem. 281, 4117–4125) implicated Pin1 in PD pathology. Therefore, we sought to systematically characterize the role of Pin1 in PD using cell culture and animal models. To our surprise we observed a dramatic up-regulation of Pin1 mRNA and protein levels in dopaminergic MN9D neuronal cells treated with the parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP+) as well as in the substantia nigra of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Notably, a marked expression of Pin1 was also observed in the substantia nigra of human PD brains along with a high co-localization of Pin1 within dopaminergic neurons. In functional studies, siRNA-mediated knockdown of Pin1 almost completely prevented MPP+-induced caspase-3 activation and DNA fragmentation, indicating that Pin1 plays a proapoptotic role. Interestingly, multiple pharmacological Pin1 inhibitors, including juglone, attenuated MPP+-induced Pin1 up-regulation, α-synuclein aggregation, caspase-3 activation, and cell death. Furthermore, juglone treatment in the MPTP mouse model of PD suppressed Pin1 levels and improved locomotor deficits, dopamine depletion, and nigral dopaminergic neuronal loss. Collectively, our findings demonstrate for the first time that Pin1 is up-regulated in PD and has a pathophysiological role in the nigrostriatal dopaminergic system and suggest that modulation of Pin1 levels may be a useful translational therapeutic strategy in PD. 相似文献
23.
Hua Jiang Yueqing Xie Andrew Burnette John Roach Steven L. Giardina Toby T. Hecht Stephen P. Creekmore Gautam Mitra Jianwei Zhu 《Applied microbiology and biotechnology》2013,97(2):621-632
Immunotoxins are rationally designed cancer targeting and killing agents. Disulfide stabilized antibody Fv portion—toxin conjugates (dsFv-toxin) are third generation immunotoxins containing only the antibody fragment variable portions and a toxin fused to the VH or VL. Pseudomonas exotoxin fragment (PE-38) is a commonly used toxin in immunotoxin clinical trials. dsFv-toxin purification was previously published, but the recovery was not satisfactory. This report describes the development of a cGMP production process of the dsFv-toxin that incorporated a novel purification method. The method has been successfully applied to the clinical manufacturing of two dsFv-PE38 immunotoxins, MR1-1 targeting EGFRvIII and HA22 targeting CD22. The two subunits, VL and VH PE-38 were expressed separately in Escherichia coli using recombinant technology. Following cell lysis, inclusion bodies were isolated from the biomass harvested from fermentation in animal source component-free media. The dsFv-toxin was formed after denaturation and refolding, and subsequently purified to homogeneity through ammonium sulfate precipitation, hydrophobic interaction and ion-exchange chromatography steps. It was shown, in a direct comparison experiment using MR1-1 as model protein, that the recovery from the new purification method was improved three times over that from previously published method. The improved recovery was also demonstrated during the clinical production of two dsFv-PE38 immunotoxins—MR1-1 and HA22. 相似文献
24.
Shailendra Kumar Dhar Dwivedi Krishnananda Samanta Manisha Yadav Amit Kumar Jana Abhishek Kumar Singh Bandana Chakravarti Sankalan Mondal Rituraj Konwar Arun Kumar Trivedi Naibedya Chattopadhyay Sabyasachi Sanyal Gautam Panda 《Bioorganic & medicinal chemistry letters》2013,23(24):6816-6821
Two series of new benzoxazepines substituted with different alkyl amino ethyl chains were synthesized comprising synthetic steps of inter and intramolecular Mitsunobu reaction, lithium aluminium hydride (LAH) reduction, debenzylation, bimolecular nucleophilic substitution (SN2) reaction. The present study investigates the effect of a tyrosine-based benzoxazepine derivative in human breast cancer cells MCF-7 and MDA-MB-231 and in breast cancer animal model. The anti-proliferative effect of 15a on MCF-7 cells was associated with G1 cell-cycle arrest. This G1 growth arrest was followed by apoptosis as 15a dose dependently increased phosphatidylserine exposure, PARP cleavage and DNA fragmentation that are hallmarks of apoptotic cell death. Interestingly, 15a activated components of both intrinsic and extrinsic pathways of apoptosis characterized by activation of caspase-8 and -9, mitochondrial membrane depolarization and increase in Bax/Bcl2 ratio. However, use of selective caspase inhibitors revealed that the caspase-8-dependent pathway is the major contributor to 15a-induced apoptosis. Compound 15a also significantly reduced the growth of MCF-7 xenograft tumors in athymic nude mice. Together, 15a could serve as a base for the development of a new group of effective breast cancer therapeutics. 相似文献
25.
26.
Fill Factor Losses in Cu2ZnSn(SxSe1−x)4 Solar Cells: Insights from Physical and Electrical Characterization of Devices and Exfoliated Films 下载免费PDF全文
Kong Fai Tai Oki Gunawan Masaru Kuwahara Shi Chen Subodh Gautam Mhaisalkar Cheng Hon Alfred Huan David B. Mitzi 《Liver Transplantation》2016,6(3)
Besides the open circuit voltage (VOC) deficit, fill factor (FF) is the second most significant parameter deficit for earth‐abundant kesterite solar cell technology. Here, various pathways for FF loss are discussed, with focus on the series resistance issue and its various contributing factors. Electrical and physical characterizations of the full range of bandgap (Eg = 1.0–1.5 eV) Cu2ZnSn(SxSe1?x)4 (CZTSSe) devices, as well as bare and exfoliated films with various S/(S + Se) ratios, are performed. High intensity Suns‐VOC measurement indicates a nonohmic junction developing in high bandgap CZTSSe. Grazing incidence X‐ray diffraction, Raman mapping, field emission scanning electron microscopy, and X‐ray photoelectron spectroscopy indicate the formation of Sn(S,Se)2, Mo(S,Se)2, and Zn(S,Se) at the high bandgap CZTSSe/Mo interface, contributing to the increased series resistance (RS) and nonohmic back contact characteristics. This study offers some clues as to why the record‐CZTSSe solar cells occur within a bandgap range centered around 1.15 eV and offers some direction for further optimization. 相似文献
27.
28.
Andrew S. Krueger Christian Munck Gautam Dantas George M. Church James Galagan Joseph Lehár Morten O. A. Sommer 《PloS one》2016,11(1)
Flux balance analysis (FBA) is an increasingly useful approach for modeling the behavior of metabolic systems. However, standard FBA modeling of genetic knockouts cannot predict drug combination synergies observed between serial metabolic targets, even though such synergies give rise to some of the most widely used antibiotic treatments. Here we extend FBA modeling to simulate responses to chemical inhibitors at varying concentrations, by diverting enzymatic flux to a waste reaction. This flux diversion yields very similar qualitative predictions to prior methods for single target activity. However, we find very different predictions for combinations, where flux diversion, which mimics the kinetics of competitive metabolic inhibitors, can explain serial target synergies between metabolic enzyme inhibitors that we confirmed in Escherichia coli cultures. FBA flux diversion opens the possibility for more accurate genome-scale predictions of drug synergies, which can be used to suggest treatments for infections and other diseases. 相似文献
29.
Suhrid Banskota Jaya Gautam Sushil C. Regmi Pallavi Gurung Myo-Hyeon Park Seung Joo Kim Tae-gyu Nam Byeong-Seon Jeong Jung-Ae Kim 《PloS one》2016,11(1)
5-Hydroxytryptamine (5-HT) induces proliferation of cancer cells and vascular cells. In addition to 5-HT production by several cancer cells including gastrointestinal and breast cancer, a significant level of 5-HT is released from activated platelets in the thrombotic environment of tumors, suggesting that inhibition of 5-HT signaling may constitute a new target for antiangiogenic anticancer drug discovery. In the current study we clearly demonstrate that 5-HT-induced angiogenesis was mediated through the 5-HT1 receptor-linked Gβγ/Src/PI3K pathway, but not through the MAPK/ERK/p38 pathway. In addition, 5-HT induced production of NADPH oxidase (NOX)-derived reactive oxygen species (ROS). In an effort to develop new molecularly targeted anticancer agents against 5-HT action in tumor growth, we demonstrate that BJ-1108, a derivative of 6-amino-2,4,5-trimethylpyridin-3-ol, significantly inhibited 5-HT-induced angiogenesis. In addition, BJ-1108 induced a significant reduction in the size and weight of excised tumors in breast cancer cell-inoculated CAM assay, showing proportionate suppression of tumor growth along with inhibition of angiogenesis. In human umbilical vein endothelial cells (HUVECs), BJ-1108 significantly suppressed 5-HT-induced ROS generation and phosphorylation of PI3K/Akt but not of Src. Unlike NOX inhibitors, BJ-1108, which showed better antioxidant activity than vitamin C, barely suppressed superoxide anion induced by mevalonate or geranylgeranyl pyrophosphate which directly activates NOX without help from other signaling molecules in HUVECs, implying that the anti-angiogenic action of BJ-1108 was not mediated through direct action on NOX activation, or free radical scavenging activity. In conclusion, BJ-1108 inhibited 5-HT-induced angiogenesis through PI3K/NOX signaling but not through Src, ERK, or p38. 相似文献
30.
Sachiko?OhdeEmail author Emily?McFadden Gautam?A.?Deshpande Hiroshi?Yokomichi Osamu?Takahashi Tsuguya?Fukui Rafael?Perera Zentaro?Yamagata 《BMC endocrine disorders》2016,16(1):65