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101.
Identification of neural progenitors in the adult mammalian eye 总被引:27,自引:0,他引:27
We have shown that the embryonic mammalian retina contains neural progenitors which display stem cell properties in vitro. Here we report the characterization of neural progenitors isolated from the adult mammalian eye. These quiescent cells, located in the pigmented ciliary bodies, proliferate in the presence of FGF2 and express the neuroectodermal marker nestin. The proliferating cells give rise to neural spheres and are multipotential; they express cell type-specific markers corresponding to neurons and glia. In addition, neural progenitors can generate secondary neural spheres, thus displaying potential to self-renew. The ciliary body-derived neural progenitors display retina-specific properties; the undifferentiated cells express Chx10, a retinal progenitor marker, and upon differentiation express markers corresponding to specific retinal cell types. Therefore, the pigmented ciliary body in the adult mammalian eye harbors neural progenitors that display stem cell properties and have the capacity to give rise to retinal neurons in vitro. 相似文献
102.
Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure 总被引:2,自引:0,他引:2
Hernandez JF Gagnon J Chiche L Nguyen TM Andrieu JP Heitz A Trinh Hong T Pham TT Le Nguyen D 《Biochemistry》2000,39(19):5722-5730
Three trypsin inhibitors (TIs), from the seeds of the squash Momordica cochinchinensis (MCo), have been isolated and purified using gel filtration, ion exchange chromatography, and reverse-phase HPLC. Their sequences could be determined only after proteolytic cleavages. In the case of MCoTI-I and -II, it was shown that their polypeptide backbones are cyclic, a structure that has never been described in squash TIs. They contain 34 amino acid residues with 3 disulfide bridges and measured molecular masses of 3453.0 and 3480.7, respectively. They are the largest known macrocyclic peptides containing disulfide bridges. Their sequences show strong homology to other squash TIs, suggesting a similar three-dimensional structure and an analogous mechanism of action. A model of MCoTI-II was constructed by analogy to the crystal structure of the complex between bovine trypsin and CMTI-I, indicating that the linker connecting the two termini is flexible and does not impose significant geometrical constraints. This flexibility allows an Asp-Gly peptide bond rearrangement to occur in this region, giving rise to two isoforms of MCoTI-II. Although the importance of cyclization is not clear, it might confer increased stability and resistance to proteolysis. A minor species, MCoTI-III, was also characterized as containing 30 amino acid residues with a molecular mass of 3379.6. This component possesses a linear backbone with a blocked N-terminus. MCoTIs represent interesting candidates for drug design, either by changing their specificity of inhibition or by using their structure as natural scaffolds bearing new binding activities. 相似文献
103.
A kinetic model of overflow metabolism in Saccharomyces cerevisiae was used for simulation of aerobic fed-batch cultivations. An inhibitory effect of ethanol on the maximum respiration of the yeast was observed in the experiments and included in the model. The model predicts respiration, biomass, and ethanol formation and the subsequent ethanol consumption, and was experimentally validated in fed-batch cultivations. Oscillating sugar feed with resulting oscillating carbon dioxide production did not influence the maximum respiration rate, which indicates that the pyruvate dehydrogenase complex is not involved as a bottleneck causing aerobic ethanol formation. 相似文献
104.
Phan Tu Quy Nguyen Khoa Hien Nguyen Chi Bao Doan Thanh Nhan Dang Van Khanh Nguyen Thi Ai Nhung Truong Quy Tung Nguyen Dinh Luyen Duong Tuan Quang 《Luminescence》2015,30(3):325-329
A new rhodamine–ethylenediamine–nitrothiourea conjugate (RT) was synthesized and its sensing property as a fluorescent chemodosimeter toward metal ions was explored in water media. Analytical results from absorption and fluorescence spectra revealed that the addition of Hg2+ ions to the aqueous solution of the chemodosimeter RT caused a distinct fluorescence OFF–ON response with a remarkable visual color change from colorless to pink; however, no clear spectral and color changes were observed from other metal ions including: Zn2+, Cu2+, Cd2+, Pb2+, Ag+, Fe2+, Cr3+, Co3+, Ni2+, Ca2+, Mg2+, K+ and Na+. The sensing results and the molecular structure suggested that a Hg2+‐induced a desulfurization reaction and cyclic guanylation of the thiourea moiety followed by ring‐opening of the rhodamine spirolactam in RT are responsible for a distinct fluorescence turn‐on signal, indicating that RT is a remarkably sensitive and selective chemodosimeter for Hg2+ ions in aqueous solution. Hg2+ within a concentration range from 0.1 to 25 μM can be determined using RT as a chemodosimeter and a detection limit of 0.04 μM is achieved. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
105.
A Comparison of ToxCast Test Results with In Vivo and Other In Vitro Endpoints for Neuro,Endocrine, and Developmental Toxicities: A Case Study Using Endosulfan and Methidathion
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106.
107.
Serena P. Koenig Alexandra Bornstein Karine Severe Elizabeth Fox Jessy G. Dévieux Patrice Severe Patrice Joseph Adias Marcelin Dgndy Alexandre Bright Ngoc Pham Pierre Cremieux Jean William Pape 《PloS one》2015,10(11)
Objective
We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin.Design
Cohort study of adult patients on ART.Setting
GHESKIO Clinic in Port-au-Prince, Haiti.Participants
4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008.Main Outcome Measure
Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin.Results
In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30–2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used.Conclusions
If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted. 相似文献108.
Cheryl Carson Pichai Raman Jennifer Tullai Lei Xu Martin Henault Emily Thomas Sarita Yeola Jianmin Lao Mark McPate J. Martin Verkuyl George Marsh Jason Sarber Adam Amaral Scott Bailey Danuta Lubicka Helen Pham Nicolette Miranda Jian Ding Hai-Ming Tang Haisong Ju Pamela Tranter Nan Ji Philipp Krastel Rishi K. Jain Andrew M. Schumacher Joseph J. Loureiro Elizabeth George Giuliano Berellini Nathan T. Ross Simon M. Bushell Gül Erdemli Jonathan M. Solomon 《PloS one》2015,10(6)
Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A. Genetic experiments demonstrate that TRPC4 expression is both necessary and sufficient for englerin A induced growth inhibition. Englerin A induces calcium influx and membrane depolarization in cells expressing high levels of TRPC4 or its close ortholog TRPC5. Electrophysiology experiments confirmed that englerin A is a TRPC4 agonist. Both the englerin A induced current and the englerin A induced growth inhibition can be blocked by the TRPC4/C5 inhibitor ML204. These experiments confirm that activation of TRPC4/C5 channels inhibits tumor cell line proliferation and confirms the TRPC4 target hypothesis generated by the cell line profiling. In selectivity assays englerin A weakly inhibits TRPA1, TRPV3/V4, and TRPM8 which suggests that englerin A may bind a common feature of TRP ion channels. In vivo experiments show that englerin A is lethal in rodents near doses needed to activate the TRPC4 channel. This toxicity suggests that englerin A itself is probably unsuitable for further drug development. However, since englerin A can be synthesized in the laboratory, it may be a useful chemical starting point to identify novel modulators of other TRP family channels. 相似文献
109.
Marcela Parra Xia Liu Steven C. Derrick Amy Yang Alvaro Molina-Cruz Carolina Barillas-Mury Hong Zheng Phuong Thao Pham Martha Sedegah Arnel Belmonte Dianne D. Litilit Thomas A. Waldmann Sanjai Kumar Sheldon L. Morris Liyanage P. Perera 《PloS one》2015,10(10)
Malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of RTS,S immunization (when used alone) on global malaria transmission. Here we describe the development and characterization of a novel modified vaccinia virus Ankara (MVA)–based malaria vaccine which co-expresses the Plasmodium yoelii circumsporozoite protein (CSP) and IL-15. Vaccination/challenge studies showed that C57BL/6 mice immunized with the MVA-CSP/IL15 vaccine were protected significantly better against a P. yoelii 17XNL sporozoite challenge than either mice immunized with an MVA vaccine expressing only CSP or naïve controls. Importantly, the levels of total anti-CSP IgG were elevated about 100-fold for the MVA-CSP/IL15 immunized group compared to mice immunized with the MVA-CSP construct that does not express IL-15. Among the IgG subtypes, the IL-15 expressing MVA-CSP vaccine induced levels of IgG1 (8 fold) and IgG2b (80 fold) higher than the MVA-CSP construct. The significantly enhanced humoral responses and protection detected after immunization with the MVA-CSP/IL15 vaccine suggest that this IL-15 expressing MVA construct could be considered in the development of future malaria immunization strategies. 相似文献
110.
A. Heckel M. Weiler A. Xia M. Ruetters M. Pham M. Bendszus S. Heiland P. Baeumer 《PloS one》2015,10(6)