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121.
122.
Spermatogenesis, involving multiple transit amplification divisions and meiosis, occurs within an enclosure formed by two somatic cells. As the cohort of germline cells divide and grow, the surface areas of the somatic cells expand maintaining a tight encapsulation throughout the developmental period. Correlation between the somatic cell growth and germline development is unclear. Here, we report standardization of a quantitative assay developed for estimating the somatic roles of target molecules on germline division and differentiation in Drosophila testis. Using the assay, we studied the somatic roles of phosphatidylinositol-3-kinase (PI3K). It revealed that the expression of PI3KDN is likely to facilitate the early germline development at all stages, and an increase in the somatic PI3K activity during the early stages delays the transition to spermatocyte stage. Together, these results suggest that somatic cell growth plays an important role in regulating the rate of germline development. 相似文献
123.
Hamaia SW Pugh N Raynal N Némoz B Stone R Gullberg D Bihan D Farndale RW 《The Journal of biological chemistry》2012,287(31):26019-26028
Integrins are well characterized cell surface receptors for extracellular matrix proteins. Mapping integrin-binding sites within the fibrillar collagens identified GFOGER as a high affinity site recognized by α2β1, but with lower affinity for α1β1. Here, to identify specific ligands for α1β1, we examined binding of the recombinant human α1 I domain, the rat pheochromocytoma cell line (PC12), and the rat glioma Rugli cell line to our collagen Toolkit II and III peptides using solid-phase and real-time label-free adhesion assays. We observed Mg(2+)-dependent binding of the α1 I domain to the peptides in the following rank order: III-7 (GLOGEN), II-28 (GFOGER), II-7 and II-8 (GLOGER), II-18 (GAOGER), III-4 (GROGER). PC12 cells showed a similar profile. Using antibody blockade, we confirmed that binding of PC12 cells to peptide III-7 was mediated by integrin α1β1. We also identified a new α1β1-binding activity within peptide II-27. The sequence GVOGEA bound weakly to PC12 cells and strongly to activated Rugli cells or to an activated α1 I domain, but not to the α2 I domain or to C2C12 cells expressing α2β1 or α11β1. Thus, GVOGEA is specific for α1β1. Although recognized by both α2β1 and α11β1, GLOGEN is a better ligand for α1β1 compared with GFOGER. Finally, using biosensor assays, we show that although GLOGEN is able to compete for the α1 I domain from collagen IV (IC(50) ~3 μm), GFOGER is much less potent (IC(50) ~90 μm), as shown previously. These data confirm the selectivity of GFOGER for α2β1 and establish GLOGEN as a high affinity site for α1β1. 相似文献
124.
Yanting Wang Michael S. Sharbaugh Andrew D. Althouse Suresh Mulukutla Samir Saba 《Indian pacing and electrophysiology journal》2019,19(1):4-6
Introduction
With the recent publication of the negative DANISH trial, the mortality benefit of the implantable cardioverter-defibrillator (ICD) has been put in question in patients with non-ischemic cardiomyopathy (NICM). Because a majority of patients in DANISH receive cardiac resynchronization therapy (CRT) devices, we investigated in the present study the survival of recipients of CRT pacemakers (CRT-P) versus CRT ICDs (CRT-D) in a cohort of older (≥75 years) NICM patients at our institution.Methods
A total of 135 NICM patients with CRT device were identified (42 with CRT-P and 93 with CRT-D) and were followed to the endpoint of all-cause mortality. Overall survival was compared between the CRT-P and CRT-D groups with adjustment for differences in baseline characteristics.Results
Over a median follow-up of 46 months from the time of CRT device implantation, there were 54 total deaths (40%): 14 in the CRT-P (33%) and 40 in the CRT-D (43%) groups. Overall, CRT-P recipients had similar unadjusted mortality compared to CRT-D recipients (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.56–1.93), and this remained unchanged after adjusting for unbalanced covariates (HR 0.95, 95% CI 0.47–1.89) including left ventricular ejection fraction, used of angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and the Charlson comorbidity index.Conclusion
Our data support that in older NICM patients with CRT devices, the addition of ICD therapy does not improve survival. 相似文献125.
Mineem Saliba Nick Ramalanjaona Sandrine Gulberti Isabelle Bertin-Jung Aline Thomas Samir Dahbi Chrystel Lopin-Bon Jean-Claude Jacquinet Christelle Breton Mohamed Ouzzine Sylvie Fournel-Gigleux 《The Journal of biological chemistry》2015,290(12):7658-7670
Among glycosaminoglycan (GAG) biosynthetic enzymes, the human β1,4-galactosyltransferase 7 (hβ4GalT7) is characterized by its unique capacity to take over xyloside derivatives linked to a hydrophobic aglycone as substrates and/or inhibitors. This glycosyltransferase is thus a prime target for the development of regulators of GAG synthesis in therapeutics. Here, we report the structure-guided design of hβ4GalT7 inhibitors. By combining molecular modeling, in vitro mutagenesis, and kinetic measurements, and in cellulo analysis of GAG anabolism and decorin glycosylation, we mapped the organization of the acceptor binding pocket, in complex with 4-methylumbelliferone-xylopyranoside as prototype substrate. We show that its organization is governed, on one side, by three tyrosine residues, Tyr194, Tyr196, and Tyr199, which create a hydrophobic environment and provide stacking interactions with both xylopyranoside and aglycone rings. On the opposite side, a hydrogen-bond network is established between the charged amino acids Asp228, Asp229, and Arg226, and the hydroxyl groups of xylose. We identified two key structural features, i.e. the strategic position of Tyr194 forming stacking interactions with the aglycone, and the hydrogen bond between the His195 nitrogen backbone and the carbonyl group of the coumarinyl molecule to develop a tight binder of hβ4GalT7. This led to the synthesis of 4-deoxy-4-fluoroxylose linked to 4-methylumbelliferone that inhibited hβ4GalT7 activity in vitro with a Ki 10 times lower than the Km value and efficiently impaired GAG synthesis in a cell assay. This study provides a valuable probe for the investigation of GAG biology and opens avenues toward the development of bioactive compounds to correct GAG synthesis disorders implicated in different types of malignancies. 相似文献
126.
Biological Trace Element Research - Instrumental neutron activation analysis (INAA) has been used to determine the concentration of some toxic chemical elements in a variety of aromatic plants... 相似文献
127.
Samir?F. El-Mashtoly Daniel Niedieker Dennis Petersen Sascha?D. Krauss Erik Freier Abdelouahid Maghnouj Axel Mosig Stephan Hahn Carsten K?tting Klaus Gerwert 《Biophysical journal》2014,106(9):1910-1920
Coherent anti-Stokes Raman scattering (CARS) is an emerging tool for label-free characterization of living cells. Here, unsupervised multivariate analysis of CARS datasets was used to visualize the subcellular compartments. In addition, a supervised learning algorithm based on the “random forest” ensemble learning method as a classifier, was trained with CARS spectra using immunofluorescence images as a reference. The supervised classifier was then used, to our knowledge for the first time, to automatically identify lipid droplets, nucleus, nucleoli, and endoplasmic reticulum in datasets that are not used for training. These four subcellular components were simultaneously and label-free monitored instead of using several fluorescent labels. These results open new avenues for label-free time-resolved investigation of subcellular components in different cells, especially cancer cells. 相似文献
128.
Racemic ethyl 2,3-dibromopropionate, commercially available at low price, is a key intermediate used in the synthesis of several heterocycle fragments, which are present in many biologically active compounds. Surprisingly, the enantiomers are not commercially available and have never been described in the literature. In this work, we undertook two different strategies to obtain these enantiomers, which are enantioselective synthesis and preparative HPLC enantioseparation of commercially available racemate on multigram scale. The first strategy has proved inadequate because racemization occurred during the synthesis (ee ≈ 9-50%). Conversely, the second strategy produced a very good enantioseparation of commercially available racemate (ee > 99.5% for both enantiomers) on multigram scale. 相似文献
129.
Mukhopadhyay P Horváth B Zsengellér Z Zielonka J Tanchian G Holovac E Kechrid M Patel V Stillman IE Parikh SM Joseph J Kalyanaraman B Pacher P 《Free radical biology & medicine》2012,52(2):497-506
Cisplatin is a widely used antineoplastic agent; however, its major limitation is the development of dose-dependent nephrotoxicity whose precise mechanisms are poorly understood. Here we show not only that mitochondrial dysfunction is a feature of cisplatin nephrotoxicity, but also that targeted delivery of superoxide dismutase mimetics to mitochondria largely prevents the renal effects of cisplatin. Cisplatin induced renal oxidative stress, deterioration of mitochondrial structure and function, an intense inflammatory response, histopathological injury, and renal dysfunction. A single systemic dose of mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently prevented cisplatin-induced renal dysfunction. Mito-CP also prevented mitochondrial injury and dysfunction, renal inflammation, and tubular injury and apoptosis. Despite being broadly renoprotective against cisplatin, Mito-CP did not diminish cisplatin's antineoplastic effect in a human bladder cancer cell line. Our results highlight the central role of mitochondrially generated oxidants in the pathogenesis of cisplatin nephrotoxicity. Because similar compounds seem to be safe in humans, mitochondrially targeted antioxidants may represent a novel therapeutic approach against cisplatin nephrotoxicity. 相似文献
130.
Omenn GS States DJ Adamski M Blackwell TW Menon R Hermjakob H Apweiler R Haab BB Simpson RJ Eddes JS Kapp EA Moritz RL Chan DW Rai AJ Admon A Aebersold R Eng J Hancock WS Hefta SA Meyer H Paik YK Yoo JS Ping P Pounds J Adkins J Qian X Wang R Wasinger V Wu CY Zhao X Zeng R Archakov A Tsugita A Beer I Pandey A Pisano M Andrews P Tammen H Speicher DW Hanash SM 《Proteomics》2005,5(13):3226-3245
HUPO initiated the Plasma Proteome Project (PPP) in 2002. Its pilot phase has (1) evaluated advantages and limitations of many depletion, fractionation, and MS technology platforms; (2) compared PPP reference specimens of human serum and EDTA, heparin, and citrate-anti-coagulated plasma; and (3) created a publicly-available knowledge base (www.bioinformatics.med.umich.edu/hupo/ppp; www.ebi.ac.uk/pride). Thirty-five participating laboratories in 13 countries submitted datasets. Working groups addressed (a) specimen stability and protein concentrations; (b) protein identifications from 18 MS/MS datasets; (c) independent analyses from raw MS-MS spectra; (d) search engine performance, subproteome analyses, and biological insights; (e) antibody arrays; and (f) direct MS/SELDI analyses. MS-MS datasets had 15 710 different International Protein Index (IPI) protein IDs; our integration algorithm applied to multiple matches of peptide sequences yielded 9504 IPI proteins identified with one or more peptides and 3020 proteins identified with two or more peptides (the Core Dataset). These proteins have been characterized with Gene Ontology, InterPro, Novartis Atlas, OMIM, and immunoassay-based concentration determinations. The database permits examination of many other subsets, such as 1274 proteins identified with three or more peptides. Reverse protein to DNA matching identified proteins for 118 previously unidentified ORFs. We recommend use of plasma instead of serum, with EDTA (or citrate) for anticoagulation. To improve resolution, sensitivity and reproducibility of peptide identifications and protein matches, we recommend combinations of depletion, fractionation, and MS/MS technologies, with explicit criteria for evaluation of spectra, use of search algorithms, and integration of homologous protein matches. This Special Issue of PROTEOMICS presents papers integral to the collaborative analysis plus many reports of supplementary work on various aspects of the PPP workplan. These PPP results on complexity, dynamic range, incomplete sampling, false-positive matches, and integration of diverse datasets for plasma and serum proteins lay a foundation for development and validation of circulating protein biomarkers in health and disease. 相似文献