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Target Identification (target + identification)
Selected AbstractsChromatin immunoprecipitation-mediated target identification proved aquaporin 5 is regulated directly by estrogen in the uterusGENES TO CELLS, Issue 10 2006Mika Kobayashi Estrogens play a central role in the reproduction of vertebrates and affect a variety of biological processes. The major target molecules of estrogens are nuclear estrogen receptors (ERs), which have been studied extensively at the molecular level. In contrast, our knowledge of the genes that are regulated directly by ERs remains limited, especially at the level of the whole organism rather than cultured cells. In order to identify genes that are regulated directly by ERs in vivo, we used estrogen treated mouse uterus and performed chromatin immunoprecipitation. Sequence analysis of a precipitated DNA fragment enabled alignment with the mouse genomic sequence and revealed that the promoter region of the gene encoding aquaporin 5 (AQP5) was precipitated with antibody against ER,. Quantitative PCR and DNA microarray analyses confirmed that AQP5 is activated soon after administration of estrogen. In addition, the promoter region of AQP5 contained a functional estrogen response element that was activated directly by estrogen. Although several AQP genes are expressed in the uterus, only direct activation of AQP5 could be detected following treatment with estrogen. This chromatin immunopreciptation-mediated target identification may be applicable to the study of other transcription factor networks. [source] Development of a computerized assessment for visual maskingINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 2 2002Michael Foster Green Abstract Visual masking provides a highly informative means of assessing the earliest stages of visual processing. This procedure is frequently used in psychopathology research, most commonly in the study of schizophrenia. Deficits in visual masking tasks appear to reflect vulnerability factors in schizophrenia, as opposed to the symptoms of the illness. Visual masking procedures are typically conducted on a tachistoscope, which limits standardization across sites, as well as the number of variables that can be examined in a testing session. Although visual masking can be administered on a computer, most methods used so far have had poor temporal resolution and yielded a limited range of variables. We describe the development of a computerized visual masking battery. This battery includes a staircase procedure to establish an individual's threshold for target detection, and a relatively dense sampling of masking intervals. It includes both forward and backward masking trials for three different masking conditions that have been used previously in experimental psychopathology (target location, target identification with high-energy mask, and target identification with low-energy mask). Copyright © 2002 Whurr Publishers Ltd. [source] Evaluation of semi-autonomous convoy drivingJOURNAL OF FIELD ROBOTICS (FORMERLY JOURNAL OF ROBOTIC SYSTEMS), Issue 11-12 2008James Davis Autonomous mobility technologies may have applications to manned vehicle convoy operations,they have the ability to enhance both system performance and operator capability. This effort examines the potential impact of introducing semi-autonomous mobility [Convoy Active Safety Technologies (CAST)] into manned vehicles. Twelve civilians with experience driving military vehicles in convoy-type operations participated in this experiment. For the experiment, they were tasked with following a lead vehicle while completing a concurrent security task (scanning the local environment for targets). The control of the manned vehicle was varied between CAST and manual control at several different speed levels. Several objective speed and accuracy variables along with subjective operator assessment variables were examined for each task. The results support the potential benefits of incorporating semi-autonomous mobility technologies into manned vehicle convoy operations. The semi-autonomous mobility system was associated with significantly better performance in several aspects of operator situational awareness and convoy integrity, including enhanced target identification, improved maintenance of following distance, and improved performance for unanticipated stops. This experiment also highlighted a critical human factors issue associated with the incorporation of autonomy in real-world applications: participants felt that, overall, they outperformed the semi-autonomous system on the simulated convoy operation. The operator's perception of the system's performance could potentially affect his or her willingness to use the system in real-world applications. This experiment demonstrated that enhancements to overall system performance in real-world applications are achieved by considering both technological and human factors solutions. Published 2008 Wiley Periodicals, Inc., [source] Analysis of expressed sequence tags from a significant livestock pest, the stable fly (Stomoxys calcitrans), identifies transcripts with a putative role in chemosensation and sex determination,ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 3 2010Pia Untalan Olafson Abstract The stable fly, Stomoxys calcitrans L. (Diptera: Muscidae), is one of the most significant pests of livestock in the United States. The identification of targets for the development of novel control for this pest species, focusing on those molecules that play a role in successful feeding and reproduction, is critical to mitigating its impact on confined and rangeland livestock. A database was developed representing genes expressed at the immature and adult life stages of the stable fly, comprising data obtained from pyrosequencing both immature and adult stages and from small-scale sequencing of an antennal/maxillary palp,expressed sequence tag library. The full-length sequence and expression of 21 transcripts that may have a role in chemosensation is presented, including 13 odorant-binding proteins, 6 chemosensory proteins, and 2 odorant receptors. Transcripts with potential roles in sex determination and reproductive behaviors are identified, including evidence for the sex-specific expression of stable fly doublesex - and transformer -like transcripts. The current database will be a valuable tool for target identification and for comparative studies with other Diptera. Published 2010 Wiley Periodicals, Inc., [source] Investigation of the Substrate Specificity of Lacticin 481 Synthetase by Using Nonproteinogenic Amino AcidsCHEMBIOCHEM, Issue 5 2009Matthew R. Levengood Abstract One enzyme, many substrates. The substrate specificity of a lantibiotic biosynthetic enzyme, lacticin 481 synthetase, was probed by using synthetic prepeptides containing a variety of nonproteinogenic amino acids, including unnatural ,-amino acids, ,-amino acids, D -amino acids, and peptoids. Lantibiotics are peptide antimicrobial compounds that are characterized by the thioether-bridged amino acids lanthionine and methyllanthionine. For lacticin 481, these structures are installed in a two-step post-translational modification process by a bifunctional enzyme, lacticin 481 synthetase (LctM). LctM catalyzes the dehydration of Ser and Thr residues to generate dehydroalanine or dehydrobutyrine, respectively, and the subsequent intramolecular regio- and stereospecific Michael-type addition of cysteines onto the dehydroamino acids. In this study, semisynthetic substrates containing nonproteinogenic amino acids were prepared by expressed protein ligation and [3+2]-cycloaddition of azide and alkyne-functionalized peptides. LctM demonstrated broad substrate specificity toward substrates containing ,-amino acids, D -amino acids, and N -alkyl amino acids (peptoids) in certain regions of its peptide substrate. These findings showcase its promise for use in lantibiotic and peptide-engineering applications, whereby nonproteinogenic amino acids might impart improved stability or modulated biological activities. Furthermore, LctM permitted the incorporation of an alkyne-containing amino acid that can be utilized for the site-selective modification of mature lantibiotics and used in target identification. [source] Are MAP Kinases Drug Targets?CHEMMEDCHEM, Issue 8 2007but Difficult Ones Abstract Pharmaceutical companies are facing an increasing interest in new target identification and validation. In particular, extensive efforts are being made in the field of protein kinase inhibitors research and development, and the past ten years of effort in this field have altered our perception of the potential of kinases as drug targets. Therefore, in the drug discovery process, the selection of relevant, susceptible protein kinase targets combined with searches for leads and candidates have become a crucial approach. The success of recent launches of protein kinase inhibitors (Gleevec, Imatinib, Sutent, Iressa, Nexavar, Sprycel) gave another push to this field. Numerous other kinase inhibitors are currently undergoing clinical trials or clinical development. Some questions are nevertheless unanswered, mostly related to the great number of known kinases in the human genome, to their similarity with each other, to the existence of functionally redundant kinases for specific pathways, and also because the connection between particular pathways and diseases is not always clear. The review is leading the reader through a panoramic view of protein kinase inhibition with a major focus on MAPK, successful examples and clinical candidates. [source] | ||||||||||