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Powerful Strategy (powerful + strategy)
Selected AbstractsConditional ablation of neurones in transgenic miceDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Anthony R. Isles Abstract Conditional targeted ablation of specific cell populations in living transgenic animals is a very powerful strategy to determine cell functions in vivo. This approach would be of particular value to study the functions of distinct neuronal populations; however, the transgene of choice for conditional cell ablation studies in mice, the herpes simplex virus thymidine kinase gene, cannot be used to ablate neurones as its principal mode of action relies on cell proliferation. Here we report that expression of the E.coli nitroreductase gene (Ntr) and metabolism of the prodrug CB1954 (5-aziridin-1-yl-2-4-dinitrobenzamide) to its cytotoxic derivative can be used to conditionally and acutely ablate specific neuronal populations in vivo. As proof of principal, we have ablated olfactory and vomeronasal receptor neurones by expressing Ntr under the control of the olfactory marker protein (OMP) gene promoter. We demonstrate that following CB1954 administration, olfactory and vomeronasal receptor neurones expressing the transgene were selectively eliminated from the olfactory epithelium (OE), and projections to the olfactory bulb (OB) were lost. The functional efficacy of cell ablation was demonstrated using a highly sensitive behavioural test to show that ablated mice had lost the olfactory ability to discriminate distinct odors and were consequently rendered anosmic. Targeted expression of Ntr to specific neuronal populations using conventional transgenes, as described here, or by "knock-in" gene targeting using embryonic stem cells may be of significant value to address the functions of distinct neuronal populations in vivo. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 183,193, 2001 [source] The evolution of floral scent and insect chemical communicationECOLOGY LETTERS, Issue 5 2010Florian P. Schiestl Ecology Letters (2010) 13: 643,656 Abstract Plants have evolved a range of strategies to manipulate the behaviour of their insect partners. One powerful strategy is to produce signals that already have a role in the animals' own communication systems. To investigate to what extent the evolution of floral scents is correlated with chemical communication in insects, I analyse the occurrence, commonness, and evolutionary patterns of the 71 most common ,floral' volatile organic compounds (VOCs) in 96 plant families and 87 insect families. I found an overlap of 87% in VOCs produced by plants and insects. ,Floral' monoterpenes showed strong positive correlation in commonness between plants (both gymnosperms and angiosperms) and herbivores, whereas the commonness of ,floral' aromatics was positively correlated between angiosperms and both pollinators and herbivores. According to a multivariate regression analysis the commonness of ,floral' aromatics was best explained by their commonness in pollinators, whereas monoterpenes were best explained by herbivores. Among pollinator orders, aromatics were significantly more common in Lepidoptera than in Hymenoptera, whereas monoterpenes showed no difference among the two orders. Collectively, these patterns suggest that plants and insects converge in overall patterns of volatile production, both for attraction and defence. Monoterpenes seem to have evolved primarily for defence under selection by herbivores, whereas aromatics evolved signalling functions in angiosperms, primarily for pollinator attraction. [source] 2-D difference gel electrophoresis of the lung squamous cell carcinoma versus normal sera demonstrates consistent alterations in the levels of ten specific proteinsELECTROPHORESIS, Issue 23 2007Paul Dowling Dr. Abstract Most lung cancers are diagnosed too late for curative treatment to be possible, therefore early detection is crucial. Serum proteins are a rich source of biomarkers and have the potential to be used as diagnostic and prognostic indicators for lung cancer. In order to examine differences in serum levels of specific proteins associated with human lung squamous carcinoma, immunodepletion of albumin and five other high-abundant serum proteins followed by 2-D difference gel electrophoresis (DIGE) analysis and subsequent MS was used to generate a panel of proteins found to be differentially expressed between the cancer and normal samples. Proteins found to have increased abundance levels in squamous cell carcinoma sera compared to normal sera included apolipoprotein A-IV precursor, chain F; human complement component C3c, haptoglobin, serum amyloid A protein precursor and Ras-related protein Rab-7b. Proteins found to have lower abundance levels in squamous cell carcinoma sera compared to normal sera included alpha-2-HS glycoprotein, hemopexin precursor, proapolipoprotein, antithrombin III and SP40; 40. The data presented here demonstrate that high-abundant protein removal combined with 2-D DIGE is a powerful strategy for the discovery of potential biomarkers. The identification of lung cancer-specific biomarkers is crucial to early detection, which in turn could lead to a dramatic increase in survival rates. [source] Episodic memory,From brain to mindHIPPOCAMPUS, Issue 9 2006Janina Ferbinteanu Abstract Neuronal mechanisms of episodic memory, the conscious recollection of autobiographical events, are largely unknown because electrophysiological studies in humans are conducted only in exceptional circumstances. Unit recording studies in animals are thus crucial for understanding the neurophysiological substrate that enables people to remember their individual past. Two features of episodic memory,autonoetic consciousness, the self-aware ability to "travel through time", and one-trial learning, the acquisition of information in one occurrence of the event,raise important questions about the validity of animal models and the ability of unit recording studies to capture essential aspects of memory for episodes. We argue that autonoetic experience is a feature of human consciousness rather than an obligatory aspect of memory for episodes, and that episodic memory is reconstructive and thus its key features can be modeled in animal behavioral tasks that do not involve either autonoetic consciousness or one-trial learning. We propose that the most powerful strategy for investigating neurophysiological mechanisms of episodic memory entails recording unit activity in brain areas homologous to those required for episodic memory in humans (e.g., hippocampus and prefrontal cortex) as animals perform tasks with explicitly defined episodic-like aspects. Within this framework, empirical data suggest that the basic structure of episodic memory is a temporally extended representation that distinguishes the beginning from the end of an event. Future research is needed to fully understand how neural encodings of context, sequences of items/events, and goals are integrated within mnemonic representations of autobiographical events. © 2006 Wiley-Liss, Inc. [source] Applications of novel affinity cassette methods: use of peptide fusion handles for the purification of recombinant proteinsJOURNAL OF MOLECULAR RECOGNITION, Issue 6 2001Milton T W Hearn Abstract In this article, recent progress related to the use of different types of polypeptide fusion handles or ,tags' for the purification of recombinant proteins are critically discussed. In addition, novel aspects of the molecular cassette concept are elaborated, together with areas of potential application of these fundamental principles in molecular recognition. As evident from this review, the use of these concepts provides a powerful strategy for the high throughput isolation and purification of recombinant proteins and their derived domains, generated from functional genomic or zeomic studies, as part of the bioprocess technology leading to their commercial development, and in the study of molecular recognition phenomena per se. In addition, similar concepts can be exploited for high sensitivity analysis and detection, for the characterisation of protein bait/prey interactions at the molecular level, and for the immobilisation and directed orientation of proteins for use as biocatalysts/biosensors. Copyright © 2001 John Wiley & Sons, Ltd. [source] Single-Nucleotide Polymorphisms in Corticotropin Releasing Hormone Receptor 1 Gene (CRHR1) Are Associated With Quantitative Trait of Event-Related Potential and Alcohol DependenceALCOHOLISM, Issue 6 2010Andrew C. H. Chen Background:, Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models. The aim of the present study was to test the potential associations between single-nucleotide polymorphisms (SNPs) in the CRHR1 gene and the quantitative trait, P3 amplitude during the processing of visual target signals in an oddball paradigm, as well as alcohol dependence diagnosis. Methods:, We analyzed a sample from the Collaborative Study on the Genetics of Alcoholism (COGA) comprising 1049 Caucasian subjects from 209 families (including 472 alcohol-dependent individuals). Quantitative transmission disequilibrium test (QTDT) and family-based association test (FBAT) were used to test the association, and false discovery rate (FDR) was applied to correct for multiple comparisons. Results:, Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. Conclusions:, Our results suggest that CRHR1 may be involved in modulating the P3 component of the ERP during information processing and in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders. [source] Biological,synthetic hybrid block copolymers: Combining the best from two worldsJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 1 2005Harm-Anton Klok Abstract Although biopolymers and synthetic polymers share many common features, each of these two classes of materials is also characterized by a distinct and very specific set of advantages and disadvantages. Combining biopolymer elements with synthetic polymers into a single macromolecular conjugate is an interesting strategy for synergetically merging the properties of the individual components and overcoming some of their limitations. This article focuses on a special class of biological,synthetic hybrids that are obtained by site-selective conjugation of a protein or peptide and a synthetic polymer. The first part of the article gives an overview of the different liquid-phase and solid-phase techniques that have been developed for the synthesis of well-defined, that is, site-selectively conjugated, synthetic polymer,protein hybrids. In the second part, the properties and potential applications of these materials are discussed. The conjugation of biological and synthetic macromolecules allows the modulation of protein binding and recognition properties and is a powerful strategy for mediating the self-assembly of synthetic polymers. Synthetic polymer,protein hybrids are already used as medicines and show significant promise for bioanalytical applications and bioseparations. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1,17, 2005 [source] Water-Soluble Carbon Nanotubes by Redox Radical PolymerizationMACROMOLECULAR RAPID COMMUNICATIONS, Issue 15 2007Dimitrios Tasis Abstract Water-soluble single- and multi-walled carbon nanotubes (CNTs) were prepared by grafting polyacrylamide chains from the graphitic surface via ceric ion-induced redox radical polymerization. The reducing functionalities were covalently attached to the tubes by peroxide-assisted radical reaction. The results showed that polymer chains were grafted onto CNTs by the redox process. The redox radical polymerization initiated by carbon nanotube-bearing functionalities not only provides a powerful strategy for modifying the carbon nanostructures but also gives us the knowledge of their sidewall chemistry. [source] Citizen minds, citizen bodies: the citizenship experience and the government of mentally ill personsNURSING PHILOSOPHY, Issue 2 2010Amelie Perron RN PhD Abstract The concept of citizenship is becoming more and more prominent in specific fields, such as psychiatry/mental health, where it is constituted as a solution to the issues of exclusion, discrimination, and poverty often endured by the mentally ill. We argue that such discourse of citizenship represents a break in the history of psychiatry and constitutes a powerful strategy to counter the effects of equally powerful psychiatric labelling. However, we call into question the emancipatory promise of a citizenship agenda. Foucault's concept of governmentality is helpful in understanding the production of the citizen subject, its location within the ,art of government', as well as the ethical and political implications of citizenship in the context of mental health. [source] Statistical Tests for ClonalityBIOMETRICS, Issue 2 2007Colin B. Begg Summary Cancer investigators frequently conduct studies to examine tumor samples from pairs of apparently independent primary tumors with a view to determine whether they share a "clonal" origin. The genetic fingerprints of the tumors are compared using a panel of markers, often representing loss of heterozygosity (LOH) at distinct genetic loci. In this article we evaluate candidate significance tests for this purpose. The relevant information is derived from the observed correlation of the tumors with respect to the occurrence of LOH at individual loci, a phenomenon that can be evaluated using Fisher's exact test. Information is also available from the extent to which losses at the same locus occur on the same parental allele. Data from these combined sources of information can be evaluated using a simple adaptation of Fisher's exact test. The test statistic is the total number of loci at which concordant mutations occur on the same parental allele, with higher values providing more evidence in favor of a clonal origin for the two tumors. The test is shown to have high power for detecting clonality for plausible models of the alternative (clonal) hypothesis, and for reasonable numbers of informative loci, preferably located on distinct chromosomal arms. The method is illustrated using studies to identify clonality in contralateral breast cancer. Interpretation of the results of these tests requires caution due to simplifying assumptions regarding the possible variability in mutation probabilities between loci, and possible imbalances in the mutation probabilities between parental alleles. Nonetheless, we conclude that the method represents a simple, powerful strategy for distinguishing independent tumors from those of clonal origin. [source] The Application of 199Hg NMR and 199mHg Perturbed Angular Correlation (PAC) Spectroscopy to Define the Biological Chemistry of HgII: A Case Study with Designed Two- and Three-Stranded Coiled CoilsCHEMISTRY - A EUROPEAN JOURNAL, Issue 33 2007Olga Iranzo Dr. Abstract The use of de novo designed peptides is a powerful strategy to elucidate HgII,protein interactions and to gain insight into the chemistry of HgII in biological systems. Cysteine derivatives of the designed ,-helical peptides of the TRI family [Ac-G-(LaKbAcLdEeEfKg)4 -G-NH2] bind HgII at high pH values and at peptide/HgII ratios of 3:1 with an unusual trigonal thiolate coordination mode. The resulting HgII complexes are good water-soluble models for HgII binding to the protein MerR. We have carried out a parallel study using 199Hg NMR and 199mHg perturbed angular correlation (PAC) spectroscopy to characterize the distinct species that are generated under different pH conditions and peptide TRI,L9C/HgII ratios. These studies prove for the first time the formation of [Hg{(TRI,L9C)2 -(TRI,L9CH)}], a dithiolate,HgII complex in the hydrophobic interior of the three-stranded coiled coil (TRI,L9C)3. 199Hg NMR and 199mHg PAC data demonstrate that this dithiolate,HgII complex is different from the dithiolate [Hg(TRI,L9C)2], and that the presence of third ,-helix, containing a protonated cysteine, breaks the symmetry of the coordination environment present in the complex [Hg(TRI,L9C)2]. As the pH is raised, the deprotonation of this third cysteine generates the trigonal thiolate,HgII complex Hg(TRI,L9C)3, on a timescale that is slower than the NMR timescale (0.01,10,ms). The formation of the species [Hg{(TRI,L9C)2(TRI,L9CH)}] is the result of a compromise between the high affinity of HgII to form dithiolate complexes and the preference of the peptide to form a three-stranded coiled coil. [source] Effective Manipulation of the Electronic Effects and Its Influence on the Emission of 5-Substituted Tris(8-quinolinolate) Aluminum(III) ComplexesCHEMISTRY - A EUROPEAN JOURNAL, Issue 17 2006Victor A. Montes Abstract The unique electron-transport and emissive properties of tris(8-quinolinolate) aluminum(III) (Alq3) have resulted in extensive use of this material for small molecular organic light-emitting diode (OLED) fabrication. So far, efforts to prepare stable and easy-to-process red/green/blue (RGB)-emitting Alq3 derivatives have met with only a limited success. In this paper, we describe how the electronic nature of various substituents, projected via an arylethynyl or aryl spacer to the position of the highest HOMO density (C5), may be used for effective emission tuning to obtain blue-, green-, and red-emitting materials. The synthetic strategy consists of four different pathways for the attachment of electron-donating and electron-withdrawing aryl or arylethynyl substituents to the 5-position of the quinolinolate ring. Successful tuning of the emission color covering the whole visible spectrum (,=450,800 nm) was achieved. In addition, the photophysical properties of the luminophores were found to correlate with the Hammett constant of the respective substituents, providing a powerful strategy with which to predict the optical properties of new materials. We also demonstrate that the electronic nature of the substituent affects the emission properties of the resulting complex through effective modification of the HOMO levels of the quinolinolate ligand. [source] | |||||||||||||||||||