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Mechanistic Insights (mechanistic + insight)
Kinds of Mechanistic Insights Selected AbstractsEnantioselective Michael Addition of Aromatic Ketones to Nitroolefins Catalyzed by Bifunctional Thioureas and Mechanistic InsightEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2010Bai-Lin Li Abstract A highly enantioselective Michael reaction of aromatic ketones with nitroolefins was accomplished in the presence of a chiral bifunctional primary amine,thiourea catalyst and 4-nitrobenzoic acid as the co-catalyst; the corresponding adducts were obtained in excellent enantioselectivities (up to 99,%,ee) and yields (up to 98,%). The catalytic mechanism of the Michael reaction was confirmed through the ESI-MS detection of proposed reaction intermediates and the 1H NMR detection of hydrogen bonding between thiourea and the nitroolefins. DFT calculations showed that chiral moieties of the thiourea impacted the yields and enantioselectivities of the adducts remarkably, which corresponds to the observed experimental results. [source] Proton-Coupled Electron Transfer of Unsaturated Fatty Acids and Mechanistic Insight into LipoxygenaseHELVETICA CHIMICA ACTA, Issue 10 2006Shunichi Fukuzumi Abstract A proton-coupled electron transfer (PCET) process plays an important role in the initial step of lipoxygenases to produce lipid radicals which can be oxygenated by reaction with O2 to yield the hydroperoxides stereoselectively. The EPR spectroscopic detection of free lipid radicals and the oxygenated radicals (peroxyl radicals) together with the analysis of the EPR spectra has revealed the origin of the stereo- and regiochemistry of the reaction between O2 and linoleyl (=,(2Z)-10-carboxy-1-[(1Z)-hept-1-enyl]dec-2-enyl) radical in lipoxygenases. The direct determination of the absolute rates of H-atom-transfer reactions from a series of unsaturated fatty acids to the cumylperoxyl (=,(1-methyl-1-phenylethyl)dioxy) radical by use of time-resolved EPR at low temperatures together with detailed kinetic investigations on both photoinduced and thermal electron-transfer oxidation of unsaturated fatty acids provides the solid energetic basis for the postulated PCET process in lipoxygenases. A strong interaction between linoleic acid (=,(9Z,12Z)-octadeca-9,12-dienoic acid) and the reactive center of the lipoxygenases (FeIIIOH) is suggested to be involved to make a PCET process to occur efficiently, when an inner-sphere electron transfer from linoleic acid to the FeIII state is strongly coupled with the proton transfer to the OH group. [source] Mechanistic Insight into Enzymatic Glycosyl Transfer with Retention of Configuration through Analysis of Glycomimetic Inhibitors,ANGEWANDTE CHEMIE, Issue 7 2010James Strukturelle ,Valid"-ierung: Der Mechanismus des enzymkatalysierten konfigurationserhaltenden Glycosyltransfers gibt Rätsel auf, zumal aussagekräftige 3D-Strukturen ternärer Inhibitor-Enzym-Komplexe fehlen. Durch die Synthese und mehrdimensionale kinetische Analyse von Validoxylaminderivaten wurde die 3D-Struktur eines ternären Komplexes erhalten (siehe Bild; U=Uridyl), der Einblick in die Geometrie und das Donor-Akzeptor-Wechselspiel am Glycosyltransferzentrum gibt. [source] Mechanistic Insight into the Palladium-Catalyzed 1,4-Oxidation of 1,3-Dienes to 1,4-Dicarboxy-alk-2-enes,ANGEWANDTE CHEMIE, Issue 32 2009Martin Ein Nebenprodukt spielt mit: Die Dien-1,4-Oxidation überführt einen einfachen Kohlenwasserstoff in ein sehr nützliches Intermediat. Ein Komplex, der in,situ aus Palladium und einem bicyclischen Diels-Alder-Addukt , einem Nebenprodukt der Reaktion , gebildet wird, wurde als Grund für die hohe Reaktionsgeschwindigkeit und Diastereoselektivität bei der Oxidation von Cyclohexadien identifiziert (siehe Schema). [source] ChemInform Abstract: Rh(I)-Catalyzed Arylation of Heterocycles via C,H Bond Activation: Expanded Scope Through Mechanistic Insight.CHEMINFORM, Issue 29 2008Jared C. Lewis Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Mild and Selective Hydrozirconation of Amides to Aldehydes Using Cp2Zr(H)Cl: Scope and Mechanistic Insight.CHEMINFORM, Issue 30 2007Jared T. Spletstoser Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Ruthenium-Catalyzed Intermolecular Coupling Reactions of Arylamines with Ethylene and 1,3-Dienes: Mechanistic Insight on Hydroamination vs ortho-C,H Bond Activation.CHEMINFORM, Issue 42 2005Chae S. Yi Abstract For Abstract see ChemInform Abstract in Full Text. [source] Mechanistic Insights into Acetophenone Transfer Hydrogenation Catalyzed by Half-Sandwich Ruthenium(II) Complexes Containing 2-(Diphenylphosphanyl)aniline , A Combined Experimental and Theoretical StudyEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 28 2008Alessia Bacchi Abstract Several new half-sandwich ruthenium(II) complexes containing 2-(diphenyphosphanyl)aniline (PNH2) of formula {Ru[(,2P,N)PNH2](p -cymene)Cl}Y [Y = Cl (1a), PF6 (1b), BF4 (1c), BPh4 (1d), TfO (1e)] were synthesized and fully characterized both in solution (1H NMR and 31P{1H} NMR spectroscopy) and in the solid state (FTIR, X-ray analysis on single crystal). Complexes 1a and 1b are active precatalysts in the hydrogen transfer reaction of acetophenone, leading to tof values up to 4440 h,1. In comparison, the {Ru[(,2P,N)PNMe2](p -cymene)Cl}Cl complex leads to a tof value of 100 h,1 under the same catalytic conditions. The mechanism through which the precatalysts operate was deeply explored by high-resolution MS (ESI) and DFT/PCM studies. The results reveal that the complexes containing PNH2 operate through a bifunctional mechanism analogous to that proposed for diamines and amino alcohol ligands. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] (,6 -Arene)ruthenium(N-heterocyclic carbene) Complexes for the Chelation-Assisted Arylation and Deuteration of Arylpyridines: Catalytic Studies and Mechanistic InsightsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 7 2010Amparo Prades Abstract A series of (,6 -arene)ruthenium complexes have been tested in the arylation of arylpyridines. One (,6 - p -cymene)ruthenium(N-heterocyclic carbene) complex (labelled as 1 in the text) was found to be the most effective, being capable of arylating a wide set of substantially different arylpyridines. Complex 1 is also able to promote the regioselective deuteration of a series of arylated N-heterocycles, via a nitrogen-directed mechanism. Two of the deuterated amines were used to measure the kinetic isotope effect (KIE) in the arylation process. The detection of an inverse KIE, together with the observation that the CH activation process does not require the addition of a base, suggest that the rate-limiting step in the arylation process may be different to that of previously reported studies. [source] Mechanistic Insights into Copper(I)-Catalyzed Azide-Alkyne Cycloadditions using Continuous Flow ConditionsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 2-3 2010Michael Fuchs Abstract The copper-catalyzed azide-alkyne cycloaddition (CuAAC, "click chemistry") was studied employing copper-in-charcoal (Cu/C) and a variety of copper metal sources as "heterogeneous" catalysts. The type and pretreatment conditions of the different copper sources on the CuAAC were investigated. In addition, the effect of copper leaching from the catalyst over time and in dependence on the reaction mixture composition was studied by ICP-MS analysis in the continuous flow mode. These investigations confirm a "homogeneous" mechanism and suggest surface layer copper(I) oxide as the catalytically active species in CuAAC chemistry involving zerovalent copper metal. [source] A Basket Full of Mechanistic Insights into Pulmonary Vein Arrhythmogenicity: Reentry, Focal Activity, or Fibrillatory Conduction?JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2007STEPHAN WILLEMS M.D. No abstract is available for this article. [source] Mechanistic Insights into Direct Amide Bond Formation Catalyzed by Boronic Acids: Halogens as Lewis Bases,ANGEWANDTE CHEMIE, Issue 38 2010Dr. Tommaso Marcelli Wasser raus! DFT-Rechnungen sagen voraus, dass eine Wassereliminierung aus einem tetraedrischen Intermediat der geschwindigkeitsbestimmende Schritt der Titelreaktion ist. Diese Umwandlung ist den Rechnungen zufolge hoch stereoselektiv und liefert cis -Amide als die kinetischen Produkte (siehe Schema). Die überlegene Aktivität von ortho -Halogenphenylboronsäuren resultiert aus dem Lewis-basischen Charakter von Halogenatomen. [source] Stereoselective Ring Expansion of Vinyl Oxiranes: Mechanistic Insights and Natural Product Total Synthesis,ANGEWANDTE CHEMIE, Issue 9 2010Matthew Brichacek Spannungsabbau: Die erste breit anwendbare, katalytische und stereoselektive Vinyloxiran-Ringerweiterung wird beschrieben (siehe Schema; hfacac=Hexafluoracetylacetonat). Die Stereoselektivität wird durch etliche Reaktionsparameter beeinflusst, und kinetische Studien sprechen für die In-situ-Bildung einer katalytisch aktiven Spezies. Die Reaktion wurde in der asymmetrischen Totalsynthese von (+)-Goniothalesdiol eingesetzt. [source] Mechanistic Insights into the Formation of InP Quantum Dots,ANGEWANDTE CHEMIE, Issue 4 2010Peter Auf Molekülebene wurde der Bildungsmechanismus kolloidaler InP-Quantenpunkte (QDs) mithilfe von NMR-Spektroskopie untersucht. Anders als bei der Bildung von monodispersem PbSe und CdSe werden bei InP-Synthesen üblicherweise die molekularen Phosphorspezies nach der Keimbildung vollständig verbraucht, sodass die QDs ausschließlich durch Reifungsprozesse wachsen. Amine verhindern den Verbrauch der Vorstufen durch Solvatisierung (siehe Bild). [source] Mechanistic Insights into Water Activation in SAM Hydroxide Adenosyltransferase (duf-62)CHEMBIOCHEM, Issue 15 2009Hai Deng Dr. Breaking waters: The substrate analogue S -adenosyl- L -homocysteine (SAH) was co-crystallised with SAM hydroxide adenosyltransferase from Pyrococcus horikoshii. Of the two active site water molecules one appears to be structural and the other is a candidate for nucleophilic attack, to become the C5, adenosyl hydroxyl group. The data support a mechanism in which the Arg,Asp ion pair is important for positioning both water molecules. [source] ChemInform Abstract: Acceleration Effect of an Allylic Hydroxy Group on Ring-Closing Enyne Metathesis of Terminal Alkynes: Scope, Application, and Mechanistic Insights.CHEMINFORM, Issue 13 2009Tatsushi Imahori Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Dimethyl Sulfoxide Mediated Elimination Reactions in 3-Aryl 2,3-Dihalopropanoates: Scope and Mechanistic Insights.CHEMINFORM, Issue 50 2007Wei Li Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Palladium,NHC Complexes Do Catalyze the Diboration of Alkenes: Mechanistic Insights.CHEMINFORM, Issue 50 2007Vanesa Lillo Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Catalytic Intermolecular Amination of C,H Bonds: Method Development and Mechanistic Insights.CHEMINFORM, Issue 22 2007Kristin Williams Fiori Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Scope and Mechanistic Insights into the Use of Tetradecyl(trihexyl)phosphonium Bistriflimide: A Remarkably Selective Ionic Liquid Solvent for Substitution Reactions.CHEMINFORM, Issue 14 2007James McNulty Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Synthesis of (,)-Cubebol by Face-Selective Platinum-, Gold-, or Copper-Catalyzed Cycloisomerization: Evidence of Chirality Transfer and Mechanistic InsightsCHEMISTRY - A EUROPEAN JOURNAL, Issue 38 2009Charles Fehr Dr. Abstract We describe in detail a direct, stereoselective synthesis of (,)-cubebol based on a Pt-, Au-, or Cu-catalyzed cycloisomerization in which control of the configuration of the propargylic center is essential for the facial selectivity. In addition, we show that cycloisomerization reactions of enantioenriched propargyl pivalates occur with substantial chirality transfer. We confirm a mechanism by means of cyclization followed by an [1,2]-acyl migration for the Pt- and the Au-catalyzed cycloisomerization. So far, no evidence supports that the Cu-catalyzed cycloisomerization follows the same reaction course. [source] Stereocontrolled Intramolecular Aziridination of Glycals: Ready Access to Aminoglycosides and Mechanistic Insights from DFT StudiesCHEMISTRY - A EUROPEAN JOURNAL, Issue 5 2008Rujee Lorpitthaya Abstract Stereocontrolled intramolecular aziridination of the glycal-derived sulfamates offers a highly efficient strategy to divergently prepare aminoglycosides. Rhodium-catalyzed nitrogen-atom transfer to CC bonds formed semistable aziridines, which were subjected to various nucleophiles (C, O, S, and N) to give cyclic sulfamate-containing aminosugar derivatives selectively. The second nucleophilic displacement of sulfonyloxy moieties of [1,2,3]-oxathiazepane-2,2- dioxides allows straightforward access to aminoglycosides with selective ,- or ,-linkages. This approach is operationally simple, complements existing methods, and is a versatile protocol for the synthesis of polyfunctionalized amino sugars. In addition, the mechanism of the rhodium-catalyzed intramolecular aziridination of glycals and its ring-opening reaction was extensively studied by using DFT calculations. [source] Scope and Mechanistic Insights into the Use of Tetradecyl(trihexyl)phosphonium Bistriflimide: A Remarkably Selective Ionic Liquid Solvent for Substitution ReactionsCHEMISTRY - A EUROPEAN JOURNAL, Issue 36 2006James McNulty Abstract A survey of substitution reactions conducted in a phosphonium bistriflimide ionic liquid is presented. The results demonstrate high selectivity favoring substitution over typically competitive elimination and solvolytic processes even when challenging secondary and tertiary electrophiles are employed. The first reports of Kornblum substitution reactions in an ionic liquid are described that proceed with very high chemoselectivity in favor of nitro over nitroso products and elimination side products. The structure,reactivity study indicates that these reactions proceed through a narrow spectrum of pathways ranging from straight SN2 to a preassociation pathway along a saddle point that approaches the SN1 limit. The barrier to the formation of dissociated carbocations is attributed to the structural features of this ionic liquid that favor intervention of the associated nucleophile over dissociation, also preventing cross over to E1 processes. The lack of any basic entity in the phosphonium bistriflimide ionic liquid appears to prevent any potential base-mediated elimination reactions, which makes this a highly selective medium for use in general substitution reactions. [source] Mechanistic Insights into Selectivity Control for Heterogeneous Olefin Oxidation: Styrene Oxidation on Au(111)CHEMISTRY - AN ASIAN JOURNAL, Issue 1 2010Abstract We demonstrate that intermolecular interactions, controlled by both oxygen and styrene coverage, alter reaction selectivity for styrene oxidation on oxygen-covered Au(111). Several partial oxidation products are formed,styrene oxide, acetophenone, benzoic acid, benzeneacetic acid, and phenylketene,in competition with combustion. The maximum ratio of the yields of styrene oxide to the total CO2 produced is obtained for the maximum styrene coverage for the first two layers (0.28,ML) adsorbed on Au(111) precovered with 0.2,ML of O. Furthermore, our reactivity and infrared studies support a mechanism whereby styrene oxidation proceeds via two oxametallacycle intermediates which, under oxygen-lean conditions, lead to the formation of styrene oxide, acetophenone, and phenylketene. Benzoate, identified on the basis of infrared reflection absorption spectroscopy, is converted into benzoic acid during temperature-programmed reaction. These results demonstrate the ability to tune the epoxidation selectivity using reactant coverages and provide important mechanistic insight into styrene oxidation reactions. [source] Fitness versus fatness: Moving beyond weight loss in nonalcoholic fatty liver disease,,HEPATOLOGY, Issue 1 2010Nathan A. Johnson The rapid emergence of nonalcoholic fatty liver disease (NAFLD) as a cause of both liver-related morbidity and mortality and cardiometabolic risk has led to the search for effective lifestyle strategies to reduce liver fat. Lifestyle intervention comprising dietary restriction in conjunction with increased physical activity has shown clear hepatic benefits when weight loss approximating 3%-10% of body weight is achieved. Yet, the poor sustainability of weight loss challenges the current therapeutic focus on body weight and highlights the need for alternative strategies for NAFLD management. Epidemiologic data show an independent relationship between liver fat, physical activity, and fitness, and a growing body of longitudinal research demonstrates that increased physical activity participation per se significantly reduces hepatic steatosis and serum aminotransferases in individuals with NAFLD, independent of weight loss. Mechanistic insights to explain this interaction are outlined, and recommendations for the implementation of lifestyle intervention involving physical activity are discussed. In light of the often poor sustainability of weight loss strategies, and the viability of physical activity therapy, clinicians should assess physical fitness and physical activity habits, educate patients on the benefits of fitness outside of weight loss, and focus on behavior change which promotes physical activity adoption. (HEPATOLOGY 2010) [source] Mechanistic insights into oxidosqualene cyclizations through homology modelingJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2003Gasch, Tanja Schulz Abstract 2,3-Oxidosqualene cyclases (OSC) are key enzymes in sterol biosynthesis. They catalyze the stereoselective cyclization and skeletal rearrangement of (3S)-2,3-oxidosqualene to lanosterol in mammals and fungi and to cycloartenol in algae and higher plants. Sequence information and proposed mechanism of 2,3-oxidosqualene cyclases are closely related to those of squalene-hopene cyclases (SHC), which represent functional analogs of OSCs in bacteria. SHCs catalyze the cationic cyclization cascade converting the linear triterpene squalene to fused ring compounds called hopanoids. High stereoselectivity and precision of the skeletal rearrangements has aroused the interest of researchers for nearly half a century, and valuable data on studying mechanistic details in the complex enzyme-catalyzed cyclization cascade has been collected. Today, interest in cyclases is still unbroken, because OSCs became targets for the development of antifungal and hypocholesterolemic drugs. However, due to the large size and membrane-bound nature of OSCs, three-dimensional structural information is still not available, thus preventing a complete understanding of the atomic details of the catalytic mechanism. In this work, we discuss results gained from homology modeling of human OSC based on structural information of SHC from Alicyclobacillus acidocaldarius and propose a structural model of human OSC. The model is in accordance with previously performed experimental studies with mechanism-based suicide inhibitors and mutagenesis experiments with altered activity and product specificity. Structural insight should strongly stimulate structure-based design of antifungal or cholesterol-lowering drugs. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 741,753, 2003 [source] Signal Processing during Developmental Multicellular PatterningBIOTECHNOLOGY PROGRESS, Issue 1 2008Claudiu A. Giurumescu Developing design strategies for tissue engineering and regenerative medicine is limited by our nascent understanding of how cell populations "self-organize" into multicellular structures on synthetic scaffolds. Mechanistic insights can be gleaned from the quantitative analysis of biomolecular signals that drive multicellular patterning during the natural processes of embryonic and adult development. This review describes three critical layers of signal processing that govern multicellular patterning: spatiotemporal presentation of extracellular cues, intracellular signaling networks that mediate crosstalk among extracellular cues, and finally, intranuclear signal integration at the level of transcriptional regulation. At every level in this hierarchy, the quantitative attributes of signals have a profound impact on patterning. We discuss how experiments and mathematical models are being used to uncover these quantitative features and their impact on multicellular phenotype. [source] Basolateral junctions are sufficient to suppress epithelial invasion during Drosophila oogenesisDEVELOPMENTAL DYNAMICS, Issue 2 2007Przemyslaw Szafranski Abstract Epithelial junctions play crucial roles during metazoan evolution and development by facilitating tissue formation, maintenance, and function. Little is known about the role of distinct types of junctions in controlling epithelial transformations leading to invasion of neighboring tissues. Discovering the key junction complexes that control these processes and how they function may also provide mechanistic insight into carcinoma cell invasion. Here, using the Drosophila ovary as a model, we show that four proteins of the basolateral junction (BLJ), Fasciclin-2, Neuroglian, Discs-large, and Lethal-giant-larvae, but not proteins of other epithelial junctions, directly suppress epithelial tumorigenesis and invasion. Remarkably, the expression pattern of Fasciclin-2 predicts which cells will invade. We compared the apicobasal polarity of BLJ tumor cells to border cells (BCs), an epithelium-derived cluster that normally migrates during mid-oogenesis. Both tumor cells and BCs differentiate a lateralized membrane pattern that is necessary but not sufficient for invasion. Independent of lateralization, derepression of motility pathways is also necessary, as indicated by a strong linear correlation between faster BC migration and an increased incidence of tumor invasion. However, without membrane lateralization, derepression of motility pathways is also not sufficient for invasion. Our results demonstrate that spatiotemporal patterns of basolateral junction activity directly suppress epithelial invasion by organizing the cooperative activity of distinct polarity and motility pathways. Developmental Dynamics 236:364,373, 2007. © 2006 Wiley-Liss, Inc. [source] Variation in leaf functional trait values within and across individuals and species: an example from a Costa Rican dry forestFUNCTIONAL ECOLOGY, Issue 1 2010Catherine M. Hulshof Summary 1.,Patterns of species co-existence and species diversity in plant communities remain an important research area despite over a century of intensive scrutiny. To provide mechanistic insight into the rules governing plant species co-existence and diversity, plant community ecologists are increasingly quantifying functional trait values for the species found in a wide range of communities. 2.,Despite the promise of a quantitative functional trait approach to plant community ecology, we suggest that, along with examining trait variation across species, an assessment of trait variation within species should also be a key component of a trait-based approach to community ecology. Variability within and between individuals and populations is likely widespread due to plastic responses to highly localized abiotic and biotic interactions. 3.,In this study, we quantify leaf trait variation within and across ten co-existing tree species in a dry tropical forest in Costa Rica to ask: (i) whether the majority of trait variation is located between species, within species, within individuals or within the leaves themselves; (ii) whether trait values collected using standardized methods correlate with those collected using unstandardized methods; and (iii) to what extent can we differentiate plant species on the basis of their traits? 4.,We find that the majority of variation in traits was often explained by between species differences; however, between leaflet trait variation was very high for compound-leaved species. We also show that many species are difficult to reliably differentiate on the basis of functional traits even when sampling many individuals. 5.,We suggest an ideal sample size of at least 10, and ideally 20, individuals be used when calculating mean trait values for individual species for entire communities, though even at large sample sizes, it remains unclear if community level trait values will allow comparisons on a larger geographic scale or if species traits are generally similar across scales. It will thus be critical to account for intraspecific variation by comparing species mean trait values across space in multiple microclimatic environments within local communities and along environmental gradients. Further, quantifying trait variability due to plasticity and inheritance will provide a better understanding of the underlying patterns and drivers of trait variation as well as the application of functional traits in outlining mechanisms of species co-existence. [source] Phospho-proteomic immune analysis by flow cytometry: from mechanism to translational medicine at the single-cell levelIMMUNOLOGICAL REVIEWS, Issue 1 2006Omar D. Perez Summary:, Understanding a molecular basis for cellular function is a common goal of biomedicine. The complex and dynamic cellular processes underlying physiological processes become subtly or grossly perturbed in human disease. A primary objective is to demystify this complexity by creating and establishing relevant model systems to study important aspects of human disease. Although significant technological advancements over the last decade in both genomic and proteomic arenas have enabled progress, accessing the complexity of cellular interactions that occur in vivo has been a difficult arena in which to make progress. Moreover, there are extensive challenges in translating research tools to clinical applications. Flow cytometry, over the course of the last 40 years, has revolutionized the field of immunology, in both the basic science and clinical settings, as well as having been instrumental to new and exciting areas of discovery such as stem cell biology. Multiparameter machinery and systems exist now to access the heterogeneity of cellular subsets and enable phenotypic characterization and functional assays to be performed on material from both animal models and humans. This review focuses primarily on the development and application of using activation-state readouts of intracellular activity for phospho-epitopes. We present recent work on how a flow cytometric platform is used to obtain mechanistic insight into cellular processes as well as highlight the clinical applications that our laboratory has explored. Furthermore, this review discusses the challenges faced with processing high-content multidimensional and multivariate data sets. Flow cytometry, as a platform that is well situated in both the research and clinical settings, can contribute to drug discovery as well as having utility for both biomarker and patient-stratification. [source] | |||||||||||||||||||||||||||||||