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Structural Similarity (structural + similarity)
Selected AbstractsEstimation of Compartmental Half-lives of Organic Compounds , Structural Similarity versus EPI-SuiteMOLECULAR INFORMATICS, Issue 4 2007Ralph Kühne Abstract A k Nearest Neighbors (KNN) approach is developed to extrapolate from existing semiquantitative compartmental half-lives of organic compounds to respective data for untested substances. It is based on the evaluation of structural similarity through atom-centered fragments (ACFs). For the model development and leave-one-out cross-validation, a set of 293 compounds with reference half-lives for the four compartments air, water, soil, and sediment was taken from literature. Comparative analysis of the model performance with results based on EPI-Suite predictions of degradation rates due to indirect photolysis, biodegradation, and hydrolysis demonstrates the superiority of the new approach to predict compartmental half-lives. The latter are needed as input information for modeling the multimedia fate and life-time of organic compounds. The discussion includes an analysis of the problems associated with converting process-specific loss rates into compartmental half-lives. [source] ChemInform Abstract: Structural Similarity and Its Surprises: Endothelin Receptor Antagonists , Process Research and Development Report.CHEMINFORM, Issue 23 2001R. Jansen Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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] Negation , An Overview of Typological ResearchLINGUISTICS & LANGUAGE COMPASS (ELECTRONIC), Issue 5 2007Matti Miestamo This article is an overview of the current state of typological research on negation. Structures expressing standard negation , the negation of declarative verbal main clauses , can be classified on the basis of the status of the negative marker, or on the basis of the structure of the negative clause as a whole. Structural similarities and differences (symmetry and asymmetry) between negatives and affirmatives can be observed and classified into different types which can then be offered functional explanations. Negative strategies used in imperatives, existentials and nonverbal clauses often differ from standard negation; these differences are exemplified and discussed. The interaction between negative indefinite pronouns and standard negation shows interesting cross-linguistic variation in terms of whether the latter co-occurs with the indefinite and whether the indefinite is inherently negative. Some cross-linguistic observations on diachronic developments and on the interaction between negation and modality and negation and focus are also briefly discussed. [source] Comparative analysis of changes in gene expression due to RNA melting activities of translation initiation factor IF1 and a cold shock protein of the CspA familyGENES TO CELLS, Issue 11 2009Sangita Phadtare In Escherichia coli, temperature downshift elicits cold shock response, which is characterized by induction of cold shock proteins. CspA, the major cold shock protein of E. coli, helps cells to acclimatize to low temperature by melting the secondary structures in nucleic acids and acting as a transcription antiterminator. CspA and its homologues contain the cold shock domain and belong to the oligomer binding protein family, which also includes S1 domain proteins such as IF1. Structural similarity between IF1 and CspA homologues suggested a functional overlap between these proteins. Indeed IF1 can melt secondary structures in RNA and acts as transcription antiterminator in vivo and in vitro. Here, we show that in spite of having these critical activities, IF1 does not complement cold-sensitivity of a csp quadruple deletion strain. DNA microarray analysis shows that overproduction of IF1 and Csp leads to changes in expression of different sets of genes. Importantly, several genes which were previously shown to require Csp proteins for their expression at low temperature did not respond to IF1. Moreover, in vitro, we show that a transcription terminator responsive to Csp does not respond to IF1. Our results suggest that Csp proteins and IF1 have different sets of target genes as they may be suppressing the function of different types of transcription termination elements in specific genes. [source] Autoxidation of linalyl acetate, the main component of lavender oil, creates potent contact allergensCONTACT DERMATITIS, Issue 1 2008Maria Sköld Background:, Fragrances are among the most common causes of allergic contact dermatitis. We have in previous studies shown that linalool, present in lavender oil, autoxidizes on air exposure, forming allergenic oxidation products. Oxidized linalool was found to be a frequent cause of contact allergy in a patch test study on consecutive dermatitis patients. Linalyl acetate, the main component of lavender oil is commonly used as a fragrance chemical in scented products. Because of structural similarities, linalyl acetate should also be susceptible to oxidation on air exposure, forming similar oxidation products as linalool. Objective:, The aim of the present study was to investigate the autoxidation of linalyl acetate and the influence of oxidation on its sensitizing potency. Methods:, Analyses were performed using gas chromatography, nuclear magnetic resonance spectrometry and mass spectrometry. Sensitizing potencies of compounds were determined using the local lymph node assay (LLNA) in mice. Results:, Analyses showed that the content of linalyl acetate decreased over time on air exposure and other compounds were formed. Hydroperoxides, an epoxide and an alcohol were identified as oxidation products from linalyl acetate. In the LLNA, linalyl acetate of high purity showed a weak sensitizing potency (EC3 25%). Autoxidation increased the sensitizing potency of linalyl acetate, and a 10 weeks oxidized sample gave an EC3 value of 3.6%. As for linalool, the hydroperoxides were shown to be the oxidation products with the highest sensitizing potency. Conclusion:, It is concluded that autoxidation of the weakly allergenic linalyl acetate leads to formation of allergenic oxidation products. [source] Opening up the Solution Space: The Role of Analogical Thinking for Breakthrough Product InnovationCREATIVITY AND INNOVATION MANAGEMENT, Issue 2 2008Oliver Gassmann The purpose of this paper is to investigate the approach of analogical thinking for product innovation. We collected data on projects from four engineering firms where analogical thinking was successfully applied for the development of breakthrough innovations. Results show that abstracting the problem by in-depth technical and contextual analysis is pivotal when searching for analogical solutions. Furthermore, the chances of identifying highly novel analogous solutions are increased if the problem is abstracted to the level of its structural similarities to other settings. We also found that the identification of structural similarities is supported when firms not only rely on the cognitive abilities of the individual but also employ an active search based on abstract search terms. Based on these insights, we propose a process model for the development of product innovations by means of analogical thinking. [source] Bioelectrochemical Characterization of Horseradish and Soybean PeroxidasesELECTROANALYSIS, Issue 21 2009Marco Frasconi Abstract Heme peroxidase are ubiquitous enzymes catalyzing the oxidation of a broad range of substrates by hydrogen peroxide. In this paper the bioelectrochemical characterization of horseradish peroxidase (HRP) and soybean peroxidase (SBP), belonging to class III of the plant peroxidase superfamily, was studied. The homogeneous reactions between peroxidases and some common redox mediators in the presence of hydrogen peroxide have been carried out by cyclic voltammetry. The electrochemical characterization of the reactions involving enzyme, substrate and mediators concentrations allowed us to calculate the kinetic parameters for the substrate,enzyme reaction (KMS) and for the redox mediator,enzyme reaction (KMM). A full characterization of the direct electron transfer kinetic parameters between the electrode and enzyme active site was also performed by opportunely modeling data obtained from cyclic voltammetry and square wave voltammetry experiments. The experimental data obtained with immobilized peroxidases show enhanced direct electron transfer and excellent electrocatalytical performance for H2O2. Despite the structural similarities and common catalytic cycle, HRP and SBP exhibit differences in their substrate affinity and catalytic efficiency. Basing on our results, it can be concluded that peroxidase from soybean represents an interesting alternative to the classical and largely employed one obtained from horseradish as biorecognition element of electrochemical mediated biosensors. [source] Emergence of a subfamily of xylanase inhibitors within glycoside hydrolase family 18FEBS JOURNAL, Issue 7 2005Anne Durand The xylanase inhibitor protein I (XIP-I), recently identified in wheat, inhibits xylanases belonging to glycoside hydrolase families 10 (GH10) and 11 (GH11). Sequence and structural similarities indicate that XIP-I is related to chitinases of family GH18, despite its lack of enzymatic activity. Here we report the identification and biochemical characterization of a XIP-type inhibitor from rice. Despite its initial classification as a chitinase, the rice inhibitor does not exhibit chitinolytic activity but shows specificities towards fungal GH11 xylanases similar to that of its wheat counterpart. This, together, with an analysis of approximately 150 plant members of glycosidase family GH18 provides compelling evidence that xylanase inhibitors are largely represented in this family, and that this novel function has recently emerged based on a common scaffold. The plurifunctionality of GH18 members has major implications for genomic annotations and predicted gene function. This study provides new information which will lead to a better understanding of the biological significance of a number of GH18 ,inactivated' chitinases. [source] Rubber tree (Hevea brasiliensis) trunk phloem necrosis: aetiological investigations failed to confirm any biotic causal agentFOREST PATHOLOGY, Issue 1 2007F. Pellegrin Summary Trunk phloem necrosis (TPN) is currently a main constraint in rubber (Hevea brasiliensis) plantations. The apparent spread of the disease, from tree to tree along the planting line, strongly supported the implication of a pathogen that could be transmitted mechanically via the tapping knife. In order to detect a causal agent of the disease, studies focusing on characterization of the known mechanically transmitted pathogens (e.g. viroids, cryptic viruses or phytoplasma) were initiated. RNA strands of low molecular weight (200,400 and >500 bp) displaying structural similarities with viroids and viral dsRNAs were observed in various tested samples. However, attempts to show the potential role of these RNA molecules in the spread of the disease failed. First of all, there was no significant or reproducible correlation between the health status of the rubber trees sampled and these RNA molecules. Moreover, no sequence homology with known pathogens could be found when randomly amplified cDNA fragments isolated from trees presenting the disease symptoms were sequenced. In conclusion, the aetiological investigations, in order to show the presence of a pathogen responsible of the TPN disease, were non-conclusive, which tends to disprove the hypothesis of a biotic causal agent. [source] Gemcitabine-induced severe pulmonary toxicityFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2004Fabrice Barlési Abstract Gemcitabine is a relatively new deoxycytidine analog (2,,2,-difluorodeoxycytidine) with structural similarities to cytosine arabinoside (Ara-C). Activity of gemcitabine is demonstrated in the treatment of many solid tumors, like pancreas, ovarian and nonsmall cell lung cancer (NSCLC). Although gemcitabine is considered as a drug with a good safety profile, cases of gemcitabine-induced severe pulmonary toxicity (GISPT) were reported as for Ara-C. We performed a systematic review of reported cases on the GISPT. Twenty-nine clinical trials especially interesting NSCLC patients (21) and 21 reported cases recording 40 patients were analyzed. The incidence of the GISPT varies from 0 to 5%. The clinical presentation is a subacute clinical syndrome and is frequently nonspecific. The predominant radiographic pattern on chest X-ray are reticulo-nodular interstitial infiltrates. It was postulated that the physio-pathological mechanism of the GISPT was an inflammatory reaction of the alveolar capillary wall cytokine-mediated, which created an abnormal permeability of its membrane. After the differential diagnosis were ruled out, the discontinuation of the drug and the early initiation of steroids and diuretics are the most frequently performed treatments. Under these conditions, the outcome was favorable in a delay of few days generally for a majority of patients but 20% of patients died. Some risk factors, as a previous pulmonary disease or a previous thoracic irradiation, for the occurrence of the GISPT were proposed. GISPT is rare but sometimes fatal. Its a necessity to increase awareness about it to enhanced an early and suitable management of patients developing such a toxicity after gemcitabine administration. [source] Roles of the novel interleukin-12-associated cytokine, interleukin-23, in the regulation of T-cell-mediated immunityHEPATOLOGY RESEARCH, Issue 2007Masanori Matsui Interleukin (IL)-12 is a heterodimeric proinflammatory cytokine formed by a 35-kDa light chain (p35) and a 40-kDa heavy chain (p40). This cytokine is a key regulator of cell-mediated immunity, and therefore should have therapeutic potential in infectious diseases and tumors. Recently, a novel IL-12-associated cytokine, IL-23 has been discovered. IL-23 is also a heterodimer that consists of the p40 subunit of IL-12 and a novel subunit, p19. Several studies have shown that IL-23 possesses immunoadjuvant activity against tumor and infectious diseases as well as IL-12. On the other hand, there is increasing evidence that IL-12 and IL-23 have discrete roles in the regulation of T-cell-mediated immunity despite their structural similarities. IL-12 leads to the development ofinterferon-,-producing T-helper type 1 (Th1) cells, whereas IL-23 amplifies and stabilizes a new CD4+ T-cell subset, Th17 producing IL-17. The IL-23/Th17 axis rather than the IL-12/Th1 axis contributes to several immune-mediated inflammatory autoimmune diseases. Furthermore, IL-23/IL-17 promotes tumor incidence and growth. Therefore, IL-23 and Th17 are attracting considerable attention at present. Taken together, these findings suggest that IL-23 may be an immunoadjuvant against infectious diseases and tumors, and a viable target for the treatment of inflammatory diseases. [source] The protein family of glucose transport facilitators: It's not only about glucose after allIUBMB LIFE, Issue 5 2010Robert Augustin Abstract The protein family of facilitative glucose transporters comprises 14 isoforms that share common structural features such as 12 transmembrane domains, N- and C-termini facing the cytoplasm of the cell, and a N-glycosylation side either within the first or fifth extracellular loop. Based on their sequence homology, three classes can be distinguished: class I includes GLUT1-4 and GLUT14, class II the "odd transporters" GLUT5, 7, 9, 11, and class III the "even transporters" GLUT6, 8, 10, 12 and the proton driven myoinositol transporter HMIT (or GLUT13). With the cloning and characterization of the more recent class II and III isoforms, it became apparent that despite their structural similarities, the different isoforms not only show a distinct tissue-specific expression pattern but also show distinct characteristics such as alternative splicing, specific (sub)cellular localization, and affinities for a spectrum of substrates. This review summarizes the current understanding of the physiological role for the various transport facilitators based on human genetically inherited disorders or single-nucleotide polymorphisms and knockout mice models. The emphasis of the review will be on the potential functional role of the more recent isoforms. © 2010 IUBMB IUBMB Life, 62(5): 315,333, 2010 [source] Cholesterol and Kir channelsIUBMB LIFE, Issue 8 2009Irena Levitan Abstract To date, most of the major types of Kir channels, Kir2s, Kir3s, Kir4s, and Kir6s, have been found to partition into cholesterol-rich membrane domains and/or to be regulated by changes in the level of membrane cholesterol. Surprisingly, however, in spite of the structural similarities between different Kirs, effects of cholesterol on different types of Kir channels vary from cholesterol-induced decrease in the current density (Kir2 channels) to the loss of channel activity by cholesterol depletion (Kir4 channels) and loss of channel coupling by different mediators (Kir3 and Kir6 channels). Recently, we have gained initial insights into the mechanisms responsible for cholesterol-induced suppression Kir2 channels, but mechanisms underlying cholesterol sensitivity of other Kir channels are mostly unknown. The goal of this review is to present a summary of the current knowledge of the distinct effects of cholesterol on different types of Kir channels in vitro and in vivo. © 2009 IUBMB IUBMB Life 61(8): 781,790, 2009 [source] In Vitro Selection of Self-Interacting Transmembrane Segments--Membrane Proteins Approached from a Different PerspectiveIUBMB LIFE, Issue 3 2002Dieter Langosch Abstract The principles underlying the folding of integral membrane proteins are uncovered in an increasingly detailed way. Experimental determination of high-resolution structures followed by analysis of packing reveal structural similarities as well as differences to soluble globular proteins. At the same time, protein/protein interactions at the level of membrane-embedded domains have been investigated for different model proteins. More recently, self-interacting transmembrane helices have been selected from combinatorial libraries in vitro to study the mechanistic basis of protein/protein interaction in membranes in a systematic way. With an emphasis on the latter approach, this review discusses insights emerging from an integrated view on the recent advances. [source] Antibody structure, instability, and formulationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2007Wei Wang Abstract The number of therapeutic monoclonal antibody in development has increased tremendously over the last several years and this trend continues. At present there are more than 23 approved antibodies on the US market and an estimated 200 or more are in development. Although antibodies share certain structural similarities, development of commercially viable antibody pharmaceuticals has not been straightforward because of their unique and somewhat unpredictable solution behavior. This article reviews the structure and function of antibodies and the mechanisms of physical and chemical instabilities. Various aspects of formulation development have been examined to identify the critical attributes for the stabilization of antibodies. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1,26, 2007 [source] Correlations and predictions of solvent effects on reactivity: some limitations of multi-parameter equations and comparisons with similarity models based on one solvent parameterJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 6 2006T. William Bentley Abstract Three recent publications on multi-parameter correlations of solvent effects on solvolytic reactivity are re-examined, by considering ,similarity' and/or ,analogy'. Systematic errors due to compensation effects and to comparisons between dissimilar processes are found. Models for solvent nucleophilicity involving dissimilar spectroscopic processes (e.g. , or B parameters) give insensitive measures of low nucleophilicity. From qualitative considerations based on structural similarities, it is predicted that the sensitivities to changes to solvent polarity for solvolyses of chloroalkanes should be in the order: 1-adamantyl (3),>,2-methyl-2-adamantyl (1),>,t -butyl (2). The predictions are confirmed quantitatively by simple linear free-energy relationships and similarity models, involving correlations with YCl (based on solvolyses of 1-chloroadamantane) or ET(30) (based on solvatochromism). Multi-parameter correlations, indicating that solvolyses of 1 show a low sensitivity to both solvent polarity and electrophilicity, and also a negative sensitivity to solvent nucleophilicity, are shown to be unreliable. Large errors are also evident in recent KOMPH2 calculations. Conclusions are supported by comparing several multi-parameter treatments of solvolyses of 4-methoxyneophyl tosylate, for which there is a reliable set of kinetic data and a generally accepted mechanism. Copyright © 2006 John Wiley & Sons, Ltd. [source] Reported symptoms to peanut between 4 and 8 years among children sensitized to peanut and birch pollen , results from the BAMSE birth cohortALLERGY, Issue 2 2010A. Asarnoj To cite this article: Asarnoj A, Östblom E, Ahlstedt S, Hedlin G, Lilja G, van Hage M, Wickman M. Reported symptoms to peanut between 4 and 8 years among children sensitized to peanut and birch pollen , results from the BAMSE birth cohort. Allergy 2010; 65: 213,219. Abstract Background:, Specific IgE tests are sometimes difficult to interpret due to structural similarities between certain food and pollen allergens. This may be the reason why concomitant sensitization to peanut and birch pollen is frequently seen. The aim of this study was to investigate reported symptoms to peanut- and birch pollen in relation to sensitization. Methods:, The data originate from 1928 children in the BAMSE birth cohort. Background factors and clinical parameters were obtained and the levels of IgE antibodies to peanut and birch pollen measured at 4 and 8 years. Results:, IgE antibodies to peanut were found in 5.5% and 7.4% of the children at 4 and 8 years, respectively. The IgE antibody levels to peanut were higher in children sensitized to peanut but not birch than in children sensitized to peanut and birch among both 4- and 8-year-olds (P = 0.093 and P = 0.003, respectively). Eight-year-olds sensitized to peanut but not birch, more often reported symptoms to peanut than children sensitized to both peanut and birch pollen (76%vs 46%, P = 0.002). The probability of reported symptoms to peanut increased significantly with increasing IgE levels to peanut, especially in 8-year-olds not sensitized to birch. Conclusions:, Children sensitized to both peanut and birch pollen are less likely to report symptoms to peanut than children sensitized to peanut but not to birch pollen at 8 years. This is likely due to cross reactions between birch pollen and peanut and can explain the high sensitization rate to peanut in areas where birch trees are common. [source] Medicinal chemistry approaches for the treatment and prevention of Alzheimer's diseaseMEDICINAL RESEARCH REVIEWS, Issue 1 2003S.O. Bachurin Abstract Alzheimer's disease (AD) is the most common form of dementia, which is characterised by progressive deterioration of memory and higher cortical functions that ultimately result in total degradation of intellectual and mental activities. Modern strategies in the search of new therapeutic approaches are based on the morphological and biochemical characteristics of AD, and focused on following directions: agents that compensate the hypofunction of cholinergic system, agents that interfere with the metabolism of beta-amyloid peptide, agents that protect nerve cells from toxic metabolites formed in neurodegenerative processes, agents that activate other neurotransmitter systems that indirectly compensate for the deficit of cholinergic functions, agents that affect the process of the formation of neurofibrillary tangles, anti-inflammatory agents that prevent the negative response of nerve cells to the pathological process. The goal of the present review is the validation and an analysis from the point of view of medicinal chemistry of the principles of the directed search of drugs for the treatment and prevention of AD and related neurodegenerative disorders. It is based on systematization of the data on biochemical and structural similarities in the interaction between physiologically active compounds and their biological targets related to the development of such pathologies. The main emphasis is on cholinomimetic, anti-amyloid and anti-metabolic agents, using the data that were published during the last 3 to 4 years, as well as the results of clinical trials presented on corresponding websites. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 1, 48,88, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10026 [source] Low-molecular-weight post-translationally modified microcinsMOLECULAR MICROBIOLOGY, Issue 6 2007Konstantin Severinov Summary Microcins are a class of ribosomally synthesized antibacterial peptides produced by Enterobacteriaceae and active against closely related bacterial species. While some microcins are active as unmodified peptides, others are heavily modified by dedicated maturation enzymes. Low-molecular-weight microcins from the post-translationally modified group target essential molecular machines inside the cells. In this review, available structural and functional data about three such microcins , microcin J25, microcin B17 and microcin C7-C51 , are discussed. While all three low-molecular-weight post-translationally modified microcins are produced by Escherichia coli, inferences based on sequence and structural similarities with peptides encoded or produced by phylogenetically diverse bacteria are made whenever possible to put these compounds into a larger perspective. [source] p73: Structure and functionPATHOLOGY INTERNATIONAL, Issue 8 2000Shingo Ichimiya Alteration of the p53 tumor suppressor gene is a common, if not general, observation in human malignant tumors. p73 Is a novel member of the p53 family at chromosome 1p36.3, at which locus frequent defects are seen in many tumors including neuroblastoma. Besides structural similarities, the fact that p73 functions in the regulation of the cell cycle and apoptosis promotes the expansion of the research field concerning p53-associated tumor progression. In this paper, we review the structure and function of p73 as well as the mutational status in various human tumors. In addition, possibilities for new therapeutic applications with p73 for cancer cell control are discussed. [source] Functional Expression, Targeting and Ca2+ Signaling of a Mouse Melanopsin-eYFP Fusion Protein in a Retinal Pigment Epithelium Cell Line,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2008Maikel E. Giesbers Melanopsin, first discovered in Xenopus melanophores, is now established as a functional sensory photopigment of the intrinsically photosensitive retinal ganglion cells. These ganglion cells drive circadian rhythm and pupillary adjustments through projection to the brain. Melanopsin shares structural similarities with all known opsins. Comprehensive characterization of melanopsin with respect to its spectral properties, photochemical cascade and signaling partners requires a suitable recombinant system and high expression levels. This combination has not yet been described. To address this issue, we have expressed recombinant mouse melanopsin in several cell lines. Using enhanced yellow fluorescent protein (eYFP) as a visualization tag, expression was observed in all cell lines. Confocal microscopy revealed that melanopsin was properly routed to the plasma membrane only in retinal pigment epithelium (RPE)-derived D407 cells and in human embryonic kidney (HEK) cells. Further, we performed intracellular calcium measurements in order to probe the melanopsin signaling activity of this fusion protein. Transfected cells were loaded with the calcium indicator Fura2-AM. Upon illumination, an immediate but transient calcium response was observed in HEK as well as in D407 cells, while mock-transfected cells showed no calcium response under identical conditions. Supplementation with 11- cis retinal or all- trans retinal enhanced the response. After prolonged illumination the cells became desensitized. Thus, RPE-derived cells expressing recombinant melanopsin may constitute a suitable system for the study of the structural and functional characteristics of melanopsin. [source] An in vitro enzymatic assay coupled to proteomics analysis reveals a new DNA processing activity for Ewing sarcoma and TAF(II)68 proteinsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 22 2006Olivier Guipaud Abstract Based on structural and functional similarities, translocated in liposarcoma/fusion (TLS/FUS) protein, Ewing sarcoma,(EWS) protein and human TATA binding protein-associated factor (hTAF(II)68) have been grouped in the TLS-EWS-TAF(II)68 (TET) protein family. Translocations involving their genes lead to sarcomas. Polypyrimidine tract-binding protein-associated splicing factor,(PSF), although not grouped in this family, presents structural and functional similarities with TET proteins and is involved in translocation leading to carcinoma. Beside their role in RNA metabolism, the precise cellular functions of these multifunctional proteins are not yet fully elucidated. We previously showed that both TLS/FUS and PSF display activities able to pair homologous DNA on membrane in an in,vitro assay. In the present study, we address the question whether EWS and hTAF(II)68 also display pairing on membrane activities, and to a larger extent whether other proteins also exhibit such activity. We applied the pairing on membrane assay to 2-DE coupled to MS analysis for a global screening of DNA pairing on membrane activities. In addition to TLS/FUS and PSF, this test allowed us to identify EWS and hTAF(II)68, but no other proteins, indicating a feature specific to a protein family whose members share extensive structural similarities. This common activity suggests a role for TET proteins and PSF in genome plasticity control. [source] Vajra Brother, Vajra Sister: Renunciation, Individualism and the Household in Tibetan Buddhist MonasticismTHE JOURNAL OF THE ROYAL ANTHROPOLOGICAL INSTITUTE, Issue 1 2000Martin A. Mills This article challenges two connected notions in the study of Tibetan Buddhism: that Buddhist monasticism is characterized by a pronounced move towards individualism, systematically detaching monks from relational social life; and that Tibetan Buddhist doctrines of karma represent an alternative mode of identity to those constructed within household life. By comparing the ritual practices and inheritance patterns associated with household groups in Ladakh with tantric ritual forms in local Buddhist (Gelukpa) monasteries, it is argued that they demonstrate pronounced structural similarities, centred on the shared symbolic construct of the household/temple as the source of socialized agency. An analysis of the meditative disciplines of Gelukpa monasticism is used to show how such training serves not to renounce kinship and household values, but to transform them into modes of religious authority, essential to the social position of monks (trapa) and incarnate lamas (tulku) in Tibetan Buddhism. [source] Separation and quantification of N -acetyl- l -cysteine and N -acetyl-cysteine-amide by HPLC with fluorescence detectionBIOMEDICAL CHROMATOGRAPHY, Issue 5 2006Wei Wu Abstract N- acetyl- l -cysteine (NAC) is a well-known antioxidant that is capable of facilitating glutathione (GSH) biosynthesis and replenishing intracellular GSH under oxidatively challenging circumstances. N- acetyl-cysteine-amide (NACA), the amide form of NAC, is a newly designed and synthesized thiol-containing compound which is believed to be more lipophilic and permeable through cell membranes than NAC. The metabolic and antioxidant effects of these compounds in vitro and in vivo are under investigation. However, an analytical method that can separate and quantify both compounds simultaneously is not yet available, to the best of our knowledge. Because of their structural similarities, the two compounds are difficult to separate using earlier HPLC methods which were designed for NAC quantification. Therefore, the goal of this work was to develop an HPLC method with fluorescence detection for simultaneous quantification of NAC and NACA in biological blood and tissue samples. A gradient HPLC program with fluorescence detection (,ex = 330 nm, ,em = 376 nm) using N -(1-pyrenyl)maleimide (NPM) as the derivatizing agent was developed. The calibration curves were linear over a concentration range of 25,5000 nm (r2 > 0.997). The coefficients of variation for within-run precision and between-run precision ranged from 0.67 to 5.23% and for accuracy ranged from 0.98 to 10.54%; the percentage relative recovery ranged from 94.5 to 102.8%. This new method provides satisfactory separation of NAC and NACA, along with other biological thiols, in 20 min with a 5 nm limit of detection (LOD) per 5 µL injection volume. Copyright © 2005 John Wiley & Sons, Ltd. [source] 2331: Are the Meibomian glands "hair follicles without a hair shaft" ?ACTA OPHTHALMOLOGICA, Issue 2010E KNOP Purpose The Meibomian glands (MG) are atypically large sebaceous glands in the eyelids with numerous generations of secretory acini along an extensive central duct. They share similarities with the ciliary hairs in development, and hyper-keratinisation leading to obstructive MG dysfunction (MGD) represents the typical pathology. It was hence investigated which structural similarities they share with cilia. Methods Conjunctival whole-mounts including the lid margin from ten normal human body donors were embedded in paraffin. Serial sections were stained by H&E, Masson-Goldners stain and by immunohistochemistry (IHC) against cytokeratins and associated proteins. Results The terminal part (excretory duct) of the MG central duct is an ingrowth of epidermis similar to the hair follicles of the cilia. Characterization of individual cytokeratinis by IHC showed that CK14, a marker for undifferentiated cells, was expressed in the basal cell layer of the skin, MG ducts and the secretory acini. The excretory duct epithelium expressed the skin keratin CK10 and the keratinisation marker involucrin but in proximal direction along the central duct full cornification as well as both markers were gradually lost. Filaggrin, however, a marker for incipient stages of keratinisation located in keratohyalin granules continued in the superficial epithelial layer all along the MG ductal system. Conclusion All parts of the normal human MG ductal system have signs of incipient keratinisation and preserve a commitment to full cornification. This supports the assumption that the MG are basically "hair follicles without a hair shaft" in which the progression to full epithelial cornification is apparently blocked during embryological development but may reoccur under pathological influences. Support DFG KN317/11 [source] STRUCTURAL COVARIATES OF U.S. COUNTY HOMICIDE RATES: INCORPORATING SPATIAL EFFECTS,CRIMINOLOGY, Issue 3 2001ROBERT D. BALLER Spatial analysis is statistically and substantively important for macrolevel criminological inquiry. Using county-level data for the decennial years in the 1960 to 1990 time period, we reexamine the impact of conventional structural covariates on homicide rates and explicitly model spatial effects. Important findings are: (1) homicide is strongly clustered in space; (2) this clustering cannot be completely explained by common measures of the structural similarity of neighboring counties; (3) noteworthy regional differences are observed in the effects of structural covariates on homicide rates; and (4) evidence consistent with a diffusion process for homicide is observed in the South throughout the 1960,1990 period. [source] Interaction of stilbene compounds with human and rainbow trout estrogen receptorsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2008Denina Bobbie Dawn Simmons Abstract Compounds with stilbene structures are widely used as pharmaceuticals and personal care products (PPCPs) and are present in plants. A suite of stilbene-related compounds, including PPCPs and plant-derived compounds were tested in vitro for interactions with the human and rainbow trout estrogen receptors and in vivo with rainbow trout using vitellogenin levels as a biomarker. Among the compounds with antagonistic activity, the common structural similarity was (in addition to the stilbene backbone) the presence of 4-hydroxy substitution. Stilbene-related compounds found to act as inhibitors at the estrogen receptor included the plant-derived compound resveratrol and two formulations of fluorescent whitening agents used in detergents, 4,4,-bis(2-sulfostyryl)biphenyl and diaminostilbene-1. In the yeast estrogenicity screening assay, the concentrations which caused a 50% inhibition in estrogenic response (IC50s) with the human estrogen receptor ranged from 2.56 × 10,6 to 2.56 × 10,6 M. In the rainbow trout estrogen receptor assay, the IC50s ranged from 7.75 × 10,8 to 1.11 × 10,5 M. However, in the in vivo rainbow trout vitellogenin assay, tamoxifen was the only stilbene of the compounds tested to have a significant effect as an inhibitor of estrogenicity. [source] Analogy retrieval and processing with distributed vector representationsEXPERT SYSTEMS, Issue 1 2000Tony A. Plate Holographic reduced representations (HRRs) are a method for encoding nested relational structures in fixed-width vector representations. HRRs encode relational structures as vector representations in such a way that the superficial similarity of the vectors reflects both superficial and structural similarity of the relational structures. HRRs also support a number of operations that could be very useful in psychological models of human analogy processing: fast estimation of superficial and structural similarity via a vector dot-product; finding corresponding objects in two structures; and chunking of vector representations. Although similarity assessment and discovery of corresponding objects both theoretically take exponential time to perform fully and accurately, with HRRs one can obtain approximate solutions in constant time. The accuracy of these operations with HRRs mirrors patterns of human performance on analog retrieval and processing tasks. [source] Crystal structure of the parasite inhibitor chagasin in complex with papain allows identification of structural requirements for broad reactivity and specificity determinants for target proteasesFEBS JOURNAL, Issue 3 2009Izabela Redzynia A complex of chagasin, a protein inhibitor from Trypanosoma cruzi, and papain, a classic family C1 cysteine protease, has been crystallized. Kinetic studies revealed that inactivation of papain by chagasin is very fast (kon = 1.5 × 106 m,1·s,1), and results in the formation of a very tight, reversible complex (Ki = 36 pm), with similar or better rate and equilibrium constants than those for cathepsins L and B. The high-resolution crystal structure shows an inhibitory wedge comprising three loops, which forms a number of contacts responsible for the high-affinity binding. Comparison with the structure of papain in complex with human cystatin B reveals that, despite entirely different folding, the two inhibitors utilize very similar atomic interactions, leading to essentially identical affinities for the enzyme. Comparisons of the chagasin,papain complex with high-resolution structures of chagasin in complexes with cathepsin L, cathepsin B and falcipain allowed the creation of a consensus map of the structural features that are important for efficient inhibition of papain-like enzymes. The comparisons also revealed a number of unique interactions that can be used to design enzyme-specific inhibitors. As papain exhibits high structural similarity to the catalytic domain of the T. cruzi enzyme cruzipain, the present chagasin,papain complex provides a reliable model of chagasin,cruzipain interactions. Such information, coupled with our identification of specificity-conferring interactions, should be important for the development of drugs for treatment of the devastating Chagas disease caused by this parasite. [source] Actin-binding domain of mouse plectinFEBS JOURNAL, Issue 10 2004Crystal structure, binding to vimentin Plectin, a large and widely expressed cytolinker protein, is composed of several subdomains that harbor binding sites for a variety of different interaction partners. A canonical actin-binding domain (ABD) comprising two calponin homology domains (CH1 and CH2) is located in proximity to its amino terminus. However, the ABD of plectin is unique among actin-binding proteins as it is expressed in the form of distinct, plectin isoform-specific versions. We have determined the three-dimensional structure of two distinct crystalline forms of one of its ABD versions (pleABD/2,) from mouse, to a resolution of 1.95 and 2.0 Ĺ. Comparison of pleABD/2, with the ABDs of fimbrin and utrophin revealed structural similarity between plectin and fimbrin, although the proteins share only low sequence identity. In fact, pleABD/2, has been found to have the same compact fold as the human plectin ABD and the fimbrin ABD, differing from the open conformation described for the ABDs of utrophin and dystrophin. Plectin harbors a specific binding site for intermediate filaments of various types within its carboxy-terminal R5 repeat domain. Our experiments revealed an additional vimentin-binding site of plectin, residing within the CH1 subdomain of its ABD. We show that vimentin binds to this site via the amino-terminal part of its rod domain. This additional amino-terminal intermediate filament protein binding site of plectin may have a function in intermediate filament dynamics and assembly, rather than in linking and stabilizing intermediate filament networks. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||