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New Pathway (new + pathway)
Selected AbstractsNew Pathway to Furo[2,3-b]quinoline Derivatives.CHEMINFORM, Issue 52 2002V. F. Traven Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: New Pathway to Thia-2-cyclanones.CHEMINFORM, Issue 32 2002L. G. Shagun 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] Preparation of Imidazolin-2-iminato Molybdenum and Tungsten Benzylidyne Complexes: A New Pathway to Highly Active Alkyne Metathesis CatalystsCHEMISTRY - A EUROPEAN JOURNAL, Issue 29 2010Birte Haberlag Dipl.-Chem. Abstract The reaction of [PhCMBr3(dme)] (dme=1,2-dimethoxyethane) with the hexafluoro- tert- butoxides LiX or KX [X=OC(CF3)2Me] afforded the benzylidyne complexes [PhCMX3(dme)] (2,a: M=W, 2,b: M=Mo), which further reacted with the lithium reagent Li(ImtBuN), generated with MeLi from 1,3-di- tert -butylimidazolin-2-imine (ImtBuNH), to form the imidazolin-2-iminato complexes [PhCMX2(ImtBuN)] (3,a: M=W, 3,b: M=Mo). The propylidyne complex [EtCMoX2(NImtBu)] (4) was obtained by treatment of 3,b with an excess of 3-hexyne. Complexes 3,a and 3,b are able to efficiently catalyse alkyne cross metathesis of various 3-pentynyl benzyl ethers 5 and benzoic esters 7 at room temperature, to afford 2-butyne and the corresponding diethers 6 and diesters 8. The tungsten complex 3,a proved to be a superior catalyst for ring-closing alkyne metathesis, and the [10]cyclophanes 10 and 12 were synthesised in high yield from 1,3-bis(3-pentynyloxymethyl)benzene (9) and bis(3-pentynyl) phthalate (11), respectively. The molecular structures of compounds 2,a, 2,b, 3,a, 3,b, 4, and 12 were determined by single-crystal X-ray diffraction. DFT calculations have been carried out for catalyst systems based on the imidazolin-2-iminato tungsten and molybdenum complexes 3,a and 3,b by choosing the alkyne metathesis of 2-butyne as the model reaction; the studies revealed a lower activation barrier for the tungsten system. [source] New Pathways in International Development: Gender and Civil Society in EU Policy , Edited by M. Lister and M. CarboneJCMS: JOURNAL OF COMMON MARKET STUDIES, Issue 2 2007GIULIA PIETRANGELI No abstract is available for this article. [source] The ,oestrogen hypothesis', where do we stand now?,INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2003Richard M. Sharpe Summary The original ,oestrogen hypothesis' postulated that the apparent increase in human male reproductive developmental disorders (testis cancer, cryptorchidism, hypospadias, low sperm counts) might have occurred because of increased oestrogen exposure of the human foetus/neonate; five potential routes of exposure were considered. This review revisits this hypothesis in the light of the data to have emerged since 1993. It addresses whether there is a secular increasing trend in the listed disorders and highlights the limitations of available data and how these are being addressed. It considers whether new data has emerged to support the suggestion that increased oestrogen exposure could cause these abnormalities and reviews new data on potential routes via which such increased exposure could have occurred. Secular trends: The disorders listed above are now considered to represent a syndrome of disorders (testicular dysgenesis syndrome, TDS) with a common origin in foetal life. Testicular cancer has increased in incidence in Caucasian men worldwide and lifetime risk is 0.3,0.8%. Secular trends in cryptorchidism are unclear but it is by far the commonest (2,4% at birth) congenital abnormality in either sex. Secular trends for hypospadias are not robust, although most studies suggest a progressive increase; registry data probably under-estimates incidence, but based on this data hypospadias is the second most common (0.3,0.7% at birth) congenital malformation. Retrospective analyses of sperm count data show a global downward trend but this is inconclusive , prospective studies using standardized methodology show significant differences between countries and very low sperm counts in the youngest cohort of men. For all disorders, other then testis cancer, standardized prospective studies are the best way forward and are in progress across Europe. Oestrogen effects: Evidence that foetal exposure to oestrogens can induce the above disorders has strengthened. New pathways via which such changes could be induced have been identified, including suppression of testosterone production by the foetal testis, suppression of androgen receptor expression and suppression of insulin-like factor-3 (InsL3) production by foetal Leydig cells. Other evidence suggests that the balance between androgen and oestrogen action may be important in induction of reproductive tract abnormalities. Oestrogen exposure: Although many new environmental oestrogens have been identified, their uniformly weak oestrogenicity excludes the possibility that they could induce the above disorders. However, emerging data implicates various environmental chemicals in being able to alter endogenous levels of androgens (certain phthalates) and oestrogens (polychlorinated biphenyls, polyhalogenated hydrocarbons), and the former have been shown to induce a similar collection of disorders to TDS. Other mechanisms via which increased fetal exposure to pregnancy oestrogens might occur (increasing trend in obesity, dietary changes) are also discussed. [source] New pathways for evaluating potential acute stroke therapiesINTERNATIONAL JOURNAL OF STROKE, Issue 2 2006Marc Fisher Many neuroprotective drugs and a few other thrombolytics were evaluated in clinical trials, but none demonstrated unequivocal success and were approved by regulatory agencies. The development paradigm for such therapies needs to provide convincing evidence of efficacy and safety to obtain approval by the Food and Drug Administration (FDA). The FDA modernization act of 1997 stated that such evidence could be derived from one large phase III trial with a clinical endpoint and supportive evidence. Drugs being developed for acute ischemic stroke can potentially be approved under this act by coupling a major phase III trial with supportive evidence provided by a phase IIB trial demonstrating an effect on a relevant biomarker such as magnetic resonance imaging or computed tomography assessment of ischemic lesion growth. Statistical approaches have been developed to optimize the design of such an imaging-based phase IIB study, for example approaches that modify randomization probabilities to assign larger proportions of patients to the ,winning' strategy (i.e. ,pick the winner' strategies) with an interim assessment to reduce the sample size requirement. Demonstrating a treatment effect on a relevant imaging-based biomarker should provide supportive evidence for a new drug application, if a subsequent phase III trial with a clinical outcome demonstrates a significant treatment effect. [source] Predicting the biodiversity benefits of the Saltshaker Project, Boorowa, NSWECOLOGICAL MANAGEMENT & RESTORATION, Issue 1 2004David Freudenberger Did the 2-year Saltshaker Project nudge the Boorowa Catchment along a new pathway towards improved biodiversity? [source] Microbial Fuel Cells in Relation to Conventional Anaerobic Digestion TechnologyENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 3 2006H. Pham Abstract Conventional anaerobic digestion based bioconversion processes produce biogas and have as such been widely applied for the production of renewable energy so far. An innovative technology, based on the use of microbial fuel cells, is considered as a new pathway for bioconversion processes towards electricity. In comparison with conventional anaerobic digestion, the microbial fuel cell technology holds some specific advantages, such as its applicability for the treatment of low concentration substrates at temperatures below 20,°C, where anaerobic digestion generally fails to function. This provides some specific application niches of the microbial fuel cell technology where it does not compete with but complements the anaerobic digestion technology. However, microbial fuel cells still face important limitations in terms of large-scale application. The limitations involve the investment costs, upscale technical issues and the factors limiting the performance, both in terms of anodic and cathodic electron transfer. Research to render the microbial fuel cell technology more economically feasible and applicable should focus on reactor configuration, power density and the material costs. [source] Vesicles as reactors of nanoparticles: an anomalous small-angle X-ray scattering study of the domains rich in copper ionsJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 2007Attila Bóta The formation of copper hydroxide and copper oxide particles in the gaps among the stacks of multilamellar vesicles is described, illustrating a new pathway in the preparation of nanometre-scale particles. The in situ structural characterization of both the solid particles and the vesicles as a reaction medium was performed in the initial and final states of the process by using anomalous small-angle X-ray scattering (ASAXS) and freeze-fracture methods. The ASAXS method provides a description of the particle-size distribution of the copper nanoparticles, in spite of the fact that they are present in low concentration. This method allows the particle formation and growth to be monitored throughout the whole time range of the synthesis. [source] Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brainJOURNAL OF INTERNAL MEDICINE, Issue 6 2006I. BJÖRKHEM Abstract. A normal brain function requires constant levels of cholesterol, and the need for constancy seems to be higher here than in any other organ. Nature has met this need by isolation of brain cholesterol by a highly efficient blood,brain barrier. As a low synthesis of cholesterol is present in the brain, a mechanism for compensatory elimination is required. A decade ago we made the unexpected finding that the favoured mechanism for this involves conversion into 24S-hydroxycholesterol, followed by diffusion over the blood,brain barrier. Recent studies by us and others on this new pathway have given new insights into the mechanisms by which cholesterol homeostasis is maintained in the brain. We recently demonstrated a flux of another oxygenated product of cholesterol, 27-hydroxycholesterol, in the opposite direction. The latter flux may be important for neurodegeneration, and may be the link between hypercholesterolaemia and Alzheimer's disease. An overview of the above studies is presented and the possibility that the cholesterol 24S-hydroxylase in the brain may be important for memory and learning and that it may be a new drug target is discussed. [source] Production of l -2,3-butanediol by a new pathway constructed in Escherichia coliLETTERS IN APPLIED MICROBIOLOGY, Issue 6 2004S. Ui Abstract Aims:, A metabolic pathway for l -2,3-butanediol (BD) as the main product has not yet been found. To rectify this situation, we attempted to produce l -BD from diacetyl (DA) by producing simultaneous expression of diacetyl reductase (DAR) and l -2,3-butanediol dehydrogenase (BDH) using transgenic bacteria, Escherichia coli JM109/pBUD-comb. Methods and Results:, The meso -BDH of Klebsiella pneumoniae was used for its DAR activity to convert DA to l -acetoin (AC) and the l -BDH of Brevibacterium saccharolyticum was used to reduce l -AC to l -BD. The respective gene coding each enzyme was connected in tandem to the MCS of pFLAG-CTC (pBUD-comb). The divided addition of DA as a source, addition of 2% glucose, and the combination of static and shaking culture was effective for the production. Conclusions:,l -BD (2200 mg l,1) was generated from 3000 mg l,1 added of DA, which corresponded to a 73% conversion rate. Meso -BD as a by-product was mixed by 2% at most. Significance and Impact of the Study:, An enzyme system for converting DA to l -BD was constructed with a view to using DA-producing bacteria in the future. [source] A new pathway for the synthesis of ,-ribazole-phosphate in Listeria innocuaMOLECULAR MICROBIOLOGY, Issue 6 2010Michael J. Gray Summary The genomes of Listeria spp. encode all but one of 25 enzymes required for the biosynthesis of adenosylcobalamin (AdoCbl; coenzyme B12). Notably, all Listeria genomes lack CobT, the nicotinamide mononucleotide:5,6-dimethylbenzimidazole (DMB) phosphoribosyltransferase (EC 2.4.2.21) enzyme that synthesizes the unique ,-linked nucleotide N1 -(5-phospho-,- d -ribosyl)-DMB (,-ribazole-5,-P, ,-RP), a precursor of AdoCbl. We have uncovered a new pathway for the synthesis of ,-RP in Listeria innocua that circumvents the lack of CobT. The cblT and cblS genes (locus tags lin1153 and lin1110) of L. innocua encode an ,-ribazole (,-R) transporter and an ,-R kinase respectively. Results from in vivo experiments indicate that L. innocua depends on CblT and CblS activities to salvage exogenous ,-R, allowing conversion of the incomplete corrinoid cobinamide (Cbi) into AdoCbl. Expression of the L. innocua cblT and cblS genes restored AdoCbl synthesis from Cbi and ,-R in a Salmonella enterica cobT strain. LinCblT transported ,-R across the cell membrane, but not ,-RP or DMB. UV-visible spectroscopy and mass spectrometry data identified ,-RP as the product of the ATP-dependent ,-R kinase activity of LinCblS. Bioinformatics analyses suggest that ,-R salvaging occurs in important Gram-positive human pathogens. [source] Bacterial hydrolytic dehalogenases and related enzymes: Occurrences, reaction mechanisms, and applicationsTHE CHEMICAL RECORD, Issue 2 2008Tatsuo Kurihara Abstract Dehalogenases catalyze the cleavage of the carbon,halogen bond of organohalogen compounds. They have been attracting a great deal of attention partly because of their potential applications in the chemical industry and bioremediation. In this personal account, we describe occurrences, reaction mechanisms, and applications of bacterial hydrolytic dehalogenases and related enzymes, particularly L -2-haloacid dehalogenase, DL -2-haloacid dehalogenase, fluoroacetate dehalogenase, and 2-haloacrylate reductase. L -2-Haloacid dehalogenase is a representative enzyme of the haloacid dehalogenase (HAD) superfamily, which includes the P-type ATPases and other hydrolases. Structural and mechanistic analyses of this enzyme have yielded important insights into the mode of action of the HAD superfamily proteins. Fluoroacetate dehalogenase is unique in that it catalyzes the cleavage of the highly stable CF bond of a fluorinated aliphatic compound. In the reactions of L -2-haloacid dehalogenase and fluoroacetate dehalogenase, the carboxylate group of Asp performs a nucleophilic attack on the ,-carbon atom of the substrate, displacing the halogen atom. This mechanism is common to haloalkane dehalogenase and 4-chlorobenzoyl-CoA dehalogenase. DL -2-Haloacid dehalogenase is unique in that a water molecule directly attacks the substrate, displacing the halogen atom. The occurrence of 2-haloacrylate reductase was recently reported, revealing a new pathway for the degradation of unsaturated aliphatic organohalogen compounds. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 67,74; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20141 [source] Interaction between two mitogen-activated protein kinases during tobacco defense signalingTHE PLANT JOURNAL, Issue 2 2003Yidong Liu Summary Plant mitogen-activated protein kinases (MAPKs) represented by tobacco wounding-induced protein kinase (WIPK) have unique regulation at the level of transcription in response to stresses. By using transcriptional and translational inhibitors, it has been shown previously that WIPK gene expression and de novo protein synthesis are required for the high-level activity of WIPK in cells treated with elicitins from Phytophthora spp. However, regulation of WIPK expression and the role(s) of WIPK in plant disease resistance are unknown. In this report, we demonstrate that WIPK gene transcription is regulated by phosphorylation and de-phosphorylation events. Interestingly, salicylic acid-induced protein kinase (SIPK) was identified as the kinase involved in regulating WIPK gene expression based on both gain-of-function and loss-of-function analyses. This finding revealed an additional level of interaction between SIPK and WIPK, which share an upstream MAPKK, NtMEK2. Depending on whether WIPK shares its downstream targets with SIPK, it could either function as a positive feed-forward regulator of SIPK or initiate a new pathway. Consistent with the first scenario, co-expression of WIPK with the active mutant of NtMEK2 leads to accelerated hypersensitive response (HR)-like cell death in which SIPK also plays a role. Mutagenesis analysis revealed that the conserved common docking domain in WIPK is required for its function. Together with prior reports that (i) WIPK is activated in NN tobacco infected with tobacco mosaic virus, and (ii) PVX virus-induced gene silencing of WIPK attenuated N gene-mediated resistance, we concluded that WIPK plays a positive role in plant disease resistance, possibly through accelerating the pathogen-induced HR cell death. [source] An objective definition of the Indian summer monsoon season and a new perspective on the ENSO,monsoon relationshipTHE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue 624 2007Prince K. Xavier The concept of an interannually varying Indian summer monsoon season is introduced here, considering that the duration of the primary driving of the Indian monsoon,the large-scale meridional gradient of the deep tropospheric heat source,may vary from one year to another. Onset (withdrawal) is defined as the day when the tropospheric heat source shifts from south to north (north to south). This physical principle leads to a new thermodynamic index of the seasonal mean monsoon. While the traditional measure of seasonal rainfall, averaged from 1 June to 30 September, indicates a breakdown of the ENSO,monsoon relationship in recent decades, it is argued that this breakdown is partly due to the inappropriate definition of a fixed monsoon season. With a new physically based definition of the seasonal mean, the ENSO,monsoon relationship has remained steady over the decades. El Niño (La Niña) events contract (expand) the season, and thus decrease (increase) the seasonal mean monsoon by setting up persistent negative (positive) tropospheric temperature (TT) anomalies over the southern Eurasian region. Thus, we propose a new pathway, whereby the Indian summer monsoon could be influenced by remote climatic phenomena via modification of TT over Eurasia. Diagnostics of the onset and withdrawal processes suggest that onset delay is due to the enhanced adiabatic subsidence that inhibits vertical mixing of sensible heating from warm landmass during the pre-monsoon months. On the other hand, the major factor that determines whether the withdrawal is early or late is the horizontal advective cooling. Most of the late (early) onsets and early (late) withdrawals are associated with El Niño (La Niña). This link between the ENSO and the monsoon is realized through vertical and horizontal advections associated with the stationary waves in the upper troposphere set up by the tropical ENSO heating. Copyright © 2007 Royal Meteorological Society [source] Fine mapping of the FecL locus influencing prolificacy in Lacaune sheepANIMAL GENETICS, Issue 6 2009L. Drouilhet Summary In the Lacaune sheep population, two major loci influencing ovulation rate are segregating: FecX and FecL. The FecXL mutation is a non-conservative substitution (p.Cys53Tyr) in BMP15 that prevents the processing of the protein. Using a statistical approach, FecL has been shown to be an autosomal major gene. A full genome scan localized the FecL locus on sheep chromosome 11. Fine mapping reduced the interval containing FecL to markers BM17132 and FAM117A, corresponding to a synteny block of 1.1 megabases on human chromosome 17, which encompasses 20 genes. The expression of 16 genes from this interval was observed in tissues of the reproductive axis, but expression was not affected in homozygous FecLL females. In this interval, a unique haplotype was associated with the FecLL mutation. This particular haplotype could be predicted by the DLX3:c.*803A>G SNP in the 3, UTR sequence of the DLX3 gene. This SNP provided accurate classification of animals (99.5%) as carriers or non-carriers of the mutation and therefore maybe useful in marker assisted selection. A synergistic action of FecLL and FecXL mutations on both ovulation rate and litter size was demonstrated. Until now, all the Fec genes identified in sheep belong to the bone morphogenetic protein (BMP) system. Based on the human orthologous region, none of the 20 genes in the FecL region corresponds to known molecules in the BMP system. The identification of the FecLL mutation could lead to the discovery of a new pathway involved in the regulation of ovulation rate. [source] Electric field induced desorption of bacteria from a conditioning film covered substratumBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2001Albert T. Poortinga Abstract Desorption of three oral bacterial strains from a salivary conditioning film on an indium tin oxide electrode during application of a positive (bacterial adhesion to the anode) or a negative electric current was studied in a parallel plate flow chamber. Bacterial adhesion was from a flowing suspension of high ionic strength, after which the bacterial suspension was replaced by a low ionic strength solution without bacteria and currents ranging from ,800 to +800 ,A were applied. Streptococcus oralis J22 desorbed during application of a positive and negative electric current with a desorption probability that increased with increasing electric current. Two actinomyces strains, however, could not be stimulated to desorb by the electric currents applied. The desorption forces acting on adhering bacteria are electroosmotic in origin and working parallel to the electrode surface in case of a positive current, whereas they are electrophoretic and electrostatic in origin and working perpendicular to the surface in case of a negative current. By comparison of the effect of positive and negative electric currents, it can be concluded that parallel forces are more effective in stimulating bacterial desorption than perpendicular forces. The results of this study point to a new pathway of cleaning industrial and biomedical surfaces without the use of detergents or biocides. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 76: 395,399, 2001. [source] Alignment of Emergency Medicine Research Efforts with Clinical and Translational Science AwardsACADEMIC EMERGENCY MEDICINE, Issue 7 2008Chadwick D. Miller MD Abstract The Clinical and Translational Science Awards (CTSA) represent a major new funding pathway for health science investigators seeking National Institutes of Health (NIH) funds. This new pathway provides institutional-level support for clinical and translational research and is not tied to one organ system or disease process, fitting well with emergency medicine (EM) research needs. These awards open unique opportunities for advancing EM research. The CTSA mechanism provides institutional support from the NIH to promote both clinical and translational science. Of the 60 expected awards, 38 sites are currently funded. EM investigators can benefit the institutions applying for these awards and simultaneously gain from involvement. Some opportunities for participation provided by the CTSA include research training programs, joining multidisciplinary research teams, seed grant funding, and use of the CTSA-developed research infrastructure. Involvement of EM can benefit institutions by enhancing acute care research collaboration both within and among institutions. Emergency medicine researchers at institutions either planning to submit a CTSA application or with funded CTSA grants are encouraged to become actively involved in CTSA-related research programs. [source] Two Distinct Mechanisms of Alkyne Insertion into the Metal,Sulfur Bond: Combined Experimental and Theoretical Study and Application in CatalysisCHEMISTRY - A EUROPEAN JOURNAL, Issue 7 2010Valentine Abstract The present study reports the evidence for the multiple carbon,carbon bond insertion into the metal,heteroatom bond via a five-coordinate metal complex. Detailed analysis of the model catalytic reaction of the carbon,sulfur (CS) bond formation unveiled the mechanism of metal-mediated alkyne insertion: a new pathway of CS bond formation without preliminary ligand dissociation was revealed based on experimental and theoretical investigations. According to this pathway alkyne insertion into the metal,sulfur bond led to the formation of intermediate metal complex capable of direct CS reductive elimination. In contrast, an intermediate metal complex formed through alkyne insertion through the traditional pathway involving preliminary ligand dissociation suffered from "improper" geometry configuration, which may block the whole catalytic cycle. A new catalytic system was developed to solve the problem of stereoselective SS bond addition to internal alkynes and a cost-efficient Ni-catalyzed synthetic procedure is reported to furnish formation of target vinyl sulfides with high yields (up to 99,%) and excellent Z/E selectivity (>99:1). [source] Asymmetric Hydrogenation with Water/Silane as the Hydrogen SourceCHEMISTRY - A EUROPEAN JOURNAL, Issue 4 2010Da-Wei Wang Dr. Water as a hydride source: A new pathway to form metal,hydride bonds has been developed through the reaction of easily available metal,silyl compounds with water. This method has been successfully applied to asymmetric hydrogenation of heteroaromatic compounds with up to 93,%,ee under mild autoclave-free conditions (see scheme). [source] Delusional parasitosis: a new pathway for diagnosis and treatmentCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2 2008P. Lepping Summary Delusional parasitosis is an uncommon disorder that presents particular challenges to the dermatologist. Patients often resist psychiatric referral. Evidence of efficacy of treatment options is generally weak, but some studies exist. By identifying whether the disorder is primary or secondary to another illness, by attempting to involve the liaison psychiatry team if possible and by treating the patient with a modern antipsychotic, remission is achievable. A pathway for diagnostics and therapy is presented. Treatments of choice are ,atypical' or second-generation antipsychotics such as amisulpride, risperidone or olanzapine in age-appropriate doses. Pimozide is no longer the treatment of choice, owing to a higher risk of adverse drug reactions and lower concordance. In some cases, depot antipsychotics can be considered. For diagnostics and treatment, close collaboration of dermatologists and psychiatrists is recommended. [source] The self in conflict: The evolution of mediationCONFLICT RESOLUTION QUARTERLY, Issue 2 2007Richard McGuigan Developmentalists such as Baldwin (1975); Basseches (1984); Cook-Greuter (1990, 1999, 2000); Kegan (1982, 1994, 2001); Loevinger (1976, 1979, 1983, 1993, 1997, 1998, 2002); Piaget (1970); and Wade (1996) have devoted their research to the growth of different lines of development in individuals. A developmental understanding of conflict has implications for conflict theorists and interveners. In applying Kegan's staged model of adult psychological development to the experi-ence of conflict, we can better understand the meaning-making that underlies the behaviors that disputants exhibit in conflict, thereby allowing interveners to help the disputants expand their understanding of the conflict situation and find new pathways to its resolution. [source] THE FACE OF MONEY: Currency, Crisis, and Remediation in Post-Suharto IndonesiaCULTURAL ANTHROPOLOGY, Issue 1 2009KAREN STRASSLER ABSTRACT In the period of transition following Suharto's resignation as president of Indonesia in 1998, the image of the 50,000Rp bill bearing his face became a visual shorthand for the corruption and abuse of power that had characterized his regime. Accessible, decentralized consumer technologies enabled people to alter money's appearance, transforming it from a fetish of the state into a malleable surface available for popular reinscription. As the medium of money was "remediated",absorbed into other media, refashioned, and circulated along new pathways,it became a means by which people engaged questions of state power, national integrity, political authenticity, and economic relations opened up by the crisis of Reformasi (Reform). The essay argues that remediations of public forms play a crucial role in times of political transition by enabling people to materialize alternative visions of political authority and authenticity. Moreover, remediated forms have become a characteristic modality of political communication in the post-Suharto period under conditions of democratization and an increasingly diversified media ecology. [source] Microbiology's principle of biofilms as a major factor in the pathogenesis of acne vulgarisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2003Craig N. Burkhart MSBS Propionibacterium acnes reside within the pilosebaceous unit in a biofilm. As such, they live in a community of bacteria that encase themselves within an extracellular polysaccharide lining, which the organisms secrete after adherence to the surface. This gylcocalyx polymer acts as a protective exoskeleton and serves as a physical barrier, limiting effective antimicrobial concentrations within the biofilm microenvironment. The gylcocalyx polymer secreted by P. acnes as a biofilm may explain the immunogenicity of the organism as well as the clinical course of the disease. The P. acnes' biofilm model explains many aspects of acne pathogenesis and therapy, including why prolonged antibiotic treatment is needed, why antibiotic resistance is not a reliable assessment of treatment outcome, why accutane offers long-lasting effectiveness, and why benzoyl peroxide radicals are beneficial. This microbiologic principle of biofilms as applied to acne leads to numerous new pathways of assessment and exploration. [source] Rho-GTPases: New members, new pathwaysJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Elena M. Sorokina Abstract Proteins comprising the Rho family of GTPases mediate reorganization of the actin cytoskeleton as well as transcription of genes. Recent findings from genome sequencing efforts, genetic screens, and signal transduction research have revealed that the Rho family contains several new, hitherto unrecognized members. In this review, we focus on these newly discovered Rho-GTPases and discuss their role in signaling to the cytoskeleton and the nucleus. © 2004 Wiley-Liss, Inc. [source] Alcohol Stimulates Activation of Snail, Epidermal Growth Factor Receptor Signaling, and Biomarkers of Epithelial,Mesenchymal Transition in Colon and Breast Cancer CellsALCOHOLISM, Issue 1 2010Christopher B. Forsyth Background:, Alcohol consumption is associated with the risk of progressive cancers including colon and breast cancer. The mechanisms for the alcohol-induced aggressive behavior of these epithelial cancer cells have not been fully identified. Epithelial,mesenchymal transition (EMT) is a developmental program recently shown to play a role in cancer progression and metastases. We hypothesized that alcohol might promote cancer progression by inducing EMT in cancer cells and tested this hypothesis by assessing alcohol-stimulated changes in phenotypic markers of EMT as well as the EMT transcription factor Snail and its related cell signaling. Methods:, Colon and breast cancer cell lines and a normal intestinal epithelial cell line were tested as well as colonic mucosal biopsy samples from alcoholic subjects. Cells were treated with alcohol and assessed for EMT-related changes using immunofluorescent microscopy, western blotting, reporter assays, RT-PCR, and knockdown of Snail with siRNA. Results:, We show alcohol upregulated the signature EMT phenotypic marker vimentin as well as matrix metalloprotease (MMP)-2, MMP-7, and MMP-9 and cell migration in colon and breast cancer cells,all characteristics of EMT. Alcohol also stimulated nuclear localization of Snail phosphorylated at Ser246, transcription from a Snail reporter plasmid, and Snail mRNA expression by RT-PCR. Snail siRNA knockdown prevented alcohol-stimulated vimentin expression. In vivo, Snail expression was significantly elevated in colonic mucosal biopsies from alcoholics. Also, we found alcohol stimulated activation of epidermal growth factor receptor (EGFR) signaling and an EGFR inhibitor blocked alcohol-induced cell migration and Snail mRNA expression. Conclusions:, Collectively, our data support a novel mechanism for alcohol promoting cancer progression through stimulating the EMT program in cancer cells via an EGFR-Snail mediated pathway. This study reveals new pathways for alcohol-mediated promotion of cancer that could be targeted for therapy or prevention of alcohol-related cancers. [source] Long,term culture of multibacillary leprosy macrophages isolated from skin lesions: a new model to study Mycobacterium leprae,human cell interactionBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2007D.F. Moura Summary Background, Leprosy is characterized by a disease spectrum having two polar clinical forms dependent on the presence or not of cell-mediated immunity. In the tuberculoid forms, granuloma-activated macrophages kill Mycobacterium leprae in conjunction with a Th1 response while, in multibacillary (MB) lesions, M. leprae nonactivated macrophages infiltrate the nerves and internal organs together with a Th2 response. The functional properties and activation pathways of macrophages isolated from patients with MB leprosy remain only partially understood. Objectives, To establish an ex vivo methodology capable of evaluating the activation pathways, grade and fate of cultured macrophages isolated from MB lesions. Methods, Skin biopsies from patients with borderline tuberculoid, bordeline lepromatous and lepromatous leprosy (LL) were characterized by immunohistochemistry and transcriptional analysis. To isolate inflammatory cells, a portion of the samples was submitted to enzymatic digestion. These same cells, maintained in culture for a minimum 7-day period, were characterized morphologically and via flow cytometry at different culture time points. Cytokine [interferon (IFN)-,, tumour necrosis factor (TNF)-, and interleukin (IL)-10] mRNA levels were quantified by real-time polymerase chain reaction and protein secretion in the culture supernatants was measured by enzyme-linked immunosorbent assay and the nitric oxide levels by Griess reagent. Results, RNA expression in tuberculoid and MB lesions showed the profile expected of characteristic Th1 and Th2 responses, respectively. The inflammatory cells in all biopsies were successfully isolated. Although the number of cells varied between biopsies, it was highest in LL biopsies. The frequency of isolated CD14+ and CD3+ cells measured by flow cytometry correlated with the percentages of macrophages and lymphocytes in the lesions. Throughout the culture period, CD68+ macrophages showed morphological changes. A progressive increase in cell number and reduction of infected cells were perceptible in the cultures. In contrast to the biopsies, TNF-,, IFN-, and IL-10 expression in the tuberculoid and MB leprosy cells in 24-h culture and the cytokine levels in the supernatants did not differ significantly. During the culture period, cytokine expression in the MB cells progressively declined, whereas, from days 1 to 7, nitrite levels progressively increased. After day 40, the remaining macrophages were able to ingest fluorescein isothiocyanate-labelled M. leprae. These data need to be confirmed. Conclusions, This study confirmed the feasibility of obtaining ex vivo macrophages from leprosy lesions and keeping them in long-term culture. This procedure may open new pathways to studying the interaction between M. leprae and human macrophages, which might, in turn, lead to the development of therapeutic tools capable of overcoming the specific anergy found in patients with MB leprosy. [source] Solid,Solid Phase Transitions: Interface Controlled Reactivity and Formation of Intermediate StructuresCHEMISTRY - A EUROPEAN JOURNAL, Issue 36 2007Stefano Leoni Dr. Abstract Finding new pathways to novel materials is an open challenge in modern solid-state chemistry. Among the reasons that still prevent a rational planning of synthetic routes is the lack of an atomistic understanding at the moment of phase formation. Metastable phases are, in this respect, powerful points of access to new materials. For the synthetic efforts to fully take advantage of such peculiar intermediates, a precise atomistic understanding of critical processes in the solid state in its many facets, that is, nucleation patterns, formation and propagation of interfaces, intermediate structures, and phase growth, is mandatory. Recently we have started a systematic theoretical study of phase transitions, especially of processes with first-order thermodynamics, to reach a firm understanding of the atomistic mechanisms governing polymorphism in the solid state. A clear picture is emerging of the interplay between nucleation patterns, the evolution of domain interfaces and final material morphology. Therein intermediate metastable structural motifs with distinct atomic patterns are identified, which become exciting targets for chemical synthesis. Accordingly, a new way of implementing simulation strategies as a powerful support to the chemical intuition is emerging. Simulations of real materials under conditions corresponding to the experiments are shedding light onto yet elusive aspects of solid,solid transformations. Particularly, sharp insights into local nucleation and growth events allow the formulation of new concepts for rationalizing interfaces formed during phase nucleation and growth. Structurally different and confined in space, metastable interfaces occurring during polymorph transformations bring about distinct diffusion behavior of the chemical species involved. More generally, stable structures emerge as a result of the concurrence of the transformation mechanism and of chemical reactions within the phase-growth fronts. [source] | ||||||||||||||||||||||