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Selected AbstractsProtein profiling of organic stone matrix and urine from dogs with urolithiasisJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5-6 2006S. Forterre Summary Two-thirds of the organic matrix in urinary stones consists of proteins. Their relationship to calculogenesis remains controversial with regard to their effect as inhibitors or promoters during stone formation. The purpose of the present study was to determine the differences in peptide and protein pattern between the urine of stone formers (n = 23) and control dogs (n = 12), as well as between organic matrix of different urinary stones (struvite n = 11, calcium oxalate n = 8, uric acid n = 4) using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Specific differences in protein and peptide profiles were found in the organic matrix of different mineral compositions. Characteristic differences were also found in urinary peptide and protein pattern especially in molecular masses below 20 kDa between affected and healthy dogs. Based on the obtained molecular masses they were in some cases tentatively identified as proteins that are known to be involved in stone formation in humans. The study shows that in dogs, specific-urinary peptides and proteins might be associated with urolithiasis. It indicates the importance to further characterize those proteins for possible diagnostic purposes in prognosis and therapy. [source] Differences in clinical trial conduct in US and EU investigational sitesQUALITY ASSURANCE JOURNAL, Issue 1 2001Douglas R. Mackintosh Abstract Observations by clinical auditors about good clinical practice (GCP) compliance in US and EU investigational sites are described. Specific differences between the two regions are noted for institutional review boards (IRBs) and ethics committees; subject recruiting and consenting; investigator/study coordinator qualifications and functions; organization and recording of source data; health care delivery; quality of monitoring; and filing of regulatory documents. Neither region of the world demonstrated GCP superiority in the conduct of its clinical trials. Copyright © 2001 John Wiley & Sons, Ltd. [source] Networks of Empire: Linkage and Reciprocity in Nineteenth-Century Irish and Indian HistoryHISTORY COMPASS (ELECTRONIC), Issue 3 2009Barry Crosbie Recent debates surrounding Ireland's historical relationship with the British empire have focused almost exclusively upon its constitutional and political ties with Britain. The question of Ireland's colonial status continues to be heavily debated in Irish historiography and has been a contributing factor in obscuring our wider understanding of the complexity of Ireland's involvement in empire. For over 200 years, Ireland and India were joined together by an intricate series of networks that were borne out of direct Irish involvement in British imperialism overseas. Whether as migrants, soldiers, administrators, doctors, missionaries or educators, the Irish played an important role in administering, governing and populating vast areas of Britain's eastern empire. This article discusses new approaches to the study of Ireland's imperial past that allow us to move beyond the old ,coloniser-colonised' debate, to address the key issue of whether Ireland or the varieties of Irishness of its imperial servants and settlers made a specific difference to the experience of empire. By highlighting the multiplicity of Irish connections within the context of the nineteenth-century British empire in India, this article describes how imperial networks were used by contemporaries (settlers, migrants and indigenous agents) as mechanisms for the exchange of a whole set of ideas, practices and goods between Ireland and India during the colonial era. [source] Discussion of laser-assisted liposuction,LASERS IN SURGERY AND MEDICINE, Issue 10 2009Brian D. Zelickson MD Abstract There has been a significant advancement in the use of lasers for body contouring over the past several years. This article will review the recent past and discuss the future of this trend. Introduction There is much confusion over the definition of procedures using lasers for lipolysis and liposuction. This review article discusses the definitions of suction-assisted liposuction, laser lipolysis, and laser-assisted liposuction in detail. The development of these procedures is then discussed and pertinent articles are reviewed. Materials and Methods Pubmed and FDA.gov web sites were searched for published articles and FDA approved devices employing lasers for targeting fat for body contouring. This information along with the authors' personal experience was used to review and discuss this topic. Discussion There is a specific difference between suction-assisted liposuction, laser-assisted liposuction, and laser lipolysis. This review article clarifies these definitions and highlights the recent articles employing lasers for minimally invasive fat reduction. Lasers Surg. Med. 41:709,713, 2009. © 2009 Wiley-Liss, Inc. [source] Wedged between bottom-up and top-down processes: aphids on tansyECOLOGICAL ENTOMOLOGY, Issue 1 2004Bernhard Stadler Abstract., 1. Many species of aphids exploit a single host-plant species and have to cope with changing environmental conditions. They often vary greatly in abundance even when feeding on the same host. In a field experiment, the bottom-up (plant quality/patch type frequency) and top-down (ant attendance/predation) effects on the abundance of four species of aphids feeding on tansy (Tanacetum vulgare) were tested using a full factorial design. In addition, a model was used to examine these patch characteristics for their relative effects on the population dynamics and abundance of different aphid species. 2. Aphid numbers changed significantly depending on the quality of the host plant and the presence/absence of attending ants. The obligate myrmecophile, Metopeurum fuscoviride, was abundant on high-quality plants, while on poor quality plants or on plants without attending ants these aphids did not survive until the end of the experiment. The facultative myrmecophiles, Aphis fabae and Brachycaudus cardui, and the unattended aphid species, Macrosiphoniella tanacetaria, all reached similar peak population densities, but M. tanacetaria did best in poor quality patches. 3. Natural enemies reduced aphid numbers, but those species feeding on high-quality plants survived longer than those on poor-quality plants, which existed only for a short period of time, especially when associated with ants. Losses due to migration of winged morphs and mortality caused by parasitoids were insignificant. 4. Varying the frequency of different patch types in a model indicates that different degrees of associations with ants are favoured in different environments. If the proportion of high-quality patches in a habitat is large, obligate myrmecophiles do best. On increasing the number of poor-quality patches, unattended species become more abundant. 5. The results suggest that, in spite of large species specific differences in growth rates, degree of myrmecophily or life cycle features, the temporal and spatial variability in top-down and bottom-up forces differentially affects aphid species and allows the simultaneous exploitation of a shared host-plant species. [source] Proteomics of snake venoms from Elapidae and Viperidae families by multidimensional chromatographic methodsELECTROPHORESIS, Issue 16 2003Jiraporn Nawarak Abstract Snake venoms contain a large number of biologically active substances and the venom components are very useful for pharmaceutical applications. Our goal is to separate and identify components of snake venoms in ten snake species from the Elapidae and Viperidae families using multidimensional chromatographic methods. The multidimensional chromatographic methods include reversed-phase high-performance liquid chromatography (RP-HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), lab-on-a-chip, two-dimensional electrophoresis (2-DE), and mass spectrometry. The venoms of eight snake species demonstrated major differences in hydrophobicity, molecular weight separations, and 2-DE protein distribution patterns. The 2-DE images showed major differences between families, within each family and even between the same species. Venoms of the Elapidae family showed many basic proteins with a wide range of molecular weights, while venoms of the Viperidae family showed wide ranges of pI and molecular weights, especially for Trimeresurus sp. The multidimensional chromatographic methods revealed specific differences in venom proteins intra-species as well as between species and families. We have isolated and identified proteins that may be unique for each species for further studies in the proteome of snake venoms and their potentially use in the pharmaceutical applications. [source] Long-term effects of crop rotation and fertilization on soil organic matter compositionEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 6 2007M. Kaiser Summary Long-term effects of crop rotation and fertilization are mostly observed with respect to the amount of soil organic matter (SOM) and measured in terms of soil organic carbon (SOC). In this paper, we analyze the SOM composition of samples from long-term agricultural field experiments at sandy and clayey sites that include complex crop rotations and farm-yard manure applications. The organic matter (OM) composition of the soil samples, OM(Soil), and that of sequentially extracted water, OM(W), and sodium pyrophosphate, OM(PY), soluble fractions was analyzed using Fourier Transform Infrared Spectroscopy (FTIR). The fraction OM(PY) represented between 13 and 34% of SOC, about 10 times that of OM(W). Site specific differences in OM(Soil) composition were larger than those between crop rotations and fertilizer applications. The smaller C=O group content in FTIR spectra of OM(W) compared with OM(PY) suggests that analysis of the more stable OM(PY) fraction is preferable over OM(W) or OM(Soil) for identifying long-term effects, the OM(Soil) and OM(W) fractions and the content of CH groups being less indicative. Farm-yard manure application leads to a more similar content of C=O groups in OM(PY) between crop rotations and fertilizer plots at both sites. Short-term effects from soil tillage or potato harvesting on composition of OM require further studies. [source] Protein farnesyltransferase inhibitors interfere with farnesyl diphosphate binding by rubber transferaseFEBS JOURNAL, Issue 19 2003Christopher J. D. Mau Rubber transferase, a cis -prenyltransferase, catalyzes the addition of thousands of isopentenyl diphosphate (IPP) molecules to an allylic diphosphate initiator, such as farnesyl diphosphate (FPP, 1), in the presence of a divalent metal cofactor. In an effort to characterize the catalytic site of rubber transferase, the effects of two types of protein farnesyltransferase inhibitors, several chaetomellic acid A analogs (2, 4,7) and ,-hydroxyfarnesylphosphonic acid (3), on the ability of rubber transferase to add IPP to the allylic diphosphate initiator were determined. Both types of compounds inhibited the activity of rubber transferases from Hevea brasiliensis and Parthenium argentatum, but there were species,specific differences in the inhibition of rubber transferases by these compounds. Several shorter analogs of chaetomellic acid A did not inhibit rubber transferase activity, even though the analogs contained chemical features that are present in an elongating rubber molecule. These results indicate that the initiator-binding site in rubber transferase shares similar features to FPP binding sites in other enzymes. [source] Reproductive success of the rotifer Brachionus calyciflorus feeding on ciliates and flagellates of different trophic modesFRESHWATER BIOLOGY, Issue 10 2002Silvia Mohr SUMMARY 1. The nutritional value of the bacterivorous ciliate Tetrahymena pyriformis and the algivorous ciliate Coleps sp., as well as the heterotrophic flagellate Chilomonas paramecium and the autotrophic flagellate Cryptomonas ovata, were investigated in population growth experiments using the rotifer B. calyciflorus. The two ciliates, both flagellates, which were of similar size, shape and mobility, were each offered as a sole diet and as a supplement to the alga Monoraphidium minutum, known to support reproduction of B. calyciflorus. 2. To further test nutritional differences between the prey organisms, prey selection experiments were conducted in which B. calyciflorus was able to select between the bacterivorous and algivorous ciliate, and between the heterotrophic and autotrophic flagellate. 3. The results demonstrated that both ciliates and the heterotrophic flagellate were not sufficient to support reproduction of B. calyciflorus when offered as a sole diet. They were, however, a good supplement to algal prey (except for the bacterivorous ciliate T. pyriformis). In the prey selection experiments, B. calyciflorus positively selected for the algivorous Coleps sp. and the autotrophic C. ovata. 4. Overall, ciliates and heterotrophic flagellates may enhance survival of B. calyciflorus, but reproduction of the rotifer is likely to rely on algal prey. Both higher population growth of B. calyciflorus when fed the algivorous Coleps and the autotrophic Cryptomonas, along with their positive selection, give evidence for prey specific differences in nutrition, with algivorous or autotrophic prey species tending to be of higher nutritional value. [source] Mechanisms of cell death induced by suicide genes encoding purine nucleoside phosphorylase and thymidine kinase in human hepatocellular carcinoma cells in vitroHEPATOLOGY, Issue 3 2001Tim U. Krohne For gene therapy of hepatocellular carcinoma (HCC), the Escherichia coli purine nucleoside phosphorylase (PNP)/fludarabine suicide gene system may be more useful than the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system as a result of a stronger bystander effect. To analyze the molecular mechanisms involved in PNP/fludarabine-mediated cell death in human HCC cells in comparison with HSV-tk/GCV, we transduced human HCC cells of the cell lines, HepG2 and Hep3B, with PNP or HSV-tk using adenoviral vectors, followed by prodrug incubation. Both systems predominantly induced apoptosis in HepG2 and Hep3B cells. PNP/fludarabine induced strong p53 accumulation and a more rapid onset of apoptosis in p53-positive HepG2 cells as compared with p53-negative Hep3B cells, but efficiency of tumor cell killing was similar in both cell lines. In contrast, HSV-tk/GCV,induced apoptosis was reduced in p53-negative Hep3B cells as compared with p53-positive HepG2 cells. HSV-tk/GCV, but not PNP/fludarabine, caused up-regulation of Fas in p53-positive HepG2 cells and of Fas ligand (FasL) in both HCC cell lines. These results demonstrate cell line,specific differences in response to treatment with PNP/fludarabine and HSV-tk/GCV, respectively, and indicate that PNP/fludarabine may be superior to HSV-tk/GCV for the treatment of human HCC because of its independence from p53 and the Fas/FasL system. (HEPATOLOGY 2001;34:511-518.) [source] Specialized rules of gene transcription in male germ cells: the CREM paradigm*INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2004Lucia Monaco Summary Specialized transcription complexes that coordinate the differentiation programme of spermatogenesis have been found in germ cells, which display specific differences in the components of the general transcription machinery. The TATA-binding protein family and its associated cofactors, for example, show upregulated expression in testis. In this physiological context, transcriptional control mediated by the activator cAMP response element modulator (CREM) represents an established paradigm. Somatic cell activation by CREM requires its phosphorylation at a unique regulatory site (Ser117) and subsequent interaction with the ubiquitous coactivator CREB-binding protein. In testis, CREM transcriptional activity is controlled through interaction with a tissue-specific partner, activator of CREM in the testis (ACT), which confers a powerful, phosphorylation-independent activation capacity. The function of ACT was found to be regulated by the testis-specific kinesin KIF17b. Here we discuss some aspects of the testis-specific transcription machinery, whose function is essential for the process of spermatogenesis. [source] The Relationship between Categories of Non-Audit Services and Audit Fees: Evidence from UK CompaniesINTERNATIONAL JOURNAL OF AUDITING, Issue 1 2002M. Ezzamel Using survey data we examine the relationship between various categories of non-audit services and audit fees. Compared to previous research, we use a more refined classification of non-audit services both for incumbent and non-incumbent auditors, and control for the existence of an internal audit function and basis of disclosure. Our results suggest that the relationship between levels of audit fees and non-audit services varies by category of non-audit service. These results support explanations of the positive association between fees paid for non-audit services and audit fees in terms either of client specific differences, e.g. organisational complexity, or of events giving rise to the purchase of more audit and non-audit services rather than in terms of direct economic linkages between the cost functions for audit and non-audit services. We speculate that the presence of another auditing firm at the client in a consulting capacity may exert competitive pressure on the fee for external audit. [source] 31Phosphorus magnetic resonance spectroscopy study of tissue specific changes in high energy phosphates before and after sertraline treatment of geriatric depressionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2009Brent P. Forester Abstract Introduction We investigated tissue specific differences in markers of energy metabolism, including high energy phosphate compounds (beta and total NTP, PCr) and pH, in older adults with depression compared with healthy controls, before and after a 12-week treatment trial of sertraline. Methods Thirteen older adults, age ,55, with Major Depressive Disorder (HAMD17 score of ,18) were recruited along with ten age-matched controls. The depression subjects had a pre- and post-treatment 4T 31P-MRS scan using a three-dimensional chemical shift imaging sequence. The extracted brain images were segmented into white matter (WM), gray matter (GM) and CSF. A linear mixed effects model analyzed the effects of pre-treatment and post-treatment depression on phosphorus metabolite concentration estimates (including calculated pH and Mg++). Results Total tissue beta-NTP (,8%, t(18.66),=,3.50; p,=,0.0024) and total tissue total NTP (,6%, t(17.41),=,2.68; p,=,0.0156) were lower in subjects with geriatric depression compared with healthy controls. Total tissue levels of total-NTP changed significantly with treatment (,2%, t(14.84),=,,2.47; p,=,0.0259). Total NTP was reduced in the WM, but not the GM, in the pre-treatment depression group (t(51.65),=,4.02; p,=,0.0002). Intracellular pH was higher in the GM of subjects with pre-treatment depression (t(1133.84),=,,2.10; p,=,0.0353) and decreased to approximate control levels after treatment (t(648.86),=,,2.53; p,=,0.0115). Discussion These findings demonstrate bioenergetic changes including tissue specific differences in 31P-MRS metabolites in geriatric depression. Decreased white matter total NTP may reflect alterations in white matter function. Copyright © 2009 John Wiley & Sons, Ltd. [source] The detection of elements in larval otoliths from Atlantic herring using laser ablation ICP-MSJOURNAL OF FISH BIOLOGY, Issue 4 2003D. Brophy Trace element concentrations of otoliths from larval herring Clupea harengus collected from known spawning beds in the Celtic and Irish Seas, were investigated using laser ablation ICP-MS and compared with concentrations in the larval cores of juvenile otoliths from the same populations and year class. A range of elements (Mg, Zn, Sr, Ba and Pb) was detectable in early larval otoliths (20,40 µm diameter). Larval otolith concentrations exceeded the larval core concentrations of juvenile otoliths and also the concentrations reported in the literature, for Mg, Zn, Ba and Pb, indicating that the measurement of elements in larval otoliths was severely affected by post-mortem contamination, most likely due to adherence of tissue and endolymph residue on the otolith surface. Comparison of otolith composition between larvae from two freezing treatments showed that contamination from Mg and Zn was more serious in otoliths that had remained in frozen larvae for prolonged periods. Larval populations from the two seas showed significant differences in otolith Sr concentrations, which were consistent over two sampling years. Similar differences were seen in the corresponding juvenile populations. The results show that while early larval otoliths are extremely susceptible post-mortem contamination, Sr concentrations can be reliably measured using laser ablation ICP-MS and for this element, the detection of region specific differences is possible. [source] A Comparison of Echocardiographic Modalities to Guide Structural Heart Disease InterventionsJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 6 2008PAUL A. HUDSON M.D. Percutaneous techniques to treat structural heart disease are rapidly evolving based on innovative interventions and the considerable advancement in image guidance technology. While two-dimensional transthoracic and transesophageal echocardiography have been integral to procedural planning and execution, intracardiac and three-dimensional echocardiography supply unique visualization of target structures with a potential improvement in patient safety and procedural efficacy. The choice of image guidance modality is based on specific differences between imaging systems, as well as other variables including cost, patient safety, operator expertise, and complexity of procedure. We will compare the adjunctive imaging tools for structural heart disease interventions, with a focus on intracardiac echocardiography and real-time three-dimensional transesophageal echocardiography. [source] Expression and molecular diversity of Tcf7l2 in the developing murine cerebellum and brainJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2009Tommy A. Nazwar Abstract The Wingless family of secreted proteins impinges on multiple aspects of vertebrate nervous system development, from early global patterning and cell fate decision to synaptogenesis. Here, we mapped the developmental expression of the Tcf7l2, which is key to the canonical Wingless signaling cascade, in the developing cerebellum. The exclusive and transient expression of Tcf7l2 in ventricular and Olig2-defined precursor cells within the cerebellar anlage, and its predominant expression in postmitotic neurons in the midbrain/inferior colliculus allowed us to ask whether cell type,specific differences are also reflected in splice isoform variability. We also included in this analysis intestinal epithelia, where Tcf7l2 function has been intensively studied. Our data reveal extensive variability of Tcf7l2 splicing in the central nervous system. Additional variability in brain-expressed Tcf7l2 is generated by a length polymorphism of expressed mRNAs in a stretch of normally nine adenines found at the beginning of exon 18, reminiscent of variability observed at the same site in cancers with microsatellite instability. A consensus emerging from our data is that the expression of isoforms comprising or lacking the C-clamp motif, which has been linked by in vitro studies to the regulation of cell growth, is indeed tightly correlated with the proliferative status in vivo. © 2009 Wiley-Liss, Inc. [source] AN SEM-BASED ANALYSIS OF THE MORPHOLOGY, ANATOMY, AND REPRODUCTION OF LITHOTHAMNION TOPHIFORME (ESPER) UNGER (CORALLINALES, RHODOPHYTA), WITH A COMPARATIVE STUDY OF ASSOCIATED NORTH ATLANTIC ARCTIC/SUBARCTIC MELOBESIOIDEAE,JOURNAL OF PHYCOLOGY, Issue 5 2005Walter H. Adey Lithothamnion tophiforme (Esper) Unger is a dominant, arctic, saxicolous species that extends southward, albeit with reduced cover, into the deeper colder waters of the North Atlantic subarctic, where it also occurs in significant rhodolith deposits with L. glaciale. The external appearance of L. tophiforme is distinctive, but typification, anatomy, reproduction, ecology, and biogeography have not been previously analyzed. These topics are now addressed, with extensive use of SEM, in comparison with other North Atlantic arctic and subarctic melobesioid genera and species. The species considered in this article comprise 95% of the coralline biomass of the colder North Atlantic and adjacent arctic (i.e. less than 12° C summer and less than 0° C winter). In the outer thallus region of coralline algae, crust extension proceeds, calcification develops, surface sloughing and grazing occur, and reproductive structures are initiated. Analysis of the ultrastructure of the outer thallus region (epithallium, meristem, and perithallium) of L. tophiforme shows distinctive generic similarities and specific differences from the other Lithothamnion species discussed here. Considerable generic differences from the Clathromorpum and Leptophytum species also encountered in the region considered are highlighted as well. We discuss the functional and taxonomic implications of these distinguishing features and recommend that they be more widely considered in future research on coralline algae to understand more fully the ecology and evolution of the Corallinales. [source] General and specific host responses to bacterial infection in Peyer's patches: a role for stromelysin-1 (matrix metalloproteinase-3) during Salmonella enterica infectionMOLECULAR MICROBIOLOGY, Issue 1 2007Scott A. Handley Summary Salmonella enterica serovar Typhimurium (S. typhimurium) and Yersinia enterocolitica are enteric pathogens capable of colonizing and inducing inflammatory responses in Peyer's patches (PPs) and mesenteric lymph nodes (MLNs). Although the tissue colonization pattern is similar between these two pathogens, their pathogenic lifestyles are quite different. For example, while S. typhimurium is primarily an intracellular pathogen, Y. enterocolitica survives primarily extracellularly. We determined and compared the transcriptional changes occurring in response to S. typhimurium and Y. enterocolitica colonization of PP using Affymetrix GeneChip technology. Both pathogens elicited a general inflammatory response indicated by the upregulation of cytokines and chemokines. However, specific differences were also observed, most notably in the transcriptional regulation of gamma interferon (IFN-,) and IFN-,-regulated genes in response to S. typhimurium but not Y. enterocolitica. Of particular note, a group of genes encoding matrix metalloproteinases (MMPs) had increased transcript numbers in the PPs following infection with both pathogens. The experiments described here compare oral S. typhimurium or Y. enterocolitica infection in stromelysin-1 (MMP-3)-deficient mice (mmp-3,/,) with mice possessing functional MMP-3 (mmp-3+/+). There was little difference in the survival of MMP-3-deficient mice infected with Y. enterocolitica when compared with littermate controls. Surprisingly though, mmp-3,/, mice were markedly more resistant to S. typhimurium infection than the control mice. S. typhimurium was able to colonize mmp-3,/, mice, albeit in a delayed fashion, to equivalent levels as mmp-3+/+ mice. Nevertheless, significantly lower levels of inflammatory cytokines were detected in tissues and serum in the mmp-3,/, mice in comparison with mmp-3+/+ mice. We hypothesize that MMP-3 is involved in initiating an early and lethal cytokine response to S. typhimurium colonization. [source] DE-loop mutations affect ,2 microglobulin stability, oligomerization, and the low-pH unfolded formPROTEIN SCIENCE, Issue 7 2010Carlo Santambrogio Abstract ,2 microglobulin (,2m) is the light chain of class-I major histocompatibility complex (MHC-I). Its accumulation in the blood of patients affected by kidney failure leads to amyloid deposition around skeletal joints and bones, a severe condition known as Dialysis Related Amyloidosis (DRA). In an effort to dissect the structural determinants of ,2m aggregation, several ,2m mutants have been previously studied. Among these, three single-residue mutations in the loop connecting strands D and E (W60G, W60V, D59P) have been shown to affect ,2m amyloidogenic properties, and are here considered. To investigate the biochemical and biophysical properties of wild-type (w.t.) ,2m and the three mutants, we explored thermal unfolding by Trp fluorescence and circular dichroism (CD). The W60G mutant reveals a pronounced increase in conformational stability. Protein oligomerization and reduction kinetics were investigated by electrospray-ionization mass spectrometry (ESI-MS). All the mutations analyzed here reduce the protein propensity to form soluble oligomers, suggesting a role for the DE-loop in intermolecular interactions. A partially folded intermediate, which may be involved in protein aggregation induced by acids, accumulates for all the tested proteins at pH 2.5 under oxidizing conditions. Moreover, the kinetics of disulfide reduction reveals specific differences among the tested mutants. Thus, ,2m DE-loop mutations display long-range effects, affecting stability and structural properties of the native protein and its low-pH intermediate. The evidence presented here hints to a crucial role played by the DE-loop in determining the overall properties of native and partially folded ,2m. [source] Multiple approaches to data-mining of proteomic data based on statistical and pattern classification methodsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 9 2003Jacob W. Tatay Abstract The data-mining challenge presented is composed of two fundamental problems. Problem one is the separation of forty-one subjects into two classifications based on the data produced by the mass spectrometry of protein samples from each subject. Problem two is to find the specific differences between protein expression data of two sets of subjects. In each problem, one group of subjects has a disease, while the other group is nondiseased. Each problem was approached with the intent to introduce a new and potentially useful tool to analyze protein expression from mass spectrometry data. A variety of methodologies, both conventional and nonconventional were used in the analysis of these problems. The results presented show both overlap and discrepancies. What is important is the breadth of the techniques and the future direction this analysis will create. [source] Atypical Fetal Prostate Development is Associated with Ipsilateral Hypoplasia of the Wolffian Ducts in the ACI RatTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2010Luke E. Hofkamp Abstract For over a half century, the ACI (August × Copenhagen) rat has been a primary model for studying renal agenesis and ipsilateral hypoplasia (IHP) of the Wolffian-derived structures (WDS). Because the ACI rat is also used as a model for prostate research, it is important to examine the relationship of IHP and urogenital sinus (UGS) development. The prostate is dependent on androgens for proper growth and differentiation. Alteration in androgen production and/or delivery to the UGS has the potential to perturbate normal development. In this study, we investigate whether the ipsilateral loss of the WDS is associated with altered prostate development. Digital images of serial-sectioned fetal ACI rat UGS were used to create three-dimensional (3-D) surface-rendered models of the developing prostate, seminal vesicle, vas deferens, and utricle on gestational day 21. The number and volume of prostate ducts developing from the UGS were calculated from the 3-D model data. Animals exhibiting IHP had a significant decrease in total fetal prostate volume (40%; P < 0.005) with significant regional specific differences when compared with normal male ACI rats. Anatomical and histological differences in the utricle, abnormal histology of the ipsilateral testes, and a truncation of the ipsilateral Wolffian ductal mesenchyme were also seen in the animals with IHP. Additional research is needed to further understand the mechanisms and consequences of IHP on prostate growth and development. Alterations to normal prenatal development of the male accessory sex organs can have important consequences for the growth and morphology of the adult gland. Anat Rec, 2010. © 2010 Wiley-Liss, Inc. [source] Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 10 2009Christina Charles-Schoeman Objective To characterize the antiinflammatory function of high-density lipoprotein (HDL) in patients with rheumatoid arthritis (RA) and to identify specific differences in HDL-associated proteins and enzymes that distinguish proinflammatory HDL from normal, antiinflammatory HDL. Methods We studied 132 RA patients. The antiinflammatory function of HDL was assessed by a cell-free assay, and proinflammatory HDL was defined by an HDL inflammatory index ,1. Plasma and HDL-associated protein levels of apolipoprotein A-I (Apo A-I), haptoglobin, hemopexin, hemoglobin, and myeloperoxidase (MPO) were measured by direct and sandwich enzyme-linked immunosorbent assays, respectively. Lecithin:cholesterol acyltransferase (LCAT) activity was measured by a commercially available assay. Results Age, disease activity, the presence of erosive disease, non-Caucasian race, and smoking were significantly associated with proinflammatory HDL on multivariate analysis. Patients with proinflammatory HDL had higher measures of systemic inflammation, and a significant correlation was observed between RA disease activity (using the Disease Activity Score in 28 joints) and the HDL inflammatory index (r = 0.54, P < 0.0001). Compared with patients with antiinflammatory HDL, patients with proinflammatory HDL had significantly higher levels of haptoglobin, hemoglobin, Apo A-I, and MPO associated with HDL (P < 0.05 for all comparisons except MPO, which was P = 0.05). LCAT activity was lowest in patients with proinflammatory HDL, but was also significantly reduced in RA patients with antiinflammatory HDL as compared with healthy controls (P = 0.001). Conclusion Proinflammatory HDL in this RA patient cohort was associated with active disease and an altered protein cargo as compared with antiinflammatory HDL in RA patients and in healthy controls. The antiinflammatory function of HDL was inversely correlated with systemic inflammation in RA patients and may warrant further investigation as a mechanism by which active RA increases cardiovascular morbidity and mortality. [source] An evaluation of laparoscopic tissue harvesting for human adult urological smooth muscle physiological experimentationBJU INTERNATIONAL, Issue 3 2005John F. Bolton OBJECTIVE To evaluate the properties of laparoscopically harvested bladder neck and ureteric smooth muscle, compared with tissue obtained at open surgery. MATERIALS AND METHODS Bladder neck was harvested from patients undergoing open (eight) or laparoscopic radical prostatectomy (11). Ureter was obtained from patients undergoing nephrectomy (laparoscopic or open) and cystectomy (open only); obtained openly from 16 and laparoscopically from seven. Muscle strips dissected from these samples were perfused in a Brading-Sibley organ bath, and stimulated using standard agonists (100 µmol/L carbachol for bladder neck, 100 mmol/L KCl-enriched Krebs' solution for ureteric muscle). Tensions produced were recorded using strain gauges and analysed using data-acquisition software. Results were compared by a two-tailed Fisher's exact test to determine significance. RESULTS Openly harvested bladder neck muscle strips from six patients showed a measurable response to the standard agonist. Laparoscopically harvested bladder neck strips from only two patients showed any measurable response. Openly harvested ureteric muscle strips from 12 patients responded to K-enriched solution, while one patient's laparoscopically harvested strips responded to stimulation. This difference was significant in both tissue groups separately (P < 0.025). Histological evaluation identified no specific differences between openly and laparoscopically harvested tissue. CONCLUSION The yield of smooth muscle available for research is significantly less when the resection is laparoscopic; this might be a result of diathermy damage at a subcellular level. With the increasing use of the laparoscopic approach in urological surgery, the effect on tissue availability for human smooth muscle physiological study is important to researchers in this field. [source] Gene expression in actinic keratoses: pharmacological modulation by imiquimodBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2004B. Lysa Summary Background, Actinic keratoses (AKs) are premalignant lesions that can progress into squamous cell carcinoma. Imiquimod, which belongs to the new class of immune-response modifiers, was recently shown to be effective in the treatment of AKs. The underlying mechanisms are not fully understood. Objectives, To study the expression of individual genes in uninvolved skin and AKs before therapy and to elucidate the way in which the expression of these genes is influenced by imiquimod therapy. Methods, We treated 13 patients with AK with imiquimod and compared gene expression before, during (five patients) and after (eight patients) therapy with that in uninvolved skin. We analysed genes coding for inflammatory cytokines or their receptors, adhesion molecules, anti-apoptotic proteins, p53 and toll-like receptors (TLRs) by reverse-transcriptase polymerase chain reaction. Results, Comparing uninvolved skin and untreated AK, we found significant differences in the expression of interleukin (IL)-6, hurpin, TLR7 and TLR8. During imiquimod therapy, we detected a further upregulation of interferon-,, IL-6, IL-10 receptor 1 and TLR7. In contrast, two anti-apoptotic genes, hurpin and HAX-1, were downregulated. We did not detect significant differences in gene expression for p53, tumour necrosis factor-, and ,- and ,-catenins. Clinically, the upregulated expression of the proinflammatory cytokines correlated with the local inflammation induced by imiquimod. Conclusions, Our results indicate that specific differences in gene expression are detectable between AK and uninvolved skin. Imiquimod influenced the expression of most genes analysed in this study. This work extends previous findings on the effects of imiquimod on gene regulation in AKs. [source] Aberrant processing of deviant stimuli in schizophrenia revealed by fusion of fMRI and EEG dataACTA NEUROPSYCHIATRICA, Issue 3 2010Vince D. Calhoun Calhoun VD, Wu L, Kiehl KA, Eichele T, Pearlson GD. Aberrant processing of deviant stimuli in schizophrenia revealed by fusion of fMRI and EEG data. Background: Aberrant electrophysiological and haemodynamic processing of auditory oddball stimuli is among the most robustly documented findings in patients with schizophrenia. However, no study to date has directly examined linked patterns of electrical and haemodynamic differences in patients and controls. Methods: In a recent paper we demonstrated a data-driven approach, joint independent component analysis (jICA) to fuse together functional magnetic resonance imaging (fMRI) and event-related potential (ERP) data and elucidated the chronometry of auditory oddball target detection in healthy control subjects. In this paper we extend our fusion method to identify specific differences in the neuronal chronometry of target detection for chronic schizophrenia patients compared to healthy controls. Results: We found one linked source, consistent with the N2 response, known to be related to cognitive processing of deviant stimuli, spatially localized to bilateral fronto-temporal regions. This source showed significant between-group differences both in amplitude response and in the fMRI/ERP distribution pattern. These findings are consistent with previous work showing N2 amplitude and latency abnormalities in schizophrenia, and provide new information about the linkage between the two. Conclusions: In summary, we use a novel approach to isolate and identify a linked fMRI/ERP component which shows marked differences in chronic schizophrenia patients. We also show that jointly using both fMRI and ERP measures provides a fully picture of the underlying haemodynamic and electrical changes which are present in patients. Our approach also has broad applicability to other diseases such as autism, Alzheimer's disease, or bipolar disorder. [source] | ||||||||||||||||||||||