bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal Mammary Nodes in Breast Cancer: Diagnosis and Implications for Patient Management—A Systematic Review
Authors: Chen Ronald C. , Lin Nancy U. , Golshan Mehra , Harris Jay R. , Bellon Jennifer R.
Published: August 2008

The management of internal mammary nodes (IMNs) in breast cancer is controversial. Surgical series from the 1950s showed that one third of breast cancer patients had IMN involvement, with a higher risk in patients with medial tumors and/or positive axillary nodes. IMN metastasis has similar prognostic importance as axillary nodal involvement. However, after three randomized trials showed no survival benefit from extended mastectomy compared with radical or modified radical mastectomy, IMN dissection was largely abandoned. Recently, lymphoscintigraphy studies have renewed interest in IMN evaluation. Approximately one fifth of internal mammary sentinel nodes are pathologic, although most centers do not perform IMN biopsies because of concerns about morbidity and lack of established survival benefit. In addition, results from randomized trials testing the value of postmastectomy irradiation and a meta-analysis of 78 randomized trials have provided high levels of evidence that local-regional tumor control is associated with long-term survival improvements. This benefit was limited to trials that used systemic therapy, which was not routinely administered in the earlier surgical studies, although the contribution from IMN treatment is unclear. IMN irradiation has also been shown to cause increased cardiac morbidity. Before mature results from current randomized trials assessing the benefit of IMN irradiation become available, lymphoscintigraphy may be used to help guide decisions regarding systemic and local-regional treatment. However, even in patients with visualized primary IMN drainage, the potential benefit of treatment should be balanced against the risk of added morbidity.
Urgent Need for a New Staging System in Advanced Colorectal Cancer
Authors: Poston Graeme J. , Figueras Joan , Giuliante Felice , Nuzzo Gennaro , Sobrero Alberto F. , Gigot Jean-Francois , Nordlinger Bernard , Adam Rene , Gruenberger Thomas , Choti Michael A. , Bilchik Anton J. , Van Cutsem Eric J.D. , Chiang Jy-Ming , D'Angelica Michael I.
Published: August 2008

Despite recent advances in the medical treatment of metastatic colorectal cancer (mCRC), which include irinotecan- and oxaliplatin-based first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patient's treatment and the increasing use of targeted monoclonal antibodies, 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with CRC liver metastases, liver resection remains the only chance of cure, with 5-year survival rates ranging from 25% to 40%. However, 80% to 85% of patients with stage IV CRC have liver disease which is considered unresectable at presentation. The rapid expansion in the use of improved combination chemotherapy regimens plus or minus biologics, to render initially unresectable metastases resectable has increased the percentage of patients eligible for potentially curative surgery. However, the current staging criteria for CRC patients with metastatic disease do not reflect these recent changes or the fact that there is also a large variation in the survival of patients with stage IV CRC. For example the survival for a patient with a solitary, resectable liver metastasis is better than that for a patient with stage III disease. A new staging system is therefore needed that acknowledges both the improvements that have been made in surgical techniques for resectable metastases and the impact of modern chemotherapy on rendering initially unresectable CRC liver metastases resectable, while at the same time distinguishing between patients with a chance of cure at presentation and those for whom only palliative treatment is possible.
Self-Abasement and Republican Insecurity: Paul Fane in Its Political Context
Authors: Grant David
Published: August 2008

Nathaniel Parker Willis's novel Paul Fane (1856), which tells the story of a painter who journeys to Europe to learn the significance of a slight he has received in America from an Englishwoman, is the meeting place of two traditions that were already converging in the discourse of the new Republican party: the long-standing American resentment of foreign aristocratic judgment and the growing belief that the slave oligarchy worked its will by overawing Northerners into a sense of inferiority. The novel helped to strengthen the parallel between these two anxieties by representing the content of the older complaint in the tone and with the emphasis of the newer political fear. The novel thus contributed to those Republican warnings against self-abasement that gave the new party a fresh power derived from a traditional feature of patriotic rhetoric. Paul's seduction into and recovery from the lure of an aristocracy willing to sanction his gentility only on the condition that he perpetuate through his art its system of class recognition dramatized the core Republican proposition: the politics of compromise was degrading and the nation would be saved only when the North resolved to demystify rather than reproduce the slave oligarchy's cultural authority. Through this means, the novel helped the Republicans to set the stakes of political victory as the survival of a Northern subject capable of keeping its distance from the residual standards and ideological reflexes whose effect was to annul its role in history.
Impostors of Freedom: Southern White Manhood, Hypodermic Morphine, and E. P. Roe's Without a Home
Authors: Zieger Susan
Published: August 2008

The essay examines the first U.S. novel about hypodermic morphine addiction, Edward Payson Roe's Without a Home (1881) in the context of the broader cultural history of addiction. When habituation to hypodermic morphine became a noted phenomenon in the years following the Civil War, writers described it by the temperance movement's familiar metaphor for habituation to alcohol: self-enslavement. “Opium slaves” joined the ranks of figurative “slaves to the bottle,” as implicitly white men who had ironically squandered their freedom in exchange for a degrading compulsion. At the same time, the temperance plot was updated to include the idea that such habituations might be nervous illnesses afflicting modern professional workers. Through its addicted protagonist Martin Jocelyn, Roe's novel engages these unevenly developing medical, reform, and popular early representations of addiction. A Confederate veteran inured to the slave-owning economy of the South, Jocelyn fails to become a modern professional when he moves to New York City after the end of the war. The cause of his downfall is his dependence on morphine, which is portrayed both as a diagnosable condition and as the shameful, emasculating servitude of self-enslavement. Attempting to pass as a breadwinner, husband, and professional, Jocelyn's addiction makes him an impostor of freedom. But it also shows how the history of chattel slavery haunted the late nineteenth-century conceptualization of addiction, in spite of the nation's attempt to forget its own shameful dependency on chattel slave labor.
Signifyin(g) on Reparation in Toni Morrison's Jazz
Authors: Pryse Marjorie
Published: August 2008

In Jazz, Morrison explores the transferential relation between book and reader, invoking Kleinian object relations, Gates's Talking Book, and her characters' search for lost mothers to drive the reader into his or her own psychoanalytic search for origins. Joe, Violet, and Dorcas have been scarred by maternal abandonment, suicide, or early death. Joe and Violet share an object relation with Golden Gray, the white-raised son of Hunter's Hunter who is present at Joe's birth. Golden is also the boy who haunts Violet's childhood, as True Belle tells Violet stories about him when she raises Violet after the death of Violet's mother. At the same time, Joe and Violet have never met Golden Gray and cannot locate this particular object relation: it exists within the novel's subconscious, recognizable only to narrator and reader. Jazz itself becomes the reader's transitional object, Gates's Signifyin(g) Monkey; and the narrator's own “unreliability” reflects on the black-authored text's “distrust” of the (white) American reader, a Kleinian “paranoid defence” against allowing the possibility of love to overcome hatred. As the talking book that is Jazz finds its Derridean “trace” in Wild, the narrator accomplishes what Joe Trace could not. Locating her own origins in Wild's “chamber of gold,” the narrator discovers the ways in which reading itself can become a site within which to work through “paranoid” feelings and to arrive at reparation.
Turkish Politics
Authors: Payne Donald M.
Published: August 2008

Donald M. Payne, Democrat from New Jersey, is a member of the US House of Representatives and chairman of the Subcommittee on Africa and Global Health of the House Foreign Affairs Committee.
Russia and the Black Sea's Frozen Conflicts in Strategic Perspective
Authors: Blank Stephen
Published: August 2008

Stephen Blank is professor of national security affairs at the Strategic Studies Institute, US Army War College.
Back to the Future: Rediscovering America's Foreign Policy Traditions
Authors: Eland Ivan
Published: August 2008

Ivan Eland is senior fellow at the Independent Institute and author of the books The Empire Has No Clothes: US Foreign Policy Exposed and Putting “Defense” Back into US Defense Policy.
Promoting the Theory and Practice of Criminology: The Australian and New Zealand Society of Criminology and Its Founding Moment
Authors: Finnane Mark
Published: August 2008

The Australian and New Zealand Society of Criminology was an initiative of Australia's first criminology department, at Melbourne, from where the proposal to establish a journal also evolved. The society was of its time, its priorities reflecting above all the negligible research knowl-edge of crime and criminal justice in the antipodes. But local initiative had a regional (Asia-Pacific) and international (disciplinary as well as geo -graphical) context. In this article I explore some of this context, consider the ways in which it delayed the establishment of the almost contempora-neous Australian Institute of Criminology, and discuss the potential of a regional engagement that was only partly fulfilled in subsequent years. In doing so I also ask how adequate are interpretations of criminology's mid-century history as above all conservative, pragmatic, technocratic and administrative.
Theories of Indigenous Violence: A Preliminary Empirical Assessment
Authors: Snowball Lucy , Weatherburn Don
Published: August 2008

A number of theories have been put forward to explain the high level of violence among Australia's Indigenous population. Up until 2002, lack of suitable data on the risk factors associated with Indigenous violent victimisation made it very difficult to assess the adequacy of these theories. In 2002, the Australian Bureau of Statistics conducted a national survey (the NATSISS) of Aboriginal and Torres Strait Islander peoples. That survey made it possible to examine a range of correlates of Indigenous violent victimisation. Analysis of the NATSISS victimisation data, however, has so far been limited to a few bivariate comparisons. This article presents the results of the first multivariate analysis of risk factors for violent victimisation among Indigenous Australians using the NATSISS. The results provide strong support for lifestyle/routine activity theories, moderate support for social disorganisation and social deprivation theories, but little support for cultural theories of Indigenous violence.
School-Based Drug Prevention Programs: A Review of What Works
Authors: Soole David W. , Mazerolle Lorraine , Rombouts Sacha
Published: August 2008

This article examines the effectiveness of school-based drug prevention programs in preventing illicit drug use. Our article reports the results of a systematic review of the evaluation literature to answer three fundamental questions: (1) do school-based drug prevention programs reduce rates of illicit drug use? (2) what features are characteristic of effective programs? and (3) do these effective program characteristics differ from those identified as effective in reviews of school-based drug prevention of licit substance use (such as alcohol and tobacco)? Using systematic review and meta-analytic techniques, we identify the characteristics of school-based drug prevention programs that have a significant and beneficial impact on ameliorating illicit substance use (i.e., narcotics) among young people. Successful intervention programs typically involve high levels of interactivity, time-intensity, and universal approaches that are delivered in the middle school years. These program characteristics aligned with many of the effective program elements found in previous reviews exploring the impact of school-based drug prevention on licit drug use. Contrary to these past reviews, however, our analysis suggests that the inclusion of booster sessions and multifaceted drug prevention programs have little impact on preventing illicit drug use among school-aged children. Limitations of the current review and policy implications are discussed.
Criminology's Darkest Hour: Biocriminology in Nazi Germany
Authors: Rafter Nicole
Published: August 2008

This article deals with criminology and its effects during Hitler's Third Reich (1933–1945). For comparative purposes, it also examines the nature and effects of criminology in fascist Italy (1922–1943). In both states, criminology became an extension of political power, but only in Nazi Germany did it fully reach its murderous potential, working to justify the genocide of not only Jews and Gypsies but of criminals as well. Key questions include: How did biological ideas shape explanations of crime in Nazi Germany? How did Nazi science define ‘criminals’? What were the consequences of Nazi criminology? And what does the study of scientific criminology under the Nazis reveal about the nature of criminology itself?
Predictors of Indigenous Arrest: An Exploratory Study
Authors: Weatherburn Don , Snowball Lucy , Hunter Boyd
Published: August 2008

The Royal Commission into Aboriginal Deaths in Custody attributed Indigenous overrepresentation in the criminal justice system to Indigenous disadvantage. Others have attributed it to alcohol abuse and substance use and/or passive welfare dependence. To date, however, there has been little rigorous empirical research into the factors that distinguish Indigenous Australians who come into contact with the criminal justice system from those who do not. The study reported here uses the 2002 National Aboriginal and Torres Strait Islander Social Survey (NATSISS) to explore the correlates of Indigenous arrest. The analyses suggest that factors like economic stress, welfare dependence and unemployment are strongly correlated with whether or not an Indigenous respondent has been arrested and with the number of times an Indigenous respondent has been arrested in the past 5 years. The strongest correlate, however, is alcohol abuse. The implications of these findings for research and policy on Indigenous contact with the justice system are discussed.
Intestine-specific expression of green fluorescent protein-tagged cathepsin B: proof-of-principle experiments
Authors: Mayer Kristina , Iolyeva Maria E. , Meyer-Grahle Ulf , Brix Klaudia
Published: August 2008

We hypothesized that tissue-specific expression of cathepsin B-enhanced green fluorescent protein (CB-EGFP) can be driven by the A33-antigen promoter that contains positive cis-regulatory elements, including caudal-related homeobox (CDX) binding sites. The intestine-specific transcription factor Cdx1 is crucial for A33-antigen promoter activation and could thereby induce expression of CB-EGFP. This concept was tested by construction of the vector pA33-CathB-EGFP encoding CB-EGFP downstream of the A33-antigen promoter. Its Cdx1 dependence, as an indication of its intestine-specific expression, was tested in Cdx1-negative CHO-K1 cells. Cdx1 expression was achieved upon transfection with pCdx1-DsRed-Express and was indicated by red fluorescence of the simultaneously translated reporter protein. Immunolabeling with Cdx1-specific antibodies showed correct targeting of the transcription factor to its point of action in nuclei of transfected cells. Co-transfection experiments with plasmids pA33-CathB-EGFP and pCdx1-DsRed-Express confirmed the hypothesis that Cdx1 indeed activates CB-EGFP expression in a manner dependent on the A33-antigen promoter. Co-localization with compartment-specific markers and subcellular fractionation confirmed CB-EGFP trafficking along the expected route to endolysosomal compartments. Hence, the A33-antigen promoter represents a potent tool for induction of Cdx1-dependent CB-EGFP expression in vitro. Our proof-of-principle studies confirm the suitability of this approach in visualizing protease transport in Cdx1-positive tissues of the gastrointestinal tract.
How Na+ activates thrombin – a review of the functional and structural data
Authors: Huntington James A.
Published: August 2008

Thrombin is the ultimate coagulation factor; it is the final protease generated in the blood coagulation cascade and is the effector of clot formation. Regulation of thrombin activity is thus of great relevance to determining the correct haemostatic balance, with dysregulation leading to bleeding or thrombosis. One of the most enigmatic and controversial regulators of thrombin activity is the monovalent cation Na+. When bound to Na+, thrombin adopts a ‘fast’ conformation which cleaves all procoagulant substrates more rapidly, and when free of Na+, thrombin reverts to a ‘slow’ state which preferentially activates the protein C anticoagulant pathway. Thus, Na+-binding allosterically modulates the activity of thrombin and helps determine the haemostatic balance. Over the last 30 years, there has been much research investigating the structural basis of thrombin allostery. Biochemical and mutagenesis studies established which regions and residues are involved in the slow→fast conformational change, and recently several crystal structures of the putative slow form have been solved. In this article, the biochemical and crystallographic data are reviewed to see if we are any closer to understanding the conformational basis of the Na+ activation of thrombin.
Conformational changes in bovine lactoferrin induced by slow or fast temperature increases
Authors: Schwarcz Waleska D. , Carnelocce Lorena , Silva Jerson L. , Oliveira Andréa C. , Gonçalves Rafael B.
Published: August 2008

Lactoferrin (LF) is an iron-binding protein present in several secreted substances, such as milk, and has broad antimicrobial and physiological properties. Because high temperatures may affect protein stability and its functional properties, we investigated the effect of heat on bovine LF structure and stability. The effects of temperatures used during the pasteurization process on LF and its relationship to protein functionality were studied. Conformational changes were monitored using spectroscopic techniques, such as circular dichroism (CD) and fluorescence spectroscopy. The CD data at 70°C showed that LF's secondary structure is drastically and irreversibly affected when the temperature is gradually increased. The same effect is observed when the temperature is gradually raised from 25°C to 105°C and changes are monitored by tryptophan fluorescence emission. We also verified the effects of simulating the pasteurization process; LF remained well structured during the entire process and this result was not time-dependent. Owing to preservation of the secondary structure with changes in the tertiary structure, we thus believe that pasteurization might cause LF to change into an intermediate partially folded state. A better understanding of heat stability is important for the use of LF as a bioactive component in food.
Human monocytes augment invasiveness and proteolytic activity of inflammatory breast cancer
Authors: Mohamed Mona Mostafa , Cavallo-Medved Dora , Sloane Bonnie F.
Published: August 2008

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and here, we examined in vitro the interactions between the human IBC cell line SUM149 and U937 human naive monocytes. We found an altered morphology, enhanced invasiveness and proteolytic activity of SUM149 cells when cultured with U937 cells or in U937-conditioned media (U937-CM). Increases in expression and activity of the cysteine protease cathepsin B and expression of caveolin-1 were also detected in SUM149 cells grown in U937-CM, thus suggesting a contribution of these proteins to the augmented invasion through and proteolysis of the extracellular matrix by the IBC cells.
Substrate specificity determination of mouse implantation serine proteinase and human kallikrein-related peptidase 6 by phage display
Authors: Sharma Navneet , Oikonomopoulou Katerina , Ito Kenichi , Renaux Bernard , Diamandis Eleftherios P. , Hollenberg Morley D. , Rancourt Derrick E.
Published: August 2008

We constructed a random library of hexapeptides displayed on the surface of bacteriophage T7 to determine the substrate specificity of proteinases. The phage-displayed library was subjected to repeated rounds of biopanning with native implantation serine proteinase and recombinant human kallikrein-related peptidase 6 (KLK6) followed by selection and identification of putative substrates. For both enzymes, the results obtained demonstrate a preference for arginine and lysine at multiple positions in the recognition cleavage motif, confirming their previously reported trypsin-like substrate specificity. In the case of KLK6, there is also a pronounced presence of tryptophan within the cleaved peptide sequences, indicating its potential dual substrate specificity, acting as both a trypsin and chymotrypsin-like enzyme.
Metastasis-associated C4.4A, a GPI-anchored protein cleaved by ADAM10 and ADAM17
Authors: Esselens Cary W. , Malapeira Jordi , Colomé Núria , Moss Marcia , Canals Francesc , Arribas Joaquín
Published: August 2008

Metalloproteases play a complex role in tumor progression. While the activity of some ADAM, ADAMTS and matrix metalloproteases (MMPs) seems to be protumorigenic, the activity of others seems to prevent tumor progression. The identification of the array of substrates of a given metalloprotease (degradome) seems an adequate approach to predict the effect of the inhibition of a metalloprotease in tumors. Here, we present the proteomic identification of a novel substrate for ADAM10 and -17. We used SILAC (Stable Isotope Labeling by Amino acids in Cell culture), a proteomic technique based on the differential metabolic labeling of cells in different conditions. This was applied to MCF7 cells derived from an invasive mammary tumor, and the same cells expressing shRNAs that knock down ADAM10 or -17. Following this approach, we have identified C4.4A as a substrate to both metalloproteases. Since C4.4A is likely involved in tumor invasion, these results indicate that the cleavage of C4.4A by ADAM10 and ADAM17 contributes to tumor progression.
The role of glycosylation and domain interactions in the thermal stability of human angiotensin-converting enzyme
Authors: O'Neill Hester G. , Redelinghuys Pierre , Schwager Sylva L.U. , Sturrock Edward D.
Published: August 2008

The N and C domains of somatic angiotensin-converting enzyme (sACE) differ in terms of their substrate specificity, inhibitor profiling, chloride dependency and thermal stability. The C domain is thermally less stable than sACE or the N domain. Since both domains are heavily glycosylated, the effect of glycosylation on their thermal stability was investigated by assessing their catalytic and physicochemical properties. Testis ACE (tACE) expressed in mammalian cells, mammalian cells in the presence of a glucosidase inhibitor and insect cells yielded proteins with altered catalytic and physicochemical properties, indicating that the more complex glycans confer greater thermal stabilization. Furthermore, a decrease in tACE and N-domain N-glycans using site-directed mutagenesis decreased their thermal stability, suggesting that certain N-glycans have an important effect on the protein's thermodynamic properties. Evaluation of the thermal stability of sACE domain swopover and domain duplication mutants, together with sACE expressed in insect cells, showed that the C domain contained in sACE is less dependent on glycosylation for thermal stabilization than a single C domain, indicating that stabilizing interactions between the two domains contribute to the thermal stability of sACE and are decreased in a C-domain-duplicating mutant.
Fluoride complexes of oncogenic Ras mutants to study the Ras-RasGAP interaction
Authors: Gremer Lothar , Gilsbach Bernd , Reza Ahmadian Mohammad , Wittinghofer Alfred
Published: August 2008

Down-regulation of Ras signalling is mediated by specific GTPase-activating proteins (GAPs), which stimulate the very slow GTPase reaction of Ras by 105-fold. The basic features of the GAP activity involve the stabilisation of both switch regions of Ras in the transition state, and the insertion of an arginine finger. In the case of oncogenic Ras mutations, the features of the active site are disturbed. To understand these features in more detail, we investigated the effects of oncogenic mutations of Ras and compared the GAP-stimulated GTPase reaction with the ability to form GAP-mediated aluminium or beryllium fluoride complexes. In general, we found a correlation between the size of the amino acid at position 12, the GTPase activity and ability to form aluminium fluoride complexes. While Gly12 is very sensitive to even the smallest possible structural change, Gly13 is much less sensitive to steric hindrance, but is sensitive to charge. Oncogenic mutants of Ras defective in the GTPase activity can however form ground-state GppNHp complexes with GAP, which can be mimicked by beryllium fluoride binding. We show that beryllium fluoride complexes are less sensitive to structural changes and report on a state close to but different from the ground state of the GAP-stimulated GTPase reaction.
Docking of tryptophan analogs to trytophanyl-tRNA synthetase: implications for non-canonical amino acid incorporations
Authors: Azim M. Kamran , Budisa Nediljko
Published: August 2008

Non-canonical amino acids (NAA), as building blocks for peptides and proteins during ribosomal translation, represent a nearly infinite supply of novel functions. The specific selection, activation and tRNA-charging of amino acids by aminoacyl-tRNA synthetases (AARS) in the aminoacylation reaction are essential steps. In most cases, aminoacylation of NAAis a good indication that the related amino acid will participate in ribosomal translation as well. However, testing the translational capacity of amino acid analogs has technical limitations. Therefore, a rapid and reliablein silicotest for NAArecognition by AARS would be advantageous in experimental design. We chose tryptophanyl-tRNA synthetase fromEscherichia colias a model system for docking studies with various tryptophan analogs using the FlexX-Pharm strategy. We were able to calculate relative binding energies for Trp analogs in TrpRS that correlate well with their translational activities inE. coli. In particular, FlexX-Pharm predicted the binding sites of fluoro-, amino-, hydroxyl- and aza-containing Trp analogs within 1.5 Å of Trp in the homology model ofE. coliTrpRS. Therefore, the use of ligand docking prior to NAAincorporation experiments might provide a straightforward means for determining NAAthat can be efficiently incorporated into a protein.
Homologous and heterologous expression and maturation processing of extracellular glutamyl endopeptidase of Staphylococcus epidermidis
Authors: Ohara-Nemoto Yuko , Ono Toshio , Shimoyama Yu , Kimura Shigenobu , Nemoto Takayuki K.
Published: August 2008

The extracellular serine endopeptidase GluSE (EC 3.4.21.19) is considered to be one of the virulence factors of Staphylococcus epidermidis. The present study investigated maturation processing of native GluSE and that heterologously expressed in Escherichia coli. In addition to the 28-kDa mature protease, small amounts of proenzymes with molecular masses of 32, 30, and 29 kDa were identified in the extracellular and cell wall-associated fractions. We defined the pre (M1-A27)- and pro (K28-S66)-segments, and found that processing at the E32-S33 and D48-I49 bonds was responsible for production of the 30- and 29-kDa intermediates, respectively. The full-length form of C-terminally His-tagged GluSE was purified as three proenzymes equivalent to the native ones. These molecules possessing an entire or a part of the pro-segment were proteolytically latent and converted to a mature 28-kDa form by thermolysin cleavage at the S66-V67 bond. Mutation of the essential amino acid S235 suggested auto-proteolytic production of the 30- and 29-kDa intermediates. Furthermore, an undecapeptide (I56-S66) of the truncated pro-segment not only functions as an inhibitor of the protease but also facilitates thermolysin processing. These findings could offer clues to the molecular mechanism involved in the regulation of proteolytic activity of pathogenic proteases secreted from S. epidermidis.
Mechanism of methaemoglobin breakdown by the lysine-specific gingipain of the periodontal pathogen Porphyromonas gingivalis
Authors: Smalley John W. , Birss Andrew J. , Szmigielski Borys , Potempa Jan
Published: August 2008

The R- and K-gingipain proteases of Porphyromonas gingivalis are involved in proteolysis of haemoglobin from which the defensive dimeric haem pigment is formed. Whilst oxyhaemoglobin is refractory towards K-gingipain, methaemoglobin is rapidly degraded. Ligation of methaemoglobin with N3
-, which effectively blocks haem dissociation from the protein, prevented haemoglobin breakdown. Haem-free globin was rapidly degraded by K-gingipain. These data emphasise the need for haemoglobin oxidation which encourages haem dissociation and makes the haem-free globin susceptible to proteolytic attack.
Fast in vitro translation system immobilized on a surface via specific biotinylation of the ribosome
Authors: Stapulionis Romualdas , Wang Yuhong , Dempsey Graham T. , Khudaravalli Rama , Nielsen Karen Margrethe , Cooperman Barry S. , Goldman Yale E. , Knudsen Charlotte R.
Published: August 2008

The ribosome is the macromolecular machine responsible for translating the genetic code into polypeptide chains. Despite impressive structural and kinetic studies of the translation process, a number of challenges remain with respect to understanding the dynamic properties of the translation apparatus. Single-molecule techniques hold the potential of characterizing the structural and mechanical properties of macromolecules during their functional cycles in real time. These techniques often necessitate the specific coupling of biologically active molecules to a surface. Here, we describe a procedure for such coupling of functionally active ribosomes that permits single-molecule studies of protein synthesis. Oxidation with NaIO4 at the 3′ end of 23S rRNA and subsequent reaction with a biotin hydrazide produces biotinylated 70S ribosomes, which can be immobilized on a streptavidin-coated surface. The surface-attached ribosomes are fully active in poly(U) translation in vitro, synthesizing poly(Phe) at a rate of 3–6 peptide bonds/s per active ribosome at 37°C. Specificity of binding of biotinylated ribosomes to a streptavidin-coated quartz surface was confirmed by observation of individual fluorescently labeled, biotinylated 70S ribosomes, using total internal reflection fluorescence microscopy. Functional interactions of the immobilized ribosomes with various components of the protein synthesis apparatus are shown by use of surface plasmon resonance.
RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade
Authors: Pleschka Stephan
Published: August 2008

The Raf/MEK/ERK signal transduction cascade belongs to the mitogen-activated protein kinase (MAPK) cascades. Raf/MEK/ERK signaling leads to stimulus-specific changes in gene expression, alterations in cell metabolism or induction of programmed cell death (apoptosis), and thus controls cell differentiation and proliferation. It is induced by extracellular agents, including pathogens such as RNA viruses. Many DNA viruses are known to induce cellular signaling via this pathway. As these pathogens partly use the DNA synthesis machinery for their replication, they aim to drive cells into a proliferative state. In contrast, the consequences of RNA virus-induced Raf/MEK/ERK signaling were less clear for a long time, but since the turn of the century the number of publications on this topic has rapidly increased. Research on this virus/host-interaction will broaden our understanding of its relevance in viral replication. This important control center of cellular responses is differently employed to support the replication of several important human pathogenic RNA viruses including influenza, Ebola, hepatitis C and SARS corona viruses.
Sabotage of antiviral signaling and effectors by influenza viruses
Authors: Wolff Thorsten , Zielecki Florian , Abt Marion , Voss Daniel , Semmler Ilia , Matthaei Markus
Published: August 2008

Vertebrate cells activate multiple signaling modules upon virus infection to eliminate the invading pathogen and to prevent the establishment of a persistent infection. A major immediate response pathway is controlled by the RNA helicases RIG-I and MDA5, which, after recognition of viral nucleic acids, signal induction of the interferon (IFN)-α/β cytokine family that upregulates numerous antiviral effector proteins. Virulent viruses, in contrast, have learned during co-evolution with their hosts to manipulate or avoid this response in order to prevail in a repulsive environment. Focusing on the influenza viruses and their IFN-antagonistic NS1 proteins, we summarize recent progress in this rapidly evolving field at the intersection of virology and immunobiology involving studies of how viral pathogens induce and sabotage cellular defenses.
Specific inhibition of transcriptional activity of the constitutive androstane receptor (CAR) by the splicing factor SF3a3
Authors: Yun Hye Jin , Kwon Jungsun , Seol Wongi
Published: August 2008

The constitutive androstane receptor (CAR) is a member of the nuclear receptor superfamily and plays an important role in the degradation of xenobiotics in the liver. Using yeast two-hybrid screening, we identified SF3a3, a 60-kDa subunit of the splicing factor 3a complex, as a specific CAR-interacting protein. We further confirmed their interaction by both co-immunoprecipitation and GST pull-down assay. Functional studies showed that overexpression of SF3a3 inhibited the reporter activity driven by a promoter containing CAR binding sequences by up to 50%, whereas reduced expression of SF3a3 activated the same reporter activity by approximately three-fold. The inhibitory function of SF3a3 is independent of the presence of TCPOBOP, a CAR ligand. These data suggest that SF3a3 functions as a co-repressor of CAR transcriptional activity, in addition to its canonical function.
Impaired synthesis of heme oxygenase-1 in Fanconi anemia cells can be rescued by transfection of Fanconi wild-type cDNA
Authors: Kontou Maria , Hirsch-Kauffmann Monica , Schweiger Manfred
Published: August 2008

Fanconi anemia is a fatal, hereditary chromosome instability syndrome of early childhood with progressive pancytopenia and cancer-proneness. Hypersensitivity to alkylating agents points to DNA repair inefficiency. Excess reactive oxygen intermediates and hypersensitivity to oxygen, all features of Fanconi anemia cells, give evidence for a disturbed oxidative metabolism. Here, we report that expression of the inducible heme oxygenase-1, an essential antioxidative defense protein, is impaired in Fanconi anemia cells and can be reinstated with the transfection of Fanconi A wild-type cDNA. A causative interaction of Fanconi anemia proteins with transcription of selected proteins is indicated. The results enlighten the oxygen sensitivity in Fanconi anemia.
Alien marine macrophytes in Greece: a review
Authors: Tsiamis Konstantinos , Panayotidis Panayotis , Zenetos Argyro
Published: August 2008

By October 2007, a total of 31 alien marine macrophytic species had been recorded on Greek coasts. Following a critical review of these findings, these species were classified as established (9 species), casual (8 species) and debatable (14 species). There were also 23 species found in the Greek marine flora that are excluded from the list of alien macroalgae. Brief remarks are provided for the debatable species. Based on the distribution of the alien species, four are considered as invasive, although their impact on the native vegetation has not yet been documented. A trend analysis revealed that most alien species (65% of current total) were found in the period 1971–2007. Shipping contributes to most alien macroalgal immigration (48%), followed by progressive immigration via the Suez Canal (33%), while aquaculture plays a minor role (16%), unlike the western Mediterranean Sea where aquaculture accounts for 73% of the macrophyte introductions.
Dynamics and patterns of algal colonization on mechanically damaged and dead colonies of the coral Porites lutea
Authors: Titlyanov Eduard A. , Titlyanova Tamara V. , Chapman David J.
Published: August 2008

We studied (1) the dynamics of colonization by epilithic algae on mechanically damaged colonies of the coral Porites lutea, (2) the dynamics of algal colonization on dead coral fragments (coral pebbles), (3) and regeneration rates of the damaged corals under a broad range of natural light conditions on the fringing reef of Sesoko Island (Okinawa, Japan). After 1 month (of the experiment), 26 algal species occupied damaged coral areas with a projected areal cover of 1–7%. Colonizers were mainly diatoms, Cyanobacteria, filamentous green, brown and red algae. During this period, the algal settlers were not an impediment to coral polyp recovery. The recovery rate of damaged coral tissue was highest after the first month, amounting to approximately 0.15 mm day-1 under bright light (70–90% of incident surface photosynthetically active radiation, PAR0), 0.14 mm day-1 under moderate light (20–30% PAR0) and 0.07 mm day-1 under low light (2–5% PAR0). After 3 months, 58 algal species had settled onto lesions and 43 species onto coral pebbles. Projected areal cover of the algae was 30–90%. After the second month of the experiment, the recovery rates of corals declined sharply to 0.02–0.04 mm day-1. Under high and moderate light intensities, the measured parameters were similar (with the exception of the number of algal settlers). Under low light, the number, the density of algal settlers and the regeneration rate of polyps on damaged corals were significantly reduced. The algal turf community was formed under light intensities from 20% to 90% PAR0, but was not formed under low light.
Blended Museum – Perspektiven für eine vielfältige Besuchererfahrung (Enhancing Visitor Experience through Information Design and Interaction)
Authors: Klinkhammer Daniel , Reiterer Harald
Published: August 2008

Durch den Einsatz von Informations- und Kommunikationstechnologien (IuK) hat sich das Spektrum musealer Informations-präsentation und Besucherpartizipation erweitert. Museale Inhalte können hierdurch nicht nur real, sondern auch virtuell zugänglich gemacht werden. Im Ansatz des Blended Museums wird dem Konzept des Blended Learning folgend versucht, durch Kombination verschiedener Medien und Methoden eine didaktisch sinnvolle Verknüpfung zwischen dem realen und virtuellen Museum zu erstellen. Ziel dieser Vermischung ist es vielfältige Besuchererfahrungen (Visitor Experience) zu ermöglichen, welche durch innovative Interaktionstechniken, holistisches Informationsdesign und neuartige Vermittlungs-strategien erzielt werden sollen.
Wer sind die Besucher des virtuellen Museums und welche Interessen haben sie? (Who are the Visitors of the Virtual Museum and What are they Interested in?)
Authors: Schweibenz Werner
Published: August 2008

Der Beitrag basiert auf einer Analyse der internationalen Forschungsliteratur und geht folgenden Fragen nach: wie ist das Verhältnis von Museumsbesuch und Internetnutzung in Deutschland, welche Informationsbedürfnisse haben virtuelle Museumsbesucher im Internet und wie verhalten sie sich, wie stehen sie zu hohen technischen Anforderungen von Web-Angeboten? Aus der Literaturanalyse werden Schlussfolgerungen für die Vermittlung und den Einsatz von Wissensmedien für virtuelle Museen im Internet gezogen.
Digitale Museumsanwendungen (Digital Museum Appliances)
Authors: Göbel Stefan , Geelhaar Jens
Published: August 2008

Viele Museen suchen heutzutage neue Methoden und Wege, um Museen attraktiver zu gestalten und weitere Museumsbesucher und Zielgruppen anzusprechen. Eine Ausprägung davon stellen Science Center oder Themenparks dar, aber auch Kinder-, Kunst- und Technikmuseen mit digitalen Museum Guides oder „Exponaten zum Anfassen”. Basierend auf diesem Trend haben das ZGDV Darmstadt und die Bauhaus-Universität Weimar unabhängig voneinander multimediale Museumsanwendungen entwickelt, die insbesondere das jüngere Publikum in die Museen locken als auch „etablierte” Museumsgänger durch einen digital erweiterten Wissens- und Erlebnisraum ansprechen soll. Die Fallbeispiele des ZGDV „DinoSim Senckenberg”, „art-E-fact” und das innovative Präsentationssystem „iPX” repräsentieren interaktive Museumsanwendungen zur wissenschaftlich-technischen Simulation von Dinosaurier Laufstudien und der Exploration von Gemälden und Kunstobjekten sowie des menschlichen Körpers innerhalb der seitens des Heinz Nixdorf Museumsforum initiierten Sonderausstellung „Computer.Mensch” direkt vor Ort im Museum; „DinoExplorer Senckenberg” bietet eine virtuelle Umgebung zur spielerischen Exploration von Museumsräumen und Exponaten in Form einer emulierten Museumsrallye. Das digitale Osmantinum spricht den Literatur interessierten Besucher an und ist als mobiles Informations- und Führungssystem auf der Basis eines PDA's konzipiert, ohne die besondere Stimmung der Museumsräume zu stören.
Accessibility-orientierte Anforderungsanalyse (AORA) (Accessibility-oriented Requirement Analysis (AORA))
Authors: Siegemund Katja
Published: August 2008

Der Artikel stellt Richtlinien für eine Accessibility-orientierte Anforderungsanalyse (AORA) dar, die auf dem Konzept der Benutzerorientierung, dem Usage-Centered Design und dem Usability Engineering Lifecycle (Mayhew 1999) beruht. Ziel ist es, das oft vorherrschende Kommunikationsproblem zwischen Kunden und Softwareentwicklern mittels einer für beide Seiten einfachen, intuitiven und weiterverwendbaren Möglichkeit der Anforderungserfassung zu kompensieren. Accessibility-Belange werden dabei bereits während der Anforderungsanalyse einbezogen. Besonderer Wert wird dabei auf die Nutzerpartizipation, die Berücksichtigung von Accessibility-Kriterien sowie die Einbeziehung von Stakeholdern gelegt. Um die Ergebnisse wiederverwendbar zu gestalten, wurden Techniken der Domänen-Analyse eingesetzt. Um die oft schwierige Identifikation und Darstellung von Beziehungen zwischen nicht-funktionalen Eigenschaften und Aspekten des Nutzungskontexts (z.B. Nutzereigenschaften, Arbeitsumfeld) zu ermöglichen, wurde CONFEAT (Context-driven Feature Tree Generation) entwickelt – eine Methode zur kontextbasierten Erstellung von Eigenschaftsbäumen. Hierfür wurden Kreuztabellen aus der formalen Begriffsanalyse (FCA) mit Eigenschaftsbäumen (Feature Trees) aus der Softwaretechnik kombiniert.
Inflammatory Gene Polymorphisms and Susceptibility to Kawasaki Disease and Its Arterial Sequelae
Authors: Cheung Yiu-fai , Huang Guo-ying , Chen Shu-bao , Liu Xiao-qin , Xi Li , Liang Xue-cun , Huang Mei-rong , Chen Sun , Huang Li-su , Liu Xiao-qing , Chan Koon-wing , Lau Yu-lung
Published: August 2008

OBJECTIVE. We tested the hypothesis that single-nucleotide polymorphisms of inflammatory genes C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) may exert influence on susceptibility to Kawasaki disease and its arterial sequelae.

METHODS. We analyzed the CRP +1444 C→T and TNF-α −308 G→A polymorphisms in 167 patients aged 8.9 ± 4.1 years with a history of Kawasaki disease (73 with and 94 without coronary aneurysms) and 124 healthy control subjects. For patients with Kawasaki disease, we further determined whether these single-nucleotide polymorphisms were associated with coronary aneurysms, carotid arterial stiffening, and intima-media thickness.

RESULTS. Genotypic and allelic frequencies of CRP +1444 for T carrier and TNF-α −308 for A carrier were significantly higher in patients than in control subjects. The genotypic and allelic distributions did not differ between patients with and those without coronary aneurysms; however, patients with CRP +1444 CT/TT genotype compared with those with a CC genotype and patients with TNF-α −308 GA/AA genotype compared with those with a GG genotype had significantly greater carotid arterial stiffness and intima-media thickness. Carriers of both CRP +1444 T allele and TNF-α −308 A allele had the highest susceptibility to Kawasaki disease and a significant trend of increased arterial stiffness and intima-media thickness compared with those who carried either 1 or none of the rare alleles. Multiple linear regression analysis identified CRP +1444 allele carrier as a significant determinant of both carotid stiffness and carotid intima-media thickness and TNF-α −308 A allele carrier as a determinant of only intima-media thickness.

CONCLUSIONS. Our findings suggest that CRP +1444 C→T and TNF-α −308 G→A polymorphisms are associated with predisposition to Kawasaki disease and, in patients with Kawasaki disease, increased carotid arterial stiffness and intima-media thickness in the long-term.
Plano amostral da Pesquisa Nacional sobre Comportamento Sexual e Percepções sobre HIV/Aids, 2005
Authors: Bussab Wilton de Oliveira
Published: August 2008

OBJETIVO: Descrever o plano amostral e os métodos de estimação utilizados na coleta e análise dos dados da Pesquisa sobre o Comportamento Sexual e Percepções sobre HIV/Aids da População Brasileira em 2005. MÉTODOS: São apresentadas as decisões adotadas quanto à definição do universo da pesquisa, estratos de interesse da pesquisa e do plano amostral, principais procedimentos para análise dos dados e desempenho da amostra no campo. RESULTADOS DA AMOSTRAGEM: Foi elaborado plano probabilístico, com 5.040 unidades amostrais, obtidas sobre a população brasileira: indivíduos com idades entre 16 e 65 anos, residentes nos grandes centros urbanos brasileiros. Trata-se de plano amostral complexo, distribuído em oito domínios principais de estimação, desenhado em múltiplos estágios, com um homem ou mulher entrevistada no último desses estágios. Cada unidade entrevistada e cada domicílio têm probabilidade específica de pertencer à amostra.