bluuebunny/crossref_metadata_2025 huggingface dataset:
Anxious Sexualities: Masculinity, Nationalism and Violence
Authors: Anand Dibyesh
Published: April 2007

An ethnographic research among activists subscribing to majoritarian Hindu nationalism in India reveals that anxiety, masculinity and sexuality are crucial ingredients in their identity politics. The inimical figure used to mobilise the Hindu nationalist identity is a stereotyped Muslim masculinity which in turn is imagined as dangerous owing to a mix of negative images of Islam, history, physicality and culture. The specificities of anti-Muslim riots in Gujarat in 2002, and especially the pervasiveness of sexual violence there, can be understood as an assertion of the new Hindu identity which conflates nationalism with masculinity and violence. And yet it was the complicity of the institutions of the state that accounted for the lethality of violence in Gujarat. The article argues that masculinised nationalism and embedded statehood are crucial features of contemporary (inter) national politics.
Rethinking Globalised Resistance: Feminist Activism and Critical Theorising in International Relations
Authors: Eschle Catherine , Maiguashca Bice
Published: April 2007

This article argues that a feminist approach to the ‘politics of resistance’ offers a number of important empirical insights which, in turn, open up lines of theoretical inquiry which critical theorists in IR would do well to explore. Concretely, we draw on our ongoing research into feminist ‘anti-globalisation’ activism to rethink the nature of the subject of the politics of resistance, the conditions under which resistance emerges and how resistance is enacted and expressed. We begin by discussing the relationship of feminism to critical IR theory as a way of situating and explaining the focus and approach of our research project. We then summarise our key empirical arguments regarding the emergence, structure, beliefs, identities and practices of feminist ‘anti-globalisation’ activism before exploring the implications of these for a renewed critical theoretical agenda in IR.
Do We Understand Each Other Yet? Troubling Feminist Encounters with(in) International Relations
Authors: Zalewski Marysia
Published: April 2007

This article suggests that although a distinction between ‘International Relations’ and ‘Gender and International Relations’ may be untenable, there is a continued need for feminist analysis of international politics. Yet to imagine gendered scholarship on international politics as more than IR's ‘other’ remains a challenge—though resisted as the articles in this issue demonstrate. This resistance is reassuring, especially given that ambitions to imagine (G)IR as ‘one’ have been unsettled by a growing schism between feminist scholarship and gender analyses, particularly in ‘neo-feminist’ work that has gained prominence of late within IR. This article explores feminist encounters with(in) IR, firstly by considering the ways in which the ‘doing’ of feminism is simultaneously the ‘undoing’ of IR, and secondly by considering the growing trend to alleviate gendered analyses of their feminist commitments.
Beyond Being Marginal: Gender and International Relations in Britain
Authors: Squires Judith , Weldes Jutta
Published: April 2007

In this introduction, we situate ‘gender and international relations in Britain’. We discuss our understandings of gender, I/international R/relations and GIR. In the second section we discuss the relationship of feminist to gendered IR, arguing that while intimately related, they are nonetheless not synonymous. We turn in the third section to a critical discussion of feminist IR's tendency to see itself as marginal to mainstream IR, a move that contributes to the marginalisation it laments. In the fourth section we compare the development of GIR with gender in Politics, which has been less concerned from the outset with issues of marginality. In the final section we argue that GIR has come into its own, introducing the articles in this issue as instances of self-assured gendered analyses of ‘things international’.
Social Democracy or Social Liberalism? Ideological Sources of Liberal Democrat Policy
Authors: GRAYSON RICHARD S.
Published: April 2007

Liberal Democrat policy has been labelled as social democratic, yet the party has been reluctant to so describe itself. Taking Crosland's The Future of Socialism as a reference point, there appears to be much shared ground between social democracy and Liberal Democrat policy. Meanwhile, the party's tax policy adopted in 2006 takes the Croslandite approach of taxing wealth rather than income. Despite this, the article argues that the party is a social liberal rather than a social democratic one. These two political philosophies have so much in common that it is understandable that some commentators see the influence of social democracy where they might instead perceive social liberalism. Yet the two differ in their attitudes to the state. Both see a positive role for the state in furthering social goods. However, social liberalism shares classical liberal concerns about the dangers of an over‐mighty state. This approach underpins Liberal Democrat policy.
Liberal Democrat Leadership: The Cases of Ashdown and Kennedy
Authors: BRACK DUNCAN
Published: April 2007

Effective leadership of the Liberal Democrats requires a combination of strengths: communications skills, a clear agenda, the ability to manage the party and personal abilities, including stamina, self‐confidence and a love for the party itself. This article assesses Paddy Ashdown's and Charles Kennedy's periods as leader. It concludes that the first two phases of Ashdown's leadership were successful: he first ensured the party's survival and then positioned it so that it was able to benefit from the rise in support for the centre‐left without being squeezed out by Labour. In the third phase, however, the attempt to deliver a common agenda with Labour was a failure, and Ashdown increasingly lost touch with his own party. Kennedy's first two years as leader were also relatively successful, but after that his leadership fell apart, suffering from a lack of an agenda, a failure of party management, a weakness in communication skills and a lack of self‐confidence. His underlying problem was not alcoholism; it was that he was not capable of being an effective leader.
Liberal Democrat Councillors: Community Politics, Local Campaigning and the Role of the Political Party
Authors: COPUS COLIN
Published: April 2007

Liberal Democrats have long displayed the success of community politics since its adoption at the Liberal Party Assembly in 1970. Community politics, however, brings with it not only electoral success but an expectation amongst voters that Liberal Democrat councillors will act in certain ways as local representatives. The article presents the results of national research conducted amongst councillors of the three main parties, and compares the attitudes of Liberal Democrat councillors to aspects of local democracy with those of their Labour and Conservative counterparts. It identifies two types of Liberal Democrat councillor and uses these to explain the attitudinal differences and similarities found with Labour and Conservative councillors.
100 Years On: Who are the Inheritors of the ‘New Liberal’ Mantle?
Authors: HOLMES ALISON
Published: April 2007

The ‘great divorce’ of progressive politics at the end of the nineteenth century permanently altered British politics. While the philosophies of the Labour movement and the Liberal Party had many common elements, ideologically they diverged on issues of the role of liberty and the state in relation to the individual and the community to the point that they became irreconcilable. New Liberalism was one result of that debate. Contemporary political debate reflects many of the same features as the turmoil present a century ago, and the Labour Party and the Liberal Democrats are again contesting much of the same ground. This article seeks to draw out the salient aspects of this debate to conclude which, if either, party is the inheritor of the New Liberal tradition.
Writing texts with Radical Change characteristics
Authors: Pantaleo Sylvia
Published: April 2007

Research has revealed how students draw upon other texts when writing their own texts. This article explores how the writing of Alyssa, a 10‐year‐old Grade 5 student, was influenced by her engagement with literature with Radical Change characteristics, as well as by her knowledge of and experience with other texts. Dresang's Radical Change taxonomy is used as a framework for analysing the storybook created by Alyssa. The article concludes with discussions of the intertextual nature of the literature used in the study, and the social nature of intertextuality in the research classroom.
“Busting with blood and gore and full of passion”: the impact of an oral retelling of theIliadin the primary classroom
Authors: Reedy David , Lister Bob
Published: April 2007

This paper describes the impact of an oral retelling of Homer'sIliadon pupils' learning in Key Stage 2 classrooms (children aged 9–11) in schools in East London. We argue that the oral nature of the retelling and responses promoted high levels of engagement and inclusion, leading to enhanced understanding by the pupils. The use of a complex and emotionally powerful text also encouraged a changing of the nature of the discourse between teachers and pupils. Finally we argue for the use of texts like theIliadas an integral part of the literacy curriculum.
Handwriting: what do we know and what do we need to know?
Authors: Medwell Jane , Wray David
Published: April 2007

Handwriting has a low status and profile in literacy education in England and in recent years has attracted little attention from teachers, policy‐makers or researchers into mainstream educational processes. This article identifies a substantial programme of research into handwriting, including studies located in the domains of special needs education and psychology, suggesting that it is time to re‐evaluate the importance of handwriting in the teaching of literacy. Explorations of the way handwriting affects composing have opened up new avenues for research, screening and intervention, which have the potential to make a significant contribution to children's progress in learning to write. In particular, the role of orthographic motor integration and automaticity in handwriting is now seen as of key importance in composing. Evidence from existing studies suggests that handwriting intervention programmes may have a real impact on the composing skills of young writers. In particular, they could positively affect the progress of the many boys who struggle with writing throughout the primary school years.
Synthetic phonics and the teaching of reading: the debate surrounding England's ‘Rose Report’
Authors: Wyse Dominic , Styles Morag
Published: April 2007

The Rose Report, commissioned by the Secretary of State for Education for England, recommended in March 2006 that early reading instruction must include synthetic phonics. This paper evaluates the extent to which research evidence supports this recommendation. In particular, a review of international research into the teaching of early reading shows that the Rose Report's main recommendation on synthetic phonics contradicts the powerful body of evidence accumulated over the last 30 years. In this paper it is argued that action already taken by the UK government to change the National Curriculum in line with the Rose Report's recommendations represents a change in pedagogy not justified by research.
Suburbanisation, Mobility and the ‘Good Life in the Country’: A Lifestyle Approach to the Sociology of Urban Sprawl in Germany
Authors: Jetzkowitz Jens , Schneider Jörg , Brunzel Stefan
Published: April 2007

It seems to be almost a law of nature that cities are expanding into their hinterlands and that networks of low density settlements are forming along transport routes. What is driving this process? Who is settling in the urban sprawl, and why? These questions are explored in the following article. In the suburbanised region to the north of Frankfurt am Main in Germany, a total of 1359 households in 67 locations were investigated with respect to their lifestyles and mobility habits. The results show that the spread of urban sprawl is not due to the living preferences of the general populace. The assumption can be made that elements of the common societal structure, such as the financing structure of communities and municipalities, promote the urban sprawl in Germany. Furthermore, the usefulness of the lifestyle approach is discussed.
Discourse variation, grammaticalisation and stuff like that1
Authors: Cheshire Jenny
Published: April 2007

General extenders (such as and stuff) are analysed here in the speech of adolescents from three English towns. There were no consistent patterns of gender or social class variation in their use, but a clear social class difference in the use of certain forms, with and that favoured by the working‐class speakers and and stuff and and things preferred by the middle‐class adolescents. The most frequent forms were analysed in terms of phonetic reduction, decategorisation, semantic change and pragmatic shift, changes that together make up the process of grammaticalisation. And that and and everything were the most grammaticalised, followed by or something, with and stuff and and things lagging behind. The multifunctionality of the general extenders caused problems for a rigorous analysis of their pragmatic functions. The paper argues that we must consider their functions within the local contexts in which they occur, to take account of their interaction with other linguistic forms. It is also important to avoid generalising about their functions and, instead, to prioritise the fact that as pragmatic particles they are multifunctional. In this data the general extenders had functions in every communicative domain, often simultaneously. The implications for the quantitative analysis of discourse forms are also considered.
ARE LONG‐RUN PRICE STABILITY AND SHORT‐RUN OUTPUT STABILIZATION ALL THAT MONETARY POLICY CAN AIM FOR?
Authors: Fontana Giuseppe , Palacio‐Vera Alfonso
Published: April 2007

A central tenet of the so‐called new consensus view in macroeconomics is that there is no long‐run trade‐off between inflation and unemployment. The main policy implication of this principle is that all monetary policy can aim for is (modest) short‐run output stabilization and long‐run price stability, i.e. monetary policy is neutral with respect to output and employment in the long run. However, research on the different sources of path dependency in the economy suggests that persistent but nevertheless transitory changes in aggregate demand may have a permanent effect on output and employment. If this is the case, then, the way monetary policy is run does have long‐run effects on real variables. This paper provides an overview of this research and explores conceptually how monetary policy should be implemented once these long‐run effects are acknowledged.
EVOLUTION IN IMPERFECT COMMITMENT BARGAINING—STRATEGIC VERSUS IGNORANT TYPES
Authors: Fischer Sven , Güth Werner , Pull Kerstin
Published: April 2007

To commit in bargaining is crucial: in the ultimatum game with its one‐sided commitment power the ‘proposer’ (almost) receives the whole pie while the ‘responder’ is left with (almost) nothing. When bargaining parties commit simultaneously the symmetric Nash (Econometrica, 1950, vol. 18, pp. 155–162) bargaining solution predicts equal shares. Continuously connecting these two games yields a one‐parameter family of games (Fischer et al., Experimental Economics, 2006, vol. 9, pp. 17–33) for which we distinguish two behavioral dispositions, namely (1) neglecting commitment power and (2) reacting to it strategically. Their pay‐off implications define the evolutionary set‐up for which we derive the evolutionarily stable behavioral disposition. Our analysis sheds light on the hypothesis that in experiments participants neglect strategic aspects such as commitment power.
Detection of electrocardiogram beats using a fuzzy similarity index
Authors: Übeyli Elif Derya
Published: April 2007

Abstract: A new approach based on the computation of a fuzzy similarity index (FSI) is presented for the detection of electrocardiogram (ECG) beats. Four types of ECG beats (normal beat, congestive heart failure beat, ventricular tachyarrhythmia beat, atrial fibrillation beat) obtained from the Physiobank database were analysed. The ECG signals were decomposed into time–frequency representations using the discrete wavelet transform and wavelet coefficients were calculated to represent the signals. The aim of the study is detection of ECG beats by the combination of wavelet coefficients and the FSI. Toward achieving this aim, fuzzy sets were obtained from the feature sets (wavelet coefficients) of the signals under study. The results demonstrated that the similarity between the fuzzy sets of the studied signals indicated the variabilities in the ECG signals. Thus, the FSI could discriminate the normal beat and the other three types of beats (congestive heart failure beat, ventricular tachyarrhythmia beat, atrial fibrillation beat).
Spiralling or Stabilising? The Compensation Culture and Our Propensity to Claim Damages for Personal Injury
Authors: Morris Annette
Published: April 2007

The propensity of accident victims in England and Wales to claim compensation through the tort system has generally increased since the 1970s. Contrary to popular belief, however, it has remained relatively stable since 2000, if not since 1997/1998. The upward trend in claims abated, therefore, when no‐win no‐fee advertising achieved prominence. Whether this long‐term increase in our propensity to claim supports the notion that a compensation culture has developed is largely a matter of interpretation. Our understanding of recent trends in our propensity to claim has clearly, however, been distorted through the media. This distorted legal consciousness may not only have affected our views of the tort system but may also have influenced our readiness to use it and thereby contributed to the stabilisation of accident claims in recent years.
‘Manifest Madness’: Towards a New Understanding of the Insanity Defence
Authors: Loughnan Arlie
Published: April 2007

This article introduces a new concept which can serve as a theoretical frame for understanding the way in which insanity is proved for the purposes of the criminal law. With reference to George Fletcher's concept of ‘manifest criminality’, it introduces the concept of ‘manifest madness’. This concept constructs madness (a shorthand for the types of mental abnormality known to the criminal law as insanity) in criminal law as evident to lay observers, and its meanings, which are derived from collective knowledge of it, as encoded in the defendant's acts. Through an historical analysis of the way in which insanity has been proved in criminal law, the article argues that ‘manifest madness’ is useful for understanding how knowledge about insanity is structured in the criminal courtroom. The concept of ‘manifest madness’ provides a frame that incorporates evidentiary and procedural features of the insanity defence that have resisted systematic theoretical analysis.
Use of nonparametric statistical tests in defining the number of periods to include in an intertemporal DEA analysis
Authors: Sowlati Taraneh
Published: April 2007

In any type of intertemporal efficiency analyses either locally or globally, units in different periods are compared against each other, and therefore it is assumed that no frontier shift exists within the periods of study. This assumption extends in window analysis to each window. In almost all studies in the past, the number of periods included in an intertemporal data envelopment analysis or the width of a window in a window analysis is determined without validating this assumption analytically. This is a problem which has not been fully addressed in the literature. This paper presents a new approach using nonparametric statistical tests to examine a frontier shift and determine the number of periods to include in an intertemporal analysis. The case of sawmills in Vancouver, Canada is used to demonstrate how to apply this new approach.
Flash flooding in Spain: geomorphological approaches supporting flood frequency analysis, and the implications for the design of structures
Authors: López‐Avilés Alma
Published: April 2007

Conventional methods for the estimation of flood frequency are generally based on the statistical analysis of data series resulting from the measurement of water levels at specific locations, which are translated into discharges (m3/s) using standard stage/discharge relationships. Subsequently, these gauged flows are used to identify the largest flood event experienced by a river or catchment, and to produce growth curves used in the estimation of the return periods of specific flood events, as well as in the calculation of discharges for specific required design events (e.g. return period 1 in 100 year). In areas where gauging data records are scarce, and/or the data series are short or interrupted, geomorphological interpretation of the physical environment, dating of fluvial deposits and flooding episodes and hydraulic reconstruction of past flood events can be used as complementary tools aiding conventional hydrological and flood frequency analysis methods. This paper will discuss the undertaking of this approach in the Guadalope Catchment in northeast Spain. It will examine the findings in relation to the inadequate design of existing structures such as dams, spillways, canals and reservoirs, and will also look at the potential risks associated with flooding at present.
Why did China Benefit from a Joint Venture Policy? A Case Study of Shanghai
Authors: Bishop Bernard
Published: April 2007

Mandatory joint venture requirements have played an important role in many developing countries’ foreign investment policies. However, such policies have been criticized in some of the economic literatures on the grounds that they deter investment and lead to the development of inefficient industries. A significant amount of foreign direct investment in Shanghai has been in the form of joint ventures. Yet, by many measures, Shanghai has benefited enormously. This article argues that there are three reasons to explain Shanghai's successful use of the joint venture for its industrial development. First, local firms and industries have had the capability and willingness to learn from joint ventures and other foreign invested firms. Second, the joint venture policy has been more likely than not to have “crowded in” local investment rather than crowd it out. Third, investment authorities in Shanghai have had sufficient bureaucratic capacity and political insulation to prevent the joint venture policy from being manipulated by rent seekers.
Developing Language Awareness Materials for Nonlinguists: Lessons Learned from the Do You Speak American? Curriculum Development Project
Authors: Reaser Jeffrey , Adger Carolyn
Published: April 2007

Current work in linguistics is not well represented in the school curriculum in the USA, partly because of a mismatch with traditional foci in the K‐12 (kindergarten through twelfth grade) standard course of studies and because there are very few materials for teaching about the nature of language and language variation. This article sketches the process of developing curricular materials to accompany the 3‐hour video documentary, Do You Speak American? and suggests some of the decisions that must be made in developing materials for educational settings concerning scientific knowledge about language.
Diabetes mellitus reduces the therapeutic effectiveness of interferon‐α2b plus ribavirin therapy in patients with chronic hepatitis C
Authors: Konishi Ichiro , Horiike Norio , Hiasa Yoichi , Tokumoto Yoshio , Mashiba Toshie , Michitaka Kojiro , Miyake Yasuyuki , Nonaka Suguru , Joukou Kouji , Matsuura Bunzo , Onji Morikazu
Published: April 2007

Aim:  Patients with chronic hepatitis C (CHC) often have diabetes mellitus (DM). However, it is unknown whether DM affects patient response to interferon (IFN) plus ribavirin therapy. Therefore, the aim of this study was to examine the influence of DM on the outcome of IFN‐α2b plus ribavirin therapy.

Methods:  In a cohort of 110 patients with CHC, the outcome of 6 months of IFN‐α2b plus ribavirin therapy was evaluated by comparing the patients with and without DM.

Results:  There were 46 sustained‐responders; 64 patients did not become sustained responders. Higher age (P = 0.015), lower platelet counts (P = 0.036), hepatitis C virus (HCV) serotype 1 (P = 0.001), advanced liver fibrosis (P = 0.004), and the presence of DM (P = 0.007) were significantly associated with not becoming a sustained‐responder. Seventeen CHC (15%) patients had DM. Sex ratio, age, body mass index, alanine aminotransferase levels, HCV‐RNA titer, and HCV serotypes did not significantly differ between the patients with and without DM, while fasting plasma glucose, hemoglobin A1c and liver histological staging were significantly different. On multiple logistic regression analysis, HCV serotype 1 (odds ratio 8.743, 95% confidence interval 2.215–34.517; P = 0.002) and the presence of DM (odds ratio 8.657, 95% confidence interval 1.462–51.276; P = 0.014) were independently associated with not becoming a sustained‐responder.

Conclusions:  The findings indicate that DM reduces the response to IFN‐α2b plus ribavirin therapy in CHC patients.
Hepatitis C virus genotype distribution in Myanmar: Predominance of genotype 6 and existence of new genotype 6 subtype
Authors: Lwin Aye Aye , Shinji Toshiyuki , Khin Myo , Win Ne , Obika Mikako , Okada Shigeru , Koide Norio
Published: April 2007

Aim:  This study was performed to determine the prevalence and distribution of hepatitis C virus (HCV) genotypes in Myanmar.

Methods:  A total of 1333 peripheral blood samples were collected from four different border cities of Myanmar. The anti‐HCV antibody‐positive serum samples were identified. HCV was genotyped by reverse transcriptase polymerase chain reaction, direct DNA sequencing and phylogenetic analysis on the partial core genome.

Results:  The overall prevalence of HCV infection was 11.6% (154/1333). Regionally, it was 13.5% (47/349) in the north‐eastern city, 12.8% (64/501) in the north‐western city, 4.2% (16/380) in the southern city and 26.2% (27/103) in the western city. HCV was genotyped in 145/154 (94.2%) samples. Genotype 6 was the most prevalent genotype in this study (71/145, 49%), followed by genotype 3 (57/145, 39.3%), genotype 1 (16/145, 11%), and genotype 2 (1/145, 0.7%). Genotype 6 was mostly found in the northern cities and genotype 3 in the southern and western cities of Myanmar. Multiple HCV genotypes/subtypes were successfully characterized as 1a, 1b, 2a, 3a, 3b, 6m, 6n, and a new 6 subtype. Among them, subtype 6n was the most predominant subtype (38.6%), followed by subtype 3b (29.7%), 3a (9.6%), 6m (9%), 1b (6.9%), 1a (4.1%), new 6 subtype (1.4%) and 2a (0.7%). Subtype 6n was more widely distributed in the northern cities whereas subtype 3b was more common in the western city. The newly discovered genotype 6 subtype was from the northern cities.

Conclusions:  The results indicate there are regional differences of HCV genotype distribution in Myanmar. There is a distinct geographic variation from other South‐East Asian countries in terms of the existence of the new genotype 6 subtype.
Isoniazid Induces Its Own Resistance in Nonreplicating
Mycobacterium tuberculosis
Authors: Siddiqi Salman , Takhar Param , Baldeviano Christian , Glover William , Zhang Ying
Published: April 2007

Isoniazid (INH) resistance is most frequent among drug-resistant
Mycobacterium tuberculosis
clinical isolates. This study was conducted to investigate whether INH could induce its own resistance. During INH susceptibility testing in BACTEC 12B and MGIT 960 media, weekly subcultures were made from the drug-containing media into fresh medium without drug and susceptibility testing was performed. Rifampin (RIF) was used as a control drug.
M. tuberculosis
H37Rv and three clinical isolates were tested in this study. INH-resistant subcultures were analyzed for catalase activity, INH susceptibility, and mutations associated with INH resistance. With inoculum size (10
4
bacilli) smaller than a size that contains spontaneously INH-resistant mutants, INH was found to induce resistance to itself in INH-tolerant persisters but not to other drugs. The minimum time required for induction of INH resistance was 5 to 6 days. In contrast, RIF did not induce RIF resistance. Eight subcultures with INH-induced resistance were analyzed, and two had a MIC of 0.4 μg/ml INH and six had MICs of over 2 μg/ml INH. Four of the eight subcultures with INH-induced resistance had lost catalase activity, with three having
katG
mutations. Despite being a powerful frontline tuberculosis drug, INH has the potential drawback of inducing its own stable genetic resistance in INH-tolerant persisters. This finding helps to explain the higher frequency and prevalence of INH-resistant isolates than isolates with resistance to other drugs in patients.
Antiplasmodial Activity of Aryltetralone Lignans from
Holostylis reniformis
Authors: de Andrade-Neto Valter F. , da Silva Tito , Lopes Lucia M. Xavier , do Rosário Virgílio E. , de Pilla Varotti Fernando , Krettli Antoniana U.
Published: April 2007

Extracts from
Holostylis reniformis
were tested in vivo against
Plasmodium berghei
and in vitro against a chloroquine-resistant strain of
Plasmodium falciparum
. The hexane extract of the roots was the most active, causing 67% reduction of parasitemia in vivo. From this extract, six lignans, including a new (7′
R
,8
S
,8′
S
)-3′,4′-methylenedioxy-4,5-dimethoxy-2,7′-cyclolignan-7-one, were isolated and tested in vitro against
P. falciparum.
The three most active lignans showed 50% inhibitor concentrations of ≤0.32 μM. An evaluation of minimum lethal dose (30%) values showed low toxicity for these lignans in a hepatic cell line (Hep G2A16). Therefore, these compounds are potential candidates for the development of antimalarial drugs.
Polyamine Effects on Antibiotic Susceptibility in Bacteria
Authors: Kwon Dong-Hyeon , Lu Chung-Dar
Published: April 2007

Biogenic polyamines (e.g., spermidine and spermine) are a group of essential polycationic compounds found in all living cells. The effects of spermine and spermidine on antibiotic susceptibility were examined with gram-negative
Escherichia coli
and
Salmonella enterica
serovar Typhimurium bacteria and clinical isolates of
Pseudomonas aeruginosa
and with gram-positive
Staphylococcus aureus
bacteria, including methicillin-resistant
S. aureus
(MRSA). Exogenous spermine exerted a dose-dependent inhibition effect on the growth of
E. coli
,
S. enterica
serovar Typhimurium, and
S. aureus
but not
P. aeruginosa
, as depicted by MIC and growth curve measurements. While the MICs of polymyxin and ciprofloxacin were in general increased by exogenous spermine and spermidine in
P. aeruginosa
, this adverse effect was not observed in enteric bacteria and
S. aureus
. It was found that spermine and spermidine can decrease the MICs of β-lactam antibiotics in all strains as well as other types of antibiotics in a strain-dependent manner. Significantly, the MICs of oxacillin for MRSA Mu50 and N315 were decreased more than 200-fold in the presence of spermine, and this effect of spermine was retained when assessed in the presence of divalent ions (magnesium or calcium; 3 mM) or sodium chloride (150 mM). The effect of spermine on the sensitization of
P. aeruginosa
and MRSA to antibiotics was further demonstrated by population analysis and time-killing assays. The results of checkerboard assays with
E. coli
and
S. aureus
indicated a strong synergistic effect of spermine in combination with β-lactams and chloramphenicol. The decreased MICs of β-lactams implied that the possible blockage of outer membrane porins by exogenous spermine or spermidine did not play a crucial role in most cases. In contrast, only the MIC of imipenem against
P. aeruginosa
was increased by exogenous spermine and spermidine, and this resistance effect was abolished in a mutant strain devoid of the outer membrane porin OprD. In
E. coli
, the MICs of carbenicillin, chloramphenicol, and tetracycline were decreased in two
acrA
mutants devoid of a major efflux pump, AcrAB. However, retention of the spermine effect on antibiotic susceptibility in two
acrA
mutants of
E. coli
suggested that the AcrAB efflux pump was not the target for a synergistic effect by spermine and antibiotics and ruled out the hypothesis of spermine serving as an efflux pump inhibitor in this organism. In summary, this interesting finding of the effect of spermine on antibiotic susceptibility provides the basis for a new potential approach against drug-resistant pathogens by use of existing β-lactam antibiotics.
Association between
embB
Codon 306 Mutations and Drug Resistance in
Mycobacterium tuberculosis
Authors: Shen Xin , Shen Guo-miao , Wu Jie , Gui Xiao-hong , Li Xia , Mei Jian , DeRiemer Kathryn , Gao Qian
Published: April 2007

embB306
mutants were detected in both ethambutol (EMB)-resistant and EMB-susceptible strains of
Mycobacterium tuberculosis
. Multidrug-resistant (MDR) strains had a higher proportion of
embB306
mutants than non-MDR strains (odds ratio, 6.78;
P
< 0.001). The
embB306
locus is a candidate marker for rapid detection of MDR and extremely drug resistant tuberculosis.
A Novel
Giardia lamblia
Nitroreductase, GlNR1, Interacts with Nitazoxanide and Other Thiazolides
Authors: Müller Joachim , Wastling Jonathan , Sanderson Sanya , Müller Norbert , Hemphill Andrew
Published: April 2007

The nitrothiazole analogue nitazoxanide [NTZ; 2-acetolyloxy-
N
-(5-nitro-2-thiazolyl)benzamide] represents the parent compound of a class of drugs referred to as thiazolides and exhibits a broad spectrum of activities against a wide variety of helminths, protozoa, and enteric bacteria infecting animals and humans. NTZ and other thiazolides are active against a wide range of other intracellular and extracellular protozoan parasites in vitro and in vivo, but their mode of action and respective subcellular target(s) have only recently been investigated. In order to identify potential targets of NTZ and other thiazolides in
Giardia lamblia
trophozoites, we have developed an affinity chromatography system using the deacetylated derivative of NTZ, tizoxanide (TIZ), as a ligand. Affinity chromatography on TIZ-agarose using cell extracts of
G. lamblia
trophozoites resulted in the isolation of an approximately 35-kDa polypeptide, which was identified by mass spectrometry as a nitroreductase (NR) homologue (EAA43030.1). NR was overexpressed as a six-histidine-tagged recombinant protein in
Escherichia coli
, purified, and then characterized using an assay for oxygen-insensitive NRs with dinitrotoluene as a substrate. This demonstrated that the NR was functionally active, and the protein was designated GlNR1. In this assay system, NR activity was severely inhibited by NTZ and other thiazolides, demonstrating that the antigiardial activity of these drugs could be, at least partially, mediated through inhibition of GlNR1.
Identification of Transferrin-Binding Domains in TbpB Expressed by
Neisseria gonorrhoeae
Authors: DeRocco Amanda J. , Cornelissen Cynthia Nau
Published: April 2007

The transferrin iron acquisition system of
Neisseria gonorrhoeae
is necessary for iron uptake from transferrin in the human host and requires the participation of two distinct proteins: TbpA and TbpB. TbpA is a TonB-dependent outer membrane transporter responsible for the transport of iron into the cell. TbpB is a lipid-modified protein, for which a precise role in receptor function has not yet been elucidated. These receptor complex proteins show promise as vaccine candidates; therefore, it is important to identify surface-exposed regions of the proteins required for wild-type functions. In this study we examined TbpB, which has been reported to be surface exposed in its entirety; however, this hypothesis has never been tested experimentally. We placed the hemagglutinin (HA) epitope into TbpB with the dual purpose of examining the surface exposure of particular epitopes as well as their impact on receptor function. Nine insertion mutants were created, placing the epitope downstream of the signal peptidase II cleavage site. We report that the HA epitope is surface accessible in all mutants, indicating that the full-length TbpB is completely surface exposed. By expressing the TbpB-HA fusion proteins in
N. gonorrhoeae
, we were able to examine the impact of each insertion on the function of TbpB and the transferrin acquisition process. We propose that TbpB is comprised of two transferrin-binding-competent lobes, both of which are critical for efficient iron uptake from human transferrin.
Memory CD4 T Cells Enhance Primary CD8 T-Cell Responses
Authors: Krawczyk Connie M. , Shen Hao , Pearce Edward J.
Published: April 2007

CD4 T-cell help is required for optimal memory CD8 T-cell responses. We have found that engaging preexisiting CD4 Th1, but not Th2, memory cells at the time of CD8 T-cell priming results in increased CD8 effector responses to both bacterial and viral pathogens. The enhanced responses are characterized by increased numbers of cytokine-producing, antigen-specific cells. These findings suggest that engaging endogenous memory Th1 cells may increase cellular responses in an immunotherapy or vaccination setting.
Rapid Escape of thedot/icmMutants ofLegionella pneumophilainto the Cytosol of Mammalian and Protozoan Cells
Authors: Molmeret Maëlle , Santic’ Marina , Asare Rexford , Carabeo Reynold A. , Kwaik Yousef Abu
Published: April 2007

TheLegionella pneumophila-containing phagosome evades endocytic fusion and intercepts endoplasmic reticulum (ER)-to-Golgi vesicle traffic, which is believed to be mediated by the Dot/Icm type IV secretion system. Although phagosomes harboringdot/icmmutants are thought to mature through the endosomal-lysosomal pathway, colocalization studies with lysosomal markers have reported contradictory results. In addition, phagosomes harboring thedot/icmmutants do not interact with endocytosed materials, which is inconsistent with maturation of the phagosomes in the endosomal-lysosomal pathway. Using multiple strategies, we show that thedot/icmmutants defective in the Dot/Icm structural apparatus are unable to maintain the integrity of their phagosomes and escape into the cytoplasm within minutes of entry into various mammalian and protozoan cells in a process independent of the type II secretion system. In contrast, mutants defective in cytoplasmic chaperones of Dot/Icm effectors andrpoS,letA/S, andletEregulatory mutants are all localized within intact phagosomes. Importantly, non-dot/icm L. pneumophilamutants whose phagosomes acquire late endosomal-lysosomal markers are all located within intact phagosomes. Using high-resolution electron microscopy, we show that phagosomes harboring thedot/icmtransporter mutants do not fuse to lysosomes but are free in the cytoplasm. Inhibition of ER-to-Golgi vesicle traffic by brefeldin A does not affect the integrity of the phagosomes harboring the parental strain ofL. pneumophila. We conclude that the Dot/Icm transporter is involved in maintaining the integrity of theL. pneumophilaphagosome, independent of interception of ER-to-Golgi vesicle traffic, which is a novel function of type IV secretion systems.
T Cells Are Essential for Bacterial Clearance, and Gamma Interferon, Tumor Necrosis Factor Alpha, and B Cells Are Crucial for Disease Development inCoxiella burnetiiInfection in Mice
Authors: Andoh Masako , Zhang Guoquan , Russell-Lodrigue Kasi E. , Shive Heather R. , Weeks Brad R. , Samuel James E.
Published: April 2007

Coxiella burnetii, the etiological agent of Q fever, has two phase variants. Phase I has a complete lipopolysaccharide (LPS), is highly virulent, and causes Q fever in humans and pathology in experimental animals. Phase II lacks an LPS O side chain, is avirulent, and does not grow well in immunocompetent animals. To understand the pathogenicity of Q fever, we investigated the roles of immune components in animals infected with Nine Mile phase I (NM I) or Nine Mile phase II (NM II) bacteria. Immunodeficient mice, including SCID mice (deficient in T and B cells), SCIDbg mice (deficient in T, B, and NK cells), nude mice (deficient in T cells), muMT mice (deficient in B cells), bg mice (deficient in NK cells), mice deficient in tumor necrosis factor alpha (TNF-α−/−mice), and mice deficient in gamma interferon (IFN-γ−/−mice), were compared for their responses to infection. SCID, SCIDbg, nude, and IFN-γ−/−mice showed high susceptibility to NM I, and TNF-α−/−mice showed modest susceptibility. Disease caused by NM I in SCID, SCIDbg, and nude mice progressed slowly, while disease in IFN-γ−/−and TNF-α−/−mice advanced rapidly. B- and NK-cell deficiencies did not enhance clinical disease development or alter bacterial clearance but did increase the severity of histopathological changes, particularly in the absence of B cells. Mice infected with NM II showed no apparent clinical disease, but T-cell-deficient mice had histopathological changes. These results suggest that T cells are critical for clearance ofC. burnetii, either NM I or NM II, that IFN-γ and TNF-α are essential for the early control of infection, and that B cells are important for the prevention of tissue damage.
The Cytotoxic Necrotizing Factors from
Yersinia pseudotuberculosis
and from
Escherichia coli
Bind to Different Cellular Receptors but Take the Same Route to the Cytosol
Authors: Blumenthal Britta , Hoffmann Claudia , Aktories Klaus , Backert Steffen , Schmidt Gudula
Published: April 2007

The cytotoxic necrotizing factors CNF1 and CNF2 produced by pathogenic
Escherichia coli
strains and CNF
Y
of
Yersinia pseudotuberculosis
constitutively activate small GTPases of the Rho family. They deamidate a glutamine (Gln63 in RhoA), which is crucial for GTP hydrolysis. CNF1 and CNF
Y
exhibit 61% identity on the amino acid level, with equal distribution over the whole molecule. Although the two toxins are homologous in the receptor binding domain, we show that they bind to different cellular receptors. CNF
Y
does not enter Caco-2 and CHO-K1 cells, which are responsive to CNF1. In contrast, HeLa, Hep-2, and HEK 293 cells do respond to both toxins. Competition studies with catalytically inactive mutants of the toxins revealed that binding of CNF1 has no influence on the uptake of CNF
Y
into HeLa cells. In contrast, uptake of CNF1 is retarded after preincubation of HeLa cells with the catalytically inactive mutant of CNF
Y
, suggesting that the toxin receptors overlap. Moreover, we compared the pathways of the toxins from receptor binding into the cytosol and showed that both toxins are taken up independent of the presence of clathrin or lipid rafts and are released into the cytosol from acidified endosomes.
A Functional NADPH Oxidase Prevents Caspase Involvement in the Clearance of Phagocytic Neutrophils
Authors: Wilkie Rachel P. , Vissers Margret C. M. , Dragunow Mike , Hampton Mark B.
Published: April 2007

Neutrophils play a prominent role in host defense. Phagocytosis of bacteria leads to the formation of an active NADPH oxidase complex that generates reactive oxygen species for bactericidal purposes. A critical step in the resolution of inflammation is the uptake of neutrophils by macrophages; however, there are conflicting reports on the mechanisms leading to the apoptosis of phagocytic neutrophils. The aim of this study was to clarify the role of effector caspases in these processes. Caspase activity was measured by DEVDase activity assays or immunofluorescence detection of active caspase-3. With normal human and wild-type murine neutrophils there was no caspase activation following phagocytosis ofStaphylococcus aureus. However, caspase activity was observed in phagocytic neutrophils with a defective NADPH oxidase, including neutrophils isolated from X-linked gp91phoxknockout chronic granulomatous disease mice. These results indicate that a functional NADPH oxidase and the generation of oxidants in the neutrophil phagosome prevent the activation of the cytoplasmic caspase cascade.
Adipose tissue distribution in relation to insulin resistance in type 2 diabetes mellitus
Authors: Azuma Koichiro , Heilbronn Leonie K. , Albu Jeanine B. , Smith Steven R. , Ravussin Eric , Kelley David E.
Published: April 2007

Insulin resistance (IR) is typically more severe in obese individuals with type 2 diabetes (T2DM) than in similarly obese non-diabetics but whether there are group differences in body composition and whether such differences contribute to the more severe IR of T2DM is uncertain. DEXA and regional CT imaging were conducted to assess adipose tissue (AT) distribution and fat content in liver and muscle in 67 participants with T2DM (F39/M28, age 60 ± 7 yr, BMI 34 ± 3 kg/m2) and in 35 similarly obese, non-DM volunteers (F20/M15, age 55 ± 8 yr, BMI 33 ± 2 kg/m2). A biopsy of subcutaneous abdominal AT was done to measure adipocyte size. A glucose clamp was performed at an insulin infusion of 80 mU·min−1·m−2. There was more severe IR in T2DM (6.1 ± 2.3 vs. 9.9 ± 3.3 mg·min−1·kg FFM−1; P < 0.01). Group comparisons of body composition parameters was performed after adjusting for the effect of age, gender, race, height and total fat mass (FM). T2DM was associated with less leg FM (−1.2 ± 0.4 kg, P < 0.01), more trunk FM (+1.1 ± 0.4 kg, P < 0.05), greater hepatic fat ( P < 0.05), and more subfascial adipose tissue around skeletal muscle ( P < 0.05). There was a significant group × sex interaction for VAT ( P < 0.01), with greater VAT in women with T2DM ( P < 0.01). Mean adipocyte size (AS) did not significantly differ across groups, and smaller AS was associated with increased leg FM, whereas larger AS was related to more trunk FM (both P < 0.05). Group differences in IR were less after adjusting for group differences in leg FM, trunk FM, and hepatic fat, but these adjustments only partially accounted for the greater severity of IR in T2DM. In summary, T2DM, compared with similarly obese nondiabetic men and women, is associated with less leg FM and greater trunk FM and hepatic fat.
Regions of Different Confinement in Low-Dimensional AlyInxGa1−x−yN Quantum Structures
Authors: Gröning A. , Pérez-Solórzano V. , Jetter M. , Schweizer H.
Published: April 2007

The optical properties of metal-organic vapor phase epitaxy grown AlyInxGa1−x−yN quantum dot structures have been studied by time-resolved photoluminescence experiments. We investigated the recombination dynamics of the photo-exited carriers in dependence of the growth parameters such as aluminium flow and the duration of the growth interruption after the dot deposition. Our results confirm the presence of localized states, where the degree of localization is strongly dependent on the growth conditions. To describe this behavior, we propose a band structure with coupled potentials for these nanostructures. Finally, we demonstrate state filling to prove the zero-dimensional character of the strongly localized states in our quaternary quantum dots.