Characterization of apxIVA, a new RTX determinant of Actinobacillus pleuropneumoniae

A fourth type of RTX determinant was identified in Actinobacillus pleuropneumoniae and was designated apxIVA. When expressed in Escherichia coli, recombinant ApxIVA showed a weak haemolytic activity and co-haemolytic synergy with the sphingomyelinase (beta-toxin) of Staphylococcus aureus. These activities required the presence of an additional gene, ORF1, that is located immediately upstream of apxIVA. The apxIVA gene product could not be detected in A. pleuropneumoniae cultures grown under various conditions in vitro; however, pigs experimentally infected with A. pleuropneumoniae serotypes 1, 5 and 7 started to produce antibodies that reacted with recombinant ApxIVA 14 d post-infection, indicating that apxIVA is expressed in vivo. In addition, sera from pigs naturally and experimentally infected with any of the serotypes all reacted with recombinant ApxIVA. The apxIVA gene from the serotype 1 A. pleuropneumoniae type strain Shope 4074T encodes a protein with a predicted molecular mass of 202 kDa which has typical features of RTX proteins including hydrophobic domains in the N-terminal half and 24 glycine-rich nonapeptides in the C-terminal half that bind Ca2+. The glycine-rich nonapeptides are arranged in a modular structure and there is some variability in the number of modules in the ApxIVA proteins of different serotypes of A. pleuropneumoniae. The deduced amino acid sequences of the ApxIVA proteins have significant similarity with the Neisseria meningitidis iron-regulated RTX proteins FrpA and FrpC, and to a much lesser extent with other RTX proteins. The apxIVA gene could be detected in all A. pleuropneumoniae serotypes and seems to be species-specific. Although the precise role of this new RTX determinant in pathogenesis of porcine pleuropneumonia needs to be determined, apxIVA is the first in vivo induced toxin gene that has been described in A. pleuropneumoniae.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Morphology and evolution of the ejecta of Hale crater in Argyre basin, Mars: Results from high resolution mapping

We use various data sets, including images from the High Resolution Imaging Science Experiment camera (HiRISE), to examine the ejecta of the generally fresh-looking Hale crater that occurs in the rugged mountain terrain of Nereidum Montes in the northern rim materials of the Argyre impact structure on Mars. Our investigation reveals that the distal parts of the Hale crater ejecta and other basin deposits behave like viscous flows, which we attribute to the secondary flow of ejecta mixed with water–ice-rich basin materials. Consistent with water-enrichment of the basin materials, our mapping further reveals occasionally deformed surfaces, including highly conspicuous features such as mounds and fractured plateaus that we interpret to be a result of periglacial modification, subsequent (including possibly present-day) to the transient localized melting and fluvial erosion caused by Hale-impact-generated heating. In particular, our morphometric analysis of a well-defined valley system west of Hale crater suggests that it may have been formed through hydrologic/glacial activity prior to the Hale impact, with additional modification resulting from the impact and subsequent geologic and hydrologic phenomena including glacial and periglacial activity.

First foot prints of chemistry on the shore of the Island of Superheavy Elements

Chemistry has arrived on the shore of the Island of Stability with the first chemical investigation of the superheavy elements Cn, 113, and 114. The results of three experimental series leading to first measured thermodynamic data and qualitatively evaluated chemical properties for these elements are described. An interesting volatile compound class has been observed in the on-line experiments for the elements Bi and Po. Hence, an exciting chemical study of their heavier transactinide homologues, elements 115 and 116 is suggested.

Evaluating Learner Perceptions of Use of Simulations for New nurses – A Collaboration Between the UT SON and the Methodist Hospital

The purpose of this evaluation project was to describe the integration of simulation into a nursing internship program and to help prepare new graduate nurses for patient care. Additionally, learning styles and perceptions of active learning, collaboration among peers, ways of learning, expectation of simulation, satisfaction, self-confidence, and design of simulation were examined. [See PDF for complete abstract]

TB research at UT-Houston--a review of cord factor: new approaches to drugs, vaccines and the pathogenesis of tuberculosis.

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950's providing compelling evidence that cord factor (trehalose 6,6 dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time to have immediate impact. We can now recognize that the physical and biologic properties of cord factor are unprecedented in science, especially its ability to switch between two sets of biologic activities with changes in conformation. While TDM remains on organisms, it protects them from killing within macrophages, reduces antibiotic effectiveness and inhibits the stimulation of protective immune responses. If it comes off organisms and associates with lipid, TDM becomes a driver of tissue damage and necrosis. Studies emanating from cord factor research have produced (1) a rationale for improving vaccines, (2) an approach to new drugs that overcome natural resistance to antibiotics, (3) models of caseating granulomas that reproduce multiple manifestations of human tuberculosis. (4) evidence that TDM is a key T cell antigen in destructive lesions of tuberculosis, and (5) a new understanding of the pathology and pathogenesis of postprimary tuberculosis that can guide more informative studies of long standing mysteries of tuberculosis.

IDENTIFICATION OF FACTORS INVOLVED IN DNA METHYLATION OF CPG-ISLAND-PROMOTERS

Repression of many tumor suppressor genes (TSGs) in cancer is mediated by aberrantly increased DNA methylation levels at promoter CpG islands (CGI). About one-fourth of empirically defined human promoters are surrounded by or contain clustered repetitive elements. It was previously observed that a sharp transition of methylation occurs between highly methylated repetitive elements (SINE or LINE) and unmethylated CGI-promoters (e.g. P16, VHL, CDH and RIL) in normal tissues. The functions that lead to increased CGI methylation in cancer remain poorly understood. We propose that CGI-promoters contain cis-elements for triggering de novo DNA methylation. In the first part of our project, we established a site-specific integration system with enforced local transcriptional repression in colorectal cancer cells and monitored the occurrence of de novo DNA methylation in exogenous fragments containing a CGI-promoter and repetitive elements. Initial de novo methylation was seeded at specific CG sites in a repetitive element, and accelerated by persistent binding of a KRAB-containing transcriptional repressor. Furthermore, additional repetitive elements (LINE and SINE) located adjacent to the promoter could confer DNA methylation spreading into the CGI particularly in the setting of KRAB-factor binding. However, a repressive chromatin alone was not sufficient to initiate DNA methylation, which required specific DNA sequences and was integration-site (and/or cell-line) specific. In addition, all the methylation observed showed slow and gradual accumulation over several months of culture. Overall, these results demonstrate a requirement for specific DNA sequences to trigger de novo DNA methylation, and repetitive elements as cis-regulatory factors to cooperate with strengthened transcriptional repression in promoting methylation spreading. In the second part, we re-introduced disrupted DNMT3B or DNMT1 into HCT116 DKO cells and mapped the remethylation pattern through a profiling method (DREAM). Moderate remethylation occurred when DNMT3B was re-expressed with a preference toward non-CGI and non-promoter regions. Hence, there exists a set of genomic regions with priority to be targets for DNMT3B in somatic cells.

The Changing Environment of Audiovisual Media. New Technologies, New Patterns of Consumer/Business Behaviour and Their Implications for Audiovisual Media Regulation

Digital TV offers of 200 channels and 500 video-on-demand films, podcasting, mobile television, a new web blog being created every two seconds - these are some of the factual elements depicting contemporary audiovisual media in the digital environment. The present article looks into some of these technological advances and sketches their implications for the markets of media content, in particular as newly emerging patterns of consumer and business behaviour are concerned. Ultimately, it puts forward the question of whether the existing audiovisual media regulatory models, which are still predominantly analogue-based, have been rendered obsolete by the transformed (and continually transforming) digital environment.

Geophysical and Hydrological Evaluation of Two Bog Complexes in a Northern Peatland: Implications for the Distribution of Biogenic Gases at the Basin Scale

Ground penetrating radar (GPR) was used to determine peat basin geometry and the spatial distribution of free-phase biogenic gasses in two separate units of a northern peatland (Central and Southern Unit of Caribou Bog, Maine). The Central Unit is characterized by a deep basin structure (15 m maximum depth) and a raised (eccentric) bog topographic profile (up to 2 m topographic variation). Here numerous regions of electromagnetic (EM) wave scattering are considered diagnostic of the presence of extensive free-phase biogenic gas. In contrast, the Southern Unit is shallower (8 m maximum depth) and has a slightly convex upwards bog profile (less than 1 m topographic variation), and areas of EM wave scattering are notably absent. The biogenic gas zones interpreted from GPR in the Central Unit are associated with: (1) wooded heath vegetation at the surface, (2) open pools at the surface, (3) high water table elevations near the center of the basin, and (4) a region of overpressure (at approximately 5 m depth) immediately below the zone of free-phase gas accumulation. The latter suggests (1) a transient pressure head associated with low hydraulic conductivity resulting from the biogenic gasses themselves or confining layers in the peat that restrict both gas release and groundwater flow and/or (2) overpressure in the peat column as a result of the gas buildup itself. In contrast, the Southern Unit, where zones of EM scattering are absent, is characterized by: (1) predominantly shrub vegetation, (2) a lack of open pools, (3) only minor variations (less than 1 m) in water table elevation throughout the entire unit; and (4) generally upward groundwater flow throughout the basin. The results illustrate the nonuniformity of free-phase biogenic gas distribution at the peat basin scale and provide insights into the processes and controls associated with CH4 and CO2 accumulation in peatlands.

The role of brand marketing in snowboarding: A comparative study of Switzerland and New Zealand

Introduction: Brands play an essential role in the organizational structure of snowboarding by sponsoring athletes, arranging events, contributing to product development and developing long-term partnerships with other key actors. However, the specialities of their role in scene sports, such as creating identities, networking and brand marketing strategies, have not been extensively researched. This study aims to provide an analysis of the function of brands within the snowboarding subculture by comparing how the sport is organized in Switzerland and New Zealand. Sociological theories of subcultures (Hitzler & Niederbacher, 2010) and social networks (Stegbauer, 2008) are used to defi ne the structures of the sport, whereas marketing and branding theories (Adjouri & Stastny, 2006) help to understand the role of the brands. Snowboarding will be defi ned as an alternative sports subculture based on characteristics such as aesthetics, adventure and new resources of performance (Schwier, 2006). Such a defi nition also begs for a novel form of analyzing its organization. Unlike more conventional structures, the organization of snowboarding allows a variety of actors to get involved in leading the sport. By portraying and encouraging differentiated identities and lifestyles, athletes provide a space for other actors to fi nd their place within the sport (Wheaton, 2005). According to Stegbauers network theory, individual actors are able to obtain high positions and defi ne their identity depending on their ties to actors and networks within the subculture (Stegbauer, 2008). For example, social capital, contacts within the sport and insider knowledge on subculture-related information enable actors to get closer to the core (Hitzler & Niederbacher, 2010). Actors who do not have close networks and allies within the subculture are less likely to engage successfully in the culture, whether as an individual or as a commercial actor (Thorpe, 2011). This study focuses on the organizational structure of snowboarding by comparing the development of the sport in Switzerland and New Zealand. An analysis of snowboarding in two nations with diverse cultures and economic systems allows a further defi nition of the structural organization of the sport and explains how brands play an important role in the sport. Methods: The structural organization of the sport will be analyzed through an ethnographic approach, using participant observation at various leading events in Switzerland (Freestyle.ch, European Open) and New Zealand (World Heli Challenge, New Zealand Open, New Zealand Winter Games). The data is analyzed using grounded theory (Glaser & Strauss 1967) and gives an overview of the actors that are playing an important role in the local development of snowboarding. Participant observation was also used as a tool to get inside the sport culture and opened up the possibility to make over 40 semi-structured qualitative expert interviews with international core actors from 11 countries. Obtaining access to one actor as a partner early on helped to get inside the local sport culture. The ‘snowball effect’ allowed the researcher to acquire access, build trust and conduct interviews with experts within the core scene. All the interviewed actors have a direct infl uence on the sport in one or both countries, which permit a cross-analysis. The data of the interviews was evaluated through content analysis (Mayring 2010). The two methods together provided suffi cient data to analyze the organizational structure and discuss the role of brand marketing within snowboarding. Results: An actors mapping by means of a center-periphery framework has identifi ed fi ve main core groups: athletes, media representatives, brand-marketing managers, resort managers and event organizers. In both countries the same grouping of actors were found. Despite possessing different and frequently multiple roles and responsibilities, core actors appear to have a strong common identifi cation as ‘snowboarders’, are considered to be part of the organizational elite of the sport and tend to advocate similar goals. The author has found that brands in Switzerland tend to have a larger impact on the broader snowboarding culture due to a number of factors discussed below. Due to a larger amount of snowboarders and stronger economic power in Europe, snowboarders are making attempts to differentiate themselves from other winter sports, while competing with each other to develop niche markets. In New Zealand, on the other hand, the smaller market enables more cooperation and mutual respect within snowboarders. Further they are more closely linked to other winter sports and are satisfi ed with being lumped together. In both countries, brands have taken up the role of supporting young athletes, organizing competitions and feeding media with subculture-related content. Brands build their image and identity through the collaboration with particular athletes who can represent the values of the brand. Local and global communities with similar lifestyles and interests are being built around brands that share a common vision of the sport. The dominance of brands in snowboarding has enabled them with the power to organize and rule the sport through its fan base and supporters. Brands were defi ned by interviewees as independent institutions led by insiders who know the codes and symbols of the sport and were given trust and credibility. The brands identify themselves as the engines of the sport by providing the equipment, opportunities for athletes to get exposure, allowing media to get exclusive information on activities, events and sport-related stories. Differences between the two countries are more related to the economic system. While Switzerland is well integrated in the broader European market, New Zealand’s geographical isolation and close proximity to Australia tends to limit its market. Further, due to different cultural lifestyles, access to resorts and seasonal restrictions, to name a few, the amount of people practicing winter sports in New Zealand is much smaller than in Switzerland. However, this also presents numerous advantages. For example, the short southern hemisphere winter season in New Zealand enables them to attract international sports athletes, brands and representatives in a period when Europe and North America is in summer. Further, the unique snow conditions in New Zealand and majestic landscape is popular for attracting world renowned photo- and cinematographers. Another advantage is the less populated network as it provides the opportunity for individuals to gain easier access to the core of the sport, obtain diverse positions and form a unique identity and market. In Switzerland, on the other hand, the snowboarding network is dense with few positions available for the taking. Homegrown brands with core recognition are found in both countries. It was found that the Swiss brands tend to have a larger impact on the market, whereas in New Zealand, the sport is more dependent on import products by foreign brands. Further, athletes, events and resorts in New Zealand are often dependent on large brand sponsorships from abroad such as from brand headquarters in the Unites States. Thus, due to its location in the centre of Europe, Swiss brands can take advantage of brands which are closer in proximity and culture to sponsor athletes and events. In terms of media coverage, winter sports in New Zealand tend to have a minor coverage and tradition in local mass media, which leads to less exposure, recognition and investment into the sport. This is also related to how snowboarding is more integrated into other winter sports in New Zealand. Another difference is the accessibility of the ski resort by the population. While in Switzerland the resorts are mostly being visited by day-travelers, ‘weekend warriors’ and holiday makers, the location of the resorts in New Zealand make it diffi cult to visit for one day. This is in part due to the fact that Swiss ski resorts and villages are usually the same location and are accessible through public transportation, while the ski resorts in New Zealand have been built separately from the villages. Further, the villages have not been built to accommodate to high tourist arrivals. Thus, accommodation and food facilities are limited and there is a lack of public transportation to the resorts. Discussion: The fi ndings show that networks and social relations combined with specifi c knowledge on scene-related attributes are crucial in obtaining opportunities within the sport. Partnerships as well as competition between these different actors are necessary for core acceptance, peer credibility and successful commercial interests. Brands need to maintain effective marketing strategies and identities which incorporate subcultural forms of behavior and communication. In order to sustain credibility from its fans, athletes and other snowboarding actors, brands need to maintain their insider status through social networks and commercial branding strategies. The interaction between all actors is a reciprocated process, where social capital, networks and identities are being shared. While the overall structure of snowboard subcultures in Europe and New Zealand are similar, there are some distinct characteristics which make each one unique. References Adjouri, N. & Stastny, P. (2006). Sport-Branding: Mit Sport-Sponsoring zum Markenerfolg. Wiesbaden: Gabler. Glaser, B. & Strauss, K. (1967). The discovery of grounded theory: Strategies for qualitative research. Chicago: Aldine. Hebdige, D. (2009). Subculture; The meaning of style. New York: Routledge. Hitzler, R. & Niederbacher, A. (2010). Leben in Szenen: Formen juveniler Vergemeinschaftung heute. Wiesbaden: Verlag für Sozialwissenschaften. Mayring, P. (2010). Qualitative Inhaltsanalyse: Grundlagen und Techniken. Weinheim: Beltz. Schwier, J. (2006). Repräsentationen des Trendsports. Jugendliche Bewegungskulturen, Medien und Marketing. In: Gugutzer, R. (Hrsg.). body turn. Perspektiven der Soziologie des Körpers und des Sports. Bielefeld: transcript (S. 321-340). Stegbauer, C. (2008). Netzwerkanalyse und Netzwerktheorie. Ein neues Paradigma in den Sozialwissenschaften. Wiesbaden: VS Verlag für Sozialwissenschaften. Thorpe, H. (2011). Snowboarding bodies in theory and practice. Basingstoke: Palgrave Macmillan. Wheaton, B. (2005). Understanding lifestyle sports; consumption, identity and difference. New York: Routledge.

The Transmission of Manuscripts and the Genetics of Texts. A new critical edition of Wolfram von Eschenbach’s Parzival

The discussion on the New Philology triggered by French and North American scholars in the last decade of the 20th century emphasized the material character of textual transmission inside and outside the written evidences of medieval manuscripts by downgrading the active role of the historical author. However, the reception of the ideas propagated by the New Philology adherents was rather divided. Some researchers questioned its innovative status (K. Stackmann: “Neue Philologie?”), others saw a new era of the “powers of philology” evoked (H.-U. Gumbrecht). Besides the debates on the New Philology another concept of textual materiality strengthened in the last decade, maintaining that textual alterations somewhat relate to biogenetic mutations. In a matter of fact, phenomena such as genetic and textual variation, gene recombination and ‘contamination’ (the mixing of different exemplars in one manuscript text) share common features. The paper discusses to what extent the biogenetic concepts can be used for evaluating manifestations of textual production (as the approach of ‘critique génétique’ does) and of textual transmission (as the phylogenetic analysis of manuscript variation does). In this context yet the genealogical concept of stemmatology – the treelike representation of textual development abhorred by the New Philology adepts – might prove to be useful for describing the history of texts. The textual material to be analyzed will be drawn from the Parzival Project, which is currently preparing a new electronic edition of Wolfram von Eschenbach’s Parzival novel written shortly after 1200 and transmitted in numerous manuscripts up to the age of printing (www.parzival.unibe.ch). Researches of the project have actually resulted in suggesting that the advanced knowledge of the manuscript transmission yields a more precise idea on the author’s own writing process.

Steroidogenesis of the testis - new genes and pathways

Defects of androgen biosynthesis cause 46,XY disorder of sexual development (DSD). All steroids are produced from cholesterol and the early steps of steroidogenesis are common to mineralocorticoid, glucocorticoid and sex steroid production. Genetic mutations in enzymes and proteins supporting the early biosynthesis pathways cause adrenal insufficiency (AI), DSD and gonadal insufficiency. The classic androgen biosynthesis defects with AI are lipoid CAH, CYP11A1 and HSD3B2 deficiencies. Deficiency of CYP17A1 rarely causes AI, and HSD17B3 or SRD5A2 deficiencies only cause 46,XY DSD and gonadal insufficiency. All androgen biosynthesis depends on 17,20 lyase activity of CYP17A1 which is supported by P450 oxidoreductase (POR) and cytochrome b5 (CYB5). Therefore 46,XY DSD with apparent 17,20 lyase deficiency may be due to mutations in CYP17A1, POR or CYB5. Illustrated by patients harboring mutations in SRD5A2, normal development of the male external genitalia depends largely on dihydrotestosterone (DHT) which is converted from circulating testicular testosterone (T) through SRD5A2 in the genital skin. In the classic androgen biosynthetic pathway, T is produced from DHEA and androstenedione/-diol in the testis. However, recently found mutations in AKR1C2/4 genes in undervirilized 46,XY individuals have established a role for a novel, alternative, backdoor pathway for fetal testicular DHT synthesis. In this pathway, which has been first elucidated for the tammar wallaby pouch young, 17-hydroxyprogesterone is converted directly to DHT by 5α-3α reductive steps without going through the androgens of the classic pathway. Enzymes AKR1C2/4 catalyse the critical 3αHSD reductive reaction which feeds 17OH-DHP into the backdoor pathway. In conclusion, androgen production in the fetal testis seems to utilize two pathways but their exact interplay remains to be elucidated.