Human TOP1 residues implicated in species specificity of HIV-1 infection are required for interaction with BTBD2, and RNAi of BTBD2 in old world monkey and human cells increases permissiveness to HIV-1 infection

Host determinants of HIV-1 viral tropism include factors from producer cells that affect the efficiency of productive infection and factors in target cells that block infection after viral entry. TRIM5 restricts HIV-1 infection at an early post-entry step through a mechanism associated with rapid disassembly of the retroviral capsid. Topoisomerase I (TOP1) appears to play a role in HIV-1 viral tropism by incorporating into or otherwise modulating virions affecting the efficiency of a post-entry step, as the expression of human TOP1 in African Green Monkey (AGM) virion-producing cells increased the infectivity of progeny virions by five-fold. This infectivity enhancement required human TOP1 residues 236 and 237 as their replacement with the AGM counterpart residues abolished the infectivity enhancement. Our previous studies showed that TOP1 interacts with BTBD1 and BTBD2, two proteins which co-localize with the TRIM5 splice variant TRIM5 in cytoplasmic bodies. Because BTBD1 and BTBD2 interact with one HIV-1 viral tropism factor, TOP1, and co-localize with a splice variant of another, we investigated the potential involvement of BTBD1 and BTBD2 in HIV-1 restriction.

Seroprevalence and characterization of pestivirus infections in small ruminants and new world camelids in Switzerland

The seroprevalence of pestivirus infections in small ruminants and new world camelids in Switzerland was determined. In 5'059 sera of sheep from 382 herds, 503 sera of goats from 54 herds and 109 sera of alpacas and lamas from 53 herds, population prevalences of 16.1% (sheep), 25.4% (goats) and 4.6% (new world camelids), respectively, were found. In order to determine the source of infection, the serological reactions were further characterized by cross-neutralization against two pestiviruses representing the genotypes BVDV (Bovine Virus Diarrhea Virus)-1 and BDV (Border Disease Virus)-1. Based on the ratio of respective antibody titres, 56.1% of the infections in sheep were induced by a BDV-1, 12.9% by a BVDV-1 and 31.0% by an unresolved pestivirus. In goats, the corresponding proportions were 23.4%, 10.2% and 66.4%, respectively. In Alpacas and Lamas, the source of infection of 1 animal was BDV-1 and that of 4 seropositive animals remained unresolved. In view of the phylogenetic relationship between pestiviruses, the unresolved source of infection is most probably attributable to other pestivirus genotypes circulating in small ruminants and new world camelids. Due to the predominance of pestiviral genotypes other than BVDV-1, the risk of transmission of BVDV from persistently infected small ruminants and new world camelids to cattle appears to be moderate, apart from close direct contact in mixed animal husbandry, communal pasturing and grazing in the Alps.

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.

John Garstang at Sirkeli Höyük, Cilician Plain, in 1936-1937: Old Photographs and New Evidence from the Renewed Excavations

During the winter of 1936-1937, British archaeologist John Garstang (1876-1956) excavated several trenches at the site of Sirkeli Höyük, located in the Plain of Cilicia (18 km west of modern-day Ceyhan). After a single campaign, however, he left the site and his interest shifted to site of Yumuktepe/Mersin, where he then excavated for a number of years. Apart from two very brief preliminary reports of his excavations at Sirkeli Höyük, which were published in the journal 'Annals of Archaeology and Anthropology of the University of Liverpool', not much is known about the trenches and their associated finds. Unpublished photographs kept in the Special Archives of University College London shed new light on the location and orientation of some of Garstang’s trenches at the site. Furthermore, in the 2012 campaign of the renewed Turkish-Swiss excavations at the site, a trench was found in the western part of the northern terrace that most probably was excavated by Garstang, but was not mentioned by him in his reports. This hitherto unknown trench may be related to his discovery of a lion-shaped column base made of basalt that is now kept in the collections of the Archaeological Museum of Adana.

[Old and new interventional therapies in the treatment of symptomatic benign prostate hyperplasia (BPH)]

Benign Prostatic Hyperplasia is a common entity among the aging male population. Its prevalence is increasing with age and is around 80% in the over 80-years old. The androgen-estrogen ratio changes in favor of the estrogens, which leads to a growth of prostatic tissue, presenting histologically as hyperplasia. BPH can cause irritative or obstructive symptoms or both. Nowadays we speak of bladder storage or bladder voiding symptoms, summarised as LUTS (Lower Urinary Tract Symptoms). LUTS has a structural and a functional component, the structural being caused by the size of the adenoma itself the functional depending on the muscle tone of the bladder neck and the prostatic urethra. To investigate LUTS, we use validated symptom scores, sonography for residual urine and eventually a urodynamic evaluation. There are 3 grades of BPH. The indication for an interventional therapy is relative in BPH II, and absolute in BPH III. Prior to treatment, other diseases mimicking the same symptoms, have to be ruled out and adequatly treated. Electro-resection of the prostate (TUR-P) remains the standard therapy and the benchmark any new technology has to compete with. TUR-P has good short- and longterm results, but can be associated with a considerable perioperative morbidity, and the learning curve for the operator is long. The most promising of the newer techniques is the Holmium-Laser-Enucleation of the prostate (Laser-TUR-P), showing at least identical short- and median-term results, but a lower perioperative morbidity than TUR-P For several minimally-invasive techniques, indications are limited. TUMT TUNA, WIT and laser-coagulation all produce a coagulation necrosis of the prostatic tissue by thermic damage with secondary tissue shrinking. Urodynamic results however, are not comparable to TUR-P or Laser-TUR-P, and significantly more secondary interventions within 2 to 5 years are required. Minimal-invasive techniques present a favorable alternative for younger patients without complications of BPH, and for older patients with relevant comorbidities, and can usually be performed under local anaesthesia. The morbidity is low and further therapies remain possible later, if necessary.

Treatment of premenopausal women with early breast cancer: old challenges and new opportunities

Breast cancer occurring in women before the age of menopause continues to be a major medical and psychological challenge. Endocrine therapy has emerged as the mainstay of adjuvant treatment for women with estrogen receptor-positive tumours. Although the suppression of ovarian function (by oophorectomy, irradiation of the ovaries or gonadotropin releasing factor analogues) is effective as adjuvant therapy if used alone, its value has not been proven after chemotherapy. This is presumably because of the frequent occurrence of chemotherapy-induced amenorrhoea. Tamoxifen reduces the risk of recurrence by approximately 40%, irrespective of age and the ovarian production of estrogens. The worth of ovarian function suppression in combination with tamoxifen is unproven and is being investigated in an intergroup randomised clinical trial (SOFT [Suppression of Ovarian Function Trial]). Aromatase inhibitors are more effective than tamoxifen in postmenopausal women but are only being investigated in younger patients. The use of chemotherapies is identical in younger and older patients; however, at present the efficacy of chemotherapy in addition to ovarian function suppression plus tamoxifen is unknown in premenopausal patients with endocrine responsive disease. 'Targeted' therapies such as monoclonal antibodies to human epidermal growth factor receptor (HER)-2, HER1 and vascular endothelial growth factor, 'small molecule' inhibitors of tyrosine kinases and breast cancer vaccines are rapidly emerging. Their use depends on the function of the targeted pathways and is presently limited to clinical trials. Premenopausal patients are best treated in the framework of a clinical trial.

Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: a 6-year prospective candidaemia survey from the fungal infection network of Switzerland

We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre® YeastOne™ test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.

New results and new ice-borne finds from high-alpine passes in the Bernese Alps (Switzerland)

Archaeological finds from Schnidejoch (2756 m a.s.l.) and Lötschenpass (2690 m a.s.l.) cover the periods from the Early Neolithic to the Middle Ages (4800 BC - 1000 AD). The numerous finds from Schnidejoch discovered since 2003 can now be seen in relationship with Neolithic and Bronze Age settlements in the Rhone valley and together with the early use of alpine meadows and early transhumance. Finds of Early Bronze Age bows from Lötschenpass go back to the 1930ies. New finds of wooden objects and objects made from birch bark melted out from the ice in the summer of 2011. The lecture presents these new finds and an actualized view of Schnidejoch finds.