Search for π0→νμνˉμ\pi^0 \to \nu_{\mu}\bar\nu_{\mu} Decay in LSND

We observe a net beam-excess of $8.7 \pm 6.3$ (stat) $\pm 2.4$ (syst) events, above 160 MeV, resulting from the charged-current reaction of $\nu_{\mu}$ and/or $\bar\nu_{\mu}$ on C and H in the LSND detector. No beam related muon background is expected in this energy regime. Within an analysis framework of $\pi^0 \to \nu_{\mu}\bar\nu_{\mu}$, we set a direct upper limit for this branching ratio of $\Gamma(\pi^0 \to \nu_\mu \bar\nu_\mu) / \Gamma(\pi^0 \to all) < 1.6 \times 10^{-6}$ at 90% confidence level.Comment: 4 pages, 4 figure

The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM

The activation of ATR-ATRIP in response to double-stranded DNA breaks (DSBs) depends upon ATM in human cells and Xenopus egg extracts. One important aspect of this dependency involves regulation of TopBP1 by ATM. In Xenopus egg extracts, ATM associates with TopBP1 and thereupon phosphorylates it on S1131. This phosphorylation enhances the capacity of TopBP1 to activate the ATR-ATRIP complex. We show that TopBP1 also interacts with the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. This interaction involves the Nbs1 subunit of the complex. ATM can no longer interact with TopBP1 in Nbs1-depleted egg extracts, which suggests that the MRN complex helps to bridge ATM and TopBP1 together. The association between TopBP1 and Nbs1 involves the first pair of BRCT repeats in TopBP1. In addition, the two tandem BRCT repeats of Nbs1 are required for this binding. Functional studies with mutated forms of TopBP1 and Nbs1 suggested that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. These findings suggest that the MRN complex is a crucial mediator in the process whereby ATM promotes the TopBP1-dependent activation of ATR-ATRIP in response to DSBs

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Rethinking “democratic backsliding” in Central and Eastern Europe – looking beyond Hungary and Poland

This essay introduces contributions to a special issue of East European Politics on “Rethinking democratic backsliding in Central and Eastern Europe”, which seeks to expand the study of democratic regression in CEE beyond the paradigmatic cases of Hungary and Poland. Reviewing these contributions, we identify several directions for research: 1) the need to critique “democratic backsliding”, not simply as a label, but also as an assumed regional trend; 2) a need to better integrate the role of illiberal socio-economic structures such as oligarchical structures or corrupt networks; and 3) a need to (re-)examine the trade-offs between democratic stability and democratic quality. We also note how insights developed researching post-communist regions such as Western Balkans or the post-Soviet space could usefully inform work on CEE backsliding. We conclude by calling for the study of CEE democracy to become more genuinely interdisciplinary, moving beyond some narrowly institutionalist comparative political science assumptions

Clostridioides difficile positivity rate and PCR ribotype distribution on retail potatoes in 12 European countries, January to June 2018

Background While human-to-human transmission of Clostridioides difficile occurs often, other infection sources, including food, animals and environment, are under investigation. Aim We present a large study on C. difficile in a food item in Europe, encompassing 12 European countries (Austria, France, Greece, Ireland, Italy, the Netherlands, Poland, Slovakia, Spain, Sweden, Romania and the United Kingdom). Methods Potato was selected because of availability, ease of sampling and high C. difficile positivity rates. Identical protocols for sampling and isolation were used, enabling a direct comparison of the C. difficile positivity rate. Results From C. difficile-positive potato samples (33/147; 22.4%), we obtained 504 isolates, grouped into 38 PCR ribotypes. Positivity rates per country varied (0–100%) and were at least 10% in 9/12 countries. No geographical clustering of samples with high positivity rates or in PCR ribotype distribution was observed. The most frequently detected PCR ribotypes (014/020, 078/126, 010 and 023) are also commonly reported in Europe among human clinically relevant isolates, in animal isolates and in the environment. Whole genome sequencing revealed several genetically related strain pairs (Spain/RT126, France/RT010, Austria and Sweden/RT276) and a cluster of very similar strains in RT078/126. Conclusion Our results suggest, the high potato contamination rates could have public health relevance. They indicate potatoes can serve as a vector for introducing C. difficile spores in the household environment, where the bacterium can then multiply in sensitive hosts with disrupted or unmature microbiota. Potato contamination with PCR ribotypes shared between humans, animals and soil is supportive of this view

Comparative genomic analysis of toxin-negative strains of Clostridium difficile from humans and animals with symptoms of gastrointestinal disease

Background: Clostridium difficile infections (CDI) are a significant health problem to humans and food animals. Clostridial toxins ToxA and ToxB encoded by genes tcdA and tcdB are located on a pathogenicity locus known as the PaLoc and are the major virulence factors of C. difficile. While toxin-negative strains of C. difficile are often isolated from faeces of animals and patients suffering from CDI, they are not considered to play a role in disease. Toxin-negative strains of C. difficile have been used successfully to treat recurring CDI but their propensity to acquire the PaLoc via lateral gene transfer and express clinically relevant levels of toxins has reinforced the need to characterise them genetically. In addition, further studies that examine the pathogenic potential of toxin-negative strains of C. difficile and the frequency by which toxin-negative strains may acquire the PaLoc are needed. Results: We undertook a comparative genomic analysis of five Australian toxin-negative isolates of C. difficile that lack tcdA, tcdB and both binary toxin genes cdtA and cdtB that were recovered from humans and farm animals with symptoms of gastrointestinal disease. Our analyses show that the five C. difficile isolates cluster closely with virulent toxigenic strains of C. difficile belonging to the same sequence type (ST) and have virulence gene profiles akin to those in toxigenic strains. Furthermore, phage acquisition appears to have played a key role in the evolution of C. difficile. Conclusions: Our results are consistent with the C. difficile global population structure comprising six clades each containing both toxin-positive and toxin-negative strains. Our data also suggests that toxin-negative strains of C. difficile encode a repertoire of putative virulence factors that are similar to those found in toxigenic strains of C. difficile, raising the possibility that acquisition of PaLoc by toxin-negative strains poses a threat to human health. Studies in appropriate animal models are needed to examine the pathogenic potential of toxin-negative strains of C. difficile and to determine the frequency by which toxin-negative strains may acquire the PaLoc

International Clostridium difficile animal strain collection and large diversity of animal associated strains

Background: Clostridium difficile is an important cause of intestinal infections in some animal species and animals might be a reservoir for community associated human infections. Here we describe a collection of animal associated C. difficile strains from 12 countries based on inclusion criteria of one strain (PCR ribotype) per animal species per laboratory. Results: Altogether 112 isolates were collected and distributed into 38 PCR ribotypes with agarose based approach and 50 PCR ribotypes with sequencer based approach. Four PCR ribotypes were most prevalent in terms of number of isolates as well as in terms of number of different host species: 078 (14.3% of isolates; 4 hosts), 014/020 (11.6%; 8 hosts); 002 (5.4%; 4 hosts) and 012 (5.4%; 5 hosts). Two animal hosts were best represented; cattle with 31 isolates (20 PCR ribotypes; 7 countries) and pigs with 31 isolates (16 PCR ribotypes; 10 countries). Conclusions: This results show that although PCR ribotype 078 is often reported as the major animal C. difficile type, especially in pigs, the variability of strains in pigs and other animal hosts is substantial. Most common human PCR ribotypes (014/020 and 002) are also among most prevalent animal associated C. difficile strains worldwide. The widespread dissemination of toxigenic C. difficile and the considerable overlap in strain distribution between species furthers concerns about interspecies, including zoonotic, transmission of this critically important pathogen

1989 as a mimetic revolution: Russia and the challenge of post-communism

Various terms have been used to describe the momentous events of 1989, including Jürgen Habermas’s ‘rectifying revolution,’ and my own notion of 1989 as a type of ‘anti-revolution’: repudiating not only what had come before, but also denying the political logic of communist power, as well as the emancipatory potential of revolutionary socialism in its entirety. In the event, while the negative agenda of 1989 has been fulfilled, it failed in the end to transcend the political logic of the systems that collapsed at that time. This paper explores the unfulfilled potential of 1989. Finally, 1989 became more of a counter- rather than an anti-revolution, replicating in an inverted form the practices of the mature state socialist regimes. The paucity of institutional and intellectual innovation arising from 1989 is striking. The dominant motif was ‘returnism,’ the attempt to join an established enterprise rather than transforming it. Thus, 1989 can be seen as mimetic revolution, in the sense that it emulated systems that were not organically developed in the societies in which they were implanted. For Eastern Europe ‘returning’ to Europe appeared natural, but for Russia the civilizational challenge of post-communism was of an entirely different order. There could be no return, and instead of a linear transition outlined by the classic transitological literature, Russia’s post-communism demonstrated that the history of others could not be mechanically transplanted from one society to another