Emergence of zoonotic arboviruses by animal trade and migration

Arboviruses are transmitted in nature exclusively or to a major extend by arthropods. They belong to the most important viruses invading new areas in the world and their occurrence is strongly influenced by climatic changes due to the life cycle of the transmitting vectors. Several arboviruses have emerged in new regions of the world during the last years, like West Nile virus (WNV) in the Americas, Usutu virus (USUV) in Central Europe, or Rift Valley fever virus (RVFV) in the Arabian Peninsula. In most instances the ways of introduction of arboviruses into new regions are not known. Infections acquired during stays in the tropics and subtropics are diagnosed with increasing frequency in travellers returning from tropical countries, but interestingly no attention is paid on accompanying pet animals or the hematophagous ectoparasites that may still be attached to them. Here we outline the known ecology of the mosquito-borne equine encephalitis viruses (WEEV, EEEV, and VEEV), WNV, USUV, RVFV, and Japanese Encephalitis virus, as well as Tick-Borne Encephalitis virus and its North American counterpart Powassan virus, and will discuss the most likely mode that these viruses could expand their respective geographical range. All these viruses have a different epidemiology as different vector species, reservoir hosts and virus types have adapted to promiscuous and robust or rather very fine-balanced transmission cycles. Consequently, these viruses will behave differently with regard to the requirements needed to establish new endemic foci outside their original geographical ranges. Hence, emphasis is given on animal trade and suitable ecologic conditions, including competent vectors and vertebrate hosts

The Fermi Bubbles. I. Possible Evidence for Recent AGN Jet Activity in the Galaxy

The Fermi Gamma-ray Space Telescope reveals two large gamma-ray bubbles in the Galaxy, which extend about 50 degrees (~ 10 kpc) above and below the Galactic center (GC) and are symmetric about the Galactic plane. Using axisymmetric hydrodynamic simulations with a self-consistent treatment of the dynamical cosmic ray (CR) - gas interaction, we show that the bubbles can be created with a recent active galactic nucleus (AGN) jet activity about 1 - 3 Myr ago, which was active for a duration of ~ 0.1 - 0.5 Myr. The bipolar jets were ejected into the Galactic halo along the rotation axis of the Galaxy. Near the GC, the jets must be moderately light with a typical density contrast 0.001 <~ \eta <~ 0.1 relative to the ambient hot gas. The jets are energetically dominated by kinetic energy, and over-pressured with either CR or thermal pressure which induces lateral jet expansion, creating fat CR bubbles as observed. The sharp edges of the bubbles imply that CR diffusion across the bubble surface is strongly suppressed. The jet activity induces a strong shock, which heats and compresses the ambient gas in the Galactic halo, potentially explaining the ROSAT X-ray shell features surrounding the bubbles. The Fermi bubbles provide plausible evidence for a recent powerful AGN jet activity in our Galaxy, shedding new insights into the origin of the halo CR population and the channel through which massive black holes in disk galaxies release feedback energy during their growth.Comment: Revised version, accepted for publication in ApJ. 17 pages, 11 figure

LinSets.zip: Compressing Linear Set Diagrams

Linear diagrams are used to visualize set systems by depicting set memberships as horizontal line segments in a matrix, where each set is represented as a row and each element as a column. Each such line segment of a set is shown in a contiguous horizontal range of cells of the matrix indicating that the corresponding elements in the columns belong to the set. As each set occupies its own row in the matrix, the total height of the resulting visualization is as large as the number of sets in the instance. Such a linear diagram can be visually sparse and intersecting sets containing the same element might be represented by distant rows. To alleviate such undesirable effects, we present LinSets.zip, a new approach that achieves a more space-efficient representation of linear diagrams. First, we minimize the total number of gaps in the horizontal segments by reordering columns, a criterion that has been shown to increase readability in linear diagrams. The main difference of LinSets.zip to linear diagrams is that multiple non-intersecting sets can be positioned in the same row of the matrix. Furthermore, we present several different rendering variations for a matrix-based representation that utilize the proposed row compression. We implemented the different steps of our approach in a visualization pipeline using integer-linear programming, and suitable heuristics aiming at sufficiently fast computations in practice. We conducted both a quantitative evaluation and a small-scale user experiment to compare the effects of compressing linear diagrams.Comment: To be presented at PacificVis 202

Bildung 12- bis 40-gliedriger Oligolide aus enantiomerenreinen 3-Hydroxybuttersäure-Derivaten – Bausteine für eine 2₁- und eine 3₁-Helix

Trimeric, tetrameric, and pentameric oligolides are formed preferentially from (S)-βbutyrolactone, or from methyl (R)-3-hydroxybutanoate, upon prolonged treatment with catalytic amounts of tetraoxadistannacyclodecane (Shanzer's macrolactonization catalyst) in refluxing xylene. The crystal structure of the tetramer is described. Substructures of the larger folded oligolides are used for the construction of a left-handed 21-helix, as found in the biopolymer PHB, and a heretofore unknown right-handed 31-helix

VirtualToxLab – in silico Prediction of the Endocrine-Disrupting Potential of Drugs and Chemicals

In the last decade, we have developed and validated an in silico concept based on multidimensional QSAR (mQSAR) for the prediction of the toxic potential of drugs and environmental chemicals. Presently, the VirtualToxLab includes eleven so-called virtual test kits for estrogen (?/?), androgen, thyroid (?/?), glucocorticoid, aryl hydrocarbon, mineralocorticoid and peroxisome proliferator-activated receptor ? as well as for the enzymes cytochrome P450 3A4 and 2A13. The surrogates have been tested against a total of 824 compounds and are able to predict the binding affinity close to the experimental uncertainty with only six of the 194 test compounds giving calculated results more than a factor of 10 off the experimental binding affinity and the maximal individual deviation not exceeding a factor of 15. These results suggest that our approach is suited for the in silico identification of endocrine-disrupting effects triggered by drugs and environmental chemicals. Most recently, the technology has been made available through the Internet for academic laboratories, hospitals and environmental organizations

Chikungunya Fever – Invading Tropical Virus in the Mediterranean Region?

Chikungunya groznica je virusna infekcija koju uzrokuje virus roda Alphavirus, iz obitelji Togaviridae. U prirodi se prenosi isključivo komarcima roda Aedes. Uzrokuje febrilnu bolest s izraženim artritisom i artralgijama koje mogu trajati i do nekoliko mjeseci. Godine 2004., zabilježena je velika epidemija u istočnoj Africi koja se proširila preko Indije do jugoistočne Azije, uzrokujući, prema procjenama, zarazu nekoliko milijuna stanovnika zahvaćenih zemalja. Godine 2007., Chikungunya virus je unesen u Italiju preko zaraženog putnika uzrokujući epidemiju sa više od 200 zaraženih osoba. Virus je tamo prenio azijski tigrasti komarac (Aedes albopictus). Chikungunya virus u kombinaciji sa Aedes albopictus čini cjelinu s visokim potencijalom za pojavljivanjem u do sada nezahvaćenim područjima. U radu se donosi pregled trenutne situacije i definiraju kriteriji za otkrivanje klinički suspektnih slučajeva koji zahtijevaju brzu intervenciju.Chikungunya fever is a virus infection caused by a virus of the genus Alphavirus, family Togaviridae. It is transmitted in nature exclusively by mosquitoes of the genus Aedes. It causes a febrile illness with prominent arthritis and incapacitating arthralgias, which may last for months. In 2004, a large outbreak started in East Africa, spread over India to Southeast Asia and caused an estimated several million human cases in the affected countries. In 2007, Chikungunya virus was introduced by a viremic traveller into Italy and there caused an outbreak with more than 200 human cases. The virus there was transmitted by the Asian tiger mosquito (Aedes albopictus). Chikungunya virus in combination with Aedes albopictus forms a complex with high potential for emergence in so far unaffected regions. The actual paper reviews the current situation and presents a case definition for detection of clinically suspicious cases for rapid intervention of transmission

Comparison of Three Serological Methods for the Epidemiological Investigation of TBE in Dogs

Tick-borne encephalitis (TBE) virus is an emerging pathogen that causes severe infections in humans. Infection risk areas are mostly defined based on the incidence of human cases, a method which does not work well in areas with sporadic TBE cases. Thus, sentinel animals may help to better estimate the existing risk. Serological tests should be thoroughly evaluated for this purpose. Here, we tested three test formats to assess the use of dogs as sentinel animals. A total of 208 dog sera from a known endemic area in Southern Germany were tested in an All-Species-ELISA and indirect immunofluorescence assays (IIFA), according to the manufacturer’s instructions. Sensitivity and specificity for both were determined in comparison to the micro-neutralization test (NT) results. Of all 208 samples, 22.1% tested positive in the micro-NT. A total of 18.3% of the samples showed characteristic fluorescence in the IIFA and were, thus, judged positive. In comparison to the micro-NT, a sensitivity of 78.3% and a specificity of 98.8% was obtained. In the ELISA, 19.2% of samples tested positive, with a sensitivity of 84.8% and a specificity of 99.4%. The ELISA is a highly specific test for TBE-antibody detection in dogs and should be well suited for acute diagnostics. However, due to deficits in sensitivity, it cannot replace the NT, at least for epidemiological studies. With even lower specificity and sensitivity, the same applies to IIFA

The Red Fox (Vulpes vulpes) as Sentinel for Tick-Borne Encephalitis Virus in Endemic and Non-Endemic Areas

Tick-borne encephalitis (TBE) is one of the most important viral zoonosis caused by a neurotropic arbovirus (TBEV). In Germany, TBE is classified as a notifiable disease with an average of 350 autochthonous human cases annually. The incidence-based risk assessment in Germany came under criticism because every year, a number of autochthonous human TBE cases have been detected outside of the official risk areas. Therefore, it is necessary to find additional parameters to strengthen TBEV surveillance. The aim of this study was to examine red foxes as sentinels for TBE. Thus far, there are no published data about the sensitivity and specificity for serological methods testing fox samples. Hence, we aimed to define a system for the screening of TBEV-specific antibodies in red foxes. A total of 1233 fox sera were collected and examined by ELISA and IIFA and confirmed by micro-NT. The overall seroprevalence of antibodies against TBEV in red foxes from Germany confirmed by micro-NT was 21.1%. The seroprevalence differed significantly between risk (30.5%) and non-risk areas (13.1%), with good correlations to local TBE incidence in humans. In conclusion, serological monitoring of red foxes represents a promising surrogate marker system and may even determine unexpected TBEV foci in regions currently regarded as non-risk areas

Fermi Bubbles in the Milky Way: the closest AGN feedback laboratory courtesy of Sgr A*?

Deposition of a massive ($10^4$ to 10^5 \msun) giant molecular cloud (GMC) into the inner parsec of the Galaxy is widely believed to explain the origin of over a hundred unusually massive young stars born there $\sim 6$ Myr ago. An unknown fraction of that gas could have been accreted by Sgr A*, the supermassive black hole (SMBH) of the Milky Way. It has been recently suggested that two observed $\gamma$-ray-emitting bubbles emanating from the very center of our Galaxy were inflated by this putative activity of Sgr A*. We run a suite of numerical simulations to test whether the observed morphology of the bubbles could be due to the collimation of a wide angle outflow from Sgr A* by the disc-like Central Molecular Zone (CMZ), a well known massive repository of molecular gas in the central $\sim 200$ pc. We find that an Eddington-limited outburst of Sgr A* lasting $\simeq 1$ Myr is required to reproduce the morphology of the {\it Fermi} bubbles, suggesting that the GMC mass was \sim 10^5 \msun and it was mainly accreted by Sgr A* rather than used to make stars. We also find that the outflow from Sgr A* enforces strong angular momentum mixing in the CMZ disc, robustly sculpting it into a much narrower structure -- a ring -- perhaps synonymous with the recently reported "Herschel ring". In addition, we find that Sgr A* outflow is likely to have induced formation of massive star-forming GMCs in the CMZ. In this scenario, the Arches and Quintuplet clusters, the two observed young star clusters in the central tens of parsecs of the Galaxy, and also GMCs such as Sgr B2, owe their existence to the recent Sgr A* activity.Comment: 18 pages, 10 figures, submitted to MNRA

Serological differentiation of antibodies against Rickettsia helvetica, R. raoultii, R. slovaca, R. monacensis and R. felis in dogs from Germany by a micro-immunofluorescent antibody test

Background Spotted Fever Group (SFG) Rickettsiae can cause febrile diseases with or without rash in humans worldwide. In Germany only limited data are available about their medical significance. Serological screening tests for antibodies against rickettsiae usually only distinguish between SFG and Typhus Group (TG) Rickettsiae due to the strong cross reactivities within the groups. Seroprevalence rates in dogs, as possible sentinels for tick-borne diseases, could serve as an indicator for the distribution of different Rickettsia species. Methods In this study, a micro-immunofluorescence assay (micro-IFA) was established for detection and differentiation of antibodies against five Rickettsia species in dogs (R. helvetica, R. raoultii, R. slovaca, R. monacensis and R. felis). Dogs that never left Germany (n = 605) previously investigated with an SFG-ELISA were included in this study and screened at a 1:128 dilution. Endpoint titres of fifty randomly selected seropositive samples of each of the five investigated regions in Germany were determined in order to allow a differentiation of the causative Rickettsia species. Sensitivity and specificity of the micro-IFA were compared with ELISA results of the previous study. Results A total of 93.9% of the dogs were positive for antibodies of the SFG Rickettsiae at the screening titer of 1:128. Differentiation of SFG Rickettsiae with the micro-IFA was possible in 70.4%, but in 29.6% of the cases the detected antibodies were not differentiable. Considering a clear differentiation by a twofold titre difference between observed reactions, the seroprevalence rates were 66.0% for R. helvetica, 2.8% for R. raoultii, 1.6% for R. slovaca, but no serological reaction could be clearly attributed to R. monacensis or R. felis. No statistically significant regional differences were found for R. helvetica, R. slovaca and R. raoultii comparing the five regions of Germany. Comparison of micro-IFA with ELISA revealed a sensitivity of 82.0% and a specificity of 83.8% for the Rickettsia SFG ELISA. Conclusions The micro-IFA is a useful serological tool to differentiate antibodies against different Rickettsia species in dogs. Seroprevalence rates in dogs correspond to the prevalence rates and distribution of Rickettsia-carrying tick species