Induction and regulation of antiviral defence mechanisms through intracytoplasmic sensors

Das Wechselspiel zwischen Viren und ihren Wirtszellen beginnt meist an pattern recognition-Rezeptoren (PRRs), die für die Erkennung unterschiedlichster Pathogene anhand bestimmter Strukturen, sogenannten pathogen-associated molecular patterns (PAMPs), zuständig sind. Nach Detektion lösen die PRRs über verschiedene Signalkaskaden eine antivirale Antwort aus, die zur Expression antiviraler Gene führt. RIG-I und MDA5 sind zytoplasmatisch lokalisierte PRRs und erkennen RNA-Strukturen, die insbesondere während der viralen Replikation und Transkription verfügbar sind. Hantaviren sind humanpathogene RNA-Viren mit einem einzelsträngigen, segmentierten Genom. Die Konsequenzen hantaviraler Infektionen auf molekularer Ebene wurden bereits detailliert untersucht, aber die Mechanismen, die zur Induktion der Immunantwort führen, wie auch mögliche Immunevasionsstrategien, die wahrscheinlich in Zusammenhang mit der Pathogenität des jeweiligen Hantavirusstamms variieren, konnten bisher nicht identifiziert werden. Da Hantaviren im Cytoplasma ihrer Wirtszellen replizieren, stellen RIG-I und MDA5 potentielle Detektoren dar. In dieser Doktorarbeit wird die Bedeutung von RIG-I und MDA5 für die Erkennung von Hantavirus-Infektionen untersucht. Wachstumskinetiken zeigten, daß RIG-I die Replikation von pathogenen wie auch apathogenen Hantaviren beeinträchtigt. Außerdem konnte die RNA hantaviraler Nukleocapsid- (N-) ORFs als eine virale Komponente identifiziert werden, die Typ I Interferon über RIG-I induziert. Das Ausmaß der Interferon-Aktivierung korrelierte hierbei tendenziell mit dem Virulenzgrad der Virusstämme und war für die nicht-pathogenen Hantaviren nicht nachweisbar. Unterschiede in der Aktivierungsstärke können anhand vorläufiger Daten wahrscheinlich auf noch nicht identifizierte Motive zurückgeführt werden, die am 3’-Ende der N ORFs liegen. Im Gegensatz dazu wurde keine Interferon-Aktivierung durch hantavirale Komponenten über MDA5 festgestellt.Host-virus interaction is usually initated by pattern recognition receptors (PRRs) which are responsible for the recognition of various pathogens based on so-called pathogen-associated molecular patterns (PAMPs). Upon detection, PRRs trigger an antiviral immune response through different signalling cascades that lead to the expression of antiviral genes including interferon genes. RIG-I and MDA5 are cytoplasmically localised PRRs and recognise RNA patterns that are particularly available during viral replication and transcription. Hantaviruses are RNA viruses with single-stranded segmented genomes. The consequences of hantaviral infections have been analysed in detail, but the mechanisms that lead to the induction of the innate immune response as well as immune evasion strategies depending on the pathogenicity of the respective hantavirus strains have not been identified yet. Since hantaviruses replicate in the cytoplasm of their host cells, RIG-I and MDA5 represent potential PRRs for hantaviral detection. This thesis investigates the impact of RIG-I and MDA5 on recognition of hantaviral infections. Growth kinetics show that RIG-I impairs the replication of pathogenic as well as non-pathogenic hantaviruses. Furthermore, the RNA of hantaviral nucleocapsid protein (N) ORF could be identified as a viral component responsible for the induction of RIG-I signalling. It is shown that the degree of interferon promotor activation correlates with the virulence of the hantavirus strain from which the N ORF was derived. Based on preliminary data, differences in activation strength may be attributed to not yet identified motifs at the 3’ end of the ORF. In contrast, no interferon activation through MDA5 could be observed

The Effectiveness of Moxibustion: An Overview During 10 Years

Moxibustion has been used to treat various types of disease. However, there is still insufficient evidence regarding its effectiveness. This study was performed to summarize and evaluate the effectiveness of moxibustion. A search was performed for all randomized controlled trials in PubMed between January 1998 and July 2008 with no language restriction. The results yielded 47 trials in which six moxibustion types were applied to 36 diseases ranging from breech presentation to digestive disorders. Moxibustion was compared to three types of control group: general care, Oriental medical therapies or waiting list. Moxibustion was superior to the control in 14 out of 54 control groups in 46 studies. There were no significant differences among groups in 7 studies, and the outcome direction was not determined in 33 studies. Seven studies were included in a meta-analysis. Moxibustion was more effective than medication in two ulcerative colitis studies (relative risk (95% CI), 2.20 (1.37, 3.52), P = .001, I2 = 0%). Overall, our results did not support the effectiveness of moxibustion in specific diseases due to the limited number and low quality of the studies and inadequate use of controls. In order to provide appropriate evidence regarding the effectiveness of moxibustion, more rigorous clinical trials using appropriate controls are warranted

Spatiotemporal Characteristics of Drought Occurrences over Japan

The drought climate of Japan from 1902 to 2009 was analyzed using an effective drought index (EDI). Drought regions were identified by hierarchical cluster analysis using drought characteristics (duration, severity, and onset and end dates) obtained from 50 observation stations. The results indicated that droughts could be divided into four groups (G1–G4) that reflected the local climate. The four groups were related to precipitation as follows. The summer rainy season affected groups G2–G4, in which droughts occurred mainly during spring and summer and were relieved before and after the rainy season. The G1 group was not affected by the summer rainy season and droughts were spread evenly throughout the year; it even had cases of droughts relieved by winter snow. All groups included dry conditions over the 108-yr period, and the driest conditions occurred in the late twentieth century. The statistical analysis of drought data showed that a total of 23 country-wide droughts occurred and that the most extreme droughts occurred in 1939–41 and 1984–85, with an EDI of −1.55. In addition, four dry seasons (1939–45, 1997–98, 1994–97, and 2005–09) were found using regime shift analysis. Regional droughts occurred 54, 54, 49, and 59 times in groups G1–G4, respectively. On average, short-term droughts with a duration shorter than 6 months occurred 3.5 times per decade, whereas long-term droughts extending over 1 yr occurred 0.3 times per decade. The drought duration and intensity were used to calculate the statistical return period of country-wide droughts. The 1939–41 drought had the longest return period, at 104.7 yr. The 1987–88 and 1995–97 droughts had return periods of 65.9 and 65.5 yr, respectively

The GIBACHT fellowship: a multilateral initiative for strengthening capacity in biosafety and biosecurity towards pandemic preparedness

The German Biosecurity Programme was launched in 2013 with the aim to support partner countries overcome biological threats including natural outbreaks or the intentional misuse of highly pathogenic agents. As part of this programme, this paper describes the development and implementation of a multilateral biosafety and biosecurity training initiative, called ‘Global Partnership Initiated Biosecurity Academia for Controlling Health Threats’ (GIBACHT). To achieve its objectives, GIBACHT implemented a blended-learning approach with self-directed, distance-based learning phases and three training-of-trainer workshops. The programme follows Kirkpatrick’s model of learning to guarantee sustainable effects of improved knowledge and skills. One hundred nine fellows from 26 countries have been trained in seven cohorts. Many GIBACHT alumni have established additional biosafety/biosecurity trainings in their home countries. The knowledge exchange is strengthened by the implementation of a Moodle-based alumni network. GIBACHT has the potential to contribute to strengthening the capacities of partner countries in Africa, the Middle East, and South and Central Asia to respond and build resilience to biological threats

Determination of Polyphenol Components of Korean Prostrate Spurge ( Euphorbia supina

The Korean prostrate spurge Euphorbia supina is a weed that has been used in folk medicine in Korea against a variety of diseases. Nine polyphenols were characterized for this plant by using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and the results were compared with the literature data. The individual components were validated using the calibration curves of structurally related external standards and quantified for the first time by using the validated method. Correlation coefficients (r (2)) were >0.9907. The limit of detection and limit of quantification of the method were >0.028 mg/L and 0.094 mg/L, respectively. Recoveries measured at 50 mg/L and 100 mg/L were 76.1–102.8% and 85.2–98.6%, respectively. The total amount of the identified polyphenols was 3352.9 ± 2.8 mg/kg fresh plant. Quercetin and kaempferol derivatives formed 84.8% of the total polyphenols. The antioxidant activities of the flavonoids were evaluated in terms of 1,1-diphenyl-2-picrylhydrazyl and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation-scavenging activity, and the reducing power showed a dose-dependent increase. Cell viability was effectively suppressed at polyphenol mixture concentrations >250 mg/L

Active pulmonary tuberculosis and latent tuberculosis infection among homeless people in Seoul, South Korea: a cross-sectional study

Background : The aim of this study was to determine the prevalence rate of latent TB infection (LTBI) and active TB among homeless in Seoul metropolitan city, South Korea, and to compare the TB burden among homeless people with that of a control group. Methods : The homeless participants were recruited from five sites between October 30, 2009 and April 12, 2010. LTBI was diagnosed through the QuantiFERON(R) TB Gold In-Tube(QFT-GIT) assay and a tuberculin skin test(TST) and, and active PTB was diagnosed based on chest radiography. Results : Among 313 participants, the prevalence of LTBI was 75.9% (95% CI, 71.1-80.8%) and 79.8% (95% CI, 74.9-84.7%) based on a QFT-GIT assay and the TST, respectively, and that of active PTB was 5.8% (95% CI, 3.2-8.3%). The prevalence of LTBI among homeless participants was about five times higher than controls. Also, the age-specific prevalence rate ratio of active PTB was as high as 24.86. Conclusions : The prevalence rate of LTBI as well as active PTB among homeless people was much higher than that of the general population in South Korea. Thus, adequate strategies to reduce the TB burden among homeless people are needed.Peer Reviewe