Increased APOBEC3G and APOBEC3F expression is associated with low viral load and prolonged survival in simian immunodeficiency virus infected rhesus monkeys

<p>Abstract</p> <p>Background</p> <p>The cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) are innate cellular factors that inhibit replication of a number of viruses, including HIV-1. Since antiviral activity of APOBEC3 has been mainly confirmed by <it>in vitro </it>data, we examined their role for disease progression in the SIV/macaque model for AIDS.</p> <p>Results</p> <p>We quantified A3G and A3F mRNA in PBMC and leukocyte subsets of uninfected and SIVmac-infected rhesus macaques. Compared with uninfected animals, we found increased A3G and A3F mRNA levels in PBMC, purified CD4+ T-cells and CD14+ monocytes as well as lymph node cells from asymptomatic SIV-infected macaques. APOBEC3 mRNA levels correlated negatively with plasma viral load, and highest amounts of APOBEC3 mRNA were detected in long term non-progressors (LTNPs). During acute viremia, A3G mRNA increased in parallel with MxA, a prototype interferon-stimulated gene indicating a common regulation by the initial interferon response. This association disappeared during the asymptomatic stage.</p> <p>Conclusion</p> <p>Our findings suggest a protective effect of APOBEC3 for HIV and SIV <it>in vivo </it>and indicate regulation of APOBEC3 by interferon during early infection and by contribution of other, hitherto undefined factors at later disease stages. Elucidating the regulatory mechanisms leading to increased APOBEC3 mRNA levels in LTNPs could help to develop new therapies against HIV.</p

African swine fever epidemiology and control

African swine fever is a devastating disease that can result in death in almost all infected pigs. The continuing spread of African swine fever from Africa to Europe and recently to the high–pig production countries of China and others in Southeast Asia threatens global pork production and food security. The African swine fever virus is an unusual complex DNA virus and is not related to other viruses. This has presented challenges for vaccine development, and currently none is available. The virus is extremely well adapted to replicate in its hosts in the sylvatic cycle in East and South Africa. Its spread to other regions, with different wildlife hosts, climatic conditions, and pig production systems, has revealed unexpected epidemiological scenarios and different challenges for control. Here we review the epidemiology of African swine fever in these different scenarios and methods used for control. We also discuss progress toward vaccine development and research priorities to better understand this complex disease and improve control

Cytoprotective mechanisms in cultured cardiomyocytes

Tumor necrosis factor-α (TNF-α), a potent cytokine mainly secreted by macrophages exerts pleiotropic effects on different cell types. However, the intracellular mediators of its action are not yet well characterized. To get an insight into endogenous cytoprotective mechanisms, we developed an in vitro model based on cultured cardiomyocytes treated with TNF-α at which we examined gene expression of heat shock proteins (HSP-27, HSP-70 and ubiquitin). Cardiomyocytes were isolated from the hearts of 18 day old fetal mice by enzymatic dissociation and grown in minimum essential medium containing 10% fetal calf serum. Spontaneously contractile cells were serum deprived for 24 h and treated with TNF-α(25 ng/ml) for 1, 2, 4, 6, 8, 12, and 24 h After each incubation, cells were processed to extract total proteins for Western and total RNA for Northern blot analyses. TNF-α induced arrhythmias and cessation of spontaneous contractions in a concentration and time dependent manner. Steady state (ubiquitin) or undetectable mRNA levels (HSP-27, HSP-70) were drastically induced (> 4 fold for all three genes vs untreated control cells) by TNF-α, reaching maximal values between 6-8 h of stimulation. Thereafter, the expression of these stress genes declined but remained elevated as compared to control. By Western blot analysis, we found increased multiple bands of ubiquitin protein conjugates in TNF-α treated cells whereas no significant change in HSP-27 protein accumulation until 12 h was observed as compared to control. 24 h of TNF-α incubation resulted in partial cellular necrosis. Our results indicate that TNF-α induces in cardiomyocytes transiently gene expression for cytoprotective molecules like HSP-27, HSP-70 and ubiquitin, suggesting these stress proteins to participate in subsequent defense mechanisms, for example in postischemic myocardial recovery

The Diversity Factor: How Cultural Diversity Impacts Innovations in Germany

The 2018 Reinhard Mohn Prize on “Living Diversity – Shaping Society” is meant to bring new momentum and perspectives to how Germany lives diversity and shapes society. The present study “The Diversity Factor – How Cultural Diversity Impacts Innovations in Germany” examines the question of whether and how cultural diversity affects the innovative power of both companies and society. There is much to suggest that a culturally diverse workforce – e.g. people with different experiences, mindsets and interpretive contexts – fosters creativity and innovation. The current publication is based on evaluations of empirical studies that examine the correlation between cultural diversity and innovation. This analysis of the literature was carried out using a narrow definition of cultural diversity, one that includes, in particular, the dimensions of “ethnicity,” “religion/world view” and “nationality.” Innovation was measured in each study based on the number of patents, patent citations or companies’ self-assessments of their product and process innovations or overall factor productivity. The results of this research were then considered more deeply in interviews and conversations with business experts, public administrators and civil society leaders

Transcriptome sequencing and comparative transcriptome analysis of the scleroglucan producer Sclerotium rolfsii

Schmid J, Müller-Hagen D, Bekel T, et al. Transcriptome sequencing and comparative transcriptome analysis of the scleroglucan producer Sclerotium rolfsii. BMC Genomics. 2010;11(1): 329.Background The plant pathogenic basidiomycete Sclerotium rolfsii produces the industrially exploited exopolysaccharide scleroglucan, a polymer that consists of (1 -> 3)-[beta]-linked glucose with a (1 -> 6)-(beta)-glycosyl branch on every third unit. Although the physicochemical properties of scleroglucan are well understood, almost nothing is known about the genetics of scleroglucan biosynthesis. Similarly, the biosynthetic pathway of oxalate, the main by-product during scleroglucan production, has not been elucidated yet. In order to provide a basis for genetic and metabolic engineering approaches, we studied scleroglucan and oxalate biosynthesis in S. rolfsii using different transcriptomic approaches. Results Two S. rolfsii transcriptomes obtained from scleroglucan-producing and scleroglucan-nonproducing conditions were pooled and sequenced using the 454 pyrosequencing technique yielding ~350,000 reads. These could be assembled into 21,937 contigs and 171,833 singletons, for which 6,951 had significant matches in public protein data bases. Sequence data were used to obtain first insights into the genomics of scleroglucan and oxalate production and to predict putative proteins involved in the synthesis of both metabolites. Using comparative transcriptomics, namely Agilent microarray hybridization and suppression subtractive hybridization, we identified ~800 unigenes which are differently expressed under scleroglucan-producing and non-producing conditions. From these, candidate genes were identified which could represent potential leads for targeted modification of the S. rolfsii metabolism for increased scleroglucan yields. Conclusions The results presented in this paper provide for the first time genomic and transcriptomic data about S. rolfsii and demonstrate the power and usefulness of combined transcriptome sequencing and comparative microarray analysis. The data obtained allowed us to predict the biosynthetic pathways of scleroglucan and oxalate synthesis and to identify important genes putatively involved in determining scleroglucan yields. Moreover, our data establish the first sequence database for S. rolfsii, which allows research into other biological processes of S. rolfsii, such as host-pathogen interaction

Not-So-Risky Business? Assessing the Risk of Integrating Large RPVs into the Current Air Traffic System

In spite of considerable efforts to commercialize large remotely piloted vehicles (RPV), an integration of these RPVs into the existing Air Transportation System (ATS) and Airspace Structure is pending. The purpose of this paper was to assess the risks of an exemplary integration of a Heron 1 type RPV into the existing European air space structure within the current regulatory framework and without the availability of sense and avoid technology. Six incident occurrence scenarios were investigated, based on a modified Fault Tree Analysis and Eurocontrol’s risk matrix. It was found that without the implementation of technological or procedural changes, an integration of a Heron 1 RPV presents a low to medium risk to air traffic. Recommended risk mitigation measures include equipping the RPV-operator with a recognized air picture, equipping the RPV with TCAS, installing a conventional telephone land line between the RPV-operator and air traffic control, and commencing the integration of large RPVs into air traffic at night. Further, simulation and flight based research is necessary to demonstrate whether these control measures would reduce the risk to an overall low level

Measuring CRM Aptitude: Is NOTECHS a Suitable Tool for Pilot Selection?

Airline pilot’s primary job requirements have shifted from stick-and-rudder to CRM skills. At the same time, eliminating airline pilots from the job due to a lack of CRM skills is highly inefficient. Hence, an efficient and usable selection tool that helps to evaluate airline pilot candidates’ CRM skills prior their advanced training is needed. This paper examines the usability of the NOTECHS CRM assessment tool for already trained airline pilots for the purpose of pilot selection. CRM skills were evaluated during a scripted simple flying scenario in a Flight Navigation Procedure Trainer 2 (FNPT 2). Results indicate that the standard JAR TEL NOTECHS score form, which is subdivided into two social (cooperation; leadership & managerial skills) and two cognitive (situation awareness; decision making) categories, is efficiently usable by examiners who do not have to be psychologists, such as Human Resource personnel and airline pilots. Based on the experiment, some modifications to the NOTECHS score form were suggested