1,720,977 research outputs found
Virus-host interactions resolved through manipulation of viral and host gene expression
No full textViruses existed long before modern humans evolved and might have been there from the beginning of the evolution of living cells. The corona virus pandemic shows us the danger of acute infections and how easy viruses can spread and evolve. While SARS-CoV-2 is omnipresent, general awareness of herpesvirus infections, which can cause severe and fatal illnesses, is limited. Both coronaviruses and herpesviruses share the ability to evolve with their hosts to develop sophisticated mechanisms to interfere with their host’s immune system to prevent clearance. While EBV, for example, can limit the expression of viral proteins to curtail immune recognition, viral miRNAs are expressed during all stages of infection and likely play important role in EBV infection. Therefore methods to research, control and understand viral miRNAs are of great importance.
Chapter 2 shows the generation and optimization of potent EBV miRNA inhibitors whose efficiency depends on their thermodynamic properties. These inhibitors were subsequently employed in chapter 3 to pinpoint which EBV miRNAs target specific host genes that were identified in a screen for EBV miRNA targets. Here, we identified many new host genes that are regulated by EBV miRNAs. We characterized one specific miRNA that downregulated two genes involved in autophagy resulting in enhanced autophagic flux, which could subsequently aid in viral survival.
Herpesvirus are not only adept in evading immune responses, they furthermore establish latency. Since latent infections cannot be cleared yet with traditional treatments, new methods are needed to tackle this problem. Genome engineering with CRISPR/Cas9 shows great promise in clearing cells of latent viral genomes. Therefore, in Chapter 4 we review how CRISPR/Cas9 is being utilized as an anti-viral tool to target pathogenic human viruses. In chapter 5 we employ CRISPR/Cas9 as a genetic tool to screen for host factors involved in HCMV infection. Here we identified and characterized known and novel genes that are involved in the HCMV infection cycle.
Viruses can interfere with their detection by the host to ensure their survival by e.g. limiting the presentation of viral antigens on the surface of infected cells thereby evading recognition by surveying cytotoxic T cells, thus preventing the clearance of virus infected cells.
Chapter 6 describes a flow cytometry-based method to assess how viral proteins can interfere with the MHC class I antigen pathway. The method can also aid to pinpoint the possible mode of action. In chapter 7 we screened the viral proteins of SARS-CoV-2 for their effect on MHC class I expression and identified a single gene product that interferes with surface expression of HLA-I.
Finally, chapter 8 provides a summarizing discussion and points at potential future research
Viral evasion of the MHC class I antigen presentation pathway. It's a T(r)AP
No full textHerpesviruses use a broad set of immune modulating mechanisms to escape the immune system; causing lifelong infections with these viruses. In this thesis we discuss newly identified interactions between viral evasins and host proteins and how these evasins influence essential processes in the host
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
We are all on the same team: Growing together towards RSV prevention
No full textThe harmonious dance between academia and industry
This is an exciting time for RSV research. With the recent approval of the first-ever RSV vaccines and monoclonal antibody (mAb) for all infants, we are on the cusp of major advances in the prevention of RSV disease. Of these RSV vaccines, many are a result of joint research between academia and industry. The rationale is that these PPPs overcome challenges in financing, implementation and delivery of infrastructure and public services, based on the assumption that the private sector brings additional finance and competence and that private companies are inherently more efficient than the public sector in delivering high-quality public services. While the concept of PPPs appears straightforward, the implementation may face multiple challenges. PPPs are complex as the value for money is often ethically questioned and the procurement processes can be lenghty because of legal and regulatory barriers. Lack of transparency and accountability may be the top barrier of PPPs, however, legal barriers including approval and permits and law and regulation changes may also slow down the process. With RSV prevention within reach and the potential risk of PPPs creating complex challenges, we have explored how PPPs co-create value in RSV research.
Is industry-funded RSV research on balance beneficial? Clearly it is. Ultimately, the positives of PPPs in RSV research heavily outweigh the negatives. The question is not whether there may be conflicts of interest for – there are. Rather, the goal is to work around those and achieve a fair, transparent, unbiased, and scientifically valid result that benefits all. We cannot pretend that the public sector owns public health: promoting clarity and transparency in clinical research is an intrinsic public health good and a shared responsibility of both academia and industry. While pure academic research is an important adjuvant to industry-supported development, it cannot replace the focus or scope of industry funding.
In the graceful choreography uniting academia and industry, the orchestrated symphony of PPPs unveils not just scientific advancements, but also weaves a melodic tapestry of collaborative determination that forges a future fortified against RSV
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Roles and regulation of Epstein-Barr virus microRNAs
No full textMicroRNAs are posttranscriptional gene regulators that play important roles in many cellular processes. These short non-coding RNA molecules regulate gene expression by binding to complementary target mRNAs, thereby inducing RNA destabilization and inhibition of translation. Several DNA viruses hijack the cellular miRNA machinery to produce their own miRNAs, which offers opportunities to regulate both cellular and viral gene expression. The human herpesvirus Epstein-Barr Virus (EBV) encodes more than 40 different miRNAs, which are expressed during all stages of the virus lifecycle and in EBV-associated tumours. EBV is carried as a lifelong latent infection in more than 90% of the adult human population. The virus is the causative agent of infectious mononucleosis and is associated with various malignancies of B cell and epithelial origin.
In this thesis we provide a detailed analysis of the EBV miRNA expression profiles in EBV-positive cell lines of different origins. We discovered that the organization of the Epstein-Barr virus (EBV) miRNAs in clusters enhances their functional expression. Furthermore, we developed extensive lentiviral tools to express and inhibit specific miRNAs in cells, to be able to study their biological function. By performing whole-genome transcriptome profiling we identified and validated new EBV miRNA targets. We identified several EBV-encoded miRNAs as novel viral immune evasion factors that interfere with the type I IFN signaling pathway, amongst others.
Understanding the specific functions of EBV miRNAs leads to new insights into EBV biology that open new avenues for antiviral therapy development by specifically targeting viral and host genes involved in infection and oncogenic transformation
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