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    Cdk1-regulated diphosphodegron tags for controlled protein expression

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    Cyclin dependent kinases (CDKs) regulate the cell cycle by phosphorylating downstream proteins in an ordered manner. In yeast S. cerevisiae, Cdk1 regulates the cell cycle progression from G1 to M phase. Cdk1 phosphorylation can have various effects on the proteins, for example, they can be activated or targeted for degradation. The latter was used in this work to design a regulatory network for controlled protein expression that could be used in cell factories. For this, Far1-based diphosphodegron tags that are degraded in response to phosphorylation by Cdk1, were used to differentially regulate the levels of the transcriptional repressor TetR. Furthermore, as cell factories require dynamic control of protein levels over the cultivation process, the effect of cell culture density on cell cycle and the degron tags was studied. The work shows that Far1-based degron tags can be used as modular tags to regulate exogenous proteins by switching them on or off in an OD-dependent manner using the endogenous Cdk1 machinery. Finally, it was shown that more complex patterns of regulation can be achieved by inducing expression of cyclins at high OD

    Inimese rasvumise geneetilised ja keskkonnamõjud

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    Obesity is a rising global problem, clinically defined as having a body mass index (BMI) > 30 or a waist-to-hip ratio >0.9 for males and >0.85 for females. It is a complex disease with both genetic and environmental factors affecting its development and progression. However, although BMI is highly heritable (60-90% according to twin studies), only ~6% of the variance is explained by additive genetic variation discovered in large genome-wide association studies. Possible sources of unexplained BMI variance are gene-gene (GxG) and gene-environment (GxE) interactions, but to date, only a few studies have addressed this question, and mostly focused on the UK biobank and data from smaller longitudinal studies This study used data from the Estonian biobank to investigate the potential of using the Brown-Forsythe (BF) test to detect heteroscedasticity in BMI based on the genotype and phenotype groups. Moreover, in this work, the BF test was used to select genotypes and environmental variables that were significantly associated with BMI and WHR variance. The study demonstrated sex and age-dependent differences in heteroscedasticity, with higher levels of heteroscedasticity in females compared to males and decreasing heteroscedasticity with increasing age for both sexes. Next, the gene-environment interactions for the outcome variables BMI and WHR were modeled and studied for two genes (FTO and MC4R) and environmental factors, such as physical activity, smoking, and education level. The study found evidence for significant interaction of FTO with smoking for the age group of 31-50 years for males, along with significant interaction of FTO with physical activity for Females (18-30 age group) and males (31-50 age group) in the case of BMI as the outcome variable. Moreover, the evidence for significant interaction of FTO and physical activity was found for females (age group 18-30) for the WHR as the outcome variable. Furthermore, the significant interaction was observed in the case of MC4R and physical activity for BMI in males (18-30 year old group). Additionally, it was shown that the significant interaction between MC4R and education level for males (31-50 age group) was present for BMI. Finally, the study outlined the ground for future research work in the area of gene-environment interactions and statistical modeling, indicating potential environmental factors that can be studied for possible gene-environment interactions

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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