78 research outputs found

    Chain Reversion for Detecting Associations in Interacting Variables-St. Nicolas House Analysis

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    (1) Background: We present a new statistical approach labeled as "St. Nicolas House Analysis" (SNHA) for detecting and visualizing extensive interactions among variables. (2) Method: We rank absolute bivariate correlation coefficients in descending order according to magnitude and create hierarchic "association chains" defined by sequences where reversing start and end point does not alter the ordering of elements. Association chains are used to characterize dependence structures of interacting variables by a graph. (3) Results: SNHA depicts association chains in highly, but also in weakly correlated data, and is robust towards spurious accidental associations. Overlapping association chains can be visualized as network graphs. Between independent variables significantly fewer associations are detected compared to standard correlation or linear model-based approaches. (4) Conclusion: We propose reversible association chains as a principle to detect dependencies among variables. The proposed method can be conceptualized as a non-parametric statistical method. It is especially suited for secondary data analysis as only aggregate information such as correlations matrices are required. The analysis provides an initial approach for clarifying potential associations that may be subject to subsequent hypothesis testing

    Significant, but not biologically relevant: Nosema ceranae infections and winter losses of honey bee colonies

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    The Western honey bee Apis mellifera, which provides about 90% of commercial pollination, is under threat from diverse abiotic and biotic factors. The ectoparasitic mite Varroa destructor vectoring deformed wing virus (DWV) has been identified as the main biotic contributor to honey bee colony losses worldwide, while the role of the microsporidium Nosema ceranae is still controversially discussed. In an attempt to solve this controversy, we statistically analyzed a unique data set on honey bee colony health collected from a cohort of honey bee colonies over 15 years and comprising more than 3000 data sets on mite infestation levels, Nosema spp. infections, and winter losses. Multivariate statistical analysis confirms that V. destructor is the major cause of colony winter losses. Although N. ceranae infections are also statistically significantly correlated with colony losses, determination of the effect size reveals that N. ceranae infections are of no or low biological relevance

    A global view of gene expression in lithium and zinc treated sea urchin embryos: new components of gene regulatory networks

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    Novel territory-specific markers from the sea urchin Strongylocentrotus purpuratus have been identified using screens for genes that are differentially expressed in lithium-treated embryos, which form an excess of endomesoderm, and in zinc-treated embryos, in which endomesoderm specification is blocked

    Generation, Annotation, Evolutionary Analysis, and Database Integration of 20,000 Unique Sea Urchin EST Clusters

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    Together with the hemichordates, sea urchins represent basal groups of nonchordate invertebrate deuterostomes that occupy a key position in bilaterian evolution. Because sea urchin embryos are also amenable to functional studies, the sea urchin system has emerged as one of the leading models for the analysis of the function of genomic regulatory networks that control development. We have analyzed a total of 107,283 cDNA clones of libraries that span the development of the sea urchin Strongylocentrotus purpuratus. Normalization by oligonucleotide fingerprinting, EST sequencing and sequence clustering resulted in an EST catalog comprised of 20,000 unique genes or gene fragments. Around 7000 of the unique EST consensus sequences were associated with molecular and developmental functions. Phylogenetic comparison of the identified genes to the genome of the urochordate Ciona intestinalis indicate that at least one quarter of the genes thought to be chordate specific were already present at the base of deuterostome evolution. Comparison of the number of gene copies in sea urchins to those in chordates and vertebrates indicates that the sea urchin genome has not undergone extensive gene or complete genome duplications. The established unique gene set represents an essential tool for the annotation and assembly of the forthcoming sea urchin genome sequence. All cDNA clones and filters of all analyzed libraries are available from the resource center of the German genome project at http://www.rzpd.de

    PRI: Re-Analysis of a Public Mass Cytometry Dataset Reveals Patterns of Effective Tumor Treatments

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    Recently, mass cytometry has enabled quantification of up to 50 parameters for millions of cells per sample. It remains a challenge to analyze such high-dimensional data to exploit the richness of the inherent information, even though many valuable new analysis tools have already been developed. We propose a novel algorithm “pattern recognition of immune cells (PRI)” to tackle these high-dimensional protein combinations in the data. PRI is a tool for the analysis and visualization of cytometry data based on a three or more-parametric binning approach, feature engineering of bin properties of multivariate cell data, and a pseudo-multiparametric visualization. Using a publicly available mass cytometry dataset, we proved that reproducible feature engineering and intuitive understanding of the generated bin plots are helpful hallmarks for re-analysis with PRI. In the CD4 + T cell population analyzed, PRI revealed two bin-plot patterns (CD90/CD44/CD86 and CD90/CD44/CD27) and 20 bin plot features for threshold-independent classification of mice concerning ineffective and effective tumor treatment. In addition, PRI mapped cell subsets regarding co-expression of the proliferation marker Ki67 with two major transcription factors and further delineated a specific Th1 cell subset. All these results demonstrate the added insights that can be obtained using the non-cluster-based tool PRI for re-analyses of high-dimensional cytometric data

    Growth, Nutrition and Economy : Proceedings of the 27th Aschauer Soiree, held at Krobielowice, Poland, November 16th 2019

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    Twenty-three scientists met at Krobielowice, Poland to discuss the role of growth, nutrition and economy on body size. Contrasting prevailing concepts, re-analyses of studies in Indonesian and Guatemalan school children with high prevalence of stunting failed to provide evidence for an association between nutritional status and body height. Direct effects of parental education on growth that were not transmitted via nutrition were shown in Indian datasets using network analysis and novel statistical methods (St. Nicolas House Analysis) that translate correlation matrices into network graphs. Data on Polish children suggest significant impact of socioeconomic sensitivity on child growth, with no effect of maternal money satisfaction. Height and maturation tempo affect the position of a child among its peers. Correlations also exist between mood disorders and height. Secular changes in height and weight varied across decades independent of population size. Historic and recent Russian data showed that height of persons whose fathers performed manual work were on average four cm shorter than persons whose fathers were high-degree specialists. Body height, menarcheal age, and body proportions are sensitive to socioeconomic variables. Additional topics included delayed motherhood and its associations with newborn size; geographic and socioeconomic indicators related to low birth weight, prematurity and stillbirth rate; data on anthropometric history of Brazil, 1850-1950; the impact of central nervous system stimulants on the growth of children with attention-deficit/hyperactivity disorder; and pituitary development and growth hormone secretion. Final discussions debated on reverse causality interfering between social position, and adolescent growth and developmental tempo.Facultad de Ciencias Naturales y Muse

    development of liposomal gene transfer vesicles based on optimized cationic lipids

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    Titelblatt, Inhaltsverzeichnis, Abstracts, Literaturverzeichnis 1\. Einleitung 13 2\. Material und Methoden 33 3\. Ergebnisse 55 3.1. Biophysik der Gentransfervesikel 55 3.2. Transfektionsergebnisse 65 4\. Diskussion 93 4\. Literaturverzeichnis 122Die vorliegende Arbeit wurde mit dem Ziel der Herstellung stabiler liposomaler Gentransfervesikel fĂŒr den in vitro und in vivo Gentransfer angefertigt. Diese Vesikel sollen auch fĂŒr eine klinische Anwendung am Menschen geeignet sein. Anforderungen an solche Vesikel sind: hohe Transfereffizienz, StabilitĂ€t und Sicherheit fĂŒr Patient und Anwender. Die Arbeit beinhaltete Untersuchungen zu der Herstellung, den biophysikalischen Eigenschaften, der in vitro Gentransfereffizienz sowie zur StabilitĂ€t und LagerfĂ€higkeit der Gentransfervesikel. Die Ergebnisse zeigen, daß die Gentransfereffizienz von folgenden Faktoren beeinflußt wird: den Bestandteilen der Gentransfervesikel, der Herstellung der Vesikel, dem Ablauf der Transfektion, der Zellart und deren Kulturbedingungen. BezĂŒglich der Vesikelbestandteile wurde festgestellt, daß sich fĂŒr hohe in vitro Transfektionsraten Lipide mit einer Sperminkopfgruppe besonders eignen. Die aus solchen Lipiden hergestellten liposomalen Gentransfervesikel sind jedoch nur kurzzeitig aktiv und fĂŒr eine lĂ€ngere Lagerung nicht geeignet. Dagegen waren aus monokationischen Lipiden (DAC-Chol) hergestellte Liposomen fĂŒr eine Formulierung von lĂ€ngerfristig stabilen Gentransferkomplexen geeignet. Die Effizienz und LagerfĂ€higkeit dieser Vesikel konnte durch den Zusatz von Protaminsulfat noch gesteigert werden. Eine weiter erhöhte StabilitĂ€t und die Möglichkeit eines Einfrierens der vorformulierten Gentransferkomplexe wurde durch den Zusatz von Saccharose ermöglicht. Saccharose senkte jedoch die KurzzeitaktivitĂ€t der Gentransfervesikel auf etwa ein Drittel der AktivitĂ€t von Gentransfervesikeln, welche ohne Zuckerzusatz hergestellt worden waren. Die verringerte KurzzeitaktivitĂ€t konnte durch eine erhöhte Dosierung der Gentransferkomplexe ausgeglichen werden. Die Untersuchungen zeigen, daß die Verwendung von Lipid/Protaminsulfat/DNA- Komplexen, welche in saccharosehaltiger Lösung hergestellt wurden, einen effektiven Gentransfer in vitro gewĂ€hrleistet und ein vielversprechender Ansatz fĂŒr in vivo Untersuchungen sowie mögliche klinische Anwendungen ist.The aim of this work was the preparation of stable liposomal gene transfer vesicles for the in vitro and in vivo gene transfer. It should be possible to use these vesicles for clinical issues on humans. The requirements for such vesicles are: high efficiency, stability and security for the user and the patient. The work contained investigations to the production, the biophysical characteristics, that in vitro gene transfer efficiency as well as for stability and shelf-life of the gene transfer vesicles. Our results show that the gene transfer efficiency is in uenced by the following factors: the constituents of the gene transfer vesicles, the production of the vesicles, the ow of the transfection, the cell type and their culture conditions. Concerning the vesicle constituents it was stated that for high in vitro transfection rates lipids with a spermin headgroup are particularly suitable. Out such lipids manufactured liposomal gene transfer vesicles are however only briefly active and for a longer storage not suitably. On the other hand from monocationic lipids (DAC-Chol) manufactured liposomes were suitable for the preparation of long term stable gene transfer complexes. The efficiency and shelf-life of these vesicles could be still increased by the addition of protaminsulfate. An even more increased stability and the possibility of freezing the preformulated gene transfer complexes was enabled by the addition of saccharose. Saccharose lowered however the short time activity of the gene transfer vesicles to a third of the activity of gene transfer vesicles, which had been manufactured without sugar addition. However the reduced short time activity could become balanced by an increased dosage of the gene transfer complexes. The investigations show that the use of lipid/protaminsulfate/DNA complexes, which were manufactured in a saccharose containing solution ensures an effective gene transfer in vitro and a promising beginning for in vivo investigations as well as possible clinical applications is

    Continuous Spread of Nosema ceranae, an Emerging Pathogen of Honey Bees (Apis mellifera), but No General Replacement of Nosema apis

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    The Western honey bee (Apis mellifera) is widely used as commercial pollinator in worldwide agriculture and, therefore, plays an important role in global food security. Among the parasites and pathogens threatening health and survival of honey bees are two species of microsporidia, Nosema apis and Nosema ceranae. Nosema ceranae is considered an emerging pathogen of the Western honey bee. Reports on the spread of N. ceranae suggested that this presumably highly virulent species is replacing its more benign congener N. apis in the global A. mellifera population. We here present a 12 year longitudinal cohort study on the prevalence of N. apis and N. ceranae in Northeast Germany. Between 2005 and 2016, a cohort of about 230 honey bee colonies originating from 23 apiaries was sampled twice a year (spring and autumn) resulting in a total of 5,600 bee samples which were subjected to microscopic and molecular analysis for determining the presence of infections with N. apis or/and N. ceranae. Throughout the entire study period, both N. apis- and N. ceranae-infections could be diagnosed within the cohort. Logistic regression analysis of the prevalence data demonstrated a significant increase of N. ceranae-infections over the last 12 years, both in autumn (reflecting the development during the summer) and in spring (reflecting the development over winter) samples. Cell culture experiments confirmed that N. ceranae has a higher proliferative potential than N. apis at 27° and 33°C potentially explaining the increase in N. ceranae prevalence during summer. In autumn, characterized by generally low infection prevalence, this increase was accompanied by a significant decrease in N. apis-infection prevalence. In contrast, in spring, the season with a higher prevalence of infection, no significant decrease of N. apis infections despite a significant increase in N. ceranae infections could be observed. Therefore, our data do not support a general advantage of N. ceranae over N. apis and an overall replacement of N. apis by N. ceranae in the studied honey bee population
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