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

(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

Editorial Perceiving stunting - student research and the "Lieschen Mueller effect" in nutrition science

Editorial Perceiving stunting - student research and the "Lieschen Mueller effect" in nutrition scienc

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

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

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

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

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

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

Networks in Auxology: proceedings of the 31st Aschauer Soiree, held at Aschau, Germany, June 17th 2023

Thirty-four scientists met for the annual Auxological conference held at Aschau, Germany, to particularly discuss the interaction between social factors and human growth, and to highlight several topics of general interest for the regulation of human growth. Humans are social mammals. We show and share personal interests and needs, and we are able to strategically adjust size according to social position, with love and hope being prime factors in the regulation of growth. In contrast to Western societies, where body size has been shown to be an important predictor of socioeconomic status, egalitarian societies without formalized hierarchy and material wealth-dependent social status do not appear to similarly integrate body size and social network. Social network structures can be modeled by Monte Carlo simulation. Modeling dominance hierarchies suggests that winner-loser effects play a pivotal role in robust self-organization that transcends the specifics of the individual. Further improvements of the St. Nicolas House analysis using re-sampling/bootstrap techniques yielded encouraging results for exploring dense networks of interacting variables. The D-score scale, the Infancy-Childhood-Puberty (ICP) growth model and the SuperImposition by Translation And Rotation (SITAR) technique were presented, as well as customized pediatric growth references, and approaches towards a Digital Rare Disease Growth Chart Library. First attempts with a mobile phone application were presented to investigate the associations between maternal pre-pregnancy overweight, gestational weight gain, and the child’s future motor development. Clinical contributions included growth patterns of individuals with Silver-Russell syndrome, and treatment burden in children with growth hormone deficiency. Contributions on sports highlighted the fallacy inherent in disregarding the biological maturation status when interpreting physical performance outcomes. The meeting explored the complex influence of nutrition and lifestyle on menarcheal age of Lithuanian girls and emphasized regional trends in height of Austrian recruits. Examples of the psychosocial stress caused by the forced migration of modern Kyrgyz children and Polish children after World War II were presented, as well as the effects of nutritional stress during and after World War I. The session concluded with a discussion of recent trends in gun violence affecting children and adolescents in the United States, and aspects of life history theory using the example of ”Borderline Personality Disorder.” The features of this disorder are consistent with the notion that it reflects a ”fast” life history strategy, with higher levels of allostatic load, higher levels of aggression, and greater exposure to both childhood adversity and chronic stress. The results were discussed in light of evolutionary guided research. In all contributions presented here, written informed consent was obtained from all participants in accordance with institutional Human investigation committee guidelines in accordance with the Declaration of Helsinki amended October 2013, after information about the procedures used

development of liposomal gene transfer vesicles based on optimized cationic lipids

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 für den in vitro und in vivo Gentransfer angefertigt. Diese Vesikel sollen auch für eine klinische Anwendung am Menschen geeignet sein. Anforderungen an solche Vesikel sind: hohe Transfereffizienz, Stabilität und Sicherheit für Patient und Anwender. Die Arbeit beinhaltete Untersuchungen zu der Herstellung, den biophysikalischen Eigenschaften, der in vitro Gentransfereffizienz sowie zur Stabilität und Lagerfähigkeit 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. Bezüglich der Vesikelbestandteile wurde festgestellt, daß sich für hohe in vitro Transfektionsraten Lipide mit einer Sperminkopfgruppe besonders eignen. Die aus solchen Lipiden hergestellten liposomalen Gentransfervesikel sind jedoch nur kurzzeitig aktiv und für eine längere Lagerung nicht geeignet. Dagegen waren aus monokationischen Lipiden (DAC-Chol) hergestellte Liposomen für eine Formulierung von längerfristig stabilen Gentransferkomplexen geeignet. Die Effizienz und Lagerfähigkeit dieser Vesikel konnte durch den Zusatz von Protaminsulfat noch gesteigert werden. Eine weiter erhöhte Stabilität und die Möglichkeit eines Einfrierens der vorformulierten Gentransferkomplexe wurde durch den Zusatz von Saccharose ermöglicht. Saccharose senkte jedoch die Kurzzeitaktivität der Gentransfervesikel auf etwa ein Drittel der Aktivität von Gentransfervesikeln, welche ohne Zuckerzusatz hergestellt worden waren. Die verringerte Kurzzeitaktivität 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 gewährleistet und ein vielversprechender Ansatz für 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