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Institute
Biomarkers are used to predict phenotypical properties before these features become apparent and, therefore, are valuable tools for both fundamental and applied research. Diagnostic biomarkers have been discovered in medicine many decades ago and are now commonly applied. While this is routine in the field of medicine, it is of surprise that in agriculture this approach has never been investigated. Up to now, the prediction of phenotypes in plants was based on growing plants and assaying the organs of interest in a time intensive process. For the first time, we demonstrate in this study the application of metabolomics to predict agronomic important phenotypes of a crop plant that was grown in different environments. Our procedure consists of established techniques to screen untargeted for a large amount of metabolites in parallel, in combination with machine learning methods. By using this combination of metabolomics and biomathematical tools metabolites were identified that can be used as biomarkers to improve the prediction of traits. The predictive metabolites can be selected and used subsequently to develop fast, targeted and low-cost diagnostic biomarker assays that can be implemented in breeding programs or quality assessment analysis. The identified metabolic biomarkers allow for the prediction of crop product quality. Furthermore, marker-assisted selection can benefit from the discovery of metabolic biomarkers when other molecular markers come to its limitation. The described marker selection method was developed for potato tubers, but is generally applicable to any crop and trait as it functions independently of genomic information.
Many deep evolutionary divergences still remain unresolved, such as those among major taxa of the Lophotrochozoa. As alternative phylogenetic markers, the intron-exon structure of eukaryotic genomes and the patterns of absence and presence of spliceosomal introns appear to be promising. However, given the potential homoplasy of intron presence, the phylogenetic analysis of this data using standard evolutionary approaches has remained a challenge. Here, we used Mutual Information (MI) to estimate the phylogeny of Protostomia using gene structure data, and we compared these results with those obtained with Dollo Parsimony. Using full genome sequences from nine Metazoa, we identified 447 groups of orthologous sequences with 21,732 introns in 4,870 unique intron positions. We determined the shared absence and presence of introns in the corresponding sequence alignments and have made this data available in "IntronBase", a web-accessible and downloadable SQLite database. Our results obtained using Dollo Parsimony are obviously misled through systematic errors that arise from multiple intron loss events, but extensive filtering of data improved the quality of the estimated phylogenies. Mutual Information, in contrast, performs better with larger datasets, but at the same time it requires a complete data set, which is difficult to obtain for orthologs from a large number of taxa. Nevertheless, Mutual Information-based distances proved to be useful in analyzing this kind of data, also because the estimation of MI-based distances is independent of evolutionary models and therefore no pre-definitions of ancestral and derived character states are necessary.
Polyadenylation of pre-mRNAs is critical for efficient nuclear export, stability, and translation of the mature mRNAs, and thus for gene expression. The bulk of pre-mRNAs are processed by canonical nuclear poly(A) polymerase (PAPS). Both vertebrate and higher-plant genomes encode more than one isoform of this enzyme, and these are coexpressed in different tissues. However, in neither case is it known whether the isoforms fulfill different functions or polyadenylate distinct subsets of pre-mRNAs. Here we show that the three canonical nuclear PAPS isoforms in Arabidopsis are functionally specialized owing to their evolutionarily divergent C-terminal domains. A strong loss-of-function mutation in PAPS1 causes a male gametophytic defect, whereas a weak allele leads to reduced leaf growth that results in part from a constitutive pathogen response. By contrast, plants lacking both PAPS2 and PAPS4 function are viable with wild-type leaf growth. Polyadenylation of SMALL AUXIN UP RNA (SAUR) mRNAs depends specifically on PAPS1 function. The resulting reduction in SAUR activity in paps1 mutants contributes to their reduced leaf growth, providing a causal link between polyadenylation of specific pre-mRNAs by a particular PAPS isoform and plant growth. This suggests the existence of an additional layer of regulation in plant and possibly vertebrate gene expression, whereby the relative activities of canonical nuclear PAPS isoforms control de novo synthesized poly(A) tail length and hence expression of specific subsets of mRNAs.
Background: Human populations differ in height. Recent evidence suggests that social networks play an important role in the regulation of adolescent growth and adult height. We further investigated the effect of physical connectedness on height.
Material and methods: We considered Switzerland as a geographic network with 169 nodes (district capitals) and 335 edges (connecting roads) and studied effects of connectedness on height in Swiss conscript from 1884-1891, 1908-1910, and 2004-2009. We also created exponential-family random graph models to separate possible unspecific effects of geographic vicinity.
Results: In 1884-1891, in 1908-1910, and in 2004-2009, 1st, 2nd and 3rd order neighboring districts significantly correlate in height (p<0.01). The correlations depend on the order of connectedness, they decline with increasing distance. Short stature districts tend to have short, tall stature districts tend to have tall neighbors. Random network analyses suggest direct road effects on height. Whereas in 1884-1891, direct road effects were only visible between 1st order neighbors, direct road effects extended to 2nd and 3rd in 1908-1910, and in 2004-2009, also to 4th order neighbors, and might reflect historic improvements in transportation. The spatial correlations did not significantly change when height was controlled for goiter (1884-1889) and for median per capita income (2006), suggesting direct road effects also in goiter-allowed-for height and income-allowed-for height.
Conclusion: Height in a district depends on height of physically connected neighboring districts. The association decreases with increasing distance in the net. The present data suggest that people can be short because their neighbors are short; or tall because their neighbors are tall (community effect on growth). Psycho-biological effects seem to control growth and development within communities that go far beyond our current understanding of growth regulation.
Transitory starch metabolism is a nonlinear and highly regulated process. It originated very early in the evolution of chloroplast-containing cells and is largely based on a mosaic of genes derived from either the eukaryotic host cell or the prokaryotic endosymbiont. Initially located in the cytoplasm, starch metabolism was rewired into plastids in Chloroplastida. Relocation was accompanied by gene duplications that occurred in most starch-related gene families and resulted in subfunctionalization of the respective gene products. Starch-related isozymes were then evolutionary conserved by constraints such as internal starch structure, posttranslational protein import into plastids and interactions with other starch-related proteins. 25 starch-related genes in 26 accessions of Arabidopsis thaliana were sequenced to assess intraspecific diversity, phylogenetic relationships, and modes of selection. Furthermore, sequences derived from additional 80 accessions that are publicly available were analyzed. Diversity varies significantly among the starch-related genes. Starch synthases and phosphorylases exhibit highest nucleotide diversities, while pyrophosphatases and debranching enzymes are most conserved. The gene trees are most compatible with a scenario of extensive recombination, perhaps in a Pleistocene refugium. Most genes are under purifying selection, but disruptive selection was inferred for a few genes/substitutiones. To study transcript levels, leaves were harvested throughout the light period. By quantifying the transcript levels and by analyzing the sequence of the respective accessions, we were able to estimate whether transcript levels are mainly determined by genetic (i.e., accession dependent) or physiological (i.e., time dependent) parameters. We also identified polymorphic sites that putatively affect pattern or the level of transcripts.
Recent studies have provided evidence for both intracellular and extracellular roles of the potent hepatotoxin microcystin (MC) in the bloom-forming cyanobacterium Microcystis. Here, we surveyed transcriptomes of the wild-type strain M. aeruginosa PCC 7806 and the microcystin-deficient Delta mcyB mutant under low light conditions with and without the addition of external MC of the LR variant (MC-LR). Transcriptomic data acquired by microarray and quantitative PCR revealed substantial differences in the relative expression of genes of the central intermediary metabolism, photosynthesis, and energy metabolism. In particular, the data provide evidence for a lower photosystem I (PSI)-to-photosystem II (PSII) ratio and a more pronounced carbon limitation in the microcystin-deficient mutant. Interestingly, only 6% of the transcriptional differences could be complemented by external microcystin-LR addition. This MC signaling effect was seen exclusively for genes of the secondary metabolism category. The orphan polyketide synthase gene cluster IPF38-51 was specifically downregulated in response to external MC-LR under low light. Our data suggest a hierarchical and light-dependent cross talk of secondary metabolites and support both an intracellular and an extracellular role of MC in Microcystis.
Height and skeletal morphology strongly relate to life style. Parallel to the decrease in physical activity and locomotion, modern people are slimmer in skeletal proportions. In German children and adolescents, elbow breadth and particularly relative pelvic breadth (50th centile of bicristal distance divided by body height) have significantly decreased in recent years. Even more evident than the changes in pelvic morphology are the rapid changes in body height in most modern countries since the end-19th and particularly since the mid-20th century. Modern Japanese mature earlier; the age at take-off (ATO, the age at which the adolescent growth spurt starts) decreases, and they are taller at all ages. Preece-Baines modelling of six national samples of Japanese children and adolescents, surveyed between 1955 and 2000, shows that this gain in height is largely an adolescent trend, whereas height at take-off (HTO) increased by less than 3 cm since 1955; adolescent growth (height gain between ATO and adult age) increased by 6 cm. The effect of globalization on the modern post-war Japanese society ("community effect in height") on adolescent growth is discussed.
Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hifla) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes.
BACKGROUND/OBJECTIVES: Recent evidence suggests clustering of human body height. We want to assess the consequences of connectedness in a spatial network on height clustering in an artificial society. SUBJECTS/METHODS: We used an agent-based computer modelling technique (Monte Carlo simulation) and compared simulated height in a spatial network with characteristics of the observed geographic height distribution of three historic cohorts of Swiss military conscripts (conscripted in 1884-1891; 1908-1910; and 2004-2009). RESULTS: Conscript height shows several characteristic features: (1) height distributions are overdispersed. (2) Conscripts from districts with direct inter-district road connections tend to be similar in height. (3) Clusters of tall and clusters of short stature districts vary over time. Autocorrelations in height between late 19th and early 21st century districts are low. (4) Mean district height depends on the number of connecting roads and on the number of conscripts per district. Using Monte Carlo simulation, we were able to generate these natural characteristics in an artificial society. Already 5% height information from directly connected districts is sufficient to simulate the characteristics of natural height distribution. Very similar observations in regular rectangular networks indicate that the characteristics of Swiss conscript height distributions do not so much result from the particular Swiss geography but rather appear to be general features of spatial networks. CONCLUSIONS: Spatial connectedness can affect height clustering in an artificial society, similar to that seen in natural cohorts of military conscripts, and strengthen the concept of connectedness being involved in the regulation of human height.
Twenty-four scientists met at Aschauhof, Altenhof, Germany, to discuss the associations between child growth and development, and nutrition, health, environment and psychology. Meta-analyses of body height, height variability and household inequality, in historic and modern growth studies published since 1794, highlighting the enormously flexible patterns of child and adolescent height and weight increments throughout history which do not only depend on genetics, prenatal development, nutrition, health, and economic circumstances, but reflect social interactions. A Quality of Life in Short Stature Youth Questionnaire was presented to cross-culturally assess health-related quality of life in children. Changes of child body proportions in recent history, the relation between height and longevity in historic Dutch samples and also measures of body height in skeletal remains belonged to the topics of this meeting. Bayesian approaches and Monte Carlo simulations offer new statistical tools for the study of human growth.
Modeling a secular trend by Monte Carlo simulation of height biased migration in a spatial network
(2017)
Background: In a recent Monte Carlo simulation, the clustering of body height of Swiss military conscripts within a spatial network with characteristic features of the natural Swiss geography was investigated. In this study I examined the effect of migration of tall individuals into network hubs on the dynamics of body height within the whole spatial network. The aim of this study was to simulate height trends. Material and methods: Three networks were used for modeling, a regular rectangular fishing net like network, a real world example based on the geographic map of Switzerland, and a random network. All networks contained between 144 and 148 districts and between 265-307 road connections. Around 100,000 agents were initially released with average height of 170 cm, and height standard deviation of 6.5 cm. The simulation was started with the a priori assumption that height variation within a district is limited and also depends on height of neighboring districts (community effect on height). In addition to a neighborhood influence factor, which simulates a community effect, body height dependent migration of conscripts between adjacent districts in each Monte Carlo simulation was used to re-calculate next generation body heights. In order to determine the direction of migration for taller individuals, various centrality measures for the evaluation of district importance within the spatial network were applied. Taller individuals were favored to migrate more into network hubs, backward migration using the same number of individuals was random, not biased towards body height. Network hubs were defined by the importance of a district within the spatial network. The importance of a district was evaluated by various centrality measures. In the null model there were no road connections, height information could not be delivered between the districts. Results: Due to the favored migration of tall individuals into network hubs, average body height of the hubs, and later, of the whole network increased by up to 0.1 cm per iteration depending on the network model. The general increase in height within the network depended on connectedness and on the amount of height information that was exchanged between neighboring districts. If higher amounts of neighborhood height information were exchanged, the general increase in height within the network was large (strong secular trend). The trend in the homogeneous fishnet like network was lowest, the trend in the random network was highest. Yet, some network properties, such as the heteroscedasticity and autocorrelations of the migration simulation models differed greatly from the natural features observed in Swiss military conscript networks. Autocorrelations of district heights for instance, were much higher in the migration models. Conclusion: This study confirmed that secular height trends can be modeled by preferred migration of tall individuals into network hubs. However, basic network properties of the migration simulation models differed greatly from the natural features observed in Swiss military conscripts. Similar network-based data from other countries should be explored to better investigate height trends with Monte Carlo migration approach.
Background: We investigated height of Norwegian conscripts in view of the hypothesis of a "community effect on height" using autocorrelation analysis of district heights within a time-span of 20 years at the end of the 19th century and correlations between neighboring districts at this time. Material and methods: After digitalizing available body height data of Norwegian draftees in 1877-1878, 1880 (averaged as 1878), and 1895-1897 (averaged as 1896) we calculated the magnitude of autocorrelation of body height within the same municipality at different time points. Furthermore, we generated three different neighborhood networks, (1) based on Euclidean distances, (2) a minimum spanning tree build on those distances, (3) a network founded on real world road connections. The networks were used to determine the correlation between body height of neighboring districts depending on the number of edges required to connect two municipalities. Results: The autocorrelation value for body heights was around r = 0.5 (for all p < 0.001) in the years 1878 and 1896. The correlation between neighboring districts varied in the Euclidean distance based network between 0.47 and 0.27 approximately for both years in a sorted order, descending from nearest (0-50 km) to farthest (150-200 km, for all p < 0.001). First order neighbors in the minimum spanning tree network correlation was 0.36 in 1878 and 0.42 in 1896 (for all p < 0.001). The values of neighbor correlation in the road connection based network ranged in 1878 from 0.42 (first order neighbors) to 0.17 (forth order neighbors, for all p < 0.01) and in 1896 from 0.46 (first order neighbors) to 0.12 (forth order neighbors, for all p < 0.05). Conclusion: This initial study of Norwegian conscript height data from the 19th century showed significant medium sized effects for the within district autocorrelation between 1878 and 1896 as well as medium neighborhood correlation, slightly lower in comparison to a recent study regarding Swiss conscripts. Digitalizing more data from other years in this and later time spans as well as using older road and ship connections instead of the actual road data might stabilize and improve those findings.
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 degrees 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.
The aim of the study was to investigate the correlation of heights of conscripts living in neighboring districts in Poland. The study used 10% of a nationally representative sample of 26,178 males 18.5-19.5 years old examined during the National survey of Polish conscripts conducted in 2001. The sample represented all regions and social strata of the country and included 354 different districts within 16 voivodships (provinces). Analyses were performed with the R statistical software. A small but significant correlation (0.24, p < 0.0001) was observed for height between 1st order neighboring districts. Correlations decreased with increased distances between neighboring districts, but remained significant for 7th node neighbors (0.18, p < 0.0001). Regarding voivodships (provinces), average height showed a geographical trend from the northwest (relatively tall) to the southeast (relatively short), and the correlation was stronger for first order neighboring provinces (0.796, p < 0.001). This study revealed clusters of tall people and short people, providing a support for hypothesis of the community effect in height. Small correlations between 1st order neighbors than in another country (Switzerland) may be associated with differences in geography, since in Poland there are no natural barriers (e.g., mountains) and road infrastructure is well-developed.
Eighteen scientists met at Jurata, Poland, to discuss various aspects of the transition from adolescence to adulthood. This transition is a delicate period facing complex interactions between the adolescents and the social group they belong to. Social identity, group identification and identity signalling, but also stress affecting basal salivary cortisol rhythms, hypertension, inappropriate nutrition causing latent and manifest obesity, moreover, in developing and under-developed countries, parasitosis causing anaemia thereby impairing growth and development, are issues to be dealt with during this period of the human development. In addition, some new aspects of the association between weight, height and head circumference in the newborns were discussed, as well as intrauterine head growth and head circumference as health risk indicators.
Background
The unisexual Amazon molly (Poecilia formosa) originated from a hybridization between two sexual species, the sailfin molly (Poecilia latipinna) and the Atlantic molly (Poecilia mexicana). The Amazon molly reproduces clonally via sperm-dependent parthenogenesis (gynogenesis), in which the sperm of closely related species triggers embryogenesis of the apomictic oocytes, but typically does not contribute genetic material to the next generation. We compare for the first time the gonadal transcriptome of the Amazon molly to those of both ancestral species, P. mexicana and P. latipinna.
Results
We sequenced the gonadal transcriptomes of the P. formosa and its parental species P. mexicana and P. latipinna using Illumina RNA-sequencing techniques (paired-end, 100 bp). De novo assembly of about 50 million raw read pairs for each species was performed using Trinity, yielding 106,922 transcripts for P. formosa, 115,175 for P. latipinna, and 133,025 for P. mexicana after eliminating contaminations. On the basis of sequence similarity comparisons to other teleost species and the UniProt databases, functional annotation, and differential expression analysis, we demonstrate the similarity of the transcriptomes among the three species. More than 40% of the transcripts for each species were functionally annotated and about 70% were assigned to orthologous genes of a closely related species. Differential expression analysis between the sexual and unisexual species uncovered 2035 up-regulated and 564 down-regulated genes in P. formosa. This was exemplary validated for six genes by qRT-PCR.
Conclusions
We identified more than 130 genes related to meiosis and reproduction within the apomictically reproducing P. formosa. Overall expression of these genes seems to be down-regulated in the P. formosa transcriptome compared to both ancestral species (i.e., 106 genes down-regulated, 29 up-regulated). A further 35 meiosis and reproduction related genes were not found in the P. formosa transcriptome, but were only expressed in the sexual species. Our data support the hypothesis of general down-regulation of meiosis-related genes in the apomictic Amazon molly. Furthermore, the obtained dataset and identified gene catalog will serve as a resource for future research on the molecular mechanisms behind the reproductive mode of this unisexual species.
Introduction: Body height is influenced by biological factors such as genetics, nutrition and health, but also by the social network, and environmental and economical factors. During centuries, the Japanese society has developed on islands. This setting provides ideal natural conditions for studying the influence of social networks on human height. Material and methods: We investigated body height of male Japanese students aged 17.5 years obtained in 47 prefectures, from the Japanese school health survey of the years 1955, 1975, 1995, and 2015. Results: Japanese students increased in height from 163.23 cm in 1955 to 170.84 cm in 1995, with no further increase thereafter (170.63 cm in 2015). Students living in neighboring prefectures were similar in height. The correlation of height between neighboring prefectures ranged between r = 0.79 and r = 0.49 among first degree neighbors, between r = 0.49 and r = 0.21 among second degree neighbors and dropped to insignificance among third degree neighbors indicating psychosocial effects of the community on body height. Tall stature and short stature prefectures did not remain tall or short throughout history. Autocorrelations of height within the same prefectures decreased from the 20 years periods of 1955-1975, 1975-1995 and 1995-2015 (r = 0.52, r = 0.61, r = 0.63, respectively) to the 40 years periods of 1955-1995 and 1975-2015 (r = 0.49, r = 0.52), down to the 60 years period of 1955-2015 (r = 0.27), indicating significant volatility of height. Conclusion: Body height of 17.5 years old Japanese students increased since 1955. Body height depended on height of the neighboring prefecture, but was volatile with decreasing autocorrelation during a period of 60 years.
Background: The association between stature and social dominance is known. Dominance within social groups and current politics are related issues. We therefore aimed to compare estimates of the opinion of a population about their current political issues, with physical growth. Material and methods: We used data on the 2012 and the 2014 elections for the Japanese House of Representatives and the percent proportion of votes of the 47 prefectures of Japan, and regional data on body height of 17.5 year old men and women. Information on capita income, possession of mobile phones, urban/rural population ratio, and age distribution were added to capture socioeconomic factors. Four political parties were present in most of the 47 prefectures: the Liberal Democratic Party (LDP), the Democratic Party of Japan (DPJ), the New Komeito Party (Kom) that is known for their social network community, and the Japanese Communist Party (JCP). Results: A dense network of associations exists between height, age distribution, per capita income, number of smartphones, and voting results. Male and female body height was inversely related with the proportion of votes for New Komeito Party. Average stature decreases by one mm per percent votes for this political party. Medium strong positive associations were found for male body height and voting results of the DPJ and for female body height with the JCP election results. Conclusion: In modern Japan, popular preferences for conservative political structures coincide with shorter stature.
Twenty-two scientists met at Krobielowice, Poland, to discuss the impact of the social environment, spatial proximity, migration, poverty, but also psychological factors such as body perception and satisfaction, and social stressors such as elite sports, and teenage pregnancies, on child and adolescent growth. The data analysis included linear mixed effects models with different random effects, Monte Carlo analyses, and network simulations. The work stressed the importance of the peer group, but also included historic material, some considerations about body proportions, and growth in chronic liver, and congenital heart disease.
Background: The polymorphism in FTO gene (rs9939609) is known to be associated with higher BMI and body fat mass content. However, environmental factors can modify this effect. The purpose of the present study was to investigate an association between sport specialization and the rs9939609 SNP in FTO gene in the cohort of professional and amateur young athletes. Methods: A total number of 250 young individuals 8-18 years old living in Moscow or Moscow district participated in the study. Individuals were divided into 3 groups in accordance with their physical activity level: control group (n = 49), amateurs (n = 67) and professionals (n = 137). Amateur and professional athletes were subdivided into groups according to their sport specialization. Quantile regression was used as a regression model, where the dependent (outcome) variable was BMI, along with percentage of body fat mass, and the independent variables (predictors) were the rs9939609 SNP in FTO gene, physical activity (active versus inactive), sport specialization (aerobic, intermittent sports and martial arts), nationality, level of sport experience (in years), gender and percentage of free fat mass content. Results: The regression analysis revealed that physical activity and sport specialization had greater impact compared to FTO allele in the group of physically active individuals. Physical activity, in particular aerobic, had negative associations with body fat mass and BMI. The rs9939609 SNP in FTO gene is associated with physical activity and aerobic activity. The magnitude of association becomes significantly larger at the upper quantiles of the body fat mass distribution. Conclusion: Physical activity and sport specialization explained more variance in body composition of physically active young individuals compared to the FTO polymorphism. Effect of interaction of physical activity, in particular aerobic, with the FTO polymorphism on body composition of young athletes was found.
Background: Recent research reported height biased migration of taller individuals and a Monte Carlo simulation showed that such preferential migration of taller individuals into network hubs can induce a secular trend of height. In the simulation model taller agents in the hubs raise the overall height of all individuals in the network by a community effect. However, it could be seen that the actual network structure influences the strength of this effect. In this paper the background and the influence of the network structure on the strength of the secular trend by migration is investigated. Material and methods: Three principal network types are analyzed: networks derived from street connections in Switzerland, more regular fishing net like networks and randomly generated ones. Our networks have between 10 and 152 nodes and between 20 and 307 edges connecting the nodes. Depending on the network size between 5.000 and 90.000 agents with an average height of 170 cm (SD 6.5 cm) are initially released into the network. In each iteration new agents are regenerated based on the actual average body height of the previous iteration and, to a certain proportion, corrected by body heights in the neighboring nodes. After generating new agents, a certain number of them migrated into neighbor nodes, the model let preferentially taller agents migrate into network hubs. Migration is balanced by back migration of the same number of agents from nodes with high centrality measures to less connected nodes. The latter is random as well, but not biased by the agents height. Furthermore the distribution of agents per node and their correlation to the centrality of the nodes is varied in a systematic manner. After 100 iterations, the secular trend, i.e. the gain in body height for the different networks, is investigated in relation to the network properties. Results: We observe an increase of average agent body height after 100 iterations if height biased migration is enabled. The increase rate depends on the height of the neighboring factor, the population distribution, the relationship between population in the nodes and their centrality as well as on the network topology. Networks with uniform like distributions of the agents in the nodes, uncorrelated associations between node centrality and agent number per node, as well as very heterogeneous networks with very different node centralities lead to biggest gains in average body height. Conclusion: Our simulations show, that height biased migration into network hubs can possibly contribute to the secular trend of height increase in the human population. The strength of this "tall by migration" event depends on the actual properties of the underlying network. There is a possible significance of this mechanism for social networks, when hubs are represented by individuals and edges as their personal relationships. However, the required high number of iterations to achieve significant effects in more natural network structures in our models requires further studies to test the relevance and real effect sizes in real world scenarios.
Meeting Reports
(2019)
Thirty-one scientists met at Aschauhof, Germany to discuss the role of beliefs and self-perception on body size. In view of apparent growth stimulatory effects of dominance within the social group that is observed in social mammals, they discussed various aspects of competitive growth strategies and growth adjustments. Presentations included new data from Indonesia, a cohort-based prospective study from Merida, Yucatan, and evidence from recent meta-analyses and patterns of growth in the socially deprived. The effects of stress experienced during pregnancy and adverse childhood events were discussed, as well as obesity in school children, with emphasis on problems when using z-scores in extremely obese children. Aspects were presented on body image in African-American women, and body perception and the disappointments of menopause in view of feelings of attractiveness in different populations. Secular trends in height were presented, including short views on so called 'racial types' vs bio-plasticity, and historic data on early-life nutritional status and later-life socioeconomic outcomes during the Dutch potato famine. New tools for describing body proportions in patients with variable degrees of phocomelia were presented along with electronic growth charts. Bio-statisticians discussed the influence of randomness, community and network structures, and presented novel tools and methods for analyzing social network data.
Background: We investigated average body height in the central provinces of the Russian empire in the middle of XIX century in view of the concept of "community effects on height". We analyzed body height correlations between neighboring districts at this time. We added information about secular changes in body height during the 19th century of this territory. Material and methods: The study used height data of conscripts, which were born in the years 1853-1863, and age 21 at the time of measurement. The territory of seven provinces was considered as a network with 105 nodes, each node representing one district with information on average male body height. In order to define neighboring districts three different approaches were used: based on the "common borders" method, based on Euclidean distances (from 60 to 120 km), based on real road connections. Results: Small but significant correlation coefficients were observed between 1st order districts in the network based on Euclidean distance of 100 km (r = 0.256, p-value = 0.006) and based on "the common borders" approach (r = 0.25, p-value = 0.02). Wherein no significant correlations were observed in the network based on road connections and between second order neighbors regardless of the method. Conclusion: Height correlation coefficients between 1st order neighboring districts observed in the Russian districts were very similar to values observed in the Polish study (r = 0.24). The considered Russian territory and the territory of Poland have a lot in common. They consist of both plains without mountains. In contradistinction to Poland the transport infrastructure in Russia was weakly developed in the middle of XIX century. In addition, the mobility of people was limited by serfdom. In this context the absent of significant correlation of second order neighbors can be explained by low population density and lack of migration and communication between the districts.
Background: Multiple linear correlations between parameters can be shown in correlation matrices. Correlations can be ranked, but can also be visualized in network graphs. Yet, translating a correlation matrix into a network graph is not trivial. In view of a popular child game, we propose to name this method St. Nicolas House Analysis. Material and methods: We present a new method (St. Nicolas House Analysis) that helps translating correlation matrices into network graphs. The performance of this and other network reconstruction methods was tested in randomly created virtual scale-free networks, networks consisting of bands or hubs, using balanced classification rate and the F1-Score for correctly predicting existing and non-existing edges. Thereafter we analyzed anthropometric data and information on parental education, obtained from an anthropometric survey in 908 Indonesian boys and 808 Indonesian girls. Seven parameters were analyzed: child height standard deviation score (hSDS), child BMI standard deviation scores (BMI_SDS), mid-upper-arm circumference (MUAC), mean thickness of subscapular and triceps skinfold (mean SF), and elbow breadth; as well as maternal and paternal education (years of schooling). The parameters were considered as the nodes of the network; the edges represent the correlations between the nodes. Results: Performance measures, balanced classification rate and the F1-score, showed that St. Nicolas’ House Analysis was superior to methods using sophisticated correlation value thresholds and methods based on partial correlations for analyzing bands and hubs. We applied this method also in an Indonesia data set. Ranking correlations showed the direct association between parental education and child growth. Conclusion: St. Nicolas House Analysis confirmed that growth of Indonesian school children directly depends on maternal education, with no evidence that this effect is mediated by the state of nutrition.
In nature, dominance is often shown by body size; even in humans many studies report that social status is associated with body height. In today's society, educational status is an important factor for social classification. Since growing children do not have their own educational or social status, they are often affected by the status of their parents. Therefore, the question appears, whether parental educational status measurably affects the growth of a child. If so, is this explainable by the nutritional factors? To test this hypothesis, seven different Indian data sets where reexamined using the St. Nicolas House Analysis. The results show a direct association between parental education and body height (hSDS) of the child, but there was no influence of parental education on the nutritional status. We conclude that education has a direct effect on height that is not mediated via nutrition.
Aim: We aimed to examine the distribution and secular changes of conscript body height in the geographic network of Norway since 1878 and to study its association with the degree of urbanization, and population density. Material and methods: Data on body height of Norwegian military conscripts were provided by the Statistics Norway Department (SSB). The sample comprised eight cohorts with the following measurement years: 1st 1877, 1878 and 1880, 2nd 18951897, 3rd 1915-1917, 4th 1935-1937, 5th 1955-1957, 6th 1975-1977, 7th 1995-1997, and 8th 2009-2011. For determining neighborhood correlations, a network was created consisting of neighboring counties, sharing a common border. Results: Average body height of Norwegian men increased by 10.9 cm between 1878 and 2010, but this trend was heterogeneous. Some counties increased by more than 1 cm per decade (Finmark) others by only 7 mm per decade (Sor-Trondelag). Urban counties and counties with higher population density showed stronger height trends than rural counties. The largest spread in body height between the various counties was observed in 1936 when for the first time people living in the more urban counties got taller than rural people. The height advantage of urban counties however, disappeared after 1996. At this time, also the secular trend in height had come to a halt. The secular trend in height had become obvious after the dissolution of the union between Norway and Sweden in 1905 and World War I, and was strongest between 1936 and 1956. During this period maximum between-county heterogeneity in height existed with body height differences of more than 6 cm between the tallest and the shortest county. The end of this period was characterized by social democratic reforms that flattened the income distribution, eliminated poverty, and ensured social services after World War II. Conclusion: The temporal coincidence between the trends in height, the degree of urbanization and the onset of the political transition of Norway from a Swedish province into an independent democratic wealthy modern European state after World War I and particularly after World War II, and the abatement of this trend after this period of transition had stabilized, suggest social and political components interfering with the regulation of physical growth in humans.
Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception
(2020)
Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)". PRI uncovered a subpopulation of IL-21(+) IFN-gamma(high) PD-1(low) CD40L(high) CXCR5(-) Bcl-6(-) T cells specifically expanded in diseased mice. In addition, these cells express high levels of TNF-alpha and IL-2, and provide B cell help for IgG production in an IL-21 and CD40L dependent manner. This super-functional T cell subset might be a superior driver of autoimmune processes due to a polyfunctional and high cytokine expression combined with Tfh-like properties.
No correlation between short term weight gain and lower leg length gain in healthy German children
(2020)
Background:
Length-for-age is considered the indicator of choice in monitoring the long-term impact of chronic nutritional deficiency. Aim: We hypothesized that short term increments of body weight cross-correlate with increments of the lower leg length.
Sample and methods:
We re-analyzed the association between weekly measurements of weight and of lower leg length in 34 healthy German children, aged 2.9-15.9 years. The data are a subset of measurements originally published in 1988 (Hermanussen et al. 1988a). As the growth measurements were often not equally spaced in time due to interposed holidays and illness, the incremental rates for weight and lower leg length were smoothed using spline functions. Autocorrelation and cross-correlation functions were calculated for weight increments and lower leg length increments.
Results:
Height and weight increments are pulsatile. Autocorrelations indicated that mini growth spurts occur at irregular intervals. Lack of cross-correlations between weight and lower leg length indicated that mini spurts in weight gain do not coincide with mini spurts in length gain even when considering lag times of up to 10 weeks. Short term changes of weight gain and lower leg length gain in healthy children show no temporal association.
Life history theory predicts that experiencing stress during the early period of life will result in accelerated growth and earlier maturation. Indeed, animal and some human studies documented a faster pace of growth in the offspring of stressed mothers. Recent advances in epigenetics suggest that the effects of early developmental stress might be passed across the generations. However, evidence for such intergenerational transmission is scarce, at least in humans. Here we report the results of the study investigating the association between childhood trauma in mothers and physical growth in their children during the first months of life. Anthropometric and psychological data were collected from 99 mothers and their exclusively breastfed children at the age of 5 months. The mothers completed the Early Life Stress Questionnaire to assess childhood trauma. The questionnaire includes questions about the most traumatic events that they had experienced before the age of 12 years. Infant growth was evaluated based on the anthropometric measurements of weight, length, and head circumference. Also, to control for the size of maternal investment, the composition of breast milk samples taken at the time of infant anthropometric measurements was investigated. The children of mothers with higher early life stress tended to have higher weight and bigger head circumference. The association between infant anthropometrics and early maternal stress was not affected by breast milk composition, suggesting that the effect of maternal stress on infant growth was independent of the size of maternal investment. Our results demonstrate that early maternal trauma may affect the pace of growth in the offspring and, in consequence, lead to a faster life history strategy. This effect might be explained via changes in offspring epigenetics.
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.
Twenty-one scientists met for this year’s virtual conference on Auxology held at the University Potsdam, Germany, to discuss child and adolescent growth during times of fear and emotional stress. Growth within the broad range of normal for age and sex is considered a sign of good general health whereas fear and emotional stress can lead to growth faltering. Stunting is a sign of social disadvantage and poor parental education. Adverse childhood experiences affect child development, particularly in families with low parental education and low socioeconomic status. Negative effects were also shown in Indian children exposed prenatally and in early postnatal life to the cyclone Aila in 2009. Distrust, fears and fake news regarding the current Corona pandemic received particular attention though the effects generally appeared weak. Mean birth weight was higher; rates of low, very and extremely low birth weight were lower. Other topics discussed by the participants, were the influences of economic crises on birth weight, the measurement of self-confidence and its impact on growth, the associations between obesity, peer relationship, and behavior among Turkish adolescents, height trends in Indonesia, physiological neonatal weight loss, methods for assessing biological maturation in sportsmen, and a new method for skeletal age determination. The participants also discussed the association between acute myocardial infarction and somatotype in Estonia, rural-urban growth differences in Mongolian children, socio-environmental conditions and sexual dimorphism, biological mortality bias, and new statistical techniques for describing inhomogeneity in the association of bivariate variables, and for detecting and visualizing extensive interactions among variables.
Background: Network models are useful tools for researchers to simplify and understand investigated systems. Yet, the assessment of methods for network construction is often uncertain. Random resampling simulations can aid to assess methods, provided synthetic data exists for reliable network construction.
Objectives: We implemented a new Monte Carlo algorithm to create simulated data for network reconstruction, tested the influence of adjusted parameters and used simulations to select a method for network model estimation based on real-world data. We hypothesized, that reconstructs based on Monte Carlo data are scored at least as good compared to a benchmark.
Methods: Simulated data was generated in R using the Monte Carlo algorithm of the mcgraph package. Benchmark data was created by the huge package. Networks were reconstructed using six estimator functions and scored by four classification metrics. For compatibility tests of mean score differences, Welch’s t-test was used. Network model estimation based on real-world data was done by stepwise selection.
Samples: Simulated data was generated based on 640 input graphs of various types and sizes. The real-world dataset consisted of 67 medieval skeletons of females and males from the region of Refshale (Lolland) and Nordby (Jutland) in Denmark.
Results: Results after t-tests and determining confidence intervals (CI95%) show, that evaluation scores for network reconstructs based on the mcgraph package were at least as good compared to the benchmark huge. The results even indicate slightly better scores on average for the mcgraph package.
Conclusion: The results confirmed our objective and suggested that Monte Carlo data can keep up with the benchmark in the applied test framework. The algorithm offers the feature to use (weighted) un- and directed graphs and might be useful for assessing methods for network construction.
Background: In the animal kingdom body size is often linked to dominance and subsequently the standing in social hierarchy. Similarly, human growth has been associated and linked to socioeconomic factors, including one’s social status. This has already been proposed in the early 1900s where data on young German school girls from different social strata have been compared.
Objectives: This paper aims to summarize and analyze these results and make them accessible for non-German speakers. The full English translation of the historic work of Dikanski (Dikanski, 1914) is available as a supplement. Further, this work aims to compare the historical data with modern references, to test three hypotheses: (1) higher social class is positively associated with body height and weight, (2) affluent people from the used historical data match modern references in weight and height and (3) weight distributions are skewed in both modern and historical populations.
Methods: Comparison of historical data from 1914 with WHO and 1980s German data. The data sets, for both body weight and height for 6.0- and 7.0-year-old girls, were fitted onto centile curves and quantile correlation coefficients were calculated.
Results: In historical data social status is positively associated with body height and weight while both are also normally distributed, which marks a significant difference to modern references.
Conclusion: Social status is positively associated with height, signaling social dominance, making children of affluent classes taller. Children from the historical data do not reach the average height of modern children, even under the best environmental conditions. The children of the upper social class were not skewed in weight distribution, although they had the means to become as obese as modern children.
Students learn by repetition. Repetition is essential, but repetition needs questioning, and questioning the repertoire belongs to the essential tasks of student education. Guiding students to questioning was and is our prime motive to offer our International Student Summer Schools. The data were critically discussed among the students, in the twilight of Just So Stories, common knowledge, and prompted questioning of contemporary solutions. For these schools, the students bring their own data, carry their preliminary concepts, and in group discussions, they may have to challenge these concepts. Catch-up growth is known to affect long bone growth, but different opinions exist to what extent it also affects body proportions. Skeletal age and dental development are considered appropriate measures of maturation, but it appears that both system develop independently and are regulated by different mechanisms. Body weight distributions are assumed to be skewed, yet, historic data disproved this assumption. Many discussions focused on current ideas of global growth standards as a common yardstick for all populations world-wide, with new statistical tools being developed including network reconstruction and evaluation of the reconstructs to determine the confidence of graph prediction methods.
PRI: Re-analysis of a public mass cytometry dataset reveals patterns of effective tumor treatments
(2022)
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.
Twenty-four scientists met for the annual Auxological conference held at Krobielowice castle, Poland, to discuss the diverse influences of the environment and of social behavior on growth following last year’s focus on growth and public health concerns (Hermanussen et al., 2022b). Growth and final body size exhibit marked plastic responses to ecological conditions. Among the shortest are the pygmoid people of Rampasasa, Flores, Indonesia, who still live under most secluded insular conditions. Genetics and nutrition are usually considered responsible for the poor growth in many parts of this world, but evidence is accumulating on the prominent impact of social embedding on child growth. Secular trends not only in the growth of height, but also in body proportions, accompany the secular changes in the social, economic and political conditions, with major influences on the emotional and educational circumstances under which the children grow up (Bogin, 2021). Aspects of developmental tempo and aspects of sports were discussed, and the impact of migration by the example of women from Bangladesh who grew up in the UK. Child growth was considered in particular from the point of view of strategic adjustments of individual size within the network of its social group. Theoretical considerations on network characteristics were presented and related to the evolutionary conservation of growth regulating hypothalamic neuropeptides that have been shown to link behavior and physical growth in the vertebrate species. New statistical approaches were presented for the evaluation of short term growth measurements that permit monitoring child growth at intervals of a few days and weeks.
Human growth data analysis and statistics – the 5th Gülpe International Student Summer School
(2023)
The Summer School in Gülpe (Ecological Station of the University of Potsdam) offers an exceptional learning opportunity for students to apply their knowledge and skills to real-world problems. With the guidance of experienced human biologists, statisticians, and programmers, students have the unique chance to analyze their own data and gain valuable insights. This interdisciplinary setting not only bridges different research areas but also leads to highly valuable outputs. The progress of students within just a few days is truly remarkable, especially when they are motivated and receive immediate feedback on their questions, problems, and results. The Summer School covers a wide range of topics, with this year’s focus mainly on two areas: understanding the impact of socioeconomic and physiological factors on human development and mastering statistical techniques for analyzing data such as changepoint analysis and the St. Nicolas House Analysis (SNHA) to visualize interacting variables. The latter technique, born out of the Summer School’s emphasis on gaining comprehensive data insights and understanding major relationships, has proven to be a valuable tool for researchers in the field. The articles in this special issue demonstrate that the Summer School in Gülpe stands as a testament to the power of practical learning and collaboration. Students who attend not only gain hands-on experience but also benefit from the expertise of professionals and the opportunity to engage with peers from diverse disciplines.
The St. Nicolas House Algorithm (SNHA) finds association chains of direct dependent variables in a data set. The dependency is based on the correlation coefficient, which is visualized as an undirected graph. The network prediction is improved by a bootstrap routine. It enables the computation of the empirical p-value, which is used to evaluate the significance of the predicted edges. Synthetic data generated with the Monte Carlo method were used to firstly compare the Python package with the original R package, and secondly to evaluate the predicted network using the sensitivity, specificity, balanced classification rate and the Matthew's correlation coefficient (MCC). The Python implementation yields the same results as the R package. Hence, the algorithm was correctly ported into Python. The SNHA scores high specificity values for all tested graphs. For graphs with high edge densities, the other evaluation metrics decrease due to lower sensitivity, which could be partially improved by using bootstrap,while for graphs with low edge densities the algorithm achieves high evaluation scores. The empirical p-values indicated that the predicted edges indeed are significant.