Meeting Report: The Role of Beliefs and Perception on Body Size. Proceedings of the 26th Aschauer Soiree, Held at Aschauhof, Altenhof, Germany, May 26th, 2018.

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.

The gonadal transcriptome of the unisexual Amazon molly Poecilia formosa in comparison to its sexual ancestors, Poecilia mexicana and Poecilia latipinna.

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.

Meeting Report: Growth and Social Environment. Proceedings of the 25th Aschauer Soiree, held at Krobielowice, Poland, November 18th 2017.

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.

Target specificity among canonical nuclear poly(A) polymerases in plants modulates organ growth and pathogen response.

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.

Stunted Growth. Proceedings of the 23rd Aschauer Soiree, Held at Aschauhof, Germany, November 7th 2015.

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.

Sequence variation, differential expression, and divergent evolution in starch-related genes among accessions of Arabidopsis thaliana.

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.

Transcriptomics-aided dissection of the intracellular and extracellular roles of microcystin in Microcystis aeruginosa PCC 7806.

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 ΔmcyB 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.

"Proceedings of the 22nd Aschauer Soiree on Growth and Health Screening", held at Altenhof, Germany, November 15th, 2014.

Twenty-five scientists met at Aschauhof, Altenhof, Germany, to discuss various aspects of the complex network of modern health screening, focusing on current scientific topics including medical sciences, human biology, and mathematics; on problems in implementing these results at the practical level of physicians, nurses, technicians, and engineers; and the level of administrative and political decisions. Whereas major scientific advancements have been published in the understanding and the bio-statistical evaluation of anthropometric screening parameters such as serial measurements of height and weight for preventive medical check-ups, BMI screening and surveillance in schools, etc., the implementation of these advancements into current health screening concepts, strategies and decision-making is poor. Fear of discrimination, misperception of body image, behavioural responses and political concerns, meanwhile dominate and negatively interfere with the implementation of recent scientific results into public health screening concepts and practices.

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.

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.

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.

Discovering plant metabolic biomarkers for phenotype prediction using an untargeted approach.

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.

Positive influence of parental education on growth of children - statistical analysis of correlation between social and nutritional factors on children's height using the St. Nicolas House Analysis.

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.

The end of the secular trend in Norway: spatial trends in body height of Norwegian conscripts in the 19th, 20th and 21st century.

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 1895-1897, 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.

Association of anthropometric indices of nutritional status with growth in height among Limboo children of Sikkim, India.

Aim: Influence of nutrition in human growth failure, especially stunting, is a well-accepted idea. The present study assesses the influence of nutrition and non-nutritional factors on height growth in a short stature population. Material and methods: The present study was conducted among the children and adolescents of Sikkim, India. The sample size was 538 (boys and girls) of age 2-18 years. The anthropometric indices mid upper arm circumference-for-age Z-scores (MUACZ) and BMI-for-age Z-scores (BAZ) were utilised as proxy of nutritional status and growth was assessed using height-for-age Z-scores (HAZ). Associations were assessed using correlation, St. Nicolas house analysis (SNHA), principal component analysis (PCA) and regression. Results: Nutritional status of the participating children and adolescents as assessed by MUACZ and BAZ were largely normal. Despite variation in HAZ from -4 to +2 there was no influence of the nutritional indices on height. Further, there was clear lack of association between HAZ and socio-economic variables in the present study. Conclusion: The findings of the present study suggest nutrition is not the primary regulator of human growth. The possible influence of community effects on height is discussed.

No correlation between short term weight gain and lower leg length gain in healthy German children.

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.

Environmental stimulation on height: The story from Indonesia.

Background: Since the 19th century, sexual dimorphism has been known to be sensitive to adverse environmental conditions. Migrants are sensitive to economic and political affluence, and tend to adjust in height towards height of their hosts. We aim to study growth, sexual dimorphism, and height of native and migrant children in three primary schools in Nabire, Papua, Indonesia. Material and Methods 1: Cross-sectional data on height were obtained from 186 children (59 and 56 native Papuan girls and boys, respectively; 38 and 33 trans-migrant girls and boys respectively; who are aged 7.0-7.7 (mean 7.45) years from three primary schools in Nabire, Papua, Indonesia. The Indonesian National Growth Charts were used as references for height. Results 1: With 118.4 cm (SD 6.7) cm, trans-migrant 7-year old boys were almost 3 cm taller compared to their native-age-matched-peers (115.7 cm (5.0 SD) cm, p < 0.05). The case was different among the girls. Trans-migrant girls were not significantly taller than native girls. Material and Method 2: We re-analyzed the height data from over 300,000 infants, children and adolescents, age 0-18 year, from 34 Indonesian provinces. The data were obtained from the latest Indonesian 2013 National Basic Health Survey (NHBS), and have previously been used to construct National Indonesian Growth Charts. St. Nicolas House Analysis was used to translate correlation matrices into network graphs and visualizing chains of associations between parameters that were multiply correlated. Results 2: St. Nicolas House Analysis suggested that the growth of male sex were more sensitive to population crowding, and that crowding contributes to the greater height dimorphism in taller populations. Conclusion: Economic prosperity and increased population density stimulate male adult height to a greater extent than female adult height, and increase the sexual dimorphism in height among the tall populations of densely populated wealthy countries.

Traumatized women's infants are bigger than children of mothers without traumas.

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.

Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception.

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-γhigh PD-1low CD40Lhigh CXCR5- Bcl-6- T cells specifically expanded in diseased mice. In addition, these cells express high levels of TNF-α 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.