Mixtures of Regression Models for Time-Course Gene Expression Data: Evaluation of Initialization and Random Effects

Finite mixture models are routinely applied to time course microarray data. Due to the complexity and size of this type of data the choice of good starting values plays an important role. So far initialization strategies have only been investigated for data from a mixture of multivariate normal distributions. In this work several initialization procedures are evaluated for mixtures of regression models with and without random effects in an extensive simulation study on different artificial datasets. Finally these procedures are also applied to a real dataset from E. coli

Cluster Analysis for Diminishing Heterogeneous Opinions of Service Quality Public Transport Passengers

[EN] One of the principal measures that public transport administrations are following for reaching a sustainable transportation in the cities consists on attract a higher number of citizens towards the use of public transport modes, by offering high quality services. Collecting users opinions is the best way of detecting where the service is failing and which aspects are been provided successfully. The main problem that has to be faced for analyzing service quality is the subjective nature of its measurement, offering heterogeneous assessments among passengers about the service. Stratifying the sample of users on segments of passengers which have more uniform opinions about the service can help to reduce this heterogeneity. This stratification usually is conducted based on the social and demographic characteristics of the passengers. However, there are more advance techniques that permits to identify more homogeneous groups of users. One of these techniques is the Cluster Analysis, which is a data mining technique that can be used for segmenting the sample of passengers on groups that share some common characteristics, and that have more homogeneous perceptions about the service. This technique has been applied in other fields of transport engineering but it has never been applied for searching homogeneous groups of users with regards to service quality evaluation in a public transport service. For this reason, the aim of this work is to find groups of passengers that perceive the quality of the service in a more homogeneous way, and to apply to this clusters a suitable statistic technique that permit us to discover which are the variables that more influence the passengers¿ overall evaluation about the service. The comparison among the results of each cluster will show considerable differences among them and also with the results obtained using the global sample.This study is sponsored by the Consejería de Innovación, Ciencia y Economía of the Junta de Andalucía (Spain) through the Excellence Research Project denominated Q-METROBUS-Quality of service indicator for METROpolitan public BUS transport services . The authors also acknowledge the Granada Consorcio de Transportes for making the data set available for this study. Likewise, Griselda López wishes to express her acknowledgement to the regional ministry of Economy, Innovation and Science of the regional government of Andalusia (Spain) for their scholarship to train teachers and researchers in Deficit AreasDe Oña, R.; López-Maldonado, G.; Díez De Los Ríos, F.; De Oña, J. (2014). Cluster Analysis for Diminishing Heterogeneous Opinions of Service Quality Public Transport Passengers. Procedia - Social and Behavioral Sciences. 162:459-466. https://doi.org/10.1016/j.sbspro.2014.12.227S45946616

Neural Crest Cell Survival Is Dependent on Rho Kinase and Is Required for Development of the Mid Face in Mouse Embryos

Neural crest cells (NCC) give rise to much of the tissue that forms the vertebrate head and face, including cartilage and bone, cranial ganglia and teeth. In this study we show that conditional expression of a dominant-negative (DN) form of Rho kinase (Rock) in mouse NCC results in severe hypoplasia of the frontonasal processes and first pharyngeal arch, ultimately resulting in reduction of the maxilla and nasal bones and severe craniofacial clefting affecting the nose, palate and lip. These defects resemble frontonasal dysplasia in humans. Disruption of the actin cytoskeleton, which leads to abnormalities in cell-matrix attachment, is seen in the RockDN;Wnt1-cre mutant embryos. This leads to elevated cell death, resulting in NCC deficiency and hypoplastic NCC-derived craniofacial structures. Rock is thus essential for survival of NCC that form the craniofacial region. We propose that reduced NCC numbers in the frontonasal processes and first pharyngeal arch, resulting from exacerbated cell death, may be the common mechanism underlying frontonasal dysplasia

A pathway-specific microarray analysis highlights the complex and co-ordinated transcriptional networks of the developing grain of field-grown barley

The aim of the study was to describe the molecular and biochemical interactions associated with amino acid biosynthesis and storage protein accumulation in the developing grains of field-grown barley. Our strategy was to analyse the transcription of genes associated with the biosynthesis of storage products during the development of field-grown barley grains using a grain-specific microarray assembled in our laboratory. To identify co-regulated genes, a distance matrix was constructed which enabled the identification of three clusters corresponding to early, middle, and late grain development. The gene expression pattern associated with the clusters was investigated using pathway-specific analysis with specific reference to the temporal expression levels of a range of genes involved mainly in the photosynthesis process, amino acid and storage protein metabolism. It is concluded that the grain-specific microarray is a reliable and cost-effective tool for monitoring temporal changes in the transcriptome of the major metabolic pathways in the barley grain. Moreover, it was sensitive enough to monitor differences in the gene expression profiles of different homologues from the storage protein families. The study described here should provide a strong complement to existing knowledge assisting further understanding of grain development and thereby provide a foundation for plant breeding towards storage proteins with improved nutritional quality

Shear Stress Modulation of Smooth Muscle Cell Marker Genes in 2-D and 3-D Depends on Mechanotransduction by Heparan Sulfate Proteoglycans and ERK1/2

During vascular injury, vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts (FBs/MFBs) are exposed to altered luminal blood flow or transmural interstitial flow. We investigate the effects of these two types of fluid flows on the phenotypes of SMCs and MFBs and the underlying mechanotransduction mechanisms.Exposure to 8 dyn/cm(2) laminar flow shear stress (2-dimensional, 2-D) for 15 h significantly reduced expression of alpha-smooth muscle actin (alpha-SMA), smooth muscle protein 22 (SM22), SM myosin heavy chain (SM-MHC), smoothelin, and calponin. Cells suspended in collagen gels were exposed to interstitial flow (1 cmH(2)O, approximately 0.05 dyn/cm(2), 3-D), and after 6 h of exposure, expression of SM-MHC, smoothelin, and calponin were significantly reduced, while expression of alpha-SMA and SM22 were markedly enhanced. PD98059 (an ERK1/2 inhibitor) and heparinase III (an enzyme to cleave heparan sulfate) significantly blocked the effects of laminar flow on gene expression, and also reversed the effects of interstitial flow on SM-MHC, smoothelin, and calponin, but enhanced interstitial flow-induced expression of alpha-SMA and SM22. SMCs and MFBs have similar responses to fluid flow. Silencing ERK1/2 completely blocked the effects of both laminar flow and interstitial flow on SMC marker gene expression. Western blotting showed that both types of flows induced ERK1/2 activation that was inhibited by disruption of heparan sulfate proteoglycans (HSPGs).The results suggest that HSPG-mediated ERK1/2 activation is an important mechanotransduction pathway modulating SMC marker gene expression when SMCs and MFBs are exposed to flow. Fluid flow may be involved in vascular remodeling and lesion formation by affecting phenotypes of vascular wall cells. This study has implications in understanding the flow-related mechanobiology in vascular lesion formation, tumor cell invasion, and stem cell differentiation

A Role for the Juxtamembrane Cytoplasm in the Molecular Dynamics of Focal Adhesions

Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRAP studies in live cells, with in silico simulations and mathematical modeling, we show that the FA plaque proteins paxillin and vinculin exist in four dynamic states: an immobile FA-bound fraction, an FA-associated fraction undergoing exchange, a juxtamembrane fraction experiencing attenuated diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs displays a gradient of FA plaque proteins with respect to both concentration and dynamics. Based on these findings, we propose a new model for the regulation of FA dynamics in which this juxtamembrane domain acts as an intermediary layer, enabling an efficient regulation of FA formation and reorganization

Anxiety profiles and protective factors: A latent profile analysis in children

The current study investigated the presence of different anxiety profiles in schoolchildren in order to understand whether Mathematics and Test Anxiety are a manifestation of a general form of anxiety, or the expression of specific forms of anxiety. Moreover, we also examined the influence of personal protective factors. The results of a latent profile analysis, conducted on 664 children attending grades 3 to 6, clearly identified three different profiles distinguished on the basis of the level of general, test and mathematics anxiety. Protective factors, such as self-concept and resilience, were differently related to anxiety: the former was clearly lower when the risk profile was higher, whereas students were able to maintain a certain level of resilience up to an average risk of developing forms of anxiety. The implications of these findings may lead to the development of specific intervention programs aimed at reducing students’ anxiety and fostering self-concept and resilience. © 2017 Elsevier Lt

Cultural Aspects of Attachment Anxiety, Avoidance, and Life Satisfaction: Comparing the US and Turkey

Attachment insecurity can interfere with the experience, expression, and benefits of positive emotions, including happiness and life satisfaction (LS). However, both the pattern and effects of insecure attachment orientations on LS vary across cultures. Considering that attachment anxiety is higher in collectivist cultures and attachment avoidance is relatively high in individualistic cultures, the present chapter elaborates on the idea that anxious and avoidant attachment would have varying effects on LS in individualistic and collectivistic cultural contexts. Study 1 (N = 2456) involved a community sample of married couples in Turkey and demonstrated that attachment avoidance was a stronger predictor of LS than attachment anxiety in Turkish collectivist context. Study 2 tested the hypothesis that the roles of attachment anxiety and avoidance in predicting LS would vary between collectivistic and individualistic cultures. Mothers’ adult attachment dimensions and LS in Turkey (N = 89) and the United States (N = 91) were measured. As expected, results indicated that LS was predicted only by attachment avoidance in Turkey and by attachment anxiety in the United States. These findings are in line with the cultural fit hypothesis, suggesting that culturally incongruent attachment orientations have a stronger negative impact on individuals’ LS

Reconstructing the reproductive mode of an Ediacaran macro-organism.

Enigmatic macrofossils of late Ediacaran age (580-541 million years ago) provide the oldest known record of diverse complex organisms on Earth, lying between the microbially dominated ecosystems of the Proterozoic and the Cambrian emergence of the modern biosphere. Among the oldest and most enigmatic of these macrofossils are the Rangeomorpha, a group characterized by modular, self-similar branching and a sessile benthic habit. Localized occurrences of large in situ fossilized rangeomorph populations allow fundamental aspects of their biology to be resolved using spatial point process techniques. Here we use such techniques to identify recurrent clustering patterns in the rangeomorph Fractofusus, revealing a complex life history of multigenerational, stolon-like asexual reproduction, interspersed with dispersal by waterborne propagules. Ecologically, such a habit would have allowed both for the rapid colonization of a localized area and for transport to new, previously uncolonized areas. The capacity of Fractofusus to derive adult morphology by two distinct reproductive modes documents the sophistication of its underlying developmental biology.This work has been supported by the Natural Environment Research Council [grant numbers NE/I005927/1 to C.G.K., NE/J5000045/1 to J.J.M., NE/L011409/1 to A.G.L. and NE/G523539/1 to E.G.M.], and a Henslow Junior Research Fellowship from Cambridge Philosophical Society to A.G.L.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nature1464

Theoretical Model for Cellular Shapes Driven by Protrusive and Adhesive Forces

The forces that arise from the actin cytoskeleton play a crucial role in determining the cell shape. These include protrusive forces due to actin polymerization and adhesion to the external matrix. We present here a theoretical model for the cellular shapes resulting from the feedback between the membrane shape and the forces acting on the membrane, mediated by curvature-sensitive membrane complexes of a convex shape. In previous theoretical studies we have investigated the regimes of linear instability where spontaneous formation of cellular protrusions is initiated. Here we calculate the evolution of a two dimensional cell contour beyond the linear regime and determine the final steady-state shapes arising within the model. We find that shapes driven by adhesion or by actin polymerization (lamellipodia) have very different morphologies, as observed in cells. Furthermore, we find that as the strength of the protrusive forces diminish, the system approaches a stabilization of a periodic pattern of protrusions. This result can provide an explanation for a number of puzzling experimental observations regarding cellular shape dependence on the properties of the extra-cellular matrix