WorldWideScience

Sample records for human variation application

  1. Estimating mobility using sparse data: Application to human genetic variation.

    Science.gov (United States)

    Loog, Liisa; Mirazón Lahr, Marta; Kovacevic, Mirna; Manica, Andrea; Eriksson, Anders; Thomas, Mark G

    2017-11-14

    Mobility is one of the most important processes shaping spatiotemporal patterns of variation in genetic, morphological, and cultural traits. However, current approaches for inferring past migration episodes in the fields of archaeology and population genetics lack either temporal resolution or formal quantification of the underlying mobility, are poorly suited to spatially and temporally sparsely sampled data, and permit only limited systematic comparison between different time periods or geographic regions. Here we present an estimator of past mobility that addresses these issues by explicitly linking trait differentiation in space and time. We demonstrate the efficacy of this estimator using spatiotemporally explicit simulations and apply it to a large set of ancient genomic data from Western Eurasia. We identify a sequence of changes in human mobility from the Late Pleistocene to the Iron Age. We find that mobility among European Holocene farmers was significantly higher than among European hunter-gatherers both pre- and postdating the Last Glacial Maximum. We also infer that this Holocene rise in mobility occurred in at least three distinct stages: the first centering on the well-known population expansion at the beginning of the Neolithic, and the second and third centering on the beginning of the Bronze Age and the late Iron Age, respectively. These findings suggest a strong link between technological change and human mobility in Holocene Western Eurasia and demonstrate the utility of this framework for exploring changes in mobility through space and time. Copyright © 2017 the Author(s). Published by PNAS.

  2. Application of Method of Variation to Analyze and Predict Human Induced Modifications of Water Resource Systems

    Science.gov (United States)

    Dessu, S. B.; Melesse, A. M.; Mahadev, B.; McClain, M.

    2010-12-01

    Water resource systems have often used gravitational surface and subsurface flows because of their practicality in hydrological modeling and prediction. Activities such as inter/intra-basin water transfer, the use of small pumps and the construction of micro-ponds challenge the tradition of natural rivers as water resource management unit. On the contrary, precipitation is barely affected by topography and plot harvesting in wet regions can be more manageable than diverting from rivers. Therefore, it is indicative to attend to systems where precipitation drives the dynamics while the internal mechanics constitutes spectrum of human activity and decision in a network of plots. The trade-in volume and path of harvested precipitation depends on water balance, energy balance and the kinematics of supply and demand. Method of variation can be used to understand and predict the implication of local excess precipitation harvest and exchange on the natural water system. A system model was developed using the variational form of Euler-Bernoulli’s equation for the Kenyan Mara River basin. Satellite derived digital elevation models, precipitation estimates, and surface properties such as fractional impervious surface area, are used to estimate the available water resource. Four management conditions are imposed in the model: gravitational flow, open water extraction and high water use investment at upstream and downstream respectively. According to the model, the first management maintains the basin status quo while the open source management could induce externality. The high water market at the upstream in the third management offers more than 50% of the basin-wide total revenue to the upper third section of the basin thus may promote more harvesting. The open source and upstream exploitation suggest potential drop of water availability to downstream. The model exposed the latent potential of economic gradient to reconfigure the flow network along the direction where the

  3. Understanding human DNA sequence variation.

    Science.gov (United States)

    Kidd, K K; Pakstis, A J; Speed, W C; Kidd, J R

    2004-01-01

    Over the past century researchers have identified normal genetic variation and studied that variation in diverse human populations to determine the amounts and distributions of that variation. That information is being used to develop an understanding of the demographic histories of the different populations and the species as a whole, among other studies. With the advent of DNA-based markers in the last quarter century, these studies have accelerated. One of the challenges for the next century is to understand that variation. One component of that understanding will be population genetics. We present here examples of many of the ways these new data can be analyzed from a population perspective using results from our laboratory on multiple individual DNA-based polymorphisms, many clustered in haplotypes, studied in multiple populations representing all major geographic regions of the world. These data support an "out of Africa" hypothesis for human dispersal around the world and begin to refine the understanding of population structures and genetic relationships. We are also developing baseline information against which we can compare findings at different loci to aid in the identification of loci subject, now and in the past, to selection (directional or balancing). We do not yet have a comprehensive understanding of the extensive variation in the human genome, but some of that understanding is coming from population genetics.

  4. Size variation in Middle Pleistocene humans.

    Science.gov (United States)

    Arsuaga, J L; Carretero, J M; Lorenzo, C; Gracia, A; Martínez, I; Bermúdez de Castro, J M; Carbonell, E

    1997-08-22

    It has been suggested that European Middle Pleistocene humans, Neandertals, and prehistoric modern humans had a greater sexual dimorphism than modern humans. Analysis of body size variation and cranial capacity variation in the large sample from the Sima de los Huesos site in Spain showed instead that the sexual dimorphism is comparable in Middle Pleistocene and modern populations.

  5. Anatomy, Medical Education, and Human Ancestral Variation

    Science.gov (United States)

    Strkalj, Goran; Spocter, Muhammad A.; Wilkinson, A. Tracey

    2011-01-01

    It is argued in this article that the human body both in health and disease cannot be fully understood without adequately accounting for the different levels of human variation. The article focuses on variation due to ancestry, arguing that the inclusion of information pertaining to ancestry in human anatomy teaching materials and courses should…

  6. The genetics of regulatory variation in the human genome

    OpenAIRE

    Stranger Barbara E; Dermitzakis Emmanouil T

    2005-01-01

    Abstract The regulation of gene expression plays an important role in complex phenotypes, including disease in humans. For some genes, the genetic mechanisms influencing gene expression are well elucidated; however, it is unclear how applicable these results are to gene expression on a genome-wide level. Studies in model organisms and humans have clearly documented gene expression variation among individuals and shown that a significant proportion of this variation has a genetic basis. Recent...

  7. Anatomy, medical education, and human ancestral variation.

    Science.gov (United States)

    Strkalj, Goran; Spocter, Muhammad A; Wilkinson, A Tracey

    2011-01-01

    It is argued in this article that the human body both in health and disease cannot be fully understood without adequately accounting for the different levels of human variation. The article focuses on variation due to ancestry, arguing that the inclusion of information pertaining to ancestry in human anatomy teaching materials and courses should be carried out and implemented with care and in line with latest developments in biological anthropology and related sciences. This seems to be of particular importance in the education of health professionals, as recent research suggests that better knowledge of human variation can improve clinical skills. It is also argued that relatively small curricular changes relating to the teaching of human variation can produce significant educational gains. Copyright © 2011 American Association of Anatomists.

  8. Extensive Variation in Chromatin States Across Humans

    KAUST Repository

    Kasowski, M.

    2013-10-17

    The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.

  9. Variational continuum multiphase poroelasticity theory and applications

    CERN Document Server

    Serpieri, Roberto

    2017-01-01

    This book collects the theoretical derivation of a recently presented general variational macroscopic continuum theory of multiphase poroelasticity (VMTPM), together with its applications to consolidation and stress partitioning problems of interest in several applicative engineering contexts, such as in geomechanics and biomechanics. The theory is derived based on a purely-variational deduction, rooted in the least-Action principle, by considering a minimal set of kinematic descriptors. The treatment herein considered keeps a specific focus on the derivation of most general medium-independent governing equations. It is shown that VMTPM recovers paradigms of consolidated use in multiphase poroelasticity such as Terzaghi's stress partitioning principle and Biot's equations for wave propagation. In particular, the variational treatment permits the derivation of a general medium-independent stress partitioning law, and the proposed variational theory predicts that the external stress, the fluid pressure, and the...

  10. A global reference for human genetic variation

    DEFF Research Database (Denmark)

    Auton, Adam; Abecasis, Goncalo R.; M. Altshuler, David

    2015-01-01

    The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals...

  11. A global reference for human genetic variation

    DEFF Research Database (Denmark)

    Auton, Adam; Abecasis, Goncalo R.; M. Altshuler, David

    2015-01-01

    The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals...... from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short...

  12. Big Data Analysis of Human Genome Variations

    KAUST Repository

    Gojobori, Takashi

    2016-01-25

    Since the human genome draft sequence was in public for the first time in 2000, genomic analyses have been intensively extended to the population level. The following three international projects are good examples for large-scale studies of human genome variations: 1) HapMap Data (1,417 individuals) (http://hapmap.ncbi.nlm.nih.gov/downloads/genotypes/2010-08_phaseII+III/forward/), 2) HGDP (Human Genome Diversity Project) Data (940 individuals) (http://www.hagsc.org/hgdp/files.html), 3) 1000 genomes Data (2,504 individuals) http://ftp.1000genomes.ebi.ac.uk/vol1/ftp/release/20130502/ If we can integrate all three data into a single volume of data, we should be able to conduct a more detailed analysis of human genome variations for a total number of 4,861 individuals (= 1,417+940+2,504 individuals). In fact, we successfully integrated these three data sets by use of information on the reference human genome sequence, and we conducted the big data analysis. In particular, we constructed a phylogenetic tree of about 5,000 human individuals at the genome level. As a result, we were able to identify clusters of ethnic groups, with detectable admixture, that were not possible by an analysis of each of the three data sets. Here, we report the outcome of this kind of big data analyses and discuss evolutionary significance of human genomic variations. Note that the present study was conducted in collaboration with Katsuhiko Mineta and Kosuke Goto at KAUST.

  13. Genetic variation in an individual human exome.

    Directory of Open Access Journals (Sweden)

    Pauline C Ng

    2008-08-01

    Full Text Available There is much interest in characterizing the variation in a human individual, because this may elucidate what contributes significantly to a person's phenotype, thereby enabling personalized genomics. We focus here on the variants in a person's 'exome,' which is the set of exons in a genome, because the exome is believed to harbor much of the functional variation. We provide an analysis of the approximately 12,500 variants that affect the protein coding portion of an individual's genome. We identified approximately 10,400 nonsynonymous single nucleotide polymorphisms (nsSNPs in this individual, of which approximately 15-20% are rare in the human population. We predict approximately 1,500 nsSNPs affect protein function and these tend be heterozygous, rare, or novel. Of the approximately 700 coding indels, approximately half tend to have lengths that are a multiple of three, which causes insertions/deletions of amino acids in the corresponding protein, rather than introducing frameshifts. Coding indels also occur frequently at the termini of genes, so even if an indel causes a frameshift, an alternative start or stop site in the gene can still be used to make a functional protein. In summary, we reduced the set of approximately 12,500 nonsilent coding variants by approximately 8-fold to a set of variants that are most likely to have major effects on their proteins' functions. This is our first glimpse of an individual's exome and a snapshot of the current state of personalized genomics. The majority of coding variants in this individual are common and appear to be functionally neutral. Our results also indicate that some variants can be used to improve the current NCBI human reference genome. As more genomes are sequenced, many rare variants and non-SNP variants will be discovered. We present an approach to analyze the coding variation in humans by proposing multiple bioinformatic methods to hone in on possible functional variation.

  14. Cosmic Rays Variations and Human Physiological State

    Science.gov (United States)

    Dimitrova, S.

    2009-12-01

    It was obtained in our previous investigations that geomagnetic activity as an indirect indicator of solar activity correlates with some human physiological and psycho-physiological parameters. A lot of studies indicate that other parameters of space weather like cosmic rays Forbush decreases affect myocardial infarction, brain stroke, car accidents, etc. The purpose of that work was to study the effect of cosmic rays variations on human physiological status. It was established that the decrease in cosmic rays intensity was related to an increase in systolic and diastolic blood pressure and reported subjective psycho-physiological complaints in healthy volunteers.

  15. Probability analysis of variational crystallization and its application to gp120, the exterior envelope glycoprotein of type 1 human immunodeficiency virus (HIV-1).

    Science.gov (United States)

    Kwong, P D; Wyatt, R; Desjardins, E; Robinson, J; Culp, J S; Hellmig, B D; Sweet, R W; Sodroski, J; Hendrickson, W A

    1999-02-12

    The extensive glycosylation and conformational mobility of gp120, the envelope glycoprotein of type 1 human immunodeficiency virus (HIV-1), pose formidable barriers for crystallization. To surmount these difficulties, we used probability analysis to determine the most effective crystallization approach and derive equations which show that a strategy, which we term variational crystallization, substantially enhances the overall probability of crystallization for gp120. Variational crystallization focuses on protein modification as opposed to crystallization screening. Multiple variants of gp120 were analyzed with an iterative cycle involving a limited set of crystallization conditions and biochemical feedback on protease sensitivity, glycosylation status, and monoclonal antibody binding. Sources of likely conformational heterogeneity such as N-linked carbohydrates, flexible or mobile N and C termini, and variable internal loops were reduced or eliminated, and ligands such as CD4 and antigen-binding fragments (Fabs) of monoclonal antibodies were used to restrict conformational mobility as well as to alter the crystallization surface. Through successive cycles of manipulation involving 18 different variants, we succeeded in growing six different types of gp120 crystals. One of these, a ternary complex composed of gp120, its receptor CD4, and the Fab of the human neutralizing monoclonal antibody 17b, diffracts to a minimum Bragg spacing of at least 2.2 A and is suitable for structural analysis.

  16. Ionization potentials some variations, implications and applications

    CERN Document Server

    Ahrens, L H

    1983-01-01

    Ionization Potentials: Some Variations, Implications and Applications covers several aspects of ionization potential that is a highly significant parameter in controlling the properties of electric discharge. Comprised of 17 chapters, the book covers topic relevant to ionization potentials, such as properties, concepts, and applications, in order to understand and fully comprehend all aspects of ionization potential. The opening chapter is a review of ionization potentials and a discussion of trends and features. The succeeding chapters then tackle complex topics such as the s and p electrons;

  17. HGVA: the Human Genome Variation Archive.

    Science.gov (United States)

    Lopez, Javier; Coll, Jacobo; Haimel, Matthias; Kandasamy, Swaathi; Tarraga, Joaquin; Furio-Tari, Pedro; Bari, Wasim; Bleda, Marta; Rueda, Antonio; Gräf, Stefan; Rendon, Augusto; Dopazo, Joaquin; Medina, Ignacio

    2017-05-23

    High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic data for key reference projects in a clean, fast and integrated fashion. HGVA provides an efficient and intuitive web-interface for easy data mining, a comprehensive RESTful API and client libraries in Python, Java and JavaScript for fast programmatic access to its knowledge base. HGVA calculates population frequencies for these projects and enriches their data with variant annotation provided by CellBase, a rich and fast annotation solution. HGVA serves as a proof-of-concept of the genome analysis developments being carried out by the University of Cambridge together with UK's 100 000 genomes project and the National Institute for Health Research BioResource Rare-Diseases, in particular, deploying open-source for Computational Biology (OpenCB) software platform for storing and analyzing massive genomic datasets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Seasonal variation in human gut microbiome composition.

    Directory of Open Access Journals (Sweden)

    Emily R Davenport

    Full Text Available The composition of the human gut microbiome is influenced by many environmental factors. Diet is thought to be one of the most important determinants, though we have limited understanding of the extent to which dietary fluctuations alter variation in the gut microbiome between individuals. In this study, we examined variation in gut microbiome composition between winter and summer over the course of one year in 60 members of a founder population, the Hutterites. Because of their communal lifestyle, Hutterite diets are similar across individuals and remarkably stable throughout the year, with the exception that fresh produce is primarily served during the summer and autumn months. Our data indicate that despite overall gut microbiome stability within individuals over time, there are consistent and significant population-wide shifts in microbiome composition across seasons. We found seasonal differences in both (i the abundance of particular taxa (false discovery rate <0.05, including highly abundant phyla Bacteroidetes and Firmicutes, and (ii overall gut microbiome diversity (by Shannon diversity; P = 0.001. It is likely that the dietary fluctuations between seasons with respect to produce availability explain, at least in part, these differences in microbiome composition. For example, high levels of produce containing complex carbohydrates consumed during the summer months might explain increased abundance of Bacteroidetes, which contain complex carbohydrate digesters, and decreased levels of Actinobacteria, which have been negatively correlated to fiber content in food questionnaires. Our observations demonstrate the plastic nature of the human gut microbiome in response to variation in diet.

  19. Interindividual variation in human T regulatory cells

    Science.gov (United States)

    Ferraro, Alessandra; D’Alise, Anna Morena; Raj, Towfique; Asinovski, Natasha; Phillips, Roxanne; Ergun, Ayla; Replogle, Joseph M.; Bernier, Angelina; Laffel, Lori; Stranger, Barbara E.; De Jager, Philip L.; Mathis, Diane; Benoist, Christophe

    2014-01-01

    FOXP3+ regulatory T (Treg) cells enforce immune self-tolerance and homeostasis, and variation in some aspects of Treg function may contribute to human autoimmune diseases. Here, we analyzed population-level Treg variability by performing genome-wide expression profiling of CD4+ Treg and conventional CD4+ T (Tconv) cells from 168 donors, healthy or with established type-1 diabetes (T1D) or type-2 diabetes (T2D), in relation to genetic and immunologic screening. There was a range of variability in Treg signature transcripts, some almost invariant, others more variable, with more extensive variability for genes that control effector function (ENTPD1, FCRL1) than for lineage-specification factors like FOXP3 or IKZF2. Network analysis of Treg signature genes identified coregulated clusters that respond similarly to genetic and environmental variation in Treg and Tconv cells, denoting qualitative differences in otherwise shared regulatory circuits whereas other clusters are coregulated in Treg, but not Tconv, cells, suggesting Treg-specific regulation of genes like CTLA4 or DUSP4. Dense genotyping identified 110 local genetic variants (cis-expression quantitative trait loci), some of which are specifically active in Treg, but not Tconv, cells. The Treg signature became sharper with age and with increasing body-mass index, suggesting a tuning of Treg function with repertoire selection and/or chronic inflammation. Some Treg signature transcripts correlated with FOXP3 mRNA and/or protein, suggesting transcriptional or posttranslational regulatory relationships. Although no single transcript showed significant association to diabetes, overall expression of the Treg signature was subtly perturbed in T1D, but not T2D, patients. PMID:24610777

  20. ENGINES: exploring single nucleotide variation in entire human genomes

    Directory of Open Access Journals (Sweden)

    Salas Antonio

    2011-04-01

    Full Text Available Abstract Background Next generation ultra-sequencing technologies are starting to produce extensive quantities of data from entire human genome or exome sequences, and therefore new software is needed to present and analyse this vast amount of information. The 1000 Genomes project has recently released raw data for 629 complete genomes representing several human populations through their Phase I interim analysis and, although there are certain public tools available that allow exploration of these genomes, to date there is no tool that permits comprehensive population analysis of the variation catalogued by such data. Description We have developed a genetic variant site explorer able to retrieve data for Single Nucleotide Variation (SNVs, population by population, from entire genomes without compromising future scalability and agility. ENGINES (ENtire Genome INterface for Exploring SNVs uses data from the 1000 Genomes Phase I to demonstrate its capacity to handle large amounts of genetic variation (>7.3 billion genotypes and 28 million SNVs, as well as deriving summary statistics of interest for medical and population genetics applications. The whole dataset is pre-processed and summarized into a data mart accessible through a web interface. The query system allows the combination and comparison of each available population sample, while searching by rs-number list, chromosome region, or genes of interest. Frequency and FST filters are available to further refine queries, while results can be visually compared with other large-scale Single Nucleotide Polymorphism (SNP repositories such as HapMap or Perlegen. Conclusions ENGINES is capable of accessing large-scale variation data repositories in a fast and comprehensive manner. It allows quick browsing of whole genome variation, while providing statistical information for each variant site such as allele frequency, heterozygosity or FST values for genetic differentiation. Access to the data mart

  1. Genomic variation landscape of the human gut microbiome

    DEFF Research Database (Denmark)

    Schloissnig, Siegfried; Arumugam, Manimozhiyan; Sunagawa, Shinichi

    2013-01-01

    polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates......Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal...

  2. Inherited and de novo variation in human genomes

    NARCIS (Netherlands)

    Francioli, L.C.

    2015-01-01

    Most human traits, ranging from physical appearance to behavior and disease susceptibility, are in part inherited through genetic material. Whole-genome sequencing has enabled the complete characterization of human genetic variation. While most of common DNA sequence variation has been observed in

  3. Child Development and Structural Variation in the Human Genome

    Science.gov (United States)

    Zhang, Ying; Haraksingh, Rajini; Grubert, Fabian; Abyzov, Alexej; Gerstein, Mark; Weissman, Sherman; Urban, Alexander E.

    2013-01-01

    Structural variation of the human genome sequence is the insertion, deletion, or rearrangement of stretches of DNA sequence sized from around 1,000 to millions of base pairs. Over the past few years, structural variation has been shown to be far more common in human genomes than previously thought. Very little is currently known about the effects…

  4. HUMAN INTERACTION WITH MOBILE APPLICATIONS

    OpenAIRE

    Alin Zamfiroiu; Emanuel Herteliu; Bogdan Vintila

    2012-01-01

    Computing - human interaction is a very important paradigm because informatics applications are created to be used by people via human interaction. Nowadays mobile applications are more used so is necessarily to talk about mobile - human interaction. In this paper types of mobile devices are presented. Citizen oriented character of mobile application and his utility are described. Different means of interactions with mobile devices are analyzed and in the end of the paper direction of mobile ...

  5. Applications of Pharmacogenetics in Revealing Variations in ...

    African Journals Online (AJOL)

    acer

    In the past two decades many drugs were discovered through the developments taking place in molecular biology techniques. Drug action is now more defined. In addition to known pharmacogenetic variations on drug metabolism, variations in drug targets are also emerging. These targets include receptors, transporters,.

  6. Cyclic Variations in Sustained Human Performance

    Science.gov (United States)

    Aue, William R.; Arruda, James E.; Kass, Steven J.; Stanny, Claudia J.

    2009-01-01

    Biological rhythms play a prominent role in the modulation of human physiology and behavior. [Smith, K., Valentino, D., & Arruda, J. (2003). "Rhythmic oscillations in the performance of a sustained attention task." "Journal of Clinical and Experimental Neuropsychology," 25, 561-570] suggested that sustained human performance may systematically…

  7. Evolutionary perspectives on human height variation

    NARCIS (Netherlands)

    Stulp, Gert; Barrett, Louise

    Human height is a highly variable trait, both within and between populations, has a high heritability, and influences the manner in which people behave and are treated in society. Although we know much about human height, this information has rarely been brought together in a comprehensive,

  8. Temperamental variation in learned irrelevance in humans

    OpenAIRE

    Gruszka-Gosiewska, Aleksandra; Owen, Adrian M.

    2015-01-01

    Background Learned irrelevance (LIRR) represents one of the mechanisms of attentional set-shifting and refers to the inability to attend to, or to learn about, any aspect of a stimulus previously experienced as irrelevant. Although it has been extensively studied in the context of clinical populations, not much is known about LIRR effects in relation to normal variation in individual differences. The present study was designed to assess how temperamental factors may modulate LIRR. ...

  9. Handling large variations in mechanics: Some applications

    Indian Academy of Sciences (India)

    MS received 11 October 2014; revised 17 February 2015; accepted 1 March 2015. Abstract. There is a need to use probability distributions with power-law decaying tails to describe the large variations exhibited by some of the physical phenomena. The Weierstrass Random Walk (WRW) shows promise for modeling such ...

  10. Applications of Pharmacogenetics in Revealing Variations in ...

    African Journals Online (AJOL)

    This review article presents the latest findings of genetic variations in pharmacological targets related to disorders of major systems such as central nervous system, cardiovascular system, and the respiratory system especially in relation to asthma and the HLA antigen genotype in hypersensitivity reactions. East and Central ...

  11. Structural Variation of Element and Human Disease

    Directory of Open Access Journals (Sweden)

    Songmi Kim

    2016-09-01

    Full Text Available Transposable elements are one of major sources to cause genomic instability through various mechanisms including de novo insertion, insertion-mediated genomic deletion, and recombination-associated genomic deletion. Among them is Alu element which is the most abundant element, composing ~10% of the human genome. The element emerged in the primate genome 65 million years ago and has since propagated successfully in the human and non-human primate genomes. Alu element is a non-autonomous retrotransposon and therefore retrotransposed using L1-enzyme machinery. The 'master gene' model has been generally accepted to explain Alu element amplification in primate genomes. According to the model, different subfamilies of Alu elements are created by mutations on the master gene and most Alu elements are amplified from the hyperactive master genes. Alu element is frequently involved in genomic rearrangements in the human genome due to its abundance and sequence identity between them. The genomic rearrangements caused by Alu elements could lead to genetic disorders such as hereditary disease, blood disorder, and neurological disorder. In fact, Alu elements are associated with approximately 0.1% of human genetic disorders. The first part of this review discusses mechanisms of Alu amplification and diversity among different Alu subfamilies. The second part discusses the particular role of Alu elements in generating genomic rearrangements as well as human genetic disorders.

  12. The Evolution of Personality Variation in Humans and Other Animals

    Science.gov (United States)

    Nettle, Daniel

    2006-01-01

    A comprehensive evolutionary framework for understanding the maintenance of heritable behavioral variation in humans is yet to be developed. Some evolutionary psychologists have argued that heritable variation will not be found in important, fitness-relevant characteristics because of the winnowing effect of natural selection. This article…

  13. A Model of Genetic Variation in Human Social Networks

    CERN Document Server

    Fowler, James H; Christakis, Nicholas A

    2008-01-01

    Social networks influence the evolution of cooperation and they exhibit strikingly systematic patterns across a wide range of human contexts. Both of these facts suggest that variation in the topological attributes of human social networks might have a genetic basis. While genetic variation accounts for a significant portion of the variation in many complex social behaviors, the heritability of egocentric social network attributes is unknown. Here we show that three of these attributes (in-degree, transitivity, and centrality) are heritable. We then develop a "mirror network" method to test extant network models and show that none accounts for observed genetic variation in human social networks. We propose an alternative "attract and introduce" model that generates significant heritability as well as other important network features, and we show that this model with two simple forms of heterogeneity is well suited to the modeling of real social networks in humans. These results suggest that natural selection ...

  14. Human gut microbiota: repertoire and variations.

    Science.gov (United States)

    Lagier, Jean-Christophe; Million, Matthieu; Hugon, Perrine; Armougom, Fabrice; Raoult, Didier

    2012-01-01

    The composition of human gut microbiota and their relationship with the host and, consequently, with human health and disease, presents several challenges to microbiologists. Originally dominated by culture-dependent methods for exploring this ecosystem, the advent of molecular tools has revolutionized our ability to investigate these relationships. However, many biases that have led to contradictory results have been identified. Microbial culturomics, a recent concept based on a use of several culture conditions with identification by MALDI-TOF followed by the genome sequencing of the new species cultured had allowed a complementarity with metagenomics. Culturomics allowed to isolate 31 new bacterial species, the largest human virus, the largest bacteria, and the largest Archaea from human. Moreover, some members of this ecosystem, such as Eukaryotes, giant viruses, Archaea, and Planctomycetes, have been neglected by the majority of studies. In addition, numerous factors, such as age, geographic provenance, dietary habits, antibiotics, or probiotics, can influence the composition of the microbiota. Finally, in addition to the countless biases associated with the study techniques, a considerable limitation to the interpretation of studies of human gut microbiota is associated with funding sources and transparency disclosures. In the future, studies independent of food industry funding and using complementary methods from a broad range of both culture-based and molecular tools will increase our knowledge of the repertoire of this complex ecosystem and host-microbiota mutualism.

  15. Variational adaptive image denoising model based on human visual system

    Science.gov (United States)

    Li, Wenjun; Liu, Chanjuan; Zou, Hailin

    2011-11-01

    A variational image adaptive denoising model based on human visual system is proposed by introducing control parameter p which can determine the diffusion intensity to Total Variation (TV) model. The model can adaptively select the value of parameter p according to human visual system noise visibility value of each pixel which makes diffusion intensity close to edges smaller than those far away from edges. For this method is more consistent with human perception, human eyes can perceive the improvement of image quality intuitively. Numerical experiments show that the proposed method can overcome staircase effect, remove the noise while preserving significant image details and better performance has been achieved.

  16. Variational and linearly implicit integrators, with applications

    OpenAIRE

    Tao, Molei; Owhadi, Houman

    2016-01-01

    We show that symplectic and linearly implicit integrators proposed by Zhang & Skeel (1997, Cheap implicit symplectic integrators. Appl. Numer. Math., 25, 297–302) are variational linearizations of Newmark methods. When used in conjunction with penalty methods (i.e., methods that replace constraints by stiff potentials), these integrators permit coarse time-stepping of holonomically constrained mechanical systems and bypass the resolution of nonlinear systems. Although penalty methods are wide...

  17. Genetic variation and the de novo assembly of human genomes.

    Science.gov (United States)

    Chaisson, Mark J P; Wilson, Richard K; Eichler, Evan E

    2015-11-01

    The discovery of genetic variation and the assembly of genome sequences are both inextricably linked to advances in DNA-sequencing technology. Short-read massively parallel sequencing has revolutionized our ability to discover genetic variation but is insufficient to generate high-quality genome assemblies or resolve most structural variation. Full resolution of variation is only guaranteed by complete de novo assembly of a genome. Here, we review approaches to genome assembly, the nature of gaps or missing sequences, and biases in the assembly process. We describe the challenges of generating a complete de novo genome assembly using current technologies and the impact that being able to perfectly sequence the genome would have on understanding human disease and evolution. Finally, we summarize recent technological advances that improve both contiguity and accuracy and emphasize the importance of complete de novo assembly as opposed to read mapping as the primary means to understanding the full range of human genetic variation.

  18. Variation of Human Salivary O-Glycome.

    Directory of Open Access Journals (Sweden)

    Radoslaw P Kozak

    Full Text Available The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. Saliva is rich in glycoproteins which are secreted from the bloodstream or produced by salivary glands. Mucins, which are highly O-glycosylated proteins, are particularly abundant in human saliva. Their glycosylation is associated with blood group and secretor status, and represents a reservoir of potential disease biomarkers. This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR coupled to electrospray ionization mass spectrometry (ESI-MS/MS. The sample preparation method showed excellent reproducibility and can therefore be used for biomarker discovery. Our data demonstrates that the O-glycosylation in human saliva changes significantly during the day. These changes may be related to changes in the salivary concentrations of specific proteins.

  19. Normal human variation: refocussing the enhancement debate.

    Science.gov (United States)

    Kahane, Guy; Savulescu, Julian

    2015-02-01

    This article draws attention to several common mistakes in thinking about biomedical enhancement, mistakes that are made even by some supporters of enhancement. We illustrate these mistakes by examining objections that John Harris has recently raised against the use of pharmacological interventions to directly modulate moral decision-making. We then apply these lessons to other influential figures in the debate about enhancement. One upshot of our argument is that many considerations presented as powerful objections to enhancement are really strong considerations in favour of biomedical enhancement, just in a different direction. Another upshot is that it is unfortunate that much of the current debate focuses on interventions that will radically transform normal human capacities. Such interventions are unlikely to be available in the near future, and may not even be feasible. But our argument shows that the enhancement project can still have a radical impact on human life even if biomedical enhancement operated entirely within the normal human range. © 2013 The Authors. Bioethics published by John Wiley & Sons Ltd.

  20. Variations in microanatomy of the human cochlea.

    Science.gov (United States)

    Avci, Ersin; Nauwelaers, Tim; Lenarz, Thomas; Hamacher, Volkmar; Kral, Andrej

    2014-10-01

    The human cochlea shows considerable interindividual variability in size and morphology. In order to develop atraumatic cochlear implant (CI) electrodes, high-precision details of the variability of human anatomy are required. Sixteen human temporal bones were cut around the cochlea in blocks of approximately 3.5 × 3.5 cm. The bones were scanned by using a Skyscan 1173 micro-computed tomography (μCT) device. Mimics software (Materialise, Leuven, Belgium) was used to segment out the scala tympani (ST) from the μCT images. A three-dimensional surface model of the segmented area was generated for each cochlea. Cross-sectional images were taken and analyzed by custom-designed software in MATLAB. Comparison of different STs showed large variability in cross-sectional diameter (CSD), vertical trajectory, and height of the ST. Relative standard deviations of the CSD were between 9 and 15%. Heights measured at the center of the ST exceeded those in the modiolar and lateral regions of the scala. At the lateral region, the height decreased significantly at the beginning of the second turn. In the vertical trajectory, critical anatomic features were observed, such as dips, vertical jumps, and peaks. Rosenthal's canal (RC) extended to between 560 and 650°. We found a correlation between the length of the RC and that of the ST. The ST was segmented and the internal dimensions measured by using μCT. We observed large dimensional variability between different STs. These differences could have considerable implications for approaches to the design of CI arrays, especially in terms of their ability to preserve residual hearing during insertion of the electrode array. © 2014 Wiley Periodicals, Inc.

  1. Human performance variation analysis: A process for human performance problem solving

    Directory of Open Access Journals (Sweden)

    Anerie Rademeyer

    2009-04-01

    Full Text Available Problem-solving ability is a much sought-after trait in executives, especially if it includes the ability to solve human performance problems. This paper proposes a systematic root cause analysis process that effectively and consistently uncovers the root causes of human performance problems and controls the causes in a way that prevents the problems from recurring. Applying action research the study brings into being a Human Performance Variation Analysis (HPVA process, which consists of three phases: (1 performance variation assessment, (2 performance variation analysis, and (3 performance variation resolution. The HPVA provides much-needed capability in solving human performance problems in organisations.

  2. Human Footprint Variation while Performing Load Bearing Tasks

    OpenAIRE

    Wall-Scheffler, Cara M.; Wagnild, Janelle; Wagler, Emily

    2015-01-01

    Human footprint fossils have provided essential evidence about the evolution of human bipedalism as well as the social dynamics of the footprint makers, including estimates of speed, sex and group composition. Generally such estimates are made by comparing footprint evidence with modern controls; however, previous studies have not accounted for the variation in footprint dimensions coming from load bearing activities. It is likely that a portion of the hominins who created these fossil footpr...

  3. Landscape and variation of novel retroduplications in 26 human populations.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2017-06-01

    Full Text Available Retroduplications come from reverse transcription of mRNAs and their insertion back into the genome. Here, we performed comprehensive discovery and analysis of retroduplications in a large cohort of 2,535 individuals from 26 human populations, as part of 1000 Genomes Phase 3. We developed an integrated approach to discover novel retroduplications combining high-coverage exome and low-coverage whole-genome sequencing data, utilizing information from both exon-exon junctions and discordant paired-end reads. We found 503 parent genes having novel retroduplications absent from the reference genome. Based solely on retroduplication variation, we built phylogenetic trees of human populations; these represent superpopulation structure well and indicate that variable retroduplications are effective population markers. We further identified 43 retroduplication parent genes differentiating superpopulations. This group contains several interesting insertion events, including a SLMO2 retroduplication and insertion into CAV3, which has a potential disease association. We also found retroduplications to be associated with a variety of genomic features: (1 Insertion sites were correlated with regular nucleosome positioning. (2 They, predictably, tend to avoid conserved functional regions, such as exons, but, somewhat surprisingly, also avoid introns. (3 Retroduplications tend to be co-inserted with young L1 elements, indicating recent retrotranspositional activity, and (4 they have a weak tendency to originate from highly expressed parent genes. Our investigation provides insight into the functional impact and association with genomic elements of retroduplications. We anticipate our approach and analytical methodology to have application in a more clinical context, where exome sequencing data is abundant and the discovery of retroduplications can potentially improve the accuracy of SNP calling.

  4. Variational principles of continuum mechanics. Vol. 2. Applications

    Energy Technology Data Exchange (ETDEWEB)

    Berdichevsky, Victor L. [Wayne State Univ., Detroit, MI (United States). Dept. of Mechanical Engineering

    2009-07-01

    The book reviews the two features of the variational approach: its use as a universal tool to describe physical phenomena and as a source for qualitative and quantitative methods of studying particular problems. Berdichevsky's work differs from other books on the subject in focusing mostly on the physical origin of variational principles as well as establishing their interrelations. For example, the Gibbs principles appear as a consequence of the Einstein formula for thermodynamic fluctuations rather than as the first principles of the theory of thermodynamic equilibrium. Mathematical issues are considered as long as they shed light on the physical outcomes and/or provide a useful technique for the direct study of variational problems. In addition, a thorough account of variational principles discovered in various branches of continuum mechanics is given. This book, the second volume, describes how the variational approach can be applied to constructing models of continuum media, such as the theory of elastic plates; shells and beams; shallow water theory; heterogeneous mixtures; granular materials; and turbulence. It goes on to apply the variational approach to asymptotical analysis of problems with small parameters, such as the derivation of the theory of elastic plates, shells and beams from three-dimensional elasticity theory; and the basics of homogenization theory. A theory of stochastic variational problems is considered in detail too, along with applications to the homogenization of continua with random microstructures. (orig.)

  5. Application of New Variational Homotopy Perturbation Method For ...

    African Journals Online (AJOL)

    This paper discusses the application of the New Variational Homotopy Perturbation Method (NVHPM) for solving integro-differential equations. The advantage of the new Scheme is that it does not require discretization, linearization or any restrictive assumption of any form be fore it is applied. Several test problems are ...

  6. Demography and ecology drive variation in cooperation across human populations.

    Science.gov (United States)

    Lamba, Shakti; Mace, Ruth

    2011-08-30

    Recent studies argue that cross-cultural variation in human cooperation supports cultural group selection models of the evolution of large-scale cooperation. However, these studies confound cultural and environmental differences between populations by predominantly sampling one population per society. Here, we test the hypothesis that behavioral variation between populations is driven by environmental differences in demography and ecology. We use a public goods game played with money and a naturalistic measure of behavior involving the distribution of salt, an essential and locally valued resource, to demonstrate significant variation in levels of cooperation across 16 discrete populations of the same small-scale society, the Pahari Korwa of central India. Variation between these populations of the same cultural group is comparable to that found between different cultural groups in previous studies. Demographic factors partly explain this variation; age and a measure of social network size are associated with contributions in the public goods game, while population size and the number of adult sisters residing in the population are associated with decisions regarding salt. That behavioral variation is at least partly contingent on environmental differences between populations questions the existence of stable norms of cooperation. Hence, our findings call for reinterpretation of cross-cultural data on cooperation. Although cultural group selection could theoretically explain the evolution of large-scale cooperation, our results make clear that existing cross-cultural data cannot be taken as empirical support for this hypothesis.

  7. Variation in human gape cycle kinematics and occlusal topography.

    Science.gov (United States)

    Laird, Myra F

    2017-11-01

    This study tested hypotheses relating intraspecific variation in occlusal morphology and intraspecific variation in jaw movements during feeding. Gape cycle kinematic variation was hypothesized to correlate with gape cycle number within a chewing sequence as well as with food toughness and stiffness. Gape cycle kinematic variation was also hypothesized to correlate with variation in occlusal area, slope, and volume. Twenty-six adult human subjects chewed four foods with varying material properties while their jaw movements were recorded using three-dimensional coordinates of facial markers captured with a Vicon camera system. Post-canine occlusal morphology of each subject was quantified in ArcGIS using dental topographic analysis of dental casts. Gape cycle duration did not vary with gape cycle number, food toughness, or food stiffness. Gape cycle vertical and lateral displacement correlated negatively with gape cycle number, while foods with higher toughness and Young's modulus had greater jaw vertical and lateral displacement. Subjects with steeper occlusal slopes had longer gape cycle durations and greater amounts of vertical displacement during the slow closing phase of the gape cycle. The results suggest that gape cycle durations are relatively consistent despite changes in food properties and gape cycle number, while occlusal slope affects gape cycle duration and vertical displacement during inferred occlusal contact. However, gape cycle number and bolus properties explain greater amounts of kinematic variation than does occlusal morphology. © 2017 Wiley Periodicals, Inc.

  8. DNA methylation-based variation between human populations.

    Science.gov (United States)

    Kader, Farzeen; Ghai, Meenu

    2017-02-01

    Several studies have proved that DNA methylation affects regulation of gene expression and development. Epigenome-wide studies have reported variation in methylation patterns between populations, including Caucasians, non-Caucasians (Blacks), Hispanics, Arabs, and numerous populations of the African continent. Not only has DNA methylation differences shown to impact externally visible characteristics, but is also a potential biomarker for underlying racial health disparities between human populations. Ethnicity-related methylation differences set their mark during early embryonic development. Genetic variations, such as single-nucleotide polymorphisms and environmental factors, such as age, dietary folate, socioeconomic status, and smoking, impacts DNA methylation levels, which reciprocally impacts expression of phenotypes. Studies show that it is necessary to address these external influences when attempting to differentiate between populations since the relative impacts of these factors on the human methylome remain uncertain. The present review summarises several reported attempts to establish the contribution of differential DNA methylation to natural human variation, and shows that DNA methylation could represent new opportunities for risk stratification and prevention of several diseases amongst populations world-wide. Variation of methylation patterns between human populations is an exciting prospect which inspires further valuable research to apply the concept in routine medical and forensic casework. However, trans-generational inheritance needs to be quantified to decipher the proportion of variation contributed by DNA methylation. The future holds thorough evaluation of the epigenome to understand quantification, heritability, and the effect of DNA methylation on phenotypes. In addition, methylation profiling of the same ethnic groups across geographical locations will shed light on conserved methylation differences in populations.

  9. Human footprint variation while performing load bearing tasks.

    Directory of Open Access Journals (Sweden)

    Cara M Wall-Scheffler

    Full Text Available Human footprint fossils have provided essential evidence about the evolution of human bipedalism as well as the social dynamics of the footprint makers, including estimates of speed, sex and group composition. Generally such estimates are made by comparing footprint evidence with modern controls; however, previous studies have not accounted for the variation in footprint dimensions coming from load bearing activities. It is likely that a portion of the hominins who created these fossil footprints were carrying a significant load, such as offspring or foraging loads, which caused variation in the footprint which could extend to variation in any estimations concerning the footprint's maker. To identify significant variation in footprints due to load-bearing tasks, we had participants (N = 30, 15 males and 15 females walk at a series of speeds carrying a 20kg pack on their back, side and front. Paint was applied to the bare feet of each participant to create footprints that were compared in terms of foot length, foot width and foot area. Female foot length and width increased during multiple loaded conditions. An appreciation of footprint variability associated with carrying loads adds an additional layer to our understanding of the behavior and morphology of extinct hominin populations.

  10. Human footprint variation while performing load bearing tasks.

    Science.gov (United States)

    Wall-Scheffler, Cara M; Wagnild, Janelle; Wagler, Emily

    2015-01-01

    Human footprint fossils have provided essential evidence about the evolution of human bipedalism as well as the social dynamics of the footprint makers, including estimates of speed, sex and group composition. Generally such estimates are made by comparing footprint evidence with modern controls; however, previous studies have not accounted for the variation in footprint dimensions coming from load bearing activities. It is likely that a portion of the hominins who created these fossil footprints were carrying a significant load, such as offspring or foraging loads, which caused variation in the footprint which could extend to variation in any estimations concerning the footprint's maker. To identify significant variation in footprints due to load-bearing tasks, we had participants (N = 30, 15 males and 15 females) walk at a series of speeds carrying a 20kg pack on their back, side and front. Paint was applied to the bare feet of each participant to create footprints that were compared in terms of foot length, foot width and foot area. Female foot length and width increased during multiple loaded conditions. An appreciation of footprint variability associated with carrying loads adds an additional layer to our understanding of the behavior and morphology of extinct hominin populations.

  11. The impact of human copy number variation on gene expression.

    Science.gov (United States)

    Gamazon, Eric R; Stranger, Barbara E

    2015-09-01

    Recent years have witnessed a flurry of important technological and methodological developments in the discovery and analysis of copy number variations (CNVs), which are increasingly enabling the systematic evaluation of their impact on a broad range of phenotypes from molecular-level (intermediate) traits to higher-order clinical phenotypes. Like single nucleotide variants in the human genome, CNVs have been linked to complex traits in humans, including disease and drug response. These recent developments underscore the importance of incorporating complex forms of genetic variation into disease mapping studies and promise to transform our understanding of genome function and the genetic basis of disease. Here we review some of the findings that have emerged from transcriptome studies of CNVs facilitated by the rapid advances in -omics technologies and corresponding methodologies. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. The Human Pelvis: Variation in Structure and Function During Gait.

    Science.gov (United States)

    Lewis, Cara L; Laudicina, Natalie M; Khuu, Anne; Loverro, Kari L

    2017-04-01

    The shift to habitual bipedalism 4-6 million years ago in the hominin lineage created a morphologically and functionally different human pelvis compared to our closest living relatives, the chimpanzees. Evolutionary changes to the shape of the pelvis were necessary for the transition to habitual bipedalism in humans. These changes in the bony anatomy resulted in an altered role of muscle function, influencing bipedal gait. Additionally, there are normal sex-specific variations in the pelvis as well as abnormal variations in the acetabulum. During gait, the pelvis moves in the three planes to produce smooth and efficient motion. Subtle sex-specific differences in these motions may facilitate economical gait despite differences in pelvic structure. The motions of the pelvis and hip may also be altered in the presence of abnormal acetabular structure, especially with acetabular dysplasia. Anat Rec, 300:633-642, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Nonneutral mitochondrial DNA variation in humans and chimpanzees

    Energy Technology Data Exchange (ETDEWEB)

    Nachman, M.W.; Aquadro, C.F. [Cornell Univ., Ithaca, NY (United States); Brown, W.M. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others

    1996-03-01

    We sequenced the NADH dehydrogenase subunit 3 (ND3) gene from a sample of 61 humans, five common chimpanzees, and one gorilla to test whether patterns of mitochondrial DNA (mtDNA) variation are consistent with a neutral model of molecular evolution. Within humans and within chimpanzees, the ratio of replacement to silent nucleotide substitutions was higher than observed in comparisons between species, contrary to neutral expectations. To test the generality of this result, we reanalyzed published human RFLP data from the entire mitochondrial genome. Gains of restriction sites relative to a known human mtDNA sequence were used to infer unambiguous nucleotide substitutions. We also compared the complete mtDNA sequences of three humans. Both the RFLP data and the sequence data reveal a higher ratio of replacement to silent nucleotide substitutions within humans than is seen between species. This pattern is observed at most or all human mitochondrial genes and is inconsistent with a strictly neutral model. These data suggest that many mitochondrial protein polymorphisms are slightly deleterious, consistent with studies of human mitochondrial diseases. 59 refs., 2 figs., 8 tabs.

  14. The study of human Y chromosome variation through ancient DNA.

    Science.gov (United States)

    Kivisild, Toomas

    2017-05-01

    High throughput sequencing methods have completely transformed the study of human Y chromosome variation by offering a genome-scale view on genetic variation retrieved from ancient human remains in context of a growing number of high coverage whole Y chromosome sequence data from living populations from across the world. The ancient Y chromosome sequences are providing us the first exciting glimpses into the past variation of male-specific compartment of the genome and the opportunity to evaluate models based on previously made inferences from patterns of genetic variation in living populations. Analyses of the ancient Y chromosome sequences are challenging not only because of issues generally related to ancient DNA work, such as DNA damage-induced mutations and low content of endogenous DNA in most human remains, but also because of specific properties of the Y chromosome, such as its highly repetitive nature and high homology with the X chromosome. Shotgun sequencing of uniquely mapping regions of the Y chromosomes to sufficiently high coverage is still challenging and costly in poorly preserved samples. To increase the coverage of specific target SNPs capture-based methods have been developed and used in recent years to generate Y chromosome sequence data from hundreds of prehistoric skeletal remains. Besides the prospects of testing directly as how much genetic change in a given time period has accompanied changes in material culture the sequencing of ancient Y chromosomes allows us also to better understand the rate at which mutations accumulate and get fixed over time. This review considers genome-scale evidence on ancient Y chromosome diversity that has recently started to accumulate in geographic areas favourable to DNA preservation. More specifically the review focuses on examples of regional continuity and change of the Y chromosome haplogroups in North Eurasia and in the New World.

  15. Genome-wide associations of gene expression variation in humans.

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    2005-12-01

    Full Text Available The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis- to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

  16. Genome-Wide Associations of Gene Expression Variation in Humans.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis- to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

  17. Morphological variation in great ape and modern human mandibles

    Science.gov (United States)

    HUMPHREY, L. T.; DEAN, M. C.; STRINGER, C. B.

    1999-01-01

    Adult mandibles of 317 modern humans and 91 great apes were selected that showed no pathology. Adult mandibles of Pan troglodytes troglodytes, Pongo pygmaeus pygmaeus and Gorilla gorilla gorilla and from 2 modern human populations (Zulu and Europeans from Spitalfields) were reliably sexed. Thirteen measurements were defined and included mandibular height, length and breadth in representative positions. Univariate statistical techniques and multivariate (principal component analysis and discriminant analysis) statistical techniques were used to investigate interspecific variability and sexual dimorphism in human and great ape mandibles, and intraspecific variability among the modern human mandibles. Analysis of interspecific differences revealed some pairs of variables with a tight linear relationship and others where Homo and the great apes pulled apart from one another due to shape differences. Homo and Pan are least sexually dimorphic in the mandible, Pan less so than Homo sapiens, but both the magnitude of sexual dimorphism and the distribution of sexually dimorphic measurements varied both among and between modern humans and great apes. Intraspecific variation among the 10 populations of modern humans was less than that generally reported in studies of crania (74.3% of mandibles were correctly classified into 1 of 10 populations using discriminant functions based on 13 variables as compared with 93% of crania from 17 populations based on 70 variables in one extensive study of crania). A subrecent European population (Poundbury) emerged as more different from a recent European population (Spitalfields) than other more diverse modern populations were from each other, suggesting considerable morphological plasticity in the mandible through time. This study forms a sound basis on which to explore mandibular variation in Neanderthals, early Homo sapiens and other more ancient fossil hominids. PMID:10634689

  18. Human genetic variation is associated with Plasmodium falciparum drug resistance.

    Science.gov (United States)

    Paganotti, Giacomo M; Gallo, Baba C; Verra, Federica; Sirima, Bienvenu S; Nebié, Issa; Diarra, Amidou; Coluzzi, Mario; Modiano, David

    2011-12-01

    One approach to investigate if human genetic variation influences the selection of Plasmodium falciparum drug resistance is to compare the frequency of resistant infections among human populations differing in their genetic background and living in the same epidemiological context. A further complementary approach consists in comparing drug resistance among subjects differing for genes involved in drug metabolism. Here we report, from malariological surveys performed in Burkina Faso, that the prevalence of P. falciparum chloroquine-resistant infections (pfcrt 76T and/or pfmdr1 86Y alleles) differs among sympatric ethnic groups, being higher in the Mossi and Rimaibé groups than in the Fulani group (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.27-3.92; P = .007). The association analysis revealed that the human CYP2C8*2 variant, known to determine a poor drug metabolizer phenotype, was associated with P. falciparum chloroquine-resistant infections (OR, 1.66; 95% CI, 1.13-2.43; P = .008). This variant is more frequent in the Mossi-Rimaibé group (23.7% ± 1.4%) than in the Fulani group (9.9% ± 2.5%; P = .0003). This study provides an example of how host genetic variation may influence the selection dynamics of a pathogen's drug resistance.

  19. Variational image segmentation for endoscopic human colonic aberrant crypt foci.

    Science.gov (United States)

    Figueiredo, Isabel N; Figueiredo, Pedro N; Stadler, Georg; Ghattas, Omar; Araujo, Adérito

    2010-04-01

    The aim of this paper is to introduce a variational image segmentation method for assessing the aberrant crypt foci (ACF) in the human colon captured in vivo by endoscopy. ACF are thought to be precursors for colorectal cancer, and therefore their early detection may play an important clinical role. We enhance the active contours without edges model of Chan and Vese to account for the ACF's particular structure. We employ level sets to represent the segmentation boundaries and discretize in space by finite elements and in (artificial) time by finite differences. The approach is able to identify the ACF, their boundaries, and some of the internal crypts' orifices.

  20. Genome Architecture and Its Roles in Human Copy Number Variation

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-12-01

    Full Text Available Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs, are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.

  1. Human feeding biomechanics: performance, variation, and functional constraints

    Directory of Open Access Journals (Sweden)

    Justin A. Ledogar

    2016-07-01

    Full Text Available The evolution of the modern human (Homo sapiens cranium is characterized by a reduction in the size of the feeding system, including reductions in the size of the facial skeleton, postcanine teeth, and the muscles involved in biting and chewing. The conventional view hypothesizes that gracilization of the human feeding system is related to a shift toward eating foods that were less mechanically challenging to consume and/or foods that were processed using tools before being ingested. This hypothesis predicts that human feeding systems should not be well-configured to produce forceful bites and that the cranium should be structurally weak. An alternate hypothesis, based on the observation that humans have mechanically efficient jaw adductors, states that the modern human face is adapted to generate and withstand high biting forces. We used finite element analysis (FEA to test two opposing mechanical hypotheses: that compared to our closest living relative, chimpanzees (Pan troglodytes, the modern human craniofacial skeleton is (1 less well configured, or (2 better configured to generate and withstand high magnitude bite forces. We considered intraspecific variation in our examination of human feeding biomechanics by examining a sample of geographically diverse crania that differed notably in shape. We found that our biomechanical models of human crania had broadly similar mechanical behavior despite their shape variation and were, on average, less structurally stiff than the crania of chimpanzees during unilateral biting when loaded with physiologically-scaled muscle loads. Our results also show that modern humans are efficient producers of bite force, consistent with previous analyses. However, highly tensile reaction forces were generated at the working (biting side jaw joint during unilateral molar bites in which the chewing muscles were recruited with bilateral symmetry. In life, such a configuration would have increased the risk of joint

  2. Human feeding biomechanics: performance, variation, and functional constraints

    Science.gov (United States)

    Dechow, Paul C.; Wang, Qian; Gharpure, Poorva H.; Baab, Karen L.; Smith, Amanda L.; Weber, Gerhard W.; Grosse, Ian R.; Ross, Callum F.; Richmond, Brian G.; Wright, Barth W.; Byron, Craig; Wroe, Stephen; Strait, David S.

    2016-01-01

    The evolution of the modern human (Homo sapiens) cranium is characterized by a reduction in the size of the feeding system, including reductions in the size of the facial skeleton, postcanine teeth, and the muscles involved in biting and chewing. The conventional view hypothesizes that gracilization of the human feeding system is related to a shift toward eating foods that were less mechanically challenging to consume and/or foods that were processed using tools before being ingested. This hypothesis predicts that human feeding systems should not be well-configured to produce forceful bites and that the cranium should be structurally weak. An alternate hypothesis, based on the observation that humans have mechanically efficient jaw adductors, states that the modern human face is adapted to generate and withstand high biting forces. We used finite element analysis (FEA) to test two opposing mechanical hypotheses: that compared to our closest living relative, chimpanzees (Pan troglodytes), the modern human craniofacial skeleton is (1) less well configured, or (2) better configured to generate and withstand high magnitude bite forces. We considered intraspecific variation in our examination of human feeding biomechanics by examining a sample of geographically diverse crania that differed notably in shape. We found that our biomechanical models of human crania had broadly similar mechanical behavior despite their shape variation and were, on average, less structurally stiff than the crania of chimpanzees during unilateral biting when loaded with physiologically-scaled muscle loads. Our results also show that modern humans are efficient producers of bite force, consistent with previous analyses. However, highly tensile reaction forces were generated at the working (biting) side jaw joint during unilateral molar bites in which the chewing muscles were recruited with bilateral symmetry. In life, such a configuration would have increased the risk of joint dislocation and

  3. Variational analysis of regular mappings theory and applications

    CERN Document Server

    Ioffe, Alexander D

    2017-01-01

    This monograph offers the first systematic account of (metric) regularity theory in variational analysis. It presents new developments alongside classical results and demonstrates the power of the theory through applications to various problems in analysis and optimization theory. The origins of metric regularity theory can be traced back to a series of fundamental ideas and results of nonlinear functional analysis and global analysis centered around problems of existence and stability of solutions of nonlinear equations. In variational analysis, regularity theory goes far beyond the classical setting and is also concerned with non-differentiable and multi-valued operators. The present volume explores all basic aspects of the theory, from the most general problems for mappings between metric spaces to those connected with fairly concrete and important classes of operators acting in Banach and finite dimensional spaces. Written by a leading expert in the field, the book covers new and powerful techniques, whic...

  4. DNA methylation variation of human-specific Alu repeats

    Science.gov (United States)

    Bakshi, Arundhati; Herke, Scott W.; Batzer, Mark A.; Kim, Joomyeong

    2016-01-01

    ABSTRACT DNA methylation is the major repression mechanism for human retrotransposons, such as the Alu family. Here, we have determined the methylation levels associated with 5238 loci belonging to 2 Alu subfamilies, AluYa5 and AluYb8, using high-throughput targeted repeat element bisulfite sequencing (HT-TREBS). The results indicate that ∼90% of loci are repressed by high methylation levels. Of the remaining loci, many of the hypomethylated elements are found near gene promoters and show high levels of DNA methylation variation. We have characterized this variation in the context of tumorigenesis and interindividual differences. Comparison of a primary breast tumor and its matched normal tissue revealed early DNA methylation changes in ∼1% of AluYb8 elements in response to tumorigenesis. Simultaneously, AluYa5/Yb8 elements proximal to promoters also showed differences in methylation of up to one order of magnitude, even between normal individuals. Overall, the current study demonstrates that early loss of methylation occurs during tumorigenesis in a subset of young Alu elements, suggesting their potential clinical relevance. However, approaches such as deep-bisulfite-sequencing of individual loci using HT-TREBS are required to distinguish clinically relevant loci from the background observed for AluYa5/Yb8 elements in general with regard to high levels of interindividual variation in DNA methylation. PMID:26890526

  5. Quantifying variation in human scalp hair fiber shape and pigmentation.

    Science.gov (United States)

    Lasisi, Tina; Ito, Shosuke; Wakamatsu, Kazumasa; Shaw, Colin N

    2016-06-01

    This study aims to evaluate the use of quantitative methods of measuring variation in scalp hair fiber shape and pigmentation and carry out exploratory data analysis on a limited sample of individuals from diverse populations in order to inform future avenues of research for the evolution of modern human hair variation. Cross-sectional area and shape and average curvature of scalp hair fibers were quantified using ImageJ. Pigmentation was analyzed using chemical methods estimating total melanin content through spectrophotometric methods, and eumelanin and pheomelanin content through HLPC analysis of melanin-specific degradation products. The initial results reinforced findings from earlier, traditional studies. African and African Diaspora scalp hair was significantly curled, (East) Asian hair was significantly thick, and European hair was significantly lighter in color. However, pigmentation analyses revealed a high level of variability in the melanin content of non-European populations and analysis of curvature found a large range of variation in the average curvature of East African individuals. Overall, these results suggest the usefulness of chemical methods for the elucidation of nonperceptible differences in scalp hair color and highlight the need for improvements in our assessment and understanding of hair fiber curvature. Am J Phys Anthropol 160:341-352, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Variation in the SHC1 gene and longevity in humans.

    Science.gov (United States)

    Mooijaart, Simon P; van Heemst, Diana; Schreuder, Jeroen; van Gerwen, Suzan; Beekman, Marian; Brandt, Bernd W; Eline Slagboom, P; Westendorp, Rudi G J

    2004-02-01

    Mice in which the p66(SHC) specific region of the SHC gene is deleted live 30% longer without apparent disease. These mice have lower levels of oxidative stress and apoptosis, both of which have been linked to old age survival in man. This makes SHC1 an important candidate gene for longevity in humans. We found no variations in the p66 specific region of the SHC1 gene in 30 young and 30 extreme long-lived subjects. Thus in man, no common sequence variations occur in p66 specific region of the SHC1 gene. In two independent cohorts of respectively 730 and 563 subjects aged 85 and over, we tested the only known non-synonymous polymorphism, Met(410)Val, for association with longevity using a prospective follow-up design. In the first cohort, we found increasing valine allele frequency in three strata of increasing age at death (2.8-5.2%). Moreover, compared to Met/Met carriers, mortality rate was a factor of 0.71 (95% CI 0.45-1.13) reduced for Met/Val carriers in the combined cohorts, with similar risk estimates in both cohorts. Low valine allele frequency resulted, however, in low power to detect statistical significance. These data suggest that an association between the Met(410)Val polymorphism and longevity in humans may exist.

  7. Morphological structure and variations of lumbar plexus in human fetuses.

    Science.gov (United States)

    Yasar, Soner; Kaya, Serdar; Temiz, Cağlar; Tehli, Ozkan; Kural, Cahit; Izci, Yusuf

    2014-04-01

    The objective of this study is to study the anatomy of lumbar plexus on human fetuses and to establish its morphometric characteristics and differences compared with adults. Twenty lumbar plexus of 10 human fetal cadavers in different gestational ages and genders were dissected. Lumbar spinal nerves, ganglions, and peripheral nerves were exposed. Normal anatomical structure and variations of lumbar plexus were investigated and morphometric analyses were performed. The diameters of lumbar spinal nerves increased from L1 to L4. The thickest nerve forming the plexus was femoral nerve, the thinnest was ilioinguinal nerve, the longest nerve through posterior abdominal wall was iliohypogastric nerve, and the shortest nerve was femoral nerve. Each plexus had a single furcal nerve and this arose from L4 nerve in all fetuses. No prefix or postfix plexus variation was observed. In two plexuses, L1 nerve was in the form of a single branch. Also, in two plexuses, genitofemoral nerve arose only from L2 nerve. Accessory obturator nerve was observed in four plexuses. According to these findings, the morphological pattern of the lumbar plexus in the fetus was found to be very similar to the lumbar plexus in adults. Copyright © 2012 Wiley Periodicals, Inc.

  8. Genetic and metabolic determinants of human epigenetic variation.

    Science.gov (United States)

    Haggarty, Paul

    2015-07-01

    Epigenetics has emerged in recent years as one of the most important biological mechanisms linking exposures across the life course to long-term health. This article reviews recent developments in our understanding of the metabolic and genetic determinants of epigenetic variation in human populations. Epigenetic status is influenced by a range of environmental exposures, including diet and nutrition, social status, the early emotional environment, and infertility and its treatment. The period around conception is particularly sensitive to environmental exposures with evidence for effects on epigenetic imprinting within the offspring. Epigenetic status is also influenced by genotype, and genetic variation in methylene tetrahydrofolate reductase, and the DNA methytransferase and ten-eleven translocation methylcytosine dioxygenase proteins has been linked to the epigenetic status, biological function and disease. Epigenetics is at the heart of a series of feedback loops linking the environment to the human genome in a way that allows crosstalk between the genome and the environment it exists within. It offers the potential for modification of adverse epigenetic states resulting from events/exposures at earlier life stages. We need to better understand the nutritional programming of epigenetic states, the persistence of these marks in time and their effect on biological function and health in current and future generations.

  9. Environmental and biomedical applications of natural metal stable isotope variations

    Science.gov (United States)

    Bullen, T.D.; Walczyk, T.

    2009-01-01

    etal stable isotopes are now being used to trace metal contaminants in the environment and as indicators of human systemic function where metals play a role. Stable isotope abundance variations provide information about metal sources and the processes affecting metals in complex natural systems, complementing information gained from surrogate tracers, such as metal abundance ratios or biochemical markers of metal metabolism. The science is still in its infancy, but the results of initial studies confirm that metal stable isotopes can provide a powerful tool for forensic and biomedical investigations.

  10. Patterns of cis regulatory variation in diverse human populations.

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    Full Text Available The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for

  11. The offspring quantity–quality trade-off and human fertility variation

    Science.gov (United States)

    Lawson, David W.; Borgerhoff Mulder, Monique

    2016-01-01

    The idea that trade-offs between offspring quantity and quality shape reproductive behaviour has long been central to economic perspectives on fertility. It also has a parallel and richer theoretical foundation in evolutionary ecology. We review the application of the quantity–quality trade-off concept to human reproduction, emphasizing distinctions between clutch size and lifetime fertility, and the wider set of forces contributing to fertility variation in iteroparous and sexually reproducing species like our own. We then argue that in settings approximating human evolutionary history, several factors limit costly sibling competition. Consequently, while the optimization of quantity–quality trade-offs undoubtedly shaped the evolution of human physiology setting the upper limits of reproduction, we argue it plays a modest role in accounting for socio-ecological and individual variation in fertility. Only upon entering the demographic transition can fertility limitation be clearly interpreted as strategically orientated to advancing offspring quality via increased parental investment per child, with low fertility increasing descendant socio-economic success, although not reproductive success. We conclude that existing economic and evolutionary literature has often overemphasized the centrality of quantity–quality trade-offs to human fertility variation and advocate for the development of more holistic frameworks encompassing alternative life-history trade-offs and the evolved mechanisms guiding their resolution. PMID:27022072

  12. Cortical activity predicts good variation in human motor output.

    Science.gov (United States)

    Babikian, Sarine; Kanso, Eva; Kutch, Jason J

    2017-04-01

    Human movement patterns have been shown to be particularly variable if many combinations of activity in different muscles all achieve the same task goal (i.e., are goal-equivalent). The nervous system appears to automatically vary its output among goal-equivalent combinations of muscle activity to minimize muscle fatigue or distribute tissue loading, but the neural mechanism of this "good" variation is unknown. Here we use a bimanual finger task, electroencephalography (EEG), and machine learning to determine if cortical signals can predict goal-equivalent variation in finger force output. 18 healthy participants applied left and right index finger forces to repeatedly perform a task that involved matching a total (sum of right and left) finger force. As in previous studies, we observed significantly more variability in goal-equivalent muscle activity across task repetitions compared to variability in muscle activity that would not achieve the goal: participants achieved the task in some repetitions with more right finger force and less left finger force (right > left) and in other repetitions with less right finger force and more left finger force (left > right). We found that EEG signals from the 500 milliseconds (ms) prior to each task repetition could make a significant prediction of which repetitions would have right > left and which would have left > right. We also found that cortical maps of sites contributing to the prediction contain both motor and pre-motor representation in the appropriate hemisphere. Thus, goal-equivalent variation in motor output may be implemented at a cortical level.

  13. Global variation in copy number in the human genome.

    Science.gov (United States)

    Redon, Richard; Ishikawa, Shumpei; Fitch, Karen R; Feuk, Lars; Perry, George H; Andrews, T Daniel; Fiegler, Heike; Shapero, Michael H; Carson, Andrew R; Chen, Wenwei; Cho, Eun Kyung; Dallaire, Stephanie; Freeman, Jennifer L; González, Juan R; Gratacòs, Mònica; Huang, Jing; Kalaitzopoulos, Dimitrios; Komura, Daisuke; MacDonald, Jeffrey R; Marshall, Christian R; Mei, Rui; Montgomery, Lyndal; Nishimura, Kunihiro; Okamura, Kohji; Shen, Fan; Somerville, Martin J; Tchinda, Joelle; Valsesia, Armand; Woodwark, Cara; Yang, Fengtang; Zhang, Junjun; Zerjal, Tatiana; Zhang, Jane; Armengol, Lluis; Conrad, Donald F; Estivill, Xavier; Tyler-Smith, Chris; Carter, Nigel P; Aburatani, Hiroyuki; Lee, Charles; Jones, Keith W; Scherer, Stephen W; Hurles, Matthew E

    2006-11-23

    Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.

  14. Multiplication rate variation in the human malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Murray, Lee; Stewart, Lindsay B; Tarr, Sarah J; Ahouidi, Ambroise D; Diakite, Mahamadou; Amambua-Ngwa, Alfred; Conway, David J

    2017-07-25

    It is important to understand intrinsic variation in asexual blood stage multiplication rates of the most virulent human malaria parasite, Plasmodium falciparum. Here, multiplication rates of long-term laboratory adapted parasite clones and new clinical isolates were measured, using a newly standardised assay of growth from low starting density in replicate parallel cultures with erythrocytes from multiple different donors, across multiple cycles. Multiplication rates of long-term established clones were between 7.6 and 10.5 fold per 48 hours, with clone Dd2 having a higher rate than others (clones 3D7, HB3 and D10). Parasite clone-specific growth was then analysed in co-culture assays with all possible heterologous pairwise combinations. This showed that co-culture of different parasites did not affect their replication rates, indicating that there were no suppressive interactions operating between parasites. Multiplication rates of eleven new clinical isolates were measured after a few weeks of culture, and showed a spectrum of replication rates between 2.3 and 6.0 fold per 48 hours, the entire range being lower than for the long-term laboratory adapted clones. Multiplication rate estimates remained stable over time for several isolates tested repeatedly up to three months after culture initiation, indicating considerable persistence of this important trait variation.

  15. Human Variome Project Quality Assessment Criteria for Variation Databases.

    Science.gov (United States)

    Vihinen, Mauno; Hancock, John M; Maglott, Donna R; Landrum, Melissa J; Schaafsma, Gerard C P; Taschner, Peter

    2016-06-01

    Numerous databases containing information about DNA, RNA, and protein variations are available. Gene-specific variant databases (locus-specific variation databases, LSDBs) are typically curated and maintained for single genes or groups of genes for a certain disease(s). These databases are widely considered as the most reliable information source for a particular gene/protein/disease, but it should also be made clear they may have widely varying contents, infrastructure, and quality. Quality is very important to evaluate because these databases may affect health decision-making, research, and clinical practice. The Human Variome Project (HVP) established a Working Group for Variant Database Quality Assessment. The basic principle was to develop a simple system that nevertheless provides a good overview of the quality of a database. The HVP quality evaluation criteria that resulted are divided into four main components: data quality, technical quality, accessibility, and timeliness. This report elaborates on the developed quality criteria and how implementation of the quality scheme can be achieved. Examples are provided for the current status of the quality items in two different databases, BTKbase, an LSDB, and ClinVar, a central archive of submissions about variants and their clinical significance. © 2016 WILEY PERIODICALS, INC.

  16. Religious influences on human capital variations in imperial Russia

    Directory of Open Access Journals (Sweden)

    Tomila Lankina

    2012-01-01

    Full Text Available Historical legacies, particularly imperial tutelage and religion, have featured prominently in recent scholarship on political regime variations in post-communist settings, challenging earlier temporally proximate explanations. The overlap between tutelage, geography, and religion has complicated the uncovering of the spatially uneven effects of the various legacies. The author addresses this challenge by conducting sub-national analysis of religious influences within one imperial domain, Russia. In particular, the paper traces how European settlement in imperial Russia has had a bearing on human development in the imperial periphery. The causal mechanism that the paper proposes to account for this influence is the Western communities’ impact on literacy, which is in turn linked in the analysis to the Western Christian, particularly Protestant, roots, of settler populations. The author makes this case by constructing an original dataset based on sub-national data from the hitherto underutilised first imperial census of 1897.

  17. Variation in human performance in the hypoxic mountain environment.

    Science.gov (United States)

    Martin, Daniel S; Levett, Denny Z H; Grocott, Mike P W; Montgomery, Hugh E

    2010-03-01

    Ascent to altitude is associated with a fall in barometric pressure, and with it a decline in the partial pressure of atmospheric (and thus alveolar) oxygen. As a result, a variety of adaptive physiological processes are engaged to mitigate the fall in tissue convective oxygen delivery which might otherwise occur. The magnitude and nature of such changes is also modified with time, a process known as acclimatization. However, other phenomena are at work; the ability to perform physical work at altitude falls in a manner which is not wholly related to changes in arterial oxygen content. Indeed, alterations in local skeletal muscle blood flow and metabolism may play an axial role. Thus, for those who are not native to high altitude, the ability to compete at altitude is likely to be impaired. The magnitude of such impairment in performance, however, differs greatly between individuals, and it seems that genetic variation underpins much of this difference. The identification of the relevant genetic elements is in its infancy in humans, but ongoing work is likely to help us gain an increasing understanding of how humans adapt to altitude and to develop mitigating interventions.

  18. Complex variational mode decomposition for signal processing applications

    Science.gov (United States)

    Wang, Yanxue; Liu, Fuyun; Jiang, Zhansi; He, Shuilong; Mo, Qiuyun

    2017-03-01

    Complex-valued signals occur in many areas of science and engineering and are thus of fundamental interest. The complex variational mode decomposition (CVMD) is proposed as a natural and a generic extension of the original VMD algorithm for the analysis of complex-valued data in this work. Moreover, the equivalent filter bank structure of the CVMD in the presence of white noise, and the effects of initialization of center frequency on the filter bank property are both investigated via numerical experiments. Benefiting from the advantages of CVMD algorithm, its bi-directional Hilbert time-frequency spectrum is developed as well, in which the positive and negative frequency components are formulated on the positive and negative frequency planes separately. Several applications in the real-world complex-valued signals support the analysis.

  19. Human Genome Variation and the Concept of Genotype Networks

    Science.gov (United States)

    Dall'Olio, Giovanni Marco; Bertranpetit, Jaume; Wagner, Andreas; Laayouni, Hafid

    2014-01-01

    Genotype networks are a concept used in systems biology to study sets of genotypes having the same phenotype, and the ability of these to bring forth novel phenotypes. In the past they have been applied to determine the genetic heterogeneity, and stability to mutations, of systems such as metabolic networks and RNA folds. Recently, they have been the base for reconciling the neutralist and selectionist views on evolution. Here, we adapted this concept to the study of population genetics data. Specifically, we applied genotype networks to the human 1000 genomes dataset, and analyzed networks composed of short haplotypes of Single Nucleotide Variants (SNV). The result is a scan of how properties related to genetic heterogeneity and stability to mutations are distributed along the human genome. We found that genes involved in acquired immunity, such as some HLA and MHC genes, tend to have the most heterogeneous and connected networks, and that coding regions tend to be more heterogeneous and stable to mutations than non-coding regions. We also found, using coalescent simulations, that regions under selection have more extended and connected networks. The application of the concept of genotype networks can provide a new opportunity to understand the evolutionary processes that shaped our genome. Learning how the genotype space of each region of our genome has been explored during the evolutionary history of the human species can lead to a better understanding on how selective pressures and neutral factors have shaped genetic diversity within populations and among individuals. Combined with the availability of larger datasets of sequencing data, genotype networks represent a new approach to the study of human genetic diversity that looks to the whole genome, and goes beyond the classical division between selection and neutrality methods. PMID:24911413

  20. Human genome variation and the concept of genotype networks.

    Science.gov (United States)

    Dall'Olio, Giovanni Marco; Bertranpetit, Jaume; Wagner, Andreas; Laayouni, Hafid

    2014-01-01

    Genotype networks are a concept used in systems biology to study sets of genotypes having the same phenotype, and the ability of these to bring forth novel phenotypes. In the past they have been applied to determine the genetic heterogeneity, and stability to mutations, of systems such as metabolic networks and RNA folds. Recently, they have been the base for reconciling the neutralist and selectionist views on evolution. Here, we adapted this concept to the study of population genetics data. Specifically, we applied genotype networks to the human 1000 genomes dataset, and analyzed networks composed of short haplotypes of Single Nucleotide Variants (SNV). The result is a scan of how properties related to genetic heterogeneity and stability to mutations are distributed along the human genome. We found that genes involved in acquired immunity, such as some HLA and MHC genes, tend to have the most heterogeneous and connected networks, and that coding regions tend to be more heterogeneous and stable to mutations than non-coding regions. We also found, using coalescent simulations, that regions under selection have more extended and connected networks. The application of the concept of genotype networks can provide a new opportunity to understand the evolutionary processes that shaped our genome. Learning how the genotype space of each region of our genome has been explored during the evolutionary history of the human species can lead to a better understanding on how selective pressures and neutral factors have shaped genetic diversity within populations and among individuals. Combined with the availability of larger datasets of sequencing data, genotype networks represent a new approach to the study of human genetic diversity that looks to the whole genome, and goes beyond the classical division between selection and neutrality methods.

  1. Inter-chromosomal variation in the pattern of human population genetic structure

    Directory of Open Access Journals (Sweden)

    Baye Tesfaye M

    2011-05-01

    application of complementary statistical and functional network analysis in human genetic variation studies.

  2. Application of Humanized Mice in Immunological Research.

    Science.gov (United States)

    Tu, Wenwei; Zheng, Jian

    2016-01-01

    During the past decade, the development of humanized mouse models and their general applications in biomedical research greatly accelerated the translation of outcomes obtained from basic research into potential diagnostic and therapeutic strategies in clinic. In this chapter, we firstly present an overview on the history and current progress of diverse humanized mouse models and then focus on those equipped with reconstituted human immune system. The update advancement in the establishment of humanized immune system mice and their applications in the studies of the development of human immune system and the pathogenesis of multiple human immune-related diseases are intensively reviewed here, while the shortcoming and perspective of these potent tools are discussed as well. As a valuable bridge across the gap between bench work and clinical trial, progressive humanized mouse models will undoubtedly continue to play an indispensable role in the wide area of biomedical research.

  3. Application of variational mode decomposition to seismic random noise reduction

    Science.gov (United States)

    Liu, Wei; Cao, Siyuan; Wang, Zhiming

    2017-08-01

    We have proposed a new denoising method for the simultaneous noise reduction and preservation of seismic signals based on variational mode decomposition (VMD). VMD is a recently developed adaptive signal decomposition method and an advance in non-stationary signal analysis. It solves the mode-mixing and non-optimal reconstruction performance problems of empirical mode decomposition that have existed for a long time. By using VMD, a multi-component signal can be non-recursively decomposed into a series of quasi-orthogonal intrinsic mode functions (IMFs), each of which has a relatively local frequency range. Meanwhile, the signal will focus on a smaller number of obtained IMFs after decomposition, and thus the denoised result is able to be obtained by reconstructing these signal-dominant IMFs. Synthetic examples are given to demonstrate the effectiveness of the proposed approach and comparison is made with the complete ensemble empirical mode decomposition, which demonstrates that the VMD algorithm has lower computational cost and better random noise elimination performance. The application of on field seismic data further illustrates the superior performance of our method in both random noise attenuation and the recovery of seismic events.

  4. Mine, yours, ours? Sharing data on human genetic variation.

    Science.gov (United States)

    Milia, Nicola; Congiu, Alessandra; Anagnostou, Paolo; Montinaro, Francesco; Capocasa, Marco; Sanna, Emanuele; Destro Bisol, Giovanni

    2012-01-01

    The achievement of a robust, effective and responsible form of data sharing is currently regarded as a priority for biological and bio-medical research. Empirical evaluations of data sharing may be regarded as an indispensable first step in the identification of critical aspects and the development of strategies aimed at increasing availability of research data for the scientific community as a whole. Research concerning human genetic variation represents a potential forerunner in the establishment of widespread sharing of primary datasets. However, no specific analysis has been conducted to date in order to ascertain whether the sharing of primary datasets is common-practice in this research field. To this aim, we analyzed a total of 543 mitochondrial and Y chromosomal datasets reported in 508 papers indexed in the Pubmed database from 2008 to 2011. A substantial portion of datasets (21.9%) was found to have been withheld, while neither strong editorial policies nor high impact factor proved to be effective in increasing the sharing rate beyond the current figure of 80.5%. Disaggregating datasets for research fields, we could observe a substantially lower sharing in medical than evolutionary and forensic genetics, more evident for whole mtDNA sequences (15.0% vs 99.6%). The low rate of positive responses to e-mail requests sent to corresponding authors of withheld datasets (28.6%) suggests that sharing should be regarded as a prerequisite for final paper acceptance, while making authors deposit their results in open online databases which provide data quality control seems to provide the best-practice standard. Finally, we estimated that 29.8% to 32.9% of total resources are used to generate withheld datasets, implying that an important portion of research funding does not produce shared knowledge. By making the scientific community and the public aware of this important aspect, we may help popularize a more effective culture of data sharing.

  5. Estimated biological variation of the mature human milk fatty acid composition

    NARCIS (Netherlands)

    Smit, EN; Martini, IA; Mulder, H; Boersma, ER; Muskiet, FAJ

    2002-01-01

    We estimated the biological variation (CVbiol) of 28 fatty acids (FA) in 465 mature human milk samples from The Netherlands, Caribbean, Jerusalem, Tanzania and Pakistan, by using data from the observed variation (CVobs) and analytical variation (CVanal). CVbiol of the various regions was remarkably

  6. APPLICATION OF MODERN HUMAN RESOURCE MANAGEMENT ...

    African Journals Online (AJOL)

    The purpose of this study was to explore the application of modern human resource management practices by women SME owner/managers in Kenya. The objectives of the study were two: to examine to what extend the women SME owner/managers applied human resources management practices in their organizations ...

  7. Application of New Variational Homotopy Perturbation Method For ...

    African Journals Online (AJOL)

    ... proposed method is very efficient, simple and is more user friendly. Keywords: Variational Iteration Method, Homotopy Perturbation Method, New Variational Homotopy Perturbation Method, Integro-Differential Equations Journal of the Nigerian Association of Mathematical Physics, Volume 20 (March, 2012), pp 497 – 504 ...

  8. Application of New Variational Homotopy Perturbation Method I ...

    African Journals Online (AJOL)

    Numerical comparisons are made between VIM/HPM and NVHPM results. Keywords: Painlevé Equations, Variational Iteration Method, Homotopy Perturbation Method, New Variational Homotopy Perturbation Method, Ordinary Differential Equations Journal of the Nigerian Association of Mathematical Physics, Volume 19 ...

  9. Variations in Humanized and Defined Culture Conditions Supporting Derivation of New Human Embryonic Stem Cell Lines

    DEFF Research Database (Denmark)

    Fletcher, Judy M; Ferrier, Patricia M; Gardner, John O

    2006-01-01

    The evolution of "humanized" (i.e., free of animal sourced reagents) and ultimately chemically defined culture systems for human embryo stem cell (hESC) isolation and culture is of importance to improving their efficacy and safety in research and therapeutic applications. This can be achieved...... serum-free medium (SFM) containing only human sourced and recombinant protein. Further, outgrowth of embryonic cells from whole blastocysts in both media could be achieved for up to 1 week without reliance on feeder cells. All variant conditions sustained undifferentiated cell status, a stable karyotype......, with a transitional requirement for human feeder cells. This represents another sequential step in the generation of therapeutic grade stem cells with reduced risk of zoonotic pathogen transmission....

  10. Human footprint variation while performing load bearing tasks

    National Research Council Canada - National Science Library

    Wall-Scheffler, Cara M; Wagnild, Janelle; Wagler, Emily

    2015-01-01

    Human footprint fossils have provided essential evidence about the evolution of human bipedalism as well as the social dynamics of the footprint makers, including estimates of speed, sex and group composition...

  11. 41 CFR 50-204.35 - Application for variations from radiation levels.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Application for variations from radiation levels. 50-204.35 Section 50-204.35 Public Contracts and Property Management Other... FOR FEDERAL SUPPLY CONTRACTS Radiation Standards § 50-204.35 Application for variations from radiation...

  12. The molecular basis of variation in human color vision.

    Science.gov (United States)

    Deeb, S S

    2005-05-01

    Common variation in red-green color vision exists among both normal and color-deficient subjects. Differences at amino acids involved in tuning the spectra of the red and green cone pigments account for the majority of this variation. One source of variation is the very common Ser180Ala polymorphism that accounts for two spectrally different red pigments and that plays an important role in variation in normal color vision as well as in determining the severity of defective color vision. This polymorphism most likely resulted from gene conversion by the green-pigment gene. Another common source of variation is the existence of several types of red/green pigment chimeras with different spectral properties. The red and green-pigment genes are arranged in a head-to-tail tandem array on the X-chromosome with one red-pigment gene followed by one or more green-pigment genes. The high homology between these genes has predisposed the locus to relatively common unequal recombination events that give rise to red/green hybrid genes and to deletion of the green-pigment genes. Such events constitute the most common cause of red-green color vision defects. Only the first two pigment genes of the red/green array are expressed in the retina and therefore contribute to the color vision phenotype. The severity of red-green color vision defects is inversely proportional to the difference between the wavelengths of maximal absorption of the photopigments encoded by the first two genes of the array. Women who are heterozygous for red and green pigment genes that encode three spectrally distinct photopigments have the potential for enhanced color vision.

  13. Application of Green's operator to quadratic variational problems

    Directory of Open Access Journals (Sweden)

    Nikolay V. Azbelev

    2006-01-01

    Full Text Available We use Green's function of a suitable boundary value problem to convert the variational problem with quadratic functional and linear constraints to the equivalent unconstrained extremal problem in some subspace of the space \\(L_2\\ of quadratically summable functions. We get the necessary and sufficient criterion for unique solvability of the variational problem in terms of the spectrum of some integral Hilbert-Schmidt operator in \\(L_2\\ with symmetric kernel. The numerical technique is proposed to estimate this criterion. The results are demonstrated on examples: 1 a variational problem with deviating argument, and 2 the problem of the critical force for the vertical pillar with additional support point (the qualities of the pillar may vary discontinuously along the pillar's axis.

  14. Elastic scattering of positronium: Application of the confined variational method

    KAUST Repository

    Zhang, Junyi

    2012-08-01

    We demonstrate for the first time that the phase shift in elastic positronium-atom scattering can be precisely determined by the confined variational method, in spite of the fact that the Hamiltonian includes an unphysical confining potential acting on the center of mass of the positron and one of the atomic electrons. As an example, we study the S-wave elastic scattering for the positronium-hydrogen scattering system, where the existing 4% discrepancy between the Kohn variational calculation and the R-matrix calculation is resolved. © Copyright EPLA, 2012.

  15. Epigenetic Variation between Human Induced Pluripotent Stem Cell Lines Is an Indicator of Differentiation Capacity.

    Science.gov (United States)

    Nishizawa, Masatoshi; Chonabayashi, Kazuhisa; Nomura, Masaki; Tanaka, Azusa; Nakamura, Masahiro; Inagaki, Azusa; Nishikawa, Misato; Takei, Ikue; Oishi, Akiko; Tanabe, Koji; Ohnuki, Mari; Yokota, Hidaka; Koyanagi-Aoi, Michiyo; Okita, Keisuke; Watanabe, Akira; Takaori-Kondo, Akifumi; Yamanaka, Shinya; Yoshida, Yoshinori

    2016-09-01

    Variation in the differentiation capacity of induced pluripotent stem cells (iPSCs) to specific lineages is a significant concern for their use in clinical applications and disease modeling. To identify factors that affect differentiation capacity, we performed integration analyses between hematopoietic differentiation performance and molecular signatures such as gene expression, DNA methylation, and chromatin status, using 35 human iPSC lines and four ESC lines. Our analyses revealed that hematopoietic commitment of PSCs to hematopoietic precursors correlates with IGF2 expression level, which in turn depends on signaling-dependent chromatin accessibility at mesendodermal genes. Maturation capacity for conversion of PSC-derived hematopoietic precursors to mature blood associates with the amount and pattern of DNA methylation acquired during reprogramming. Our study therefore provides insight into the molecular features that determine the differential capacities seen among human iPSC lines and, through the predictive potential of this information, highlights a way to select optimal iPSCs for clinical applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. The fractal based analysis of human face and DNA variations during aging.

    Science.gov (United States)

    Namazi, Hamidreza; Akrami, Amin; Hussaini, Jamal; Silva, Osmar N; Wong, Albert; Kulish, Vladimir V

    2017-01-16

    Human DNA is the main unit that shapes human characteristics and features such as behavior. Thus, it is expected that changes in DNA (DNA mutation) influence human characteristics and features. Face is one of the human features which is unique and also dependent on his gen. In this paper, for the first time we analyze the variations of human DNA and face simultaneously. We do this job by analyzing the fractal dimension of DNA walk and face during human aging. The results of this study show the human DNA and face get more complex by aging. These complexities are mapped on fractal exponents of DNA walk and human face. The method discussed in this paper can be further developed in order to investigate the direct influence of DNA mutation on the face variations during aging, and accordingly making a model between human face fractality and the complexity of DNA walk.

  17. an investigation into the applicability of natural load variation ...

    African Journals Online (AJOL)

    Rev. Anoliefo

    transfer from the panel. 3. METHODOLOGY. For the purpose of demonstrating the effect of varying the number of resistors in the natural load variation scheme, an experiment was conducted using Arduino mega (a microcontroller),three 30W PV modules, a number of choke resistors and TIP 31. The set up is shown in Figure ...

  18. Application of the cluster variation method to interstitial solid solutions

    NARCIS (Netherlands)

    Pekelharing, M.I.

    2008-01-01

    A thermodynamic model for interstitial alloys, based on the Cluster Variation Method (CVM), has been developed, capable of incorporating short range ordering (SRO), long range ordering (LRO), and the mutual interaction between the host and the interstitial sublattices. The obtained cluster-based

  19. A generalization of Ekeland's variational principle with applications

    Directory of Open Access Journals (Sweden)

    Abdel R. El Amrouss

    2006-09-01

    Full Text Available In this paper, we establish a variant of Ekeland's variational principle. This result suggest to introduce a generalization of the famous Palais-Smale condition. An example is provided showing how it is used to give the existence of minimizer for functions for which the Palais-Smale condition and the one introduced by Cerami are not satisfied.

  20. Numerical estimation of the effects of climatic variations on human ...

    African Journals Online (AJOL)

    temperature, humidity, solar radiation and wind speed) are used to develop a numerical model for estimating the effect of climatic changes on human thermal comfort in Botswana. Numerical values of energy load for four different comfort classes were ...

  1. Gag sequence variation in a human immunodeficiency virus type 1 transmission cluster influences viral replication fitness

    NARCIS (Netherlands)

    Gijsbers, Esther F.; van Nuenen, Ad C.; Schuitemaker, Hanneke; Kootstra, Neeltje A.

    2013-01-01

    Three men from a proven homosexual human immunodeficiency virus type 1 (HIV-1) transmission cluster showed large variation in their clinical course of infection. To evaluate the effect of evolution of the same viral variant in these three patients, we analysed sequence variation in the capsid

  2. Genetic variations of gpx-4 and male infertility in humans.

    Science.gov (United States)

    Maiorino, Matilde; Bosello, Valentina; Ursini, Fulvio; Foresta, Carlo; Garolla, Andrea; Scapin, Margherita; Sztajer, Helena; Flohe, Leopold

    2003-04-01

    Phospholipid hydroperoxide glutathione peroxidase (PHGPx), the product of gpx-4, is the major selenoprotein in sperm and is considered essential for fertilization because of its multiple roles in spermatogenesis, such as hydroperoxide detoxification, formation of the mitochondrial capsule, and chromatin condensation. Genomic DNA sequences of 3.148 kilobases covering the whole gpx-4 and its flanking regions were amplified from 63 men using the polymerase chain reaction and were analyzed for polymorphisms by direct sequencing. A total of 23 variant sites were detected; 2 were present only in control men (proven fathers; n = 21) and 10 were common to fertile controls and infertile patients (n = 42). A further 11 variant sites were seen in five of the infertile men only. Four of the gpx-4 variants were considered irrelevant to GPx-4-related fertility problems because they occurred homozygously in controls. The majority of the remaining variant sites are also of questionable relevance because they are located in introns or, as third base exchanges, do not affect the protein sequence. However, one of the exon variations leads to an Ala93-Thr exchange that reduces activity in a porcine GPx-4 homologue. Two detected promoter variations were shown by reporter gene constructs to affect transcription in somatic cell lines. These results indicate that gpx-4 polymorphism cannot generally account for the correlation of PHGPx content of sperm and fertility-related parameters, but further examination of this gene as a potential cause of infertility in particular cases is warranted.

  3. Mitochondrial DNA copy number variation across human cancers.

    Science.gov (United States)

    Reznik, Ed; Miller, Martin L; Şenbabaoğlu, Yasin; Riaz, Nadeem; Sarungbam, Judy; Tickoo, Satish K; Al-Ahmadie, Hikmat A; Lee, William; Seshan, Venkatraman E; Hakimi, A Ari; Sander, Chris

    2016-02-22

    Mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), are observed throughout cancers. Here, we survey mtDNA copy number variation across 22 tumor types profiled by The Cancer Genome Atlas project. We observe a tendency for some cancers, especially of the bladder, breast, and kidney, to be depleted of mtDNA, relative to matched normal tissue. Analysis of genetic context reveals an association between incidence of several somatic alterations, including IDH1 mutations in gliomas, and mtDNA content. In some but not all cancer types, mtDNA content is correlated with the expression of respiratory genes, and anti-correlated to the expression of immune response and cell-cycle genes. In tandem with immunohistochemical evidence, we find that some tumors may compensate for mtDNA depletion to sustain levels of respiratory proteins. Our results highlight the extent of mtDNA copy number variation in tumors and point to related therapeutic opportunities.

  4. Variation of Metabolite and Hormone Contents in Human Milk.

    Science.gov (United States)

    Demmelmair, Hans; Koletzko, Berthold

    2017-03-01

    Animal studies show that the lactation period contributes to metabolic programming of the offspring and that oral leptin and insulin show bioactivity. Stage of lactation, duration of gestation, maternal body composition, and maternal diet seem to influence the concentrations of small molecules in human milk. Variability of small molecule concentrations seems higher in preterm milk than in term milk. Insulin in human milk shows concentrations similar to plasma. Leptin concentration is lower in milk than in plasma and reflects maternal body mass index. Early in lactation, leptin could contribute to mediating the association between maternal and infant body composition. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Original article Temperamental variation in learned irrelevance in humans

    Directory of Open Access Journals (Sweden)

    Aleksandra Gruszka

    2015-07-01

    Full Text Available Background Learned irrelevance (LIRR represents one of the mechanisms of attentional set-shifting and refers to the inability to attend to, or to learn about, any aspect of a stimulus previously experienced as irrelevant. Although it has been extensively studied in the context of clinical populations, not much is known about LIRR effects in relation to normal variation in individual differences. The present study was designed to assess how temperamental factors may modulate LIRR. Participants and procedures Sixty-eight healthy volunteers performed a visual discrimination learning task modelled after Wisconsin Card Sorting Test. To test the susceptibility to learned irrelevance, participants were expected to shift their attention either to a dimension that prior to the extra-dimensional shift was completely irrelevant, or to a dimension that was previously partly correlated with reinforcement. Temperamental traits were assessed using the Formal Characteristics of Behaviour-Temperament Inventory (Zawadzki & Strelau, 1997. Intelligence level was stratified according to Raven’s Advanced Progressive Matrices (Raven, Raven, & Court, 2003. Results Low level of Briskness and high level of Perseverance were related to enhanced susceptibility to LIRR. High levels of Activity and Emotional Reactivity were related to the poorer performance on the extra-dimensional set-shifting. No effects of other temperament characteristics or intelligence on LIRR were observed. Conclusions The results confirm a strong variation in LIRR related to individual differences in temperament, which appears to be unrelated to DA function. Our results highlight the importance of considering individual differences in studies on cognitive control.

  6. Regional quantitative histological variations in human oral mucosa.

    Science.gov (United States)

    Ciano, Joseph; Beatty, Brian Lee

    2015-03-01

    Oral mucosa demonstrates regional variations that reflect contact with food during mastication. Though known qualitatively, our aim was to quantitatively assess regions to establish a measurable baseline from which one could compare in pathological and comparative studies, in which the abrasiveness of diets may differ. We assessed variations in the epithelial-connective tissue junction (rete ridges counts), collagen organization within the lamina propria, and elastin composition of the lamina propria of 15 regions of the labial (buccal) gingiva, lingual gingiva, vestibule, and palate. All characteristics varied more between regions within the same individual than between individuals. Lingual gingiva had high rete ridges counts, high level of collagen organization, and moderate elastin composition compared to other regions. The labial gingiva had few rete ridges, high collagen organization, and low elastin. The vestibule had the fewest average of rete ridges, least organized collagen, and high elastin. The hard palate had the highest average of rete ridges, high collagen organization, and the lowest elastin content. The soft palate conversely had the smallest average of rete ridges, moderate collagen organization, and the highest elastin composition. Our results indicate that comparison of these quantitative histological differences is warranted only for collagen organization and elastin composition. Differences in rete ridges counts were not statistically significant. Most histological characteristics observed were not significantly different between dentulous and edentulous cadavers, and the group containing all individuals. An exception was the level of collagen fiber organization within the lamina propria, which was higher in most regions when teeth were present. © 2014 Wiley Periodicals, Inc.

  7. Geomagnetic Secular Variation and Its Applications to the Core

    DEFF Research Database (Denmark)

    Jackson, Andrew; Finlay, Chris

    2015-01-01

    We review the observational constraints on the morphology and evolution of the magnetic field of the Earth over the last few centuries; these changes are referred to as the secular variation.Starting with a description of the available sources of original observations of the field, we thendiscuss...... of physical core processes. These divide themselves into processes associatedwith movement of core fluid, which is capable of advecting the field, and processes associated withthe finite resistivity of the core, commonly termed diffusive processes. We lay the foundations for some of the more theoretical...

  8. The Contribution of Neanderthals to Phenotypic Variation in Modern Humans.

    Science.gov (United States)

    Dannemann, Michael; Kelso, Janet

    2017-10-05

    Assessing the genetic contribution of Neanderthals to non-disease phenotypes in modern humans has been difficult because of the absence of large cohorts for which common phenotype information is available. Using baseline phenotypes collected for 112,000 individuals by the UK Biobank, we can now elaborate on previous findings that identified associations between signatures of positive selection on Neanderthal DNA and various modern human traits but not any specific phenotypic consequences. Here, we show that Neanderthal DNA affects skin tone and hair color, height, sleeping patterns, mood, and smoking status in present-day Europeans. Interestingly, multiple Neanderthal alleles at different loci contribute to skin and hair color in present-day Europeans, and these Neanderthal alleles contribute to both lighter and darker skin tones and hair color, suggesting that Neanderthals themselves were most likely variable in these traits. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

    KAUST Repository

    Sakata, Katsumi

    2016-10-24

    Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

  10. Potential applications of human saliva as diagnostic fluid.

    Science.gov (United States)

    Castagnola, M; Picciotti, P M; Messana, I; Fanali, C; Fiorita, A; Cabras, T; Calò, L; Pisano, E; Passali, G C; Iavarone, F; Paludetti, G; Scarano, E

    2011-12-01

    The use of human saliva as a diagnostic and prognostic fluid has until recently been somewhat disregarded. Although sample collection is non-invasive, physiological and genetic variations were largely responsible for its infrequent application in the past. Recently, several proteomic studies contributed to partial elucidation of the salivary proteome (more than 2400 protein components have been characterized), both in terms of composition, contributions to whole saliva and genetic/physiological variability. On this basis, is not too optimistic to believe that in the near future human saliva could become a relevant diagnostic fluid. In this review, the characterization by proteomic approaches of new salivary markers in oncology, head and neck carcinoma (oral cavity, oropharynx, larynx, and salivary glands), breast and gastric cancers, salivary gland function and disease, Sjögren syndrome, systemic sclerosis, dental and gingival pathology, systemic, psychiatric and neurological diseases, is described.

  11. Continental synchronicity of human influenza virus epidemics despite climactic variation.

    Science.gov (United States)

    Geoghegan, Jemma L; Saavedra, Aldo F; Duchêne, Sebastián; Sullivan, Sheena; Barr, Ian; Holmes, Edward C

    2018-01-01

    The factors that determine the pattern and rate of spread of influenza virus at a continental-scale are uncertain. Although recent work suggests that influenza epidemics in the United States exhibit a strong geographical correlation, the spatiotemporal dynamics of influenza in Australia, a country and continent of approximately similar size and climate complexity but with a far smaller population, are not known. Using a unique combination of large-scale laboratory-confirmed influenza surveillance comprising >450,000 entries and genomic sequence data we determined the local-level spatial diffusion of this important human pathogen nationwide in Australia. We used laboratory-confirmed influenza data to characterize the spread of influenza virus across Australia during 2007-2016. The onset of established epidemics varied across seasons, with highly synchronized epidemics coinciding with the emergence of antigenically distinct viruses, particularly during the 2009 A/H1N1 pandemic. The onset of epidemics was largely synchronized between the most populous cities, even those separated by distances of >3000 km and those that experience vastly diverse climates. In addition, by analyzing global phylogeographic patterns we show that the synchronized dissemination of influenza across Australian cities involved multiple introductions from the global influenza population, coupled with strong domestic connectivity, rather than through the distinct radial patterns of geographic dispersal that are driven by work-flow transmission as observed in the United States. In addition, by comparing the spatial structure of influenza A and B, we found that these viruses tended to occupy different geographic regions, and peak in different seasons, perhaps indicative of moderate cross-protective immunity or viral interference effects. The highly synchronized outbreaks of influenza virus at a continental-scale revealed here highlight the importance of coordinated public health responses in the

  12. Extensive variation in gene copy number at the killer immunoglobulin-like receptor locus in humans.

    Directory of Open Access Journals (Sweden)

    Sanne Vendelbosch

    Full Text Available Killer immunoglobulin-like receptors (KIRs are involved in the regulation of natural killer cell cytotoxicity. Within the human genome seventeen KIR genes are present, which all contain a large number of allelic variants. The high level of homology among KIR genes has hampered KIR genotyping in larger cohorts, and determination of gene copy number variation (CNV has been difficult. We have designed a multiplex ligation-dependent probe amplification (MLPA technique for genotyping and CNV determination in one single assay and validated the results by next-generation sequencing and with a KIR gene-specific short tandem repeat assay. In this way, we demonstrate in a cohort of 120 individuals a high level of CNV for all KIR genes except for the framework genes KIR3DL3 and KIR3DL2. Application of our MLPA assay in segregation analyses of families from the Centre d'Etude du Polymorphisme Humaine, previously KIR-genotyped by classical techniques, confirmed an earlier reported duplication and resulted in the identification of a novel duplication event in one of these families. In summary, our KIR MLPA assay allows rapid and accurate KIR genotyping and CNV detection, thus rendering improved transplantation programs and oncology treatment feasible, and enables more detailed studies on the role of KIRs in human (autoimmunity and infectious disease.

  13. Extensive variation in gene copy number at the killer immunoglobulin-like receptor locus in humans.

    Science.gov (United States)

    Vendelbosch, Sanne; de Boer, Martin; Gouw, Remko A T W; Ho, Cynthia K Y; Geissler, Judy; Swelsen, Wendy T N; Moorhouse, Michael J; Lardy, Neubury M; Roos, Dirk; van den Berg, Timo K; Kuijpers, Taco W

    2013-01-01

    Killer immunoglobulin-like receptors (KIRs) are involved in the regulation of natural killer cell cytotoxicity. Within the human genome seventeen KIR genes are present, which all contain a large number of allelic variants. The high level of homology among KIR genes has hampered KIR genotyping in larger cohorts, and determination of gene copy number variation (CNV) has been difficult. We have designed a multiplex ligation-dependent probe amplification (MLPA) technique for genotyping and CNV determination in one single assay and validated the results by next-generation sequencing and with a KIR gene-specific short tandem repeat assay. In this way, we demonstrate in a cohort of 120 individuals a high level of CNV for all KIR genes except for the framework genes KIR3DL3 and KIR3DL2. Application of our MLPA assay in segregation analyses of families from the Centre d'Etude du Polymorphisme Humaine, previously KIR-genotyped by classical techniques, confirmed an earlier reported duplication and resulted in the identification of a novel duplication event in one of these families. In summary, our KIR MLPA assay allows rapid and accurate KIR genotyping and CNV detection, thus rendering improved transplantation programs and oncology treatment feasible, and enables more detailed studies on the role of KIRs in human (auto)immunity and infectious disease.

  14. Perspectives on human genetic variation from the HapMap Project.

    Science.gov (United States)

    McVean, Gil; Spencer, Chris C A; Chaix, Raphaelle

    2005-10-01

    The completion of the International HapMap Project marks the start of a new phase in human genetics. The aim of the project was to provide a resource that facilitates the design of efficient genome-wide association studies, through characterising patterns of genetic variation and linkage disequilibrium in a sample of 270 individuals across four geographical populations. In total, over one million SNPs have been typed across these genomes, providing an unprecedented view of human genetic diversity. In this review we focus on what the HapMap Project has taught us about the structure of human genetic variation and the fundamental molecular and evolutionary processes that shape it.

  15. Size variation in small-bodied humans from palau, micronesia.

    Directory of Open Access Journals (Sweden)

    Andrew Gallagher

    Full Text Available BACKGROUND: Recent discoveries on Palau are claimed to represent the remains of small-bodied humans that may display evidence insular size reduction. This claim has yet to be statistically validated METHODOLOGY/PRINCIPAL FINDINGS: Published postcranial specimens (n = 16 from Palau were assessed relative to recent small-bodied comparative samples. Resampling statistical approaches were employed to test specific hypotheses relating to body size in the Palau sample. Results confirm that the Palau postcranial sample is indisputably small-bodied. CONCLUSIONS/SIGNIFICANCE: A single, homogenous body size morph is represented in early prehistoric postcrania from Palau. Small body size in early Palauans is an ancestral characteristic and was likely not a consequence of in-situ size reduction. Specimens from Palau have little bearing upon hypothesised insular size reduction in the ancestral lineage of Homo floresiensis.

  16. An analysis on spatial variation of urban human thermal comfort in Hangzhou, China.

    Science.gov (United States)

    Wang, Wei-wu; Zhu, Li-zhong; Wang, Ren-chao

    2004-01-01

    Urban human thermal comfort (UHTC) is affected for interacting of weather condition and underlying surface framework of urban area. Urban underlying surface temperature value and Normalized Difference Vegetation Index (NDVI) were calculated using image interpreting and supervised classification technique by ERDAS IMAGE software using 1991 and 1999 Landsat TM images data. Reference to the relational standard of assessing human thermal comfort and other meteorology data of Hangzhou City in summer, air temperature and relative humidity variation of different land types of underlying surface were inversed. By choosing discomfort index as an indictor, the spatial distribution characteristic and the spatial variation degree of UHTC were estimated and mapped on a middle scale, that is, in six districts of Hangzhou. The main characteristics of UHTC spatial variation from 1991 to 1999 were revealed using a GIS-based calculation model. The variation mechanism were analyzed and discussed from the viewpoint of city planning, construction and environmental protection.

  17. Variation of Kozinets' framework and application to nursing research.

    Science.gov (United States)

    Witney, Cynthia; Hendricks, Joyce; Cope, Vicki

    2016-05-01

    Online communities are new sites for undertaking research, with their textual interactions providing a rich source of data in real time. 'Ethnonetnography' is a research methodology based on ethnography that can be used in these online communities. In this study, the researcher and a specialist breast care nurse (SBCN) were immersed in the online community, adding to patients' breast cancer care and providing a nursing research component to the community. To examine Kozinets' ( 2010 ) framework for ethnonetnography and how it may be varied for use in a purpose-built, disease-specific, online support community. The online community provided an area where members could communicate with each other. Kozinets' ( 2010 ) framework was varied in that the research was carried out in a purpose-built community opf which an SBCN was a member who could provide support and advice. The application of the ethnonetnographic methodology has wide implications for clinical nursing practice and research. Ethnonetnography can be used to study disease-specific communities in a focused manner and can provide immediate benefits through the inclusion of an expert nurse and contemporaneous application of research findings to patient care. With ethical permission and the permission of online community members, nurse researchers can enter already established online communities. Ethnonetnography is ideally suited to nursing research as it provides the immediacy of evidence-based interaction with an expert nurse. These real-time responses improve support for those experiencing a critical life event.

  18. Revised computational metagenomic processing uncovers hidden and biologically meaningful functional variation in the human microbiome.

    Science.gov (United States)

    Manor, Ohad; Borenstein, Elhanan

    2017-02-08

    Recent metagenomic analyses of the human gut microbiome identified striking variability in its taxonomic composition across individuals. Notably, however, these studies often reported marked functional uniformity, with relatively little variation in the microbiome's gene composition or in its overall metabolic capacity. Here, we address this surprising discrepancy between taxonomic and functional variations and set out to track its origins. Specifically, we demonstrate that the functional uniformity observed in microbiome studies can be attributed, at least partly, to common computational metagenomic processing procedures that mask true functional variation across microbiome samples. We identify several such procedures, including commonly used practices for gene abundance normalization, mapping of gene families to functional pathways, and gene family aggregation. We show that accounting for these factors and using revised metagenomic processing procedures uncovers such hidden functional variation, significantly increasing observed variation in the abundance of functional elements across samples. Importantly, we find that this uncovered variation is biologically meaningful and that it is associated with both host identity and health. Accurate characterization of functional variation in the microbiome is essential for comparative metagenomic analyses in health and disease. Our finding that metagenomic processing procedures mask underlying and biologically meaningful functional variation therefore highlights an important challenge such studies may face. Alternative schemes for metagenomic processing that uncover this hidden functional variation can facilitate improved metagenomic analysis and help pinpoint disease- and host-associated shifts in the microbiome's functional capacity.

  19. Temporal and spatial variation of the human microbiota during pregnancy.

    Science.gov (United States)

    DiGiulio, Daniel B; Callahan, Benjamin J; McMurdie, Paul J; Costello, Elizabeth K; Lyell, Deirdre J; Robaczewska, Anna; Sun, Christine L; Goltsman, Daniela S A; Wong, Ronald J; Shaw, Gary; Stevenson, David K; Holmes, Susan P; Relman, David A

    2015-09-01

    Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.

  20. A functional genetic variation of the 5-HT2a receptor affects human memory.

    Science.gov (United States)

    de Quervain, Dominique J-F; Henke, Katharina; Aerni, Amanda; Coluccia, Daniel; Wollmer, M Axel; Hock, Christoph; Nitsch, Roger M; Papassotiropoulos, Andreas

    2003-11-01

    Human memory capacity is highly variable across individuals and is influenced by both genetic and environmental factors. A roughly 50% heritability estimate indicates that naturally occurring genetic variations have an important impact on this cognitive ability. Therefore, we investigated a functional variation of a memory-related serotonin receptor in 349 healthy young volunteers, and found 21% poorer memory performance in subjects with the rare variant.

  1. Long-Term Measurements of Human Inflammatory Cytokines Reveal Complex Baseline Variations between Individuals.

    Science.gov (United States)

    Wu, Danlu; Dinh, Trinh L; Bausk, Bruce P; Walt, David R

    2017-12-01

    Comprehensive characterization of the healthy human proteome baseline is essential for personalized medicine. Baseline data are necessary to understand the variation between individuals, as well as longitudinal variation within individuals. Many important protein biomarkers, such as cytokines, exist at extremely low or undetectable levels in the healthy state. This paper describes results from a 14-week study of healthy human subjects using ultrasensitive single-molecule array (Simoa) assays to measure both intra and intersubject variation of 15 cytokines. The results show a wide variation in the ranges of some cytokines between individuals and demonstrate that individual baseline values will be essential for predicting disease presence and progression. Although all of the studied cytokines demonstrated high temporal stability (or low intrasubject variation) over the entire study period, there were two distinct groups of cytokines that demonstrated either high (IL-8, IFN-γ, IL-2, IL-6, and IL-1β) or low (IL-15, TNF-α, IL-12 p70, IL-17A, GM-CSF, IL-12 p40, IL-10, IL-7, IL-1α, and IL-5) subject-to-subject variation. This work demonstrates that ultrasensitive assays are essential for characterizing human cytokines in healthy subjects. The results show that some cytokines vary by more than two orders of magnitude between individuals, making it an imperative to obtain individual baseline measurements if they are to play a role in health and disease diagnosis. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function.

    Science.gov (United States)

    Michels, Alexander J; Hagen, Tory M; Frei, Balz

    2013-01-01

    New evidence for the regulation of vitamin C homeostasis has emerged from several studies of human genetic variation. Polymorphisms in the genes encoding sodium-dependent vitamin C transport proteins are strongly associated with plasma ascorbate levels and likely impact tissue cellular vitamin C status. Furthermore, genetic variants of proteins that suppress oxidative stress or detoxify oxidatively damaged biomolecules, i.e., haptoglobin, glutathione-S-transferases, and possibly manganese superoxide dismutase, affect ascorbate levels in the human body. There also is limited evidence for a role of glucose transport proteins. In this review, we examine the extent of the variation in these genes, their impact on vitamin C status, and their potential role in altering chronic disease risk. We conclude that future epidemiological studies should take into account genetic variation in order to successfully determine the role of vitamin C nutriture or supplementation in human vitamin C status and chronic disease risk.

  3. The genomic landscape of human cellular circadian variation points to a novel role for the signalosome.

    Science.gov (United States)

    Gaspar, Ludmila; Howald, Cedric; Popadin, Konstantin; Maier, Bert; Mauvoisin, Daniel; Moriggi, Ermanno; Gutierrez-Arcelus, Maria; Falconnet, Emilie; Borel, Christelle; Kunz, Dieter; Kramer, Achim; Gachon, Frederic; Dermitzakis, Emmanouil T; Antonarakis, Stylianos E; Brown, Steven A

    2017-09-04

    The importance of natural gene expression variation for human behavior is undisputed, but its impact on circadian physiology remains mostly unexplored. Using umbilical cord fibroblasts, we have determined by genome-wide association how common genetic variation impacts upon cellular circadian function. Gene set enrichment points to differences in protein catabolism as one major source of clock variation in humans. The two most significant alleles regulated expression of COPS7B, a subunit of the COP9 signalosome. We further show that the signalosome complex is imported into the nucleus in timed fashion to stabilize the essential circadian protein BMAL1, a novel mechanism to oppose its proteasome-mediated degradation. Thus, circadian clock properties depend in part upon a genetically-encoded competition between stabilizing and destabilizing forces, and genetic alterations in these mechanisms provide one explanation for human chronotype.

  4. Evidence for substantial fine-scale variation in recombination rates across the human genome.

    Science.gov (United States)

    Crawford, Dana C; Bhangale, Tushar; Li, Na; Hellenthal, Garrett; Rieder, Mark J; Nickerson, Deborah A; Stephens, Matthew

    2004-07-01

    Characterizing fine-scale variation in human recombination rates is important, both to deepen understanding of the recombination process and to aid the design of disease association studies. Current genetic maps show that rates vary on a megabase scale, but studying finer-scale variation using pedigrees is difficult. Sperm-typing experiments have characterized regions where crossovers cluster into 1-2-kb hot spots, but technical difficulties limit the number of studies. An alternative is to use population variation to infer fine-scale characteristics of the recombination process. Several surveys reported 'block-like' patterns of diversity, which may reflect fine-scale recombination rate variation, but limitations of available methods made this impossible to assess. Here, we applied a new statistical method, which overcomes these limitations, to infer patterns of fine-scale recombination rate variation in 74 genes. We found extensive rate variation both within and among genes. In particular, recombination hot spots are a common feature of the human genome: 47% (35 of 74) of genes showed substantive evidence for a hot spot, and many more showed evidence for some rate variation. No primary sequence characteristics are consistently associated with precise hot-spot location, although G+C content and nucleotide diversity are correlated with local recombination rate.

  5. Fractional calculus with applications in mechanics wave propagation, impact and variational principles

    CERN Document Server

    Atanackovic, Teodor M; Stankovic, Bogoljub; Zorica, Du?an

    2014-01-01

    The books Fractional Calculus with Applications in Mechanics: Vibrations and Diffusion Processes and Fractional Calculus with Applications in Mechanics: Wave Propagation, Impact and Variational Principles contain various applications of fractional calculus to the fields of classical mechanics. Namely, the books study problems in fields such as viscoelasticity of fractional order, lateral vibrations of a rod of fractional order type, lateral vibrations of a rod positioned on fractional order viscoelastic foundations, diffusion-wave phenomena, heat conduction, wave propagation, forced oscillati

  6. Human pose co-estimation and applications.

    Science.gov (United States)

    Eichner, Marcin; Ferrari, Vittorio

    2012-11-01

    Most existing techniques for articulated Human Pose Estimation (HPE)consider each person independently. Here we tackle the problem in a new setting,coined Human Pose Coestimation (PCE), where multiple people are in a common,but unknown pose. The task of PCE is to estimate their poses jointly and toproduce prototypes characterizing the shared pose. Since the poses of the individual people should be similar to the prototype, PCE has less freedom compared to estimating each pose independently, which simplifies the problem.We demonstrate our PCE technique on two applications. The first is estimating the pose of people performing the same activity synchronously, such as during aerobics, cheerleading, and dancing in a group. We show that PCE improves pose estimation accuracy over estimating each person independently. The second application is learning prototype poses characterizing a pose class directly from an image search engine queried by the class name (e.g., “lotus pose”). We show that PCE leads to better pose estimation in such images, and it learns meaningful prototypes which can be used as priors for pose estimation in novel images.

  7. Diurnal variation of human sweet taste recognition thresholds is correlated with plasma leptin levels.

    Science.gov (United States)

    Nakamura, Yuki; Sanematsu, Keisuke; Ohta, Rie; Shirosaki, Shinya; Koyano, Kiyoshi; Nonaka, Kazuaki; Shigemura, Noriatsu; Ninomiya, Yuzo

    2008-10-01

    It has recently been proposed that the peripheral taste organ is one of the targets for leptin. In lean mice, leptin selectively suppresses gustatory neural and behavioral responses to sweet compounds without affecting responses to other taste stimuli, whereas obese diabetic db/db mice with defects in leptin receptor lack this leptin suppression on sweet taste. Here, we further examined potential links between leptin and sweet taste in humans. A total of 91 nonobese subjects were used to determine recognition thresholds using a standard stair-case methodology for various taste stimuli. Plasma leptin levels were determined by an enzyme-linked immunosorbent assay at several timepoints during the day under normal and restricted-meal conditions. The recognition thresholds for sweet compounds exhibited a diurnal variation from 0800 to 2200 h that parallels variation for leptin levels, with the lowest thresholds in the morning and the highest thresholds at night. This diurnal variation is sweet-taste selective-it was not observed in thresholds for other taste stimuli (NaCl, citric acid, quinine, and mono-sodium glutamate). The diurnal variation for sweet thresholds in the normal feeding condition (three meals) was independent of meal timing and thereby blood glucose levels. Furthermore, when leptin levels were phase-shifted following imposition of one or two meals per day, the diurnal variation of thresholds for sweet taste shifted in parallel. This synchronization of diurnal variation in leptin levels and sweet taste recognition thresholds suggests a mechanistic connection between these two variables in humans.

  8. Perspectives on Human Genetic Variation from the HapMap Project

    OpenAIRE

    Gil McVean; Spencer, Chris C. A.; Raphaelle Chaix

    2005-01-01

    ABSTRACT The completion of the International HapMap Project marks the start of a new phase in human genetics. The aim of the project was to provide a resource that facilitates the design of efficient genome-wide association studies, through characterising patterns of genetic variation and linkage disequilibrium in a sample of 270 individuals across four geographical populations. In total, over one million SNPs have been typed across these genomes, providing an unprecedented view of human gene...

  9. Feedforward Object-Vision Models Only Tolerate Small Image Variations Compared to Human

    Directory of Open Access Journals (Sweden)

    Masoud eGhodrati

    2014-07-01

    Full Text Available Invariant object recognition is a remarkable ability of primates' visual system that its underlying mechanism has constantly been under intense investigations. Computational modelling is a valuable tool toward understanding the processes involved in invariant object recognition. Although recent computational models have shown outstanding performances on challenging image databases, they fail to perform well when images with more complex variations of the same object are applied to them. Studies have shown that making sparse representation of objects by extracting more informative visual features through a feedforward sweep can lead to higher recognition performances. Here, however, we show that when the complexity of image variations is high, even this approach results in poor performance compared to humans. To assess the performance of models and humans in invariant object recognition tasks, we built a parametrically controlled image database consisting of several object categories varied in different dimensions and levels, rendered from 3D planes. Comparing the performance of several object recognition models with human observers shows that only in low-level image variations the models perform similar to humans in categorization tasks. Furthermore, the results of our behavioral experiments demonstrate that, even under difficult experimental conditions (i.e. briefly presented masked stimuli with complex image variations, human observers performed outstandingly well, suggesting that the models are still far from resembling humans in invariant object recognition. Taken together, we suggest that learning sparse informative visual features, although desirable, is not a complete solution for future progresses in object-vision modelling. We show that this approach is not of significant help in solving the computational crux of object recognition (that is invariant object recognition when the identity-preserving image variations become more complex.

  10. Human-specific HERV-K insertion causes genomic variations in the human genome.

    Directory of Open Access Journals (Sweden)

    Wonseok Shin

    Full Text Available Human endogenous retroviruses (HERV sequences account for about 8% of the human genome. Through comparative genomics and literature mining, we identified a total of 29 human-specific HERV-K insertions. We characterized them focusing on their structure and flanking sequence. The results showed that four of the human-specific HERV-K insertions deleted human genomic sequences via non-classical insertion mechanisms. Interestingly, two of the human-specific HERV-K insertion loci contained two HERV-K internals and three LTR elements, a pattern which could be explained by LTR-LTR ectopic recombination or template switching. In addition, we conducted a polymorphic test and observed that twelve out of the 29 elements are polymorphic in the human population. In conclusion, human-specific HERV-K elements have inserted into human genome since the divergence of human and chimpanzee, causing human genomic changes. Thus, we believe that human-specific HERV-K activity has contributed to the genomic divergence between humans and chimpanzees, as well as within the human population.

  11. Patterns of genic intolerance of rare copy number variation in 59,898 human exomes

    Science.gov (United States)

    Ruderfer, Douglas M.; Hamamsy, Tymor; Lek, Monkol; Karczewski, Konrad J.; Kavanagh, David; Samocha, Kaitlin E.; Daly, Mark J.; MacArthur, Daniel G.; Fromer, Menachem; Purcell, Shaun M.

    2016-01-01

    Copy number variation (CNV) impacting protein-coding genes contributes significantly to human diversity and disease. Here we characterized the rates and properties of rare genic CNV (intolerance to CNVs that demonstrated moderate correlation with measures of genic constraint based on single-nucleotide variation (SNV) and was independently correlated with measures of evolutionary conservation. For individuals with schizophrenia, genes impacted by CNVs were more intolerant than in controls. ExAC CNV data constitutes a critical component of an integrated database spanning the spectrum of human genetic variation, aiding the interpretation of personal genomes as well as population-based disease studies. These data are freely available for download and visualization online. PMID:27533299

  12. Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

    Science.gov (United States)

    Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W.; Grubert, Fabian; Candille, Sophie I.; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L.; Tang, Hua; Ricci, Emiliano; Snyder, Michael P.

    2015-01-01

    Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy—many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. PMID:26297486

  13. Variation in human mate choice: Simultaneously investigating heritability, parental influence, sexual imprinting, and assortative mating

    NARCIS (Netherlands)

    Zietsch, B.P.; Verweij, K.J.H.; Heath, A.C.; Martin, N.G.

    2011-01-01

    Human mate choice is central to individuals' lives and to the evolution of the species, but the basis of variation in mate choice is not well understood. Here we looked at a large community-based sample of twins and their partners and parents (N > 20,000 individuals) to test for genetic and family

  14. An integrated map of genetic variation from 1.092 human genomes

    DEFF Research Database (Denmark)

    Abecasis, Goncalo R.; Auton, Adam; Brooks, Lisa D.

    2012-01-01

    By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination ...

  15. New Regions of the Human Genome Linked to Skin Color Variation in Some African Populations

    Science.gov (United States)

    In the first study of its kind, an international team of genomics researchers has identified new regions of the human genome that are associated with skin color variation in some African populations, opening new avenues for research on skin diseases and cancer in all populations.

  16. Variation in human mate choice: Simultaneously investigating heritability, parental influence, sexual imprinting, and assortative mating

    NARCIS (Netherlands)

    Zietsch, B.P.; Verweij, K.J.H.; Heath, A.C.; Martin, N.G.

    2011-01-01

    Human mate choice is central to individuals' lives and to the evolution of the species, but the basis of variation in mate choice is not well understood. Here we looked at a large community-based sample of twins and their partners and parents (N > 20,000 individuals) to test for genetic and

  17. Intrapopulational body size variation and cranial capacity variation in Middle Pleistocene humans: the Sima de los Huesos sample (Sierra de Atapuerca, Spain).

    Science.gov (United States)

    Lorenzo, C; Carretero, J M; Arsuaga, J L; Gracia, A; Martínez, I

    1998-05-01

    A sexual dimorphism more marked than in living humans has been claimed for European Middle Pleistocene humans, Neandertals and prehistoric modern humans. In this paper, body size and cranial capacity variation are studied in the Sima de los Huesos Middle Pleistocene sample. This is the largest sample of non-modern humans found to date from one single site, and with all skeletal elements represented. Since the techniques available to estimate the degree of sexual dimorphism in small palaeontological samples are all unsatisfactory, we have used the bootstraping method to asses the magnitude of the variation in the Sima de los Huesos sample compared to modern human intrapopulational variation. We analyze size variation without attempting to sex the specimens a priori. Anatomical regions investigated are scapular glenoid fossa; acetabulum; humeral proximal and distal epiphyses; ulnar proximal epiphysis; radial neck; proximal femur; humeral, femoral, ulnar and tibial shaft; lumbosacral joint; patella; calcaneum; and talar trochlea. In the Sima de los Huesos sample only the humeral midshaft perimeter shows an unusual high variation (only when it is expressed by the maximum ratio, not by the coefficient of variation). In spite of that the cranial capacity range at Sima de los Huesos almost spans the rest of the European and African Middle Pleistocene range. The maximum ratio is in the central part of the distribution of modern human samples. Thus, the hypothesis of a greater sexual dimorphism in Middle Pleistocene populations than in modern populations is not supported by either cranial or postcranial evidence from Sima de los Huesos.

  18. Impacts of terrain attributes and human activities on soil texture class variations in hilly areas, south-west China.

    Science.gov (United States)

    Li, Ai-Di; Guo, Peng-Tao; Wu, Wei; Liu, Hong-Bin

    2017-06-01

    Knowledge of soil texture variations is critical for agricultural and engineering applications because texture influences many other soil properties. This study used random forest method to evaluate the effects of human activities and topographic parameters on the spatial variability of soil texture in hilly areas where soil parent material was uniform. The study site covers 252 km 2 and is located in the Upper Yangtze River Basin of south-west China. A total of 3636 samples were collected from the cultivated soils at a depth of 20 cm of dryland (sloping field and terraced land) landscape. The soil texture class for each sample was estimated by experienced soil scientists in the field. Two soil texture classes (loam and clay) were observed in the watershed. Eleven terrain parameters were derived from a digital elevation model with a resolution of 30 m. Compared with loamy soils, clayey soils were mostly observed in the areas with lower elevation and gentle slopes. The outcome of random forest indicated that human activities and elevation had strong effects on soil texture class variations across the study site. Further results showed that the relative importance of terrain parameters to soil texture class variations varied with dryland landscape. Topographic wetness index and elevation were the most important variables for sloping field and terraced land landscapes, respectively.

  19. Systematic documentation and analysis of human genetic variation using the microattribution approach

    Science.gov (United States)

    Giardine, Belinda; Borg, Joseph; Higgs, Douglas R.; Peterson, Kenneth R.; Maglott, Donna; Basak, A. Nazli; Clark, Barnaby; Faustino, Paula; Felice, Alex E.; Francina, Alain; Gallivan, Monica V. E.; Georgitsi, Marianthi; Gibbons, Richard J.; Giordano, Piero C.; Harteveld, Cornelis L.; Joly, Philippe; Kanavakis, Emmanuel; Kollia, Panagoula; Menzel, Stephan; Miller, Webb; Moradkhani, Kamran; Old, John; Papachatzopoulou, Adamantia; Papadakis, Manoussos N.; Papadopoulos, Petros; Pavlovic, Sonja; Philipsen, Sjaak; Radmilovic, Milena; Riemer, Cathy; Schrijver, Iris; Stojiljkovic, Maja; Thein, Swee Lay; Traeger-Synodinos, Jan; Tully, Ray; Wada, Takahito; Waye, John; Wiemann, Claudia; Zukic, Branka; Chui, David H. K.; Wajcman, Henri; Hardison, Ross C.; Patrinos, George P.

    2013-01-01

    We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to these disorders, and then implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories 1. A total of 1,941 unique genetic variants in 37 genes, encoding globins (HBA2, HBA1, HBG2, HBG1, HBD, HBB) and other erythroid proteins (ALOX5AP, AQP9, ARG2, ASS1, ATRX, BCL11A, CNTNAP2, CSNK2A1, EPAS1, ERCC2, FLT1, GATA1, GPM6B, HAO2, HBS1L, KDR, KL, KLF1, MAP2K1, MAP3K5, MAP3K7, MYB, NOS1, NOS2, NOS3, NOX3, NUP133, PDE7B, SMAD3, SMAD6, and TOX) are currently documented in these databases with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants and now provides a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The large repository of previously reported data, together with more recent data, acquired by microattribution, demonstrates how the comprehensive documentation of human variation will provide key insights into normal biological processes and how these are perturbed in human genetic disease. Using the microattribution process set out here, datasets which took decades to accumulate for the globin genes could be assembled rapidly for other genes and disease systems. The principles established here for the globin gene system will serve as a model for other systems and the analysis of other common and/or complex human genetic diseases. PMID:21423179

  20. Variation in umami perception and in candidate genes for the umami receptor in mice and humans.

    Science.gov (United States)

    Shigemura, Noriatsu; Shirosaki, Shinya; Ohkuri, Tadahiro; Sanematsu, Keisuke; Islam, A A Shahidul; Ogiwara, Yoko; Kawai, Misako; Yoshida, Ryusuke; Ninomiya, Yuzo

    2009-09-01

    The unique taste induced by monosodium glutamate is referred to as umami taste. The umami taste is also elicited by the purine nucleotides inosine 5'-monophosphate and guanosine 5'-monophosphate. There is evidence that a heterodimeric G protein-coupled receptor, which consists of the T1R1 (taste receptor type 1, member 1, Tas1r1) and the T1R3 (taste receptor type 1, member 3, Tas1r3) proteins, functions as an umami taste receptor for rodents and humans. Splice variants of metabotropic glutamate receptors, mGluR(1) (glutamate receptor, metabotropic 1, Grm1) and mGluR(4) (glutamate receptor, metabotropic 4, Grm4), also have been proposed as taste receptors for glutamate. The taste sensitivity to umami substances varies in inbred mouse strains and in individual humans. However, little is known about the relation of umami taste sensitivity to variations in candidate umami receptor genes in rodents or in humans. In this article, we summarize current knowledge of the diversity of umami perception in mice and humans. Furthermore, we combine previously published data and new information from the single nucleotide polymorphism databases regarding variation in the mouse and human candidate umami receptor genes: mouse Tas1r1 (TAS1R1 for human), mouse Tas1r3 (TAS1R3 for human), mouse Grm1 (GRM1 for human), and mouse Grm4 (GRM4 for human). Finally, we discuss prospective associations between variation of these genes and umami taste perception in both species.

  1. Variation of topical application to skin under good clinical practice (GCP)

    DEFF Research Database (Denmark)

    Vind-Kezunovic, Dina; Serup, Jørgen Vedelskov

    2016-01-01

    clinical practice (GCP) study designed to investigate the local tolerability and safety on healthy skin of captopril 1% ointment versus a placebo ointment. Volunteers were instructed to apply an even layer of test ointment on a 51 cm(2) test area on the arm twice daily over a 3-week period. At weekly......INTRODUCTION: Application of topical products by individuals is inherently variable and accurate dosing can be difficult to control. Variation of the dose used under optimal conditions in drug trials is unknown. METHODS: This trial was part of a double-blind, randomized, placebo-controlled good...... application at week 4, with median 5.60 mg/cm(2) applied versus 2 mg/cm(2) (standard for good application) resulting in a 2.8-fold over-dosage. CONCLUSION: There was a major variation of test ointment application studied under GCP conditions with adherent participants. In dermatological practice...

  2. Human Motion Energy Harvesting for AAL Applications

    Science.gov (United States)

    Ylli, K.; Hoffmann, D.; Becker, P.; Willmann, A.; Folkmer, B.; Manoli, Y.

    2014-11-01

    Research and development into the topic of ambient assisted living has led to an increasing range of devices that facilitate a person's life. The issue of the power supply of these modern mobile systems however has not been solved satisfactorily yet. In this paper a flat inductive multi-coil harvester for integration into the shoe sole is presented. The device is designed for ambient assisted living (AAL) applications and particularly to power a self-lacing shoe. The harvester exploits the horizontal swing motion of the foot to generate energy. Stacks of opposing magnets move through a number of equally spaced coils to induce a voltage. The requirement of a flat structure which can be integrated into the shoe sole is met by a reduced form factor of the magnet stack. In order to exploit the full width of the shoe sole, supporting structures are used to parallelize the harvester and therefore increase the number of active elements, i.e. magnets and coils. The development and characterization of different harvester variations is presented with the best tested design generating an average power of up to 2.14 mW at a compact device size of 75 × 41.5 × 15 mm3 including housing.

  3. Parietal structure and function explain human variation in working memory biases of visual attention.

    Science.gov (United States)

    Soto, David; Rotshtein, Pia; Kanai, Ryota

    2014-04-01

    Recent research indicates that human attention appears inadvertently biased by items that match the contents of working memory (WM). WM-biases can lead to attentional costs when the memory content matches goal-irrelevant items and to attentional benefits when it matches the sought target. Here we used functional and structural MRI data to determine the neural basis of human variation in WM biases. We asked whether human variation in WM-benefits and WM-costs merely reflects the process of attentional capture by the contents of WM or whether variation in WM biases may be associated with distinct forms of cognitive control over internal WM signals based on selection goals. Human ability to use WM contents to facilitate selection was positively correlated with gray matter volume in the left superior posterior parietal cortex (PPC), while the ability to overcome interference by WM-matching distracters was associated with the left inferior PPC in the anterior IPS. Functional activity in the left PPC, measured by functional MRI, also predicted the magnitude of WM-costs on selection. Both structure and function of left PPC mediate the expression of WM biases in human visual attention. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Genetic variation in lipid desaturases and its impact on the development of human disease

    Directory of Open Access Journals (Sweden)

    Mutch David M

    2010-06-01

    Full Text Available Abstract Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2 and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.

  5. A review of the established and suspected causes of variations in human sex ratio at birth.

    Science.gov (United States)

    James, William H; Grech, Victor

    2017-06-01

    The human sex ratio (proportion male) at birth (SRB) varies with many variables. Some of this variation has an established proximate cause. For instance, low SRB (more females) at birth are associated with various forms of stressful events or circumstances during or prior to pregnancy. These low SRB are almost certainly mainly caused by maternal-stress-induced male foetal loss. Other types of SRB variation are thought to be caused by hormonal variation in either or both parents around the time of conception. One or other of these two types of proximate cause seems to be responsible for most of the established variation of SRB. This will be illustrated here in respect of some selected forms of SRB variation. It seems likely that a clarification of the hormonal causes of SRB variation will also help explain the striking (apparent) inconsistencies in the results of reported tests of the influential Trivers-Willard hypothesis. It is further proposed that an appreciation of the evidence that parental hormones influence SRB may enhance understanding of several important pathologies (hepatitis B, toxoplasmosis, testicular cancer, prostate cancer and autism). Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Sequence variations in human ZP genes as potential modifiers of zona pellucida architecture.

    Science.gov (United States)

    Pökkylä, Reeta-Maria; Lakkakorpi, Jouni Tapani; Nuojua-Huttunen, Sinikka Helena; Tapanainen, Juha Samuli

    2011-06-30

    To examine putative associations between zona pellucida (ZP) anomalies and sequence variations in genes expressing structural ZP glycoprotein components, sequence data of 31 volunteers participating in IVF treatments were obtained and analyzed together with morphologic data of the respective oocytes. Our results suggest that some of the most frequent zona anomalies may be at least partly explained by sequence variations in genes expressing the four human ZP proteins, especially those in ZP2 and ZP3. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. A new biophysical metric for interrogating the information content in human genome sequence variation: Proof of concept.

    Science.gov (United States)

    Lindesay, James; Mason, Tshela E; Ricks-Santi, Luisel; Hercules, William; Kurian, Philip; Dunston, Georgia M

    2012-02-01

    The 21st century emergence of genomic medicine is shifting the paradigm in biomedical science from the population phenotype to the individual genotype. In characterizing the biology of disease and health disparities in population genetics, human populations are often defined by the most common alleles in the group. This definition poses difficulties when categorizing individuals in the population who do not have the most common allele(s). Various epidemiological studies have shown an association between common genomic variation, such as single nucleotide polymorphisms (SNPs), and common diseases. We hypothesize that information encoded in the structure of SNP haploblock variation in the human leukocyte antigen-disease related (HLA-DR) region of the genome illumines molecular pathways and cellular mechanisms involved in the regulation of host adaptation to the environment. In this paper we describe the development and application of the normalized information content (NIC) as a novel metric based on SNP haploblock variation. The NIC facilitates translation of biochemical DNA sequence variation into a biophysical quantity derived from Boltzmann's canonical ensemble in statistical physics and used widely in information theory. Our normalization of this information metric allows for comparisons of unlike, or even unrelated, regions of the genome. We report here NIC values calculated for HLA-DR SNP haploblocks constructed by Haploview, a product of the International Haplotype Map Project. These haploblocks were scanned for potential regulatory elements using ConSite and miRBase, publicly available bioinformatics tools. We found that all of the haploblocks with statistically low NIC values contained putative transcription factor binding sites and microRNA motifs, suggesting correlation with genomic regulation. Thus, we were able to relate a mathematical measure of information content in HLA-DR SNP haploblocks to biologically relevant functional knowledge embedded in the

  8. Read clouds uncover variation in complex regions of the human genome.

    Science.gov (United States)

    Bishara, Alex; Liu, Yuling; Weng, Ziming; Kashef-Haghighi, Dorna; Newburger, Daniel E; West, Robert; Sidow, Arend; Batzoglou, Serafim

    2015-10-01

    Although an increasing amount of human genetic variation is being identified and recorded, determining variants within repeated sequences of the human genome remains a challenge. Most population and genome-wide association studies have therefore been unable to consider variation in these regions. Core to the problem is the lack of a sequencing technology that produces reads with sufficient length and accuracy to enable unique mapping. Here, we present a novel methodology of using read clouds, obtained by accurate short-read sequencing of DNA derived from long fragment libraries, to confidently align short reads within repeat regions and enable accurate variant discovery. Our novel algorithm, Random Field Aligner (RFA), captures the relationships among the short reads governed by the long read process via a Markov Random Field. We utilized a modified version of the Illumina TruSeq synthetic long-read protocol, which yielded shallow-sequenced read clouds. We test RFA through extensive simulations and apply it to discover variants on the NA12878 human sample, for which shallow TruSeq read cloud sequencing data are available, and on an invasive breast carcinoma genome that we sequenced using the same method. We demonstrate that RFA facilitates accurate recovery of variation in 155 Mb of the human genome, including 94% of 67 Mb of segmental duplication sequence and 96% of 11 Mb of transcribed sequence, that are currently hidden from short-read technologies. © 2015 Bishara et al.; Published by Cold Spring Harbor Laboratory Press.

  9. Combined examination of sequence and copy number variations in human deafness genes improves diagnosis for cases of genetic deafness

    OpenAIRE

    Ji, Haiting; Lu, Jingqiao; Wang, Jianjun; Li, Huawei; Lin, Xi

    2014-01-01

    Background Copy number variations (CNVs) are the major type of structural variation in the human genome, and are more common than DNA sequence variations in populations. CNVs are important factors for human genetic and phenotypic diversity. Many CNVs have been associated with either resistance to diseases or identified as the cause of diseases. Currently little is known about the role of CNVs in causing deafness. CNVs are currently not analyzed by conventional genetic analysis methods to stud...

  10. Balancing selection on a regulatory region exhibiting ancient variation that predates human-neandertal divergence.

    Science.gov (United States)

    Gokcumen, Omer; Zhu, Qihui; Mulder, Lubbertus C F; Iskow, Rebecca C; Austermann, Christian; Scharer, Christopher D; Raj, Towfique; Boss, Jeremy M; Sunyaev, Shamil; Price, Alkes; Stranger, Barbara; Simon, Viviana; Lee, Charles

    2013-04-01

    Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup) aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs) across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (pNeandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003) and positive Tajima's D (p = 0.00285) statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human-Neandertal divergence and is evolving under balancing selection, especially among European populations.

  11. Balancing selection on a regulatory region exhibiting ancient variation that predates human-neandertal divergence.

    Directory of Open Access Journals (Sweden)

    Omer Gokcumen

    2013-04-01

    Full Text Available Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10⁻¹⁵. Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003 and positive Tajima's D (p = 0.00285 statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human-Neandertal divergence and is evolving under balancing selection, especially among European

  12. Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity

    OpenAIRE

    Gupta, Vinod K.; Paul, Sandip; Dutta, Chitra

    2017-01-01

    One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats—Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review f...

  13. Adaptive potential of genomic structural variation in human and mammalian evolution.

    Science.gov (United States)

    Radke, David W; Lee, Charles

    2015-09-01

    Because phenotypic innovations must be genetically heritable for biological evolution to proceed, it is natural to consider new mutation events as well as standing genetic variation as sources for their birth. Previous research has identified a number of single-nucleotide polymorphisms that underlie a subset of adaptive traits in organisms. However, another well-known class of variation, genomic structural variation, could have even greater potential to produce adaptive phenotypes, due to the variety of possible types of alterations (deletions, insertions, duplications, among others) at different genomic positions and with variable lengths. It is from these dramatic genomic alterations, and selection on their phenotypic consequences, that adaptations leading to biological diversification could be derived. In this review, using studies in humans and other mammals, we highlight examples of how phenotypic variation from structural variants might become adaptive in populations and potentially enable biological diversification. Phenotypic change arising from structural variants will be described according to their immediate effect on organismal metabolic processes, immunological response and physical features. Study of population dynamics of segregating structural variation can therefore provide a window into understanding current and historical biological diversification. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Population and allelic variation of A-to-I RNA editing in human transcriptomes.

    Science.gov (United States)

    Park, Eddie; Guo, Jiguang; Shen, Shihao; Demirdjian, Levon; Wu, Ying Nian; Lin, Lan; Xing, Yi

    2017-07-28

    A-to-I RNA editing is an important step in RNA processing in which specific adenosines in some RNA molecules are post-transcriptionally modified to inosines. RNA editing has emerged as a widespread mechanism for generating transcriptome diversity. However, there remain significant knowledge gaps about the variation and function of RNA editing. In order to determine the influence of genetic variation on A-to-I RNA editing, we integrate genomic and transcriptomic data from 445 human lymphoblastoid cell lines by combining an RNA editing QTL (edQTL) analysis with an allele-specific RNA editing (ASED) analysis. We identify 1054 RNA editing events associated with cis genetic polymorphisms. Additionally, we find that a subset of these polymorphisms is linked to genome-wide association study signals of complex traits or diseases. Finally, compared to random cis polymorphisms, polymorphisms associated with RNA editing variation are located closer spatially to their respective editing sites and have a more pronounced impact on RNA secondary structure. Our study reveals widespread cis variation in RNA editing among genetically distinct individuals and sheds light on possible phenotypic consequences of such variation on complex traits and diseases.

  15. Common genetic variation drives molecular heterogeneity in human iPSCs.

    Science.gov (United States)

    Kilpinen, Helena; Goncalves, Angela; Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard; Stegle, Oliver; Gaffney, Daniel J

    2017-06-15

    Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

  16. Estimated biological variation of the mature human milk fatty acid composition.

    Science.gov (United States)

    Smit, E N; Martini, I A; Mulder, H; Boersma, E R; Muskiet, F A J

    2002-01-01

    We estimated the biological variation (CV(biol)) of 28 fatty acids (FA) in 465 mature human milk samples from The Netherlands, Caribbean, Jerusalem, Tanzania and Pakistan, by using data from the observed variation (CV(obs)) and analytical variation (CV(anal)). CV(biol) of the various regions was remarkably similar. The average CV(biol) of 455 samples, Pakistan excluded, ranged from 12.7% for 16:0 and 18.9% for 18:1 omega 9 to 68% for 22:6 omega 3 and about 100% for 20:5 omega 3. Those of 20:4 omega 6, 18:2 omega 6 and 18:3 omega 3 were 28.0, 33.0 and 37.3%, respectively. Because of the large CV(biol) and the many dietary changes in recent history, it seems impossible to consider the present human milk FA composition as the 'gold standard' for infant formula. Optimal human milk FA composition should rather derive from populations that consume traditional diets or from the scientific data that show the function of the individual FAs in neonatal development.

  17. Comparison of inter- and intraspecies variation in humans and fruit flies

    Directory of Open Access Journals (Sweden)

    Juliann Shih

    2015-03-01

    Full Text Available Variation is essential to species survival and adaptation during evolution. This variation is conferred by the imperfection of biochemical processes, such as mutations and alterations in DNA sequences, and can also be seen within genomes through processes such as the generation of antibodies. Recent sequencing projects have produced multiple versions of the genomes of humans and fruit flies (Drosophila melanogaster. These give us a chance to study how individual gene sequences vary within and between species. Here we arranged human and fly genes in orthologous pairs and compared such within-species variability with their degree of conservation between flies and humans. We observed that a significant number of proteins associated with mRNA translation are highly conserved between species and yet are highly variable within each species. The fact that we observe this in two species whose lineages separated more than 700 million years ago suggests that this is the result of a very ancient process. We hypothesize that this effect might be attributed to a positive selection for variability of virus-interacting proteins that confers a general resistance to viral hijacking of the mRNA translation machinery within populations. Our analysis points to this and to other processes resulting in positive selection for gene variation.

  18. Understanding variation in human fertility: what can we learn from evolutionary demography?

    Science.gov (United States)

    Sear, Rebecca; Lawson, David W; Kaplan, Hillard; Shenk, Mary K

    2016-04-19

    Decades of research on human fertility has presented a clear picture of how fertility varies, including its dramatic decline over the last two centuries in most parts of the world. Why fertility varies, both between and within populations, is not nearly so well understood. Fertility is a complex phenomenon, partly physiologically and partly behaviourally determined, thus an interdisciplinary approach is required to understand it. Evolutionary demographers have focused on human fertility since the 1980s. The first wave of evolutionary demographic research made major theoretical and empirical advances, investigating variation in fertility primarily in terms of fitness maximization. Research focused particularly on variation within high-fertility populations and small-scale subsistence societies and also yielded a number of hypotheses for why fitness maximization seems to break down as fertility declines during the demographic transition. A second wave of evolutionary demography research on fertility is now underway, paying much more attention to the cultural and psychological mechanisms underpinning fertility. It is also engaging with the complex, multi-causal nature of fertility variation, and with understanding fertility in complex modern and transitioning societies. Here, we summarize the history of evolutionary demographic work on human fertility, describe the current state of the field, and suggest future directions. © 2016 The Author(s).

  19. Early modern humans and morphological variation in Southeast Asia: fossil evidence from Tam Pa Ling, Laos.

    Science.gov (United States)

    Demeter, Fabrice; Shackelford, Laura; Westaway, Kira; Duringer, Philippe; Bacon, Anne-Marie; Ponche, Jean-Luc; Wu, Xiujie; Sayavongkhamdy, Thongsa; Zhao, Jian-Xin; Barnes, Lani; Boyon, Marc; Sichanthongtip, Phonephanh; Sénégas, Frank; Karpoff, Anne-Marie; Patole-Edoumba, Elise; Coppens, Yves; Braga, José

    2015-01-01

    Little is known about the timing of modern human emergence and occupation in Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by at least 60 ka is supported by archaeological, paleogenetic and paleoanthropological data. Recent discoveries in Laos, a modern human cranium (TPL1) from Tam Pa Ling's cave, provided the first evidence for the presence of early modern humans in mainland Southeast Asia by 63-46 ka. In the current study, a complete human mandible representing a second individual, TPL 2, is described using discrete traits and geometric morphometrics with an emphasis on determining its population affinity. The TPL2 mandible has a chin and other discrete traits consistent with early modern humans, but it retains a robust lateral corpus and internal corporal morphology typical of archaic humans across the Old World. The mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest that a large range of morphological variation was present in early modern human populations residing in the eastern Eurasia by MIS 3.

  20. Assessing endocranial variations in great apes and humans using 3D data from virtual endocasts.

    Science.gov (United States)

    Bienvenu, Thibaut; Guy, Franck; Coudyzer, Walter; Gilissen, Emmanuel; Roualdès, Georges; Vignaud, Patrick; Brunet, Michel

    2011-06-01

    Modern humans are characterized by their large, complex, and specialized brain. Human brain evolution can be addressed through direct evidence provided by fossil hominid endocasts (i.e. paleoneurology), or through indirect evidence of extant species comparative neurology. Here we use the second approach, providing an extant comparative framework for hominid paleoneurological studies. We explore endocranial size and shape differences among great apes and humans, as well as between sexes. We virtually extracted 72 endocasts, sampling all extant great ape species and modern humans, and digitized 37 landmarks on each for 3D generalized Procrustes analysis. All species can be differentiated by their endocranial shape. Among great apes, endocranial shapes vary from short (orangutans) to long (gorillas), perhaps in relation to different facial orientations. Endocranial shape differences among African apes are partly allometric. Major endocranial traits distinguishing humans from great apes are endocranial globularity, reflecting neurological reorganization, and features linked to structural responses to posture and bipedal locomotion. Human endocasts are also characterized by posterior location of foramina rotunda relative to optic canals, which could be correlated to lesser subnasal prognathism compared to living great apes. Species with larger brains (gorillas and humans) display greater sexual dimorphism in endocranial size, while sexual dimorphism in endocranial shape is restricted to gorillas, differences between males and females being at least partly due to allometry. Our study of endocranial variations in extant great apes and humans provides a new comparative dataset for studies of fossil hominid endocasts. Copyright © 2011 Wiley-Liss, Inc.

  1. A Variational Principle for Spontaneous Wiggler Radiation with Applications to Harmonic-Cascade Radiation

    CERN Document Server

    Charman, A E

    2005-01-01

    Within the framework of a Hilbert space formalism, we derive a maximum-power variational principle (MPVP) applicable to classical spontaneous radiation from prescribed current sources. The principe appears similar to, but actually is distinct from, other well-known variational principles associated with Hamilton's principle of stationary action or Rumsey's methods involving "reaction." The techniques have been developed for and applied to the case of undulator radiation from relativistic electron beams, specifically to X-ray generation using an harmonic cascade. Such processes are currently evaluated using extensive calculations or simulation codes which can be slow to evaluate and difficult to set up. The variational principle emerged as a natural step in a simple analytic algorithm to predict the output of a harmonic generation beamline in the low-gain regime based on trial functions for the output radiation. Full three-dimensional effects are included, and it may be generalized to include further effects s...

  2. Comparative Variation within the Genome of Campylobacter jejuni NCTC 11168 in Human and Murine Hosts

    Science.gov (United States)

    Selinger, L. Brent; Taboada, Eduardo N.; Uwiera, Richard R. E.; Abbott, D. Wade; Inglis, G. Douglas

    2014-01-01

    Campylobacteriosis incited by C. jejuni is a significant enteric disease of human beings. A person working with two reference strains of C. jejuni National Collection of Type Cultures (NCTC) 11168 developed symptoms of severe enteritis including bloody diarrhea. The worker was determined to be infected by C. jejuni. In excess of 50 isolates were recovered from the worker’s stool. All of the recovered isolates and the two reference strains were indistinguishable from each other based on comparative genomic fingerprint subtyping. Whole genome sequence analysis indicated that the worker was infected with a C. jejuni NCTC 11168 obtained from the American Type Culture Collection; this strain (NCTC 11168-GSv) is the genome sequence reference. After passage through the human host, major genetic changes including indel mutations within twelve contingency loci conferring phase variations were detected in the genome of C. jejuni. Specific and robust single nucleotide polymorphism (SNP) changes in the human host were also observed in two loci (Cj0144c, Cj1564). In mice inoculated with an isolate of C. jejuni NCTC 11168-GSv from the infected person, the isolate underwent further genetic variation. At nine loci, mutations specific to inoculated mice including five SNP changes were observed. The two predominant SNPs observed in the human host reverted in mice. Genetic variations occurring in the genome of C. jejuni in mice corresponded to increased densities of C. jejuni cells associated with cecal mucosa. In conclusion, C. jejuni NCTC 11168-GSv was found to be highly virulent in a human being inciting severe enteritis. Host-specific mutations in the person with enteritis occurred/were selected for in the genome of C. jejuni, and many were not maintained in mice. Information obtained in the current study provides new information on host-specific genetic adaptation by C. jejuni. PMID:24516617

  3. Comparative variation within the genome of Campylobacter jejuni NCTC 11168 in human and murine hosts.

    Directory of Open Access Journals (Sweden)

    Dallas K Thomas

    Full Text Available Campylobacteriosis incited by C. jejuni is a significant enteric disease of human beings. A person working with two reference strains of C. jejuni National Collection of Type Cultures (NCTC 11168 developed symptoms of severe enteritis including bloody diarrhea. The worker was determined to be infected by C. jejuni. In excess of 50 isolates were recovered from the worker's stool. All of the recovered isolates and the two reference strains were indistinguishable from each other based on comparative genomic fingerprint subtyping. Whole genome sequence analysis indicated that the worker was infected with a C. jejuni NCTC 11168 obtained from the American Type Culture Collection; this strain (NCTC 11168-GSv is the genome sequence reference. After passage through the human host, major genetic changes including indel mutations within twelve contingency loci conferring phase variations were detected in the genome of C. jejuni. Specific and robust single nucleotide polymorphism (SNP changes in the human host were also observed in two loci (Cj0144c, Cj1564. In mice inoculated with an isolate of C. jejuni NCTC 11168-GSv from the infected person, the isolate underwent further genetic variation. At nine loci, mutations specific to inoculated mice including five SNP changes were observed. The two predominant SNPs observed in the human host reverted in mice. Genetic variations occurring in the genome of C. jejuni in mice corresponded to increased densities of C. jejuni cells associated with cecal mucosa. In conclusion, C. jejuni NCTC 11168-GSv was found to be highly virulent in a human being inciting severe enteritis. Host-specific mutations in the person with enteritis occurred/were selected for in the genome of C. jejuni, and many were not maintained in mice. Information obtained in the current study provides new information on host-specific genetic adaptation by C. jejuni.

  4. Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences

    OpenAIRE

    Brett eWagner Mackenzie; David William Waite; Michael W Taylor

    2015-01-01

    The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extracti...

  5. Advances in variational and hemivariational inequalities theory, numerical analysis, and applications

    CERN Document Server

    Migórski, Stanisław; Sofonea, Mircea

    2015-01-01

    Highlighting recent advances in variational and hemivariational inequalities with an emphasis on theory, numerical analysis and applications, this volume serves as an indispensable resource to graduate students and researchers interested in the latest results from recognized scholars in this relatively young and rapidly-growing field. Particularly, readers will find that the volume’s results and analysis present valuable insights into the fields of pure and applied mathematics, as well as civil, aeronautical, and mechanical engineering. Researchers and students will find new results on well posedness to stationary and evolutionary inequalities and their rigorous proofs. In addition to results on modeling and abstract problems, the book contains new results on the numerical methods for variational and hemivariational inequalities. Finally, the applications presented illustrate the use of these results in the study of miscellaneous mathematical models which describe the contact between deformable bodies and a...

  6. Stable isotopic variation in tropical forest plants for applications in primatology.

    Science.gov (United States)

    Blumenthal, Scott A; Rothman, Jessica M; Chritz, Kendra L; Cerling, Thure E

    2016-10-01

    Stable isotope analysis is a promising tool for investigating primate ecology although nuanced ecological applications remain challenging, in part due to the complex nature of isotopic variability in plant-animal systems. The aim of this study is to investigate sources of carbon and nitrogen isotopic variation at the base of primate food webs that reflect aspects of primate ecology. The majority of primates inhabit tropical forest ecosystems, which are dominated by C3 vegetation. We used stable isotope ratios in plants from Kibale National Park, Uganda, a well-studied closed-canopy tropical forest, to investigate sources of isotopic variation among C3 plants related to canopy stratification, leaf age, and plant part. Unpredictably, our results demonstrate that vertical stratification within the canopy does not explain carbon or nitrogen isotopic variation in leaves. Leaf age can be a significant source of isotopic variation, although the direction and magnitude of this difference is not consistent across tree species. Some plant parts are clearly differentiated in carbon and nitrogen isotopic composition, particularly leaves compared to non-photosynthetic parts such as reproductive parts and woody stem parts. Overall, variation in the isotopic composition of floral communities, plant species, and plant parts demonstrates that stable isotope studies must include analysis of local plant species and parts consumed by the primates under study from within the study area. Am. J. Primatol. 78:1041-1054, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  7. Disentangling the spatio-environmental drivers of human settlement: an eigenvector based variation decomposition.

    Directory of Open Access Journals (Sweden)

    Ralf Vandam

    Full Text Available The relative importance of deterministic and stochastic processes driving patterns of human settlement remains controversial. A main reason for this is that disentangling the drivers of distributions and geographic clustering at different spatial scales is not straightforward and powerful analytical toolboxes able to deal with this type of data are largely deficient. Here we use a multivariate statistical framework originally developed in community ecology, to infer the relative importance of spatial and environmental drivers of human settlement. Using Moran's eigenvector maps and a dataset of spatial variation in a set of relevant environmental variables we applied a variation partitioning procedure based on redundancy analysis models to assess the relative importance of spatial and environmental processes explaining settlement patterns. We applied this method on an archaeological dataset covering a 15 km(2 area in SW Turkey spanning a time period of 8000 years from the Late Neolithic/Early Chalcolithic up to the Byzantine period. Variation partitioning revealed both significant unique and commonly explained effects of environmental and spatial variables. Land cover and water availability were the dominant environmental determinants of human settlement throughout the study period, supporting the theory of the presence of farming communities. Spatial clustering was mainly restricted to small spatial scales. Significant spatial clustering independent of environmental gradients was also detected which can be indicative of expansion into unsuitable areas or an unexpected absence in suitable areas which could be caused by dispersal limitation. Integrating historic settlement patterns as additional predictor variables resulted in more explained variation reflecting temporal autocorrelation in settlement locations.

  8. Lionel Penrose and the concept of normal variation in human intelligence.

    Science.gov (United States)

    Valles, Sean A

    2012-03-01

    Lionel Penrose (1898-1972) was an important leader during the mid-20th century decline of eugenics and the development of modern medical genetics. However, historians have paid little attention to his radical theoretical challenges to mainline eugenic concepts of mental disease. Working from a classification system developed with his colleague, E. O. Lewis, Penrose developed a statistically sophisticated and clinically grounded refutation of the popular position that low intelligence is inherently a disease state. In the early 1930s, Penrose advocated dividing "mental defect" (low intelligence) into two categories: "pathological mental defect," which is a disease state that can be traced to a distinct genetic or environmental cause, and "subcultural mental defect," which is not an inherent disease state, but rather a statistically necessary manifestation of human variation in intelligence. I explore the historical context and theoretical import of this contribution, discussing its rejection of typological thinking and noting that it preceded Theodosius Dobzhansky's better-known defense of human diversity. I illustrate the importance of Penrose's contribution with a discussion of an analogous situation in contemporary medicine, the controversial practice of using human growth hormone injections to treat "idiopathic short stature" (mere diminutive height, with no distinct cause). I show how Penrose's contributions to understanding human variation make such treatments appear quite misguided. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Cranial shape and size variation in human evolution: structural and functional perspectives.

    Science.gov (United States)

    Bruner, Emiliano

    2007-12-01

    A GLIMPSE INTO MODERN PALEOANTHROPOLOGY: In the last decades, paleoanthropology has been deeply modified, changing from a descriptive and historical science to a more quantitative and analytical discipline. The covariation of multiple traits is investigated to study the evolutionary changes of the underlying anatomical models, mostly through the introduction of digital biomedical imaging procedures and of computed geometrical analyses supported by multivariate statistics. FUNCTIONAL CRANIOLOGY: The evolution of the human cranium is consequently considered in terms of functional and structural relationships between its components, largely influenced by the allometric variations associated with the increase in the relative cranial capacity. In the human genus, the changes in the face, base, and neurocranium are characterised by a mosaic variation, in which adaptations, secondary consequences, and stochastic factors concur to generate a set of anatomical possibilities and constraints. SYSTEMIC PERSPECTIVES TO THE EVOLUTION OF THE HUMAN CRANIAL MORPHOLOGY: Concepts like morphological modularity, anatomical integration, and heterochrony represent key issues in the development of the current human evolutionary studies.

  10. Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans.

    Directory of Open Access Journals (Sweden)

    Arbel Harpak

    2016-12-01

    Full Text Available The site frequency spectrum (SFS has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the "phylogenetically-conditioned SFS" or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC, combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. In summary, we show that variable mutation rates are key determinants of the SFS in humans.

  11. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui

    2011-01-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations...... throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has...

  12. "Geographical Distribution Patterns of Various Genes": genetic studies of human variation after 1945.

    Science.gov (United States)

    Lipphardt, Veronika

    2014-09-01

    After WWII, physical anthropologists and human geneticists struggled hard to demonstrate distance from 'racial science' and 'eugenics'. This was a crucial factor in the 'revolution' of physical anthropology in the 1950s, as contemporary accounts referred to it. My paper examines the apparent turn during this period from anthropometric measurements to blood-group analysis, and from 'races' to 'small endogamous populations', or 'isolates', as the unit of study. I demonstrate that anthropometry and blood-group analysis were used simultaneously and in the same research projects until the 1960s. Isolated populations were the new target groups of human population geneticists, from large continental groups to small village populations. Colonial infrastructures provided suitable conditions for these kinds of transnational research projects. I argue that this new framework helped to translate much of the content of earlier racial studies into a less attackable approach to human variation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    Science.gov (United States)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  14. Ontogenetic variation in the mandibular ramus of great apes and humans.

    Science.gov (United States)

    Terhune, Claire E; Robinson, Chris A; Ritzman, Terrence B

    2014-06-01

    Considerable variation exists in mandibular ramus form among primates, particularly great apes and humans. Recent analyses of adult ramal morphology have suggested that features on the ramus, especially the coronoid process and sigmoid notch, can be treated as phylogenetic characters that can be used to reconstruct relationships among great ape and fossil hominin taxa. Others have contended that ramal morphology is more influenced by function than phylogeny. In addition, it remains unclear how ontogeny of the ramus contributes to adult variation in great apes and humans. Specifically, it is unclear whether differences among adults appear early and are maintained throughout ontogeny, or if these differences appear, or are enhanced, during later development. To address these questions, the present study examined a broad ontogenetic sample of great apes and humans using two-dimensional geometric morphometric analysis. Variation within and among species was summarized using principal component and thin plate spline analyses, and Procrustes distances and discriminant function analyses were used to statistically compare species and age classes. Results suggest that morphological differences among species in ramal morphology appear early in ontogeny and persist into adulthood. Morphological differences among adults are particularly pronounced in the height and angulation of the coronoid process, the depth and anteroposterior length of the sigmoid notch, and the inclination of the ramus. In all taxa, the ascending ramus of the youngest specimens is more posteriorly inclined in relation to the occlusal plane, shifting to become more upright in adults. These results suggest that, although there are likely functional influences over the form of the coronoid process and ramus, the morphology of this region can be profitably used to differentiate among great apes, modern humans, and fossil hominid taxa. Copyright © 2014 Wiley Periodicals, Inc.

  15. Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity

    Directory of Open Access Journals (Sweden)

    Vinod K. Gupta

    2017-06-01

    Full Text Available One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats—Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT. The review focuses on the general trend in the human microbiome evolution—a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota—the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome—nature or nurture, host genetics

  16. Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity

    Science.gov (United States)

    Gupta, Vinod K.; Paul, Sandip; Dutta, Chitra

    2017-01-01

    One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats—Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution—a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota—the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome—nature or nurture, host genetics or his environment

  17. Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity.

    Science.gov (United States)

    Gupta, Vinod K; Paul, Sandip; Dutta, Chitra

    2017-01-01

    One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats-Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution-a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota-the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome-nature or nurture, host genetics or his environment. Some of

  18. In silico analysis of amino acid variation in human respiratory syncytial virus: insights into immunodiagnostics.

    Science.gov (United States)

    Souza, Claudemir; Zanchin, Nilson It; Krieger, Marco A; Ludwig, Adriana

    2017-10-01

    The highly contagious nature of human respiratory syncytial virus (HRSV) and the gravity of its infection in newborns and vulnerable adults pose a serious public health problem. Thus, a rapid and sensitive diagnostic test for viral detection that can be implemented upon the first appearance of symptoms is needed. The genetic variation of the virus must be considered for immunodiagnostic purposes. To analyse HRSV genetic variation and discuss the possible consequences for capture immunoassay development. We performed a wide analysis of N, F and G protein variation based on the HRSV sequences currently available in the GenBank database. We also evaluated their similarity with homologous proteins from other viruses. The mean amino acid divergences for the N, F, and G proteins between HRSV-A and HRSV-B were determined to be approximately 4%, 10% and 47%, respectively. Due to their high conservation, assays based on the full-length N and F proteins may not distinguish HRSV from human metapneumovirus and other Mononegavirales viruses, and the full-length G protein would most likely produce false negative results due to its high divergence. We have identified specific regions in each of these three proteins that have higher potential to produce specific results, and their combined utilisation should be considered for immunoassay development.

  19. The role of humans in facilitating and sustaining coat colour variation in domestic animals.

    Science.gov (United States)

    Linderholm, Anna; Larson, Greger

    2013-01-01

    Though the process of domestication results in a wide variety of novel phenotypic and behavioural traits, coat colour variation is one of the few characteristics that distinguishes all domestic animals from their wild progenitors. A number of recent reviews have discussed and synthesised the hundreds of genes known to underlie specific coat colour patterns in a wide range of domestic animals. This review expands upon those studies by asking how what is known about the causative mutations associated with variable coat colours, can be used to address three specific questions related to the appearance of non wild-type coat colours in domestic animals. Firstly, is it possible that coat colour variation resulted as a by-product of an initial selection for tameness during the early phases of domestication? Secondly, how soon after the process began did domestic animals display coat colour variation? Lastly, what evidence is there that intentional human selection, rather than drift, is primarily responsible for the wide range of modern coat colours? By considering the presence and absence of coat colour genes within the context of the different pathways animals travelled from wild to captive populations, we conclude that coat colour variability was probably not a pleiotropic effect of the selection for tameness, that coat colours most likely appeared very soon after the domestication process began, and that humans have been actively selecting for colour novelty and thus allowing for the proliferation of new mutations in coat colour genes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Detecting genetic association of common human facial morphological variation using high density 3D image registration.

    Science.gov (United States)

    Peng, Shouneng; Tan, Jingze; Hu, Sile; Zhou, Hang; Guo, Jing; Jin, Li; Tang, Kun

    2013-01-01

    Human facial morphology is a combination of many complex traits. Little is known about the genetic basis of common facial morphological variation. Existing association studies have largely used simple landmark-distances as surrogates for the complex morphological phenotypes of the face. However, this can result in decreased statistical power and unclear inference of shape changes. In this study, we applied a new image registration approach that automatically identified the salient landmarks and aligned the sample faces using high density pixel points. Based on this high density registration, three different phenotype data schemes were used to test the association between the common facial morphological variation and 10 candidate SNPs, and their performances were compared. The first scheme used traditional landmark-distances; the second relied on the geometric analysis of 15 landmarks and the third used geometric analysis of a dense registration of ∼30,000 3D points. We found that the two geometric approaches were highly consistent in their detection of morphological changes. The geometric method using dense registration further demonstrated superiority in the fine inference of shape changes and 3D face modeling. Several candidate SNPs showed potential associations with different facial features. In particular, one SNP, a known risk factor of non-syndromic cleft lips/palates, rs642961 in the IRF6 gene, was validated to strongly predict normal lip shape variation in female Han Chinese. This study further demonstrated that dense face registration may substantially improve the detection and characterization of genetic association in common facial variation.

  1. The application of human rights for EU asylum policy

    OpenAIRE

    Tamulevičiūtė, Asta

    2008-01-01

    This paper explores the application of human rights in the EU asylum policy. The prevention of terror and the strengthening of the area of Justice, Freedom and Security require tighter border controls, which consequently reflect negatively on asylum seekers and their human rights. Therefore this paper sets the aim to explore the application of human rights for EU asylum policy in respect to international obligations. There are three main objectives to be attained in the paper: to determine if...

  2. Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences

    Directory of Open Access Journals (Sweden)

    Brett eWagner Mackenzie

    2015-02-01

    Full Text Available The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation, with a smaller proportion of variation associated with DNA extraction method (technical variation and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.

  3. Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences.

    Science.gov (United States)

    Wagner Mackenzie, Brett; Waite, David W; Taylor, Michael W

    2015-01-01

    The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation) were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation), with a smaller proportion of variation associated with DNA extraction method (technical variation) and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.

  4. Severity of infection and seasonal variation of non-typhoid Salmonelle occurence in humans

    DEFF Research Database (Denmark)

    Gradel, K.O.; Dethlefsen, Claus; Schønheyder, H.C.

    2007-01-01

    Non-typhoid Salmonella infections may present as severe gastroenteritis necessitatinghospitalization and some patients become septic with bacteraemia. We hypothesized that theseasonal variation of non-typhoid Salmonella occurrence in humans diminishes with increasedseverity of infection. We...... examined the seasonal variation of non-typhoid Salmonella infections inthree patient groups with differing severity of infection: outpatients treated for gastroenteritis(n=1490); in-patients treated for gastroenteritis (n=492); and in-patients treated for bacteraemia(n=113). The study was population......-based and included all non-typhoid Salmonella patients ina Danish county from 1994 to 2003. A periodic regression model was used to compute thepeak-to-trough ratio for the three patient groups. The peak-to-trough ratios were 4·3 [95%confidence interval (CI) 3·6–5.0] for outpatients with gastroenteritis, 3·2 (95% CI...

  5. Variation in macronutrients in human bank milk: influencing factors and implications for human milk banking

    DEFF Research Database (Denmark)

    Michaelsen, K F; Skafte, L; Badsberg, J H

    1990-01-01

    with a high P content, we have developed a "high-protein" milk with a P content of about 12 g/L (true protein) and an E content of about 725 kcal/L. Thus, by continuous monitoring of macronutrient content in human bank milk it is possible to develop a "high-protein" milk with sufficient P and E content......Protein (P), fat (F), and carbohydrate (C) concentration in expressed human bank milk was determined by infrared analysis of 2,554 samples from 224 mothers. The mean contents of P, F, C, and energy (E, calculated from P, F, and C) were 9.0 g/L, 39.0 g/L, 71.9 g/L, and 696 kcal/L, respectively....... The main results were as follows: the P and F contents increased slightly with increasing body mass index of the mother, the P content decreased with increasing amounts of milk delivered to the milk bank, and the F content was higher in mothers delivering large amounts of milk. By selecting incoming milk...

  6. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    Science.gov (United States)

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

  7. Human hand modelling : Kinematics, dynamics, applications

    NARCIS (Netherlands)

    Gustus, A.; Stillfried, G.; Visser, J.; Jörntell, H.; Van der Smagt, P.

    2012-01-01

    An overview of mathematical modelling of the human hand is given. We consider hand models from a specific background: rather than studying hands for surgical or similar goals, we target at providing a set of tools with which human grasping and manipulation capabilities can be studied, and hand

  8. Estimation of time-dependent Hurst exponents with variational smoothing and application to forecasting foreign exchange rates

    Science.gov (United States)

    Garcin, Matthieu

    2017-10-01

    Hurst exponents depict the long memory of a time series. For human-dependent phenomena, as in finance, this feature may vary in the time. It justifies modelling dynamics by multifractional Brownian motions, which are consistent with time-dependent Hurst exponents. We improve the existing literature on estimating time-dependent Hurst exponents by proposing a smooth estimate obtained by variational calculus. This method is very general and not restricted to the sole Hurst framework. It is globally more accurate and easier than other existing non-parametric estimation techniques. Besides, in the field of Hurst exponents, it makes it possible to make forecasts based on the estimated multifractional Brownian motion. The application to high-frequency foreign exchange markets (GBP, CHF, SEK, USD, CAD, AUD, JPY, CNY and SGD, all against EUR) shows significantly good forecasts. When the Hurst exponent is higher than 0.5, what depicts a long-memory feature, the accuracy is higher.

  9. Neanderthal-Derived Genetic Variation Shapes Modern Human Cranium and Brain.

    Science.gov (United States)

    Gregory, Michael D; Kippenhan, J Shane; Eisenberg, Daniel P; Kohn, Philip D; Dickinson, Dwight; Mattay, Venkata S; Chen, Qiang; Weinberger, Daniel R; Saad, Ziad S; Berman, Karen F

    2017-07-24

    Before their disappearance from the fossil record approximately 40,000 years ago, Neanderthals, the ancient hominin lineage most closely related to modern humans, interbred with ancestors of present-day humans. The legacy of this gene flow persists through Neanderthal-derived variants that survive in modern human DNA; however, the neural implications of this inheritance are uncertain. Here, using MRI in a large cohort of healthy individuals of European-descent, we show that the amount of Neanderthal-originating polymorphism carried in living humans is related to cranial and brain morphology. First, as a validation of our approach, we demonstrate that a greater load of Neanderthal-derived genetic variants (higher "NeanderScore") is associated with skull shapes resembling those of known Neanderthal cranial remains, particularly in occipital and parietal bones. Next, we demonstrate convergent NeanderScore-related findings in the brain (measured by gray- and white-matter volume, sulcal depth, and gyrification index) that localize to the visual cortex and intraparietal sulcus. This work provides insights into ancestral human neurobiology and suggests that Neanderthal-derived genetic variation is neurologically functional in the contemporary population.

  10. Local, Regional, and Global Albedo Variations on Mars From Recent Space-Based Observations: Implications for Future Human Explorers

    Science.gov (United States)

    Bell, J. F.; Wellington, D. F.

    2017-06-01

    We describe recent as well as historic albedo variations on Mars as observed by space-based telescopes, orbiters, and surface missions, and speculate that some regions might offer fewer dust-related problems for future human explorers than others.

  11. Functional analysis and applied optimization in Banach spaces applications to non-convex variational models

    CERN Document Server

    Botelho, Fabio

    2014-01-01

    This book introduces the basic concepts of real and functional analysis. It presents the fundamentals of the calculus of variations, convex analysis, duality, and optimization that are necessary to develop applications to physics and engineering problems. The book includes introductory and advanced concepts in measure and integration, as well as an introduction to Sobolev spaces. The problems presented are nonlinear, with non-convex variational formulation. Notably, the primal global minima may not be attained in some situations, in which cases the solution of the dual problem corresponds to an appropriate weak cluster point of minimizing sequences for the primal one. Indeed, the dual approach more readily facilitates numerical computations for some of the selected models. While intended primarily for applied mathematicians, the text will also be of interest to engineers, physicists, and other researchers in related fields.

  12. Utilizing population variation, vaccination, and systems biology to study human immunology

    Science.gov (United States)

    Tsang, John S.

    2016-01-01

    The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis. PMID:26187853

  13. Utilizing population variation, vaccination, and systems biology to study human immunology.

    Science.gov (United States)

    Tsang, John S

    2015-08-01

    The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  14. Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology

    DEFF Research Database (Denmark)

    Cao, Hongzhi; Hastie, Alex R.; Cao, Dandan

    2014-01-01

    BACKGROUND: Structural variants (SVs) are less common than single nucleotide polymorphisms and indels in the population, but collectively account for a significant fraction of genetic polymorphism and diseases. Base pair differences arising from SVs are on a much higher order (>100 fold) than poi...... mapping technology as a comprehensive and cost-effective method for detecting structural variation and studying complex regions in the human genome, as well as deciphering viral integration into the host genome.......BACKGROUND: Structural variants (SVs) are less common than single nucleotide polymorphisms and indels in the population, but collectively account for a significant fraction of genetic polymorphism and diseases. Base pair differences arising from SVs are on a much higher order (>100 fold) than point...... mutations; however, none of the current detection methods are comprehensive, and currently available methodologies are incapable of providing sufficient resolution and unambiguous information across complex regions in the human genome. To address these challenges, we applied a high-throughput, cost...

  15. Regional variations of cell surface carbohydrates in human oral stratified epithelium

    DEFF Research Database (Denmark)

    Vedtofte, P; Dabelsteen, Erik; Hakomori, S

    1984-01-01

    The distribution of blood group carbohydrate chains with antigen A, B, H type 2 chain (A and B precursor), and N-acetyllactosamine (H type 2 precursor) specificity was studied in human oral epithelium from different anatomical regions. These represented various epithelial differentiation patterns...... epithelium from nine blood group A, two blood group B, and nine blood group O individuals. The blood group carbohydrate chains were examined in tissue sections by immunofluorescence microscopy. The A and B blood group antigens were detected by human blood group sera, and antigen H type 2 chains and N...... antigen H type 2 chains in metaplastically keratinized buccal epithelium was found to differ significantly from that seen in normal non-keratinized buccal epithelium. The regional variations demonstrated in cell surface carbohydrates are suggested to reflect differences in tissue differentiation....

  16. Understanding Human Autonomy Teaming Through Applications

    Science.gov (United States)

    Aponso, B.; Stallmann, Summer; Lachter, Joel; Shively, Jay; Benton, J.; Kaneshige, John; Mumaw, Randy; Feary, Michael

    2017-01-01

    This presentation describes the development and demonstration of human autonomy teaming technologies for improving aviation safety and efficiency during nominal and off-nominal operations by developing and validating increasingly autonomous systems concepts, technologies, and procedures.

  17. ALDH1A2 (RALDH2 genetic variation in human congenital heart disease

    Directory of Open Access Journals (Sweden)

    Mesquita Sonia MF

    2009-11-01

    ALDH1A2 genetic variation is present in TOF patients, suggesting a possible causal role for this gene in rare cases of human CHD, but does not support the hypothesis that variation at the ALDH1A2 locus is a significant modifier of the risk for CHD in humans.

  18. Global human mandibular variation reflects differences in agricultural and hunter-gatherer subsistence strategies.

    Science.gov (United States)

    von Cramon-Taubadel, Noreen

    2011-12-06

    Variation in the masticatory behavior of hunter-gatherer and agricultural populations is hypothesized to be one of the major forces affecting the form of the human mandible. However, this has yet to be analyzed at a global level. Here, the relationship between global mandibular shape variation and subsistence economy is tested, while controlling for the potentially confounding effects of shared population history, geography, and climate. The results demonstrate that the mandible, in contrast to the cranium, significantly reflects subsistence strategy rather than neutral genetic patterns, with hunter-gatherers having consistently longer and narrower mandibles than agriculturalists. These results support notions that a decrease in masticatory stress among agriculturalists causes the mandible to grow and develop differently. This developmental argument also explains why there is often a mismatch between the size of the lower face and the dentition, which, in turn, leads to increased prevalence of dental crowding and malocclusions in modern postindustrial populations. Therefore, these results have important implications for our understanding of human masticatory adaptation.

  19. Accelerating cross-validation with total variation and its application to super-resolution imaging

    CERN Document Server

    Obuchi, Tomoyuki; Akiyama, Kazunori; Kabashima, Yoshiyuki

    2016-01-01

    We develop an approximation formula for the cross-validation error (CVE) of a sparse linear regression penalized by $\\ell_1$-norm and total variation terms, which is based on a perturbative expansion utilizing the largeness of both the data dimensionality and the model. The developed formula allows us to reduce the necessary computational cost of the CVE evaluation significantly. The practicality of the formula is tested through application to simulated black-hole image reconstruction on the event-horizon scale with super resolution. The results demonstrate that our approximation reproduces the CVE values obtained via literally conducted cross-validation with reasonably good precision.

  20. Accelerating cross-validation with total variation and its application to super-resolution imaging

    Science.gov (United States)

    Obuchi, Tomoyuki; Ikeda, Shiro; Akiyama, Kazunori; Kabashima, Yoshiyuki

    2017-12-01

    We develop an approximation formula for the cross-validation error (CVE) of a sparse linear regression penalized by ℓ_1-norm and total variation terms, which is based on a perturbative expansion utilizing the largeness of both the data dimensionality and the model. The developed formula allows us to reduce the necessary computational cost of the CVE evaluation significantly. The practicality of the formula is tested through application to simulated black-hole image reconstruction on the event-horizon scale with super resolution. The results demonstrate that our approximation reproduces the CVE values obtained via literally conducted cross-validation with reasonably good precision.

  1. STUDY ON NORTHERN AND SOUTHERN INDIA VARIATIONS OF HUMAN SKULL- A SECONDARY RESEARCH

    Directory of Open Access Journals (Sweden)

    Jameskutty Baby Jacob Kaithackal

    2016-12-01

    Full Text Available BACKGROUND Identity of a human being with regard to sex, race, age etc. can be revealed if the skull is suitably examined. The general concept of ethnic and geographic variations being reflected in the body as variations in size, shape, etc. can be checked for in the case of skeleton also. This article is formed out of a term paper study submitted by myself in 2016 to the Yenepoya University, Mangalore, Karnataka, as part of the postgraduate diploma course in Forensic Anthropology. The research was based on a question whether there is a significant difference between human skulls from North and South India. The aims/objectives were bi-fold: to analyse the difference in male and female skull from North Indian and South Indian regions from review of scholarly literature and to explore the possibility identification of individuals from cranial features unique to North and South India. MATERIALS AND METHODS The original articles available on this type of work were extensively reviewed to recognise any traits that differentiated the skulls with regard to their regional variation. RESULTS At the end of the scrutiny of such papers, a summary of the features that distinguished skulls as belonging to northern or southern parts of India was tried. The Indian cranial series, though varied widely in shape, the absence of any statistically significant difference between them made it unreliable to predict skull as male or female by morphometric estimation. The studies by different scholars did not propose for a uniform distinctiveness between north and south Indian skulls. CONCLUSION It was concluded that analysing a single specimen to be of a distinct geographic origin should be done more cautiously when compared to a setting of series analysis where variability might be there of course.

  2. Detecting genetic association of common human facial morphological variation using high density 3D image registration.

    Directory of Open Access Journals (Sweden)

    Shouneng Peng

    Full Text Available Human facial morphology is a combination of many complex traits. Little is known about the genetic basis of common facial morphological variation. Existing association studies have largely used simple landmark-distances as surrogates for the complex morphological phenotypes of the face. However, this can result in decreased statistical power and unclear inference of shape changes. In this study, we applied a new image registration approach that automatically identified the salient landmarks and aligned the sample faces using high density pixel points. Based on this high density registration, three different phenotype data schemes were used to test the association between the common facial morphological variation and 10 candidate SNPs, and their performances were compared. The first scheme used traditional landmark-distances; the second relied on the geometric analysis of 15 landmarks and the third used geometric analysis of a dense registration of ∼30,000 3D points. We found that the two geometric approaches were highly consistent in their detection of morphological changes. The geometric method using dense registration further demonstrated superiority in the fine inference of shape changes and 3D face modeling. Several candidate SNPs showed potential associations with different facial features. In particular, one SNP, a known risk factor of non-syndromic cleft lips/palates, rs642961 in the IRF6 gene, was validated to strongly predict normal lip shape variation in female Han Chinese. This study further demonstrated that dense face registration may substantially improve the detection and characterization of genetic association in common facial variation.

  3. Testing the role of predicted gene knockouts in human anthropometric trait variation

    Science.gov (United States)

    Lessard, Samuel; Manning, Alisa K.; Low-Kam, Cécile; Auer, Paul L.; Giri, Ayush; Graff, Mariaelisa; Schurmann, Claudia; Yaghootkar, Hanieh; Luan, Jian'an; Esko, Tonu; Karaderi, Tugce; Bottinger, Erwin P.; Lu, Yingchang; Carlson, Chris; Caulfield, Mark; Dubé, Marie-Pierre; Jackson, Rebecca D.; Kooperberg, Charles; McKnight, Barbara; Mongrain, Ian; Peters, Ulrike; Reiner, Alex P.; Rhainds, David; Sotoodehnia, Nona; Hirschhorn, Joel N.; Scott, Robert A.; Munroe, Patricia B.; Frayling, Timothy M.; Loos, Ruth J.F.; North, Kari E.; Edwards, Todd L.; Tardif, Jean-Claude; Lindgren, Cecilia M.; Lettre, Guillaume

    2016-01-01

    Although the role of complete gene inactivation by two loss-of-function mutations inherited in trans is well-established in recessive Mendelian diseases, we have not yet explored how such gene knockouts (KOs) could influence complex human phenotypes. Here, we developed a statistical framework to test the association between gene KOs and quantitative human traits. Our method is flexible, publicly available, and compatible with common genotype format files (e.g. PLINK and vcf). We characterized gene KOs in 4498 participants from the NHLBI Exome Sequence Project (ESP) sequenced at high coverage (>100×), 1976 French Canadians from the Montreal Heart Institute Biobank sequenced at low coverage (5.7×), and >100 000 participants from the Genetic Investigation of ANthropometric Traits (GIANT) Consortium genotyped on an exome array. We tested associations between gene KOs and three anthropometric traits: body mass index (BMI), height and BMI-adjusted waist-to-hip ratio (WHR). Despite our large sample size and multiple datasets available, we could not detect robust associations between specific gene KOs and quantitative anthropometric traits. Our results highlight several limitations and challenges for future gene KO studies in humans, in particular when there is no prior knowledge on the phenotypes that might be affected by the tested gene KOs. They also suggest that gene KOs identified with current DNA sequencing methodologies probably do not strongly influence normal variation in BMI, height, and WHR in the general human population. PMID:26908616

  4. Analysis of protein-coding genetic variation in 60,706 humans

    Science.gov (United States)

    Lek, Monkol; Karczewski, Konrad J; Minikel, Eric V; Samocha, Kaitlin E; Banks, Eric; Fennell, Timothy; O'Donnell-Luria, Anne H; Ware, James S; Hill, Andrew J; Cummings, Beryl B; Tukiainen, Taru; Birnbaum, Daniel P; Kosmicki, Jack A; Duncan, Laramie E; Estrada, Karol; Zhao, Fengmei; Zou, James; Pierce-Hoffman, Emma; Berghout, Joanne; Cooper, David N; Deflaux, Nicole; DePristo, Mark; Do, Ron; Flannick, Jason; Fromer, Menachem; Gauthier, Laura; Goldstein, Jackie; Gupta, Namrata; Howrigan, Daniel; Kiezun, Adam; Kurki, Mitja I; Moonshine, Ami Levy; Natarajan, Pradeep; Orozco, Lorena; Peloso, Gina M; Poplin, Ryan; Rivas, Manuel A; Ruano-Rubio, Valentin; Rose, Samuel A; Ruderfer, Douglas M; Shakir, Khalid; Stenson, Peter D; Stevens, Christine; Thomas, Brett P; Tiao, Grace; Tusie-Luna, Maria T; Weisburd, Ben; Won, Hong-Hee; Yu, Dongmei; Altshuler, David M; Ardissino, Diego; Boehnke, Michael; Danesh, John; Donnelly, Stacey; Elosua, Roberto; Florez, Jose C; Gabriel, Stacey B; Getz, Gad; Glatt, Stephen J; Hultman, Christina M; Kathiresan, Sekar; Laakso, Markku; McCarroll, Steven; McCarthy, Mark I; McGovern, Dermot; McPherson, Ruth; Neale, Benjamin M; Palotie, Aarno; Purcell, Shaun M; Saleheen, Danish; Scharf, Jeremiah M; Sklar, Pamela; Sullivan, Patrick F; Tuomilehto, Jaakko; Tsuang, Ming T; Watkins, Hugh C; Wilson, James G; Daly, Mark J

    2016-01-01

    Summary Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes. PMID:27535533

  5. The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model.

    Science.gov (United States)

    McEvoy, Brian; Beleza, Sandra; Shriver, Mark D

    2006-10-15

    Skin pigmentation varies substantially across human populations in a manner largely coincident with ultraviolet radiation intensity. This observation suggests that natural selection in response to sunlight is a major force in accounting for pigmentation variability. We review recent progress in identifying the genes controlling this variation with a particular focus on the trait's evolutionary past and the potential role of testing for signatures of selection in aiding the discovery of functionally important genes. We have analyzed SNP data from the International HapMap project in 77 pigmentation candidate genes for such signatures. On the basis of these results and other similar work, we provide a tentative three-population model (West Africa, East Asia and North Europe) of the evolutionary-genetic architecture of human pigmentation. These results suggest a complex evolutionary history, with selection acting on different gene targets at different times and places in the human past. Some candidate genes may have been selected in the ancestral human population, others in the 'out of Africa' proto European-Asian population, whereas most appear to have selectively evolved solely in either Europeans or East Asians separately despite the pigmentation similarities between these two populations. Selection signatures can provide important clues to aid gene discovery. However, these should be viewed as complements, rather than replacements of, functional studies including linkage and association analyses, which can directly refine our understanding of the trait.

  6. Development and application of Human Genome Epidemiology

    Science.gov (United States)

    Xu, Jingwen

    2017-12-01

    Epidemiology is a science that studies distribution of diseases and health in population and its influencing factors, it also studies how to prevent and cure disease and promote health strategies and measures. Epidemiology has developed rapidly in recent years and it is an intercross subject with various other disciplines to form a series of branch disciplines such as Genetic epidemiology, molecular epidemiology, drug epidemiology and tumor epidemiology. With the implementation and completion of Human Genome Project (HGP), Human Genome Epidemiology (HuGE) has emerged at this historic moment. In this review, the development of Human Genome Epidemiology, research content, the construction and structure of relevant network, research standards, as well as the existing results and problems are briefly outlined.

  7. Annotated bibliography of human factors applications literature

    Energy Technology Data Exchange (ETDEWEB)

    McCafferty, D.B.

    1984-09-30

    This bibliography was prepared as part of the Human Factors Technology Project, FY 1984, sponsored by the Office of Nuclear Safety, US Department of Energy. The project was conducted by Lawrence Livermore National Laboratory, with Essex Corporation as a subcontractor. The material presented here is a revision and expansion of the bibliographic material developed in FY 1982 as part of a previous Human Factors Technology Project. The previous bibliography was published September 30, 1982, as Attachment 1 to the FY 1982 Project Status Report.

  8. HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.

    Directory of Open Access Journals (Sweden)

    Stéphane Buhler

    Full Text Available Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies.Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model. However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used

  9. Human metabolic network: reconstruction, simulation, and applications in systems biology.

    Science.gov (United States)

    Wu, Ming; Chan, Christina

    2012-03-02

    Metabolism is crucial to cell growth and proliferation. Deficiency or alterations in metabolic functions are known to be involved in many human diseases. Therefore, understanding the human metabolic system is important for the study and treatment of complex diseases. Current reconstructions of the global human metabolic network provide a computational platform to integrate genome-scale information on metabolism. The platform enables a systematic study of the regulation and is applicable to a wide variety of cases, wherein one could rely on in silico perturbations to predict novel targets, interpret systemic effects, and identify alterations in the metabolic states to better understand the genotype-phenotype relationships. In this review, we describe the reconstruction of the human metabolic network, introduce the constraint based modeling approach to analyze metabolic networks, and discuss systems biology applications to study human physiology and pathology. We highlight the challenges and opportunities in network reconstruction and systems modeling of the human metabolic system.

  10. Process error rates in general research applications to the Human ...

    African Journals Online (AJOL)

    Objective. To examine process error rates in applications for ethics clearance of health research. Methods. Minutes of 586 general research applications made to a human health research ethics committee (HREC) from April 2008 to March 2009 were examined. Rates of approval were calculated and reasons for requiring ...

  11. Size variation in early human mandibles and molars from Klasies River, South Africa: comparison with other middle and late Pleistocene assemblages and with modern humans.

    Science.gov (United States)

    Royer, Danielle F; Lockwood, Charles A; Scott, Jeremiah E; Grine, Frederick E

    2009-10-01

    Previous studies of the Middle Stone Age human remains from Klasies River have concluded that they exhibited more sexual dimorphism than extant populations, but these claims have not been assessed statistically. We evaluate these claims by comparing size variation in the best-represented elements at the site, namely the mandibular corpora and M(2)s, to that in samples from three recent human populations using resampling methods. We also examine size variation in these same elements from seven additional middle and late Pleistocene sites: Skhūl, Dolní Vestonice, Sima de los Huesos, Arago, Krapina, Shanidar, and Vindija. Our results demonstrate that size variation in the Klasies assemblage was greater than in recent humans, consistent with arguments that the Klasies people were more dimorphic than living humans. Variation in the Skhūl, Dolní Vestonice, and Sima de los Huesos mandibular samples is also higher than in the recent human samples, indicating that the Klasies sample was not unusual among middle and late Pleistocene hominins. In contrast, the Neandertal samples (Krapina, Shanidar, and Vindija) do not evince relatively high mandibular and molar variation, which may indicate that the level of dimorphism in Neandertals was similar to that observed in extant humans. These results suggest that the reduced levels of dimorphism in Neandertals and living humans may have developed independently, though larger fossil samples are needed to test this hypothesis.

  12. Asymmetry quantization and application to human mandibles

    DEFF Research Database (Denmark)

    Glerup, Nanna; Nielsen, Mads; Sporring, Jon

    2004-01-01

    All biological objects exhibit some degree of asymmetry, but for some parts of the human body, excessive asymmetry is a sign of pathology. Hence, the problem is to draw the line between categorization of objects being too asymmetric and objects exhibiting normal asymmetry. With a measure of asymm......All biological objects exhibit some degree of asymmetry, but for some parts of the human body, excessive asymmetry is a sign of pathology. Hence, the problem is to draw the line between categorization of objects being too asymmetric and objects exhibiting normal asymmetry. With a measure...... in order to make the object symmetrical; or identically, how much work has been carried out in order to make the ideal symmetrical object into the current (slightly) asymmetrical object. The quantization of asymmetry is validated on a set of normal (assumed near symmetrical) mandibles, and a set...

  13. Genome-wide mapping of copy number variation in humans: comparative analysis of high resolution array platforms.

    Directory of Open Access Journals (Sweden)

    Rajini R Haraksingh

    Full Text Available Accurate and efficient genome-wide detection of copy number variants (CNVs is essential for understanding human genomic variation, genome-wide CNV association type studies, cytogenetics research and diagnostics, and independent validation of CNVs identified from sequencing based technologies. Numerous, array-based platforms for CNV detection exist utilizing array Comparative Genome Hybridization (aCGH, Single Nucleotide Polymorphism (SNP genotyping or both. We have quantitatively assessed the abilities of twelve leading genome-wide CNV detection platforms to accurately detect Gold Standard sets of CNVs in the genome of HapMap CEU sample NA12878, and found significant differences in performance. The technologies analyzed were the NimbleGen 4.2 M, 2.1 M and 3×720 K Whole Genome and CNV focused arrays, the Agilent 1×1 M CGH and High Resolution and 2×400 K CNV and SNP+CGH arrays, the Illumina Human Omni1Quad array and the Affymetrix SNP 6.0 array. The Gold Standards used were a 1000 Genomes Project sequencing-based set of 3997 validated CNVs and an ultra high-resolution aCGH-based set of 756 validated CNVs. We found that sensitivity, total number, size range and breakpoint resolution of CNV calls were highest for CNV focused arrays. Our results are important for cost effective CNV detection and validation for both basic and clinical applications.

  14. Technical communication: respiratory variation in pulse pressure and plethysmographic waveforms: intraoperative applicability in a North American academic center.

    Science.gov (United States)

    Maguire, Sinead; Rinehart, Joseph; Vakharia, Shermeen; Cannesson, Maxime

    2011-01-01

    Dynamic variables are the best predictors of fluid responsiveness in patients under general anesthesia and mechanical ventilation; namely, respiratory variations in pulse pressure and in the plethysmographic waveform. However, these variables have potential limitations. Our aim was to evaluate their intraoperative applicability. We extracted clinical data from all anesthesia procedures performed at our institution in 2009 and identified the number of cases that presented predetermined conditions of application. Among the 12,308 procedures, 39% met the criteria for the noninvasive monitoring of variations in the plethysmographic waveform of which 23% had arterial lines and met the criteria for the invasive monitoring of variations in pulse pressure.

  15. Human-computer interface incorporating personal and application domains

    Science.gov (United States)

    Anderson, Thomas G [Albuquerque, NM

    2011-03-29

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  16. Human-computer interface incorporating personal and application domains

    Science.gov (United States)

    Anderson, Thomas G.

    2004-04-20

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  17. Regional variation in tissue composition and biomechanical properties of postmenopausal ovine and human vagina.

    Science.gov (United States)

    Ulrich, Daniela; Edwards, Sharon L; Letouzey, Vincent; Su, Kai; White, Jacinta F; Rosamilia, Anna; Gargett, Caroline E; Werkmeister, Jerome A

    2014-01-01

    There are increasing numbers of reports describing human vaginal tissue composition in women with and without pelvic organ prolapse with conflicting results. The aim of this study was to compare ovine and human posterior vaginal tissue in terms of histological and biochemical tissue composition and to assess passive biomechanical properties of ovine vagina to further characterise this animal model for pelvic organ prolapse research. Vaginal tissue was collected from ovariectomised sheep (n = 6) and from postmenopausal women (n = 7) from the proximal, middle and distal thirds. Tissue histology was analyzed using Masson's Trichrome staining; total collagen was quantified by hydroxyproline assays, collagen III/I+III ratios by delayed reduction SDS PAGE, glycosaminoglycans by dimethylmethylene blue assay, and elastic tissue associated proteins (ETAP) by amino acid analysis. Young's modulus, maximum stress/strain, and permanent strain following cyclic loading were determined in ovine vagina. Both sheep and human vaginal tissue showed comparable tissue composition. Ovine vaginal tissue showed significantly higher total collagen and glycosaminoglycan values (pvagina for collagen, GAG or ETAP content. The proximal region was the stiffest (Young's modulus, pvagina, although the absolute content of proteins were similar. Knowledge of this baseline variation in the composition and mechanical properties of the vaginal wall will assist future studies using sheep as a model for vaginal surgery.

  18. The New Genomics: What Molecular Databases Can Tell Us About Human Population Variation and Endocrine Disease.

    Science.gov (United States)

    Rotwein, Peter

    2017-07-01

    Major recent advances in genetics and genomics present unique opportunities for enhancing our understanding of human physiology and disease predisposition. Here I demonstrate how analysis of genomic information can provide new insights into endocrine systems, using the human growth hormone (GH) signaling pathway as an illustrative example. GH is essential for normal postnatal growth in children, and plays important roles in other biological processes throughout life. GH actions are mediated by the GH receptor, primarily via the JAK2 protein tyrosine kinase and the STAT5B transcription factor, and inactivating mutations in this pathway all lead to impaired somatic growth. Variation in GH signaling genes has been evaluated using DNA sequence data from the Exome Aggregation Consortium, a compendium of information from >60,000 individuals. Results reveal many potential missense and other alterations in the coding regions of GH1, GHR, JAK2, and STAT5B, with most changes being uncommon. The total number of different alleles per gene varied by ~threefold, from 101 for GH1 to 338 for JAK2. Several known disease-linked mutations in GH1, GHR, and JAK2 were present but infrequent in the population; however, three amino acid changes in GHR were sufficiently prevalent (~4% to 44% of chromosomes) to suggest that they are not disease causing. Collectively, these data provide new opportunities to understand how genetically driven variability in GH signaling and action may modify human physiology and disease. Copyright © 2017 Endocrine Society.

  19. Genetic variation in human HBB is associated with Plasmodium falciparum transmission.

    Science.gov (United States)

    Gouagna, Louis Clement; Bancone, Germana; Yao, Frank; Yameogo, Bienvenue; Dabiré, Kounbobr Roch; Costantini, Carlo; Simporé, Jacques; Ouedraogo, Jean Bosco; Modiano, David

    2010-04-01

    Genetic factors are known to have a role in determining susceptibility to infectious diseases, although it is unclear whether they may also influence host efficiency in transmitting pathogens. We examine variants in HBB that have been shown to be protective against malaria and test whether these are associated with the transmission of the parasite from the human host to the Anopheles vector. We conducted cross-sectional malariological surveys on 3,739 human subjects and transmission experiments involving 60 children and 6,446 mosquitoes in Burkina Faso, West Africa. Protective hemoglobins C (HbC, beta6Glu-->Lys) and S (beta6Glu-->Val) are associated with a twofold in vivo (odds ratio 2.17, 95% CI 1.57-3.01, P = 1.0 x 10(-6)) and a fourfold ex vivo (odds ratio 4.12, 95% CI 1.90-9.29, P = 7.0 x 10(-5)) increase of parasite transmission from the human host to the Anopheles vector. This provides an example of how host genetic variation may influence the transmission dynamics of an infectious disease.

  20. Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics.

    Science.gov (United States)

    Gussow, Ayal B; Copeland, Brett R; Dhindsa, Ryan S; Wang, Quanli; Petrovski, Slavé; Majoros, William H; Allen, Andrew S; Goldstein, David B

    2017-01-01

    There is broad agreement that genetic mutations occurring outside of the protein-coding regions play a key role in human disease. Despite this consensus, we are not yet capable of discerning which portions of non-coding sequence are important in the context of human disease. Here, we present Orion, an approach that detects regions of the non-coding genome that are depleted of variation, suggesting that the regions are intolerant of mutations and subject to purifying selection in the human lineage. We show that Orion is highly correlated with known intolerant regions as well as regions that harbor putatively pathogenic variation. This approach provides a mechanism to identify pathogenic variation in the human non-coding genome and will have immediate utility in the diagnostic interpretation of patient genomes and in large case control studies using whole-genome sequences.

  1. Integrating population variation and protein structural analysis to improve clinical interpretation of missense variation: application to the WD40 domain.

    Science.gov (United States)

    Laskowski, Roman A; Tyagi, Nidhi; Johnson, Diana; Joss, Shelagh; Kinning, Esther; McWilliam, Catherine; Splitt, Miranda; Thornton, Janet M; Firth, Helen V; Wright, Caroline F

    2016-03-01

    We present a generic, multidisciplinary approach for improving our understanding of novel missense variants in recently discovered disease genes exhibiting genetic heterogeneity, by combining clinical and population genetics with protein structural analysis. Using six new de novo missense diagnoses in TBL1XR1 from the Deciphering Developmental Disorders study, together with population variation data, we show that the β-propeller structure of the ubiquitous WD40 domain provides a convincing way to discriminate between pathogenic and benign variation. Children with likely pathogenic mutations in this gene have severely delayed language development, often accompanied by intellectual disability, autism, dysmorphology and gastrointestinal problems. Amino acids affected by likely pathogenic missense mutations are either crucial for the stability of the fold, forming part of a highly conserved symmetrically repeating hydrogen-bonded tetrad, or located at the top face of the β-propeller, where 'hotspot' residues affect the binding of β-catenin to the TBLR1 protein. In contrast, those altered by population variation are significantly less likely to be spatially clustered towards the top face or to be at buried or highly conserved residues. This result is useful not only for interpreting benign and pathogenic missense variants in this gene, but also in other WD40 domains, many of which are associated with disease. © The Author 2016. Published by Oxford University Press.

  2. Intraindividual variation and short-term temporal trend in DNA methylation of human blood.

    Science.gov (United States)

    Shvetsov, Yurii B; Song, Min-Ae; Cai, Qiuyin; Tiirikainen, Maarit; Xiang, Yong-Bing; Shu, Xiao-Ou; Yu, Herbert

    2015-03-01

    Between- and within-person variation in DNA methylation levels are important parameters to be considered in epigenome-wide association studies. Temporal change is one source of within-person variation in DNA methylation that has been linked to aging and disease. We analyzed CpG-site-specific intraindividual variation and short-term temporal trend in leukocyte DNA methylation among 24 healthy Chinese women, with blood samples drawn at study entry and after 9 months. Illumina HumanMethylation450 BeadChip was used to measure methylation. Intraclass correlation coefficients (ICC) and trend estimates were summarized by genomic location and probe type. The median ICC was 0.36 across nonsex chromosomes and 0.80 on the X chromosome. There was little difference in ICC profiles by genomic region and probe type. Among CpG loci with high variability between participants, more than 99% had ICC > 0.8. Statistically significant trend was observed in 10.9% CpG loci before adjustment for cell-type composition and in 3.4% loci after adjustment. For CpG loci differentially methylated across subjects, methylation levels can be reliably assessed with one blood sample. More samples per subject are needed for low-variability and unmethylated loci. Temporal changes are largely driven by changes in cell-type composition of blood samples, but temporal trend unrelated to cell types is detected in a small percentage of CpG sites. This study shows that one measurement can reliably assess methylation of differentially methylated CpG loci. Cancer Epidemiol Biomarkers Prev; 24(3); 490-7. ©2014 AACR. ©2014 American Association for Cancer Research.

  3. Variation in the human cannabinoid receptor CNR1 gene modulates gaze duration for happy faces

    Directory of Open Access Journals (Sweden)

    Chakrabarti Bhismadev

    2011-06-01

    Full Text Available Abstract Background From an early age, humans look longer at preferred stimuli and also typically look longer at facial expressions of emotion, particularly happy faces. Atypical gaze patterns towards social stimuli are common in autism spectrum conditions (ASC. However, it is unknown whether gaze fixation patterns have any genetic basis. In this study, we tested whether variations in the cannabinoid receptor 1 (CNR1 gene are associated with gaze duration towards happy faces. This gene was selected because CNR1 is a key component of the endocannabinoid system, which is involved in processing reward, and in our previous functional magnetic resonance imaging (fMRI study, we found that variations in CNR1 modulate the striatal response to happy (but not disgust faces. The striatum is involved in guiding gaze to rewarding aspects of a visual scene. We aimed to validate and extend this result in another sample using a different technique (gaze tracking. Methods A total of 30 volunteers (13 males and 17 females from the general population observed dynamic emotional expressions on a screen while their eye movements were recorded. They were genotyped for the identical four single-nucleotide polymorphisms (SNPs in the CNR1 gene tested in our earlier fMRI study. Results Two SNPs (rs806377 and rs806380 were associated with differential gaze duration for happy (but not disgust faces. Importantly, the allelic groups associated with a greater striatal response to happy faces in the fMRI study were associated with longer gaze duration at happy faces. Conclusions These results suggest that CNR1 variations modulate the striatal function that underlies the perception of signals of social reward, such as happy faces. This suggests that CNR1 is a key element in the molecular architecture of perception of certain basic emotions. This may have implications for understanding neurodevelopmental conditions marked by atypical eye contact and facial emotion processing

  4. Shape variation in the human pelvis and limb skeleton: Implications for obstetric adaptation.

    Science.gov (United States)

    Kurki, Helen K; Decrausaz, Sarah-Louise

    2016-04-01

    Under the obstetrical dilemma (OD) hypothesis, selection acts on the human female pelvis to ensure a sufficiently sized obstetric canal for birthing a large-brained, broad shouldered neonate, while bipedal locomotion selects for a narrower and smaller pelvis. Despite this female-specific stabilizing selection, variability of linear dimensions of the pelvic canal and overall size are not reduced in females, suggesting shape may instead be variable among females of a population. Female canal shape has been shown to vary among populations, while male canal shape does not. Within this context, we examine within-population canal shape variation in comparison with that of noncanal aspects of the pelvis and the limbs. Nine skeletal samples (total female n = 101, male n = 117) representing diverse body sizes and shapes were included. Principal components analysis was applied to size-adjusted variables of each skeletal region. A multivariate variance was calculated using the weighted PC scores for all components in each model and F-ratios used to assess differences in within-population variances between sexes and skeletal regions. Within both sexes, multivariate canal shape variance is significantly greater than noncanal pelvis and limb variances, while limb variance is greater than noncanal pelvis variance in some populations. Multivariate shape variation is not consistently different between the sexes in any of the skeletal regions. Diverse selective pressures, including obstetrics, locomotion, load carrying, and others may act on canal shape, as well as genetic drift and plasticity, thus increasing variation in morphospace while protecting obstetric sufficiency. © 2015 Wiley Periodicals, Inc.

  5. Patterns of morphological variation in enamel-dentin junction and outer enamel surface of human molars.

    Science.gov (United States)

    Morita, Wataru; Yano, Wataru; Nagaoka, Tomohito; Abe, Mikiko; Ohshima, Hayato; Nakatsukasa, Masato

    2014-06-01

    Tooth crown patterning is governed by the growth and folding of the inner enamel epithelium (IEE) and the following enamel deposition forms outer enamel surface (OES). We hypothesized that overall dental crown shape and covariation structure are determined by processes that configurate shape at the enamel-dentine junction (EDJ), the developmental vestige of IEE. This this hypothesis was tested by comparing patterns of morphological variation between EDJ and OES in human permanent maxillary first molar (UM1) and deciduous second molar (um2). Using geometric morphometric methods, we described morphological variation and covariation between EDJ and OES, and evaluated the strength of two components of phenotypic variability, canalization and morphological integration, in addition to the relevant evolutionary flexibility, i.e. the ability to respond to selective pressure. The strength of covariation between EDJ and OES was greater in um2 than in UM1, and the way that multiple traits covary between EDJ and OES was different between these teeth. The variability analyses showed that EDJ had less shape variation and a higher level of morphological integration than OES, which indicated that canalization and morphological integration acted as developmental constraints. These tendencies were greater in UM1 than in um2. On the other hand, EDJ and OES had a comparable level of evolvability in these teeth. Amelogenesis could play a significant role in tooth shape and covariation structure, and its influence was not constant among teeth, which may be responsible for the differences in the rate and/or period of enamel formation. © 2014 Anatomical Society.

  6. Camera systems in human motion analysis for biomedical applications

    Science.gov (United States)

    Chin, Lim Chee; Basah, Shafriza Nisha; Yaacob, Sazali; Juan, Yeap Ewe; Kadir, Aida Khairunnisaa Ab.

    2015-05-01

    Human Motion Analysis (HMA) system has been one of the major interests among researchers in the field of computer vision, artificial intelligence and biomedical engineering and sciences. This is due to its wide and promising biomedical applications, namely, bio-instrumentation for human computer interfacing and surveillance system for monitoring human behaviour as well as analysis of biomedical signal and image processing for diagnosis and rehabilitation applications. This paper provides an extensive review of the camera system of HMA, its taxonomy, including camera types, camera calibration and camera configuration. The review focused on evaluating the camera system consideration of the HMA system specifically for biomedical applications. This review is important as it provides guidelines and recommendation for researchers and practitioners in selecting a camera system of the HMA system for biomedical applications.

  7. Computational models of human vision with applications

    Science.gov (United States)

    Wandell, Brian A.

    1987-01-01

    The research program supported by this grant was initiated in l977 by the Joint Institute for Aeronautics and Acoustics of the Department of Aeronautics and Astronautics at Stanford University. The purpose of the research was to study human performance with the goal of improving the design of flight instrumentation. By mutual agreement between the scientists at NASA-Ames and Stanford, all research activities in this area were consolidated into a single funding mechanism, NCC 2-307 (Center of Excellence Grant, 7/1/84 - present). This is the final report on this research grant.

  8. Genetic variations in the DNA replication origins of human papillomavirus family correlate with their oncogenic potential.

    Science.gov (United States)

    Yilmaz, Gulden; Biswas-Fiss, Esther E; Biswas, Subhasis B

    2017-12-27

    Human papillomaviruses (HPVs) encompasses a large family of viruses that range from benign to highly carcinogenic. The crucial differences between benign and carcinogenic types of HPV remain unknown, except that the two HPV types differ in the frequency of DNA replication. We have systematically analyzed the mechanism of HPV DNA replication initiation in low-risk and high-risk HPVs. Our results demonstrate that HPV-encoded E2 initiator protein and its four binding sites in the replication origin play pivotal roles in determining the destiny of the HPV-infected cell. We have identified strain-specific single nucleotide variations in E2 binding sites only in the high-risk HPVs. We have demonstrated that these variations result in attenuated formation of the E2-DNA complex. E2 binding to these sites is linked to the activation of the DNA replication origin as well as initiation of DNA replication. Both mobility shift assay and atomic force microscopy studies demonstrated that binding of E2 from either low- or high-risk HPVs with variant binding sequences lacked formation of multimeric E2-DNA complex formation in vitro. These results provided a molecular basis of differential DNA replication in the two types of HPVs and pointed to a correlation with the development of cancer. Copyright © 2017. Published by Elsevier B.V.

  9. Analysis of Long-Term Temperature Variations in the Human Body.

    Science.gov (United States)

    Dakappa, Pradeepa Hoskeri; Mahabala, Chakrapani

    2015-01-01

    Body temperature is a continuous physiological variable. In normal healthy adults, oral temperature is estimated to vary between 36.1°C and 37.2°C. Fever is a complex host response to many external and internal agents and is a potential contributor to many clinical conditions. Despite being one of the foremost vital signs, temperature and its analysis and variations during many pathological conditions has yet to be examined in detail using mathematical techniques. Classical fever patterns based on recordings obtained every 8-12 h have been developed. However, such patterns do not provide meaningful information in diagnosing diseases. Because fever is a host response, it is likely that there could be a unique response to specific etiologies. Continuous long-term temperature monitoring and pattern analysis using specific analytical methods developed in engineering and physics could aid in revealing unique fever responses of hosts and in different clinical conditions. Furthermore, such analysis can potentially be used as a novel diagnostic tool and to study the effect of pharmaceutical agents and other therapeutic protocols. Thus, the goal of our article is to present a comprehensive review of the recent relevant literature and analyze the current state of research regarding temperature variations in the human body.

  10. Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

    Science.gov (United States)

    Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

    2016-08-01

    The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

  11. Impact of human management on the genetic variation of wild pepper, Capsicum annuum var. glabriusculum.

    Directory of Open Access Journals (Sweden)

    Pablo González-Jara

    Full Text Available Management of wild peppers in Mexico has occurred for a long time without clear phenotypic signs of domestication. However, pre-domestication management could have implications for the population's genetic richness. To test this hypothesis we analysed 27 wild (W, let standing (LS and cultivated (C populations, plus 7 samples from local markets (LM, with nine polymorphic microsatellite markers. Two hundred and fifty two alleles were identified, averaging 28 per locus. Allele number was higher in W, and 15 and 40% less in LS and C populations, respectively. Genetic variation had a significant population structure. In W populations, structure was associated with ecological and geographic areas according to isolation by distance. When LM and C populations where included in the analysis, differentiation was no longer apparent. Most LM were related to distant populations from Sierra Madre Oriental, which represents their probable origin. Historical demography shows a recent decline in all W populations. Thus, pre-domestication human management is associated with a significant reduction of genetic diversity and with a loss of differentiation suggesting movement among regions by man. Measures to conserve wild and managed populations should be implemented to maintain the source and the architecture of genetic variation in this important crop relative.

  12. Impact of copy number variations burden on coding genome in humans using integrated high resolution arrays.

    Science.gov (United States)

    Veerappa, Avinash M; Lingaiah, Kusuma; Vishweswaraiah, Sangeetha; Murthy, Megha N; Suresh, Raviraj V; Manjegowda, Dinesh S; Ramachandra, Nallur B

    2014-12-16

    Copy number variations (CNVs) alter the transcriptional and translational levels of genes by disrupting the coding structure and this burden of CNVs seems to be a significant contributor to phenotypic variations. Therefore it was necessary to assess the complexities of CNV burden on the coding genome. A total of 1715 individuals from 12 populations were used for CNV analysis in the present investigation. Analysis was performed using Affymetrix Genome-Wide Human SNP Array 6·0 chip and CytoScan High-Density arrays. CNVs were more frequently observed in the coding region than in the non-coding region. CNVs were observed vastly more frequently in the coding region than the non-coding region. CNVs were found to be enriched in the regions containing functional genes (83-96%) compared with the regions containing pseudogenes (4-17%). CNVs across the genome of an individual showed multiple hits across many genes, whose proteins interact physically and function under the same pathway. We identified varying numbers of proteins and degrees of interactions within protein complexes of single individual genomes. This study represents the first draft of a population-specific CNV genes map as well as a cross-populational map. The complex relationship of CNVs on genes and their physically interacting partners unravels many complexities involved in phenotype expression. This study identifies four mechanisms contributing to the complexities caused by the presence of multiple CNVs across many genes in the coding part of the genome.

  13. THE VARIATIONS OF WATER IN HUMAN TISSUE UNDER CERTAIN COMPRESSION: STUDIED WITH DIFFUSE REFLECTANCE SPECTROSCOPY

    Directory of Open Access Journals (Sweden)

    CHENXI LI

    2013-01-01

    Full Text Available The reflectance spectrum has been widely adopted to extract diagnosis information of human tissue because it possesses the advantages of noninvasive and rapidity. The external pressure brought by fiber optic probe may influence the accuracy of measurement. In this paper, a systematic study is focused on the effects of probe pressure on intrinsic changes of water and scattering particles in tissue. According to the biphasic nonlinear mixture model, the pressure modulated reflectance spectrum of both in vitro and in vivo tissue is measured and processed with second-derivation. The results indicate that the variations of bulk and bonded water in tissue have a nonlinear relationship with the pressure. Differences in tissue structure and morphology contribute to site-specific probe pressure effects. Then the finite element (FEM and Monte Carlo (MC method is employed to simulate the deformation and reflectance spectrum variations of tissue before and after compression. The simulation results show that as the pressure of fiber optic probe applied to the detected skin increased to 80 kPa, the effective photon proportion form dermis decreases significantly from 86% to 76%. Future designs might benefit from the research of change of water volume inside the tissue to mitigate the pressure applied to skin.

  14. Age variations in the properties of human tibial trabecular bone and cartilage

    DEFF Research Database (Denmark)

    Ding, Ming

    2000-01-01

    such as osteoarthrosis and osteoporosis, and for the design, fixation and durability of total joint prosthesis. The specific aims of the present studies were: 1) to investigate normal age-related variations in the mechanical, physical/compositional, and structural properties of human tibial trabecular bone; and 2...... in the properties of trabecular bone and the cartilage-bone complex, and osteoarthrotic specimens were used for the investigation of changes in the mechanical properties of the cartilage-bone complex induced by this disease process. The mechanical properties and physical/compositional properties of trabecular bone...... in the microstructural properties had the same trends for both medial and lateral condyles of the tibia. The observed increase of anisotropy may be interpreted as the consequence of structural adaptation secondary to age-induced bone loss. The aging trabeculae align more strongly to the primary direction, which...

  15. Intersection of population variation and autoimmunity genetics in human T cell activation

    Science.gov (United States)

    Ye, Chun Jimmie; Feng, Ting; Kwon, Ho-Keun; Raj, Towfique; Wilson, Michael; Asinovski, Natasha; McCabe, Cristin; Lee, Michelle H.; Frohlich, Irene; Paik, Hyun-il; Zaitlen, Noah; Hacohen, Nir; Stranger, Barbara; De Jager, Philip; Mathis, Diane; Regev, Aviv; Benoist, Christophe

    2016-01-01

    T lymphocyte activation by antigen conditions adaptive immune responses and immunopathologies, but we know little about its variation in humans, and its genetic or environmental roots. We analyzed gene expression in CD4+ T cells during unbiased activation or in Th17 conditions from 348 healthy subjects representing European, Asian and African ancestries. We observed inter-individual variability, most marked for cytokine transcripts, with clear biases on the basis of ancestry, and following patterns more complex than simple Th1/2/17 partitions. We identified 39 genetic loci specifically associated in cis with activated gene expression. We further fine-mapped and validated a single-base variant that modulates YY1 binding and the activity of an enhancer element controlling the autoimmune-associated IL2RA gene, affecting its activity in activated but not regulatory T cells. Thus, inter-individual variability affects the fundamental immunologic process of T helper activation, with important connections to autoimmune disease. PMID:25214635

  16. An integrated map of genetic variation from 1.092 human genomes

    DEFF Research Database (Denmark)

    Abecasis, Goncalo R.; Auton, Adam; Brooks, Lisa D.

    2012-01-01

    By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination...... deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding...... consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites...

  17. Extent, causes, and consequences of small RNA expression variation in human adipose tissue.

    Directory of Open Access Journals (Sweden)

    Leopold Parts

    Full Text Available Small RNAs are functional molecules that modulate mRNA transcripts and have been implicated in the aetiology of several common diseases. However, little is known about the extent of their variability within the human population. Here, we characterise the extent, causes, and effects of naturally occurring variation in expression and sequence of small RNAs from adipose tissue in relation to genotype, gene expression, and metabolic traits in the MuTHER reference cohort. We profiled the expression of 15 to 30 base pair RNA molecules in subcutaneous adipose tissue from 131 individuals using high-throughput sequencing, and quantified levels of 591 microRNAs and small nucleolar RNAs. We identified three genetic variants and three RNA editing events. Highly expressed small RNAs are more conserved within mammals than average, as are those with highly variable expression. We identified 14 genetic loci significantly associated with nearby small RNA expression levels, seven of which also regulate an mRNA transcript level in the same region. In addition, these loci are enriched for variants significant in genome-wide association studies for body mass index. Contrary to expectation, we found no evidence for negative correlation between expression level of a microRNA and its target mRNAs. Trunk fat mass, body mass index, and fasting insulin were associated with more than twenty small RNA expression levels each, while fasting glucose had no significant associations. This study highlights the similar genetic complexity and shared genetic control of small RNA and mRNA transcripts, and gives a quantitative picture of small RNA expression variation in the human population.

  18. Copy number variation arising from gene conversion on the human Y chromosome.

    Science.gov (United States)

    Shi, Wentao; Massaia, Andrea; Louzada, Sandra; Banerjee, Ruby; Hallast, Pille; Chen, Yuan; Bergström, Anders; Gu, Yong; Leonard, Steven; Quail, Michael A; Ayub, Qasim; Yang, Fengtang; Tyler-Smith, Chris; Xue, Yali

    2018-01-01

    We describe the variation in copy number of a ~ 10 kb region overlapping the long intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat on the short arm of the human Y chromosome, leading to individuals with 0-3 copies of this region in the general population. Variation of this CNV is common, with 266 individuals having 0 copies, 943 (including the reference sequence) having 1, 23 having 2 copies, and two having 3 copies, and was validated by breakpoint PCR, fibre-FISH, and 10× Genomics Chromium linked-read sequencing in subsets of 1234 individuals from the 1000 Genomes Project. Mapping the changes in copy number to the phylogeny of these Y chromosomes previously established by the Project identified at least 20 mutational events, and investigation of flanking paralogous sequence variants showed that the mutations involved flanking sequences in 18 of these, and could extend over > 30 kb of DNA. While either gene conversion or double crossover between misaligned sister chromatids could formally explain the 0-2 copy events, gene conversion is the more likely mechanism, and these events include the longest non-allelic gene conversion reported thus far. Chromosomes with three copies of this CNV have arisen just once in our data set via another mechanism: duplication of 420 kb that places the third copy 230 kb proximal to the existing proximal copy. Our results establish gene conversion as a previously under-appreciated mechanism of generating copy number changes in humans and reveal the exceptionally large size of the conversion events that can occur.

  19. Diurnal variation in baseline human regional cerebral blood flow demonstrated by PET

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, D.J.; Mintun, M.A.; Moore, R.Y. [Univ. of Pittsburgh, PA (United States)] [and others

    1994-05-01

    We have previously described the diurnal variation in regional cerebral blood flow (rCBF) response to bright light in human subjects as demonstrated by the positron emission tomography (PET) activation method. In this abstract, we report the differences in rCBF (an indicator of differences in regional neuronal activity) between the evening and midday dim light baseline scans which served as the control states in the above bright light activation study. Five right-handed, healthy volunteers underwent both an evening (8pm) and a midday (12N) O-15 water PET scanning session. Each scanning session was preceded by one hour of dim light adaptation (50 lux) and consisted of six rCBF scans at three different light intensities in an AABBCC sequence (A=50 lux, B=2500 lux, C=7000lux). Significant differences in rCBF between the evening and midday 50 lux states were identified using the statistical parametric mapping method developed by Friston et al (p<.001). The evening scans demonstrated areas of greater relative blood flow in the pineal gland, the lateral temporal cortex bilaterally, the right lateral prefrontal cortex, the superior aspect of the anterior cingulate, and the left thalamus. The midday scans showed areas of greater relative blood flow in the visual cortex, the left lateral prefrontal cortex. the inferior aspect of the anterior cingulate, the left parietal cortex and the cerebellum. Our results demonstrate an extensive diurnal variation in baseline human rCBF. This indicates that time of day may be an important variable in conducting and interpreting functional brain imaging studies. Furthermore, these results suggest possible neuroanatomical substrates through which the circadian system may regulate the various physiologic and behavioral processes that manifest circadian rhythms.

  20. Variations in the concentration of total human milk proteins in the first month of lactation

    Directory of Open Access Journals (Sweden)

    Mladenović Marija

    2007-01-01

    Full Text Available Introduction. Human milk proteins are maximally adapted to physiological needs of a neonate. Thus, depending on the speed of the neonatal growth and development, the content of milk proteins changes, both in quantity and quality. Objective. The study was conducted in order to determine variations of total protein concentrations in milk in the first and third lactation week in lactating mothers of term and preterm neonates. Also, we analyzed the influence of the mode of delivery, neonatal Apgar score and parity on the concentration of human milk proteins in both lactation phases. Method. The study aims were evaluated on the sample of 48 women, of whom 33 were mothers of term neonates and 15 of neonates born between the 34th to 37th gestational weeks. Total protein level of the lactation milk from the middle phase was determined using the standard laboratory method (Lowry et al., 1951, and the obtained differences were analyzed by t-test. Results. Total protein concentration in term colostrum was 17.60-45.17 g/l (X=24.71±5.19, while in preterm colostrum it was 28.39-73.30 g/l (X=39.17±11.08. The total protein level of mature milk in women who had term delivery was 11.90-22.11 g/l (X=16.39±2.96, while in women who had preterm delivery it was 14.50-44.19 g/l (X=23.25±8.96. The obtained results indicated that total protein concentration in women who had preterm delivery was significantly higher than that of women who had term delivery, both in the colostral and mature phase of lactation. (p<0.01. Also, the difference in the protein concentration was statistically highly significant (p<0.01 in the colostral and mature phase of lactation, both in women who had term and preterm delivery. Variations in the total protein level of human milk were not significant, depending on the prematurity stage, the mode and severity of delivery and parity, both in the first and third week of lactation. Conclusion. Our results show that total protein concentration

  1. Rethinking the starch digestion hypothesis for AMY1 copy number variation in humans.

    Science.gov (United States)

    Fernández, Catalina I; Wiley, Andrea S

    2017-08-01

    Alpha-amylase exists across taxonomic kingdoms with a deep evolutionary history of gene duplications that resulted in several α-amylase paralogs. Copy number variation (CNV) in the salivary α-amylase gene (AMY1) exists in many taxa, but among primates, humans appear to have higher average AMY1 copies than nonhuman primates. Additionally, AMY1 CNV in humans has been associated with starch content of diets, and one known function of α-amylase is its involvement in starch digestion. Thus high AMY1 CNV is considered to result from selection favoring more efficient starch digestion in the Homo lineage. Here, we present several lines of evidence that challenge the hypothesis that increased AMY1 CNV is an adaptation to starch consumption. We observe that α- amylase plays a very limited role in starch digestion, with additional steps required for starch digestion and glucose metabolism. Specifically, we note that α-amylase hydrolysis only produces a minute amount of free glucose with further enzymatic digestion and glucose absorption being rate-limiting steps for glucose availability. Indeed α-amylase is nonessential for starch digestion since sucrase-isomaltase and maltase-glucoamylase can hydrolyze whole starch granules while releasing glucose. While higher AMY1 CN and CNV among human populations may result from natural selection, existing evidence does not support starch digestion as the major selective force. We report that in humans α-amylase is expressed in several other tissues where it may have potential roles of evolutionary significance. © 2017 Wiley Periodicals, Inc.

  2. Human Y chromosome copy number variation in the next generation sequencing era and beyond.

    Science.gov (United States)

    Massaia, Andrea; Xue, Yali

    2017-05-01

    The human Y chromosome provides a fertile ground for structural rearrangements owing to its haploidy and high content of repeated sequences. The methodologies used for copy number variation (CNV) studies have developed over the years. Low-throughput techniques based on direct observation of rearrangements were developed early on, and are still used, often to complement array-based or sequencing approaches which have limited power in regions with high repeat content and specifically in the presence of long, identical repeats, such as those found in human sex chromosomes. Some specific rearrangements have been investigated for decades; because of their effects on fertility, or their outstanding evolutionary features, the interest in these has not diminished. However, following the flourishing of large-scale genomics, several studies have investigated CNVs across the whole chromosome. These studies sometimes employ data generated within large genomic projects such as the DDD study or the 1000 Genomes Project, and often survey large samples of healthy individuals without any prior selection. Novel technologies based on sequencing long molecules and combinations of technologies, promise to stimulate the study of Y-CNVs in the immediate future.

  3. Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

    KAUST Repository

    Cui, Peng

    2012-03-23

    Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

  4. On Application of Least-delay Variation Problem in Ethernet Networks Using SDN Concept

    Directory of Open Access Journals (Sweden)

    Tomas Hegr

    2016-01-01

    Full Text Available The goal of this paper is to present an application idea of SDN in Smart Grids, particularly, in the area of L2 multicast as defined by IEC 61850-9-2. Authors propose an Integer Linear Formulation (ILP dealing with a Least-Delay-Variation multicast forwarding problem that has a potential to utilize Ethernet networks in a new way. The proposed ILP formulation is numerically evaluated on random graph topologies and results are compared to a shortest path tree approach that is traditionally a product of Spanning Tree Protocols. Results confirm the correctness of the ILP formulation and illustrate dependency of a solution quality on the selected graph models, especially, in a case of scale-free topologies.

  5. Dynamic history-dependent variational-hemivariational inequalities with applications to contact mechanics

    Science.gov (United States)

    Migórski, Stanislaw; Ogorzaly, Justyna

    2017-02-01

    In the paper we deliver a new existence and uniqueness result for a class of abstract nonlinear variational-hemivariational inequalities which are governed by two operators depending on the history of the solution, and include two nondifferentiable functionals, a convex and a nonconvex one. Then, we consider an initial boundary value problem which describes a model of evolution of a viscoelastic body in contact with a foundation. The contact process is assumed to be dynamic, and the friction is described by subdifferential boundary conditions. Both the constitutive law and the contact condition involve memory operators. As an application of the abstract theory, we provide a result on the unique weak solvability of the contact problem.

  6. Asymmetry quantization and application to human mandibles

    Science.gov (United States)

    Glerup, Nanna; Nielsen, Mads; Sporring, Jon; Kreiborg, Sven

    2004-05-01

    All biological objects exhibit some degree of asymmetry, but for some parts of the human body, excessive asymmetry is a sign of pathology. Hence, the problem is to draw the line between categorization of objects being too asymmetric and objects exhibiting normal asymmetry. With a measure of asymmetry, the statistics on asymmetry for normal and pathological anatomical structures can be compared. Symmetry is a well-known mathematical group theoretical concept. In this paper, we will mathematically define the concept of weak symmetry, including topological symmetry, which serves as a basis for quantizing asymmetry. The methodology is based on non-rigid registration in the sense that the "size" of a diffeomorphism describes the amount of asymmetry. We will define this size in terms of the minimum biological work needed. That is, we evaluate how much work the biological system must carry out in order to make the object symmetrical; or identically, how much work has been carried out in order to make the ideal symmetrical object into the current (slightly) asymmetrical object. The quantization of asymmetry is validated on a set of normal (assumed near symmetrical) mandibles, and a set of pathological assumed non-symmetric mandibles exhibiting a statistically significant increase of asymmetry.

  7. Potential applications and human biosafety of nanomaterials used in nanomedicine.

    Science.gov (United States)

    Su, Hong; Wang, Yafei; Gu, Yuanliang; Bowman, Linda; Zhao, Jinshun; Ding, Min

    2017-06-06

    With the rapid development of nanotechnology, potential applications of nanomaterials in medicine have been widely researched in recent years. Nanomaterials themselves can be used as image agents or therapeutic drugs, and for drug and gene delivery, biological devices, nanoelectronic biosensors or molecular nanotechnology. As the composition, morphology, chemical properties, implant sites as well as potential applications become more and more complex, human biosafety of nanomaterials for clinical use has become a major concern. If nanoparticles accumulate in the human body or interact with the body molecules or chemical components, health risks may also occur. Accordingly, the unique chemical and physical properties, potential applications in medical fields, as well as human biosafety in clinical trials are reviewed in this study. Finally, this article tries to give some suggestions for future work in nanomedicine research. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Al-Subeihi, Ala' A.A., E-mail: subeihi@yahoo.com [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); BEN-HAYYAN-Aqaba International Laboratories, Aqaba Special Economic Zone Authority (ASEZA), P. O. Box 2565, Aqaba 77110 (Jordan); Alhusainy, Wasma; Kiwamoto, Reiko; Spenkelink, Bert [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); Bladeren, Peter J. van [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); Nestec S.A., Avenue Nestlé 55, 1800 Vevey (Switzerland); Rietjens, Ivonne M.C.M.; Punt, Ans [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands)

    2015-03-01

    The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1′-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1′-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1′-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1′-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1′-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1′-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment. - Highlights: • Interindividual human differences in methyleugenol bioactivation were simulated. • This was done using in vitro incubations, PBK modeling

  9. Human-Induced Climate Variations Linked to Urbanization: From Observations to Modeling

    Science.gov (United States)

    Shepherd, J. Marshall; Jin, Menglin

    2004-01-01

    The goal of this session is to bring together scientists from interdisciplinary backgrounds to discuss the data, scientific approaches and recent results focusing on the impact of urbanization on the climate. The discussion will highlight current observational and modeling capabilities being employed for investigating the urban environment and its linkage to the change in the Earth's climate system. The goal of the session is to identify our current stand and the future direction on the topic. Urbanization is one of the extreme cases of land use change. Most of population of the world has moved to urban areas. By 1995, more than 70% of population of North America and Europe were living in cities. By 2025, the United Nations estimates that 60% of the worlds population will live in cities. Although currently only 1.2% of the land is urban, better understanding of how the atmosphere-ocean-land-biosphere components interact as a coupled system and the influence of human activities on this system is critical. Our understanding of urbanization effect is incomplete, partly because human activities induce new changes on climate in addition to the original natural variations, and partly because previously few data available for study urban effect globally. Urban construction changes surface roughness, albedo, heat capacity and vegetation coverage. Traffic and industry increase atmospheric aerosol. It is suggested that urbanization may modify rainfall processes through aerosol-cloud interactions or dynamic feedbacks. Because urbanization effect on climate is determined by many factors including land cover, the city's microscale features, population density, and human lifestyle patterns, it is necessary to study urban areas over globe.

  10. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

    Directory of Open Access Journals (Sweden)

    Adriana eBarman

    2014-04-01

    Full Text Available The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT and the logical memory section of the Wechsler Memory Scale (WMS. Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e. the myopia risk allele showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point towards pleitropic effects of RASGRF1 genetic variations on complex neural function in humans.

  11. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

    Science.gov (United States)

    Barman, Adriana; Assmann, Anne; Richter, Sylvia; Soch, Joram; Schütze, Hartmut; Wüstenberg, Torsten; Deibele, Anna; Klein, Marieke; Richter, Anni; Behnisch, Gusalija; Düzel, Emrah; Zenker, Martin; Seidenbecher, Constanze I.; Schott, Björn H.

    2014-01-01

    The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans. PMID:24808846

  12. Variations in Glycogen Synthesis in Human Pluripotent Stem Cells with Altered Pluripotent States

    Science.gov (United States)

    Chen, Richard J.; Zhang, Guofeng; Garfield, Susan H.; Shi, Yi-Jun; Chen, Kevin G.; Robey, Pamela G.; Leapman, Richard D.

    2015-01-01

    Human pluripotent stem cells (hPSCs) represent very promising resources for cell-based regenerative medicine. It is essential to determine the biological implications of some fundamental physiological processes (such as glycogen metabolism) in these stem cells. In this report, we employ electron, immunofluorescence microscopy, and biochemical methods to study glycogen synthesis in hPSCs. Our results indicate that there is a high level of glycogen synthesis (0.28 to 0.62 μg/μg proteins) in undifferentiated human embryonic stem cells (hESCs) compared with the glycogen levels (0 to 0.25 μg/μg proteins) reported in human cancer cell lines. Moreover, we found that glycogen synthesis was regulated by bone morphogenetic protein 4 (BMP-4) and the glycogen synthase kinase 3 (GSK-3) pathway. Our observation of glycogen bodies and sustained expression of the pluripotent factor Oct-4 mediated by the potent GSK-3 inhibitor CHIR-99021 reveals an altered pluripotent state in hPSC culture. We further confirmed glycogen variations under different naïve pluripotent cell growth conditions based on the addition of the GSK-3 inhibitor BIO. Our data suggest that primed hPSCs treated with naïve growth conditions acquire altered pluripotent states, similar to those naïve-like hPSCs, with increased glycogen synthesis. Furthermore, we found that suppression of phosphorylated glycogen synthase was an underlying mechanism responsible for altered glycogen synthesis. Thus, our novel findings regarding the dynamic changes in glycogen metabolism provide new markers to assess the energetic and various pluripotent states in hPSCs. The components of glycogen metabolic pathways offer new assays to delineate previously unrecognized properties of hPSCs under different growth conditions. PMID:26565809

  13. Variations in Glycogen Synthesis in Human Pluripotent Stem Cells with Altered Pluripotent States.

    Science.gov (United States)

    Chen, Richard J; Zhang, Guofeng; Garfield, Susan H; Shi, Yi-Jun; Chen, Kevin G; Robey, Pamela G; Leapman, Richard D

    2015-01-01

    Human pluripotent stem cells (hPSCs) represent very promising resources for cell-based regenerative medicine. It is essential to determine the biological implications of some fundamental physiological processes (such as glycogen metabolism) in these stem cells. In this report, we employ electron, immunofluorescence microscopy, and biochemical methods to study glycogen synthesis in hPSCs. Our results indicate that there is a high level of glycogen synthesis (0.28 to 0.62 μg/μg proteins) in undifferentiated human embryonic stem cells (hESCs) compared with the glycogen levels (0 to 0.25 μg/μg proteins) reported in human cancer cell lines. Moreover, we found that glycogen synthesis was regulated by bone morphogenetic protein 4 (BMP-4) and the glycogen synthase kinase 3 (GSK-3) pathway. Our observation of glycogen bodies and sustained expression of the pluripotent factor Oct-4 mediated by the potent GSK-3 inhibitor CHIR-99021 reveals an altered pluripotent state in hPSC culture. We further confirmed glycogen variations under different naïve pluripotent cell growth conditions based on the addition of the GSK-3 inhibitor BIO. Our data suggest that primed hPSCs treated with naïve growth conditions acquire altered pluripotent states, similar to those naïve-like hPSCs, with increased glycogen synthesis. Furthermore, we found that suppression of phosphorylated glycogen synthase was an underlying mechanism responsible for altered glycogen synthesis. Thus, our novel findings regarding the dynamic changes in glycogen metabolism provide new markers to assess the energetic and various pluripotent states in hPSCs. The components of glycogen metabolic pathways offer new assays to delineate previously unrecognized properties of hPSCs under different growth conditions.

  14. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  15. Analysis of substructural variation in families of enzymatic proteins with applications to protein function prediction

    Directory of Open Access Journals (Sweden)

    Fofanov Viacheslav Y

    2010-05-01

    Full Text Available Abstract Background Structural variations caused by a wide range of physico-chemical and biological sources directly influence the function of a protein. For enzymatic proteins, the structure and chemistry of the catalytic binding site residues can be loosely defined as a substructure of the protein. Comparative analysis of drug-receptor substructures across and within species has been used for lead evaluation. Substructure-level similarity between the binding sites of functionally similar proteins has also been used to identify instances of convergent evolution among proteins. In functionally homologous protein families, shared chemistry and geometry at catalytic sites provide a common, local point of comparison among proteins that may differ significantly at the sequence, fold, or domain topology levels. Results This paper describes two key results that can be used separately or in combination for protein function analysis. The Family-wise Analysis of SubStructural Templates (FASST method uses all-against-all substructure comparison to determine Substructural Clusters (SCs. SCs characterize the binding site substructural variation within a protein family. In this paper we focus on examples of automatically determined SCs that can be linked to phylogenetic distance between family members, segregation by conformation, and organization by homology among convergent protein lineages. The Motif Ensemble Statistical Hypothesis (MESH framework constructs a representative motif for each protein cluster among the SCs determined by FASST to build motif ensembles that are shown through a series of function prediction experiments to improve the function prediction power of existing motifs. Conclusions FASST contributes a critical feedback and assessment step to existing binding site substructure identification methods and can be used for the thorough investigation of structure-function relationships. The application of MESH allows for an automated

  16. Analysis of substructural variation in families of enzymatic proteins with applications to protein function prediction.

    Science.gov (United States)

    Bryant, Drew H; Moll, Mark; Chen, Brian Y; Fofanov, Viacheslav Y; Kavraki, Lydia E

    2010-05-11

    Structural variations caused by a wide range of physico-chemical and biological sources directly influence the function of a protein. For enzymatic proteins, the structure and chemistry of the catalytic binding site residues can be loosely defined as a substructure of the protein. Comparative analysis of drug-receptor substructures across and within species has been used for lead evaluation. Substructure-level similarity between the binding sites of functionally similar proteins has also been used to identify instances of convergent evolution among proteins. In functionally homologous protein families, shared chemistry and geometry at catalytic sites provide a common, local point of comparison among proteins that may differ significantly at the sequence, fold, or domain topology levels. This paper describes two key results that can be used separately or in combination for protein function analysis. The Family-wise Analysis of SubStructural Templates (FASST) method uses all-against-all substructure comparison to determine Substructural Clusters (SCs). SCs characterize the binding site substructural variation within a protein family. In this paper we focus on examples of automatically determined SCs that can be linked to phylogenetic distance between family members, segregation by conformation, and organization by homology among convergent protein lineages. The Motif Ensemble Statistical Hypothesis (MESH) framework constructs a representative motif for each protein cluster among the SCs determined by FASST to build motif ensembles that are shown through a series of function prediction experiments to improve the function prediction power of existing motifs. FASST contributes a critical feedback and assessment step to existing binding site substructure identification methods and can be used for the thorough investigation of structure-function relationships. The application of MESH allows for an automated, statistically rigorous procedure for incorporating structural

  17. Prebiotics from marine macroalgae for human and animal health applications.

    LENUS (Irish Health Repository)

    O'Sullivan, Laurie

    2010-01-01

    The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and\\/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date.

  18. Application of postured human model for SAR measurements

    Science.gov (United States)

    Vuchkovikj, M.; Munteanu, I.; Weiland, T.

    2013-07-01

    In the last two decades, the increasing number of electronic devices used in day-to-day life led to a growing interest in the study of the electromagnetic field interaction with biological tissues. The design of medical devices and wireless communication devices such as mobile phones benefits a lot from the bio-electromagnetic simulations in which digital human models are used. The digital human models currently available have an upright position which limits the research activities in realistic scenarios, where postured human bodies must be considered. For this reason, a software application called "BodyFlex for CST STUDIO SUITE" was developed. In its current version, this application can deform the voxel-based human model named HUGO (Dipp GmbH, 2010) to allow the generation of common postures that people use in normal life, ensuring the continuity of tissues and conserving the mass to an acceptable level. This paper describes the enhancement of the "BodyFlex" application, which is related to the movements of the forearm and the wrist of a digital human model. One of the electromagnetic applications in which the forearm and the wrist movement of a voxel based human model has a significant meaning is the measurement of the specific absorption rate (SAR) when a model is exposed to a radio frequency electromagnetic field produced by a mobile phone. Current SAR measurements of the exposure from mobile phones are performed with the SAM (Specific Anthropomorphic Mannequin) phantom which is filled with a dispersive but homogeneous material. We are interested what happens with the SAR values if a realistic inhomogeneous human model is used. To this aim, two human models, a homogeneous and an inhomogeneous one, in two simulation scenarios are used, in order to examine and observe the differences in the results for the SAR values.

  19. Human-Level AI's Killer Application: Interactive Computer Games

    OpenAIRE

    Laird, John; VanLent, Michael

    2001-01-01

    Although one of the fundamental goals of AI is to understand and develop intelligent systems that have all the capabilities of humans, there is little active research directly pursuing this goal. We propose that AI for interactive computer games is an emerging application area in which this goal of human-level AI can successfully be pursued. Interactive computer games have increasingly complex and realistic worlds and increasingly complex and intelligent computer-controlled characters. In thi...

  20. The architecture of gene regulatory variation across multiple human tissues: the MuTHER study.

    Directory of Open Access Journals (Sweden)

    Alexandra C Nica

    2011-02-01

    Full Text Available While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL, skin, and fat. The samples (156 LCL, 160 skin, 166 fat were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes. In addition, we apply factor analysis (FA to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes. The unique study design (Matched Co-Twin Analysis--MCTA permits immediate replication of eQTLs using co-twins (93%-98% and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20% have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits.

  1. Identifying the genetic variation of gene expression using gene sets: application of novel gene Set eQTL approach to PharmGKB and KEGG.

    Directory of Open Access Journals (Sweden)

    Ryan Abo

    Full Text Available Genetic variation underlying the regulation of mRNA gene expression in humans may provide key insights into the molecular mechanisms of human traits and complex diseases. Current statistical methods to map genetic variation associated with mRNA gene expression have typically applied standard linkage and/or association methods; however, when genome-wide SNP and mRNA expression data are available performing all pair wise comparisons is computationally burdensome and may not provide optimal power to detect associations. Consideration of different approaches to account for the high dimensionality and multiple testing issues may provide increased efficiency and statistical power. Here we present a novel approach to model and test the association between genetic variation and mRNA gene expression levels in the context of gene sets (GSs and pathways, referred to as gene set - expression quantitative trait loci analysis (GS-eQTL. The method uses GSs to initially group SNPs and mRNA expression, followed by the application of principal components analysis (PCA to collapse the variation and reduce the dimensionality within the GSs. We applied GS-eQTL to assess the association between SNP and mRNA expression level data collected from a cell-based model system using PharmGKB and KEGG defined GSs. We observed a large number of significant GS-eQTL associations, in which the most significant associations arose between genetic variation and mRNA expression from the same GS. However, a number of associations involving genetic variation and mRNA expression from different GSs were also identified. Our proposed GS-eQTL method effectively addresses the multiple testing limitations in eQTL studies and provides biological context for SNP-expression associations.

  2. Enzymatic modification of phospholipids forfunctional applications and human nutrition

    DEFF Research Database (Denmark)

    Guo, Zheng; Vikbjerg, Anders / Falk; Xu, Xuebing

    2005-01-01

    Rapid progress in biochemistry of phospholipids and evolution of modern bioengineering has brought forth a number of novel concepts and technical advancements in the modification of phospholipids for industrial applications and human nutrition. Highlights cover preparation of novel phospholipid...... of phospholipids. This work reviews the natural occurrence and structural characteristics of phospholipids, their updated knowledge on manifold biological and nutritional functions, traditional and novel physical and chemical approaches to modify phospholipids as well as their applications to obtain novel...

  3. Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

    NARCIS (Netherlands)

    B. Giardine (Belinda); J. Borg (Joseph); D.R. Higgs (Douglas); K.R. Peterson (Kenneth R.); J.N.J. Philipsen (Sjaak); D. Maglott (Donna); B.K. Singleton (Belinda K.); D.J. Anstee (David J.); A.N. Basak (Nazli); B.H. Clark (Bruce); F.C. Costa (Flavia C.); P. Faustino (Paula); H. Fedosyuk (Halyna); A.E. Felice (Alex); A. Francina (Alain); R. Galanello (Renzo); M.V.E. Gallivan (Monica V. E.); M. Georgitsi (Marianthi); R.J. Gibbons (Richard J.); P.C. Giordano (Piero Carlo); C.L. Harteveld (Cornelis); J.D. Hoyer (James D.); M. Jarvis (Martin); P. Joly (Philippe); E. Kanavakis (Emmanuel); P. Kollia (Panagoula); S. Menzel (Stephan); W.G. Miller (William); K. Moradkhani (Kamran); J. Old (John); A. Papachatzpoulou (Adamantia); M.N. Papadakis (Manoussos); P. Papadopoulos (Petros); S. Pavlovic (Sonja); L. Perseu (Lucia); M. Radmilovic (Milena); C. Riemer (Cathy); S. Satta (Stefania); I.A. Schrijver (Ingrid); M. Stojiljkovic (Maja); S.L. Thein; J. Traeger-Synodinos (Joanne); R. Tully (Ray); T. Wada (Takahito); J.S. Waye (John); C. Wiemann (Claudia); B. Zukic (Branka); D.H.K. Chui (David H. K.); H. Wajcman (Henri); R. Hardison (Ross); G.P. Patrinos (George)

    2011-01-01

    textabstractWe developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public

  4. Investigating different filter and rescaling methods on simulated GRACE-like TWS variations for hydrological applications

    Science.gov (United States)

    Zhang, Liangjing; Dobslaw, Henryk; Dahle, Christoph; Thomas, Maik; Neumayer, Karl-Hans; Flechtner, Frank

    2017-04-01

    By operating for more than one decade now, the GRACE satellite provides valuable information on the total water storage (TWS) for hydrological and hydro-meteorological applications. The increasing interest in use of the GRACE-based TWS requires an in-depth assessment of the reliability of the outputs and also its uncertainties. Through years of development, different post-processing methods have been suggested for TWS estimation. However, since GRACE offers an unique way to provide high spatial and temporal scale TWS, there is no global ground truth data available to fully validate the results. In this contribution, we re-assess a number of commonly used post-processing methods using a simulated GRACE-type gravity field time-series based on realistic orbits and instrument error assumptions as well as background error assumptions out of the updated ESA Earth System Model. Three non-isotropic filter methods from Kusche (2007) and a combined filter from DDK1 and DDK3 based on the ground tracks are tested. Rescaling factors estimated from five different hydrological models and the ensemble median are applied to the post-processed simulated GRACE-type TWS estimates to correct the bias and leakage. Time variant rescaling factors as monthly scaling factors and scaling factors for seasonal and long-term variations separately are investigated as well. Since TWS anomalies out of the post-processed simulation results can be readily compared to the time-variable Earth System Model initially used as "truth" during the forward simulation step, we are able to thoroughly check the plausibility of our error estimation assessment (Zhang et al., 2016) and will subsequently recommend a processing strategy that shall also be applied for planned GRACE and GRACE-FO Level-3 products for terrestrial applications provided by GFZ. Kusche, J., 2007:Approximate decorrelation and non-isotropic smoothing of time-variable GRACE-type gravity field models. J. Geodesy, 81 (11), 733-749, doi:10

  5. Weak convergence theorem for a class of split variational inequality problems and applications in a Hilbert space.

    Science.gov (United States)

    Tian, Ming; Jiang, Bing-Nan

    2017-01-01

    In this paper, we consider the algorithm proposed in recent years by Censor, Gibali and Reich, which solves split variational inequality problem, and Korpelevich's extragradient method, which solves variational inequality problems. As our main result, we propose an iterative method for finding an element to solve a class of split variational inequality problems under weaker conditions and get a weak convergence theorem. As applications, we obtain some new weak convergence theorems by using our weak convergence result to solve related problems in nonlinear analysis and optimization.

  6. [Variations in the concentration of total human milk proteins in the first month of lactation].

    Science.gov (United States)

    Mladenović, Marija; Radlović, Nedeljko; Leković, Zoran; Ristić, Dragana; Radlović, Petar; Gajić, Milan; Djurdjević, Jelena

    2007-01-01

    Human milk proteins are maximally adapted to physiological needs of a neonate. Thus, depending on the speed of the neonatal growth and development, the content of milk proteins changes, both in quantity and quality. The study was conducted in order to determine variations of total protein concentrations in milk in the first and third lactation week in lactating mothers of term and preterm neonates. Also, we analyzed the influence of the mode of delivery, neonatal Apgar score and parity on the concentration of human milk proteins in both lactation phases. The study aims were evaluated on the sample of 48 women, of whom 33 were mothers of term neonates and 15 of neonates born between the 34th to 37th gestational weeks. Total protein level of the lactation milk from the middle phase was determined using the standard laboratory method (Lowry et al., 1951), and the obtained differences were analyzed by t-test. Total protein concentration in term colostrum was 17.60-45.17 g/l (X = 24.71 +/- 5.19), while in preterm colostrum it was 28.39-73.30 g/l (X = 39.17 +/- 11.08). The total protein level of mature milk in women who had term delivery was 11.90-22.11 g/l (X = 16.39 +/- 2.96), while in women who had preterm delivery it was 14.50-44.19 g/l (X = 23.25 +/-8.96). The obtained results indicated that total protein concentration in women who had preterm delivery was significantly higher than that of women who had term delivery, both in the colostral and mature phase of lactation. (p protein concentration was statistically highly significant (p total protein level of human milk were not significant, depending on the prematurity stage, the mode and severity of delivery and parity, both in the first and third week of lactation. Our results show that total protein concentration in human milk was significantly higher in the first than the third week of lactation. In both lactation phases, milk protein content was higher in women who had preterm delivery than those having had term

  7. Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women.

    Directory of Open Access Journals (Sweden)

    Thomas R Hawn

    2009-12-01

    Full Text Available Although several studies suggest that genetic factors are associated with human UTI susceptibility, the role of DNA variation in regulating early in vivo urine inflammatory responses has not been fully examined. We examined whether candidate gene polymorphisms were associated with altered urine inflammatory profiles in asymptomatic women with or without bacteriuria.We conducted a cross-sectional analysis of asymptomatic bacteriuria (ASB in 1,261 asymptomatic women ages 18-49 years originally enrolled as participants in a population-based case-control study of recurrent UTI and pyelonephritis. We genotyped polymorphisms in CXCR1, CXCR2, TLR1, TLR2, TLR4, TLR5, and TIRAP in women with and without ASB. We collected urine samples and measured levels of uropathogenic bacteria, neutrophils, and chemokines.Polymorphism TLR2_G2258A, a variant associated with decreased lipopeptide-induced signaling, was associated with increased ASB risk (odds ratio 3.44, 95%CI; 1.65-7.17. Three CXCR1 polymorphisms were associated with ASB caused by gram-positive organisms. ASB was associated with urinary CXCL-8 levels, but not CXCL-5, CXCL-6, or sICAM-1 (P< or =0.0001. Urinary levels of CXCL-8 and CXCL-6, but not ICAM-1, were associated with higher neutrophil levels (P< or =0.0001. In addition, polymorphism CXCR1_G827C was associated with increased CXCL-8 levels in women with ASB (P = 0.004.TLR2 and CXCR1 polymorphisms were associated with ASB and a CXCR1 variant was associated with urine CXCL-8 levels. These results suggest that genetic factors are associated with early in vivo human bladder immune responses prior to the development of symptomatic UTIs.

  8. Sequence variation in human succinate dehydrogenase genes: evidence for long-term balancing selection on SDHA

    Directory of Open Access Journals (Sweden)

    Lawrence Elizabeth C

    2007-03-01

    Full Text Available Abstract Background Balancing selection operating for long evolutionary periods at a locus is characterized by the maintenance of distinct alleles because of a heterozygote or rare-allele advantage. The loci under balancing selection are distinguished by their unusually high polymorphism levels. In this report, we provide statistical and comparative genetic evidence suggesting that the SDHA gene is under long-term balancing selection. SDHA encodes the major catalytical subunit (flavoprotein, Fp of the succinate dehydrogenase enzyme complex (SDH; mitochondrial complex II. The inhibition of Fp by homozygous SDHA mutations or by 3-nitropropionic acid poisoning causes central nervous system pathologies. In contrast, heterozygous mutations in SDHB, SDHC, and SDHD, the other SDH subunit genes, cause hereditary paraganglioma (PGL tumors, which show constitutive activation of pathways induced by oxygen deprivation (hypoxia. Results We sequenced the four SDH subunit genes (10.8 kb in 24 African American and 24 European American samples. We also sequenced the SDHA gene (2.8 kb in 18 chimpanzees. Increased nucleotide diversity distinguished the human SDHA gene from its chimpanzee ortholog and from the PGL genes. Sequence analysis uncovered two common SDHA missense variants and refuted the previous suggestions that these variants originate from different genetic loci. Two highly dissimilar SDHA haplotype clusters were present in intermediate frequencies in both racial groups. The SDHA variation pattern showed statistically significant deviations from neutrality by the Tajima, Fu and Li, Hudson-Kreitman-Aguadé, and Depaulis haplotype number tests. Empirically, the elevated values of the nucleotide diversity (% π = 0.231 and the Tajima statistics (D = 1.954 in the SDHA gene were comparable with the most outstanding cases for balancing selection in the African American population. Conclusion The SDHA gene has a strong signature of balancing selection. The

  9. Potential applications of keratinocytes derived from human embryonic stem cells.

    Science.gov (United States)

    Movahednia, Mohammad M; Kidwai, Fahad K; Jokhun, Doorgesh S; Squier, Christopher A; Toh, Wei Seong; Cao, Tong

    2016-01-01

    Although skin grafting is one of the most advanced cell therapy technique, wide application of skin substitutes is hampered by the difficulty in securing sufficient amount of epidermal substitute. Additionally, in understanding the progression of skin aging and disease, and in screening the cosmetic and pharmaceutical products, there is lack of a satisfactory human skin-specific in vitro model. Recently, human embryonic stem cells (hESCs) have been proposed as an unlimited and reliable cell source to obtain almost all cell types present in the human body. This review focuses on the potential off-the-shelf use of hESC-derived keratinocytes for future clinical applications as well as a powerful in vitro skin model to study skin function and integrity, host-pathogen interactions and disease pathogenesis. Furthermore, we discuss the industrial applications of hESC-derived keratinized multi-layer epithelium which provides a human-like test platform for understanding disease pathogenesis, evaluation of new therapeutic modalities and assessment of the safety and efficacy of skin cosmetics and therapeutics. Overall, we conclude that the hESC-derived keratinocytes have great potential for clinical, research and industrial applications. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Application of Data Collection Techniques by Human Performance Technology Practitioners

    Science.gov (United States)

    Duan, Minjing

    2011-01-01

    By content-analyzing 22 published cases from a variety of professional and academic books and journals, this study examines the status quo of human performance technology (HPT) practitioners' application of five major data collection techniques in their everyday work: questionnaire, interview, focus group, observation, and document collection. The…

  11. Promise and Capability of NASA's Earth Observing System to Monitor Human-Induced Climate Variations

    Science.gov (United States)

    King, M. D.

    2003-01-01

    The Earth Observing System (EOS) is a space-based observing system comprised of a series of satellite sensors by which scientists can monitor the Earth, a Data and Information System (EOSDIS) enabling researchers worldwide to access the satellite data, and an interdisciplinary science research program to interpret the satellite data. The Moderate Resolution Imaging Spectroradiometer (MODIS), developed as part of the Earth Observing System (EOS) and launched on Terra in December 1999 and Aqua in May 2002, is designed to meet the scientific needs for satellite remote sensing of clouds, aerosols, water vapor, and land and ocean surface properties. This sensor and multi-platform observing system is especially well suited to observing detailed interdisciplinary components of the Earth s surface and atmosphere in and around urban environments, including aerosol optical properties, cloud optical and microphysical properties of both liquid water and ice clouds, land surface reflectance, fire occurrence, and many other properties that influence the urban environment and are influenced by them. In this presentation I will summarize the current capabilities of MODIS and other EOS sensors currently in orbit to study human-induced climate variations.

  12. Rare and common regulatory variation in population-scale sequenced human genomes.

    Directory of Open Access Journals (Sweden)

    Stephen B Montgomery

    2011-07-01

    Full Text Available Population-scale genome sequencing allows the characterization of functional effects of a broad spectrum of genetic variants underlying human phenotypic variation. Here, we investigate the influence of rare and common genetic variants on gene expression patterns, using variants identified from sequencing data from the 1000 genomes project in an African and European population sample and gene expression data from lymphoblastoid cell lines. We detect comparable numbers of expression quantitative trait loci (eQTLs when compared to genotypes obtained from HapMap 3, but as many as 80% of the top expression quantitative trait variants (eQTVs discovered from 1000 genomes data are novel. The properties of the newly discovered variants suggest that mapping common causal regulatory variants is challenging even with full resequencing data; however, we observe significant enrichment of regulatory effects in splice-site and nonsense variants. Using RNA sequencing data, we show that 46.2% of nonsynonymous variants are differentially expressed in at least one individual in our sample, creating widespread potential for interactions between functional protein-coding and regulatory variants. We also use allele-specific expression to identify putative rare causal regulatory variants. Furthermore, we demonstrate that outlier expression values can be due to rare variant effects, and we approximate the number of such effects harboured in an individual by effect size. Our results demonstrate that integration of genomic and RNA sequencing analyses allows for the joint assessment of genome sequence and genome function.

  13. The variation in surface morphology and hardness of human deciduous teeth samples after laser irradiation

    Science.gov (United States)

    Khalid, Arooj; Bashir, Shazia; Akram, Mahreen; Salman Ahmed, Qazi

    2017-11-01

    The variation in surface morphology and hardness of human deciduous teeth samples has been investigated after laser irradiation at different wavelengths and energies. Nd:YAG was employed as a source of irradiation for IR (1064 nm) and visible (532 nm) radiation, whereas an excimer laser was used as the source of UV (248 nm) radiation. Scanning electron microscope (SEM) analysis was carried out to reveal the surface morphological evolution of teeth samples. Vickers microhardness tester was employed to investigate the modifications in the hardness of the laser-treated samples. It is observed from SEM analysis that IR wavelength is responsible for ablation of collagen matrix and intertubular dentine. For visible radiation, the ablation of collagen along with hydroxypatite is observed. With UV radiation, the ablation of peritubular dentine is dominant and is responsible for the sealing of tubules. The decrease in hardness at lower energy for both wavelengths is due to the evaporation of carbon content. With increasing energy, evaporation of water along with carbon content, and resolidification and re-organization of inorganic content causes the increase in hardness of the treated dentine. SEM as well as microhardness analyses reveal that laser wavelengths and energy of laser radiation significantly influence the surface morphology and hardness of samples.

  14. Pesticide Residues in Bovine Milk in Punjab, India: Spatial Variation and Risk Assessment to Human Health.

    Science.gov (United States)

    Bedi, J S; Gill, J P S; Aulakh, R S; Kaur, Prabhjit

    2015-08-01

    In the present study, gas chromatographic analysis of pesticide residues in bovine milk (n = 312) from Punjab, India, showed chlorpyrifos, DDT, and γ-HCH as the predominant contaminants. In addition, the presence of β-endosulfan, endosulfan suphate, cypermethrin, cyhalothrin, fenvalerate, deltamethrin, malathion, profenofos, and ethion was reported in milk samples. In this study, it was observed that 12 milk samples exceeded the maximum residue limits (MRLs) for γ-HCH (lindane), 18 for DDT and chlorpyrifos, and 1 sample each for endosulfan, cypermethrin, and profenophos. In India, DDT is still permitted for a malaria control program, which may be the plausible reason for its occurrence in milk samples. The spatial variation for presence of pesticide residues in milk indicated greater levels in cotton-growing areas of Punjab. At current levels of pesticide residues in bovine milk, the human health risk assessment in terms of noncancer and cancer hazard was calculated based on both lower-bound [LB (mean residue levels)] and upper-bound [UP (95th percentile level)] limits. It was noticed that cancer and noncancer risk were within United States Environmental Protection Agency prescribed limits for both adults and children at the LB, but children were being exposed to greater risk for DDT and HCH at the 95th-percentile UB level.

  15. Variation in human mate choice: simultaneously investigating heritability, parental influence, sexual imprinting, and assortative mating.

    Science.gov (United States)

    Zietsch, Brendan P; Verweij, Karin J H; Heath, Andrew C; Martin, Nicholas G

    2011-05-01

    Human mate choice is central to individuals' lives and to the evolution of the species, but the basis of variation in mate choice is not well understood. Here we looked at a large community-based sample of twins and their partners and parents ([Formula: see text] individuals) to test for genetic and family environmental influences on mate choice, while controlling for and not controlling for the effects of assortative mating. Key traits were analyzed, including height, body mass index, age, education, income, personality, social attitudes, and religiosity. This revealed near-zero genetic influences on male and female mate choice over all traits and no significant genetic influences on mate choice for any specific trait. A significant family environmental influence was found for the age and income of females' mate choices, possibly reflecting parental influence over mating decisions. We also tested for evidence of sexual imprinting, where individuals acquire mate-choice criteria during development by using their opposite-sex parent as the template of a desirable mate; there was no such effect for any trait. The main discernible pattern of mate choice was assortative mating; we found that partner similarity was due to initial choice rather than convergence and also at least in part to phenotypic matching.

  16. Variation in human dental pulp stem cell ageing profiles reflect contrasting proliferative and regenerative capabilities.

    Science.gov (United States)

    Alraies, Amr; Alaidaroos, Nadia Y A; Waddington, Rachel J; Moseley, Ryan; Sloan, Alastair J

    2017-02-02

    Dental pulp stem cells (DPSCs) are increasingly being recognized as a viable cell source for regenerative medicine. Although significant variations in their ex vivo expansion are well-established, DPSC proliferative heterogeneity remains poorly understood, despite such characteristics influencing their regenerative and therapeutic potential. This study assessed clonal human DPSC regenerative potential and the impact of cellular senescence on these responses, to better understand DPSC functional behaviour. All DPSCs were negative for hTERT. Whilst one DPSC population reached >80 PDs before senescence, other populations only achieved high proliferative capacities possessing longer telomeres (18.9 kb) than less proliferative populations (5-13 kb). High proliferative capacity DPSCs exhibited prolonged stem cell marker expression, but lacked CD271. Early-onset senescence, stem cell marker loss and positive CD271 expression in DPSCs with low proliferative capacities were associated with impaired osteogenic and chondrogenic differentiation, favouring adipogenesis. DPSCs with high proliferative capacities only demonstrated impaired differentiation following prolonged expansion (>60 PDs). This study has identified that proliferative and regenerative heterogeneity is related to contrasting telomere lengths and CD271 expression between DPSC populations. These characteristics may ultimately be used to selectively screen and isolate high proliferative capacity/multi-potent DPSCs for regenerative medicine exploitation.

  17. Few single nucleotide variations in exomes of human cord blood induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Rui-Jun Su

    Full Text Available The effect of the cellular reprogramming process per se on mutation load remains unclear. To address this issue, we performed whole exome sequencing analysis of induced pluripotent stem cells (iPSCs reprogrammed from human cord blood (CB CD34(+ cells. Cells from a single donor and improved lentiviral vectors for high-efficiency (2-14% reprogramming were used to examine the effects of three different combinations of reprogramming factors: OCT4 and SOX2 (OS, OS and ZSCAN4 (OSZ, OS and MYC and KLF4 (OSMK. Five clones from each group were subject to whole exome sequencing analysis. We identified 14, 11, and 9 single nucleotide variations (SNVs, in exomes, including untranslated regions (UTR, in the five clones of OSMK, OS, and OSZ iPSC lines. Only 8, 7, and 4 of these, respectively, were protein-coding mutations. An average of 1.3 coding mutations per CB iPSC line is remarkably lower than previous studies using fibroblasts and low-efficiency reprogramming approaches. These data demonstrate that point nucleotide mutations during cord blood reprogramming are negligible and that the inclusion of genome stabilizers like ZSCAN4 during reprogramming may further decrease reprogramming-associated mutations. Our findings provide evidence that CB is a superior source of cells for iPSC banking.

  18. Variation in human mate choice: Simultaneously investigating heritability, parental influence, sexual imprinting, and assortative mating

    Science.gov (United States)

    Zietsch, Brendan P.; Verweij, Karin J. H.; Heath, Andrew C.; Martin, Nicholas G.

    2012-01-01

    Human mate choice is central to individuals’ lives and to the evolution of the species, but the basis of variation in mate choice is not well understood. Here we look at a large community-based sample of twins and their partners and parents (N > 20,000 individuals) to test for genetic and family environmental influences on mate choice, with and without controlling for the effects of assortative mating. Key traits are analyzed, including height, body mass index, age, education, income, personality, social attitudes, and religiosity. This revealed near-zero genetic influences on male and female mate choice over all traits and no significant genetic influences on mate choice for any specific trait. A significant family environmental influence was found for the age and income of females’ mate choices, possibly reflecting parental influence over mating decisions. We also tested for evidence of sexual imprinting, where individuals acquire mate-choice criteria during development by using their opposite-sex parent as the template of a desirable mate; there was no such effect for any trait. The main discernable pattern to mate choice was assortative mating; we found that partner similarity was due to initial choice rather than convergence and also due at least in part to phenotypic matching. PMID:21508607

  19. Variation Principles and Applications in the Study of Cell Structure and Aging

    Science.gov (United States)

    Economos, Angelos C.; Miquel, Jaime; Ballard, Ralph C.; Johnson, John E., Jr.

    1981-01-01

    In this report we have attempted to show that "some reality lies concealed in biological variation". This "reality" has its principles, laws, mechanisms, and rules, only a few of which we have sketched. A related idea we pursued was that important information may be lost in the process of ignoring frequency distributions of physiological variables (as is customary in experimental physiology and gerontology). We suggested that it may be advantageous to expand one's "statistical field of vision" beyond simple averages +/- standard deviations. Indeed, frequency distribution analysis may make visible some hidden information not evident from a simple qualitative analysis, particularly when the effect of some external factor or condition (e.g., aging, dietary chemicals) is being investigated. This was clearly illustrated by the application of distribution analysis in the study of variation in mouse liver cellular and fine structure, and may be true of fine structural studies in general. In living systems, structure and function interact in a dynamic way; they are "inseparable," unlike in technological systems or machines. Changes in fine structure therefore reflect changes in function. If such changes do not exceed a certain physiologic range, a quantitative analysis of structure will provide valuable information on quantitative changes in function that may not be possible or easy to measure directly. Because there is a large inherent variation in fine structure of cells in a given organ of an individual and among individuals, changes in fine structure can be analyzed only by studying frequency distribution curves of various structural characteristics (dimensions). Simple averages +/- S.D. do not in general reveal all information on the effect of a certain factor, because often this effect is not uniform; on the contrary, this will be apparent from distribution analysis because the form of the curves will be affected. We have also attempted to show in this chapter that

  20. Sensitivity Analysis and Variational Data Assimilation for ice flow - Application to the Mertz ice-tongue

    Science.gov (United States)

    Martin, N.; Monnier, J.

    2012-12-01

    To be confident in the accuracy of the modelling of ice flows requires to con- front numerical experiments to actual observations. This type of flow is strongly sensitive to its input parameters such as rheological parameters and boundary conditions like the friction on the bedrock. Using optimal control theory, we build a global 4D-Var algorithm using direct and adjoint model of the variational problem thus providing local sensitivity analysis and data assimilation (see [1]). In order to compute approximation of these flows, one consider the non newtonian velocity- pressure Stokes system described using mixed finite element method. The treat- ment of the free surface is performed using an Arbitrary Lagrangian Eulerian de- scription with robus elastic deformation and the adjoint method is constructed by algorithmic differentiation of the direct code using Tapenade software (INRIA). We lean on prior developments of the software DassFlow (see [2]). One of the major question for inverse methods in glaciology is to infer the fric- tion coefficient at bottom through data assimilation because it cannot be measured. In other respect, our first results based on real data shows that the rheological expo- nent and/or the thermal coefficient of the constitutive law (distributed parameter) has the same type of influence (see Figure 1) and can be inferred as well. Another modeling issue lies in the dynamic of the grounding line when con- sidering the floating part of the ice domain. Then, sensitivity analysis of the model response with respect to this grounding line dynamic leads to a better understand- ing of this unstable process and its empirical modelling. We present a real data application on the Mertz ice-shelf (Antarctica). Topography and surface velocities data are being provided by B. Legrésy (see [3]). References [1] Martin, N. and Monnier, J. : A three fields finite elements solver for viscoplas- tic free surface flows and variational data assimilation. In

  1. Initial studies on the variations of load-displacement curves of in vivo human healthy heel pads

    DEFF Research Database (Denmark)

    Matteoli, Sara; Wilhjelm, Jens E.; Virga, Antonio

    2011-01-01

    The aim of this study was to quantify on the measurement variation of in vivo load-displacement curves by using a group of human healthy heel pads. The recordings were done with a compression device measuring force and displacement. Twenty three heel pads, one from each of 23 subjects aged 20...

  2. Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

    NARCIS (Netherlands)

    Homburger, J.R. (Julian R.); Green, E.M. (Eric M.); Caleshu, C. (Colleen); Sunitha, M.S. (Margaret S.); Taylor, R.E. (Rebecca E.); Ruppel, K.M. (Kathleen M.); Metpally, R.P.R. (Raghu Prasad Rao); S.D. Colan (Steven); M. Michels (Michelle); Day, S.M. (Sharlene M.); I. Olivotto (Iacopo); Bustamante, C.D. (Carlos D.); Dewey, F.E. (Frederick E.); Ho, C.Y. (Carolyn Y.); Spudich, J.A. (James A.); Ashley, E.A. (Euan A.)

    2016-01-01

    textabstractMyosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac

  3. Human applications of the INEL patient treatment planning system

    Energy Technology Data Exchange (ETDEWEB)

    Wheeler, F.; Wessol, D.; Atkinson, C.; Nigg, D. [Idaho National Accelerator Lab., Idaho Falls, ID (United States)

    1995-11-01

    During the past few years, murine and large animal research, as well as human studies have provided data to the point where human clinical trials have been initiated at the BMRR using BPA-F for gliomas and at the Massachusetts Institute of Technology Reactor (MITR) using BPA for melanomas of the extremeties. It is expected that glioma trials using BSH will proceed soon at the Petten High Flux Reactor (HFR) in the Netherlands. The first human glioma epithermal boron neutron capture therapy application was performed at the BMRR in the fall of 1994. This was a collaborative effort by BNL, Beth Israel Manhattan hospital, and INEL. The INEL planning system was chosen to perform dose predictions for this application.

  4. Human walking in virtual environments perception, technology, and applications

    CERN Document Server

    Visell, Yon; Campos, Jennifer; Lécuyer, Anatole

    2013-01-01

    This book presents a survey of past and recent developments on human walking in virtual environments with an emphasis on human self-motion perception, the multisensory nature of experiences of walking, conceptual design approaches, current technologies, and applications. The use of virtual reality and movement simulation systems is becoming increasingly popular and more accessible to a wide variety of research fields and applications. While, in the past, simulation technologies have focused on developing realistic, interactive visual environments, it is becoming increasingly obvious that our everyday interactions are highly multisensory. Therefore, investigators are beginning to understand the critical importance of developing and validating locomotor interfaces that can allow for realistic, natural behaviours. The book aims to present an overview of what is currently understood about human perception and performance when moving in virtual environments and to situate it relative to the broader scientific and ...

  5. Variation in umami perception and in candidate genes for the umami receptor in mice and humans1234

    Science.gov (United States)

    Shirosaki, Shinya; Ohkuri, Tadahiro; Sanematsu, Keisuke; Islam, AA Shahidul; Ogiwara, Yoko; Kawai, Misako; Yoshida, Ryusuke; Ninomiya, Yuzo

    2009-01-01

    The unique taste induced by monosodium glutamate is referred to as umami taste. The umami taste is also elicited by the purine nucleotides inosine 5′-monophosphate and guanosine 5′-monophosphate. There is evidence that a heterodimeric G protein–coupled receptor, which consists of the T1R1 (taste receptor type 1, member 1, Tas1r1) and the T1R3 (taste receptor type 1, member 3, Tas1r3) proteins, functions as an umami taste receptor for rodents and humans. Splice variants of metabotropic glutamate receptors, mGluR1 (glutamate receptor, metabotropic 1, Grm1) and mGluR4 (glutamate receptor, metabotropic 4, Grm4), also have been proposed as taste receptors for glutamate. The taste sensitivity to umami substances varies in inbred mouse strains and in individual humans. However, little is known about the relation of umami taste sensitivity to variations in candidate umami receptor genes in rodents or in humans. In this article, we summarize current knowledge of the diversity of umami perception in mice and humans. Furthermore, we combine previously published data and new information from the single nucleotide polymorphism databases regarding variation in the mouse and human candidate umami receptor genes: mouse Tas1r1 (TAS1R1 for human), mouse Tas1r3 (TAS1R3 for human), mouse Grm1 (GRM1 for human), and mouse Grm4 (GRM4 for human). Finally, we discuss prospective associations between variation of these genes and umami taste perception in both species. PMID:19625681

  6. Host and Bacterial Phenotype Variation in Adhesion of Streptococcus mutans to Matched Human Hosts

    Science.gov (United States)

    Esberg, Anders; Löfgren-Burström, Anna; Öhman, Ulla

    2012-01-01

    The commensal pathogen Streptococcus mutans uses AgI/II adhesins to adhere to gp340 adsorbed on teeth. Here we analyzed isolates of S. mutans (n = 70 isolates) from caries and caries-free human extremes (n = 19 subjects) by multilocus sequence typing (MLST), AgI/II full-length gene sequencing, and adhesion to parotid saliva matched from the strain donors (nested from a case-control sample of defined gp340 and acidic proline-rich protein [PRP] profiles). The concatenated MLST as well as AgI/II gene sequences showed unique sequence types between, and identical types within, the subjects. The matched adhesion levels ranged widely (40% adhesion range), from low to moderate to high, between subjects but were similar within subjects (or sequence types). In contrast, the adhesion avidity of the strains was narrow, normally distributed for high, moderate, or low adhesion reference saliva or pure gp340 regardless of the sequence type. The adhesion of S. mutans Ingbritt and matched isolates and saliva samples correlated (r = 0.929), suggesting that the host specify about four-fifths (r2 = 0.86) of the variation in matched adhesion. Half of the variation in S. mutans Ingbritt adhesion to saliva from the caries cases-controls (n = 218) was explained by the primary gp340 receptor and PRP coreceptor composition. The isolates also varied, although less so, in adhesion to standardized saliva (18% adhesion range) and clustered into three major AgI/II groups (groups A, B1, and B2) due to two variable V-region segments and diverse AgI/II sequence types due to a set of single-amino-acid substitutions. Isolates with AgI/II type A versus types B1 and B2 tended to differ in gp340 binding avidity and qualitative adhesion profiles for saliva gp340 phenotypes. In conclusion, the host saliva phenotype plays a more prominent role in S. mutans adhesion than anticipated previously. PMID:22927045

  7. Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective.

    Science.gov (United States)

    Yamada, T; Manos, M M; Peto, J; Greer, C E; Munoz, N; Bosch, F X; Wheeler, C M

    1997-03-01

    We examined intratype human papillomavirus type 16 (HPV-16) sequence variation in tumor samples that were collected and analyzed in an international study of invasive cervical cancer. The collection included tumors from 22 countries in five continents. Using our recently developed E6 and L1 PCR-based hybridization systems to distinguish HPV-16 variant lineages, we analyzed material from tumors previously found to contain HPV-16 DNA. Of 408 specimens analyzed in the E6 hybridization assay, 376 (92.2%) belonged to previously reported HPV-16 variant lineages. The remaining 32 specimens (7.8%) harbored HPV-16 variants with novel hybridization patterns, novel nucleotide changes, or both. Nucleotide sequences (1,203 bp) were determined for the E6, the MY09/11 region of L1, and the long control region of each novel variant and representative specimens from each hybridization pattern observed. Based on E6 hybridization patterns, most of the variants from European and North American samples were phylogenetically classified as European prototype (E) while samples from Africa contained primarily African 1 (Af1) or African 2 (Af2) variants. The majority of Asian (As) variants were observed in Southeast Asia, and almost all Asian American (AA) variants were from Central and South America or Spain. A single North American 1 (NA1) variant was detected in a tumor from Argentina. Nucleotide changes previously shown to covary between the MY09/11 region of L1 and the E6 coding region were examined in a subset of 249 specimens. We observed 22 combined E6-L1 hybridization patterns, of which 11 (in 21 samples) were novel. No unanticipated nucleotide covariation was observed between the E class and the AA-Af1-Af2-NA1 classes, suggesting the absence or rarity of genomic recombination between HPV-16 lineages. This extensive description of HPV-16 variants forms a basis for further examining the relationship between intratype variation and basic functional differences in biological

  8. Empirical Mode Decomposition on the sphere: application to the spatial scales of surface temperature variations

    Directory of Open Access Journals (Sweden)

    N. Fauchereau

    2008-06-01

    Full Text Available Empirical Mode Decomposition (EMD is applied here in two dimensions over the sphere to demonstrate its potential as a data-adaptive method of separating the different scales of spatial variability in a geophysical (climatological/meteorological field. After a brief description of the basics of the EMD in 1 then 2 dimensions, the principles of its application on the sphere are explained, in particular via the use of a zonal equal area partitioning. EMD is first applied to an artificial dataset, demonstrating its capability in extracting the different (known scales embedded in the field. The decomposition is then applied to a global mean surface temperature dataset, and we show qualitatively that it extracts successively larger scales of temperature variations related, for example, to topographic and large-scale, solar radiation forcing. We propose that EMD can be used as a global data-adaptive filter, which will be useful in analysing geophysical phenomena that arise as the result of forcings at multiple spatial scales.

  9. Genetic Basis for Variation in Wheat Grain Yield in Response to Varying Nitrogen Application.

    Directory of Open Access Journals (Sweden)

    Saba Mahjourimajd

    Full Text Available Nitrogen (N is a major nutrient needed to attain optimal grain yield (GY in all environments. Nitrogen fertilisers represent a significant production cost, in both monetary and environmental terms. Developing genotypes capable of taking up N early during development while limiting biomass production after establishment and showing high N-use efficiency (NUE would be economically beneficial. Genetic variation in NUE has been shown previously. Here we describe the genetic characterisation of NUE and identify genetic loci underlying N response under different N fertiliser regimes in a bread wheat population of doubled-haploid lines derived from a cross between two Australian genotypes (RAC875 × Kukri bred for a similar production environment. NUE field trials were carried out at four sites in South Australia and two in Western Australia across three seasons. There was genotype-by-environment-by-treatment interaction across the sites and also good transgressive segregation for yield under different N supply in the population. We detected some significant Quantitative Trait Loci (QTL associated with NUE and N response at different rates of N application across the sites and years. It was also possible to identify lines showing positive N response based on the rankings of their Best Linear Unbiased Predictions (BLUPs within a trial. Dissecting the complexity of the N effect on yield through QTL analysis is a key step towards elucidating the molecular and physiological basis of NUE in wheat.

  10. The Application of NASA Remote Sensing Technology to Human Health

    Science.gov (United States)

    Watts, C. T.

    2007-01-01

    With the help of satellites, the Earth's environment can be monitored from a distance. Earth observing satellites and sensors collect data and survey patterns that supply important information about the environment relating to its affect on human health. Combined with ground data, such patterns and remote sensing data can be essential to public health applications. Remote sensing technology is providing information that can help predict factors that affect human health, such as disease, drought, famine, and floods. A number of public health concerns that affect Earth's human population are part of the current National Aeronautics and Space Administration (NASA) Earth Science Applications Plan to provide remotely gathered data to public health decision-makers to aid in forming and implementing policy to protect human health and preserve well-being. These areas of concern are: air quality; water quality; weather and climate change; infectious, zoonotic, and vector-borne disease; sunshine; food resource security; and health risks associated with the built environment. Collaborations within the Earth Science Applications Plan join local, state, national, or global organizations and agencies as partners. These partnerships engage in projects that strive to understand the connection between the environment and health. The important outcome is to put this understanding to use through enhancement of decision support tools that aid policy and management decisions on environmental health risks. Future plans will further employ developed models in formats that are compatible and accessible to all public health organizations.

  11. Genome structural variation discovery and genotyping

    OpenAIRE

    Alkan, Can; Coe, Bradley P.; Eichler, Evan E.

    2011-01-01

    Comparisons of human genomes show that more base pairs are altered as a result of structural variation — including copy number variation — than as a result of point mutations. Here we review advances and challenges in the discovery and genotyping of structural variation. The recent application of massively parallel sequencing methods has complemented microarray-based methods and has led to an exponential increase in the discovery of smaller structural-variation events. Some glo...

  12. Long-term variations in abundance and distribution of sewage pollution indicator and human pathogenic bacteria along the central west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Rodrigues, V.; Ramaiah, N.; Kakti, S.; Samant, D.

    Safe water quality criteria on the load and types of microbial populations are important for human use from fishery, tourism and navigational viewpoints. To understand the variations in sewage pollution indicator and certain human pathogenic...

  13. Diurnal Variations of Human Circulating Cell-Free Micro-RNA.

    Science.gov (United States)

    Heegaard, Niels H H; Carlsen, Anting Liu; Lilje, Berit; Ng, Kim Lee; Rønne, Mette E; Jørgensen, Henrik L; Sennels, Henriette; Fahrenkrug, Jan

    2016-01-01

    A 24-hour light and dark cycle-dependent rhythmicity pervades physiological processes in virtually all living organisms including humans. These regular oscillations are caused by external cues to endogenous, independent biological time-keeping systems (clocks). The rhythm is reflected by gene expression that varies in a circadian and specific fashion in different organs and tissues and is regulated largely by dynamic epigenetic and post-transcriptional mechanisms. This leads to well-documented oscillations of specific electrolytes, hormones, metabolites, and plasma proteins in blood samples. An emerging, important class of gene regulators is short single-stranded RNA (micro-RNA, miRNA) that interferes post-transcriptionally with gene expression and thus may play a role in the circadian variation of gene expression. MiRNAs are promising biomarkers by virtue of their disease-specific tissue expression and because of their presence as stable entities in the circulation. However, no studies have addressed the putative circadian rhythmicity of circulating, cell-free miRNAs. This question is important both for using miRNAs as biological markers and for clues to miRNA function in the regulation of circadian gene expression. Here, we investigate 92 miRNAs in plasma samples from 24 young male, healthy volunteers repeatedly sampled 9 times during a 24-hour stay in a regulated environment. We demonstrate that a third (26/79) of the measurable plasma miRNAs (using RT-qPCR on a microfluidic system) exhibit a rhythmic behavior and are distributed in two main phase patterns. Some of these miRNAs weakly target known clock genes and many have strong targets in intracellular MAPK signaling pathways. These novel findings highlight the importance of considering bio-oscillations in miRNA biomarker studies and suggest the further study of a set of specific circulating miRNAs in the regulation and functioning of biological clocks.

  14. Diurnal Variations of Human Circulating Cell-Free Micro-RNA.

    Directory of Open Access Journals (Sweden)

    Niels H H Heegaard

    Full Text Available A 24-hour light and dark cycle-dependent rhythmicity pervades physiological processes in virtually all living organisms including humans. These regular oscillations are caused by external cues to endogenous, independent biological time-keeping systems (clocks. The rhythm is reflected by gene expression that varies in a circadian and specific fashion in different organs and tissues and is regulated largely by dynamic epigenetic and post-transcriptional mechanisms. This leads to well-documented oscillations of specific electrolytes, hormones, metabolites, and plasma proteins in blood samples. An emerging, important class of gene regulators is short single-stranded RNA (micro-RNA, miRNA that interferes post-transcriptionally with gene expression and thus may play a role in the circadian variation of gene expression. MiRNAs are promising biomarkers by virtue of their disease-specific tissue expression and because of their presence as stable entities in the circulation. However, no studies have addressed the putative circadian rhythmicity of circulating, cell-free miRNAs. This question is important both for using miRNAs as biological markers and for clues to miRNA function in the regulation of circadian gene expression. Here, we investigate 92 miRNAs in plasma samples from 24 young male, healthy volunteers repeatedly sampled 9 times during a 24-hour stay in a regulated environment. We demonstrate that a third (26/79 of the measurable plasma miRNAs (using RT-qPCR on a microfluidic system exhibit a rhythmic behavior and are distributed in two main phase patterns. Some of these miRNAs weakly target known clock genes and many have strong targets in intracellular MAPK signaling pathways. These novel findings highlight the importance of considering bio-oscillations in miRNA biomarker studies and suggest the further study of a set of specific circulating miRNAs in the regulation and functioning of biological clocks.

  15. Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus Pneumocystis jirovecii

    Directory of Open Access Journals (Sweden)

    Emanuel Schmid-Siegert

    2017-11-01

    Full Text Available Microbial pathogens commonly escape the human immune system by varying surface proteins. We investigated the mechanisms used for that purpose by Pneumocystis jirovecii. This uncultivable fungus is an obligate pulmonary pathogen that in immunocompromised individuals causes pneumonia, a major life-threatening infection. Long-read PacBio sequencing was used to assemble a core of subtelomeres of a single P. jirovecii strain from a bronchoalveolar lavage fluid specimen from a single patient. A total of 113 genes encoding surface proteins were identified, including 28 pseudogenes. These genes formed a subtelomeric gene superfamily, which included five families encoding adhesive glycosylphosphatidylinositol (GPI-anchored glycoproteins and one family encoding excreted glycoproteins. Numerical analyses suggested that diversification of the glycoproteins relies on mosaic genes created by ectopic recombination and occurs only within each family. DNA motifs suggested that all genes are expressed independently, except those of the family encoding the most abundant surface glycoproteins, which are subject to mutually exclusive expression. PCR analyses showed that exchange of the expressed gene of the latter family occurs frequently, possibly favored by the location of the genes proximal to the telomere because this allows concomitant telomere exchange. Our observations suggest that (i the P. jirovecii cell surface is made of a complex mixture of different surface proteins, with a majority of a single isoform of the most abundant glycoprotein, (ii genetic mosaicism within each family ensures variation of the glycoproteins, and (iii the strategy of the fungus consists of the continuous production of new subpopulations composed of cells that are antigenically different.

  16. Diurnal variation of the human adipose transcriptome and the link to metabolic disease

    Directory of Open Access Journals (Sweden)

    Lamb John

    2009-02-01

    Full Text Available Abstract Background Circadian (diurnal rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation. Methods The present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted. Results The results indicated that diurnal rhythm was the most significant driver of gene expression variation in the human adipose tissue, with at least 25% of the genes having had significant changes in their expression levels during the course of the day. The mRNA expression levels of core clock genes at a specific time of day were consistent across multiple subjects on different days in all three arms, indicating robust diurnal regulation irrespective of potential confounding factors. The genes essential for energy metabolism and tissue physiology were part of the diurnal signature. We hypothesize that the diurnal transition of the expression of energy metabolism genes reflects the shift in the adipose tissue from an energy-expending state in the morning to an energy-storing state in the evening. Consistent with this hypothesis, the diurnal transition was delayed by fasting and treatment with sibutramine. Finally, an in silico comparison of the diurnal signature with data from the publicly-available Connectivity Map demonstrated a significant association with transcripts that were repressed by mTOR inhibitors, suggesting a possible link between mTOR signaling, diurnal gene expression and metabolic regulation. Conclusion Diurnal rhythm plays an important role in the physiology and regulation of energy metabolism in the adipose

  17. Assessing structural variation in a personal genome-towards a human reference diploid genome.

    Science.gov (United States)

    English, Adam C; Salerno, William J; Hampton, Oliver A; Gonzaga-Jauregui, Claudia; Ambreth, Shruthi; Ritter, Deborah I; Beck, Christine R; Davis, Caleb F; Dahdouli, Mahmoud; Ma, Singer; Carroll, Andrew; Veeraraghavan, Narayanan; Bruestle, Jeremy; Drees, Becky; Hastie, Alex; Lam, Ernest T; White, Simon; Mishra, Pamela; Wang, Min; Han, Yi; Zhang, Feng; Stankiewicz, Pawel; Wheeler, David A; Reid, Jeffrey G; Muzny, Donna M; Rogers, Jeffrey; Sabo, Aniko; Worley, Kim C; Lupski, James R; Boerwinkle, Eric; Gibbs, Richard A

    2015-04-11

    Characterizing large genomic variants is essential to expanding the research and clinical applications of genome sequencing. While multiple data types and methods are available to detect these structural variants (SVs), they remain less characterized than smaller variants because of SV diversity, complexity, and size. These challenges are exacerbated by the experimental and computational demands of SV analysis. Here, we characterize the SV content of a personal genome with Parliament, a publicly available consensus SV-calling infrastructure that merges multiple data types and SV detection methods. We demonstrate Parliament's efficacy via integrated analyses of data from whole-genome array comparative genomic hybridization, short-read next-generation sequencing, long-read (Pacific BioSciences RSII), long-insert (Illumina Nextera), and whole-genome architecture (BioNano Irys) data from the personal genome of a single subject (HS1011). From this genome, Parliament identified 31,007 genomic loci between 100 bp and 1 Mbp that are inconsistent with the hg19 reference assembly. Of these loci, 9,777 are supported as putative SVs by hybrid local assembly, long-read PacBio data, or multi-source heuristics. These SVs span 59 Mbp of the reference genome (1.8%) and include 3,801 events identified only with long-read data. The HS1011 data and complete Parliament infrastructure, including a BAM-to-SV workflow, are available on the cloud-based service DNAnexus. HS1011 SV analysis reveals the limits and advantages of multiple sequencing technologies, specifically the impact of long-read SV discovery. With the full Parliament infrastructure, the HS1011 data constitute a public resource for novel SV discovery, software calibration, and personal genome structural variation analysis.

  18. Data-Interpolating Variational Analysis (DIVA) software : recent development and application

    Science.gov (United States)

    Watelet, Sylvain; Beckers, Jean-Marie; Barth, Alexander; Back, Örjan

    2016-04-01

    The Data-Interpolating Variational Analysis (DIVA) software is a tool designed to reconstruct a continuous field from discrete measurements. This method is based on the numerical implementation of the Variational Inverse Model (VIM), which consists of a minimization of a cost function, allowing the choice of the analysed field fitting at best the data sets. The problem is solved efficiently using a finite-element method. This statistical method is particularly suited to deal with irregularly-spaced observations, producing outputs on a regular grid. Initially created to work in a two-dimensional way, the software is now able to handle 3D or even 4D analysis, in order to easily produce ocean climatologies. These analyses can easily be improved by taking advantage of the DIVA's ability to take topographic and dynamic constraints into account (coastal relief, prevailing wind impacting the advection,...). DIVA is an open-source software which is continuously upgraded and distributed for free through frequent version releases. The development is funded by the EMODnet and SeaDataNet projects and include many discussions and feedback from the users community. Here, we present two recent major upgrades : the data weighting option and the bottom-based analyses. Since DIVA works with a diagonal observation error covariance matrix, it is assumed that the observation errors are uncorrelated in space and time. In practice, this assumption is not always valid especially when dealing e.g. with cruise measurements (same instrument) or with time series at a fixed geographic point (representativity error). The data weighting option proposes to decrease the weights in the analysis of such observations. Theses weights are based on an exponential function using a 3D (x,y,t) distance between several observations. A comparison between not-weighted and weighted analyses will be shown. It has been a recurrent request from the DIVA users to improve the way the analyses near the ocean bottom

  19. Radiopharmacy: regulations and legislations in relation to human applications.

    Science.gov (United States)

    Decristoforo, Clemens; Schwarz, Sally W

    2011-01-01

    Radiopharmaceuticals (RPs) have attracted tremendous interest as molecular imaging tracers in diagnostic applications and as biomarkers in drug development, in particular using Positron Emission Tomography (PET). This article summarizes important legal documents and guidelines in relation to human application of PET-RPs that pose a major challenge in implementing the full potential of this technology, thereby differentiating the US from the European situation. Regulations are reviewed with respect to licensing, conducting clinical trials and RP production - including Good Manufacturing Practice (GMP) for radioactive compounds. Professional requirements, including education, are discussed, with an outlook on future developments.: © 2011 Elsevier Ltd . All rights reserved.

  20. Analysis of genetic variation and potential applications in genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Cardoso, Joao; Andersen, Mikael Rørdam; Herrgard, Markus

    2015-01-01

    Genetic variation is the motor of evolution and allows organisms to overcome the environmental challenges they encounter. It can be both beneficial and harmful in the process of engineering cell factories for the production of proteins and chemicals. Throughout the history of biotechnology......, there have been efforts to exploit genetic variation in our favor to create strains with favorable phenotypes. Genetic variation can either be present in natural populations or it can be artificially created by mutagenesis and selection or adaptive laboratory evolution. On the other hand, unintended genetic...... variation during a long term production process may lead to significant economic losses and it is important to understand how to control this type of variation. With the emergence of next-generation sequencing technologies, genetic variation in microbial strains can now be determined on an unprecedented...

  1. Application of toxicogenomic profiling to evaluate effects of benzene and formaldehyde: from yeast to human

    Science.gov (United States)

    McHale, Cliona M.; Smith, Martyn T.; Zhang, Luoping

    2014-01-01

    Genetic variation underlies a significant proportion of the individual variation in human susceptibility to toxicants. The primary current approaches to identify gene–environment (GxE) associations, genome-wide association studies (GWAS) and candidate gene association studies, require large exposed and control populations and an understanding of toxicity genes and pathways, respectively. This limits their application in the study of GxE associations for the leukemogens benzene and formaldehyde, whose toxicity has long been a focus of our research. As an alternative approach, we applied innovative in vitro functional genomics testing systems, including unbiased functional screening assays in yeast and a near-haploid human bone marrow cell line (KBM7). Through comparative genomic and computational analyses of the resulting data, we have identified human genes and pathways that may modulate susceptibility to benzene and formaldehyde. We have validated the roles of several genes in mammalian cell models. In populations occupationally exposed to low levels of benzene, we applied peripheral blood mononuclear cell transcriptomics and chromosome-wide aneuploidy studies (CWAS) in lymphocytes. In this review of the literature, we describe our comprehensive toxicogenomic approach and the potential mechanisms of toxicity and susceptibility genes identified for benzene and formaldehyde, as well as related studies conducted by other researchers. PMID:24571325

  2. Application of metagenomics in the human gut microbiome

    OpenAIRE

    Wang, Wei-Lin; Xu, Shao-Yan; Ren, Zhi-Gang; Tao, Liang; Jiang, Jian-Wen; Zheng, Shu-Sen

    2015-01-01

    There are more than 1000 microbial species living in the complex human intestine. The gut microbial community plays an important role in protecting the host against pathogenic microbes, modulating immunity, regulating metabolic processes, and is even regarded as an endocrine organ. However, traditional culture methods are very limited for identifying microbes. With the application of molecular biologic technology in the field of the intestinal microbiome, especially metagenomic sequencing of ...

  3. Telematics applications and their influence on the human factor

    Directory of Open Access Journals (Sweden)

    Alica KALAŠOVÁ

    2013-01-01

    Full Text Available Safety is the exemption from accidents and losses on human lives. It also deals with property protection, regulation, management and transport technology development. Human factor often caused a lot of accident because of his/her failure. One of the most frequent faults of drivers is a wrong decision in a critical situation. The decision process is very complicated since the driver has to evaluate the arisen situation correctly within fractions of a second. The implementation of telematics systems into vehicle equipment reduces its energy consumption, bad environmental impacts, increases safety etc. Total operating costs reduction of road vehicles, simplification of vehicle control and reduction of driver’s overload by information is largely stressed. Our article deals with the analysis of human factor and exploration of its demonstrations in the context of telematic applications.

  4. The Human Y-Chromosome - Introduction into Genetics and Applications.

    Science.gov (United States)

    Kayser, M

    2003-07-01

    Human Y-chromosomal DNA analysis is becoming well established in forensic sciences. That is because human Y-chromosomal DNA polymorphisms are the only genetic markers that are able to specifically characterize and identify male culprit DNA in material from sexual assault or forcible rape cases where offenders are almost always males. Appropriate Y-chromosomal DNA markers evaluated for forensic applications with standardized nomenclature, typing and statistic methodology, and haplotype frequency databases are currently available to the forensic DNA community. As with any other kind of DNA evidence, the Y-chromosomal DNA analysis in forensic science requires not only a high standard of quality assurance but also appropriate scientific background knowledge to ensure correct interpretation of DNA profiles. The following overview article will provide an introduction to the molecular genetics of the human Y-chromosome and will discuss the advantages that Y-chromosomal DNA polymorphisms can offer to forensic applications, as well as the limitations to the types of information provided by the human Y-chromosome. Copyright © 2003 Central Police University.

  5. Marine Enzymes: Production and Applications for Human Health.

    Science.gov (United States)

    Rao, T Eswara; Imchen, M; Kumavath, R

    Marine microbial enzymes have wide applications in bioindustries. Selection of microorganisms for enzyme production at the industrial level requires good yield and high production rate. A number of enzymes such as amylase, caseinase, lipase, gelatinase, and DNases have been discovered from microbes isolated from extreme marine environments. Such enzymes are thermostable, tolerant to a varied range of pH and other harsh conditions required in industrial applications. Novelty in their structure and characteristics has shown promising scope to the researchers in academia and industry. In this chapter, we present a bird's eye view on recent research works in the field of enzyme production from marine origin as well as their potential biological applications relevant to human health. © 2017 Elsevier Inc. All rights reserved.

  6. ¹³C MRS reveals a small diurnal variation in the glycogen content of human thigh muscle.

    Science.gov (United States)

    Takahashi, Hideyuki; Kamei, Akiko; Osawa, Takuya; Kawahara, Takashi; Takizawa, Osamu; Maruyama, Katsuya

    2015-06-01

    There is marked diurnal variation in the glycogen content of skeletal muscles of animals, but few studies have addressed such variations in human muscles. (13)C MRS can be used to noninvasively measure the glycogen content of human skeletal muscle, but no study has explored the diurnal variations in this parameter. This study aimed to investigate whether a diurnal variation in glycogen content occurs in human muscles and, if so, to what extent it can be identified using (13)C MRS. Six male volunteers were instructed to maintain their normal diet and not to perform strenuous exercise for at least 3 days before and during the experiment. Muscle glycogen and blood glucose concentrations were measured six times in 24 h under normal conditions in these subjects. The glycogen content in the thigh muscle was determined noninvasively by natural abundance (13)C MRS using a clinical MR system at 3 T. Nutritional analysis revealed that the subjects' mean carbohydrate intake was 463 ± 137 g, being approximately 6.8 ± 2.4 g/kg body weight. The average sleeping time was 5.9 ± 1.0 h. The glycogen content in the thigh muscle at the starting point was 64.8 ± 20.6 mM. Although absolute and relative individual variations in muscle glycogen content were 7.0 ± 2.1 mM and 11.3 ± 4.6%, respectively, no significant difference in glycogen content was observed among the different time points. This study demonstrates that normal food intake (not fat and/or carbohydrate rich), sleep and other daily activities have a negligible influence on thigh muscle glycogen content, and that the diurnal variation of the glycogen content in human muscles is markedly smaller than that in animal muscles. Moreover, the present results also support the reproducibility and availability of (13)C MRS for the evaluation of the glycogen content in human muscles. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans

    NARCIS (Netherlands)

    Verloop, H.; Dekkers, O.M.; Peeters, R.P.; Schoones, J.W.; Smit, J.W.

    2014-01-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple

  8. Sequence variation and genetic evolution at the human F12 locus: mapping quantitative trait nucleotides that influence FXII plasma levels.

    Science.gov (United States)

    Calafell, Francesc; Almasy, Laura; Sabater-Lleal, Maria; Buil, Alfonso; Mordillo, Carolina; Ramírez-Soriano, Anna; Sikora, Martin; Souto, Juan Carlos; Blangero, John; Fontcuberta, Jordi; Soria, José Manuel

    2010-02-01

    The level of Factor XII (FXII) is an important phenotype that exhibits a high genetic component and is associated with thrombotic disease. In a genome-wide linkage scan, we demonstrated that the F12 gene represents a quantitative trait locus (QTL) that influences FXII levels. The current study investigated the genetic architecture of the F12 gene to locate polymorphism(s) responsible for the variation of FXII levels. Re-sequencing of the F12 gene in 40 unrelated individuals (selected from the tails of normal distribution of FXII levels) identified 26 polymorphisms which were genotyped in 398 individuals belonging to 21 families from the GAIT Project. By a measured genotype association analysis, eight of 26 SNPs showed significant P-values less than 10(-5) (after multiple test correction) with FXII levels. In addition, the Bayesian Quantitative Trait Nucleotide method, which infers those polymorphisms most likely to have a direct influence on the trait under study, provided evidence that only rs1801020 variation accounted for the variance attributed to this QTL. Moreover, we have analyzed the evolutionary processes that produced the variation in F12 gene and concluded that is evolutionarily neutral and that the T allele of the rs1801020 appeared approximately 100 000 years ago and spread to most human populations rising to high frequencies by genetic drift. Our study provides a template for future genetic studies of human quantitative traits, as we move beyond QTL localization to the polymorphisms responsible for the variation of important biomedical phenotypes.

  9. Effect of variation in hemorheology between human and animal blood on the binding efficacy of vascular-targeted carriers.

    Science.gov (United States)

    Namdee, K; Carrasco-Teja, M; Fish, M B; Charoenphol, P; Eniola-Adefeso, O

    2015-06-26

    Animal models are extensively used to evaluate the in vivo functionality of novel drug delivery systems (DDS). However, many variations likely exist in vivo between the animals and human physiological environment that significantly alter results obtained with animal models relative to human system. To date, it is not clear if the variation in hemorheology and hemodynamics between common animal and human models affect the functionality of DDS. This study investigates the role of hemorheology of humans and various animal models in dictating the binding efficiency of model vascular-targeted carriers (VTCs) to the wall in physiological blood flows. Specifically, the adhesion of sLe(A)-coated nano- and micro-spheres to inflamed endothelial cells monolayers were conducted via a parallel plate flow chamber assay with steady and disturbed red blood cells (RBCs)-in-buffer and whole blood flows of common animal models. Our results suggest that the ratio of carrier size to RBC size dictate particle binding in blood flow. Additionally, the presence of white blood cells affects the trend of particle adhesion depending on the animal species. Overall, this work sheds light on some deviation in VTC vascular wall interaction results obtained with in vivo animal experimentation from expected outcome and efficiency in vivo in human.

  10. Divergent haplotypes and human history as revealed in a worldwide survey of X-linked DNA sequence variation.

    Science.gov (United States)

    Shimada, Makoto K; Panchapakesan, Karuna; Tishkoff, Sarah A; Nato, Alejandro Q; Hey, Jody

    2007-03-01

    The population genetic history of a 10.1-kbp noncoding region of the human X chromosome was studied using the males of the HGDP-CEPH Human Genome Diversity Panel (672 individuals from 52 populations). The geographic distribution of patterns of variation was roughly consistent with previous studies, with the major exception that 1 highly divergent haplotype (haplotype X, hX) was observed at low frequency in widely scattered non-African populations and not at all observed in sub-Saharan African populations. Microsatellite (short tandem repeat) variation within the sequenced region was low among copies of hX, even though the estimated time of ancestry of hX and other sequences was 1.44 Myr. The estimated age of the common ancestor of all hX copies was 5,230 years (95% consistency index: 2,000-75,480 years). To further address the presence of hX in Africa, additional samples from Chad and Tanzania were screened. Five additional copies of hX were observed, consistent with a history in which hX was present in Africa prior to the migration of modern humans out of Africa and with eastern Africa being the source of non-African modern human populations. Taken together, these features of hX-that it is much older than other haplotypes and uncommon and patchily distributed throughout Africa, Europe, and Asia-present a cautionary tale for interpretations of human history.

  11. Analysis of genetic variation and potential applications in genome-scale metabolic modeling

    Directory of Open Access Journals (Sweden)

    João Gonçalo Rocha Cardoso

    2015-02-01

    Full Text Available Genetic variation is the motor of evolution and allows organisms to overcome the environmental challenges they encounter. It can be both beneficial and harmful in the process of engineering cell factories for the production of proteins and chemicals. Throughout the history of biotechnology, there have been efforts to exploit genetic variation in our favor to create strains with favorable phenotypes. Genetic variation can either be present in natural populations or it can be artificially created by mutagenesis and selection or adaptive laboratory evolution. On the other hand, unintended genetic variation during a long term production process may lead to significant economic losses and it is important to understand how to control this type of variation. With the emergence of next-generation sequencing technologies, genetic variation in microbial strains can now be determined on an unprecedented scale and resolution by re-sequencing thousands of strains systematically. In this article, we review challenges in the integration and analysis of large-scale re-sequencing data, present an extensive overview of bioinformatics methods for predicting the effects of genetic variants on protein function, and discuss approaches for interfacing existing bioinformatics approaches with genome-scale models of cellular processes in order to predict effects of sequence variation on cellular phenotypes.

  12. Modelling human regulatory variation in mouse: finding the function in genome-wide association studies and whole-genome sequencing.

    Directory of Open Access Journals (Sweden)

    Jean-François Schmouth

    Full Text Available An increasing body of literature from genome-wide association studies and human whole-genome sequencing highlights the identification of large numbers of candidate regulatory variants of potential therapeutic interest in numerous diseases. Our relatively poor understanding of the functions of non-coding genomic sequence, and the slow and laborious process of experimental validation of the functional significance of human regulatory variants, limits our ability to fully benefit from this information in our efforts to comprehend human disease. Humanized mouse models (HuMMs, in which human genes are introduced into the mouse, suggest an approach to this problem. In the past, HuMMs have been used successfully to study human disease variants; e.g., the complex genetic condition arising from Down syndrome, common monogenic disorders such as Huntington disease and β-thalassemia, and cancer susceptibility genes such as BRCA1. In this commentary, we highlight a novel method for high-throughput single-copy site-specific generation of HuMMs entitled High-throughput Human Genes on the X Chromosome (HuGX. This method can be applied to most human genes for which a bacterial artificial chromosome (BAC construct can be derived and a mouse-null allele exists. This strategy comprises (1 the use of recombineering technology to create a human variant-harbouring BAC, (2 knock-in of this BAC into the mouse genome using Hprt docking technology, and (3 allele comparison by interspecies complementation. We demonstrate the throughput of the HuGX method by generating a series of seven different alleles for the human NR2E1 gene at Hprt. In future challenges, we consider the current limitations of experimental approaches and call for a concerted effort by the genetics community, for both human and mouse, to solve the challenge of the functional analysis of human regulatory variation.

  13. Application of metagenomics in the human gut microbiome.

    Science.gov (United States)

    Wang, Wei-Lin; Xu, Shao-Yan; Ren, Zhi-Gang; Tao, Liang; Jiang, Jian-Wen; Zheng, Shu-Sen

    2015-01-21

    There are more than 1000 microbial species living in the complex human intestine. The gut microbial community plays an important role in protecting the host against pathogenic microbes, modulating immunity, regulating metabolic processes, and is even regarded as an endocrine organ. However, traditional culture methods are very limited for identifying microbes. With the application of molecular biologic technology in the field of the intestinal microbiome, especially metagenomic sequencing of the next-generation sequencing technology, progress has been made in the study of the human intestinal microbiome. Metagenomics can be used to study intestinal microbiome diversity and dysbiosis, as well as its relationship to health and disease. Moreover, functional metagenomics can identify novel functional genes, microbial pathways, antibiotic resistance genes, functional dysbiosis of the intestinal microbiome, and determine interactions and co-evolution between microbiota and host, though there are still some limitations. Metatranscriptomics, metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome. This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects. The limitations of metagenomics to be overcome are also discussed. Metatranscriptomics, metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed.

  14. Human dental pulp stem cells: Applications in future regenerative medicine

    Science.gov (United States)

    Potdar, Pravin D; Jethmalani, Yogita D

    2015-01-01

    Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine. PMID:26131314

  15. Human dental pulp stem cells: Applications in future regenerative medicine.

    Science.gov (United States)

    Potdar, Pravin D; Jethmalani, Yogita D

    2015-06-26

    Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine.

  16. Selective enrichment of STRs for applications in forensic human identification.

    Science.gov (United States)

    Gadipally, Sreeja R; Sarkar, Anujit; Nandineni, Madhusudan R

    2015-08-01

    Forensic human identification (HID) is currently based on determining repeat length polymorphisms located in short tandem repeat regions in the human genome. Despite the great progress made in the area of multiplex PCR-based approaches, limitations associated with challenging forensic samples such as DNA degradation, cooccurrence of inhabited microbial DNA and PCR inhibitors significantly affect the success rate of human DNA profiling. We have developed a sequence-specific pre-PCR STR enrichment method and evaluated its efficacy using DNA samples doped with various contaminants in view of its application on compromised forensic samples. This strategy has enabled us to generate complete and reproducible DNA profiles from samples doped with fivefold excess of nonhuman DNA and three to fourfold excess of various potent PCR inhibitors than that is claimed to be tolerated by some of the widely used commercial multiplex STR kits, from as little as two nanograms of degraded human DNA. The "hybrid capture"-based STR enrichment strategy described in this study is easily adaptable and offers a sensitive, efficient, and economical approach for successful human DNA profiling from compromised and recalcitrant forensic samples that are usually encountered in mass disaster incidents and missing persons' identifications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Precision wildlife medicine: applications of the human-centred precision medicine revolution to species conservation.

    Science.gov (United States)

    Whilde, Jenny; Martindale, Mark Q; Duffy, David J

    2017-05-01

    The current species extinction crisis is being exacerbated by an increased rate of emergence of epizootic disease. Human-induced factors including habitat degradation, loss of biodiversity and wildlife population reductions resulting in reduced genetic variation are accelerating disease emergence. Novel, efficient and effective approaches are required to combat these epizootic events. Here, we present the case for the application of human precision medicine approaches to wildlife medicine in order to enhance species conservation efforts. We consider how the precision medicine revolution, coupled with the advances made in genomics, may provide a powerful and feasible approach to identifying and treating wildlife diseases in a targeted, effective and streamlined manner. A number of case studies of threatened species are presented which demonstrate the applicability of precision medicine to wildlife conservation, including sea turtles, amphibians and Tasmanian devils. These examples show how species conservation could be improved by using precision medicine techniques to determine novel treatments and management strategies for the specific medical conditions hampering efforts to restore population levels. Additionally, a precision medicine approach to wildlife health has in turn the potential to provide deeper insights into human health and the possibility of stemming and alleviating the impacts of zoonotic diseases. The integration of the currently emerging Precision Medicine Initiative with the concepts of EcoHealth (aiming for sustainable health of people, animals and ecosystems through transdisciplinary action research) and One Health (recognizing the intimate connection of humans, animal and ecosystem health and addressing a wide range of risks at the animal-human-ecosystem interface through a coordinated, collaborative, interdisciplinary approach) has great potential to deliver a deeper and broader interdisciplinary-based understanding of both wildlife and human

  18. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects

    Science.gov (United States)

    Meier-Ewert, H. K.; Ridker, P. M.; Rifai, N.; Price, N.; Dinges, D. F.; Mullington, J. M.

    2001-01-01

    BACKGROUND: The concentration of C-reactive protein (CRP) in otherwise healthy subjects has been shown to predict future risk of myocardial infarction and stroke. CRP is synthesized by the liver in response to interleukin-6, the serum concentration of which is subject to diurnal variation. METHODS: To examine the existence of a time-of-day effect for baseline CRP values, we determined CRP concentrations in hourly blood samples drawn from healthy subjects (10 males, 3 females; age range, 21-35 years) during a baseline day in a controlled environment (8 h of nighttime sleep). RESULTS: Overall CRP concentrations were low, with only three subjects having CRP concentrations >2 mg/L. Comparison of raw data showed stability of CRP concentrations throughout the 24 h studied. When compared with cutoff values of CRP quintile derived from population-based studies, misclassification of greater than one quintile did not occur as a result of diurnal variation in any of the subjects studied. Nonparametric ANOVA comparing different time points showed no significant differences for both raw and z-transformed data. Analysis for rhythmic diurnal variation using a method fitting a cosine curve to the group data was negative. CONCLUSIONS: Our data show that baseline CRP concentrations are not subject to time-of-day variation and thus help to explain why CRP concentrations are a better predictor of vascular risk than interleukin-6. Determination of CRP for cardiovascular risk prediction may be performed without concern for diurnal variation.

  19. Biotechnological Patents Applications of the Deuterium Oxide in Human Health.

    Science.gov (United States)

    da S Mariano, Reysla M; Bila, Wendell C; Trindade, Maria Jaciara F; Lamounier, Joel A; Galdino, Alexsandro S

    2017-01-01

    Deuterium oxide is a molecule that has been used for decades in several studies related to human health. Currently, studies on D2O have mobilized a "Race for Patenting" worldwide. Several patents have been registered from biomedical and technological studies of D2O showing the potential of this stable isotope in industry and health care ecosystems. Most of the patents related to the applications of the deuterium oxide in human health have been summarized in this review. The following patents databases were consulted: European Patent Office (Espacenet), the United States Patent and Trademark Office (USPTO), the United States Latin America Patents (LATIPAT), Patent scope -Search International and National Patent Collections (WIPO), Google Patents and Free Patents Online. With this review, the information was collected on recent publications including 22 patents related to deuterium oxide and its applications in different areas. This review showed that deuterium oxide is a promising component in different areas, including biotechnology, chemistry and medicine. In addition, the knowledge of this compound was covered, reinforcing its importance in the field of biotechnology and human health. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Rotating speed isolation and its application to rolling element bearing fault diagnosis under large speed variation conditions

    Science.gov (United States)

    Wang, Yi; Xu, Guanghua; Zhang, Qing; Liu, Dan; Jiang, Kuosheng

    2015-07-01

    During the past decades, the conventional envelope analysis has been one of the main approaches in vibration signal processing. However, the envelope analysis is based on stationary assumption, thus it is not applicable to the fault diagnosis of bearings under rotating speed variation conditions. This constraint limits the bearing diagnosis in industrial applications significantly. In order to extend the conventional diagnosis technique to speed variation cases, a rotating speed isolation method is proposed. This method consists of four main steps: (a) a low-pass filter is used to separate the rotating speed components and the resonance frequency band from the original signal; (b) the trend line of instantaneous rotating frequency (IRF) is extracted by ridge detection from the short-time spectrum of the low-pass filtered signal; (c) the envelope signal is obtained by fast kurtogram based resonance demodulation; (d) the trend line of instantaneous fault characteristic frequency (IFCF) is extracted by ridge detection from the short-time spectrum of the envelope signal; (e) the rotating speed is isolated and the instantaneous fault characteristic order (FCO), which is obtained by simply dividing the IFCF by IRF, can be used to identify the fault type. By rotating speed isolation, the bearing faults under speed variation conditions can be detected without additional tachometers. The effectiveness of the proposed method has been validated by both simulated and experimental bearing vibration signals. The results show that the proposed method outperforms the conventional envelope analysis method and is effective in bearing diagnosis under speed variation conditions.

  1. Deriving Sea Surface Salinity and Density Variations From Satellite and Aircraft Microwave Radiometer Measurements: Application to Coastal Plumes Using STARRS

    Science.gov (United States)

    2008-03-01

    evaluate potential applications of the satellite sensors and to (b) determine the utility of STARRS for testing satellite retrieval Nominal Ts noise Tb...large. Consequently, frontal systems may be totype tests (SMOS and Aquarius [31], [32]) giving expected best detected by identifying regions of strong...providing expert support; the where a is the scale depth for the vertical density variation, Uruguayan Air Force (Brigada de Mantenimiento, Servicio de

  2. Combined examination of sequence and copy number variations in human deafness genes improves diagnosis for cases of genetic deafness.

    Science.gov (United States)

    Ji, Haiting; Lu, Jingqiao; Wang, Jianjun; Li, Huawei; Lin, Xi

    2014-01-01

    Copy number variations (CNVs) are the major type of structural variation in the human genome, and are more common than DNA sequence variations in populations. CNVs are important factors for human genetic and phenotypic diversity. Many CNVs have been associated with either resistance to diseases or identified as the cause of diseases. Currently little is known about the role of CNVs in causing deafness. CNVs are currently not analyzed by conventional genetic analysis methods to study deafness. Here we detected both DNA sequence variations and CNVs affecting 80 genes known to be required for normal hearing. Coding regions of the deafness genes were captured by a hybridization-based method and processed through the standard next-generation sequencing (NGS) protocol using the Illumina platform. Samples hybridized together in the same reaction were analyzed to obtain CNVs. A read depth based method was used to measure CNVs at the resolution of a single exon. Results were validated by the quantitative PCR (qPCR) based method. Among 79 sporadic cases clinically diagnosed with sensorineural hearing loss, we identified previously-reported disease-causing sequence mutations in 16 cases. In addition, we identified a total of 97 CNVs (72 CNV gains and 25 CNV losses) in 27 deafness genes. The CNVs included homozygous deletions which may directly give rise to deleterious effects on protein functions known to be essential for hearing, as well as heterozygous deletions and CNV gains compounded with sequence mutations in deafness genes that could potentially harm gene functions. We studied how CNVs in known deafness genes may result in deafness. Data provided here served as a basis to explain how CNVs disrupt normal functions of deafness genes. These results may significantly expand our understanding about how various types of genetic mutations cause deafness in humans.

  3. Confidence ellipses: A variation based on parametric bootstrapping applicable on Multiple Factor Analysis results for rapid graphical evaluation

    DEFF Research Database (Denmark)

    Dehlholm, Christian; Brockhoff, Per B.; Bredie, Wender L. P.

    2012-01-01

    A new way of parametric bootstrapping allows similar construction of confidence ellipses applicable on all results from Multiple Factor Analysis obtained from the FactoMineR package in the statistical program R. With this procedure, a similar approach will be applied to Multiple Factor Analysis...... results regardless of the origin of data and the nature of the original variables. The approach is suitable for getting an overview of product confidence intervals and also applicable for data obtained from ‘one repetition’ evaluations. Furthermore, it is a convenient way to get an overview of variations...

  4. Plasmodium falciparum CS protein - prime malaria vaccine candidate: definition of the human CTL domain and analysis of its variation

    Directory of Open Access Journals (Sweden)

    Denise L. Doolan

    1992-01-01

    Full Text Available Studies in mice have shown that immunity to malaria sporozoites is mediated primarily by citotoxic T lymphocytes (CTL specific for epitopes within the circumsporozoite (CS protein. Humans, had never been shown to generate CTL against any malaria or other parasite protein. The design of a sub-unit vaccine for humans ralies on the epitopes recognized by CTL being identified and polymorphisms therein being defined. We have developed a novel technique using an entire series of overlapping synthetic peptides to define the epitopes of the Plasmodium falciparum CS protein recognized by human CTL and have analyzed the sequence variation of the protein with respect to the identified CTL epitopic domain. We have demonstrated that some humans can indeed generate CTL. against the P. falciparum CS protein. Furthermore, the extent of variation observed for the CTL recognition domain is finite and the combination of peptides necessary for inclusion in a polyvalent vaccine may be small. If ways can be found to increase immune responsiveness, then a vaccine designed to stimulate CS protein-specific CTL activity may prevent malaria.

  5. Biomechanics of human movement and its clinical applications.

    Science.gov (United States)

    Lu, Tung-Wu; Chang, Chu-Fen

    2012-02-01

    All life forms on earth, including humans, are constantly subjected to the universal force of gravitation, and thus to forces from within and surrounding the body. Through the study of the interaction of these forces and their effects, the form, function and motion of our bodies can be examined and the resulting knowledge applied to promote quality of life. Under gravity and other loads, and controlled by the nervous system, human movement is achieved through a complex and highly coordinated mechanical interaction between bones, muscles, ligaments and joints within the musculoskeletal system. Any injury to, or lesion in, any of the individual elements of the musculoskeletal system will change the mechanical interaction and cause degradation, instability or disability of movement. On the other hand, proper modification, manipulation and control of the mechanical environment can help prevent injury, correct abnormality, and speed healing and rehabilitation. Therefore, understanding the biomechanics and loading of each element during movement using motion analysis is helpful for studying disease etiology, making decisions about treatment, and evaluating treatment effects. In this article, the history and methodology of human movement biomechanics, and the theoretical and experimental methods developed for the study of human movement, are reviewed. Examples of motion analysis of various patient groups, prostheses and orthoses, and sports and exercises, are used to demonstrate the use of biomechanical and stereophotogrammetry-based human motion analysis studies to address clinical issues. It is suggested that further study of the biomechanics of human movement and its clinical applications will benefit from the integration of existing engineering techniques and the continuing development of new technology. Copyright © 2011. Published by Elsevier B.V.

  6. Applicability of non-invasively collected matrices for human biomonitoring

    Directory of Open Access Journals (Sweden)

    Nickmilder Marc

    2009-03-01

    Full Text Available Abstract With its inclusion under Action 3 in the Environment and Health Action Plan 2004–2010 of the European Commission, human biomonitoring is currently receiving an increasing amount of attention from the scientific community as a tool to better quantify human exposure to, and health effects of, environmental stressors. Despite the policy support, however, there are still several issues that restrict the routine application of human biomonitoring data in environmental health impact assessment. One of the main issues is the obvious need to routinely collect human samples for large-scale surveys. Particularly the collection of invasive samples from susceptible populations may suffer from ethical and practical limitations. Children, pregnant women, elderly, or chronically-ill people are among those that would benefit the most from non-invasive, repeated or routine sampling. Therefore, the use of non-invasively collected matrices for human biomonitoring should be promoted as an ethically appropriate, cost-efficient and toxicologically relevant alternative for many biomarkers that are currently determined in invasively collected matrices. This review illustrates that several non-invasively collected matrices are widely used that can be an valuable addition to, or alternative for, invasively collected matrices such as peripheral blood sampling. Moreover, a well-informed choice of matrix can provide an added value for human biomonitoring, as different non-invasively collected matrices can offer opportunities to study additional aspects of exposure to and effects from environmental contaminants, such as repeated sampling, historical overview of exposure, mother-child transfer of substances, or monitoring of substances with short biological half-lives.

  7. Biomechanics of human movement and its clinical applications

    Directory of Open Access Journals (Sweden)

    Tung-Wu Lu

    2012-02-01

    Full Text Available All life forms on earth, including humans, are constantly subjected to the universal force of gravitation, and thus to forces from within and surrounding the body. Through the study of the interaction of these forces and their effects, the form, function and motion of our bodies can be examined and the resulting knowledge applied to promote quality of life. Under gravity and other loads, and controlled by the nervous system, human movement is achieved through a complex and highly coordinated mechanical interaction between bones, muscles, ligaments and joints within the musculoskeletal system. Any injury to, or lesion in, any of the individual elements of the musculoskeletal system will change the mechanical interaction and cause degradation, instability or disability of movement. On the other hand, proper modification, manipulation and control of the mechanical environment can help prevent injury, correct abnormality, and speed healing and rehabilitation. Therefore, understanding the biomechanics and loading of each element during movement using motion analysis is helpful for studying disease etiology, making decisions about treatment, and evaluating treatment effects. In this article, the history and methodology of human movement biomechanics, and the theoretical and experimental methods developed for the study of human movement, are reviewed. Examples of motion analysis of various patient groups, prostheses and orthoses, and sports and exercises, are used to demonstrate the use of biomechanical and stereophotogrammetry-based human motion analysis studies to address clinical issues. It is suggested that further study of the biomechanics of human movement and its clinical applications will benefit from the integration of existing engineering techniques and the continuing development of new technology.

  8. Human hair follicle organ culture: theory, application and perspectives.

    Science.gov (United States)

    Langan, Ewan A; Philpott, Michael P; Kloepper, Jennifer E; Paus, Ralf

    2015-12-01

    For almost a quarter of a century, ex vivo studies of human scalp hair follicles (HFs) have permitted major advances in hair research, spanning diverse fields such as chronobiology, endocrinology, immunology, metabolism, mitochondrial biology, neurobiology, pharmacology, pigmentation and stem cell biology. Despite this, a comprehensive methodological guide to serum-free human HF organ culture (HFOC) that facilitates the selection and analysis of standard HF biological parameters and points out both research opportunities and pitfalls to newcomers to the field is still lacking. The current methods review aims to close an important gap in the literature and attempts to promote standardisation of human HFOC. We provide basic information outlining the establishment of HFOC through to detailed descriptions of the analysis of standard read-out parameters alongside practical examples. The guide closes by pointing out how serum-free HFOC can be utilised optimally to obtain previously inaccessible insights into human HF biology and pathology that are of interest to experimental dermatologists, geneticists, developmental biologists and (neuro-) endocrinologists alike and by highlighting novel applications of the model, including gene silencing and gene expression profiling of defined, laser capture-microdissected HF compartments. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Husbands' and Wives' Relative Earnings: Exploring Variation by Race, Human Capital, Labor Supply, and Life Stage

    Science.gov (United States)

    Winslow-Bowe, Sarah

    2009-01-01

    Whereas much research has explored the causes and consequences of the gender wage gap, far less has examined earnings differentials within marriage. This article contributes to this literature by utilizing the 2000 wave of the 1979 National Longitudinal Survey of Youth to examine variation in husbands' and wives' relative income by race/ethnicity,…

  10. Chloroplast DNA variation of oaks in western Central Europe and genetic consequences of human influences

    NARCIS (Netherlands)

    König, A.O.; Ziegenhagen, B.; Dam, van B.C.; Csaikl, U.M.; Coart, E.; Degen, B.; Burg, K.; Vries, de S.M.G.; Petit, R.J.

    2002-01-01

    Oak chloroplast DNA (cpDNA) variation was studied in a grid-based inventory in western Central Europe, including Belgium, The Netherlands, Luxembourg, Germany, the Czech Republic, and the northern parts of Upper and Lower Austria. A total of 2155 trees representing 426 populations of Quercus robur

  11. External physical stimulation of the human-fetus during episodes of low heart-rate variation

    NARCIS (Netherlands)

    Visser, G. H. A.; ZEELENBERG, HJ; DEVRIES, JIP; DAWES, GS

    1983-01-01

    The effect of shaking the fetus through the maternal abdomen during episodes of low (nonreactive) fetal heart rate variation was studied in 10 healthy nulliparous women near term. Heart rate monitoring from an abdominal electrocardiogram was combined with real-time scanning for body movements and

  12. Sources of variation in hair cortisol in wild and captive non-human primates.

    Science.gov (United States)

    Fourie, Nicolaas H; Brown, Janine L; Jolly, Clifford J; Phillips-Conroy, Jane E; Rogers, Jeffrey; Bernstein, Robin M

    2016-04-01

    Hair cortisol analysis is a potentially powerful tool for evaluating adrenal function and chronic stress. However, the technique has only recently been applied widely to studies of wildlife, including primates, and there are numerous practical and technical factors that should be considered to ensure good quality data and the validity of results and conclusions. Here we report on various intrinsic and extrinsic sources of variation in hair cortisol measurements in wild and captive primates. Hair samples from both wild and captive primates revealed that age and sex can affect hair cortisol concentrations; these effects need to be controlled for when making comparisons between individual animals or populations. Hair growth rates also showed considerable inter-specific variation among a number of primate species. We describe technical limitations of hair analyses and variation in cortisol concentrations as a function of asynchronous hair growth, anatomical site of collection, and the amount and numbers of hair/s used for cortisol extraction. We discuss these sources of variation and their implications for proper study design and interpretation of results. Published by Elsevier GmbH.

  13. A comprehensive study of the anatomical variations of the circle of willis in adult human brains.

    Science.gov (United States)

    Iqbal, S

    2013-11-01

    Cerebrovascular diseases such as stroke, aneurysms and arterio-venous malformations are very much prevalent in our country. Circle of Willis, as an anastomotic polygon at the base of the brain forms an important collateral network to maintain adequate cerebral perfusion. Changes in the normal morphology of the circle may condition the appearance and severity of symptoms of cerebrovascular disorders, such as aneurysms, infarctions and other vascular anomalies. A possible link between abnormalities of the circle of Willis and the mentally ill patients has been observed. The aim of the present study is to have an intimate knowledge of the variations in the cerebral arterial circle and to clarify the clinical importance of these variations in certain forms of cerebrovascular diseases. So an attempt was made to analyse the anatomical variations of the circle in a random population. The work was based on fifty adult brains from persons died of diverse causes. The materials were obtained during routine autopsy studies. The base of the brain including the brain stem with intact arterial circle was preserved in 10% formalin for 10 days. The circle of Willis and its major branches were carefully dissected under water using a magnifying lens. The variations were recorded and photographed. Majority of the circles (52%) showed anomalies. Hypoplasia was the most frequent anomaly and was found in 24% of the brains. Accessory vessels in the form of duplications/triplications of anterior communicating artery were seen in 12% of the circles. The embryonic origin of the posterior cerebral artery from the internal carotid persisted in 10% of the circles. An incomplete circle due to the absence of one or other posterior communicating artery was found in 6% of the specimens.Variations are more frequent in posterior half of the circle. The anatomical variations of the circle of Willis were probably genetically determined, develop in early embryonic stage and persist in post natal life

  14. Composition and Variation of Macronutrients, Immune Proteins, and Human Milk Oligosaccharides in Human Milk From Nonprofit and Commercial Milk Banks.

    Science.gov (United States)

    Meredith-Dennis, Laura; Xu, Gege; Goonatilleke, Elisha; Lebrilla, Carlito B; Underwood, Mark A; Smilowitz, Jennifer T

    2017-06-01

    When human milk is unavailable, banked milk is recommended for feeding premature infants. Milk banks use processes to eliminate pathogens; however, variability among methods exists. Research aim: The aim of this study was to compare the macronutrient (protein, carbohydrate, fat, energy), immune-protective protein, and human milk oligosaccharide (HMO) content of human milk from three independent milk banks that use pasteurization (Holder vs. vat techniques) or retort sterilization. Randomly acquired human milk samples from three different milk banks ( n = 3 from each bank) were analyzed for macronutrient concentrations using a Fourier transform mid-infrared spectroscopy human milk analyzer. The concentrations of IgA, IgM, IgG, lactoferrin, lysozyme, α-lactalbumin, α antitrypsin, casein, and HMO were analyzed by mass spectrometry. The concentrations of protein and fat were significantly ( p milk samples that had undergone retort sterilization had significantly less immune-protective proteins and total and specific HMOs compared with samples that had undergone Holder and vat pasteurization. These data suggest that further analysis of the effect of retort sterilization on human milk components is needed prior to widespread adoption of this process.

  15. Hamiltonian and Lagrangian flows on center manifolds with applications to elliptic variational problems

    CERN Document Server

    Mielke, Alexander

    1991-01-01

    The theory of center manifold reduction is studied in this monograph in the context of (infinite-dimensional) Hamil- tonian and Lagrangian systems. The aim is to establish a "natural reduction method" for Lagrangian systems to their center manifolds. Nonautonomous problems are considered as well assystems invariant under the action of a Lie group ( including the case of relative equilibria). The theory is applied to elliptic variational problemson cylindrical domains. As a result, all bounded solutions bifurcating from a trivial state can be described by a reduced finite-dimensional variational problem of Lagrangian type. This provides a rigorous justification of rod theory from fully nonlinear three-dimensional elasticity. The book will be of interest to researchers working in classical mechanics, dynamical systems, elliptic variational problems, and continuum mechanics. It begins with the elements of Hamiltonian theory and center manifold reduction in order to make the methods accessible to non-specialists,...

  16. Challenges for coexistence of machine to machine and human to human applications in mobile network

    DEFF Research Database (Denmark)

    Sanyal, R.; Cianca, E.; Prasad, Ramjee

    2012-01-01

    A key factor for the evolution of the mobile networks towards 4G is to bring to fruition high bandwidth per mobile node. Eventually, due to the advent of a new class of applications, namely, Machine-to-Machine, we foresee new challenges where bandwidth per user is no more the primal driver...... be evolved to address various nuances of the mobile devices used by man and machines. The bigger question is as follows. Is the state-of-the-art mobile network designed optimally to cater both the Human-to-Human and Machine-to-Machine applications? This paper presents the primary challenges....... As an immediate impact of the high penetration of M2M devices, we envisage a surge in the signaling messages for mobility and location management. The cell size will shrivel due to high tele-density resulting in even more signaling messages related to handoff and location updates. The mobile network should...

  17. Sparse Variational Bayesian SAGE Algorithm With Application to the Estimation of Multipath Wireless Channels

    DEFF Research Database (Denmark)

    Shutin, Dmitriy; Fleury, Bernard Henri

    2011-01-01

    the variational free energy, distributions of the multipath component parameters can be obtained instead of parameter point estimates and ii) the estimation of the number of relevant multipath components and the estimation of the component parameters are implemented jointly. The sparsity is achieved by defining......In this paper, we develop a sparse variational Bayesian (VB) extension of the space-alternating generalized expectation-maximization (SAGE) algorithm for the high resolution estimation of the parameters of relevant multipath components in the response of frequency and spatially selective wireless...

  18. Pharmacomicrobiomics : the impact of human microbiome variations on systems pharmacology and personalized therapeutics

    NARCIS (Netherlands)

    ElRakaiby, Marwa; Dutilh, Bas E; Rizkallah, Mariam R; Boleij, Annemarie; Cole, Jason N; Aziz, Ramy K

    The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome

  19. Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics

    NARCIS (Netherlands)

    ElRakaiby, M.; Dutilh, B.E.; Rizkallah, M.R.; Boleij, A.; Cole, J.N.; Aziz, R.K.

    2014-01-01

    The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome

  20. Analysis of indel variations in the human disease-associated genes ...

    Indian Academy of Sciences (India)

    Online only: http://www.ias.ac.in/jgenet/OnlineResources/91/e1.pdf]. Introduction. Recently, the human genes CDKN2AIP, ... for these indels in future studies. ∗For correspondence. E-mail: hspark@kribb.re.kr. ... studies have reported that indel mutations are key drivers causing human cancers (Ngo et al. 2011; Varela et al.

  1. Evolutionary developmental pathology and anthropology: A new field linking development, comparative anatomy, human evolution, morphological variations and defects, and medicine.

    Science.gov (United States)

    Diogo, Rui; Smith, Christopher M; Ziermann, Janine M

    2015-11-01

    We introduce a new subfield of the recently created field of Evolutionary-Developmental-Anthropology (Evo-Devo-Anth): Evolutionary-Developmental-Pathology-and-Anthropology (Evo-Devo-P'Anth). This subfield combines experimental and developmental studies of nonhuman model organisms, biological anthropology, chordate comparative anatomy and evolution, and the study of normal and pathological human development. Instead of focusing on other organisms to try to better understand human development, evolution, anatomy, and pathology, it places humans as the central case study, i.e., as truly model organism themselves. We summarize the results of our recent Evo-Devo-P'Anth studies and discuss long-standing questions in each of the broader biological fields combined in this subfield, paying special attention to the links between: (1) Human anomalies and variations, nonpentadactyly, homeotic transformations, and "nearest neighbor" vs. "find and seek" muscle-skeleton associations in limb+facial muscles vs. other head muscles; (2) Developmental constraints, the notion of "phylotypic stage," internalism vs. externalism, and the "logic of monsters" vs. "lack of homeostasis" views about human birth defects; (3) Human evolution, reversions, atavisms, paedomorphosis, and peromorphosis; (4) Scala naturae, Haeckelian recapitulation, von Baer's laws, and parallelism between phylogeny and development, here formally defined as "Phylo-Devo parallelism"; and (5) Patau, Edwards, and Down syndrome (trisomies 13, 18, 21), atavisms, apoptosis, heart malformations, and medical implications. © 2015 Wiley Periodicals, Inc.

  2. Capturing the Value: Earth Applications of Space Human Factors Research

    Science.gov (United States)

    Connors, Mary M.; Shafto, Michael G. (Technical Monitor)

    1995-01-01

    This paper details how the Space Human Factors/Life Sciences program at Ames Research Center (ARC) has provided, and continues to provide, a variety of Earth-based benefits. These benefits will be considered under five categories: aeronautics, space-like environments, general applications, human/automation interaction, and methodology. The human factors work at ARC includes a range of activities whose products serve the aerospace community. Some areas of research focus specifically on aeronautical requirements; others are driven by space needs. However, the symbiosis between these two domains allows a sharing of resources, and the insights and experimental results gathered in one domain can often be applied in the other. Aeronautics is an industry whose survival is generally viewed as critical to American competitiveness, and where benefits can result in a very high payoff. The ability to apply space-initiated research to aeronautical requirements represents one example of bringing space benefits down to Earth. The second-order value of space human factors research goes well beyond the aerospace community. Spaceflight shares with a number of other activities certain environmental characteristics that drive human factors engineering design and procedural specification. Spaceflight is an isolated activity, conducted under severely confined conditions, with a high level of risk, and where provisions are restricted and opportunities for outside help are limited. A number of Earth-based activities including submarines and other naval vessels, oil rigs, remote weather stations, and scientific and polar expeditions, share many of these characteristics. These activities serve as testbeds for space-related research and, in turn, space-related research provides beneficial insight to the conduct of these activities.

  3. Variation of stable silicon isotopes. Analytical developments and applications in Precambrian geochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, Kathrin

    2010-05-28

    The work presented in this thesis predominantly deals with bulk-rock measurements of silicon stable isotopes on a Multi Collector-ICP-MS. Analyses were performed in cooperation with the Royal Museum for Central Africa, Belgium. The first section describes how the first analysis of δ{sup 30}Si on a conventional Nu PlasmaTM Multi-Collector ICP-MS instrument can be enabled by the elimination of 14N16O interference overlying the 30Si peak. The determination of δ{sup 30}Si was rendered possible owing to new instrumental upgrades that facilitate the application of a higher mass resolution. The careful characterisation of appropriate reference materials is indispensable for the assessment of the accuracy of a measurement. The determination of U.S. Geological Survey (USGS) reference materials represents the second objective of this section. The analysis of two Hawaiian standards (BHVO-1 and BHVO-2) demonstrates precise and accurate δ{sup 30}Si determinations and provides cross-calibration data as a quality control for other laboratories. The second section focuses on coupled silicon-oxygen isotopic evidences for the origin of silicification in mafic volcanic rocks of the Barberton Greenstone Belt, South Africa. In contrast to the modern Earth, silicification of near-surface layers, including chert formation, were widespread processes on the Precambrian ocean floor, and demonstrate the ubiquity of extreme silica mobilization in the early Earth. This section outlines the investigation of silicon and oxygen isotopes on three different stratigraphic sections of variably silicified basalts and overlying bedded cherts from the 3.54 Ga, 3.45 Ga and 3.33 Ga Theespruit, Kromberg and Hooggenoeg Formations, respectively. Silicon isotopes, oxygen isotopes and the variable SiO{sub 2}-contents demonstrate a positive correlation with silicification intensity in all three sections, with varying gradients of δ{sup 30}Si vs. δ{sup 18}O arrays for different sections. Seawater has been

  4. High-throughput sequencing reveals extensive variation in human-specific L1 content in individual human genomes.

    Science.gov (United States)

    Ewing, Adam D; Kazazian, Haig H

    2010-09-01

    Using high-throughput sequencing, we devised a technique to determine the insertion sites of virtually all members of the human-specific L1 retrotransposon family in any human genome. Using diagnostic nucleotides, we were able to locate the approximately 800 L1Hs copies corresponding specifically to the pre-Ta, Ta-0, and Ta-1 L1Hs subfamilies, with over 90% of sequenced reads corresponding to human-specific elements. We find that any two individual genomes differ at an average of 285 sites with respect to L1 insertion presence or absence. In total, we assayed 25 individuals, 15 of which are unrelated, at 1139 sites, including 772 shared with the reference genome and 367 nonreference L1 insertions. We show that L1Hs profiles recapitulate genetic ancestry, and determine the chromosomal distribution of these elements. Using these data, we estimate that the rate of L1 retrotransposition in humans is between 1/95 and 1/270 births, and the number of dimorphic L1 elements in the human population with gene frequencies greater than 0.05 is between 3000 and 10,000.

  5. Seasonal variation of technetium-99 in Fucus vesiculosus and its application as an oceanographic tracer

    DEFF Research Database (Denmark)

    Shi, Keliang; Hou, Xiaolin; Roos, Per

    2013-01-01

    The concentration of 99Tc was determined in archived time series seaweed samples collected at Klint (Denmark). The results demonstrate a significantly seasonal variation of 99Tc concentrations in Fucus vesiculosus with maximum values in winter and minimum values in summer. The mechanism driving...

  6. Application of the cluster variation method to ordering in an interstitital solid solution

    DEFF Research Database (Denmark)

    Pekelharing, Marjon I.; Böttger, Amarante; Somers, Marcel A. J.

    1999-01-01

    The tetrahedron approximation of the cluster variation method (CVM) was applied to describe the ordering on the fcc interstitial sublattice of gamma-Fe[N] and gamma'-Fe4N1-x. A Lennard-Jones potential was used to describe the dominantly strain-induced interactions, caused by misfitting of the N a...

  7. A vectorial variational mode solver and its application to piecewise constant and diffused waveguides

    NARCIS (Netherlands)

    Ivanova, Alyona; Stoffer, Remco; Hammer, Manfred; van Groesen, Embrecht W.C.

    2008-01-01

    A Variational Vectorial Mode Solver for 3-D dielectric waveguides with arbitrary 2-D crosssections is proposed. It is based on expansion of each component of a mode profile as a superposition of some a priori defined functions defined on one coordinate axis times some unknown continuous coefficient

  8. [Periodical changes of various hematological parameters of the human body adaptation and gravitation fields variations].

    Science.gov (United States)

    Gederim, V V; Sokolovskiĭ, V V; Gorshkov, E S; Shapovalov, S N; Troshichev, O A

    2001-01-01

    Monitoring the content of lymphocytes and nucleated neutrophils (observation period 10.5 months) and the determination of the values of leucocytes coefficient and erythrocyte sedimentation rate in chronic patients revealed rhythms of oscillations of these parameters (from 3-5 to 33 days). The coincidence of these rhythms with the rhythms of variations of gravitational field indicates that gravitational field affects the quantitative blood cell composition and the rheological properties of blood.

  9. Convergent effects of mouse Pet-1 deletion and human PET-1 variation on amygdala fear and threat processing.

    Science.gov (United States)

    Wellman, Cara L; Camp, Marguerite; Jones, V Morgan; MacPherson, Kathryn P; Ihne, Jessica; Fitzgerald, Paul; Maroun, Mouna; Drabant, Emily; Bogdan, Ryan; Hariri, Ahmad R; Holmes, Andrew

    2013-12-01

    Serotonin is critical for shaping the development of neural circuits regulating emotion. Pet-1 (FEV-1) is an ETS-domain transcription factor essential for differentiation and forebrain targeting of serotonin neurons. Constitutive Pet-1 knockout (KO) causes major loss of serotonin neurons and forebrain serotonin availability, and behavioral abnormalities. We phenotyped Pet-1 KO mice for fear conditioning and extinction, and on a battery of assays for anxiety- and depression-related behaviors. Morphology of Golgi-stained neurons in basolateral amygdala (BLA) and prelimbic cortex was examined. Using human imaging genetics, a common variant (rs860573) in the PET-1 (FEV) gene was tested for effects on threat-related amygdala reactivity and psychopathology in 88 Asian-ancestry subjects. Pet-1 KO mice exhibited increased acquisition and expression of fear, and elevated fear recovery following extinction, relative to wild-type (WT). BLA dendrites of Pet-1 KO mice were significantly longer than in WT. Human PET-1 variation associated with differences in amygdala threat processing and psychopathology. This novel evidence for the role of Pet-1 in fear processing and dendritic organization of amygdala neurons and in human amygdala threat processing extends a growing literature demonstrating the influence of genetic variation in the serotonin system on emotional regulation via effects on structure and function of underlying corticolimbic circuitry. © 2013.

  10. Diurnal Variation of Circulating Interleukin-6 in Humans: A Meta-Analysis

    Science.gov (United States)

    Lekander, Mats; Åkerstedt, Torbjörn; Axelsson, John; Ingre, Michael

    2016-01-01

    The pleiotropic cytokine interleukin-6 (IL-6) has been proposed to contribute to circadian regulation of sleepiness by increasing in the blood at night. Earlier studies have reported diurnal variation of IL-6, but phase estimates are conflicting. We have therefore performed a meta-analysis on the diurnal variation of circulating IL-6. Studies were included if they reported IL-6 in plasma or serum recorded at least twice within 24 hours in the same individual. A systematic search resulted in the inclusion of 43 studies with 56 datasets, for a total of 1100 participants. Individual participant data were available from 4 datasets with a total of 56 participants. Mixed-effects meta-regression modelling confirmed that IL-6 varied across the day, the most conspicuous effect being a trough in the morning. These results stand in contrast to earlier findings of a peak in the evening or night, and suggest that diurnal variation should be taken into account in order to avoid confounding by time of day in studies of IL-6 in plasma or serum. PMID:27832117

  11. Structural Variations of Human Glucokinase Glu256Lys in MODY2 Condition Using Molecular Dynamics Study

    Directory of Open Access Journals (Sweden)

    Nanda Kumar Yellapu

    2013-01-01

    Full Text Available Glucokinase (GK is the predominant hexokinase that acts as glucose sensor and catalyses the formation of Glucose-6-phosphate. The mutations in GK gene influence the affinity for glucose and lead to altered glucose levels in blood causing maturity onset diabetes of the young type 2 (MODY2 condition, which is one of the prominent reasons of type 2 diabetic condition. In view of the importance of mutated GK resulting in hyperglycemic condition, in the present study, molecular dynamics simulations were carried out in intact and 256 E-K mutated GK structures and their energy values and conformational variations were correlated. Energy variations were observed in mutated GK (3500 Kcal/mol structure with respect to intact GK (5000 Kcal/mol, and it showed increased γ-turns, decreased β-turns, and more helix-helix interactions that affected substrate binding region where its volume increased from 1089.152 Å2 to 1246.353 Å2. Molecular docking study revealed variation in docking scores (intact = −12.199 and mutated = −8.383 and binding mode of glucose in the active site of mutated GK where the involvement of A53, S54, K56, K256, D262 and Q286 has resulted in poor glucose binding which probably explains the loss of catalytic activity and the consequent prevailing of high glucose levels in MODY2 condition.

  12. Isolation of human foetal myoblasts and its application for microencapsulation.

    Science.gov (United States)

    Li, Anna Aihua; Bourgeois, Jacqueline; Potter, Murray; Chang, Patricia L

    2008-01-01

    Foetal cells secrete more growth factors, generate less immune response, grow and proliferate better than adult cells. These characteristics make them desirable for recombinant modification and use in microencapsulated cellular gene therapeutics. We have established a system in vitro to obtain a pure population of primary human foetal myoblasts under several rounds of selection with non-collagen coated plates and identified by desmin staining. These primary myoblasts presented good proliferation ability and better differentiation characteristics in monolayer and after microencapsulation compared to murine myoblast C2C12 cells based on creatine phosphokinase (CPK), major histocompatibility complex (MHC) and multi-nucleated myotubule determination. The lifespan of primary myoblasts was 70 population doublings before entering into senescent state, with a population time of 18-24 hrs. Hence, we have developed a protocol for isolating human foetal primary myoblasts with excellent differentiation potential and robust growth and longevity. They should be useful for cell-based therapy in human clinical applications with microencapsulation technology.

  13. Isolation of human foetal myoblasts and its application for microencapsulation

    Science.gov (United States)

    Li, Anna Aihua; Bourgeois, Jacqueline; Potter, Murray; Chang, Patricia L

    2008-01-01

    Abstract Foetal cells secrete more growth factors, generate less immune response, grow and proliferate better than adult cells. These characteristics make them desirable for recombinant modification and use in microencapsulated cellular gene therapeutics. We have established a system in vitro to obtain a pure population of primary human foetal myoblasts under several rounds of selection with non-collagen coated plates and identified by desmin staining. These primary myoblasts presented good proliferation ability and better differentiation characteristics in monolayer and after microencapsulation compared to murine myoblast C2C12 cells based on creatine phosphokinase (CPK), major histocompatibility complex (MHC) and multi-nucleated myotubule determination. The lifespan of primary myoblasts was 70 population doublings before entering into senescent state, with a population time of 18–24 hrs. Hence, we have developed a protocol for isolating human foetal primary myoblasts with excellent differentiation potential and robust growth and longevity. They should be useful for cell-based therapy in human clinical applications with microencapsulation technology. PMID:18366454

  14. Radiocarbon analysis of human remains: a review of forensic applications.

    Science.gov (United States)

    Ubelaker, Douglas H

    2014-11-01

    Radiocarbon analysis of organic materials, with the comparison of values with those of the post-1950 modern bomb curve, has proven useful in forensic science to help evaluate the antiquity of evidence. Applications are particularly helpful in the study of human remains, especially with those displaying advanced decomposition of soft tissues. Radiocarbon analysis can reveal if the remains relate to the modern, post-1950 era and if so, also provide information needed to evaluate the death and birth date. Sample selection and interpretation of results must be guided by knowledge of the formation and remodeling of different human tissues, as well as contextual information and the approximate age at death of the individual represented. Dental enamel does not remodel and thus captures dietary radiocarbon values at the time of juvenile formation. Most other human tissues do remodel but at differing rates and therefore collectively offer key information relative to the estimation of the death date. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  15. Estimating human ovarian non-growing follicle number: the application of modern stereology techniques to an old problem.

    Science.gov (United States)

    Charleston, Jay S; Hansen, Karl R; Thyer, Angela C; Charleston, Lynne B; Gougeon, Alain; Siebert, Joseph R; Soules, Michael R; Klein, Nancy A

    2007-08-01

    BACKGROUND Previous published reports on the number of non-growing follicles (NGFs) in the human ovary have employed model-based methods for number estimates. These methods are time-intensive, and require correction factors and assumptions that ultimately limit their accuracy. Here, we describe the modification, application and validation of a modern fractionator/optical disector technique for the estimation of human ovarian NGF number. METHODS Forty-eight pairs of normal human ovaries were collected from women (age 8-51 years) undergoing elective bilateral oophorectomy, organ donation, or from autopsy. After gross pathologic examination, systematic random sampling was utilized to obtain tissue for analysis by the fractionator/optical disector method. The precision of individual NGF counts was determined by calculating the observed coefficient of error (OCE). Intra-observer variability and variation in NGF number between ovaries within a pair were also determined. RESULTS The mean OCE was 16.6% with larger variations observed at lower follicle counts. In recount experiments of the same ovary, NGF number estimates varied by 15-29%, except at very low follicle counts where variation was greater, but absolute differences were small. There was no significant difference in NGF number between ovaries within a pair (Wilcoxon signed rank test, P = 0.81). CONCLUSIONS Modern stereology methods provide an unbiased, efficient method for estimating NGF number in the human ovary. Both ovaries within a pair contain similar numbers of NGFs.

  16. Big Data and Intelligence: Applications, Human Capital, and Education

    Directory of Open Access Journals (Sweden)

    Michael Landon-Murray

    2016-06-01

    Full Text Available The potential for big data to contribute to the US intelligence mission goes beyond bulk collection, social media and counterterrorism. Applications will speak to a range of issues of major concern to intelligence agencies, from military operations to climate change to cyber security. There are challenges too: procurement lags, data stovepiping, separating signal from noise, sources and methods, a range of normative issues, and central to managing these challenges, human capital. These potential applications and challenges are discussed and a closer look at what data scientists do in the Intelligence Community (IC is offered. Effectively filling the ranks of the IC’s data science workforce will depend on the provision of well-trained data scientists from the higher education system. Program offerings at America’s top fifty universities will thus be surveyed (just a few years ago there were reportedly no degrees in data science. One Master’s program that has melded data science with intelligence is examined as well as a university big data research center focused on security and intelligence. This discussion goes a long way to clarify the prospective uses of data science in intelligence while probing perhaps the key challenge to optimal application of big data in the IC.

  17. Humans and Tits in the City: Quantifying the Effects of Human Presence on Great Tit and Blue Tit Reproductive Trait Variation

    Directory of Open Access Journals (Sweden)

    Michela Corsini

    2017-08-01

    Full Text Available Environmental conditions are key drivers of life-history evolution, and the urban environment is an extreme form of land-use readily inhabited by avian wildlife, whose life-history variation in such altered environment is still poorly understood. Recently, the study of environmental variables associated with urban living—which include shifts in temperature, light, noise or food availability—has attracted increased attention. Another environmental axis that sets the urban space at odds relative to natural habitats is high human abundance, yet very little is known about its effect on avian fitness. We developed a protocol to quantify human presence by performing repeated counts of humans on the ground within a 15 m radius of nestboxes monitored in two centrally-located study areas of a European capital city. In parallel, a GIS-based approach was used to infer nestbox distance to the nearest path and road. Multiple counts of human presence around each nestbox yielded moderate to high repeatabilities (0.6 ≤ r ≤ 0.8 while requiring considerable resources time- and people- wise. In contrast, GIS-based estimates of nestbox distance to paths and roads were time efficient and generated highly repeatable results. The effects of (i human presence around each nestbox, (ii nestbox distance to the nearest path and (iii nestbox distance to the nearest road were tested on reproductive traits of blue tits Cyanistes caeruleus and great tits Parus major breeding in two urban sites. Human presence did not influence blue tit or great tit life-history traits and reproductive success, suggesting reproductive habituation to humans in an urban landscape. In contrast, nestbox distance to roads shortened incubation time in great tits while nestbox distance to paths increased incubation time in blue tits. Moreover, blue tit offspring 2 weeks after hatching were lighter closer to roads. Our study confirms the reliability of a field protocol capturing human presence

  18. Comprehensive characterization of human genome variation by high coverage whole-genome sequencing of forty four Caucasians.

    Directory of Open Access Journals (Sweden)

    Hui Shen

    Full Text Available Whole genome sequencing studies are essential to obtain a comprehensive understanding of the vast pattern of human genomic variations. Here we report the results of a high-coverage whole genome sequencing study for 44 unrelated healthy Caucasian adults, each sequenced to over 50-fold coverage (averaging 65.8×. We identified approximately 11 million single nucleotide polymorphisms (SNPs, 2.8 million short insertions and deletions, and over 500,000 block substitutions. We showed that, although previous studies, including the 1000 Genomes Project Phase 1 study, have catalogued the vast majority of common SNPs, many of the low-frequency and rare variants remain undiscovered. For instance, approximately 1.4 million SNPs and 1.3 million short indels that we found were novel to both the dbSNP and the 1000 Genomes Project Phase 1 data sets, and the majority of which (∼96% have a minor allele frequency less than 5%. On average, each individual genome carried ∼3.3 million SNPs and ∼492,000 indels/block substitutions, including approximately 179 variants that were predicted to cause loss of function of the gene products. Moreover, each individual genome carried an average of 44 such loss-of-function variants in a homozygous state, which would completely "knock out" the corresponding genes. Across all the 44 genomes, a total of 182 genes were "knocked-out" in at least one individual genome, among which 46 genes were "knocked out" in over 30% of our samples, suggesting that a number of genes are commonly "knocked-out" in general populations. Gene ontology analysis suggested that these commonly "knocked-out" genes are enriched in biological process related to antigen processing and immune response. Our results contribute towards a comprehensive characterization of human genomic variation, especially for less-common and rare variants, and provide an invaluable resource for future genetic studies of human variation and diseases.

  19. Femoral neck-shaft angle in humans: variation relating to climate, clothing, lifestyle, sex, age and side

    Science.gov (United States)

    Gilligan, Ian; Chandraphak, Supichya; Mahakkanukrauh, Pasuk

    2013-01-01

    The femoral neck-shaft angle (NSA) varies among modern humans but measurement problems and sampling limitations have precluded the identification of factors contributing to its variation at the population level. Potential sources of variation include sex, age, side (left or right), regional differences in body shape due to climatic adaptation, and the effects of habitual activity patterns (e.g. mobile and sedentary lifestyles and foraging, agricultural, and urban economies). In this study we addressed these issues, using consistent methods to assemble a global NSA database comprising over 8000 femora representing 100 human groups. Results from the analyses show an average NSA for modern humans of 127° (markedly lower than the accepted value of 135°); there is no sex difference, no age-related change in adults, but possibly a small lateral difference which could be due to right leg dominance. Climatic trends consistent with principles based on Bergmann's rule are evident at the global and continental levels, with the NSA varying in relation to other body shape indices: median NSA, for instance, is higher in warmer regions, notably in the Pacific (130°), whereas lower values (associated with a more stocky body build) are found in regions where ancestral populations were exposed to colder conditions, in Europe (126°) and the Americas (125°). There is a modest trend towards increasing NSA with the economic transitions from forager to agricultural and urban lifestyles and, to a lesser extent, from a mobile to a sedentary existence. However, the main trend associated with these transitions is a progressive narrowing in the range of variation in the NSA, which may be attributable to thermal insulation provided by improved cultural buffering from climate, particularly clothing. PMID:23781912

  20. Early modern humans and morphological variation in Southeast Asia: fossil evidence from Tam Pa Ling, Laos

    National Research Council Canada - National Science Library

    Demeter, Fabrice; Shackelford, Laura; Westaway, Kira; Duringer, Philippe; Bacon, Anne-Marie; Ponche, Jean-Luc; Wu, Xiujie; Sayavongkhamdy, Thongsa; Zhao, Jian-Xin; Barnes, Lani; Boyon, Marc; Sichanthongtip, Phonephanh; Sénégas, Frank; Karpoff, Anne-Marie; Patole-Edoumba, Elise; Coppens, Yves; Braga, José

    2015-01-01

    .... In the current study, a complete human mandible representing a second individual, TPL 2, is described using discrete traits and geometric morphometrics with an emphasis on determining its population affinity...

  1. Exploring vague language use and voice variation in human-agent interaction

    OpenAIRE

    Clark, Leigh M.H.

    2016-01-01

    This thesis addresses the linguistic phenomenon of vague language (VL) and its effect on the creation of identity in the emerging and developing field of human-agent interaction (HAI). Current research on VL has focused on human interaction, while similar existing literature on language in HAI has focused on politeness theory and facework. This thesis brings the two research fields together and uses them as a focusing lens to investigate the issue of identity in agents – software with varying...

  2. Bacterial Community Variation in Human Body Habitats Across Space and Time

    OpenAIRE

    Costello, Elizabeth K.; Lauber, Christian L.; Hamady, Micah; Fierer, Noah; Gordon, Jeffrey I.; Knight, Rob

    2009-01-01

    Elucidating the biogeography of bacterial communities on the human body is critical for establishing healthy baselines from which to detect differences associated with diseases. To obtain an integrated view of the spatial and temporal distribution of the human microbiota, we surveyed bacteria from up to 27 sites in 7–9 healthy adults on four occasions. We found that community composition was determined primarily by body habitat. Within habitats, interpersonal variability was high, while indiv...

  3. A Cellular GWAS Approach to Define Human Variation in Cellular Pathways Important to Inflammation

    Directory of Open Access Journals (Sweden)

    Samuel I. Miller

    2016-04-01

    Full Text Available An understanding of common human diversity in innate immune pathways should be beneficial in understanding autoimmune diseases, susceptibility to infection, and choices of anti-inflammatory treatment. Such understanding could also result in definition of currently unknown components of human inflammation pathways. A cellular genome-wide association studies (GWAS platform, termed Hi-HOST (High-throughput human in vitro susceptibility testing, was developed to assay in vitro cellular phenotypes of infection in genotyped lymphoblastoid cells from genetically diverse human populations. Hi-HOST allows for measurement of multiple host and pathogen parameters of infection/inflammation including: bacterial invasion and intracellular replication, host cell death, and cytokine production. Hi-HOST has been used to successfully define a significant portion of the heritable human diversity in inflammatory cell death in response to Salmonella typhimurium. It also led to the discovery of genetic variants important to protection against systemic inflammatory response syndrome (SIRS and protection against death and bacteremia in individuals with SIRS. Our laboratory is currently using this platform to define human diversity in autophagy and the NLPR3 inflammasome pathways, and to define new components that can impact the expression of phenotypes related to these pathways.

  4. Variation in home range size of red foxes Vulpes vulpes along a gradient of productivity and human landscape alteration

    Science.gov (United States)

    2017-01-01

    Home range size is a fundamental concept for understanding animal dispersion and ecological needs, and it is one of the most commonly reported ecological attributes of free-ranging mammals. Previous studies indicate that red foxes Vulpes vulpes display great variability in home range size. Yet, there has been little consensus regarding the reasons why home range sizes of red foxes vary so extensively. In this study, we examine possible causes of variation in red fox home range sizes using data from 52 GPS collared red foxes from four study areas representing a gradient of landscape productivity and human landscape alteration in Norway and Sweden. Using 90% Local Convex Hull home range estimates, we examined how red fox home range size varied in relation to latitude, elevation, vegetation zone, proportion of agricultural land and human settlement within a home range, and sex and age. We found considerable variation in red fox home range sizes, ranging between 0.95 km2 to 44 km2 (LoCoH 90%) and 2.4 km2 to 358 km2 (MCP 100%). Elevation, proportion of agricultural land and sex accounted for 50% of the variation in home range size found amongst foxes, with elevation having the strongest effect. Red foxes residing in more productive landscapes (those in more southern vegetation zones), had home ranges approximately four times smaller than the home ranges of foxes in the northern boreal vegetation zone. Our results indicate that home range size was influenced by a productivity gradient at both the landscape (latitude) and the local (elevation) scale. The influence of the proportion of agriculture land on home range size of foxes illustrates how human landscape alteration can affect the space use and distribution of red foxes. Further, the variation in home range size found in this study demonstrates the plasticity of red foxes to respond to changing human landscape alteration as well as changes in landscape productivity, which may be contributing to red fox population

  5. An investigation of the origin, location and variations of the renal arteries in human fetuses and their clinical relevance.

    Science.gov (United States)

    Ciçekcibaşi, Aynur Emine; Ziylan, Taner; Salbacak, Ahmet; Seker, Muzaffer; Büyükmumcu, Mustafa; Tuncer, Işik

    2005-09-01

    We investigated the origin, localizations and anatomic variations of the renal artery (RA) in human fetuses with the aim of determining the distribution of these variations according to lateralization and gender. In total, 90 fetuses of spontaneous abortion (45 males, 45 females) with no congenital malformations were included to the study. The abdominal aorta and its branches were dissected after latex solution colored with red ink had been injected into the vessels from the thoracic aorta. In all, 180 RA dissections were performed bilaterally in 90 cases and the anatomic variations were photographed. Right and left RAs were found to originate from the following levels according to the columna vertebralis, respectively: 3.8% and 1.9% lower T12, 67.3% and 25.0% upper L1, 9.6% and 28.8% mid L1, 15.3% and 40.3 lower L1, 3.8% and 3.8% upper 1/3 part of L2 vertebra. The right RA originated from the lateral part and anterolateral wall of the abdominal aorta in 73.0% and 26.9% of cases while the lateral and anterolateral wall origin percentages of left RA were 90.3% and 9.6%, respectively. The origin site of the right RA from the abdominal aorta was superior to, at the same level with, and inferior to that of the left RA in 53.8%, 34.6% and 11.5% of the cases, respectively. There were no variations in 75% of the cases whereas the remaining 25% had several variation patterns. The presented morphological results are as follows: A single hilar artery in 75% of the cases, double hilar arteries in 11.1%, an inferior polar artery in 10.5%, and a superior polar artery in 3.3% of specimens studied. Anatomical variations were observed more frequently among male fetuses and on the right side. Knowledge of RA variations is important for surgeons in performing many procedures and may help to avoid clinical complications, especially, during radiological examination and/or surgical approaches in the abdominal region.

  6. Evolution of the auditory ossicles in extant hominids: metric variation in African apes and humans.

    Science.gov (United States)

    Quam, Rolf M; Coleman, Mark N; Martínez, Ignacio

    2014-08-01

    The auditory ossicles in primates have proven to be a reliable source of phylogenetic information. Nevertheless, to date, very little data have been published on the metric dimensions of the ear ossicles in African apes and humans. The present study relies on the largest samples of African ape ear ossicles studied to date to address questions of taxonomic differences and the evolutionary transformation of the ossicles in gorillas, chimpanzees and humans. Both African ape taxa show a malleus that is characterized by a long and slender manubrium and relatively short corpus, whereas humans show the opposite constellation of a short and thick manubrium and relatively long corpus. These changes in the manubrium are plausibly linked with changes in the size of the tympanic membrane. The main difference between the incus in African apes and humans seems to be related to changes in the functional length. Compared with chimpanzees, human incudes are larger in nearly all dimensions, except articular facet height, and show a more open angle between the axes. The gorilla incus resembles humans more closely in its metric dimensions, including functional length, perhaps as a result of the dramatically larger body size compared with chimpanzees. The differences between the stapedes of humans and African apes are primarily size-related, with humans being larger in nearly all dimensions. Nevertheless, some distinctions between the African apes were found in the obturator foramen and head height. Although correlations between metric variables in different ossicles were generally lower than those between variables in the same bone, variables of the malleus/incus complex appear to be more strongly correlated than those of the incus/stapes complex, perhaps reflecting the different embryological and evolutionary origins of the ossicles. The middle ear lever ratio for the African apes is similar to other haplorhines, but humans show the lowest lever ratio within primates. Very low levels

  7. Evolution of the auditory ossicles in extant hominids: metric variation in African apes and humans

    Science.gov (United States)

    Quam, Rolf M; Coleman, Mark N; Martínez, Ignacio

    2014-01-01

    The auditory ossicles in primates have proven to be a reliable source of phylogenetic information. Nevertheless, to date, very little data have been published on the metric dimensions of the ear ossicles in African apes and humans. The present study relies on the largest samples of African ape ear ossicles studied to date to address questions of taxonomic differences and the evolutionary transformation of the ossicles in gorillas, chimpanzees and humans. Both African ape taxa show a malleus that is characterized by a long and slender manubrium and relatively short corpus, whereas humans show the opposite constellation of a short and thick manubrium and relatively long corpus. These changes in the manubrium are plausibly linked with changes in the size of the tympanic membrane. The main difference between the incus in African apes and humans seems to be related to changes in the functional length. Compared with chimpanzees, human incudes are larger in nearly all dimensions, except articular facet height, and show a more open angle between the axes. The gorilla incus resembles humans more closely in its metric dimensions, including functional length, perhaps as a result of the dramatically larger body size compared with chimpanzees. The differences between the stapedes of humans and African apes are primarily size-related, with humans being larger in nearly all dimensions. Nevertheless, some distinctions between the African apes were found in the obturator foramen and head height. Although correlations between metric variables in different ossicles were generally lower than those between variables in the same bone, variables of the malleus/incus complex appear to be more strongly correlated than those of the incus/stapes complex, perhaps reflecting the different embryological and evolutionary origins of the ossicles. The middle ear lever ratio for the African apes is similar to other haplorhines, but humans show the lowest lever ratio within primates. Very low levels

  8. Variational Methods for Discontinuous Structures : Applications to Image Segmentation, Continuum Mechanics

    CERN Document Server

    Tomarelli, Franco

    1996-01-01

    In recent years many researchers in material science have focused their attention on the study of composite materials, equilibrium of crystals and crack distribution in continua subject to loads. At the same time several new issues in computer vision and image processing have been studied in depth. The understanding of many of these problems has made significant progress thanks to new methods developed in calculus of variations, geometric measure theory and partial differential equations. In particular, new technical tools have been introduced and successfully applied. For example, in order to describe the geometrical complexity of unknown patterns, a new class of problems in calculus of variations has been introduced together with a suitable functional setting: the free-discontinuity problems and the special BV and BH functions. The conference held at Villa Olmo on Lake Como in September 1994 spawned successful discussion of these topics among mathematicians, experts in computer science and material scientis...

  9. A modern theory of random variation with applications in stochastic calculus, financial mathematics, and Feynman integration

    CERN Document Server

    Muldowney, Patrick

    2012-01-01

    A Modern Theory of Random Variation is a new and radical re-formulation of the mathematical underpinnings of subjects as diverse as investment, communication engineering, and quantum mechanics. Setting aside the classical theory of probability measure spaces, the book utilizes a mathematically rigorous version of the theory of random variation that bases itself exclusively on finitely additive probability distribution functions. In place of twentieth century Lebesgue integration and measure theory, the author uses the simpler concept of Riemann sums, and the non-absolute Riemann-type integration of Henstock. Readers are supplied with an accessible approach to standard elements of probability theory such as the central limmit theorem and Brownian motion as well as remarkable, new results on Feynman diagrams and stochastic integrals. Throughout the book, detailed numerical demonstrations accompany the discussions of abstract mathematical theory, from the simplest elements of the subject to the most complex. I...

  10. A variational approach to nonsmooth dynamics applications in unilateral mechanics and electronics

    CERN Document Server

    Adly, Samir

    2017-01-01

    This brief examines mathematical models in nonsmooth mechanics and nonregular electrical circuits, including evolution variational inequalities, complementarity systems, differential inclusions, second-order dynamics, Lur'e systems and Moreau's sweeping process. The field of nonsmooth dynamics is of great interest to mathematicians, mechanicians, automatic controllers and engineers. The present volume acknowledges this transversality and provides a multidisciplinary view as it outlines fundamental results in nonsmooth dynamics and explains how to use them to study various problems in engineering. In particular, the author explores the question of how to redefine the notion of dynamical systems in light of modern variational and nonsmooth analysis. With the aim of bridging between the communities of applied mathematicians, engineers and researchers in control theory and nonlinear systems, this brief outlines both relevant mathematical proofs and models in unilateral mechanics and electronics.

  11. Spatial Variation in the Healthy Human Lung Microbiome and the Adapted Island Model of Lung Biogeography.

    Science.gov (United States)

    Dickson, Robert P; Erb-Downward, John R; Freeman, Christine M; McCloskey, Lisa; Beck, James M; Huffnagle, Gary B; Curtis, Jeffrey L

    2015-06-01

    The lung microbiome is spatially heterogeneous in advanced airway diseases, but whether it varies spatially in health is unknown. We postulated that the primary determinant of lung microbiome constitution in health is the balance of immigration and elimination of communities from the upper respiratory tract (URT; "adapted island model of lung biogeography"), rather than differences in regional bacterial growth conditions. To determine if the lung microbiome is spatially varied in healthy adults. Bronchoscopy was performed on 15 healthy subjects. Specimens were sequentially collected in the lingula and right middle lobe (by bronchoalveolar lavage [BAL]), then in the right upper lobe, left upper lobe, and supraglottic space (by protected-specimen brush). Bacterial 16S ribosmal RNA-encoding genes were sequenced using MiSeq (Illumina, San Diego, CA). There were no significant differences between specimens collected by BAL and protected-specimen brush. Spatially separated intrapulmonary sites, when compared with each other, did not contain consistently distinct microbiota. On average, intrasubject variation was significantly less than intersubject variation (P = 0.00003). By multiple ecologic parameters (community richness, community composition, intersubject variability, and similarity to source community), right upper lobe microbiota more closely resembled those of the URT than did microbiota from more distal sites. As predicted by the adapted island model, community richness decreased with increasing distance from the source community of the URT (P microbiota within an individual is significantly less than variation across individuals. The lung microbiome in health is more influenced by microbial immigration and elimination (the adapted island model) than by the effects of local growth conditions on bacterial reproduction rates, which are more determinant in advanced lung diseases. BAL of a single lung segment is an acceptable method of sampling the healthy lung

  12. Application of 3D variation-density interface inversion of gravity anomalies in South China Sea

    Science.gov (United States)

    Li, Shuling; Meng, Xiaohong

    2017-04-01

    The South China Sea (SCS) is a marginal basin with extremely complicated crustal structure and whose evolutional history is associated with continental rifting and seafloor spreading. The gravity data are among the most important data sets for studying deep crustal structures and the tectonic evolution. Density interface inversion by gravity anomalies can effectively estimate the depth of Moho interface. However, the Moho interface inversion in SCS are facing challenges due to the density contract of crust-mantle vary in three dimensions, which are associated with the complicated crustal structure (co-existing oceanic crust, continental crust and transitional crust). The regular inversion methods always assume the density contract on both sides of the interface would be constant, which is quite unrealistic since actual strata densities vary both vertically and laterally. To meet the challenges of 3D variation of density in SCS, we present an improved 3D variation-density interface inversion of gravity anomalies based on Parker-Oldenburg method. We first construct two variation density models with exponential density-depth relationships, which expressed the variation of stratum density depending on the depth in oceanic and continental crust respectively. Meanwhile, to minimize multiple solutions for potential field inversion, we collect deep seismic sounding data and employ the gravity inversion by joint using seismic data to be constraint for depth of Moho. Finally, we have estimated the depth of Moho interface which infers the tectonic significance in SCS. The inversion results agree well with seismic data in SCS show this approach is more effective and precise to quantitative estimate the depth of interface. Keywords: South China Sea; Gravity anomalies; Density interface inversion;

  13. Variation of Pore Metrics in Metal-Organic Frameworks for Enhanced Storage and Catalytic Applications

    OpenAIRE

    Brown, Jonathan Ward

    2015-01-01

    With the principles of reticular chemistry, metal-organic frameworks (MOFs)with enhanced storage and catalytic capabilities have been prepared. This dissertationpresents the synthesis of azo-IRMOF-74-III for controllable release of cargomolecules as well as the catalytic testing of MOF-525-Mn and an isoreticular seriesof MOFs based on the MOF-5 framework. The variation of pore metrics inthese frameworks show the versatility of reticular chemistry and their applicationin catalytic reactions.Fi...

  14. [Variations in the parathyroid glands. Number, situation and arterial vascularization. Anatomical study and surgical application].

    Science.gov (United States)

    Delattre, J F; Flament, J B; Palot, J P; Pluot, M

    1982-11-01

    The authors have made a study of the variations in the parathyroid glands, basing their report on 100 block dissections of the neck injected with latex. The results allow a better understanding of certain types of parathyroid insufficiency following surgery to the thyroid gland. In almost half the cases the vascular arrangement was sufficient to explain how hypoparathyroidism might come about following surgery to the thyroid gland.

  15. Applications of the Variational Integral in Iterative Numerical Solutions to the Stationary Heat Equations.

    Science.gov (United States)

    1984-03-01

    variational integ,:ral wa xnndas a -. e-thod of determining, whater thie finite-difference technrdiue or thie firnite-ele:.ent technmicue --ave a mrore...boundaries (Dirich- let boundary conditions). Other boundary conditions could produce a change in the integral that is to be extremized. A method of...t (n) HII!.( - , ___ i_(3.38) The difference between successive iterations was used to calculate the percent change in temperature I a")I t (n

  16. Sea level and climate variations

    NARCIS (Netherlands)

    Oerlemans, J.

    1985-01-01

    Review paper, ESA Symposium on Application of Satellite Data to Climate Modelling. Alpbach (Austria) Sea level is an essential component of the climate system, on which many human activities in the coastal zone depend. Climate variations leading to changes in relative sea level are

  17. Simultaneous inference of selection and population growth from patterns of variation in the human genome

    DEFF Research Database (Denmark)

    Williamson, Scott H.; Hernandez, Ryan; Fledel-Alon, Adi

    2005-01-01

    Natural selection and demographic forces can have similar effects on patterns of DNA polymorphism. Therefore, to infer selection from samples of DNA sequences, one must simultaneously account for demographic effects. Here we take a model-based approach to this problem by developing predictions fo......-specific methods, and (iii) strong evidence for very recent population growth....... for patterns of polymorphism in the presence of both population size change and natural selection. If data are available from different functional classes of variation, and a priori information suggests that mutations in one of those classes are selectively neutral, then the putatively neutral class can...

  18. Variational Iteration Method for Nonlinear Singular Two-Point Boundary Value Problems Arising in Human Physiology

    Directory of Open Access Journals (Sweden)

    Marwan Abukhaled

    2013-01-01

    Full Text Available The variational iteration method is applied to solve a class of nonlinear singular boundary value problems that arise in physiology. The process of the method, which produces solutions in terms of convergent series, is explained. The Lagrange multipliers needed to construct the correctional functional are found in terms of the exponential integral and Whittaker functions. The method easily overcomes the obstacle of singularities. Examples will be presented to test the method and compare it to other existing methods in order to confirm fast convergence and significant accuracy.

  19. Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans.

    Science.gov (United States)

    Donkin, Ida; Versteyhe, Soetkin; Ingerslev, Lars R; Qian, Kui; Mechta, Mie; Nordkap, Loa; Mortensen, Brynjulf; Appel, Emil Vincent R; Jørgensen, Niels; Kristiansen, Viggo B; Hansen, Torben; Workman, Christopher T; Zierath, Juleen R; Barrès, Romain

    2016-02-09

    Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Towards a comprehensive structural variation map of an individual human genome.

    Science.gov (United States)

    Pang, Andy W; MacDonald, Jeffrey R; Pinto, Dalila; Wei, John; Rafiq, Muhammad A; Conrad, Donald F; Park, Hansoo; Hurles, Matthew E; Lee, Charles; Venter, J Craig; Kirkness, Ewen F; Levy, Samuel; Feuk, Lars; Scherer, Stephen W

    2010-01-01

    Several genomes have now been sequenced, with millions of genetic variants annotated. While significant progress has been made in mapping single nucleotide polymorphisms (SNPs) and small (genome differs from the reference assembly, and the analysis of the genomes sequenced to date have shown varying results for copy number variation (CNV) and inversions. We have combined computational re-analysis of existing whole genome sequence data with novel microarray-based analysis, and detect 12,178 structural variants covering 40.6 Mb that were not reported in the initial sequencing of the first published personal genome. We estimate a total non-SNP variation content of 48.8 Mb in a single genome. Our results indicate that this genome differs from the consensus reference sequence by approximately 1.2% when considering indels/CNVs, 0.1% by SNPs and approximately 0.3% by inversions. The structural variants impact 4,867 genes, and >24% of structural variants would not be imputed by SNP-association. Our results indicate that a large number of structural variants have been unreported in the individual genomes published to date. This significant extent and complexity of structural variants, as well as the growing recognition of their medical relevance, necessitate they be actively studied in health-related analyses of personal genomes. The new catalogue of structural variants generated for this genome provides a crucial resource for future comparison studies.

  1. The Database of Genomic Variants: a curated collection of structural variation in the human genome.

    Science.gov (United States)

    MacDonald, Jeffrey R; Ziman, Robert; Yuen, Ryan K C; Feuk, Lars; Scherer, Stephen W

    2014-01-01

    Over the past decade, the Database of Genomic Variants (DGV; http://dgv.tcag.ca/) has provided a publicly accessible, comprehensive curated catalogue of structural variation (SV) found in the genomes of control individuals from worldwide populations. Here, we describe updates and new features, which have expanded the utility of DGV for both the basic research and clinical diagnostic communities. The current version of DGV consists of 55 published studies, comprising >2.5 million entries identified in >22,300 genomes. Studies included in DGV are selected from the accessioned data sets in the archival SV databases dbVar (NCBI) and DGVa (EBI), and then further curated for accuracy and validity. The core visualization tool (gbrowse) has been upgraded with additional functions to facilitate data analysis and comparison, and a new query tool has been developed to provide flexible and interactive access to the data. The content from DGV is regularly incorporated into other large-scale genome reference databases and represents a standard data resource for new product and database development, in particular for copy number variation testing in clinical labs. The accurate cataloguing of variants in DGV will continue to enable medical genetics and genome sequencing research.

  2. Intra- and interhemispheric variations of diffusivity in subcortical white matter in normal human brain

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiura, Takashi; Noguchi, Tomoyuki; Hiwatashi, Akio; Togao, Osamu; Yamashita, Koji; Nagao, Eiki; Kamano, Hironori; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Fukuoka (Japan)

    2010-01-15

    Our purpose was to reveal potential regional variations in water molecular diffusivity within each cerebral hemisphere and across the right and left hemispheres. Diffusion-weighted images of 44 healthy right-handed adult male subjects were obtained using a diffusion tensor imaging sequence. Mean diffusivity (MD) values in subcortical white matter (WM) within 39 regions in each hemisphere were measured using an automated method. Intrahemispheric comparisons of MDs in subcortical WM were performed among six brain regions (frontal, parietal, occipital and temporal lobes and pre- and postcentral gyri). Interhemispheric comparisons of MDs were performed between the right and left counterparts of the 39 regions. In both hemispheres, diffusivity in the precentral gyrus was lower than those in other regions, while diffusivity in the parietal lobe was higher than others. MD asymmetry in which the left was lower than the right was found in the parietal lobe, middle occipital gyrus, and medial and orbital aspects of the frontal lobe. The converse asymmetry was revealed in the frontal operculum, supplementary motor cortex, temporal lobe, limbic cortices, precuneus and cuneus. Our results revealed significant intra- and interhemispheric regional variations in MD in subcortical WM, which may be related to different densities of axons and myelin sheaths. (orig.)

  3. Common variation in ISL1 confers genetic susceptibility for human congenital heart disease.

    Directory of Open Access Journals (Sweden)

    Kristen N Stevens

    Full Text Available Congenital heart disease (CHD is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1 is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant-common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations.

  4. The variations of human sex ratio at birth during and after wars, and their potential explanations.

    Science.gov (United States)

    James, William H

    2009-03-07

    Data on wartime sex ratios (proportions male at birth) are reviewed. Two sorts of variation are empirically well supported viz. (a) rises during and just after both World Wars and (b) a fall in Iran during the Iran-Iraq War. Potential explanations are offered here for these rises and fall. The fall seems plausibly explained by psychological stress causing pregnant women disproportionately to abort male fetuses. The rises may be explained by either or both of two different forms of hypothesis viz. (i) Kanazawa's "returning soldier" hypothesis and (ii) variation in coital rates. The coital rate hypothesis potentially accounts, in slightly different ways, for the rises both during, and just after, some wars. The argument that coital rate affects sex ratio just after wars seems to be supported by evidence that in some combatant countries, dizygotic (DZ) twinning rates (which also reportedly vary with coital rate) peaked after the World Wars. The suggestion that war is associated with rises in sex ratio at birth was first made more than two centuries ago. However, I have been unable to locate direct supporting sex ratio data relating to any conflict before World War One. So it would be useful if historical demographers were to search for such data relating to these earlier wars.

  5. Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans

    DEFF Research Database (Denmark)

    Donkin, Ida; Versteyhe, Soetkin; Ingerslev, Lars R.

    2016-01-01

    Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized...... and offers insight into how obesity may propagate metabolic dysfunction to the next generation....... that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort...

  6. Cognitive representation of human action: theory, applications, and perspectives

    Directory of Open Access Journals (Sweden)

    Christian eSeegelke

    2016-02-01

    Full Text Available In this perspective article, we propose a cognitive architecture model of human action that stresses the importance of cognitive representations stored in long-term memory (LTM as reference structures underlying and guiding voluntary motor performance. We introduce an experimental approach to ascertain cognitive representation structures, and provide evidence from a variety of different studies, ranging from basic research in manual action to application-oriented research such as athlete performance and rehabilitation. As results from these studies strongly support the presence of functional links between cognitive and motor processes, we regard this approach as a suitable and valuable tool for a variety of different disciplines related to cognition and movement. We conclude this article by highlighting current advances in ongoing research projects aimed at improving interaction capabilities in technical systems, particularly for rehabilitation and everyday support of the elderly, and outline future research directions.

  7. Genetic variation and population structure in the endangered Hermann's tortoise: the roles of geography and human-mediated processes.

    Science.gov (United States)

    Perez, Melanie; Livoreil, Barbara; Mantovani, Sara; Boisselier, Marie-Catherine; Crestanello, Barbara; Abdelkrim, Jawad; Bonillo, Céline; Goutner, Vassilis; Lambourdière, Josie; Pierpaoli, Massimo; Sterijovski, Bogoljub; Tomovic, Ljiljana; Vilaça, Sibelle T; Mazzotti, Stefano; Bertorelle, Giorgio

    2014-01-01

    The Hermann's tortoise (Testudo hermanni) is an endangered land tortoise distributed in disjoint populations across Mediterranean Europe. We investigated its genetic variation by typing 1 mitochondrial locus and 9 nuclear microsatellites in approximately 300 individuals from 22 localities. Our goal was to understand the relative impact of natural and human-mediated processes in shaping the genetic structure and to identify the genetic priorities for the conservation of this species. We found that 1) all geographic areas are highly differentiated, mainly as a function of their distance but with a clear genetic discontinuity (F st values larger than 0.4) between the Eastern and the Western subspecies; 2) the contact zone between subspecies is located farthest to the west than previously believed, and it probably coincides with the delta of the largest Italian river; 3) extinction events due to climatic conditions in the Upper Palaeolithic and subsequent human-mediated translocations in the Neolithic possibly explain the unexpected similarity among Spain, Sicily, and Corsica. For conservation purposes, the large majority of genetic pools appears native although hybridization among subspecies, related to extensive 20th century trade of tortoises across Europe, is observed in Spain and some Italian samples. Most populations do not seem at immediate risk of low genetic variation, except the French population, which has very low nuclear genetic diversity (heterozygosity = 0.25) and where 50 out of 51 sampled animals shared the same mitochondrial sequence. In general, restocking and reintroduction plans should carefully consider the genetic background of the individuals.

  8. Demographic and spatio-temporal variation in human plague at a persistent focus in Tanzania

    DEFF Research Database (Denmark)

    Davis, S; Makundi, R H; Machang'u, R S

    2006-01-01

    Human plague in the Western Usambara Mountains in Tanzania has been a public health problem since the first outbreak in 1980. The wildlife reservoir is unknown and eradication measures that have proved effective elsewhere in Tanzania appear to fail in this region. We use census data from 2002 and...

  9. Recombination networks as genetic markers in a human variation study of the Old World.

    NARCIS (Netherlands)

    Javed, A.; Mele, M.; Pybus, M.; Zalloua, P.; Haber, M.; Comas, D.; Netea, M.G.; Balanovsky, O.; Balanovska, E.; Jin, L.; Yang, Y.; Arunkumar, G.; Pitchappan, R.; Bertranpetit, J.; Calafell, F.; Parida, L.

    2012-01-01

    We have analyzed human genetic diversity in 33 Old World populations including 23 populations obtained through Genographic Project studies. A set of 1,536 SNPs in five X chromosome regions were genotyped in 1,288 individuals (mostly males). We use a novel analysis employing subARG network

  10. Systematic variation of population receptive field properties across cortical depth in human visual cortex

    NARCIS (Netherlands)

    Fracasso, Alessio; Petridou, N; Dumoulin, Serge O

    2016-01-01

    Receptive fields (RFs) in visual cortex are organized in antagonistic, center-surround, configurations. RF properties change systematically across eccentricity and between visual field maps. However, it is unknown how center-surround configurations are organized in human visual cortex across lamina.

  11. Age-related variations in the microstructure of human tibial cancellous bone

    DEFF Research Database (Denmark)

    Ding, Ming; Odgaard, A; Linde, F

    2002-01-01

    -related changes in the three-dimensional (3D) microstructure of human tibial cancellous bone. One hundred and sixty cylindrical cancellous bone specimens were produced from 40 normal proximal tibiae from 40 donors, aged 16-85 years. These specimens were micro-computed tomography (micro-CT) scanned...

  12. A Functional Genomics Approach to Understand Variation in Cytokine Production in Humans

    NARCIS (Netherlands)

    Li, Y.; Oosting, M.; Smeekens, S.P.; Jaeger, M.; Aguirre-Gamboa, R.; Le, K.T.; Deelen, P.; Ricano-Ponce, I.; Schoffelen, T.; Jansen, A.F.; Swertz, M.A.; Withoff, S.; Vosse, E. van de; Deuren, M. van; Veerdonk, F. Van de; Zhernakova, A.; Meer, J.W. van der; Xavier, R.J.; Franke, L.; Joosten, L.A.; Wijmenga, C.; Kumar, V.; Netea, M.G.

    2016-01-01

    As part of the Human Functional Genomics Project, which aims to understand the factors that determine the variability of immune responses, we investigated genetic variants affecting cytokine production in response to ex vivo stimulation in two independent cohorts of 500 and 200 healthy individuals.

  13. Enamel thickness variation of deciduous first and second upper molars in modern humans and Neanderthals.

    Science.gov (United States)

    Fornai, Cinzia; Benazzi, Stefano; Svoboda, Jiří; Pap, Ildikó; Harvati, Katerina; Weber, Gerhard W

    2014-11-01

    Enamel thickness and dental tissue proportions have been recognized as effective taxonomic discriminators between Neanderthal and modern humans teeth. However, most of the research on this topic focused on permanent teeth, and little information is available for the deciduous dentition. Moreover, although worn teeth are more frequently found than unworn teeth, published data for worn teeth are scarce and methods for the assessment of their enamel thickness need to be developed. Here, we addressed this issue by studying the 2D average enamel thickness (AET) and 2D relative enamel thickness (RET) of Neanderthal and modern humans unworn to moderately worn upper first deciduous molars (dm(1)s) and upper second deciduous molars (dm(2)s). In particular, we used 3D μCT data to investigate the mesial section for dm(1)s and both mesial and buccal sections for dm(2)s. Our results confirmed previous findings of an Neanderthal derived condition of thin enamel, and thinner enamel in dm(1)s than dm(2)s in both Neanderthal and modern humans. We demonstrated that the Neanderthal 2D RET indices are significantly lower than those of modern humans at similar wear stages in both dm(1)s and dm(2)s (p Neanderthal unworn to moderately worn upper deciduous molars. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Nocturnal variations in subcutaneous blood flow rate in lower leg of normal human subjects

    DEFF Research Database (Denmark)

    Sindrup, J H; Kastrup, J; Jørgensen, B

    1991-01-01

    Subcutaneous adipose tissue blood flow rate was measured in the lower leg of 22 normal human subjects over 12- to 20-h ambulatory conditions. The 133Xe washout technique, portable CdTe(Cl) detectors, and a portable data storage unit were used. The tracer depot was applied on the medial aspect...

  15. Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans

    DEFF Research Database (Denmark)

    Donkin, Ida; Versteyhe, Soetkin; Ingerslev, Lars R.

    2016-01-01

    of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure...

  16. Variation in osteocyte lacunar morphology and density in the human femur - a synchrotron radiation micro-CT study

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Yasmin; Thomas, C David L.; Clement, John G; Peele, Andrew G; Hannah, Kevin; Cooper, David M.L. [Aust. Synch.; (La Trobe); (Saskatchewan); (Melbourne)

    2013-04-09

    In recent years there has been growing interest in the spatial properties of osteocytes (including density and morphology) and how these potentially relate to adaptation, disease and aging. This interest has, in part, arisen from the availability of increasingly high-resolution 3D imaging modalities such as synchrotron radiation (SR) micro-CT. As resolution increases, field of view generally decreases. Thus, while increasingly detailed spatial information is obtained, it is unclear how representative this information is of the skeleton or even the isolated bone. The purpose of this research was to describe the variation in osteocyte lacunar density, morphology and orientation within the femur from a healthy young male human. Multiple anterior, posterior, medial and lateral blocks (2 mm × 2 mm) were prepared from the proximal femoral shaft and SR micro-CT imaged at the Advanced Photon Source. Average lacunar densities (± standard deviation) from the anterior, posterior, medial and lateral regions were 27,169 ± 1935, 26,3643 ± 1262, 37,521 ± 6416 and 33,972 ± 2513 lacunae per mm3 of bone tissue, respectively. These values were significantly different between the medial and both the anterior and posterior regions (p < 0.05). The density of the combined anterior and posterior regions was also significantly lower (p = 0.001) than the density of the combined medial and lateral regions. Although no difference was found in predominant orientation, shape differences were found; with the combined anterior and posterior regions having more elongated (p = 0.004) and flattened (p = 0.045) lacunae, than those of the medial and lateral regions. This study reveals variation in osteocyte lacunar density and morphology within the cross-section of a single bone and that this variation can be considerable (up to 30% difference in density between regions). The underlying functional significance of the observed variation in lacunar density likely relates to localized

  17. Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV.

    Directory of Open Access Journals (Sweden)

    Debra A Wadford

    Full Text Available RT-SHIV is a chimera of simian immunodeficiency virus (SIV containing the reverse transcriptase (RT-encoding region of human immunodeficiency virus type 1 (HIV-1 within the backbone of SIVmac239. It has been used in a non-human primate model for studies of non-nucleoside RT inhibitors (NNRTI and highly active antiretroviral therapy (HAART. We and others have identified several mutations that arise in the "foreign" HIV-1 RT of RT-SHIV during in vivo replication. In this study we catalogued amino acid substitutions in the HIV-1 RT and in regions of the SIV backbone with which RT interacts that emerged 30 weeks post-infection from seven RT-SHIV-infected rhesus macaques. The virus set points varied from relatively high virus load, moderate virus load, to undetectable virus load. The G196R substitution in RT was detected from 6 of 7 animals at week 4 post-infection and remained in virus from 4 of 6 animals at week 30. Virus from four high virus load animals showed several common mutations within RT, including L74V or V75L, G196R, L214F, and K275R. The foreign RT from high virus load isolates exhibited as much variation as that of the highly variable envelope surface glycoprotein, and 10-fold higher than that of the native RT of SIVmac239. Isolates from moderate virus load animals showed much less variation in the foreign RT than the high virus load isolates. No variation was found in SIVmac239 genes known to interact with RT. Our results demonstrate substantial adaptation of the foreign HIV-1 RT in RT-SHIV-infected macaques, which most likely reflects selective pressure upon the foreign RT to attain optimal activity within the context of the chimeric RT-SHIV and the rhesus macaque host.

  18. The role of climate and human changes on inter-annual variation in stream nitrate fluxes and concentrations

    Science.gov (United States)

    Philippe, M.; Gascuel, C.; Pierre, A.; Patrick, D.; Laurent, R.; Jérome, M.

    2010-12-01

    In recent decades, temporal variations in nitrate fluxes and concentrations in temperate rivers have resulted from the interaction of anthropogenic and climatic factors. The effect of climatic drivers remains unclear, while the relative importance of the drivers seems to be highly site dependent. This paper focuses on 2-6 years variations called meso-scale variations, and analyses the climatic drivers of these variations in a study site characterized by high N inputs from intensive animal farming systems and shallow aquifers with impervious bedrock in a temperate climate. Three approaches are developed: 1) an analysis of long-term records (30-40 years) of nitrate fluxes and nitrate concentrations in 30 coastal rivers of Western France, which were well-marked by meso-scale cycles in the fluxes and concentration with a slight hysteresis; 2) a test of the climatic control using a lumped two box model, which demonstrates that hydrological assumptions are sufficient to explain these meso-scale cycles; and 3) a model of nitrate fluxes and concentrations in two contrasted catchments subjected to recent mitigation measures, which analyses nitrate fluxes and concentrations in relation to N stored in groundwater. In coastal rivers, hydrological drivers (i.e., effective rainfall), and particularly the dynamics of the water table and rather stable nitrate concentration, explain the meso-scale cyclic patterns. In the headwater catchment, agricultural and hydrological drivers can interact according their settings. The requirements to better distinguish the effect of climate and human changes in integrated water management are addressed: long term monitoring, coupling the analysis and the modelling of large sets of catchments incorporating different sizes, land uses and environmental factors. (Figure : Discharge, nitrate concentrations and fluxes in the Aulne river from 1973 to 2007.)

  19. APPLICABILITY OF A HUMAN LACTOFERRIN IN PEDIATRIC PRACTICE

    Directory of Open Access Journals (Sweden)

    T. E. Borovik

    2014-01-01

    Full Text Available Modern data on efficiency and safety of a recombinant human lactoferrin (hLf and prospects of its use in pediatric practice are presented in the review of literary data. The unique anti-infectious properties of biologically active protein of the hLf, its high antimicrobic, antiviral, antifungal and anti-parasitic activity are noted. Ability to stimulate natural immunity, to interact with other antimicrobic peptides, in particular, with lysozyme and secretory leukocyte protease inhibitor is analysed. In this regard it is indicated prospects of application of the hLf in treatment of prematurely born and hypotrophic children, patients with chronic nutritional deficiency for the purpose of prevention of infectious diseases and correction of inflammatory changes in the organism of a child, includingacute respiratory virus and enteric infections in children. It is expedient to apply hLf in surgical practice for reduction of a degree of manifestation of the acute pro-inflammatory response, and also for prevention of infectious complications, especially after abdominal operations, in complex treatment of children with a severe generalized infection and multi-organ failure, for prevention of intrahospital nosocomial infections in children hospitals.Key words: children, prematurely born, nutritional deficiency, infections, lactoferrin, recombinant human lactoferrin.

  20. Genetic Variations in the Human Cannabinoid Receptor Gene Are Associated with Happiness

    Science.gov (United States)

    Matsunaga, Masahiro; Isowa, Tokiko; Yamakawa, Kaori; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Ohira, Hideki

    2014-01-01

    Happiness has been viewed as a temporary emotional state (e.g., pleasure) and a relatively stable state of being happy (subjective happiness level). As previous studies demonstrated that individuals with high subjective happiness level rated their current affective states more positively when they experience positive events, these two aspects of happiness are interrelated. According to a recent neuroimaging study, the cytosine to thymine single-nucleotide polymorphism of the human cannabinoid receptor 1 gene is associated with sensitivity to positive emotional stimuli. Thus, we hypothesized that our genetic traits, such as the human cannabinoid receptor 1 genotypes, are closely related to the two aspects of happiness. In Experiment 1, 198 healthy volunteers were used to compare the subjective happiness level between cytosine allele carriers and thymine-thymine carriers of the human cannabinoid receptor 1 gene. In Experiment 2, we used positron emission tomography with 20 healthy participants to compare the brain responses to positive emotional stimuli of cytosine allele carriers to that of thymine-thymine carriers. Compared to thymine-thymine carriers, cytosine allele carriers have a higher subjective happiness level. Regression analysis indicated that the cytosine allele is significantly associated with subjective happiness level. The positive mood after watching a positive film was significantly higher for the cytosine allele carriers compared to the thymine-thymine carriers. Positive emotion-related brain region such as the medial prefrontal cortex was significantly activated when the cytosine allele carriers watched the positive film compared to the thymine-thymine carriers. Thus, the human cannabinoid receptor 1 genotypes are closely related to two aspects of happiness. Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater magnitude

  1. Genetic variations in the human cannabinoid receptor gene are associated with happiness.

    Science.gov (United States)

    Matsunaga, Masahiro; Isowa, Tokiko; Yamakawa, Kaori; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Ohira, Hideki

    2014-01-01

    Happiness has been viewed as a temporary emotional state (e.g., pleasure) and a relatively stable state of being happy (subjective happiness level). As previous studies demonstrated that individuals with high subjective happiness level rated their current affective states more positively when they experience positive events, these two aspects of happiness are interrelated. According to a recent neuroimaging study, the cytosine to thymine single-nucleotide polymorphism of the human cannabinoid receptor 1 gene is associated with sensitivity to positive emotional stimuli. Thus, we hypothesized that our genetic traits, such as the human cannabinoid receptor 1 genotypes, are closely related to the two aspects of happiness. In Experiment 1, 198 healthy volunteers were used to compare the subjective happiness level between cytosine allele carriers and thymine-thymine carriers of the human cannabinoid receptor 1 gene. In Experiment 2, we used positron emission tomography with 20 healthy participants to compare the brain responses to positive emotional stimuli of cytosine allele carriers to that of thymine-thymine carriers. Compared to thymine-thymine carriers, cytosine allele carriers have a higher subjective happiness level. Regression analysis indicated that the cytosine allele is significantly associated with subjective happiness level. The positive mood after watching a positive film was significantly higher for the cytosine allele carriers compared to the thymine-thymine carriers. Positive emotion-related brain region such as the medial prefrontal cortex was significantly activated when the cytosine allele carriers watched the positive film compared to the thymine-thymine carriers. Thus, the human cannabinoid receptor 1 genotypes are closely related to two aspects of happiness. Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater magnitude

  2. Considerable variation in the concentration of osteopontin in human milk, bovine milk, and infant formulas.

    Science.gov (United States)

    Schack, L; Lange, A; Kelsen, J; Agnholt, J; Christensen, B; Petersen, T E; Sørensen, E S

    2009-11-01

    Osteopontin (OPN) is a multifunctional bioactive protein that is implicated in numerous biological processes such as bone remodeling, inhibition of ectopic calcification, and cellular adhesion and migration, as well as several immune functions. Osteopontin has cytokine-like properties and is a key factor in the initiation of T helper 1 immune responses. Osteopontin is present in most tissues and body fluids, with the highest concentrations being found in milk. In the present study, ELISA for human and bovine milk OPN were developed and OPN concentration in human breast milk, bovine milk, and infant formulas was measured and compared. The OPN concentration in human milk was measured to approximately 138 mg/L, which corresponds to 2.1% (wt/wt) of the total protein in human breast milk. This is considerably higher than the corresponding OPN concentrations in bovine milk (approximately 18 mg/L) and infant formulas (approximately 9 mg/L). Moreover, bovine milk OPN is shown to induce the expression of the T helper 1 cytokine IL-12 in cultured human lamina propria mononuclear cells isolated from intestinal biopsies. Finally, the OPN concentration in plasma samples from umbilical cords, 3-mo-old infants, and pregnant and nonpregnant adults was measured. The OPN level in plasma from 3-mo-old infants and umbilical cords was found to be 7 to 10 times higher than in adults. Thus, the high levels of OPN in milk and infant plasma suggest that OPN is important to infants and that ingested milk OPN is likely to induce cytokine production in neonate intestinal immune cells.

  3. Genetic variations in the human cannabinoid receptor gene are associated with happiness.

    Directory of Open Access Journals (Sweden)

    Masahiro Matsunaga

    Full Text Available Happiness has been viewed as a temporary emotional state (e.g., pleasure and a relatively stable state of being happy (subjective happiness level. As previous studies demonstrated that individuals with high subjective happiness level rated their current affective states more positively when they experience positive events, these two aspects of happiness are interrelated. According to a recent neuroimaging study, the cytosine to thymine single-nucleotide polymorphism of the human cannabinoid receptor 1 gene is associated with sensitivity to positive emotional stimuli. Thus, we hypothesized that our genetic traits, such as the human cannabinoid receptor 1 genotypes, are closely related to the two aspects of happiness. In Experiment 1, 198 healthy volunteers were used to compare the subjective happiness level between cytosine allele carriers and thymine-thymine carriers of the human cannabinoid receptor 1 gene. In Experiment 2, we used positron emission tomography with 20 healthy participants to compare the brain responses to positive emotional stimuli of cytosine allele carriers to that of thymine-thymine carriers. Compared to thymine-thymine carriers, cytosine allele carriers have a higher subjective happiness level. Regression analysis indicated that the cytosine allele is significantly associated with subjective happiness level. The positive mood after watching a positive film was significantly higher for the cytosine allele carriers compared to the thymine-thymine carriers. Positive emotion-related brain region such as the medial prefrontal cortex was significantly activated when the cytosine allele carriers watched the positive film compared to the thymine-thymine carriers. Thus, the human cannabinoid receptor 1 genotypes are closely related to two aspects of happiness. Compared to thymine-thymine carriers, the cytosine allele carriers of the human cannabinoid receptor 1 gene, who are sensitive to positive emotional stimuli, exhibited greater

  4. A potential role for a genetic variation of AKAP5 in human aggression and anger control

    Directory of Open Access Journals (Sweden)

    Sylvia eRichter

    2011-12-01

    Full Text Available The A-kinase-anchoring protein 5 (AKAP5, a post-synaptic multi-adaptor molecule that binds G-protein-coupled receptors (GPCRs and intracellular signaling molecules has been implicated in emotional processing in rodents, but its role in human emotion and behavior is up to now still not quite clear. Here, we report an association of individual differences in aggressive behavior and anger expression with a functional genetic polymorphism (Pro100Leu in the human AKAP5 gene. Among a cohort of 527 young, healthy individuals, carriers of the less common Leu allele (15.6% allele frequency scored significantly lower in the physical aggression domain of the Buss and Perry Aggression Questionnaire (BPAQ and higher in the anger control dimension of the State-Trait Anger Expression Inventory (STAXI. In a functional magnetic resonance imaging (fMRI experiment we could further demonstrate that AKAP5 Pro100Leu modulates the interaction of negative emotional processing and executive functions. To investigate implicit control-processes of anger control, we used the well-known flanker-task in order to evoke processes of action-monitoring and error-processing and added task-irrelevant neutral or angry faces in the background of the flanker stimuli. In line with our predictions, Leu carriers showed increased activation of the anterior cingulate cortex (ACC during emotional interference, which in turn predicted shorter reaction times and might be related to stronger control of emotional interference. Conversely, Pro homozygotes exhibited increased orbitofrontal cortex (OFC activation during emotional interference, with no behavioral advantage. Immunohistochemistry revealed AKAP5 expression in the human ACC and OFC. Our results suggest that AKAP5 Pro100Leu contributes to individual differences in human aggression and anger. Further research is warranted to explore the detailed role of AKAP5 in human emotional processing.

  5. Ameliorant Application on Variation of Carbon Stock and Ash Content on Peatland South Kalimantan

    Directory of Open Access Journals (Sweden)

    Siti Nurzakiah

    2013-03-01

    Full Text Available Carbon stock on peatlands are large and will be easily emitted if the land is opened or drained, therefore the measurements of carbon stocks and ash content are important to know the amount of emissions and agricultural sustainability in peatlands. This study aimed to determine carbon stock and ash content on peatlands in the Indonesia Climate Change Trust Fund (ICCTF located in South Kalimantan on the geographic position S. 03°25’52" and E. 114°47’6.5". The experiment consisted of six treatments of ameliorant materials namely; mineral soil, peat fertilizer A, peat fertilizer T, manure, ash, and control. The results showed that the variation of peat soil properties was very high at this location. Peat thickness ranged from 36-338 cm, and this led to high variations in carbon stocks ranged between 161.8 – 1142.2 Mg ha-1. Besides ash contents of the soil were also highly varied ranged from 3.4 – 28.5%. This natural variation greatly affected the ICCTF study design. Mineral soil treatment had a mean carbon stock (961.3 ± 61.5 Mg ha-1 which was higher and different from other treatments. High ash content was obtained in the ash treatment (18.6 ± 2.5% and manure (15.7 ± 3.6%. It is recommended that the analysis of plant responses and greenhouse gas emissions using a single regression analysis and multiple regression with ash content as one of the independent variables are needed.

  6. A variational treatment of material configurations with application to interface motion and microstructural evolution

    Science.gov (United States)

    Teichert, Gregory H.; Rudraraju, Shiva; Garikipati, Krishna

    2017-02-01

    We present a unified variational treatment of evolving configurations in crystalline solids with microstructure. The crux of our treatment lies in the introduction of a vector configurational field. This field lies in the material, or configurational, manifold, in contrast with the traditional displacement field, which we regard as lying in the spatial manifold. We identify two distinct cases which describe (a) problems in which the configurational field's evolution is localized to a mathematically sharp interface, and (b) those in which the configurational field's evolution can extend throughout the volume. The first case is suitable for describing incoherent phase interfaces in polycrystalline solids, and the latter is useful for describing smooth changes in crystal structure and naturally incorporates coherent (diffuse) phase interfaces. These descriptions also lead to parameterizations of the free energies for the two cases, from which variational treatments can be developed and equilibrium conditions obtained. For sharp interfaces that are out-of-equilibrium, the second law of thermodynamics furnishes restrictions on the kinetic law for the interface velocity. The class of problems in which the material undergoes configurational changes between distinct, stable crystal structures are characterized by free energy density functions that are non-convex with respect to configurational strain. For physically meaningful solutions and mathematical well-posedness, it becomes necessary to incorporate interfacial energy. This we have done by introducing a configurational strain gradient dependence in the free energy density function following ideas laid out by Toupin (1962, Elastic materials with couple-stresses. Arch. Ration. Mech. Anal., 11, 385-414). The variational treatment leads to a system of partial differential equations governing the configuration that is coupled with the traditional equations of nonlinear elasticity. The coupled system of equations governs

  7. Plants as Factories for Human Pharmaceuticals: Applications and Challenges

    Directory of Open Access Journals (Sweden)

    Jian Yao

    2015-12-01

    Full Text Available Plant molecular farming (PMF, defined as the practice of using plants to produce human therapeutic proteins, has received worldwide interest. PMF has grown and advanced considerably over the past two decades. A number of therapeutic proteins have been produced in plants, some of which have been through pre-clinical or clinical trials and are close to commercialization. Plants have the potential to mass-produce pharmaceutical products with less cost than traditional methods. Tobacco-derived antibodies have been tested and used to combat the Ebola outbreak in Africa. Genetically engineered immunoadhesin (DPP4-Fc produced in green plants has been shown to be able to bind to MERS-CoV (Middle East Respiratory Syndrome, preventing the virus from infecting lung cells. Biosafety concerns (such as pollen contamination and immunogenicity of plant-specific glycans and costly downstream extraction and purification requirements, however, have hampered PMF production from moving from the laboratory to industrial application. In this review, the challenges and opportunities of PMF are discussed. Topics addressed include; transformation and expression systems, plant bioreactors, safety concerns, and various opportunities to produce topical applications and health supplements.

  8. Quantitative historical analysis uncovers a single dimension of complexity that structures global variation in human social organization

    Science.gov (United States)

    Turchin, Peter; Currie, Thomas E.; Whitehouse, Harvey; François, Pieter; Feeney, Kevin; Mullins, Daniel; Hoyer, Daniel; Collins, Christina; Grohmann, Stephanie; Mendel-Gleason, Gavin; Turner, Edward; Dupeyron, Agathe; Cioni, Enrico; Reddish, Jenny; Levine, Jill; Jordan, Greine; Brandl, Eva; Williams, Alice; Cesaretti, Rudolf; Krueger, Marta; Ceccarelli, Alessandro; Figliulo-Rosswurm, Joe; Tuan, Po-Ju; Peregrine, Peter; Marciniak, Arkadiusz; Preiser-Kapeller, Johannes; Kradin, Nikolay; Korotayev, Andrey; Palmisano, Alessio; Baker, David; Bidmead, Julye; Bol, Peter; Christian, David; Cook, Connie; Covey, Alan; Feinman, Gary; Júlíusson, Árni Daníel; Kristinsson, Axel; Miksic, John; Mostern, Ruth; Petrie, Cameron; Rudiak-Gould, Peter; ter Haar, Barend; Wallace, Vesna; Mair, Victor; Xie, Liye; Baines, John; Bridges, Elizabeth; Manning, Joseph; Lockhart, Bruce; Bogaard, Amy; Spencer, Charles

    2018-01-01

    Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as “Seshat: Global History Databank.” We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years. We were able to capture information on 51 variables reflecting nine characteristics of human societies, such as social scale, economy, features of governance, and information systems. Our analyses revealed that these different characteristics show strong relationships with each other and that a single principal component captures around three-quarters of the observed variation. Furthermore, we found that different characteristics of social complexity are highly predictable across different world regions. These results suggest that key aspects of social organization are functionally related and do indeed coevolve in predictable ways. Our findings highlight the power of the sciences and humanities working together to rigorously test hypotheses about general rules that may have shaped human history. PMID:29269395

  9. The Human Thioredoxin System: Modifications and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Seyed Isaac Hashemy

    2011-03-01

    Full Text Available The thioredoxin system, comprising thioredoxin (Trx, thioredoxin reductase (TrxR and NADPH, is one of the major cellular antioxidant systems, implicated in a large and growing number of biological functions. Trx acts as an oxidoreductase via a highly conserved dithiol/disulfide motif located in the active site (-Trp-Cys-Gly-Pro-Cys-Lys-. Different factors are involved in the regulation of Trx activity, including its expression level, localization, protein-protein interactions, post-translational modifications and some chemical inhibitors. Mammalian TrxRs are selenoproteins which have a –Cys-Val-Asn-Val-Gly-Cys- N-terminal active site, as well as a C-terminal selenium-containing active site. Besides two Cys-residues in the redox-regulatory domain of cytosolic Trx (Trx1, human Trx1 has three additional Cys-residues. Post-translational modifications of human Trx1 which are involved in the regulation of its activity can happen via modification of Cys-residues including thiol oxidation, glutathionylation and S-nitrosylation or via modification of other amino acid residues such as nitration of Tyr-49. Because of the numerous functions of the thioredoxin system, its inhibition (mainly happens via the targeting TrxR can result in major cellular consequences, which are potentially pro-oxidant in nature, leading to cell death via necrosis or apoptosis if overexpression of Trx and other antioxidative enzymes can not recuperate cell response. Considering this feature, several anticancer drugs have been used which can inhibit TrxR. Elevated levels of Trx and/or TrxR have been reported in many different human malignancies, positively correlated with aggressive tumor growth and poor prognosis. Moreover, anti-oxidative and anti-apoptotic effects of Trx are reasons to study its clinical application as a drug.

  10. Variational approach to magnetic dipole core polarization: applications to moments and transitions

    Energy Technology Data Exchange (ETDEWEB)

    Lipparini, E.; Stringari, S.; Richter, A.

    1985-10-10

    A variational approach to magnetic dipole core polarization is discussed which goes beyond the usual perturbative treatment and takes the coupling between the collective magnetic dipole state and single particle states into account. Using various spin-dependent effective interactions simple expressions for corrections to the g-factors of the free nucleons are derived. The effect of the coupling of the collective M1 state in UYCa, ZZr and SYPb to single particle M1 moments and transitions in the neighbouring A=48+-1, 90+-1 and 208+-1 nuclei, respectively, is pointed out. (orig.).

  11. Human decision making based on variations in internal noise: an EEG study.

    Science.gov (United States)

    Amitay, Sygal; Guiraud, Jeanne; Sohoglu, Ediz; Zobay, Oliver; Edmonds, Barrie A; Zhang, Yu-Xuan; Moore, David R

    2013-01-01

    Perceptual decision making is prone to errors, especially near threshold. Physiological, behavioural and modeling studies suggest this is due to the intrinsic or 'internal' noise in neural systems, which derives from a mixture of bottom-up and top-down sources. We show here that internal noise can form the basis of perceptual decision making when the external signal lacks the required information for the decision. We recorded electroencephalographic (EEG) activity in listeners attempting to discriminate between identical tones. Since the acoustic signal was constant, bottom-up and top-down influences were under experimental control. We found that early cortical responses to the identical stimuli varied in global field power and topography according to the perceptual decision made, and activity preceding stimulus presentation could predict both later activity and behavioural decision. Our results suggest that activity variations induced by internal noise of both sensory and cognitive origin are sufficient to drive discrimination judgments.

  12. Human decision making based on variations in internal noise: an EEG study.

    Directory of Open Access Journals (Sweden)

    Sygal Amitay

    Full Text Available Perceptual decision making is prone to errors, especially near threshold. Physiological, behavioural and modeling studies suggest this is due to the intrinsic or 'internal' noise in neural systems, which derives from a mixture of bottom-up and top-down sources. We show here that internal noise can form the basis of perceptual decision making when the external signal lacks the required information for the decision. We recorded electroencephalographic (EEG activity in listeners attempting to discriminate between identical tones. Since the acoustic signal was constant, bottom-up and top-down influences were under experimental control. We found that early cortical responses to the identical stimuli varied in global field power and topography according to the perceptual decision made, and activity preceding stimulus presentation could predict both later activity and behavioural decision. Our results suggest that activity variations induced by internal noise of both sensory and cognitive origin are sufficient to drive discrimination judgments.

  13. Anatomical variations in lymphatic drainage of the right lung: applications in lung cancer surgery.

    Science.gov (United States)

    Ndiaye, Assane; Di-Marino, V; Ba, P S; Ndiaye, Aï; Gaye, M; Nazarian, S

    2016-12-01

    To specify the topography and variations in lymphatic drainage of the right lung to the mediastinum and their therapeutic implications in non-small cell lung cancers (NSCLC). We injected a dye into the subpleural lymphatic vessels in 65 right lung segments, followed by dissection in 22 subjects. At the upper lobe, we had injected 32 segments. We noted extrasegmental overflow in one case; extrasegmental and extralobar drainage in two cases; drainage to the lymph nodes of another lobe in one case. Fifty-six percent of the segments drained directly (skipping intrapulmonary and hilar lymph nodes) into the right paratracheal lymph nodes, and one dorsal segment drained into the thoracic duct. A ventral segment drained into the inferior tracheobronchial lymph nodes. A contralateral drainage to the recurrent chain was observed in two cases. Sixteen segments of the middle lobe were injected and mainly drained into the inferior tracheobronchial lymph nodes with six direct paths; one medial segment drained into the right anterior mediastinal chain. We noted three contralateral drainages and eight downward abdominal drainages. Out of the 17 segments of the lower lobe injected, 6 segments drained into the lymph nodes of another lobe, 5 segments showed a direct route to the lower quadrant chains. We noted one time a drainage into the paraesophageal lymph nodes. The variations in lymphatic drainage of the right lung require to carry out systematically a radical mediastinal lymphadenectomy during the removal of non-small cell lung cancers and to associate an adjuvant treatment.

  14. Method of continuous variations: applications of job plots to the study of molecular associations in organometallic chemistry.

    Science.gov (United States)

    Renny, Joseph S; Tomasevich, Laura L; Tallmadge, Evan H; Collum, David B

    2013-11-11

    Applications of the method of continuous variations (MCV or the Method of Job) to problems of interest to organometallic chemists are described. MCV provides qualitative and quantitative insights into the stoichiometries underlying association of m molecules of A and n molecules of B to form A(m)B(n) . Applications to complex ensembles probe associations that form metal clusters and aggregates. Job plots in which reaction rates are monitored provide relative stoichiometries in rate-limiting transition structures. In a specialized variant, ligand- or solvent-dependent reaction rates are dissected into contributions in both the ground states and transition states, which affords insights into the full reaction coordinate from a single Job plot. Gaps in the literature are identified and critiqued. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Bacterial community variation in human body habitats across space and time.

    Science.gov (United States)

    Costello, Elizabeth K; Lauber, Christian L; Hamady, Micah; Fierer, Noah; Gordon, Jeffrey I; Knight, Rob

    2009-12-18

    Elucidating the biogeography of bacterial communities on the human body is critical for establishing healthy baselines from which to detect differences associated with diseases. To obtain an integrated view of the spatial and temporal distribution of the human microbiota, we surveyed bacteria from up to 27 sites in seven to nine healthy adults on four occasions. We found that community composition was determined primarily by body habitat. Within habitats, interpersonal variability was high, whereas individuals exhibited minimal temporal variability. Several skin locations harbored more diverse communities than the gut and mouth, and skin locations differed in their community assembly patterns. These results indicate that our microbiota, although personalized, varies systematically across body habitats and time; such trends may ultimately reveal how microbiome changes cause or prevent disease.

  16. Nocturnal variations in peripheral blood flow, systemic blood pressure, and heart rate in humans

    DEFF Research Database (Denmark)

    Sindrup, J H; Kastrup, J; Christensen, H

    1991-01-01

    Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage uni.......0001). The synchronism of the nocturnal subcutaneous hyperemia and the decrease in systemic mean arterial blood pressure point to a common, possibly central nervous or humoral, eliciting mechanism.......Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage unit...

  17. Diurnal Variation of Human Sweet Taste Recognition Thresholds Is Correlated With Plasma Leptin Levels

    OpenAIRE

    Nakamura, Yuki; Sanematsu, Keisuke; Ohta, Rie; Shirosaki, Shinya; Koyano, Kiyoshi; Nonaka, Kazuaki; Shigemura, Noriatsu; Ninomiya, Yuzo

    2008-01-01

    OBJECTIVE?It has recently been proposed that the peripheral taste organ is one of the targets for leptin. In lean mice, leptin selectively suppresses gustatory neural and behavioral responses to sweet compounds without affecting responses to other taste stimuli, whereas obese diabetic db/db mice with defects in leptin receptor lack this leptin suppression on sweet taste. Here, we further examined potential links between leptin and sweet taste in humans. RESEARCH DESIGN AND METHODS?A total of ...

  18. Understanding variation in human movement - The good and the bad in motor variability

    OpenAIRE

    Ignasiak, Niklas

    2017-01-01

    A stable gait pattern and the ability to maintain upright posture are fundamental motor functions to support human bipedal locomotion. Both gait and balance deteriorate in response to age and pathology. In the context of aging western societies, maintaining secure ambulation is key to ensure the independence and mobility of individuals. Therefore, assessment of the quality of gait and balance performance is an essential aspect in the clinical management of aging as well as diseased population...

  19. Defining the role of common variation in the genomic and biological architecture of adult human height

    DEFF Research Database (Denmark)

    Wood, Andrew R.; Esko, Tonu; Yang, Jian

    2014-01-01

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated similar to 2,0......TOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants....

  20. Seasonal variation of technetium-99 in Fucus vesiculosus and its application as an oceanographic tracer

    Science.gov (United States)

    Shi, Keliang; Hou, Xiaolin; Roos, Per; Wu, Wangsuo; Nielsen, Sven P.

    2013-07-01

    The concentration of 99Tc was determined in archived time series seaweed samples collected at Klint (Denmark). The results demonstrate a significantly seasonal variation of 99Tc concentrations in Fucus vesiculosus with maximum values in winter and minimum values in summer. The mechanism driving this seasonal cycle was explored. With the measured 99Tc concentration in seawater collected in the same location and date as for seaweed, the concentration factor of F. vesiculosus to 99Tc was investigated. Constant value of concentration factors of 99Tc independence of sampling date, with an average value of (1.9 ± 0.5) × 105 L/kg, were obtained. This indicates that F. vesiculosus can be used as a reliable bio-indicator to monitor 99Tc concentration in seawater.

  1. Mathematical methods in physics distributions, Hilbert space operators, variational methods, and applications in quantum physics

    CERN Document Server

    Blanchard, Philippe

    2015-01-01

    The second edition of this textbook presents the basic mathematical knowledge and skills that are needed for courses on modern theoretical physics, such as those on quantum mechanics, classical and quantum field theory, and related areas.  The authors stress that learning mathematical physics is not a passive process and include numerous detailed proofs, examples, and over 200 exercises, as well as hints linking mathematical concepts and results to the relevant physical concepts and theories.  All of the material from the first edition has been updated, and five new chapters have been added on such topics as distributions, Hilbert space operators, and variational methods.   The text is divided into three main parts. Part I is a brief introduction to distribution theory, in which elements from the theories of ultradistributions and hyperfunctions are considered in addition to some deeper results for Schwartz distributions, thus providing a comprehensive introduction to the theory of generalized functions. P...

  2. Application of Stochastic variational method with correlated Ground States to coulombic systems

    Energy Technology Data Exchange (ETDEWEB)

    Usukura, Junko; Suzuki, Yasuyuki [Niigata Univ. (Japan); Varga, K.

    1998-07-01

    Positronium molecule, Ps{sub 2} has not been found experimentally yet, and it has been believed theoretically that Ps{sub 2} has only one bound state with L = 0. We predicted the existence of new bound state of Ps{sub 2}, which is the excited state with L = 1 and comes from Pauli principle, by Stochastic variational method. There are two decay mode with respect to Ps{sub 2}(P); one is pair annihilation and another is electric dipole (E1) transition to the ground state. While it is difficult to tell {gamma}-ray caused by annihilation of Ps{sub 2} from that of Ps since both of them have same energy, Energy (4.94 eV) of the photon emitted in E1 transition is specific enough to distinguish from other spectra. Then the excited state is one of clues to observe Ps{sub 2}. (author)

  3. Application of stochastic variational method to 3-4 body systems with realistic nuclear force

    Energy Technology Data Exchange (ETDEWEB)

    Ohbayashi, Yoshihide [Niigata Univ. (Japan); Varga, K.; Suzuki, Yoshiyuki

    1997-05-01

    SVM (stochastic variational method) was applied to simulate triton and alpha with realistic nuclear force such as Reid V8 (RV8), Argonne V6, V8 (AV6 and aV8). 3-4 body systems were solved by about 300-400 dimensions and the results were agreed with the most accurate solution. Convergence of energy of 3-4 body systems was rapid by using AV6 and AV8 potential, but it was slow by RV8 with strong repulsive force core. The energy values using SVM and GFMC were almost same. Number of dimension to convert the energy of triton was decreased by refinement. (S.Y.)

  4. On the maximum and minimum of two modified Gamma-Gamma variates with applications

    KAUST Repository

    Al-Quwaiee, Hessa

    2014-04-01

    In this work, we derive the statistical characteristics of the maximum and the minimum of two modified1 Gamma-Gamma variates in closed-form in terms of Meijer\\'s G-function and the extended generalized bivariate Meijer\\'s G-function. Then, we rely on these new results to present the performance analysis of (i) a dual-branch free-space optical selection combining diversity undergoing independent but not necessarily identically distributed Gamma-Gamma fading under the impact of pointing errors and of (ii) a dual-hop free-space optical relay transmission system. Computer-based Monte-Carlo simulations verify our new analytical results.

  5. Variations and voids: the regulation of human cloning around the world.

    Science.gov (United States)

    Pattinson, Shaun D; Caulfield, Timothy

    2004-12-13

    No two countries have adopted identical regulatory measures on cloning. Understanding the complexity of these regulatory variations is essential. It highlights the challenges associated with the regulation of a controversial and rapidly evolving area of science and sheds light on a regulatory framework that can accommodate this reality. Using the most reliable information available, we have performed a survey of the regulatory position of thirty countries around the world regarding the creation and use of cloned embryos (see Table 1). We have relied on original and translated legislation, as well as published sources and personal communications. We have examined the regulation of both reproductive cloning (RC) and non-reproductive cloning (NRC). While most of the countries studied have enacted national legislation, the absence of legislation in seven of these countries should not be equated with the absence of regulation. Senator Morin was not correct in stating that the majority of recent legislation bans both RC and NRC. Recent regulatory moves are united only with regard to the banning of RC. While NRC is not permitted in seventeen of the countries examined, it could be permitted in up to thirteen countries. There is little consensus on the various approaches to cloning laws and policies, and the regulatory position in many countries remains uncertain.

  6. [Genetic ecological monitoring in human populations: heterozygosity, mtDNA haplotype variation, and genetic load].

    Science.gov (United States)

    Balanovskiĭ, O P; Koshel', S M; Zaporozhchenko, V V; Pshenichnov, A S; Frolova, S A; Kuznetsova, M A; Baranova, E E; Teuchezh, I E; Kuznetsova, A A; Romashkina, M V; Utevskaia, O M; Churnosov, M I; Villems, R; Balanovskaia, E V

    2011-11-01

    Yu. P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool.

  7. Biochemical and genetic variation in Mycoplasma fermentans strains from cell line, human and animal sources.

    Science.gov (United States)

    Afshar, B; Nicholas, R A J; Pitcher, D; Fielder, M D; Miles, R J

    2009-08-01

    To investigate the inter-strain variation in (i) substrate utilization and (ii) the restriction fragment length polymorphism (RFLP) pattern based on the distribution of an insertion element (IS1550) in Mycoplasma fermentans strains, and to establish any correlation between subgroups within the species and their source or habitat. Using a sensitive dynamic pH method, the pattern and kinetics of substrate utilization by a panel of 17 M. fermentans strains from various sources was determined. This study correlated the biochemical characteristics of these strains with RFLP patterns based on the distribution of an insertion sequence (IS1550) with the sources of the strains. The test isolates were divided into four major groups according to the pattern of substrates metabolized. Interestingly, two strains isolated from cell lines in RFLP cluster I failed to utilize arginine. Ovine strains showed distinct substrate utilization patterns and produced RFLP patterns not previously encountered. All strains utilized glucose, but the ability to utilize arginine, fructose and N-acetyl glucosamine varied. There was also some correlation evident between the metabolic data and the RFLP clusters. This study has provided a better understanding of the biochemical and genetic diversity of M. fermentans strains from various sources.

  8. [Variation of the sialic acid-protein ratio in the human cervical mucus (author's transl)].

    Science.gov (United States)

    Kesserü, E; Westphal, N

    1975-01-01

    Serial determinations of total protein and sialic acid concentrations were carried out in individual cervical mucus samples of normal women, throughout the menstrual cycle as well as under the influence of estrogen and progestagen steroids. Total protein was titrated by a modified micro-biuret method and sialic acid was determined using the "Direct Ehrlich" method. Both parameters diminished gradually during the follicular phase of the cycle with lowest values around the time of ovulation, and showed a strong increase during the luteal phase. Administration of ethinylestradiol yielded values significantly lower than those of normal ovulatory phase and under d-Nosgestrel treatment the values were significantly higher than in normal luteal phase. However the proportion of sialic acid as related to total protein showed an inverse behavior, i.e. increased under estrogenic and decreased under progestogenic influence. The cyclic and hormone-induced variations of this ratio were more specific than those of both separate components. Thus, estrogens produce an increase of the sialic acid containing fraction of cervical mucus proteins, while progestagens have an opposite effect. The role of these actions in reproductive physiology is discussed.

  9. Variations and voids: the regulation of human cloning around the world

    Directory of Open Access Journals (Sweden)

    Caulfield Timothy

    2004-12-01

    Full Text Available Abstract Background No two countries have adopted identical regulatory measures on cloning. Understanding the complexity of these regulatory variations is essential. It highlights the challenges associated with the regulation of a controversial and rapidly evolving area of science and sheds light on a regulatory framework that can accommodate this reality. Methods Using the most reliable information available, we have performed a survey of the regulatory position of thirty countries around the world regarding the creation and use of cloned embryos (see Table 1. We have relied on original and translated legislation, as well as published sources and personal communications. We have examined the regulation of both reproductive cloning (RC and non-reproductive cloning (NRC. Results While most of the countries studied have enacted national legislation, the absence of legislation in seven of these countries should not be equated with the absence of regulation. Senator Morin was not correct in stating that the majority of recent legislation bans both RC and NRC. Recent regulatory moves are united only with regard to the banning of RC. While NRC is not permitted in seventeen of the countries examined, it could be permitted in up to thirteen countries. Conclusions There is little consensus on the various approaches to cloning laws and policies, and the regulatory position in many countries remains uncertain.

  10. Functional human GRIN2B promoter polymorphism and variation of mental processing speed in older adults

    OpenAIRE

    Jiang, Yang; Kuan Lin, Ming; Jicha, Gregory A.; Ding, Xiuhua; McIlwrath, Sabrina L.; Fardo, David W.; Broster, Lucas S.; Schmitt, Frederick A.; Kryscio, Richard; Lipsky, Robert H.

    2017-01-01

    We investigated the role of a single nucleotide polymorphism rs3764030 (G>A) within the human GRIN2B promoter in mental processing speed in healthy, cognitively intact, older adults. In vitro DNA-binding and reporter gene assays of different allele combinations in transfected cells showed that the A allele was a gain-of-function variant associated with increasing GRIN2B mRNA levels. We tested the hypothesis that individuals with A allele will have better memory performance (i.e. faster reacti...

  11. Mechanistic understanding of human-wildlife conflict through a novel application of dynamic occupancy models.

    Science.gov (United States)

    Goswami, Varun R; Medhi, Kamal; Nichols, James D; Oli, Madan K

    2015-08-01

    Crop and livestock depredation by wildlife is a primary driver of human-wildlife conflict, a problem that threatens the coexistence of people and wildlife globally. Understanding mechanisms that underlie depredation patterns holds the key to mitigating conflicts across time and space. However, most studies do not consider imperfect detection and reporting of conflicts, which may lead to incorrect inference regarding its spatiotemporal drivers. We applied dynamic occupancy models to elephant crop depredation data from India between 2005 and 2011 to estimate crop depredation occurrence and model its underlying dynamics as a function of spatiotemporal covariates while accounting for imperfect detection of conflicts. The probability of detecting conflicts was consistently <1.0 and was negatively influenced by distance to roads and elevation gradient, averaging 0.08-0.56 across primary periods (distinct agricultural seasons within each year). The probability of crop depredation occurrence ranged from 0.29 (SE 0.09) to 0.96 (SE 0.04). The probability that sites raided by elephants in primary period t would not be raided in primary period t + 1 varied with elevation gradient in different seasons and was influenced negatively by mean rainfall and village density and positively by distance to forests. Negative effects of rainfall variation and distance to forests best explained variation in the probability that sites not raided by elephants in primary period t would be raided in primary period t + 1. With our novel application of occupancy models, we teased apart the spatiotemporal drivers of conflicts from factors that influence how they are observed, thereby allowing more reliable inference on mechanisms underlying observed conflict patterns. We found that factors associated with increased crop accessibility and availability (e.g., distance to forests and rainfall patterns) were key drivers of elephant crop depredation dynamics. Such an understanding is essential for

  12. Emerging themes and new challenges in defining the role of structural variation in human disease.

    Science.gov (United States)

    Sharp, Andrew J

    2009-02-01

    The widespread use of array-comparative genomic hybridization (array-CGH) for the detection of copy number variants (CNVs) in both research and clinical laboratories has created a renaissance in the field of molecular cytogenetics, revealing that the human genome contains both a wealth of structural polymorphism and many novel genomic disorders. A new generation of experimental platforms enable structural variants to be identified with increasing resolution, and will require the development of more sophisticated methods to assess the pathogenic significance of novel structural variants if these technologies are to be of clinical utility. Indeed, we are now entering an era in which technologies to detect CNVs have advanced much faster than our understanding of the consequences of these variants on human phenotypes, and I argue that over the last few years the problem has now become one of interpretation rather than identification. This problem is made more complex by the realization that many genomic disorders show highly variable penetrance, blurring the boundary of how to define benign vs. pathogenic variants. I discuss insights from recent research which shed light on potential mechanisms that may underlie this phenomenon, and possible methods to determine the genetic elements that are responsible for the associated phenotype. Furthermore, there is now a growing appreciation that the underlying chromosomal architecture which catalyses many genomic disorders is polymorphic within the general population, and I discuss potential mechanisms by which inversion polymorphisms might create predispositions to genomic disorders. (c) 2008 Wiley-Liss, Inc.

  13. Human parietal pleura present electrophysiology variations according to location in pleural cavity.

    Science.gov (United States)

    Kouritas, Vassilios K; Hatzoglou, Chrisi; Foroulis, Christophoros N; Gourgoulianis, Konstantinos I

    2008-08-01

    The aim of the study was to investigate if human pleura from different anatomical locations presents electrophysiology differences. Specimens were stripped over the 2nd-5th rib (cranial), 8th-10th rib (caudal), and mediastinum during open surgery and were mounted between Ussing chambers. Amiloride and ouabain were added towards mesothelial surface and trans-mesothelial potential difference (PD) was measured after 1, 5, 10 and 20 min. Trans-membrane resistance (R) was calculated from Ohm's law. R increased after amiloride addition, for cranial (net increase of 0.40 Omega x cm(2)) and caudal (1.16 Omega x cm(2)) pleural pieces. Mediastinal pleura R remained unchanged (0.09 Omega x cm(2)). R increase was higher for caudal than cranial (P=0.029) or mediastinal tissues (P=0.002). R increased after ouabain addition for caudal (1.35 Omega x cm(2)) and cranial (0.56 Omega x cm(2)) pleural pieces. Mediastinal pleural tissue did not respond (0.20 Omega x cm(2)). Caudally located pleura responded greater than cranial (P=0.043) or mediastinal (P=0.003) pleural tissues. Human pleura shows electrophysiology differences according to the location within the pleural cavity. Surgeons may waste mediastinal pleura when needed but should leave intact caudal parietal pleura, which seems to be electrophysiologically the most important part of the pleural cavity.

  14. Defining the role of common variation in the genomic and biological architecture of adult human height

    Science.gov (United States)

    Chu, Audrey Y; Estrada, Karol; Luan, Jian’an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L; Croteau-Chonka, Damien C; Day, Felix R; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C; Scherag, André; Vinkhuyzen, Anna AE; Westra, Harm-Jan; Winkler, Thomas W; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B; Feenstra, Bjarke; Feitosa, Mary F; Fischer, Krista; Fraser, Ross M; Goel, Anuj; Gong, Jian; Justice, Anne E; Kanoni, Stavroula; Kleber, Marcus E; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Lui, Julian C; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina; Nalls, Michael A; Nyholt, Dale R; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W; van Setten, Jessica; Van Vliet-Ostaptchouk, Jana V; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L; Böttcher, Yvonne; Boyd, Heather A; Bruinenberg, Marcel; Buckley, Brendan M; Buyske, Steven; Caspersen, Ida H; Chines, Peter S; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E Warwick; De Jong, Pim A; Deelen, Joris; Delgado, Graciela; Denny, Josh C; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex SF; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C.P.G.M.; Groves, Christopher J; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K; Hillege, Hans L; Hlatky, Mark A; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J; Illig, Thomas; Isaacs, Aaron; James, Alan L; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik KE; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L; McKenzie, Colin A; McLachlan, Stela; McLaren, Paul J; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L; Morken, Mario A; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M; Nöthen, Markus M; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W; Renstrom, Frida; Robertson, Neil R; Rose, Lynda M; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R; Schunkert, Heribert; Scott, Robert A; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V; Stirrups, Kathleen; Stott, David J; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorleifsson, Gudmar; Tyrer, Jonathan P; van Dijk, Suzanne; van Schoor, Natasja M; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor VA; Vermeulen, Sita H; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Wright, Alan F; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan JL; Beilby, John; Bergman, Richard N; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, Dorret I; Bornstein, Stefan R; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J; Campbell, Harry; Caulfield, Mark J; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S; Crawford, Dana C; Cupples, L Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G; Forrester, Terrence; Gansevoort, Ron T; Gejman, Pablo V; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John JP; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela AF; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, DC; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter EH; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul IW; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J.; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin NA; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S.; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L.; Lettre, Guillaume; Loos, Ruth JF; Weedon, Michael N; Ingelsson, Erik; O’Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E

    2014-01-01

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explain one-fifth of heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured the majority (60%) of heritability. The 697 variants clustered in 423 loci enriched for genes, pathways, and tissue-types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin, and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants. PMID:25282103

  15. Normal variations in the isotopic composition of metabolically relevant transition metals in human blood

    Science.gov (United States)

    Van Heghe, L.; Cloquet, C.; Vanhaecke, F.

    2012-04-01

    Cu, Fe and Zn are transition metals with great catalytic, structural and regulating importance in the human body. Hence, an aberrant metabolism of these elements can have serious implications on the health of a person. It is assumed that, due to differences in isotope fractionation, the isotopic composition of these elements in whole blood of patients can be different from that in blood of healthy subjects. Therefore, isotopic analysis of the element affected by the disease can be a promising approach for early diagnosis. A method for isotopic analysis of Cu, Fe and Zn in human whole blood was developed. The simultaneous chromatographic isolation of these elements and the conditions for isotope ratio measurement via multi-collector ICP - mass spectrometry (MC-ICP-MS) were optimized. So far, only whole blood of supposedly healthy volunteers (reference population) was analyzed. Results for Fe confirmed the known differences in isotopic composition between male and female blood. It is also shown that other parameters can have influence as well, e.g., the isotopic composition of Zn seems to be governed by the diet.

  16. Variation in human cancer cell external phosphatidylserine is regulated by flippase activity and intracellular calcium.

    Science.gov (United States)

    Vallabhapurapu, Subrahmanya D; Blanco, Víctor M; Sulaiman, Mahaboob K; Vallabhapurapu, Swarajya Lakshmi; Chu, Zhengtao; Franco, Robert S; Qi, Xiaoyang

    2015-10-27

    Viable cancer cells expose elevated levels of phosphatidylserine (PS) on the exoplasmic face of the plasma membrane. However, the mechanisms leading to elevated PS exposure in viable cancer cells have not been defined. We previously showed that externalized PS may be used to monitor, target and kill tumor cells. In addition, PS on tumor cells is recognized by macrophages and has implications in antitumor immunity. Therefore, it is important to understand the molecular details of PS exposure on cancer cells in order to improve therapeutic targeting. Here we explored the mechanisms regulating the surface PS exposure in human cancer cells and found that differential flippase activity and intracellular calcium are the major regulators of surface PS exposure in viable human cancer cells. In general, cancer cell lines with high surface PS exhibited low flippase activity and high intracellular calcium, whereas cancer cells with low surface PS exhibited high flippase activity and low intracellular calcium. High surface PS cancer cells also had higher total cellular PS than low surface PS cells. Together, our results indicate that the amount of external PS in cancer cells is regulated by calcium dependent flippase activity and may also be influenced by total cellular PS.

  17. Variation of Human Hairiness: A Possible Adaptation to Solar Radiation and Melanin

    Directory of Open Access Journals (Sweden)

    Dhugga Amrita

    2014-07-01

    Full Text Available Many theories have been advanced to explain human hairlessness, however, there is no consensus. This study of 76 males observed that skin reflectance measuring skin colouration and melanin pigmentation correlated with hair size and follicle density. Individuals with a greater concentration of melanin within the superficial layer of the skin had a lower follicle density and smaller sizes of hairs. In contrast, individuals with a lower melanin concentration and lighter skin colour had a full range of hairiness. This leads to the suggestion that over the course of human evolution, high concentrations of melanin in consistently exposed to ultraviolet radiation areas developed first and that hair loss was a consequence of competition in the skin between melanin production and hair growth. Darker pigmented skin and lower follicle density are significantly correlated (R2=0.283; p<0.05. Individuals with darker skin had a mean of 4.91 follicles per cm2 whereas those with lighter skin reflectance had 11.20 follicles per cm2. This suggests that increased concentrations of melanin in the basal layer of the epidermis may limit hairiness by negatively influencing the skin's ability to produce hair.

  18. Genetic adaptation of the human circadian clock to day-length latitudinal variations and relevance for affective disorders.

    Science.gov (United States)

    Forni, Diego; Pozzoli, Uberto; Cagliani, Rachele; Tresoldi, Claudia; Menozzi, Giorgia; Riva, Stefania; Guerini, Franca R; Comi, Giacomo P; Bolognesi, Elisabetta; Bresolin, Nereo; Clerici, Mario; Sironi, Manuela

    2014-01-01

    The temporal coordination of biological processes into daily cycles is a common feature of most living organisms. In humans, disruption of circadian rhythms is commonly observed in psychiatric diseases,including schizophrenia, bipolar disorder, depression and autism. Light therapy is the most effective treatment for seasonal affective disorder and circadian-related treatments sustain antidepressant response in bipolar disorder patients. Day/night cycles represent a major circadian synchronizing signal and vary widely with latitude. We apply a geographically explicit model to show that out-of-Africa migration, which led humans to occupy a wide latitudinal area, affected the evolutionary history of circadian regulatory genes. The SNPs we identify using this model display consistent signals of natural selection using tests based on population genetic differentiation and haplotype homozygosity. Signals of natural selection driven by annual photoperiod variation are detected for schizophrenia, bipolar disorder, and restless leg syndrome risk variants, in line with the circadian component of these conditions. Our results suggest that human populations adapted to life at different latitudes by tuning their circadian clock systems. This process also involves risk variants for neuropsychiatric conditions, suggesting possible genetic modulators for chronotherapies and candidates for interaction analysis with photoperiod-related environmental variables, such as season of birth, country of residence, shift-work or lifestyle habits.

  19. Potential applications of gut microbiota to control human physiology.

    Science.gov (United States)

    Umu, Ozgün Candan Onarman; Oostindjer, Marije; Pope, Phillip B; Svihus, Birger; Egelandsdal, Bjørg; Nes, Ingolf F; Diep, Dzung B

    2013-11-01

    The microorganisms living in our gut have been a black box to us for a long time. However, with the recent advances in high throughput DNA sequencing technologies, it is now possible to assess virtually all microorganisms in our gut including non-culturable ones. With the use of powerful bioinformatics tools to deal with multivariate analyses of huge amounts of data from metagenomics, metatranscriptomics, metabolomics, we now start to gain some important insights into these tiny gut inhabitants. Our knowledge is increasing about who they are, to some extent, what they do and how they affect our health. Gut microbiota have a broad spectrum of possible effects on health, from preventing serious diseases, improving immune system and gut health to stimulating the brain centers responsible for appetite and food intake control. Further, we may be on the verge of being capable of manipulating the gut microbiota by diet control to possibly improve our health. Diets consisting of different components that are fermentable by microbiota are substrates for different kinds of microbes in the gut. Thus, diet control can be used to favor the growth of some selected gut inhabitants. Nowadays, the gut microbiota is taken into account as a separate organ in human body and their activities and metabolites in gut have many physiological and neurological effects. In this mini-review, we discuss the diversity of gut microbiota, the technologies used to assess them, factors that affect microbial composition and metabolites that affect human physiology, and their potential applications in satiety control via the gut-brain axis.

  20. Human Locomotion in Hypogravity: From Basic Research to Clinical Applications

    Directory of Open Access Journals (Sweden)

    Francesco Lacquaniti

    2017-11-01

    Full Text Available We have considerable knowledge about the mechanisms underlying compensation of Earth gravity during locomotion, a knowledge obtained from physiological, biomechanical, modeling, developmental, comparative, and paleoanthropological studies. By contrast, we know much less about locomotion and movement in general under sustained hypogravity. This lack of information poses a serious problem for human space exploration. In a near future humans will walk again on the Moon and for the first time on Mars. It would be important to predict how they will move around, since we know that locomotion and mobility in general may be jeopardized in hypogravity, especially when landing after a prolonged weightlessness of the space flight. The combination of muscle weakness, of wearing a cumbersome spacesuit, and of maladaptive patterns of locomotion in hypogravity significantly increase the risk of falls and injuries. Much of what we currently know about locomotion in hypogravity derives from the video archives of the Apollo missions on the Moon, the experiments performed with parabolic flight or with body weight support on Earth, and the theoretical models. These are the topics of our review, along with the issue of the application of simulated hypogravity in rehabilitation to help patients with deambulation problems. We consider several issues that are common to the field of space science and clinical rehabilitation: the general principles governing locomotion in hypogravity, the methods used to reduce gravity effects on locomotion, the extent to which the resulting behavior is comparable across different methods, the important non-linearities of several locomotor parameters as a function of the gravity reduction, the need to use multiple methods to obtain reliable results, and the need to tailor the methods individually based on the physiology and medical history of each person.

  1. Human Locomotion in Hypogravity: From Basic Research to Clinical Applications

    Science.gov (United States)

    Lacquaniti, Francesco; Ivanenko, Yury P.; Sylos-Labini, Francesca; La Scaleia, Valentina; La Scaleia, Barbara; Willems, Patrick A.; Zago, Myrka

    2017-01-01

    We have considerable knowledge about the mechanisms underlying compensation of Earth gravity during locomotion, a knowledge obtained from physiological, biomechanical, modeling, developmental, comparative, and paleoanthropological studies. By contrast, we know much less about locomotion and movement in general under sustained hypogravity. This lack of information poses a serious problem for human space exploration. In a near future humans will walk again on the Moon and for the first time on Mars. It would be important to predict how they will move around, since we know that locomotion and mobility in general may be jeopardized in hypogravity, especially when landing after a prolonged weightlessness of the space flight. The combination of muscle weakness, of wearing a cumbersome spacesuit, and of maladaptive patterns of locomotion in hypogravity significantly increase the risk of falls and injuries. Much of what we currently know about locomotion in hypogravity derives from the video archives of the Apollo missions on the Moon, the experiments performed with parabolic flight or with body weight support on Earth, and the theoretical models. These are the topics of our review, along with the issue of the application of simulated hypogravity in rehabilitation to help patients with deambulation problems. We consider several issues that are common to the field of space science and clinical rehabilitation: the general principles governing locomotion in hypogravity, the methods used to reduce gravity effects on locomotion, the extent to which the resulting behavior is comparable across different methods, the important non-linearities of several locomotor parameters as a function of the gravity reduction, the need to use multiple methods to obtain reliable results, and the need to tailor the methods individually based on the physiology and medical history of each person. PMID:29163225

  2. Genetics of VEGF serum variation in human isolated populations of cilento: importance of VEGF polymorphisms.

    Directory of Open Access Journals (Sweden)

    Daniela Ruggiero

    Full Text Available Vascular Endothelial Growth Factor (VEGF is the main player in angiogenesis. Because of its crucial role in this process, the study of the genetic factors controlling VEGF variability may be of particular interest for many angiogenesis-associated diseases. Although some polymorphisms in the VEGF gene have been associated with a susceptibility to several disorders, no genome-wide search on VEGF serum levels has been reported so far. We carried out a genome-wide linkage analysis in three isolated populations and we detected a strong linkage between VEGF serum levels and the 6p21.1 VEGF region in all samples. A new locus on chromosome 3p26.3 significantly linked to VEGF serum levels was also detected in a combined population sample. A sequencing of the gene followed by an association study identified three common single nucleotide polymorphisms (SNPs influencing VEGF serum levels in one population (Campora, two already reported in the literature (rs3025039, rs25648 and one new signal (rs3025020. A fourth SNP (rs41282644 was found to affect VEGF serum levels in another population (Cardile. All the identified SNPs contribute to the related population linkages (35% of the linkage explained in Campora and 15% in Cardile. Interestingly, none of the SNPs influencing VEGF serum levels in one population was found to be associated in the two other populations. These results allow us to exclude the hypothesis that the common variants located in the exons, intron-exon junctions, promoter and regulative regions of the VEGF gene may have a causal effect on the VEGF variation. The data support the alternative hypothesis of a multiple rare variant model, possibly consisting in distinct variants in different populations, influencing VEGF serum levels.

  3. Seasonal variations of respiratory viruses and etiology of human rhinovirus infection in children.

    Science.gov (United States)

    Morikawa, Saeko; Kohdera, Urara; Hosaka, Taisuke; Ishii, Kousuke; Akagawa, Shohei; Hiroi, Satoshi; Kase, Tetsuo

    2015-12-01

    Using the polymerase chain reaction (PCR) method it is possible to detect uncultivable viruses and discover multiple viral infections. However, the clinical importance of these findings in relation to symptoms is not known. The seasonal fluctuations of respiratory viruses and the clinical outcomes of single infections and dual infections were investigated. Nasal aspirate samples were obtained from outpatients and inpatients of a children's hospital and these samples were subjected to real-time PCR to detect 16 respiratory viruses. Seasonal variations of the 16 viruses and the clinical outcomes such as wheezing, the need for oxygenation and prolonged hospitalization of patients with single viral infections and multiple infections were determined for the 5 most often detected viruses. Among 512 specimens analyzed, one or more viruses were detected in 424 (83%) specimens. Two or more viruses were detected in 160 samples (31% of all samples). The epidemic peaks of the viruses did not coincide with each other. Rhinoviruses were the most frequently detected viruses and their coinfection rates were also higher. However, the disease severity in the lower respiratory tract did not differ in most respiratory viral infections regardless of whether there was single infection or dual infection with a rhinovirus and other respiratory virus. Seasonal distribution was seen for each virus. There were no significant differences in clinical symptoms in the children studied. Because the infection of rhinoviruses is the common occurrence in children, it is hypothesized that the factors related to disease severity are mainly the underlying conditions of the children. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. High-Frequency EEG Variations in Children with Autism Spectrum Disorder during Human Faces Visualization

    Directory of Open Access Journals (Sweden)

    Celina A. Reis Paula

    2017-01-01

    Full Text Available Autism spectrum disorder (ASD is a neuropsychiatric disorder characterized by the impairment in the social reciprocity, interaction/language, and behavior, with stereotypes and signs of sensory function deficits. Electroencephalography (EEG is a well-established and noninvasive tool for neurophysiological characterization and monitoring of the brain electrical activity, able to identify abnormalities related to frequency range, connectivity, and lateralization of brain functions. This research aims to evidence quantitative differences in the frequency spectrum pattern between EEG signals of children with and without ASD during visualization of human faces in three different expressions: neutral, happy, and angry. Quantitative clinical evaluations, neuropsychological evaluation, and EEG of children with and without ASD were analyzed paired by age and gender. The results showed stronger activation in higher frequencies (above 30 Hz in frontal, central, parietal, and occipital regions in the ASD group. This pattern of activation may correlate with developmental characteristics in the children with ASD.

  5. High-Frequency EEG Variations in Children with Autism Spectrum Disorder during Human Faces Visualization.

    Science.gov (United States)

    Paula, Celina A Reis; Reategui, Camille; Costa, Bruna Karen de Sousa; da Fonseca, Caio Queiroz; da Silva, Luana; Morya, Edgard; Brasil, Fabricio Lima

    2017-01-01

    Autism spectrum disorder (ASD) is a neuropsychiatric disorder characterized by the impairment in the social reciprocity, interaction/language, and behavior, with stereotypes and signs of sensory function deficits. Electroencephalography (EEG) is a well-established and noninvasive tool for neurophysiological characterization and monitoring of the brain electrical activity, able to identify abnormalities related to frequency range, connectivity, and lateralization of brain functions. This research aims to evidence quantitative differences in the frequency spectrum pattern between EEG signals of children with and without ASD during visualization of human faces in three different expressions: neutral, happy, and angry. Quantitative clinical evaluations, neuropsychological evaluation, and EEG of children with and without ASD were analyzed paired by age and gender. The results showed stronger activation in higher frequencies (above 30 Hz) in frontal, central, parietal, and occipital regions in the ASD group. This pattern of activation may correlate with developmental characteristics in the children with ASD.

  6. Evidence for genetic variation in human mate preferences for sexually dimorphic physical traits.

    Directory of Open Access Journals (Sweden)

    Karin J H Verweij

    Full Text Available Intersexual selection has been proposed as an important force in shaping a number of morphological traits that differ between human populations and/or between the sexes. Important to these accounts is the source of mate preferences for such traits, but this has not been investigated. In a large sample of twins, we assess forced-choice, dichotomous mate preferences for height, skin colour, hair colour and length, chest hair, facial hair, and breast size. Across the traits, identical twins reported more similar preferences than nonidentical twins, suggesting genetic effects. However, the relative magnitude of estimated genetic and environmental effects differed greatly and significantly between different trait preferences, with heritability estimates ranging from zero to 57%.

  7. Predicting the Pathogenic Impact of Sequence Variation in the Human Genome.

    Science.gov (United States)

    Rogers, Mark F; Shihab, Hashem A; Ferlaino, Michael; Gaunt, Tom R; Campbell, Colin

    2017-01-01

    Sequencing data will become widely available in clinical practice within the near future. Uptake of sequence data is currently being stimulated within the UK through the government-funded 100,000 genomes project (Genomics England), with many similar initiatives being planned and supported internationally. The analysis of the large volumes of data derived from sequencing programmes poses a major challenge for data analysis. In this paper we outline progress we have made in the development of predictors for estimating the pathogenic impact of single nucleotide variants, indels and haploinsufficiency in the human genome. The accuracy of these methods is enhanced through the development of disease-specific predictors, trained on appropriate data, and used within a specific disease context. We outline current research on the development of disease-specific predictors, specifically in the context of cancer research.

  8. Seasonal variations of DNA damage in human lymphocytes: Correlation with different environmental variables

    Energy Technology Data Exchange (ETDEWEB)

    Giovannelli, Lisa [Dipartimento di Farmacologia Preclinica e Clinica, Universita di Firenze, Viale Pieraccini 6, 50139 Florence (Italy)]. E-mail: lisa.giovannelli@unifi.it; Pitozzi, Vanessa [Dipartimento di Farmacologia Preclinica e Clinica, Universita di Firenze, Viale Pieraccini 6, 50139 Florence (Italy); Moretti, Silvia [Department of Dermatological Sciences, University of Florence, Florence (Italy); Boddi, Vieri [Department of Public Health, University of Florence, Florence (Italy); Dolara, Piero [Dipartimento di Farmacologia Preclinica e Clinica, Universita di Firenze, Viale Pieraccini 6, 50139 Florence (Italy)

    2006-01-29

    Several types of DNA damage, including DNA breaks and DNA base oxidation, display a seasonal trend. In the present work, a sample of 79 healthy subjects living in the city of Florence, Italy, was used to analyse this effect. Three possible causative agents were taken into consideration: solar radiation, air temperature and air ozone level. DNA damage was measured in isolated human lymphocytes at different times during the year and the observed damage was correlated with the levels of these three agents in the days preceding blood sampling. Three time windows were chosen: 3, 7 and 30 days before blood sampling. DNA strand breaks and the oxidized purinic bases cleaved by the formamidopyrimidine glycosylase (FPG sites) were measured by means of the comet assay. The results of multivariate regression analysis showed a positive correlation between lymphocyte DNA damage and air temperature, and a less strong correlation with global solar radiation and air ozone levels.

  9. Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol

    Directory of Open Access Journals (Sweden)

    S. Fili

    2015-09-01

    Full Text Available This study focuses on the effects of the organic ligand 4-ethylresorcinol on the crystal structure of human insulin using powder X-ray crystallography. For this purpose, systematic crystallization experiments have been conducted in the presence of the organic ligand and zinc ions within the pH range 4.50–8.20, while observing crystallization behaviour around the isoelectric point of insulin. High-throughput crystal screening was performed using a laboratory X-ray diffraction system. The most representative samples were selected for synchrotron X-ray diffraction measurements, which took place at the European Synchrotron Radiation Facility (ESRF and the Swiss Light Source (SLS. Four different crystalline polymorphs have been identified. Among these, two new phases with monoclinic symmetry have been found, which are targets for the future development of microcrystalline insulin drugs.

  10. MitoLSDB: a comprehensive resource to study genotype to phenotype correlations in human mitochondrial DNA variations.

    Directory of Open Access Journals (Sweden)

    Shamnamole K

    Full Text Available Human mitochondrial DNA (mtDNA encodes a set of 37 genes which are essential structural and functional components of the electron transport chain. Variations in these genes have been implicated in a broad spectrum of diseases and are extensively reported in literature and various databases. In this study, we describe MitoLSDB, an integrated platform to catalogue disease association studies on mtDNA (http://mitolsdb.igib.res.in. The main goal of MitoLSDB is to provide a central platform for direct submissions of novel variants that can be curated by the Mitochondrial Research Community. MitoLSDB provides access to standardized and annotated data from literature and databases encompassing information from 5231 individuals, 675 populations and 27 phenotypes. This platform is developed using the Leiden Open (source Variation Database (LOVD software. MitoLSDB houses information on all 37 genes in each population amounting to 132397 variants, 5147 unique variants. For each variant its genomic location as per the Revised Cambridge Reference Sequence, codon and amino acid change for variations in protein-coding regions, frequency, disease/phenotype, population, reference and remarks are also listed. MitoLSDB curators have also reported errors documented in literature which includes 94 phantom mutations, 10 NUMTs, six documentation errors and one artefactual recombination. MitoLSDB is the largest repository of mtDNA variants systematically standardized and presented using the LOVD platform. We believe that this is a good starting resource to curate mtDNA variants and will facilitate direct submissions enhancing data coverage, annotation in context of pathogenesis and quality control by ensuring non-redundancy in reporting novel disease associated variants.

  11. Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension

    Science.gov (United States)

    Chang, Tien-Jyun; Wang, Wen-Chang; Hsiung, Chao A.; He, Chih-Tsueng; Lin, Ming-Wei; Sheu, Wayne Huey-Herng; Chang, Yi-Cheng; Quertermous, Tom; Chen, Ida; Rotter, Jerome; Chuang, Lee-Ming

    2016-01-01

    Abstract Essential hypertension is a complex disease involving multiple genetic and environmental factors. A human gene containing a sorbin homology domain and 3 SH3 domains in the C-terminal region, termed SORBS1, plays a significant role in insulin signaling. We previously found a significant association between the T228A polymorphism and insulin resistance, obesity, and type 2 diabetes. It has been hypothesized that a set of genes responsible for insulin resistance may be closely linked with genes susceptible to the development of hypertension. Identification of insulin resistance-related genetic factors may, therefore, enhance our understanding of essential hypertension. This study aimed to examine whether common SORBS1 genetic variations are associated with blood pressure and age at onset of hypertension in an ethnic Chinese cohort. We genotyped 9 common tagged single nucleotide polymorphisms of the SORBS1 gene in 1136 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. Blood pressure was measured upon enrolment. The associations of the SORBS1 single nucleotide polymorphisms with blood pressure and the presence of hypertension were analyzed with a generalized estimating equation model. We used the false-discovery rate measure Q value with a cutoff antihypertension medication were adjustment covariates in the Cox regression analysis. In this study, genetic variants of rs2281939 and rs2274490 were significantly associated with both systolic and diastolic blood pressure. A genetic variant of rs2274490 was also significantly associated with the presence of hypertension. Furthermore, genetic variants of rs2281939 and rs2274490 were associated with age at onset of hypertension after adjustment for gender, body mass index, and antihypertension medication. In conclusion, we provide evidence for an association between common SORBS1 genetic variations and blood pressure, presence of hypertension, and

  12. Variation in consumption of human milk oligosaccharides by infant gut-associated strains of Bifidobacterium breve.

    Science.gov (United States)

    Ruiz-Moyano, Santiago; Totten, Sarah M; Garrido, Daniel A; Smilowitz, Jennifer T; German, J Bruce; Lebrilla, Carlito B; Mills, David A

    2013-10-01

    Human milk contains a high concentration of complex oligosaccharides that influence the composition of the intestinal microbiota in breast-fed infants. Previous studies have indicated that select species such as Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum can utilize human milk oligosaccharides (HMO) in vitro as the sole carbon source, while the relatively few B. longum subsp. longum and Bifidobacterium breve isolates tested appear less adapted to these substrates. Considering the high frequency at which B. breve is isolated from breast-fed infant feces, we postulated that some B. breve strains can more vigorously consume HMO and thus are enriched in the breast-fed infant gastrointestinal tract. To examine this, a number of B. breve isolates from breast-fed infant feces were characterized for the presence of different glycosyl hydrolases that participate in HMO utilization, as well as by their ability to grow on HMO or specific HMO species such as lacto-N-tetraose (LNT) and fucosyllactose. All B. breve strains showed high levels of growth on LNT and lacto-N-neotetraose (LNnT), and, in general, growth on total HMO was moderate for most of the strains, with several strain differences. Growth and consumption of fucosylated HMO were strain dependent, mostly in isolates possessing a glycosyl hydrolase family 29 α-fucosidase. Glycoprofiling of the spent supernatant after HMO fermentation by select strains revealed that all B. breve strains can utilize sialylated HMO to a certain extent, especially sialyl-lacto-N-tetraose. Interestingly, this specific oligosaccharide was depleted before neutral LNT by strain SC95. In aggregate, this work indicates that the HMO consumption phenotype in B. breve is variable; however, some strains display specific adaptations to these substrates, enabling more vigorous consumption of fucosylated and sialylated HMO. These results provide a rationale for the predominance of this species in breast-fed infant feces and

  13. Regional Variation in Human Exposure to Persistent Organic Pollutants in the United States, NHANES

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    Wendy A. Wattigney

    2015-01-01

    Full Text Available We examined serum levels of persistent organic pollutants (POPs among geographical regions of the United States as defined by the US Census Bureau. National Health and Nutrition Examination Survey (NHANES data for adults aged 20 years and older are presented for selected survey periods between 1999 and 2010. From NHANES 1999 through 2004, dichlorodiphenyldichloroethylene (DDE concentration levels were consistently higher among people living in the West than in the Midwest, Northeast, or South. In 2003–2010, perfluorinated compound concentrations tended to be highest in the South. The sum of 35 polychlorinated biphenyls (PCBs congeners was significantly higher in the Northeast [GM: 189; 95% CI: 173–204 ng/g lipid] than the remaining regions. The regional differences in higher body burdens of exposure to particular POPs could be attributed to a variety of activities, including region-specific patterns of land use and industrial and agricultural chemical applications, as well as different levels of regulatory activity.

  14. Application of social domain of human mind in water management

    Science.gov (United States)

    Piirimäe, Kristjan

    2010-05-01

    , and NGOs. These people were randomly divided to two working groups and asked to criticize the proposed plan. One group was encouraged to detect cheating behind the plan. Later, a group of independent experts evaluated the criticism of both groups and each individual person. The resulting assignements rated the group of cheater detectors as significantly more adequate decision-supporters. The results confirmed that simulation of the 'cheater detection module' of human mind might improve the performance of an EDSS. The study calls for the development of special methodologies for the stimulation and application of social domain in water management. References Buchner, A., Bell, R., Mehl, B., & Musch, J., (2009). No enhanced recognition memory, but better source memory for faces of cheaters. Evolution and Human Behaviour, 30(3), 212 - 224. Byrne, R., Bates, L. (2009). Sociality, evolution and cognition. Current Biology, 17(16), R714 - R723. Cosmides, L. (1989). The logic of social exchange: Has natural selection shaped how humans reason? Studies with the Wason selection task. Cognition, 31(3), 187-276. Fiddick, L. (2004). Domains of deontic reasoning: Resolving the discrepancy between the cognitive and moral reasoning literatures. The Quartlerly Journal of Experimental Psychology, 57A(3), 447 - 474.

  15. Local variations in {sup 14}C - How is bomb-pulse dating of human tissues and cells affected?

    Energy Technology Data Exchange (ETDEWEB)

    Stenstroem, Kristina, E-mail: Kristina.Stenstrom@nuclear.lu.s [Lund University, Department of Physics, Division of Nuclear Physics, Box 118, SE-221 00 Lund (Sweden); Skog, Goeran [Lund University, GeoBiosphere Science Centre, Geocentrum II, Soelvegatan 12, SE-223 672 Lund (Sweden); Nilsson, Carl Magnus [Lund University, Department of Physics, Division of Nuclear Physics, Box 118, SE-221 00 Lund (Sweden); Lund University, Department of Medical Radiation Physics, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Hellborg, Ragnar [Lund University, Department of Physics, Division of Nuclear Physics, Box 118, SE-221 00 Lund (Sweden); Svegborn, Sigrid Leide [Lund University, Department of Medical Radiation Physics, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Georgiadou, Elisavet [Lund University, Department of Physics, Division of Nuclear Physics, Box 118, SE-221 00 Lund (Sweden); Mattsson, Soeren [Lund University, Department of Medical Radiation Physics, Malmoe University Hospital, SE-205 02 Malmoe (Sweden)

    2010-04-15

    Atmospheric nuclear weapons testing in the late 1950s and early 1960s almost doubled the amount of {sup 14}C in the atmosphere. The resulting {sup 14}C 'bomb-pulse' has been shown to provide useful age information in e.g. forensic and environmental sciences, biology and the geosciences. The technique is also currently being used for retrospective cell dating in man, in order to provide insight into the rate of formation of new cells in the human body. Bomb-pulse dating relies on precise measurements of the declining {sup 14}C concentration in atmospheric CO{sub 2} collected at clean-air sites. However, it is not always recognized that the calculations can be complicated in some cases by significant local variations in the specific activity of {sup 14}C in carbon in the air and foodstuff. This paper presents investigations of local {sup 14}C variations in the vicinities of nuclear installations and laboratories using {sup 14}C. Levels of {sup 14}C in workers using this radioisotope are also discussed.

  16. Local variations in 14C - How is bomb-pulse dating of human tissues and cells affected?

    Science.gov (United States)

    Stenström, Kristina; Skog, Göran; Nilsson, Carl Magnus; Hellborg, Ragnar; Svegborn, Sigrid Leide; Georgiadou, Elisavet; Mattsson, Sören

    2010-04-01

    Atmospheric nuclear weapons testing in the late 1950s and early 1960s almost doubled the amount of 14C in the atmosphere. The resulting 14C "bomb-pulse" has been shown to provide useful age information in e.g. forensic and environmental sciences, biology and the geosciences. The technique is also currently being used for retrospective cell dating in man, in order to provide insight into the rate of formation of new cells in the human body. Bomb-pulse dating relies on precise measurements of the declining 14C concentration in atmospheric CO 2 collected at clean-air sites. However, it is not always recognized that the calculations can be complicated in some cases by significant local variations in the specific activity of 14C in carbon in the air and foodstuff. This paper presents investigations of local 14C variations in the vicinities of nuclear installations and laboratories using 14C. Levels of 14C in workers using this radioisotope are also discussed.

  17. Antigenic variation of the human influenza A (H3N2) virus during the 2014-2015 winter season.

    Science.gov (United States)

    Hua, Sha; Li, XiYan; Liu, Mi; Cheng, YanHui; Peng, YouSong; Huang, WeiJuan; Tan, MinJu; Wei, HeJiang; Guo, JunFeng; Wang, DaYan; Wu, AiPing; Shu, YueLong; Jiang, TaiJiao

    2015-09-01

    The human influenza A (H3N2) virus dominated the 2014-2015 winter season in many countries and caused massive morbidity and mortality because of its antigenic variation. So far, very little is known about the antigenic patterns of the recent H3N2 virus. By systematically mapping the antigenic relationships of H3N2 strains isolated since 2010, we discovered that two groups with obvious antigenic divergence, named SW13 (A/Switzerland/9715293/2013-like strains) and HK14 (A/Hong Kong/5738/2014-like strains), co-circulated during the 2014-2015 winter season. HK14 group co-circulated with SW13 in Europe and the United States during this season, while there were few strains of HK14 in mainland China, where SW13 has dominated since 2012. Furthermore, we found that substitutions near the receptor-binding site on hemagglutinin played an important role in the antigenic variation of both the groups. These findings provide a comprehensive understanding of the recent antigenic evolution of H3N2 virus and will aid in the selection of vaccine strains.

  18. Effect of variation of geometric parameters on the flow within a synthetic models of lower human airways

    Science.gov (United States)

    Espinosa Moreno, Andres Santiago; Duque Daza, Carlos Alberto

    2017-11-01

    The effects of variation of two geometric parameters, such as bifurcation angle and carina rounding radius, during the respiratory inhalation process, are studied numerically using two synthetic models of lower human airways. Laminar flow simulations were performed for six angles and three rounding radius, for 500, 1000, 1500 and 2000 for Reynolds numbers. Numerical results showed the existence of a direct relationship between the deformation of the velocity profiles (effect produced by the bifurcation) and the vortical structures observed through the secondary flow patterns. It is observed that the location of the vortices (and their related saddle point) is associated with the displacement of the velocity peak. On the other hand, increasing the angle and the rounding radius seems to bring about a growth of the pressure drop, which in turn displaces the distribution and peaks of the maximum shear stresses of the carina, that is, of the bifurcation point. Some physiological effects associated with the phenomena produced by these geometric variations are also discussed.

  19. 1988 Volvo award in basic science. Proteoglycan synthesis in the human intervertebral disc. Variation with age, region and pathology.

    Science.gov (United States)

    Bayliss, M T; Johnstone, B; O'Brien, J P

    1988-09-01

    Slices of human annulus fibrosus were cultured under conditions that controlled their hydration and prevented loss of proteoglycans from the extracellular matrix. A quantitative analysis of proteoglycan synthesis was carried out. Both the absolute rate of synthesis and the topographical variation in chondrocyte activity changed with age; the most active cells in the adult were found in the mid-annulus region, whereas in the fetal disc the cells in the inner annulus were the most active. The conditions under which the tissue was stored, and changes in hydration during culture, had considerable effects on synthesis. Pathological discs had a wide range of biological activity that reflected the heterogeneous properties of these specimens. It is suggested that this culture method provides a means of investigating the way in which the synthesis of the macromolecular components of the intervertebral disc are coordinated and subsequently incorporated into the extracellular matrix.

  20. Variations in concentrations and fluxes of dissolved inorganic nutrients related to catchment scale human interventions in Pamba River, Kerala, India

    Science.gov (United States)

    David, S. E.; Jennerjahn, T. C.; Chattopadhyay, S.

    2012-12-01

    River basins are geo-hydrological units. Water flowing out of the basin bears the imprint of natural factors such as geology, soil, vegetation and rainfall along with anthropogenic factors including the type and degree of human intervention within the basin. Pamba, a small mountainous river in the SW coast of India with a population density of ~1,400 persons km-2 was studied for its varying land use and human interventions as the global database are biased towards temperate regions while little is know about the smaller catchments from tropical regions. Land use comprised of dense forest in the highland region together with forest plantation and the human impacted Sabarimala temple- the second largest pilgrim, settlement with mixed tree crop (smt) in the midland and lowland paddy cultivated region. 50-60 million devotees visiting Sabarimala during November to January every year associated with the ritual bathing, discharge of human wastes emanating from the influx of millions of pilgrims due to inadequate number of sanitary latrines and the lack of facilities for sewage collection and treatment caused several ecological variations during pilgrim season. In order to asses the effect of land use and pilgrims in combination with seasonal variations in hydrology we investigated the seasonal and spatial variations in physicochemical and nutrient concentrations. Samples were collected from March 2010 to February 2012 during premonsoon (January-May), SW(June to September) and NE monsoon(October to December), from sites varying in land use. Nutrient budgets (load and yield) were calculated to quantify the inputs from various land use segments. Spatio-temporal variations in the physicochemical and dissolved nutrient concentrations were observed along the course of the river. Upstream forest region had highest dissolved oxygen(DO) and pH together with lowest dissolved inorganic nitrogen(DIN) values indicating almost pristine conditions. DIN in the temple region had the

  1. Human tolerogenic DC-10: perspectives for clinical applications.

    Science.gov (United States)

    Amodio, Giada; Gregori, Silvia

    2012-09-28

    Dendritic cells (DCs) are critically involved in inducing either immunity or tolerance. During the last decades efforts have been devoted to the development of ad hoc methods to manipulate DCs in vitro to enhance or stabilize their tolerogenic properties. Addition of IL-10 during monocyte-derived DC differentiation allows the induction of DC-10, a subset of human tolerogenic DCs characterized by high IL-10/IL-12 ratio and co-expression of high levels of the tolerogenic molecules HLA-G and immunoglobulin-like transcript 4. DC-10 are potent inducers of adaptive type 1 regulatory T cells, well known to promote and maintain peripheral tolerance. In this review we provide an in-depth comparison of the phenotype and mechanisms of suppression mediated by DC-10 and other known regulatory antigen-presenting cells currently under clinical development. We discuss the clinical therapeutic application of DC-10 as inducers of type 1 regulatory T cells for tailoring regulatory T-cell-based cell therapy, and the use of DC-10 as adoptive cell therapy for promoting and restoring tolerance in T-cell-mediated diseases.

  2. Application of 'writing for healing' in premedical humanities education.

    Science.gov (United States)

    Ban, Jae Yu; Yeh, Byung Il

    2012-09-01

    There has been a recent tendency to attach special importance to writing education. Books on 'writing to heal' are being written in or translated into Korean. According to these texts, writing is a valuable tool for internal healing, depending on the mode of application. Writing can have positive effects and give hope to an individual or group, but it can also be a source of frustration and despair. Based on the distinct effects of writing, we cannot overemphasize the significance of writing education. Writing is generally taught during a premedical course that targets students who will eventually practice medicine. Many reports have examined immorality in medical students and health care providers, which is a reason that writing education is important for medical systems. 'Writing for Healing' is open to freshmen at Yonsei University Wonju College of Medicine. The aim of this subject is to help students identify and acknowledge internal diseases to lead a healthier life and eventually become positive and responsible health care providers. However, in addition to the vague definition of what 'healing' is, the concept of 'writing for healing' has not been defined. This paper attempts to define the concept of 'writing for healing' and considers what influences it can have on a humanities curriculum in medical colleges.

  3. Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients.

    Directory of Open Access Journals (Sweden)

    Xian-Yang Qin

    Full Text Available BACKGROUND/PURPOSE: We hypothesized that polymorphic differences among individuals might cause variations in the effect that environmental endocrine disruptors (EEDs have on male genital malformations (MGMs. In this study, individual variation in the genetic response to low-dose bisphenol A (BPA was investigated in human foreskin fibroblast cells (hFFCs derived from child cryptorchidism (CO and hypospadias (HS patients. METHODOLOGY/PRINCIPAL FINDINGS: hFFCs were collected from control children without MGMs (n=5 and child CO and HS patients (n=8 and 21, respectively. BPA exposure (10 nM was found to inhibit matrix metalloproteinase-11 (MMP11 expression in the HS group (0.74-fold, P=0.0034 but not in the control group (0.93-fold, P=0.84 and CO group (0.94-fold, P=0.70. Significantly lower levels of MMP11 expression were observed in the HS group compared with the control group (0.80-fold, P=0.0088 and CO group (0.79-fold, P=0.039 in response to 10 nM BPA. The effect of single-nucleotide polymorphism rs5000770 (G>A, located within the aryl hydrocarbon receptor nuclear translocator 2 (ARNT2 locus, on individual sensitivity to low-dose BPA was investigated in the HS group. A significant difference in neurotensin receptor 1 (NTSR1 expression in response to 10 nM BPA was observed between AA and AG/GG groups (n=6 and 15, respectively. P=0.031. However, no significant difference in ARNT2 expression was observed (P=0.18. CONCLUSIONS/SIGNIFICANCE: This study advances our understanding of the specificity of low-dose BPA effects on human reproductive health. Our results suggest that genetic variability among individuals affects susceptibility to the effects of EEDs exposure as a potential cause of HS.

  4. Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

    Science.gov (United States)

    Homburger, Julian R.; Green, Eric M.; Caleshu, Colleen; Sunitha, Margaret S.; Taylor, Rebecca E.; Ruppel, Kathleen M.; Metpally, Raghu Prasad Rao; Colan, Steven D.; Michels, Michelle; Day, Sharlene M.; Olivotto, Iacopo; Bustamante, Carlos D.; Dewey, Frederick E.; Ho, Carolyn Y.; Spudich, James A.; Ashley, Euan A.

    2016-01-01

    Myosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood. Here, we combine structural models of myosin from multiple stages of its chemomechanical cycle, exome sequencing data from two population cohorts of 60,706 and 42,930 individuals, and genetic and phenotypic data from 2,913 patients with HCM to identify regions of disease enrichment within β-cardiac myosin. We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. Then, using a spatial scan statistic modified to analyze genetic variation in protein 3D space, we found significant enrichment of disease-associated variants in the converter, a kinetic domain that transduces force from the catalytic domain to the lever arm to accomplish the power stroke. Focusing our analysis on surface-exposed residues, we identified a larger region significantly enriched for disease-associated variants that contains both the converter domain and residues on a single flat surface on the myosin head described as the myosin mesa. Notably, patients with HCM with variants in the enriched regions have earlier disease onset than patients who have HCM with variants elsewhere. Our study provides a model for integrating protein structure, large-scale genetic sequencing, and detailed phenotypic data to reveal insight into time-shifted protein structures and genetic disease. PMID:27247418

  5. Classification of the normal variation in the sagittal alignment of the human lumbar spine and pelvis in the standing position.

    Science.gov (United States)

    Roussouly, Pierre; Gollogly, Sohrab; Berthonnaud, Eric; Dimnet, Johanes

    2005-02-01

    A prospective radiographic study of 160 volunteers without symptoms of spinal disease was conducted. The objective of this study was to describe, quantify, and classify common variations in the sagittal alignment of the spine, sacrum, and pelvis. Previous publications have documented the high degree of variability in the sagittal alignment of the spine. Other studies have suggested that specific changes in alignment and the characteristics of the lumbar lordosis are responsible for degenerative changes and symptomatic back pain. In the course of this study, anteroposterior and lateral radiographs of 160 volunteers in a standardized standing position were taken. A custom computer application was used to analyze the alignment of the spine and pelvis on the lateral radiographs. A four-part classification scheme of sagittal morphology was used to classify each patient. Reciprocal relationships between the orientation of the sacrum, the sacral slope, the pelvic incidence, and the characteristics of the lumbar lordosis were evident. The global lordotic curvature, lordosis tilt angle, position of the apex, and number or lordotic vertebrae were determined by the angle of the superior endplate of S1 with respect to the horizontal axis. Understanding the patterns of variation in sagittal alignment may help to discover the association between spinal balance and the development of degenerative changes in the spine.

  6. Variational formulation of the method of lines and its application to the wave propagation problems

    CSIR Research Space (South Africa)

    Shatalov, M

    2011-07-01

    Full Text Available accuracy is ( )3 ,O h u t x???? ??? ? (for (1) the error has order ( )2 ,O h u t x??? ??? ? ). For the second order derivative: 18th International Congress on Sound and Vibration, Rio de Janeiro, Brazil, 10-14 July 2011 3... ? ??? ?? ??? ? and first derivative calculation with accuracy ( ) 2 2 2 ,u t xO h x ? ?? ?? ??? ? , gives us the same result as application of the finite difference scheme of accuracy ( ) 4 4 4 ,u t xO h x ? ?? ?? ??? ? to calculation of the second...

  7. Variations in bone density across the body of the immature human mandible.

    Science.gov (United States)

    Hutchinson, Erin F; Farella, Mauro; Hoffman, Jakobus; Kramer, Beverley

    2017-05-01

    During growth the mandible accommodates increases in biomechanical loading resulting from changes in the function of structures of the oral cavity. Biomechanical loads are thought to play an intricate and vital role in the modelling and remodelling of bone, with site-specific effects on bone mineral density. It is anticipated that the effects of this loading on bone mineral density are intensified during the functional transition from prenatal to postnatal stages. The aim of this study was thus to evaluate changes in bone mineral density across the body of the immature human mandible during the early stages of dental development. The study sample included 45 human mandibles, subdivided into three age groups: prenatal (30 gestational weeks to birth; n = 15); early postnatal (birth to 12 months; n = 18); and late postnatal (1-5 years; n = 12). Mandibles were scanned using X-ray micro-computed tomography. Eight landmarks were selected along the buccal/labial and lingual surfaces of each dental crypt for evaluation of the bone mineral density. Bone mineral density values were calculated using a reference standard and analysed using multivariate statistics. The bone mineral density of the lingual surface was found to be significantly higher (P ≤ 0.000) than that of the buccal/labial surface. Furthermore, bone mineral density in the alveolar region of the buccal/labial surface of the deciduous central incisor (P ≤ 0.001), the deciduous first molar (P ≤ 0.013) and lingual alveolar area of the deciduous second molar (P ≤ 0.032) were significantly greater in the early postnatal period than in the prenatal period. While changes in bone mineral density across the lingual surface were consistent with the progression of development and the biomechanical demand of the tongue as previously demonstrated, changes observed across the buccal/labial surface of the mandible appeared to accompany the advancing dental development. Thus, changes in bone mineral density across the

  8. Maritime adaptations and dietary variation in prehistoric Western Alaska: stable isotope analysis of permafrost-preserved human hair.

    Science.gov (United States)

    Britton, Kate; Knecht, Rick; Nehlich, Olaf; Hillerdal, Charlotta; Davis, Richard S; Richards, Michael P

    2013-07-01

    The reconstruction of diet and subsistence strategies is integral in understanding early human colonizations and cultural adaptations, especially in the Arctic-one of the last areas of North America to be permanently inhabited. However, evidence for early subsistence practices in Western Alaska varies, particularly with regards to the emergence, importance, and intensity of sea mammal hunting. Here, we present stable carbon and nitrogen isotope data from permafrost-preserved human hair from two new prehistoric sites in Western Alaska, providing a direct measure of diet. The isotope evidence indicates a heavy reliance on sea mammal protein among the earlier Norton-period group (1,750 ± 40 cal BP), confirming that the complex hunting technologies required to intensively exploit these animals were most likely already in place in this region by at least the beginning of 1st millennium AD. In contrast, analysis of the more recent Thule-period hair samples (650 ± 40 cal BP; 570 ± 30 cal BP) reveals a more mixed diet, including terrestrial animal protein. Sequential isotope analysis of two longer human hair locks indicates seasonal differences in diet in a single Norton-period individual but demonstrates little dietary variation in a Thule-period individual. These analyses provide direct evidence for dietary differences among Alaska's early Eskimo groups and confirm the antiquity of specialized sea mammal hunting and procurement technologies. The results of this study have implications for our understanding of human adaptation to maritime and high-latitude environments, and the geographical and temporal complexity in early Arctic subsistence. Copyright © 2013 Wiley Periodicals, Inc.

  9. Variation of Human Milk Glucocorticoids over 24 hour Period.

    Science.gov (United States)

    Pundir, Shikha; Wall, Clare R; Mitchell, Cameron J; Thorstensen, Eric B; Lai, Ching T; Geddes, Donna T; Cameron-Smith, David

    2017-03-01

    Human milk (HM) contains a complex array of hormones, including members of the glucocorticoid family. The predominant glucocorticoids, cortisol and cortisone may influence the growth and behaviour of the breastfed infant. However, little is understood of the factors regulating the levels of these hormones within HM. The aim of the study was to examine HM cortisol and cortisone concentration, measured in samples collected at each feed during a 24 hour period. Twenty three exclusively breastfeeding mothers collected milk, prior to and after each breastfeeding session over 24 hour period at 3.2(1.60) months. HM cortisol and cortisone levels were measured using high pressure liquid chromatography mass spectroscopy. Cortisone was the predominant glucocorticoid (3.40 ng/ml), and cortisol was detected in all samples (1.62 ng/ml). A positive correlation was found between cortisone and cortisol (r = 0.61, y = 1.93 ± 0.24, p milk expressed for collection either before or immediately after the breastfeed, or between milk collected from the left or right breast. This study shows that HM glucocorticoid concentrations exhibit a 24 hour pattern, with highest peak levels in the early morning, reflecting the circadian pattern as previously reported in plasma. Thus, HM glucocorticoid concentrations are likely to reflect those in the maternal circulation.

  10. Anatomical Variation of Human Sacral Hiatus Its Morphometry and Clinical Importance in Caudal Epidural Anesthesia.

    Directory of Open Access Journals (Sweden)

    Dr. Ashish Khokhariya

    2017-06-01

    Full Text Available Introduction: The sacrum is a bone which contributes to the formation of the pelvic girdle. It has piqued the interest of anatomists, forensic scientists and physicians, especially anaesthetists because of its unique value in gender estimation in medico- legal proceedings as well as the importance of its anatomical structure in relation to the technique of giving caudal anaesthesia. Material & Method:-This study was carried out on 200 dry human sacrum in Bone store of Anatomy Department, B.J Medical College, Ahmedabad, Gujarat. Parameters of sacral hiatus such as shape, level of apex and base, length, antero-posterior (AP diameter at apex, and intercornual distance along with distance between supero-lateral sacral crests and their distance from apex of sacral hiatus were studied. Results: Various shapes of sacral hiatus were observed which included inverted U, inverted V, irregular, dumbbell, bifid and absent of sacral hiatus. Conclusion: The understanding of the sacral hiatus anatomy helps to define landmarks clinically used during the procedure of caudal anaesthesia.

  11. Variation in sorbitol accumulation and polyol-pathway activity in cultured human proximal tubule cells.

    Science.gov (United States)

    Flath, M C; Bylander, J E; Sens, D A

    1992-09-01

    The polyol pathway is present in tissues of several organs where its activation may participate in the development of diabetic complications. We measured the accumulation of polyol-pathway intermediates in HPT cells isolated from 21 different human kidneys from nondiabetic individuals. When exposed to 27.5 mM glucose in the growth media, cells isolated from approximately 75% of individuals (accumulators) accumulated sorbitol within 1-4 days, whereas 25% (nonaccumulators) accumulated only negligible amounts, even when the period of exposure was extended to 2 wk. Surprisingly, measurement of the activities of the polyol-pathway enzymes showed no difference in the levels of either AR or SDH between accumulators and nonaccumulators, even when the conversion of galactose to galactitol was used to measure AR activity in intact cells independently of SDH. Measurement of sorbitol in the growth media indicated that nonaccumulators were not releasing sorbitol into the growth media. Fructose levels in the conditioned growth media were 4 times higher in the sorbitol-accumulating cells. Together, these results indicate that the tendency of cells from an individual to accumulate significant amounts of sorbitol may reflect the cells' ability to metabolize sorbitol in steps subsequent to the polyol pathway.

  12. Sensitivity of Storage Systems in India: Role of Human Behavior Responsive to Low Frequency Climate Variations

    Science.gov (United States)

    Devineni, N.; Perveen, S.; Lall, U.

    2010-12-01

    India is facing a mounting water resources crisis under the midst growing concerns of persistent droughts and floods. These hydroclimatic extremes often result from reduced streamflow/precipitation potential, which could occur due to varying exogenous climatic conditions such as tropical sea surface temperature (SST). As water supply systems experience shortages in supply owing to inflows natural variability, resulting deficits are further exacerbated by increased demand resulting from urbanization and population growth in the region. Given that most of the water supply systems are multipurpose, operating these systems to meet the increased demand under reduced streamflow availability could be very challenging. In this study a low frequency climate variability assessment is presented that provides directions for existing storage systems to adapt to increased and persistent variability in recharge/inflow. Preliminary analysis shows that the sensitivity of reservoirs is high to structured periodic components and this further increases as the storage capacity of the reservoirs decrease. The study also shows that interaction with human behavior is very important in managing deficits from the reservoirs. Hence it is imperative to pursue strategic adaptation measures to increase and effectively manage the storage.

  13. Dynamic knee alignment and collateral knee laxity and its variations in normal humans

    Directory of Open Access Journals (Sweden)

    Kamal eDeep

    2015-11-01

    Full Text Available Alignment of normal, arthritic and replaced human knees is a much debated subject as is the collateral ligamentous laxity. Traditional quantitative values have been challenged. Methods used to measure these are also not without flaws. Authors review the recent literature and a novel method of measurement of these values has been included. This method includes use of computer navigation technique in clinic setting for assessment of the normal or affected knee before the surgery. Computer navigation has been known for achievement of alignment accuracy during knee surgery. Now its use in clinic setting has added to the inventory of measurement methods. Authors dispel the common myth of straight mechanical axis in normal knees and also look at quantification of amount of collateral knee laxity. Based on the scientific studies it has been shown that the mean alignment is in varus in normal knees. It changes from lying non weight bearing position to standing weight bearing position in both coronal and the sagittal planes. It also varies with gender and race. The collateral laxity is also different for males and females. Further studies are needed to define the ideal alignment and collateral laxity which the surgeon should aim for individual knees.

  14. Finding missing heritability in less significant Loci and allelic heterogeneity: genetic variation in human height.

    Directory of Open Access Journals (Sweden)

    Ge Zhang

    Full Text Available Genome-wide association studies (GWAS have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of 'missing' heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus. Using a novel analytical approach we examined allelic heterogeneity of height-associated loci selected from SNPs of different significance levels based on the summary data of the GIANT (stage 1 studies. In a sample of 1,304 individuals collected from an island population of the Adriatic coast of Croatia, we assessed the extent of height variance explained by incorporating the effects of less significant height loci and multiple effective SNPs at the same loci. Our results indicate that approximately half of the 118 loci that achieved stringent genome-wide significance (p-value<5×10(-8 showed evidence of allelic heterogeneity. Additionally, including less significant loci (i.e., p-value<5×10(-4 and accounting for effects of allelic heterogeneity substantially improved the variance explained in height.

  15. Genetic, environmental and epigenetic influences on variation in human tooth number, size and shape.

    Science.gov (United States)

    Townsend, Grant; Bockmann, Michelle; Hughes, Toby; Brook, Alan

    2012-01-01

    The aim of this review is to highlight some key recent developments in studies of tooth number, size and shape that are providing better insights into the roles of genetic, environmental and epigenetic factors in the process of dental development. Advances in molecular genetics are helping to clarify how epigenetic factors influence the spatial and temporal regulation of the complex processes involved in odontogenesis. At the phenotypic level, the development of sophisticated systems for image analysis is enabling new dental phenotypes to be defined. The 2D and 3D data that are generated by these imaging systems can then be analysed with mathematical approaches, such as geometric morphometric analysis. By gathering phenotypic data and DNA from twins, it is now possible to use 'genome-wide' association studies and the monozygotic co-twin design to identify important genes in odontogenesis and also to clarify how epigenetic and environmental factors can affect this process. Given that many of the common dental anomalies affecting the human dentition are interrelated, apparently reflecting pleiotropic genetic effects, the discoveries and new directions described in this paper should have important implications for clinical dental practice in the future.

  16. Proximate causes of the variation of the human sex ratio at birth.

    Science.gov (United States)

    James, William H

    2015-12-01

    There is evidence that the human sex ratio (proportion males at birth) is the result of two processes. First, the sexes of zygotes (from which the primary sex ratio would be calculated) are thought to be partially controlled by the hormone levels of both parents around the time of conception. Second, this primary sex ratio is apparently modified downwards by male-sex-selective spontaneous abortion caused by high levels of maternal stress-induced adrenal androgens, thus yielding the sex ratio at birth (the secondary sex ratio). Since maternal stress is one cause of spontaneous abortion (and of other forms of reproductive sub-optimality), and since some forms of pharmacological treatment of maternal stress are deleterious to the foetus, best practice would suggest non-pharmacological treatment (e.g. psychotherapy, hypnosis or massage) for pregnant women who have a previous history of spontaneous abortion, preterm birth or low-birth-weight infants. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Human longevity and common variations in the LMNA gene: a meta-analysis

    Science.gov (United States)

    Conneely, Karen N.; Capell, Brian C.; Erdos, Michael R.; Sebastiani, Paola; Solovieff, Nadia; Swift, Amy J.; Baldwin, Clinton T.; Budagov, Temuri; Barzilai, Nir; Atzmon, Gil; Puca, Annibale A.; Perls, Thomas T.; Geesaman, Bard J.; Boehnke, Michael; Collins, Francis S.

    2012-01-01

    Summary A mutation in the LMNA gene is responsible for the most dramatic form of premature aging, Hutchinson-Gilford progeria syndrome (HGPS). Several recent studies have suggested that protein products of this gene might have a role in normal physiological cellular senescence. To explore further LMNA's possible role in normal aging, we genotyped 16 SNPs over a span of 75.4 kb of the LMNA gene on a sample of long-lived individuals (US Caucasians with age ≥95 years, N=873) and genetically matched younger controls (N=443). We tested all common non-redundant haplotypes (frequency ≥ 0.05) based on subgroups of these 16 SNPs for association with longevity. The most significant haplotype, based on 4 SNPs, remained significant after adjustment for multiple testing (OR = 1.56, P=2.5×10−5, multiple-testing-adjusted P=0.0045). To attempt to replicate these results, we genotyped 3448 subjects from four independent samples of long-lived individuals and control subjects from 1) the New England Centenarian Study (NECS) (N=738), 2) the Southern Italian Centenarian Study (SICS) (N=905), 3) France (N=1103), and 4) the Einstein Ashkenazi Longevity Study (N=702). We replicated the association with the most significant haplotype from our initial analysis in the NECS sample (OR = 1.60, P=0.0023), but not in the other three samples (P>.15). In a meta-analysis combining all five samples, the best haplotype remained significantly associated with longevity after adjustment for multiple testing in the initial and follow-up samples (OR = 1.18, P=7.5×10−4, multiple-testing-adjusted P=0.037). These results suggest that LMNA variants may play a role in human lifespan. PMID:22340368

  18. Relationship between human physiological parameters and geomagnetic variations of solar origin

    Science.gov (United States)

    Dimitrova, S.

    Results presented concern influence of increased geomagnetic activity on some human physiological parameters. The blood pressure and heart rate of 86 volunteers were measured on working days in autumn 2001 (01/10 09/11) and in spring 2002 (08/04 28/05). These periods were chosen because of maximal expected geomagnetic activity. Altogether 2799 recordings were obtained and analysed. Questionnaire information about subjective psycho-physiological complaints was also gathered. MANOVA was employed to check the significance of the influence of three factors on the physiological parameters under consideration. The factors were the following: (1) planetary geomagnetic activity level estimated by Ap-index and divided into five levels; (2) gender males and females; (3) blood pressure degree persons in the group examined were divided into hypotensive, normotensive and hypertensive. Post hoc analysis was performed to elicit the significance of differences in the factors’ levels. The average arterial blood pressure of the group was found to increase significantly with the increase of geomagnetic activity level. The average increment of systolic and diastolic blood pressure of the group examined reached 9%. This effect was present irrespectively of gender. Results obtained suppose that hypertensive persons have the highest sensitivity and the hypotensive persons have the lowest sensitivity of the arterial blood pressure to increase of geomagnetic activity. The results did not show significant changes in the heart rate. The percentage of the persons who reported subjective psycho-physiological complaints was also found to increase significantly with the geomagnetic activity increase and the highest sensitivity was revealed for the hypertensive females.

  19. Absolute Quantitation of Human Milk Oligosaccharides Reveals Phenotypic Variations during Lactation.

    Science.gov (United States)

    Xu, Gege; Davis, Jasmine Cc; Goonatilleke, Elisha; Smilowitz, Jennifer T; German, J Bruce; Lebrilla, Carlito B

    2017-01-01

    The quantitation of human milk oligosaccharides (HMOs) is challenging because of the structural complexity and lack of standards. The objective of our study was to rapidly measure the absolute concentrations of HMOs in milk using LC-mass spectrometry (MS) and to determine the phenotypic secretor status of the mothers. This quantitative method for measuring HMO concentration was developed by using ultraperformance LC multiple reaction monitoring MS. It was validated and applied to milk samples from Malawi (88 individuals; 88 samples from postnatal month 6) and the United States (Davis, California; 45 individuals, mean age: 32 y; 103 samples collected on postnatal days 10, 26, 71, or 120, repeated measures included). The concentrations of α(1,2)-fucosylated HMOs were used to determine the mothers' phenotypic secretor status with high sensitivity and specificity. We used Friedman's test and Wilcoxon's signed rank test to evaluate the change in HMO concentration during the course of lactation, and Student's t test was used to compare secretors and nonsecretors. A decrease (P milk collected on postnatal day 10, decreasing to 8.53 ± 1.18 g/L on day 120 (repeated measures; n = 14). On postnatal day 180, the total concentration of HMOs in Malawi milk samples from secretors (6.46 ± 1.74 mg/mL) was higher (P milk samples from secretors (4.91 ± 1.22 mg/mL) than from nonsecretors (3.42 ± 2.27 mg/mL) (P milk contains higher concentrations of total and fucosylated HMOs than does nonsecretor milk. These HMO concentrations can be correlated to the health of breastfed infants in order to investigate the protective effects of milk components. The trials were registered at clinicaltrials.gov as NCT01817127 and NCT00524446. © 2017 American Society for Nutrition.

  20. Fringe projection application for surface variation analysis on helical shaped silicon breast

    Science.gov (United States)

    Vairavan, R.; Ong, N. R.; Sauli, Z.; Shahimin, M. M.; Kirtsaeng, S.; Sakuntasathien, S.; Alcain, J. B.; Paitong, P.; Retnasamy, V.

    2017-09-01

    Breast carcinoma is rated as a second collective cause of cancer associated death among adult females. Detection of the disease at an early stage would enhance the chance for survival. Established detection methods such as mammography, ultrasound and MRI are classified as non invasive breast cancer detection modality, but however they are not entire non-invasive as physical contact still occurs to the breast. Thus requirement for a complete non invasive and non contact is evident. Therefore, in this work, a novel application of digital fringe projection for early detection of breast cancer based on breast surface analysis is reported. Phase shift fringe projection technique and pixel tracing method was utilized to analyze the breast surface change due to the incidence of breast lump. Results have shown that the digital fringe projection is capable in detecting the existence of 1 cm sized lump within the breast sample.

  1. On the sum of squared η-μ random variates with application to the performance of wireless communication systems

    KAUST Repository

    Ansari, Imran Shafique

    2013-06-01

    The probability density function (PDF) and cumulative distribution function of the sum of L independent but not necessarily identically distributed squared η-μ variates, applicable to the output statistics of maximal ratio combining (MRC) receiver operating over η-μ fading channels that includes the Hoyt and the Nakagami-m models as special cases, is presented in closed-form in terms of the Fox\\'s H function. Further analysis, particularly on the bit error rate via PDF-based approach, is also represented in closed form in terms of the extended Fox\\'s H function (H). The proposed new analytical results complement previous results and are illustrated by extensive numerical and Monte Carlo simulation results. © 2013 IEEE.

  2. Methodology and Applications of Disease Biomarker Identification in Human Serum

    Directory of Open Access Journals (Sweden)

    Ziad J. Sahab

    2007-01-01

    Full Text Available Biomarkers are biomolecules that serve as indicators of biological and pathological processes, or physiological and pharmacological responses to a drug treatment. Because of the high abundance of albumin and heterogeneity of plasma lipoproteins and glycoproteins, biomarkers are difficult to identify in human serum. Due to the clinical significance the identification of disease biomarkers in serum holds great promise for personalized medicine, especially for disease diagnosis and prognosis. This review summarizes some common and emerging proteomics techniques utilized in the separation of serum samples and identification of disease signatures. The practical application of each protein separation or identification technique is analyzed using specific examples. Biomarkers of cancers of prostate, breast, ovary, and lung in human serum have been reviewed, as well as those of heart disease, arthritis, asthma, and cystic fibrosis. Despite the advancement of technology few biomarkers have been approved by the Food and Drug Administration for disease diagnosis and prognosis due to the complexity of structure and function of protein biomarkers and lack of high sensitivity, specificity, and reproducibility for those putative biomarkers. The combination of different types of technologies and statistical analysis may provide more effective methods to identify and validate new disease biomarkers in blood.Abbreviations: 2-DE, two-dimensional gel electrophoresis; 2DLC-MS, two-dimensional liquid chromatography mass spectrometry; CA 15.3, cancer antigen 15.3; CA 19–9, cancer antigen 19–9, a tumor-associated antigen; CA125, cancer antigen 125, a mucin-like protein; CEA, carcinoembryonic antigen; CF, Cystic Fibrosis; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; ESI-MS/MS, electrospray ionization tandem mass spectrometry; FDA, Food and Drug Administration; IPG, immobilized pH gradient; MALDI-TOF-MS, matrix-assisted laser desorption

  3. Variations in the Post-weaning Human Gut Metagenome Profile As Result of Bifidobacterium Acquisition in the Western Microbiome

    Science.gov (United States)

    Soverini, Matteo; Rampelli, Simone; Turroni, Silvia; Schnorr, Stephanie L.; Quercia, Sara; Castagnetti, Andrea; Biagi, Elena; Brigidi, Patrizia; Candela, Marco

    2016-01-01

    Studies of the gut microbiome variation among human populations revealed the existence of robust compositional and functional layouts matching the three subsistence strategies that describe a trajectory of changes across our recent evolutionary history: hunting and gathering, rural agriculture, and urban post-industrialized agriculture. In particular, beside the overall reduction of ecosystem diversity, the gut microbiome of Western industrial populations is typically characterized by the loss of Treponema and the acquisition of Bifidobacterium as an abundant inhabitant of the post-weaning gut microbial ecosystem. In order to advance the hypothesis about the possible adaptive nature of this exchange, here we explore specific functional attributes that correspond to the mutually exclusive presence of Treponema and Bifidobacterium using publically available gut metagenomic data from Hadza hunter-gatherers and urban industrial Italians. According to our findings, Bifidobacterium provides the enteric ecosystem with a diverse panel of saccharolytic functions, well suited to the array of gluco- and galacto-based saccharides that abound in the Western diet. On the other hand, the metagenomic functions assigned to Treponema are more predictive of a capacity to incorporate complex polysaccharides, such as those found in unrefined plant foods, which are consistently incorporated in the Hadza diet. Finally, unlike Treponema, the Bifidobacterium metagenome functions include genes that permit the establishment of microbe–host immunological cross-talk, suggesting recent co-evolutionary events between the human immune system and Bifidobacterium that are adaptive in the context of agricultural subsistence and sedentary societies. PMID:27462302

  4. Chromatin organization in sperm may be the major functional consequence of base composition variation in the human genome.

    Directory of Open Access Journals (Sweden)

    Tanya Vavouri

    2011-04-01

    Full Text Available Chromatin in sperm is different from that in other cells, with most of the genome packaged by protamines not nucleosomes. Nucleosomes are, however, retained at some genomic sites, where they have the potential to transmit paternal epigenetic information. It is not understood how this retention is specified. Here we show that base composition is the major determinant of nucleosome retention in human sperm, predicting retention very well in both genic and non-genic regions of the genome. The retention of nucleosomes at GC-rich sequences with high intrinsic nucleosome affinity accounts for the previously reported retention at transcription start sites and at genes that regulate development. It also means that nucleosomes are retained at the start sites of most housekeeping genes. We also report a striking link between the retention of nucleosomes in sperm and the establishment of DNA methylation-free regions in the early embryo. Taken together, this suggests that paternal nucleosome transmission may facilitate robust gene regulation in the early embryo. We propose that chromatin organization in the male germline, rather than in somatic cells, is the major functional consequence of fine-scale base composition variation in the human genome. The selective pressure driving base composition evolution in mammals could, therefore, be the need to transmit paternal epigenetic information to the zygote.

  5. Variations in the post-weaning human gut metagenome profile as result of Bifidobacterium acquisition in the Western microbiome

    Directory of Open Access Journals (Sweden)

    Matteo Soverini

    2016-07-01

    Full Text Available Studies of the gut microbiome variation among human populations revealed the existence of robust compositional and functional layouts matching the three subsistence strategies that describe a trajectory of changes across our recent evolutionary history: hunting and gathering, rural agriculture, and urban post-industrialized agriculture. In particular, beside the overall reduction of ecosystem diversity, the gut microbiome of Western industrial populations is typically characterized by the loss of Treponema and the acquisition of Bifidobacterium as an abundant inhabitant of the post-weaning gut microbial ecosystem. In order to advance the hypothesis about the possible adaptive nature of this exchange, here we explore specific functional attributes that correspond to the mutually exclusive presence of Treponema and Bifidobacterium using publically available gut metagenomic data from Hadza hunter-gatherers and urban industrial Italians. According to our findings, Bifidobacterium provides the enteric ecosystem with a diverse panel of saccharolytic functions, well suited to the array of gluco- and galacto-based saccharides that abound in the Western diet. On the other hand, the metagenomic functions assigned to Treponema are more predictive of a capacity to incorporate complex polysaccharides, such as those found in unrefined plant foods, which are consistently incorporated in the Hadza diet. Finally, unlike Treponema, the Bifidobacterium metagenome functions include genes that permit the establishment of microbe-host immunological cross-talk, suggesting recent co-evolutionary events between the human immune system and Bifidobacterium that are adaptive in the context of agricultural subsistence and sedentary societies.

  6. A statistical human rib cage geometry model accounting for variations by age, sex, stature and body mass index.

    Science.gov (United States)

    Shi, Xiangnan; Cao, Libo; Reed, Matthew P; Rupp, Jonathan D; Hoff, Carrie N; Hu, Jingwen

    2014-07-18

    In this study, we developed a statistical rib cage geometry model accounting for variations by age, sex, stature and body mass index (BMI). Thorax CT scans were obtained from 89 subjects approximately evenly distributed among 8 age groups and both sexes. Threshold-based CT image segmentation was performed to extract the rib geometries, and a total of 464 landmarks on the left side of each subject׳s ribcage were collected to describe the size and shape of the rib cage as well as the cross-sectional geometry of each rib. Principal component analysis and multivariate regression analysis were conducted to predict rib cage geometry as a function of age, sex, stature, and BMI, all of which showed strong effects on rib cage geometry. Except for BMI, all parameters also showed significant effects on rib cross-sectional area using a linear mixed model. This statistical rib cage geometry model can serve as a geometric basis for developing a parametric human thorax finite element model for quantifying effects from different human attributes on thoracic injury risks. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Ethnic Variations in Perception of Human Papillomavirus and its Vaccination among Young Women in Nepal .

    Science.gov (United States)

    Sathian, Brijesh; Babu, M G Ramesh; van Teijlingen, Edwin R; Banerjee, Indrajit; Roy, Bedanta; Subramanya, Supram Hosuru; Rajesh, Elayedath; Devkota, Suresh

    2017-03-01

    The Human Papillomavirus (HPV) is strongly associated with cervical and other cancers. In women, cervical cancer is the third most common cancer. HPV infection can be largely prevented through vaccination of (adolescent) girls. At the same time, Nepal is a low-income country experiencing a cultural change in attitudes towards sex and sexual behaviour. However, in the adolescent population knowledge about HPV, factors associated with an increased risk of HPV and the existence of the vaccination is often low. This was a cross-sectional study with female students enrolled in health and non-health science courses in Pokhara, Nepal. The questionnaire included demographic details, knowledge and attitude questions related to HPV, associated risk behaviour and its vaccination. Descriptive statistics, including Chi-Square test, were used to identify statistically significant relationships. Ethical approval was granted by the relevant authority in Nepal. Hindu religion (75.0 %; 95% CI: 70.9, 78.6) and Newari caste (75.5%; CI: 61.1, 86.7) were more aware about HPV, HPV vaccination. Hindus religion (55.6%; 95% CI: 51.