Science.gov

Sample records for understanding human developmental

  1. Mouse models for understanding human developmental anomalies

    SciTech Connect

    Generoso, W.M.

    1989-01-01

    The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals.

  2. Why a developmental perspective is critical for understanding human cognition.

    PubMed

    D'Souza, Dean; Karmiloff-Smith, Annette

    2016-01-01

    The evidence that Anderson (2014) marshals in support of his theory of neural reuse is persuasive. However, his theoretical framework currently lacks a developmental dimension. We argue that an account of the fundamental aspects of developmental change, as well as the temporal context within which change occurs, would greatly enhance Anderson's theory. PMID:27561656

  3. The new dysmorphology: application of insights from basic developmental biology to the understanding of human birth defects.

    PubMed Central

    Epstein, C J

    1995-01-01

    Information obtained from studies of developmental and cellular processes in lower organisms is beginning to make significant contributions to the understanding of the pathogenesis of human birth defects, and it is now becoming possible to treat birth defects as inborn errors of development. Mutations in genes for transcription factors, receptors, cell adhesion molecules, intercellular junctions, molecules involved in signal transduction, growth factors, structural proteins, enzymes, and transporters have been identified in genetically caused human malformations and dysplasias. The identification of these mutations and the analysis of their developmental effects have been greatly facilitated by the existence of natural or engineered models in the mouse and even of related mutations in Drosophila, and in some instances a remarkable conservation of function in development has been observed, even between widely separated species. PMID:7567976

  4. Using Developmental Trajectories to Understand Developmental Disorders

    ERIC Educational Resources Information Center

    Thomas, Michael S. C.; Annaz, Dagmara; Ansari, Daniel; Scerif, Gaia; Jarrold, Chris; Karmiloff-Smith, Annette

    2009-01-01

    Purpose: In this article, the authors present a tutorial on the use of developmental trajectories for studying language and cognitive impairments in developmental disorders and compare this method with the use of matching. Method: The authors assess the strengths, limitations, and practical implications of each method. The contrast between the…

  5. NEW FRONTIER IN UNDERSTANDING THE MECHANISMS OF DEVELOPMENTAL ABNORMALITIES

    EPA Science Inventory

    Recent advancements in molecular developmental biology afford an opportunity to apply newly developed tools for understanding the mechanisms of both normal and abnormal development. lthough a number of agents have been identified as causing developmental abnormalities, knowledge ...

  6. Many human accelerated regions are developmental enhancers

    PubMed Central

    Capra, John A.; Erwin, Genevieve D.; McKinsey, Gabriel; Rubenstein, John L. R.; Pollard, Katherine S.

    2013-01-01

    The genetic changes underlying the dramatic differences in form and function between humans and other primates are largely unknown, although it is clear that gene regulatory changes play an important role. To identify regulatory sequences with potentially human-specific functions, we and others used comparative genomics to find non-coding regions conserved across mammals that have acquired many sequence changes in humans since divergence from chimpanzees. These regions are good candidates for performing human-specific regulatory functions. Here, we analysed the DNA sequence, evolutionary history, histone modifications, chromatin state and transcription factor (TF) binding sites of a combined set of 2649 non-coding human accelerated regions (ncHARs) and predicted that at least 30% of them function as developmental enhancers. We prioritized the predicted ncHAR enhancers using analysis of TF binding site gain and loss, along with the functional annotations and expression patterns of nearby genes. We then tested both the human and chimpanzee sequence for 29 ncHARs in transgenic mice, and found 24 novel developmental enhancers active in both species, 17 of which had very consistent patterns of activity in specific embryonic tissues. Of these ncHAR enhancers, five drove expression patterns suggestive of different activity for the human and chimpanzee sequence at embryonic day 11.5. The changes to human non-coding DNA in these ncHAR enhancers may modify the complex patterns of gene expression necessary for proper development in a human-specific manner and are thus promising candidates for understanding the genetic basis of human-specific biology. PMID:24218637

  7. Understanding and Counseling Gay Men: A Developmental Perspective.

    ERIC Educational Resources Information Center

    Gumaer, James

    1987-01-01

    Reviews current concepts and research concerning homosexuality with emphasis on understanding gay men and their relationship behaviors. Presents counseling considerations from a developmental perspective, and includes a case example. (Author/KS)

  8. Developmental biomechanics of the human cervical spine.

    PubMed

    Nuckley, David J; Linders, David R; Ching, Randal P

    2013-04-01

    Head and neck injuries, the leading cause of death for children in the U.S., are difficult to diagnose, treat, and prevent because of a critical void in our understanding of the biomechanical response of the immature cervical spine. The objective of this study was to investigate the functional and failure biomechanics of the cervical spine across multiple axes of loading throughout maturation. A correlational study design was used to examine the relationships governing spinal maturation and biomechanical flexibility curves and tolerance data using a cadaver human in vitro model. Eleven human cadaver cervical spines from across the developmental spectrum (2-28 years) were dissected into segments (C1-C2, C3-C5, and C6-C7) for biomechanical testing. Non-destructive flexibility tests were performed in tension, compression, flexion, extension, lateral bending, and axial rotation. After measuring their intact biomechanical responses, each segment group was failed in different modes to measure the tissue tolerance in tension (C1-C2), compression (C3-C5), and extension (C5-C6). Classical injury patterns were observed in all of the specimens tested. Both the functional (p<0.014) and failure (p<0.0001) mechanics exhibited significant relationships with age. Nonlinear flexibility curves described the functional response of the cervical spine throughout maturation and elucidated age, spinal level, and mode of loading specificity. These data support our understanding of the child cervical spine from a developmental perspective and facilitate the generation of injury prevention or management schema for the mitigation of child spine injuries and their deleterious effects. PMID:23415075

  9. How Neuropsychology Informs Our Understanding of Developmental Disorders

    ERIC Educational Resources Information Center

    Pennington, Bruce F.

    2009-01-01

    This review includes 1) an explanation of what neuropsychology is, 2) a brief history of how developmental cognitive neuroscience emerged from earlier neuropsychological approaches to understanding atypical development, 3) three recent examples that illustrate the benefits of this approach, 4) issues and challenges this approach must face, and 5)…

  10. DEVELOPMENTAL IMMUNOTOXICITY AND HUMAN DEVELOPMENT

    EPA Science Inventory

    To compile literature information for web-based dissemination. The report will be on our current understanding of the science of development of the immune system, to provide examples of perturbations that can be brought about by environmental agents and that could produce effects...

  11. Cognitive and developmental components of understanding the nature of science

    NASA Astrophysics Data System (ADS)

    Dotger, Sharon

    The purpose of this study is to determine the degree to which years of education, college major, or reflective judgment stage influences individual's understandings of the nature of science. Using a cross-sectional design influenced by the literature describing the development of reflective judgment and nature of science understandings, this study encompasses the viewpoints of 323 individuals from ninth grade through graduate study. This research involves the careful selection of instruments for assessing these two complex constructs, and the processes used to select and rate participants responses is described in detail. Multinomial ordinal regression was used to determine the significance of educational level, major, and reflective judgment on nature of science views. Results indicate that high school students as a whole are least likely to respond appropriately to questions about the nature of science. However, the performance of college students is inconsistent with predictions, college freshmen more often select the desired response than college seniors or graduate students. Additionally, college major has no significant impact on nature of science understandings. Reflective judgment, a term that describes cognitive developmental model of advanced thinking skills, is found to have the most significant correlations with nature of science views. Reflective thinkers are more likely to select the desired nature of science response than quasi-reflective and pre-reflective thinkers for six of the ten questions. Discussion of results is followed by implications for science teaching and learning in K-12 classrooms.

  12. Toward Developmental Connectomics of the Human Brain.

    PubMed

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental

  13. Toward Developmental Connectomics of the Human Brain

    PubMed Central

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental

  14. BRAF gene: From human cancers to developmental syndromes

    PubMed Central

    Hussain, Muhammad Ramzan Manwar; Baig, Mukhtiar; Mohamoud, Hussein Sheik Ali; Ulhaq, Zaheer; Hoessli, Daniel C.; Khogeer, Ghaidaa Siraj; Al-Sayed, Ranem Radwan; Al-Aama, Jumana Yousuf

    2014-01-01

    The BRAF gene encodes for a serine/threonine protein kinase that participates in the MAPK/ERK signalling pathway and plays a vital role in cancers and developmental syndromes (RASopathies). The current review discusses the clinical significance of the BRAF gene and other members of RAS/RAF cascade in human cancers and RAS/MAPK syndromes, and focuses the molecular basis and clinical genetics of BRAF to better understand its parallel involvement in both tumourigenesis and RAS/MAPK syndromes—Noonan syndrome, cardio-facio-cutaneous syndrome and LEOPARD syndrome. PMID:26150740

  15. Developmental and individual differences in understanding of fractions.

    PubMed

    Siegler, Robert S; Pyke, Aryn A

    2013-10-01

    We examined developmental and individual differences in 6th and 8th graders' fraction arithmetic and overall mathematics achievement and related them to differences in understanding of fraction magnitudes, whole number division, executive functioning, and metacognitive judgments within a cross-sectional design. Results indicated that the difference between low achieving and higher achieving children's fraction arithmetic knowledge, already substantial in 6th grade, was much greater in 8th grade. The fraction arithmetic knowledge of low achieving children was similar in the 2 grades, whereas higher achieving children showed much greater knowledge in 8th than 6th grade, despite both groups having been in the same classrooms, using the same textbooks, and having the same teachers and classmates. Individual differences in both fraction arithmetic and mathematics achievement test scores were predicted by differences in fraction magnitude knowledge and whole number division, even after the contributions of reading achievement and executive functioning were statistically controlled. Instructional implications of the findings are discussed. PMID:23244401

  16. Understanding Human Mobility from Twitter

    PubMed Central

    Jurdak, Raja; Zhao, Kun; Liu, Jiajun; AbouJaoude, Maurice; Cameron, Mark; Newth, David

    2015-01-01

    Understanding human mobility is crucial for a broad range of applications from disease prediction to communication networks. Most efforts on studying human mobility have so far used private and low resolution data, such as call data records. Here, we propose Twitter as a proxy for human mobility, as it relies on publicly available data and provides high resolution positioning when users opt to geotag their tweets with their current location. We analyse a Twitter dataset with more than six million geotagged tweets posted in Australia, and we demonstrate that Twitter can be a reliable source for studying human mobility patterns. Our analysis shows that geotagged tweets can capture rich features of human mobility, such as the diversity of movement orbits among individuals and of movements within and between cities. We also find that short- and long-distance movers both spend most of their time in large metropolitan areas, in contrast with intermediate-distance movers’ movements, reflecting the impact of different modes of travel. Our study provides solid evidence that Twitter can indeed be a useful proxy for tracking and predicting human movement. PMID:26154597

  17. Understanding individual human mobility patterns

    NASA Astrophysics Data System (ADS)

    González, Marta C.; Hidalgo, Cesar A.; Barabási, Albert-Lászlo

    2008-03-01

    Understanding human mobility patterns is of major importance for a number of areas, ranging from urban planning to traffic forecasting, transportation geography, and preventing the spread of biological and mobile viruses. Yet, in the absence of tools to monitor the time resolved location of a large number of individuals, our understanding of the basic laws governing human trajectories remains limited. Here we study the individual mobility pattern of mobile phone users whose position is tracked in a time resolved manner. We find that the displacement distribution of the whole population can be approximated with a truncated L'evy statistics, in agreement with earlier measurements. We show, however, that the main contribution to the observed distribution comes from the differences in the travel pattern of individuals. Furthermore, we find that the individual trajectories are bounded in space and are highly anisotropic, an effect that increases with the trajectory's radius of gyration. After we correct for differences in the radius of gyration and anisotropy all individuals are described by the same universal mobility pattern. These results open new avenues for modeling human motion, with important impact on agent based modeling, epidemic prevention, emergency response and urban planing.

  18. A relational framework for understanding bullying: Developmental antecedents and outcomes.

    PubMed

    Rodkin, Philip C; Espelage, Dorothy L; Hanish, Laura D

    2015-01-01

    This article reviews current research on the relational processes involved in peer bullying, considering developmental antecedents and long-term consequences. The following themes are highlighted: (a) aggression can be both adaptive and maladaptive, and this distinction has implications for bullies' functioning within peer social ecologies; (b) developmental antecedents and long-term consequences of bullying have not been well-distinguished from the extant research on aggressive behavior; (c) bullying is aggression that operates within relationships of power and abuse. Power asymmetry and repetition elements of traditional bullying definitions have been hard to operationalize, but without these specifications and more dyadic measurement approaches there may be little rationale for a distinct literature on bullying--separate from aggression. Applications of a relational approach to bullying are provided using gender as an example. Implications for future research are drawn from the study of relationships and interpersonal theories of developmental psychopathology. PMID:25961312

  19. Educational Opportunities, Developmental Challenges: Understanding Nontraditional College Students.

    ERIC Educational Resources Information Center

    Benshoff, James M.

    Over the last 20 years, the percentage of older students on college campuses has increased dramatically. Because developmental needs, issues, and stressors for adults differ from those of younger students, the college environment must be reconsidered to respond to adult students. Adult learners tend to be achievement oriented, highly motivated,…

  20. Genomic approaches to studying human-specific developmental traits.

    PubMed

    Franchini, Lucía F; Pollard, Katherine S

    2015-09-15

    Changes in developmental regulatory programs drive both disease and phenotypic differences among species. Linking human-specific traits to alterations in development is challenging, because we have lacked the tools to assay and manipulate regulatory networks in human and primate embryonic cells. This field was transformed by the sequencing of hundreds of genomes--human and non-human--that can be compared to discover the regulatory machinery of genes involved in human development. This approach has identified thousands of human-specific genome alterations in developmental genes and their regulatory regions. With recent advances in stem cell techniques, genome engineering, and genomics, we can now test these sequences for effects on developmental gene regulation and downstream phenotypes in human cells and tissues. PMID:26395139

  1. Understanding developmental pharmacodynamics: importance for drug development and clinical practice.

    PubMed

    Mulla, Hussain

    2010-08-01

    Developmental pharmacodynamics is the study of age-related maturation of the structure and function of biologic systems and how this affects response to pharmacotherapy. This may manifest as a change in the potency, efficacy, or therapeutic range of a drug. The paucity of studies exploring developmental pharmacodynamics reflects the lack of suitable juvenile animal models and the ethical and practical constraints of conducting studies in children. However, where data from animal models are available, valuable insight has been gained into how response to therapy can change through the course of development. For example, animal neurodevelopmental models have revealed that temporal differences in the maturation of norepinephrine and serotonin neurotransmitter systems may explain the lack of efficacy of some antidepressants in children. GABA(A) receptors that switch from an excitatory to inhibitory mode during early development help to explain paradoxical seizures experienced by infants after exposure to benzodiazepines. The increased sensitivity of neonates to morphine may be due to increased postnatal expression of the mu opioid receptor. An age dependency to the pharmacokinetic-pharmacodynamic relationship has also been found in some clinical studies. For example, immunosuppressive effects of ciclosporin (cyclosporine) revealed markedly enhanced sensitivity in infants compared with older children and adults. A study of sotalol in the treatment of children with supraventricular tachycardia showed that neonates exhibited a higher sensitivity towards QTc interval prolongation compared with older children. However, the data are limited and efforts to increase and establish data on developmental pharmacodynamics are necessary to achieve optimal drug therapy in children and to ensure long-term success of pediatric drug development. This requires a dual 'bottom up' (ontogeny knowledge driven) and 'top down' (pediatric pharmacokinetic-pharmacodynamic studies) approach. PMID

  2. Understanding Peace and War: A Review of Developmental Psychology Research.

    ERIC Educational Resources Information Center

    Hakvoort, Ilse; Oppenheimer, Louis

    1998-01-01

    Reviews studies of children's and adolescents' understanding of peace and war. Maintains that findings are influenced by measurement procedures and design and by a number of variables. Notes that recent studies suggest a relationship between understanding of interpersonal relationships and understanding of peace. Other variables such as social…

  3. Multidisciplinary approaches to understanding collective cell migration in developmental biology.

    PubMed

    Schumacher, Linus J; Kulesa, Paul M; McLennan, Rebecca; Baker, Ruth E; Maini, Philip K

    2016-06-01

    Mathematical models are becoming increasingly integrated with experimental efforts in the study of biological systems. Collective cell migration in developmental biology is a particularly fruitful application area for the development of theoretical models to predict the behaviour of complex multicellular systems with many interacting parts. In this context, mathematical models provide a tool to assess the consistency of experimental observations with testable mechanistic hypotheses. In this review, we showcase examples from recent years of multidisciplinary investigations of neural crest cell migration. The neural crest model system has been used to study how collective migration of cell populations is shaped by cell-cell interactions, cell-environmental interactions and heterogeneity between cells. The wide range of emergent behaviours exhibited by neural crest cells in different embryonal locations and in different organisms helps us chart out the spectrum of collective cell migration. At the same time, this diversity in migratory characteristics highlights the need to reconcile or unify the array of currently hypothesized mechanisms through the next generation of experimental data and generalized theoretical descriptions. PMID:27278647

  4. Multidisciplinary approaches to understanding collective cell migration in developmental biology

    PubMed Central

    Schumacher, Linus J.; Kulesa, Paul M.; McLennan, Rebecca; Baker, Ruth E.; Maini, Philip K.

    2016-01-01

    Mathematical models are becoming increasingly integrated with experimental efforts in the study of biological systems. Collective cell migration in developmental biology is a particularly fruitful application area for the development of theoretical models to predict the behaviour of complex multicellular systems with many interacting parts. In this context, mathematical models provide a tool to assess the consistency of experimental observations with testable mechanistic hypotheses. In this review, we showcase examples from recent years of multidisciplinary investigations of neural crest cell migration. The neural crest model system has been used to study how collective migration of cell populations is shaped by cell–cell interactions, cell–environmental interactions and heterogeneity between cells. The wide range of emergent behaviours exhibited by neural crest cells in different embryonal locations and in different organisms helps us chart out the spectrum of collective cell migration. At the same time, this diversity in migratory characteristics highlights the need to reconcile or unify the array of currently hypothesized mechanisms through the next generation of experimental data and generalized theoretical descriptions. PMID:27278647

  5. Understanding loneliness during adolescence: developmental changes that increase the risk of perceived social isolation.

    PubMed

    Laursen, Brett; Hartl, Amy C

    2013-12-01

    Loneliness is typically defined in terms of feeling states. In this review, we take a somewhat different approach, describing loneliness in terms of perceived social isolation. Vulnerabilities to perceived social isolation differ across the lifespan. Unique properties of adolescence are identified that carry special risk for perceived social isolation. These include (but are not limited to) developmental changes in companions, developmental changes in autonomy and individuation, identity exploration, cognitive maturation, developmental changes in social perspective taking, and physical maturation. Scholars are encouraged to consider loneliness through the lens of perceived social isolation so as to better understand how the experience of physical isolation varies across adolescence. PMID:23866959

  6. Developmental Changes in Children's Understandings of Intelligence and Thinking Skills

    ERIC Educational Resources Information Center

    Burke, Lynsey A.; Williams, Joanne M.

    2009-01-01

    Research on children's concepts of intelligence has not considered how children conceptualise specific thinking skills. This study extends previous research on the development of children's concepts of intelligence and produces novel data on children's understandings of effective thinking and thinking skills. Seventy-five children were sampled…

  7. Reading Comprehension and Understanding Idiomatic Expressions: A Developmental Study

    ERIC Educational Resources Information Center

    Chiara Levorato, Maria; Nesi, Barbara; Cacciari, Cristina

    2004-01-01

    The aim of the present study was to investigate idiom comprehension in school-age Italian children with different reading comprehension skills. According to our hypothesis, the level of a child's text comprehension skills should predict his/her ability to understand idiomatic meanings. Idiom comprehension in fact requires children to go beyond a…

  8. Developmental Changes in Children's Understanding of Future Likelihood and Uncertainty

    ERIC Educational Resources Information Center

    Lagattuta, Kristin Hansen; Sayfan, Liat

    2011-01-01

    Two measures assessed 4-10-year-olds' and adults' (N = 201) understanding of future likelihood and uncertainty. In one task, participants sequenced sets of event pictures varying by one physical dimension according to increasing future likelihood. In a separate task, participants rated characters' thoughts about the likelihood of future events,…

  9. Contributions of Neuropsychology to Our Understanding of Developmental Reading Problems.

    ERIC Educational Resources Information Center

    Riccio, Cynthia A.; Hynd, George W.

    1995-01-01

    Examines how neuropsychological research has increased understanding of the reading process and reading disabilities in children. Variations in impaired processes in reading disabilities can best be understood when brain-behavior relations involved in reading are conceptualized as a widespread functional system. Discusses implications for…

  10. Community College Developmental Education Students' Understanding of Foundational Fraction Concepts

    ERIC Educational Resources Information Center

    Alexander, Cathleen Marie

    2013-01-01

    Mathematics, in general, and algebra courses, in particular, have been categorized as "gatekeepers" for higher education, better jobs, and even citizenship. For many low-income and working adults, community college is the institution where they choose to develop their mathematics understanding so they can pursue their dreams.…

  11. A microbial perspective of human developmental biology.

    PubMed

    Charbonneau, Mark R; Blanton, Laura V; DiGiulio, Daniel B; Relman, David A; Lebrilla, Carlito B; Mills, David A; Gordon, Jeffrey I

    2016-07-01

    When most people think of human development, they tend to consider only human cells and organs. Yet there is another facet that involves human-associated microbial communities. A microbial perspective of human development provides opportunities to refine our definitions of healthy prenatal and postnatal growth and to develop innovative strategies for disease prevention and treatment. Given the dramatic changes in lifestyles and disease patterns that are occurring with globalization, we issue a call for the establishment of 'human microbial observatories' designed to examine microbial community development in birth cohorts representing populations with diverse anthropological characteristics, including those undergoing rapid change. PMID:27383979

  12. A Clinical Case Presentation: Understanding and Interpreting Dreams while Working Through Developmental Trauma.

    PubMed

    Levy, Joshua; Finnegan, Paul

    2016-02-01

    The purpose of this paper is to demonstrate the unique place of understanding and interpreting dreams in the psychoanalytic process while working through developmental trauma. This psychoanalytic process extended over six years and is presented in four phases: establishing the therapeutic alliance, a crisis, working through, and termination. Dreams from each of these four phases of the analysis are presented, and the collaborative work of understanding and interpreting these dreams is highlighted. Evidence is presented that from this analytic work there ensued an amelioration of the impact of developmental trauma and a furtherance of the development of internal psychic structure. PMID:26951293

  13. Understanding adverse events: human factors.

    PubMed Central

    Reason, J

    1995-01-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  14. Developmental neuroimaging of the human ventral visual cortex

    PubMed Central

    Grill-Spector, Kalanit; Golarai, Golijeh; Gabrieli, John

    2013-01-01

    Here, we review recent results that investigate the development of the human ventral stream from childhood, through adolescence and into adulthood. Converging evidence suggests a differential developmental trajectory across ventral stream regions, in which face-selective regions show a particularly long developmental time course, taking more than a decade to become adult-like. We discuss the implications of these recent findings, how they relate to age-dependent improvements in recognition memory performance and propose possible neural mechanisms that might underlie this development. These results have important implications regarding the role of experience in shaping the ventral stream and the nature of the underlying representations. PMID:18359267

  15. Characterizing Key Developmental Understandings and Pedagogically Powerful Ideas within a Statistical Knowledge for Teaching Framework

    ERIC Educational Resources Information Center

    Groth, Randall E.

    2013-01-01

    A hypothetical framework to characterize statistical knowledge for teaching (SKT) is described. Empirical grounding for the framework is provided by artifacts from an undergraduate course for prospective teachers that concentrated on the development of SKT. The theoretical notion of "key developmental understanding" (KDU) is used to identify…

  16. Have Disfluency-Type Measures Contributed to the Understanding and Treatment of Developmental Stuttering?

    ERIC Educational Resources Information Center

    Einarsdottir, Johanna; Ingham, Roger J.

    2005-01-01

    Purpose: This article critically reviews evidence to determine whether the use of disfluency typologies, such as "syllable repetitions" or "prolongations", has assisted the understanding or treatment of developmental stuttering. Consideration is given to whether there is a need for a fundamental shift in the basis for constructing measures of…

  17. Theory of Mind "Emotion", Developmental Characteristics and Social Understanding in Children and Adolescents with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Thirion-Marissiaux, Anne-Francoise; Nader-Grosbois, Nathalie

    2008-01-01

    Patterns of development of ToM-emotion abilities in intellectually disabled (ID) children and typically developing (TD) children matched on their developmental age were investigated. The links between cognition, language, social understanding and ToM-emotion abilities were examined. EDEI-R (Perron-Borelli, M. (1996). "Echelles Differentielles…

  18. The Developmental Model of Intercultural Sensitivity: A Tool for Understanding Principals' Cultural Competence

    ERIC Educational Resources Information Center

    Hernandez, Frank; Kose, Brad W.

    2012-01-01

    Principals' understanding and skills pertaining to diversity are important in leading diverse schools and preparing all students for a democratic and multicultural society. Although educational leadership scholars have theorized about exemplary leadership of and for diversity, a developmental perspective on principals' diversity or cultural…

  19. Understanding Developmental Reversals in False Memory: Reply to Ghetti (2008) and Howe (2008)

    ERIC Educational Resources Information Center

    Brainerd, C. J.; Reyna, V. F.; Ceci, S. J.; Holliday, R. E.

    2008-01-01

    S. Ghetti (2008) and M. L. Howe (2008) presented probative ideas for future research that will deepen scientific understanding of developmental reversals on false memory and establish boundary conditions for these counterintuitive patterns. Ghetti extended the purview of current theoretical principles by formulating hypotheses about how…

  20. Developmental atlas of the early first trimester human embryo.

    PubMed

    Yamada, Shigehito; Samtani, Rajeev R; Lee, Elaine S; Lockett, Elizabeth; Uwabe, Chigako; Shiota, Kohei; Anderson, Stasia A; Lo, Cecilia W

    2010-06-01

    Rapid advances in medical imaging are facilitating the clinical assessment of first-trimester human embryos at increasingly earlier stages. To obtain data on early human development, we used magnetic resonance (MR) imaging and episcopic fluorescence capture (EFIC) to acquire digital images of human embryos spanning the time of dynamic tissue remodeling and organogenesis (Carnegie stages 13 to 23). These imaging data sets are readily resectioned digitally in arbitrary planes, suitable for rapid high-resolution three-dimensional (3D) observation. Using these imaging datasets, a web-accessible digital Human Embryo Atlas (http://apps.devbio.pitt.edu/humanatlas/) was created containing serial 2D images of human embryos in three standard histological planes: sagittal, frontal, and transverse. In addition, annotations and 3D reconstructions were generated for visualizing different anatomical structures. Overall, this Human Embryo Atlas is a unique resource that provides morphologic data of human developmental anatomy that can accelerate basic research investigations into developmental mechanisms that underlie human congenital anomalies. PMID:20503356

  1. Understanding human management of automation errors

    PubMed Central

    McBride, Sara E.; Rogers, Wendy A.; Fisk, Arthur D.

    2013-01-01

    Automation has the potential to aid humans with a diverse set of tasks and support overall system performance. Automated systems are not always reliable, and when automation errs, humans must engage in error management, which is the process of detecting, understanding, and correcting errors. However, this process of error management in the context of human-automation interaction is not well understood. Therefore, we conducted a systematic review of the variables that contribute to error management. We examined relevant research in human-automation interaction and human error to identify critical automation, person, task, and emergent variables. We propose a framework for management of automation errors to incorporate and build upon previous models. Further, our analysis highlights variables that may be addressed through design and training to positively influence error management. Additional efforts to understand the error management process will contribute to automation designed and implemented to support safe and effective system performance. PMID:25383042

  2. On Expression Patterns and Developmental Origin of Human Brain Regions

    PubMed Central

    Kirsch, Lior; Chechik, Gal

    2016-01-01

    Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions. PMID:27564987

  3. A developmental approach to understanding drawings and narratives from children displaced by Hurricane Katrina.

    PubMed

    Looman, Wendy Sue

    2006-01-01

    Using art as a process to help children externalize complex feelings can add another layer of assessment in the primary care setting. In the face of trauma, drawing may help children gain symbolic control over events that are confusing and frightening. Through examples of children who were affected by Hurricane Katrina, this article describes the use of drawings and narratives to understand children's experiences related to traumatic displacement. Recommendations include using a developmental lens to understanding children's art, asking children to talk about their drawings, and considering the significance of place for children who have been traumatically displaced. PMID:16675376

  4. Short Faces, Big Tongues: Developmental Origin of the Human Chin

    PubMed Central

    Coquerelle, Michael; Prados-Frutos, Juan Carlos; Rojo, Rosa; Mitteroecker, Philipp; Bastir, Markus

    2013-01-01

    During the course of human evolution, the retraction of the face underneath the braincase, and closer to the cervical column, has reduced the horizontal dimension of the vocal tract. By contrast, the relative size of the tongue has not been reduced, implying a rearrangement of the space at the back of the vocal tract to allow breathing and swallowing. This may have left a morphological signature such as a chin (mental prominence) that can potentially be interpreted in Homo. Long considered an autopomorphic trait of Homo sapiens, various extinct hominins show different forms of mental prominence. These features may be the evolutionary by-product of equivalent developmental constraints correlated with an enlarged tongue. In order to investigate developmental mechanisms related to this hypothesis, we compare modern 34 human infants against 8 chimpanzee fetuses, whom development of the mandibular symphysis passes through similar stages. The study sets out to test that the shared ontogenetic shape changes of the symphysis observed in both species are driven by the same factor – the space restriction at the back of the vocal tract and the associated arrangement of the tongue and hyoid bone. We apply geometric morphometric methods to extensive three-dimensional anatomical landmarks and semilandmarks configuration, capturing the geometry of the cervico-craniofacial complex including the hyoid bone, tongue muscle and the mandible. We demonstrate that in both species, the forward displacement of the mental region derives from the arrangement of the tongue and hyoid bone, in order to cope with the relative horizontal narrowing of the oral cavity. Because humans and chimpanzees share this pattern of developmental integration, the different forms of mental prominence seen in some extinct hominids likely originate from equivalent ontogenetic constraints. Variations in this process could account for similar morphologies. PMID:24260566

  5. Short faces, big tongues: developmental origin of the human chin.

    PubMed

    Coquerelle, Michael; Prados-Frutos, Juan Carlos; Rojo, Rosa; Mitteroecker, Philipp; Bastir, Markus

    2013-01-01

    During the course of human evolution, the retraction of the face underneath the braincase, and closer to the cervical column, has reduced the horizontal dimension of the vocal tract. By contrast, the relative size of the tongue has not been reduced, implying a rearrangement of the space at the back of the vocal tract to allow breathing and swallowing. This may have left a morphological signature such as a chin (mental prominence) that can potentially be interpreted in Homo. Long considered an autopomorphic trait of Homo sapiens, various extinct hominins show different forms of mental prominence. These features may be the evolutionary by-product of equivalent developmental constraints correlated with an enlarged tongue. In order to investigate developmental mechanisms related to this hypothesis, we compare modern 34 human infants against 8 chimpanzee fetuses, whom development of the mandibular symphysis passes through similar stages. The study sets out to test that the shared ontogenetic shape changes of the symphysis observed in both species are driven by the same factor--space restriction at the back of the vocal tract and the associated arrangement of the tongue and hyoid bone. We apply geometric morphometric methods to extensive three-dimensional anatomical landmarks and semilandmarks configuration, capturing the geometry of the cervico-craniofacial complex including the hyoid bone, tongue muscle and the mandible. We demonstrate that in both species, the forward displacement of the mental region derives from the arrangement of the tongue and hyoid bone, in order to cope with the relative horizontal narrowing of the oral cavity. Because humans and chimpanzees share this pattern of developmental integration, the different forms of mental prominence seen in some extinct hominids likely originate from equivalent ontogenetic constraints. Variations in this process could account for similar morphologies. PMID:24260566

  6. Developmental evidence for obstetric adaptation of the human female pelvis.

    PubMed

    Huseynov, Alik; Zollikofer, Christoph P E; Coudyzer, Walter; Gascho, Dominic; Kellenberger, Christian; Hinzpeter, Ricarda; Ponce de León, Marcia S

    2016-05-10

    The bony pelvis of adult humans exhibits marked sexual dimorphism, which is traditionally interpreted in the framework of the "obstetrical dilemma" hypothesis: Giving birth to large-brained/large-bodied babies requires a wide pelvis, whereas efficient bipedal locomotion requires a narrow pelvis. This hypothesis has been challenged recently on biomechanical, metabolic, and biocultural grounds, so that it remains unclear which factors are responsible for sex-specific differences in adult pelvic morphology. Here we address this issue from a developmental perspective. We use methods of biomedical imaging and geometric morphometrics to analyze changes in pelvic morphology from late fetal stages to adulthood in a known-age/known-sex forensic/clinical sample. Results show that, until puberty, female and male pelves exhibit only moderate sexual dimorphism and follow largely similar developmental trajectories. With the onset of puberty, however, the female trajectory diverges substantially from the common course, resulting in rapid expansion of obstetrically relevant pelvic dimensions up to the age of 25-30 y. From 40 y onward females resume a mode of pelvic development similar to males, resulting in significant reduction of obstetric dimensions. This complex developmental trajectory is likely linked to the pubertal rise and premenopausal fall of estradiol levels and results in the obstetrically most adequate pelvic morphology during the time of maximum female fertility. The evidence that hormones mediate female pelvic development and morphology supports the view that solutions of the obstetrical dilemma depend not only on selection and adaptation but also on developmental plasticity as a response to ecological/nutritional factors during a female's lifetime. PMID:27114515

  7. Developmental evidence for obstetric adaptation of the human female pelvis

    PubMed Central

    Huseynov, Alik; Zollikofer, Christoph P. E.; Coudyzer, Walter; Gascho, Dominic; Kellenberger, Christian; Hinzpeter, Ricarda; Ponce de León, Marcia S.

    2016-01-01

    The bony pelvis of adult humans exhibits marked sexual dimorphism, which is traditionally interpreted in the framework of the “obstetrical dilemma” hypothesis: Giving birth to large-brained/large-bodied babies requires a wide pelvis, whereas efficient bipedal locomotion requires a narrow pelvis. This hypothesis has been challenged recently on biomechanical, metabolic, and biocultural grounds, so that it remains unclear which factors are responsible for sex-specific differences in adult pelvic morphology. Here we address this issue from a developmental perspective. We use methods of biomedical imaging and geometric morphometrics to analyze changes in pelvic morphology from late fetal stages to adulthood in a known-age/known-sex forensic/clinical sample. Results show that, until puberty, female and male pelves exhibit only moderate sexual dimorphism and follow largely similar developmental trajectories. With the onset of puberty, however, the female trajectory diverges substantially from the common course, resulting in rapid expansion of obstetrically relevant pelvic dimensions up to the age of 25–30 y. From 40 y onward females resume a mode of pelvic development similar to males, resulting in significant reduction of obstetric dimensions. This complex developmental trajectory is likely linked to the pubertal rise and premenopausal fall of estradiol levels and results in the obstetrically most adequate pelvic morphology during the time of maximum female fertility. The evidence that hormones mediate female pelvic development and morphology supports the view that solutions of the obstetrical dilemma depend not only on selection and adaptation but also on developmental plasticity as a response to ecological/nutritional factors during a female’s lifetime. PMID:27114515

  8. The EvoDevoCI: A Concept Inventory for Gauging Students' Understanding of Evolutionary Developmental Biology

    ERIC Educational Resources Information Center

    Perez, Kathryn E.; Hiatt, Anna; Davis, Gregory K.; Trujillo, Caleb; French, Donald P.; Terry, Mark; Price, Rebecca M.

    2013-01-01

    The American Association for the Advancement of Science 2011 report "Vision and Change in Undergraduate Biology Education" encourages the teaching of developmental biology as an important part of teaching evolution. Recently, however, we found that biology majors often lack the developmental knowledge needed to understand evolutionary…

  9. Human developmental enhancers conserved between deuterostomes and protostomes.

    PubMed

    Clarke, Shoa L; VanderMeer, Julia E; Wenger, Aaron M; Schaar, Bruce T; Ahituv, Nadav; Bejerano, Gill

    2012-01-01

    The identification of homologies, whether morphological, molecular, or genetic, is fundamental to our understanding of common biological principles. Homologies bridging the great divide between deuterostomes and protostomes have served as the basis for current models of animal evolution and development. It is now appreciated that these two clades share a common developmental toolkit consisting of conserved transcription factors and signaling pathways. These patterning genes sometimes show common expression patterns and genetic interactions, suggesting the existence of similar or even conserved regulatory apparatus. However, previous studies have found no regulatory sequence conserved between deuterostomes and protostomes. Here we describe the first such enhancers, which we call bilaterian conserved regulatory elements (Bicores). Bicores show conservation of sequence and gene synteny. Sequence conservation of Bicores reflects conserved patterns of transcription factor binding sites. We predict that Bicores act as response elements to signaling pathways, and we show that Bicores are developmental enhancers that drive expression of transcriptional repressors in the vertebrate central nervous system. Although the small number of identified Bicores suggests extensive rewiring of cis-regulation between the protostome and deuterostome clades, additional Bicores may be revealed as our understanding of cis-regulatory logic and sample of bilaterian genomes continue to grow. PMID:22876195

  10. Theories of Human Development that Enhance an Understanding of the College Transition Process

    ERIC Educational Resources Information Center

    Guiffrida, Douglas A.

    2009-01-01

    Background/Context: Although theories of human development often play a central role in K-12 pedagogical practices, evidence suggests that developmental theories have not been used extensively to understand the college transition process or to develop programs to support students during these transitions. Purpose/Objective/Research Question/Focus…

  11. Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective

    PubMed Central

    Zirra, Alexandra; Wiethoff, Sarah; Patani, Rickie

    2016-01-01

    Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs) became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine. PMID:27069483

  12. If you could turn back time: understanding transgenerational latent effects of developmental exposure to contaminants.

    PubMed

    Kimberly, David A; Salice, Christopher J

    2014-01-01

    Latent effects result from embryonic experiences but manifest in later stages of ontogeny. Our objective was to better understand how developmental exposure to contaminants influence life history traits and tolerance to novel stress in the freshwater gastropod, Physa pomilia. Ten egg masses were exposed to each of three initial treatments including control, 2.5 μg/L cadmium (Cd), and 10 μg/L Cd; there was no effect of this initial treatment on hatching success. At hatching, snails were transferred to cadmium-free water. Three weeks later, snails were divided among four secondary treatments including control, 50 μg/L Cd, 150 μg/L Cd, and 35 °C. Developmental Cd exposure plus secondary temperature stress caused the most adverse effects. Surprisingly, developmental Cd exposure alone was enough to cause significant decreases in reproductive success a generation later. That effects can manifest as transgenerational decrements in reproductive success suggests that latent effects are important and have longer lasting consequences than previously considered. PMID:24121266

  13. Children's understanding of the immune system: Integrating the cognitive-developmental and intuitive theories' perspectives

    NASA Astrophysics Data System (ADS)

    Landry-Boozer, Kristine L.

    Traditional cognitive-developmental researchers have provided a large body of evidence supporting the stage-like progression of children's cognitive development. Further, from this body of research comes evidence that children's understanding of HIV/AIDS develops in much the same way as their understanding of other illness-related concepts. Researchers from a newer perspective assert that biological concepts develop from intuitive theories. In general, as children are exposed to relevant content and have opportunities to organize this information, their theories become more accurate and differentiated. According to this perspective, there are no broad structural constraints on developing concepts, as asserted by cognitive developmental theorists. The purpose of the current study was two-fold: to provide support for both theoretical perspectives, while at the same time to explore children's conceptualizations of the immune system, which has not been done previously in the cognitive-developmental literature. One hundred ninety children ranging in age from 4 years old through 11 years old, and a group of adults, participated. Each participant was interviewed regarding health concepts and the body's function in maintaining health. Participants were also asked to report if they had certain experiences that would have led to relevant content exposure. Qualitative analyses were utilized to code the interviews with rubrics based on both theoretical perspectives. Quantitative analyses consisted of a series of univariate ANOVAs (and post hoc tests when appropriate) examining all three coding variables (accuracy, differentiation, and developmental level) across various age-group combinations and exposure groups. Results of these analyses provided support for both theoretical perspectives. When the data were analyzed for developmental level by all ages, a stage-like progression consistent with Piagetian stages emerged. When accuracy and differentiation were examined (intuitive

  14. Developmental pathways for social understanding: linking social cognition to social contexts

    PubMed Central

    Brink, Kimberly A.; Lane, Jonathan D.; Wellman, Henry M.

    2015-01-01

    Contemporary research, often with looking-time tasks, reveals that infants possess foundational understandings of their social worlds. However, few studies have examined how these early social cognitions relate to the child’s social interactions and behavior in early development. Does an early understanding of the social world relate to how an infant interacts with his or her parents? Do early social interactions along with social-cognitive understandings in infancy predict later preschool social competencies? In the current paper, we propose a theory in which children’s later social behaviors and their understanding of the social world depend on the integration of early social understanding and experiences in infancy. We review several of our studies, as well as other research, that directly examine the pathways between these competencies to support a hypothesized network of relations between social-cognitive development and social-interactive behaviors in the development from infancy to childhood. In total, these findings reveal differences in infant social competences that both track the developmental trajectory of infants’ understanding of people over the first years of life and provide external validation for the large body of social-cognitive findings emerging from laboratory looking-time paradigms. PMID:26074859

  15. The Social Buffering of the Hypothalamic-Pituitary-Adrenocortical Axis in Humans: Developmental and Experiential Determinants

    PubMed Central

    Gunnar, Megan R.; Hostinar, Camelia E.

    2015-01-01

    Social buffering, a subset of social support, is the process through which the availability of a conspecific reduces the activity of stress-mediating neurobiological systems. While its role in coping and resilience is significant, we know little about its developmental history in humans. This brief review presents an integrative developmental account of the social buffering of hypothalamic-pituitary-adrenocortical (HPA) stress reactivity in humans, from infancy to adulthood. During infancy, parents are powerful stress-regulators for children, but child temperament also plays a role and interacts with parenting quality to predict the magnitude of stress responses to fear or pain stimuli. Recent work indicates that parental support remains a potent stress buffer into late childhood, but that it loses its effectiveness as a buffer of the HPA axis by adolescence. Puberty may be the switch that alters the potency of parental buffering. In Beginning in middle childhood, friends may serve as stress buffers, particularly when other peers are the source of stress. By adulthood romantic partners assume this protective role, though studies often reveal sex differences that are currently not well understood. Translational research across species will be critical for developing a mechanistic understanding of social buffering and the processes involved in developmental changes noted in this review. PMID:26230646

  16. The Developmental Transcriptome of the Human Brain: Implications for Neurodevelopmental Disorders

    PubMed Central

    Tebbenkamp, Andrew T. N.; Willsey, A. Jeremy; State, Matthew W.; Šestan, Nenad

    2014-01-01

    Purpose of review Recent characterizations of the transcriptome of the developing human brain by several groups have generated comprehensive datasets on coding and noncoding RNAs that will be instrumental for illuminating the underlying biology of complex neurodevelopmental disorders. This review summarizes recent studies successfully utilizing these data to increase our understanding of the molecular mechanisms of pathogenesis. Recent findings Several approaches have successfully integrated developmental transcriptome data with gene discovery to generate testable hypotheses about when and where in the developing human brain disease-associated genes converge. Specifically, these include the projection neurons in the prefrontal and primary motor-somatosensory cortex during mid-fetal development in autism spectrum disorder and the frontal cortex during fetal development in schizophrenia. Summary Developmental transcriptome data is a key to interpreting disease-associated mutations and transcriptional changes. Novel approaches integrating the spatial and temporal dimensions of these data have increased our understanding of when and where pathology occurs. Refinement of spatial and temporal properties and expanding these findings to other neurodevelopmental disorders will provide critical insights for understanding disease biology. PMID:24565942

  17. Global expression profiling reveals genetic programs underlying the developmental divergence between mouse and human embryogenesis

    PubMed Central

    2013-01-01

    Background Mouse has served as an excellent model for studying human development and diseases due to its similarity to human. Advances in transgenic and knockout studies in mouse have dramatically strengthened the use of this model and significantly improved our understanding of gene function during development in the past few decades. More recently, global gene expression analyses have revealed novel features in early embryogenesis up to gastrulation stages and have indeed provided molecular evidence supporting the conservation in early development in human and mouse. On the other hand, little information is known about the gene regulatory networks governing the subsequent organogenesis. Importantly, mouse and human development diverges during organogenesis. For instance, the mouse embryo is born around the end of organogenesis while in human the subsequent fetal period of ongoing growth and maturation of most organs spans more than 2/3 of human embryogenesis. While two recent studies reported the gene expression profiles during human organogenesis, no global gene expression analysis had been done for mouse organogenesis. Results Here we report a detailed analysis of the global gene expression profiles from egg to the end of organogenesis in mouse. Our studies have revealed distinct temporal regulation patterns for genes belonging to different functional (Gene Ontology or GO) categories that support their roles during organogenesis. More importantly, comparative analyses identify both conserved and divergent gene regulation programs in mouse and human organogenesis, with the latter likely responsible for the developmental divergence between the two species, and further suggest a novel developmental strategy during vertebrate evolution. Conclusions We have reported here the first genome-wide gene expression analysis of the entire mouse embryogenesis and compared the transcriptome atlas during mouse and human embryogenesis. Given our earlier observation that genes

  18. WORKSHOP ON THE QUALITATIVE AND QUANTITATIVE COMPARABILITY OF HUMAN AND ANIMAL DEVELOPMENTAL NEUROTOXICITY, WORK GROUP I REPORT: COMPARABILITY OF MEASURES OF DEVELOPMENTAL NEUROTOXICITY IN HUMANS AND LABORATORY ANIMALS

    EPA Science Inventory

    Assessment measures used in developmental neurotoxicology are reviewed for their comparability in humans and laboratory animals, and their ability to detect comparable, adverse effects across species. ompounds used for these comparisons include: abuse substances, anticonvulsant d...

  19. Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics

    SciTech Connect

    West, Paul R.; Weir, April M.; Smith, Alan M.; Donley, Elizabeth L.R.; Cezar, Gabriela G.

    2010-08-15

    Teratogens, substances that may cause fetal abnormalities during development, are responsible for a significant number of birth defects. Animal models used to predict teratogenicity often do not faithfully correlate to human response. Here, we seek to develop a more predictive developmental toxicity model based on an in vitro method that utilizes both human embryonic stem (hES) cells and metabolomics to discover biomarkers of developmental toxicity. We developed a method where hES cells were dosed with several drugs of known teratogenicity then LC-MS analysis was performed to measure changes in abundance levels of small molecules in response to drug dosing. Statistical analysis was employed to select for specific mass features that can provide a prediction of the developmental toxicity of a substance. These molecules can serve as biomarkers of developmental toxicity, leading to better prediction of teratogenicity. In particular, our work shows a correlation between teratogenicity and changes of greater than 10% in the ratio of arginine to asymmetric dimethylarginine levels. In addition, this study resulted in the establishment of a predictive model based on the most informative mass features. This model was subsequently tested for its predictive accuracy in two blinded studies using eight drugs of known teratogenicity, where it correctly predicted the teratogenicity for seven of the eight drugs. Thus, our initial data shows that this platform is a robust alternative to animal and other in vitro models for the prediction of the developmental toxicity of chemicals that may also provide invaluable information about the underlying biochemical pathways.

  20. Being Human: A Handbook in Human Growth and Development for the Developmentally Disabled.

    ERIC Educational Resources Information Center

    Fletcher, Donna; Ogle, Peggy

    The handbook is intended to provide practitioners with information on establishing and organizing a Human Growth and Development program in agencies and facilities which provide training to developmentally disabled persons. The handbook discusses the legal foundation (Florida law) for establishing the program as well as specific methods for…

  1. Being Human: A Resource Guide in Human Growth and Development for the Developmentally Disabled.

    ERIC Educational Resources Information Center

    Ogle, Peggy

    The resource guide is intended to help practitioners develop curricula in human growth and development for developmentally disabled students. A matrix guide is presented for evaluating clients in three domains (social identity, health and hygiene, and physiological identity). Behavioral indicators are then noted which relate to adaptive behaviors…

  2. Understanding human behavior in times of war.

    PubMed

    Vetter, Stefan

    2007-12-01

    The Third Geneva Convention reflects on the values of humanism, declaring the rights of humaneness, honor, and protection before torture and final discharge of war prisoners after the end of a war. These days, the occurrences in Baghdad Central Detention Center (formerly known as Abu Ghraib Prison), the actions of British soldiers in Basra, and the inflamed public discussion of whether torture might be an appropriate method to obtain crucial information from terrorists put the Third Geneva Convention back in the spotlight. The aforementioned occurrences raise questions regarding the psychological mass phenomena that make us vulnerable to think and to act against our education, habits, and beliefs. Only an understanding of these phenomena will help us to act against behavior we condemn. This article is an attempt to show how cognition of societies and individuals slowly changes during longer conflicts. Furthermore, it tries to summarize the possibilities we have to confront these tendencies. PMID:18217244

  3. Chol understandings of suicide and human agency.

    PubMed

    Imberton, Gracia

    2012-06-01

    According to ethnographic material collected since 2003, the Chol Mayan indigenous people in southern Mexico have different causal explanations for suicide. It can be attributed to witchcraft that forces victims to take their lives against their own will, to excessive drinking, or to fate determined by God. However, it can also be conceived of as a conscious decision made by a person overwhelmed by daily problems. Drawing from the theoretical framework developed by Laura M. Ahearn, inspired by practice theory, the paper contends that these different explanations operate within two different logics or understandings of human agency. The first logic attributes responsibility to supernatural causes such as witchcraft or divine destiny, and reflects Chol notions of personhood. The second logic accepts personal responsibility for suicide, and is related to processes of social change such as the introduction of wage labor, education and a market economy. The contemporary Chol resort to both logics to make sense of the human drama of suicide. PMID:22382678

  4. Understanding human dynamics in microblog posting activities

    NASA Astrophysics Data System (ADS)

    Jiang, Zhihong; Zhang, Yubao; Wang, Hui; Li, Pei

    2013-02-01

    Human activity patterns are an important issue in behavior dynamics research. Empirical evidence indicates that human activity patterns can be characterized by a heavy-tailed inter-event time distribution. However, most researchers give an understanding by only modeling the power-law feature of the inter-event time distribution, and those overlooked non-power-law features are likely to be nontrivial. In this work, we propose a behavior dynamics model, called the finite memory model, in which humans adaptively change their activity rates based on a finite memory of recent activities, which is driven by inherent individual interest. Theoretical analysis shows a finite memory model can properly explain various heavy-tailed inter-event time distributions, including a regular power law and some non-power-law deviations. To validate the model, we carry out an empirical study based on microblogging activity from thousands of microbloggers in the Celebrity Hall of the Sina microblog. The results show further that the model is reasonably effective. We conclude that finite memory is an effective dynamics element to describe the heavy-tailed human activity pattern.

  5. Towards a better understanding of human eye disease: insights from the zebrafish, Danio rerio

    PubMed Central

    Bibliowicz, Jonathan; Tittle, Rachel K.; Gross, Jeffrey M.

    2011-01-01

    Visual impairment and blindness is widespread across the human population, and the development of therapies for ocular pathologies is of high priority. The zebrafish represents a valuable model organism for studying human ocular disease; it is utilized in eye research to understand underlying developmental processes, to identify potential causative genes for human disorders, and to develop therapies. Zebrafish eyes are similar in morphology, physiology, gene expression and function to human eyes. Furthermore, zebrafish are highly amenable to laboratory research. This review outlines the use of zebrafish as a model for human ocular diseases such as colobomas, glaucoma, cataracts, photoreceptor degeneration, as well as dystrophies of the cornea and retinal pigmented epithelium. PMID:21377629

  6. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    PubMed

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient. PMID:9644328

  7. Theory of Mind "emotion", developmental characteristics and social understanding in children and adolescents with intellectual disabilities.

    PubMed

    Thirion-Marissiaux, Anne-Françoise; Nader-Grosbois, Nathalie

    2008-01-01

    Patterns of development of ToM-emotion abilities in intellectually disabled (ID) children and typically developing (TD) children matched on their developmental age were investigated. The links between cognition, language, social understanding and ToM-emotion abilities were examined. EDEI-R (Perron-Borelli, M. (1996). Echelles Différentielles d'Efficiences Intellectuelles. Forme Révisée (EDEI-R). Paris: Editions et Applications Psychologiques) was used to match participants and to assess social understanding. ECOSSE (Lecocq, P. (1996). L'E.CO.S.SE. Une épreuve de compréhension syntaxico-sémantique. Paris: Presses Universitaires du Septentrion) assessed the level of syntactic and semantic comprehension of French speaking, to ensure a good comprehension of the questions in ToM-emotion tasks. Adapted tasks of the understanding of causes and consequences of emotions (Quintal, G. (2001). La compréhension des émotions chez les enfants d'âge préscolaire dans le cadre d'une théorie de l'esprit. Un-published master's thesis, University of Montreal, Québec) assessed ToM-emotion abilities (Nader-Grosbois, N., Thirion-Marissiaux, A.-F., & Grosbois, M. (2003). Adapted tests for assessment of the Theory of Mind of causes and consequences of emotions (unpublished documents). Louvain-la-Neuve, Belgium). Similarities in the development of ToM-emotion abilities and social understanding were found, respectively, in both groups (delay hypothesis in ID participants). Some differences between groups were observed in the links between social understanding and ToM-emotion abilities. Significant correlations between developmental characteristics (verbal and non-verbal cognition) and ToM-emotion abilities were obtained for both groups. Verbal cognition explained an important part of the variance of ToM results (understanding of causes and consequences of emotions). The impact of chronological age on ToM-emotion abilities was also examined and is discussed. PMID:17855050

  8. Understanding human functioning using graphical models

    PubMed Central

    2010-01-01

    Background Functioning and disability are universal human experiences. However, our current understanding of functioning from a comprehensive perspective is limited. The development of the International Classification of Functioning, Disability and Health (ICF) on the one hand and recent developments in graphical modeling on the other hand might be combined and open the door to a more comprehensive understanding of human functioning. The objective of our paper therefore is to explore how graphical models can be used in the study of ICF data for a range of applications. Methods We show the applicability of graphical models on ICF data for different tasks: Visualization of the dependence structure of the data set, dimension reduction and comparison of subpopulations. Moreover, we further developed and applied recent findings in causal inference using graphical models to estimate bounds on intervention effects in an observational study with many variables and without knowing the underlying causal structure. Results In each field, graphical models could be applied giving results of high face-validity. In particular, graphical models could be used for visualization of functioning in patients with spinal cord injury. The resulting graph consisted of several connected components which can be used for dimension reduction. Moreover, we found that the differences in the dependence structures between subpopulations were relevant and could be systematically analyzed using graphical models. Finally, when estimating bounds on causal effects of ICF categories on general health perceptions among patients with chronic health conditions, we found that the five ICF categories that showed the strongest effect were plausible. Conclusions Graphical Models are a flexible tool and lend themselves for a wide range of applications. In particular, studies involving ICF data seem to be suited for analysis using graphical models. PMID:20149230

  9. What do children know and understand about universal gravitation? Structural and developmental aspects.

    PubMed

    Frappart, Sören; Raijmakers, Maartje; Frède, Valérie

    2014-04-01

    Children's understanding of universal gravitation starts at an early age but changes until adulthood, which makes it an interesting topic for studying the development and structure of knowledge. Children's understanding of gravitation was tested for a variety of contexts and across a wide age range (5-18 years, N=144). We analyzed children's predictions and justifications for the trajectory of a stone dropped on the earth, on the moon, in a spaceship orbiting the earth, on a planet with air, on a planet with no air, and in a lift (i.e., an elevator) in free fall. Results showed that performances were related to the context and to the children's age. U-shaped developmental curves were identified for predictions for three contexts. These curves could be explained by analyzing the structure of the children's knowledge using latent class analysis. We identified three coherent patterns of predictions that were related to specific justifications. With age, children produced more scientific predictions. Children's cognitive structures, as reflected in their predictions of dropped stone trajectories, seem to be coherently built given that there were only a limited number of prediction patterns. Even by Grade 12, students had not achieved a scientific understanding of universal gravitation. PMID:24361806

  10. Understanding human perception by human-made illusions

    PubMed Central

    Carbon, Claus-Christian

    2014-01-01

    It may be fun to perceive illusions, but the understanding of how they work is even more stimulating and sustainable: They can tell us where the limits and capacity of our perceptual apparatus are found—they can specify how the constraints of perception are set. Furthermore, they let us analyze the cognitive sub-processes underlying our perception. Illusions in a scientific context are not mainly created to reveal the failures of our perception or the dysfunctions of our apparatus, but instead point to the specific power of human perception. The main task of human perception is to amplify and strengthen sensory inputs to be able to perceive, orientate and act very quickly, specifically and efficiently. The present paper strengthens this line of argument, strongly put forth by perceptual pioneer Richard L. Gregory (e.g., Gregory, 2009), by discussing specific visual illusions and how they can help us to understand the magic of perception. PMID:25132816

  11. Developmental pathways during in vitro progression of human islet neogenesis

    PubMed Central

    Dodge, Rikke; Loomans, Cindy; Sharma, Arun; Bonner-Weir, Susan

    2009-01-01

    Islet neogenesis, or the differentiation of islet cells from precursor cells, is seen in vitro and in vivo both embryonically and after birth. However, little is known about the differentiation pathways during embryonic development for human pancreas. Our previously reported in vitro generation of islets from human pancreatic tissue provides a unique system to identify potential markers of neogenesis and to determine the molecular mechanisms underlying this process. To this end, we analyzed the gene expression profiles of three different stages during in vitro islet generation: the Initial Adherent-, Expanded-, and Differentiated- stages. Samples from four human pancreases were hybridized to Affymetrix U95A GeneChips, and data analyzed using GeneSpring 7.0/9.0 software. Using Scatter plots we selected genes with a 2-fold or greater differential expression.. Of the 12,000 genes/ESTs present on these arrays, 295 genes including 38 acinar–enriched genes were selectively lost during the progression from the Initially Adherent stage to the Expanded stage; 468 genes were increased in this progression to Expanded tissue; and 529 genes had a two-fold greater expression in the Differentiated-stage than in the Expanded tissue. Besides the expected increases in insulin, glucagon and duct markers (mucin 6, aquaporin 1 and 5), the beta cell auto-antigen IA-2/phogrin was increased 5-fold in Differentiated. In addition developmentally important pathways, including Notch/jagged, Wnt/Frizzled, TGFβ superfamily (follistatin, BMPs and SMADs), retinoic acid (COUP-TFI, CRABP1, 2 and RAIG1) were differentially regulated during the expansion/differentiation. Two putative markers for islet precursor cells, UCHL1/PGP9.5 and DMBT1, were enhanced during the progression to differentiated cells, but only the latter could be a marker of islet precursor cells. We suggest that appropriate manipulation of these differentiation-associated pathways will enhance the efficiency of differentiation

  12. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics.

    PubMed

    Kleinstreuer, N C; Smith, A M; West, P R; Conard, K R; Fontaine, B R; Weir-Hauptman, A M; Palmer, J A; Knudsen, T B; Dix, D J; Donley, E L R; Cezar, G G

    2011-11-15

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox® model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. PMID:21925528

  13. Understanding Immigrant College Students: Applying a Developmental Ecology Framework to the Practice of Academic Advising

    ERIC Educational Resources Information Center

    Stebleton, Michael J.

    2011-01-01

    Immigrant college student populations continue to grow, but the complexity of their unique needs and issues remain relatively unknown. To gain a better understanding of the multiple contextual factors impacting immigrant students from a systems-based approach, I applied Bronfenbrenner's (1977) human ecology framework to the study. Students…

  14. Cellular manganese content is developmentally regulated in human dopaminergic neurons

    NASA Astrophysics Data System (ADS)

    Kumar, Kevin K.; Lowe, Edward W., Jr.; Aboud, Asad A.; Neely, M. Diana; Redha, Rey; Bauer, Joshua A.; Odak, Mihir; Weaver, C. David; Meiler, Jens; Aschner, Michael; Bowman, Aaron B.

    2014-10-01

    Manganese (Mn) is both an essential biological cofactor and neurotoxicant. Disruption of Mn biology in the basal ganglia has been implicated in the pathogenesis of neurodegenerative disorders, such as parkinsonism and Huntington's disease. Handling of other essential metals (e.g. iron and zinc) occurs via complex intracellular signaling networks that link metal detection and transport systems. However, beyond several non-selective transporters, little is known about the intracellular processes regulating neuronal Mn homeostasis. We hypothesized that small molecules that modulate intracellular Mn could provide insight into cell-level Mn regulatory mechanisms. We performed a high throughput screen of 40,167 small molecules for modifiers of cellular Mn content in a mouse striatal neuron cell line. Following stringent validation assays and chemical informatics, we obtained a chemical `toolbox' of 41 small molecules with diverse structure-activity relationships that can alter intracellular Mn levels under biologically relevant Mn exposures. We utilized this toolbox to test for differential regulation of Mn handling in human floor-plate lineage dopaminergic neurons, a lineage especially vulnerable to environmental Mn exposure. We report differential Mn accumulation between developmental stages and stage-specific differences in the Mn-altering activity of individual small molecules. This work demonstrates cell-level regulation of Mn content across neuronal differentiation.

  15. Human NK cell development requires CD56-mediated motility and formation of the developmental synapse

    PubMed Central

    Mace, Emily M.; Gunesch, Justin T.; Dixon, Amera; Orange, Jordan S.

    2016-01-01

    While distinct stages of natural killer (NK) cell development have been defined, the molecular interactions that shape human NK cell maturation are poorly understood. Here we define intercellular interactions between developing NK cells and stromal cells which, through contact-dependent mechanisms, promote the generation of mature, functional human NK cells from CD34+ precursors. We show that developing NK cells undergo unique, developmental stage-specific sustained and transient interactions with developmentally supportive stromal cells, and that the relative motility of NK cells increases as they move through development in vitro and ex vivo. These interactions include the formation of a synapse between developing NK cells and stromal cells, which we term the developmental synapse. Finally, we identify a role for CD56 in developmental synapse structure, NK cell motility and NK cell development. Thus, we define the developmental synapse leading to human NK cell functional maturation. PMID:27435370

  16. Human NK cell development requires CD56-mediated motility and formation of the developmental synapse.

    PubMed

    Mace, Emily M; Gunesch, Justin T; Dixon, Amera; Orange, Jordan S

    2016-01-01

    While distinct stages of natural killer (NK) cell development have been defined, the molecular interactions that shape human NK cell maturation are poorly understood. Here we define intercellular interactions between developing NK cells and stromal cells which, through contact-dependent mechanisms, promote the generation of mature, functional human NK cells from CD34(+) precursors. We show that developing NK cells undergo unique, developmental stage-specific sustained and transient interactions with developmentally supportive stromal cells, and that the relative motility of NK cells increases as they move through development in vitro and ex vivo. These interactions include the formation of a synapse between developing NK cells and stromal cells, which we term the developmental synapse. Finally, we identify a role for CD56 in developmental synapse structure, NK cell motility and NK cell development. Thus, we define the developmental synapse leading to human NK cell functional maturation. PMID:27435370

  17. Evolutionary and developmental contributions for understanding the organization of the basal ganglia.

    PubMed

    Medina, Loreta; Abellán, Antonio; Vicario, Alba; Desfilis, Ester

    2014-01-01

    Herein we take advantage of the evolutionary developmental biology approach in order to improve our understanding of both the functional organization and the evolution of the basal ganglia, with a particular focus on the globus pallidus. Therefore, we review data on the expression of developmental regulatory genes (that play key roles in patterning, regional specification and/or morphogenesis), gene function and fate mapping available in different vertebrate species, which are useful to (a) understand the embryonic origin and basic features of each neuron subtype of the basal ganglia (including neurotransmitter/neuropeptide expression and connectivity patterns); (b) identify the same (homologous) subpopulations in different species and the degree of variation or conservation throughout phylogeny, and (c) identify possible mechanisms that may explain the evolution of the basal ganglia. These data show that the globus pallidus of rodents contains two major subpopulations of GABAergic projection neurons: (1) neurons containing parvalbumin and neurotensin-related hexapetide (LANT6), with descending projections to the subthalamus and substantia nigra, which originate from progenitors expressing Nkx2.1, primarily located in the pallidal embryonic domain (medial ganglionic eminence), and (2) neurons containing preproenkephalin (and possibly calbindin), with ascending projections to the striatum, which appear to originate from progenitors expressing Islet1 in the striatal embryonic domain (lateral ganglionic eminence). Based on data on Nkx2.1, Islet1, LANT6 and proenkephalin, it appears that both cell types are also present in the globus pallidus/dorsal pallidum of chicken, frog and lungfish. In chicken, the globus pallidus also contains neurons expressing substance P (SP), perhaps originating in the striatal embryonic domain. In ray-finned and cartilaginous fishes, the pallidum contains at least the Nkx2.1 lineage cell population (likely representing the neurons

  18. A human fetal prostate xenograft model of developmental estrogenization.

    PubMed

    Saffarini, Camelia M; McDonnell-Clark, Elizabeth V; Amin, Ali; Boekelheide, Kim

    2015-01-01

    Prostate cancer is a common disease in older men. Rodent models have demonstrated that an early and later-life exposure to estrogen can lead to cancerous lesions and implicated hormonal dysregulation as an avenue for developing future prostate neoplasia. This study utilizes a human fetal prostate xenograft model to study the role of estrogen in the progression of human disease. Histopathological lesions were assessed in 7-, 30-, 90-, 200-, and 400-day human prostate xenografts. Gene expression for cell cycle, tumor suppressors, and apoptosis-related genes (ie, CDKN1A, CASP9, ESR2, PTEN, and TP53) was performed for 200-day estrogen-treated xenografts. Glandular hyperplasia was observed in xenografts given both an initial and secondary exposure to estradiol in both 200- and 400-day xenografts. Persistent estrogenic effects were verified using immunohistochemical markers for cytokeratin 10, p63, and estrogen receptor α. This model provides data on the histopathological state of the human prostate following estrogenic treatment, which can be utilized in understanding the complicated pathology associated with prostatic disease and early and later-life estrogenic exposures. PMID:25633637

  19. FUNCTIONAL ASPECTS OF DEVELOPMENTAL TOXICITY OF POLYHALOGENATED AROMATIC HYDROCARBONS IN EXPERIMENTAL ANIMALS AND HUMAN INFANTS

    EPA Science Inventory

    A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs)-dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in experimental animals and in human infants. ersistent neurobehavioral, reproductive, and endocrine alteration...

  20. Understanding developmental and adaptive cues in pine through metabolite profiling and co-expression network analysis

    PubMed Central

    Cañas, Rafael A.; Canales, Javier; Muñoz-Hernández, Carmen; Granados, Jose M.; Ávila, Concepción; García-Martín, María L.; Cánovas, Francisco M.

    2015-01-01

    Conifers include long-lived evergreen trees of great economic and ecological importance, including pines and spruces. During their long lives conifers must respond to seasonal environmental changes, adapt to unpredictable environmental stresses, and co-ordinate their adaptive adjustments with internal developmental programmes. To gain insights into these responses, we examined metabolite and transcriptomic profiles of needles from naturally growing 25-year-old maritime pine (Pinus pinaster L. Aiton) trees over a year. The effect of environmental parameters such as temperature and rain on needle development were studied. Our results show that seasonal changes in the metabolite profiles were mainly affected by the needles’ age and acclimation for winter, but changes in transcript profiles were mainly dependent on climatic factors. The relative abundance of most transcripts correlated well with temperature, particularly for genes involved in photosynthesis or winter acclimation. Gene network analysis revealed relationships between 14 co-expressed gene modules and development and adaptation to environmental stimuli. Novel Myb transcription factors were identified as candidate regulators during needle development. Our systems-based analysis provides integrated data of the seasonal regulation of maritime pine growth, opening new perspectives for understanding the complex regulatory mechanisms underlying conifers’ adaptive responses. Taken together, our results suggest that the environment regulates the transcriptome for fine tuning of the metabolome during development. PMID:25873654

  1. Moving Targets: A Developmental Framework for Understanding Children's Changes following Disasters

    ERIC Educational Resources Information Center

    Franks, Bridget A.

    2011-01-01

    This paper proposes a developmental framework for disaster studies with children that allows researchers to explore the interaction between developmental change (defined as change that is extended, self-regulated, qualitative, and progressive) and cataclysmic change. It outlines three levels of analysis related to disasters: 1) observing the harm…

  2. Understanding Information about Mortality among People with Intellectual and Developmental Disabilities in Canada

    ERIC Educational Resources Information Center

    Ouellette-Kuntz, Hélène; Shooshtari, Shahin; Balogh, Robert; Martens, Patricia

    2015-01-01

    Background: This paper reviews what is currently known about mortality among Canadians with intellectual and developmental disabilities and describes opportunities for ongoing monitoring. Methods: In-hospital mortality among adults with intellectual and developmental disabilities in Ontario was examined using hospital data. Mortality was compared…

  3. Multilevel developmental approaches to understanding the effects of child maltreatment: Recent advances and future challenges

    PubMed Central

    POLLAK, SETH D.

    2016-01-01

    Recent research in the field of child maltreatment has begun to shed new light on the emergence of health problems in children by emphasizing the responsiveness of developmental processes to children’s environmental and biological contexts. Here, I highlight recent trends in the field with an emphasis on the effects of early life stress across multiple levels of developmental domains. PMID:26535932

  4. Multilevel developmental approaches to understanding the effects of child maltreatment: Recent advances and future challenges.

    PubMed

    Pollak, Seth D

    2015-11-01

    Recent research in the field of child maltreatment has begun to shed new light on the emergence of health problems in children by emphasizing the responsiveness of developmental processes to children's environmental and biological contexts. Here, I highlight recent trends in the field with an emphasis on the effects of early life stress across multiple levels of developmental domains. PMID:26535932

  5. Understanding human trafficking in the United States.

    PubMed

    Logan, T K; Walker, Robert; Hunt, Gretchen

    2009-01-01

    The topic of modern-day slavery or human trafficking has received increased media and national attention. However, to date there has been limited research on the nature and scope of human trafficking in the United States. This article describes and synthesizes nine reports that assess the U.S. service organizations' legal representative knowledge of, and experience with, human trafficking cases, as well as information from actual cases and media reports. This article has five main goals: (a) to define what human trafficking is, and is not; (b) to describe factors identified as contributing to vulnerability to being trafficked and keeping a person entrapped in the situation; (c) to examine how the crime of human trafficking differs from other kinds of crimes in the United States; (d) to explore how human trafficking victims are identified; and, (e) to provide recommendations to better address human trafficking in the United States. PMID:19056686

  6. Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group I report: comparability of measures of developmental neurotoxicity in humans and laboratory animals.

    PubMed

    Stanton, M E; Spear, L P

    1990-01-01

    Assessment measures used in developmental neurotoxicology are reviewed for their comparability in humans and laboratory animals, and their ability to detect comparable adverse effects across species. Compounds used for these comparisons include: substances of abuse, anticonvulsant drugs, ethanol, methylmercury, lead, PCBs, and ionizing radiation. At the level of functional category (sensory, motivational, cognitive and motor function, and social behavior), close agreement was found across species for all neurotoxic agents reviewed, particularly at high exposure levels. This was true even though the specific end points used to assess these functions often varied substantially across species. In addition, it was found that: 1) the U.S. EPA Developmental Neurotoxicology Test Battery presented at the Workshop would have identified the hazard to humans of exposure to the above compounds, although it may have underestimated human risk in some cases; 2) assessment of developmental neurotoxicity should involve evaluation of all categories of function; 3) for most compounds reviewed, the neurotoxic effects of prenatal exposure cannot be attributed to maternal toxicity, and exposure at or just below the threshold for such toxicity is an appropriate upper level for developmental neurotoxicity testing; 4) maternal exposure during the postnatal period poses a number of serious methodological problems; and 5) animal studies would better parallel human studies if more emphasis was placed on evaluation during development. PMID:2115099

  7. The Contribution of Developmental Behavioural Genetics towards a Multifactorial Understanding of Reading Disabilities.

    ERIC Educational Resources Information Center

    Crawford, Shawn; And Others

    1990-01-01

    The utility of developmental behavioral genetics in the study of reading disability is considered. Research which has found reading disability to be partly genetically determined is cited, and future research applications are discussed. (Author/JDD)

  8. The role of mathematical models in understanding pattern formation in developmental biology.

    PubMed

    Umulis, David M; Othmer, Hans G

    2015-05-01

    In a Wall Street Journal article published on April 5, 2013, E. O. Wilson attempted to make the case that biologists do not really need to learn any mathematics-whenever they run into difficulty with numerical issues, they can find a technician (aka mathematician) to help them out of their difficulty. He formalizes this in Wilsons Principle No. 1: "It is far easier for scientists to acquire needed collaboration from mathematicians and statisticians than it is for mathematicians and statisticians to find scientists able to make use of their equations." This reflects a complete misunderstanding of the role of mathematics in all sciences throughout history. To Wilson, mathematics is mere number crunching, but as Galileo said long ago, "The laws of Nature are written in the language of mathematics[Formula: see text] the symbols are triangles, circles and other geometrical figures, without whose help it is impossible to comprehend a single word." Mathematics has moved beyond the geometry-based model of Galileo's time, and in a rebuttal to Wilson, E. Frenkel has pointed out the role of mathematics in synthesizing the general principles in science (Both point and counter-point are available in Wilson and Frenkel in Notices Am Math Soc 60(7):837-838, 2013). We will take this a step further and show how mathematics has been used to make new and experimentally verified discoveries in developmental biology and how mathematics is essential for understanding a problem that has puzzled experimentalists for decades-that of how organisms can scale in size. Mathematical analysis alone cannot "solve" these problems since the validation lies at the molecular level, but conversely, a growing number of questions in biology cannot be solved without mathematical analysis and modeling. Herein, we discuss a few examples of the productive intercourse between mathematics and biology. PMID:25280665

  9. The Role of Mathematical Models in Understanding Pattern Formation in Developmental Biology

    PubMed Central

    Umulis, David M.

    2016-01-01

    In a Wall Street Journal article published on April 5, 2013, E. O. Wilson attempted to make the case that biologists do not really need to learn any mathematics—whenever they run into difficulty with numerical issues, they can find a technician (aka mathematician) to help them out of their difficulty. He formalizes this in Wilsons Principle No. 1: “It is far easier for scientists to acquire needed collaboration from mathematicians and statisticians than it is for mathematicians and statisticians to find scientists able to make use of their equations.” This reflects a complete misunderstanding of the role of mathematics in all sciences throughout history. To Wilson, mathematics is mere number crunching, but as Galileo said long ago, “The laws of Nature are written in the language of mathematics…the symbols are triangles, circles and other geometrical figures, without whose help it is impossible to comprehend a single word.” Mathematics has moved beyond the geometry-based model of Galileo’s time, and in a rebuttal to Wilson, E. Frenkel has pointed out the role of mathematics in synthesizing the general principles in science (Both point and counter-point are available in Wilson and Frenkel in Notices Am Math Soc 60(7):837–838, 2013). We will take this a step further and show how mathematics has been used to make new and experimentally verified discoveries in developmental biology and how mathematics is essential for understanding a problem that has puzzled experimentalists for decades—that of how organisms can scale in size. Mathematical analysis alone cannot “solve” these problems since the validation lies at the molecular level, but conversely, a growing number of questions in biology cannot be solved without mathematical analysis and modeling. Herein, we discuss a few examples of the productive intercourse between mathematics and biology. PMID:25280665

  10. Imitation, Sign Language Skill and the Developmental Ease of Language Understanding (D-ELU) Model

    PubMed Central

    Holmer, Emil; Heimann, Mikael; Rudner, Mary

    2016-01-01

    Imitation and language processing are closely connected. According to the Ease of Language Understanding (ELU) model (Rönnberg et al., 2013) pre-existing mental representation of lexical items facilitates language understanding. Thus, imitation of manual gestures is likely to be enhanced by experience of sign language. We tested this by eliciting imitation of manual gestures from deaf and hard-of-hearing (DHH) signing and hearing non-signing children at a similar level of language and cognitive development. We predicted that the DHH signing children would be better at imitating gestures lexicalized in their own sign language (Swedish Sign Language, SSL) than unfamiliar British Sign Language (BSL) signs, and that both groups would be better at imitating lexical signs (SSL and BSL) than non-signs. We also predicted that the hearing non-signing children would perform worse than DHH signing children with all types of gestures the first time (T1) we elicited imitation, but that the performance gap between groups would be reduced when imitation was elicited a second time (T2). Finally, we predicted that imitation performance on both occasions would be associated with linguistic skills, especially in the manual modality. A split-plot repeated measures ANOVA demonstrated that DHH signers imitated manual gestures with greater precision than non-signing children when imitation was elicited the second but not the first time. Manual gestures were easier to imitate for both groups when they were lexicalized than when they were not; but there was no difference in performance between familiar and unfamiliar gestures. For both groups, language skills at T1 predicted imitation at T2. Specifically, for DHH children, word reading skills, comprehension and phonological awareness of sign language predicted imitation at T2. For the hearing participants, language comprehension predicted imitation at T2, even after the effects of working memory capacity and motor skills were taken into

  11. Imitation, Sign Language Skill and the Developmental Ease of Language Understanding (D-ELU) Model.

    PubMed

    Holmer, Emil; Heimann, Mikael; Rudner, Mary

    2016-01-01

    Imitation and language processing are closely connected. According to the Ease of Language Understanding (ELU) model (Rönnberg et al., 2013) pre-existing mental representation of lexical items facilitates language understanding. Thus, imitation of manual gestures is likely to be enhanced by experience of sign language. We tested this by eliciting imitation of manual gestures from deaf and hard-of-hearing (DHH) signing and hearing non-signing children at a similar level of language and cognitive development. We predicted that the DHH signing children would be better at imitating gestures lexicalized in their own sign language (Swedish Sign Language, SSL) than unfamiliar British Sign Language (BSL) signs, and that both groups would be better at imitating lexical signs (SSL and BSL) than non-signs. We also predicted that the hearing non-signing children would perform worse than DHH signing children with all types of gestures the first time (T1) we elicited imitation, but that the performance gap between groups would be reduced when imitation was elicited a second time (T2). Finally, we predicted that imitation performance on both occasions would be associated with linguistic skills, especially in the manual modality. A split-plot repeated measures ANOVA demonstrated that DHH signers imitated manual gestures with greater precision than non-signing children when imitation was elicited the second but not the first time. Manual gestures were easier to imitate for both groups when they were lexicalized than when they were not; but there was no difference in performance between familiar and unfamiliar gestures. For both groups, language skills at T1 predicted imitation at T2. Specifically, for DHH children, word reading skills, comprehension and phonological awareness of sign language predicted imitation at T2. For the hearing participants, language comprehension predicted imitation at T2, even after the effects of working memory capacity and motor skills were taken into

  12. Dental Approach to Craniofacial Syndromes: How Can Developmental Fields Show Us a New Way to Understand Pathogenesis?

    PubMed Central

    Kjær, Inger

    2012-01-01

    The paper consists of three parts. Part 1: Definition of Syndromes. Focus is given to craniofacial syndromes in which abnormal traits in the dentition are associated symptoms. In the last decade, research has concentrated on phenotype, genotype, growth, development, function, and treatment. Part 2: Syndromes before Birth. How can the initial malformation sites in these syndromes be studied and what can we learn from it? In this section, deviations observed in syndromes prenatally will be highlighted and compared to the normal human embryological craniofacial development. Specific focus will be given to developmental fields studied on animal tissue and transferred to human cranial development. Part 3: Developmental Fields Affected in Two Craniofacial Syndromes. Analysis of primary and permanent dentitions can determine whether a syndrome affects a single craniofacial field or several fields. This distinction is essential for insight into craniofacial syndromes. The dentition, thus, becomes central in diagnostics and evaluation of the pathogenesis. Developmental fields can explore and advance the concept of dental approaches to craniofacial syndromes. Discussion. As deviations in teeth persist and do not reorganize during growth and development, the dentition is considered useful for distinguishing between syndrome pathogenesis manifested in a single developmental field and in several fields. PMID:23091490

  13. Promoting positive human development and social justice: Integrating theory, research and application in contemporary developmental science.

    PubMed

    Lerner, Richard M

    2015-06-01

    The bold claim that developmental science can contribute to both enhancing positive development among diverse individuals across the life span and promoting social justice in their communities, nations and regions is supported by decades of theoretical, methodological and research contributions. To explain the basis of this claim, I describe the relational developmental systems (RDS) metamodel that frames contemporary developmental science, and I present an example of a programme of research within the adolescent portion of the life span that is associated with this metamodel and is pertinent to promoting positive human development. I then discuss methodological issues associated with using RDS-based models as frames for research and application. Finally, I explain how the theoretical and methodological ideas associated with RDS thinking may provide the scholarly tools needed by developmental scientists seeking to contribute to human thriving and to advance social justice in the Global South. PMID:25782450

  14. Understanding the ideal cooperative characteristic between two humans

    NASA Astrophysics Data System (ADS)

    Abu Bakar, Shahriman; Ikeura, Ryojun; Salleh, Ahmad Faizal; Yano, Takemi

    2009-12-01

    Observing current lifestyles and human growth performance in these past decades we can make a deduction that human workforce going to be reduced until a serious level. We believed that in critical field such as health industries, robots that cooperated with human to handle human patient will provide the help needed to fill the gap. In order to design human cooperative robot that will be able to act and react with human-like features so that the robot can replace the human counterparts, we need to understand how human communicates with human first. This paper discussed the ideal characteristic of how two humans cooperate to complete a cooperative task. The cooperative task experiment involved carrying experiment object in several direction and varying the information available to the experiment subjects. We calculated the smoothness during the cooperative task to understand the ideal cooperative characteristic between two humans.

  15. Understanding the ideal cooperative characteristic between two humans

    NASA Astrophysics Data System (ADS)

    Abu Bakar, Shahriman; Ikeura, Ryojun; Salleh, Ahmad Faizal; Yano, Takemi

    2010-01-01

    Observing current lifestyles and human growth performance in these past decades we can make a deduction that human workforce going to be reduced until a serious level. We believed that in critical field such as health industries, robots that cooperated with human to handle human patient will provide the help needed to fill the gap. In order to design human cooperative robot that will be able to act and react with human-like features so that the robot can replace the human counterparts, we need to understand how human communicates with human first. This paper discussed the ideal characteristic of how two humans cooperate to complete a cooperative task. The cooperative task experiment involved carrying experiment object in several direction and varying the information available to the experiment subjects. We calculated the smoothness during the cooperative task to understand the ideal cooperative characteristic between two humans.

  16. Understanding Youth Antisocial Behavior Using Neuroscience through a Developmental Psychopathology Lens: Review, Integration, and Directions for Research

    PubMed Central

    Hyde, Luke W.; Shaw, Daniel S.; Hariri, Ahmad R.

    2013-01-01

    Youth antisocial behavior (AB) is an important public health concern impacting perpetrators, victims, and society. Functional neuroimaging is becoming a more common and useful modality for understanding neural correlates of youth AB. Although there has been a recent increase in neuroimaging studies of youth AB and corresponding theoretical articles on the neurobiology of AB, there has been little work critically examining the strengths and weaknesses of individual studies and using this knowledge to inform the design of future studies. Additionally, research on neuroimaging and youth AB has not been integrated within the broader framework of developmental psychopathology. Thus, this paper provides an in-depth review of the youth AB functional neuroimaging literature with the following goals: 1. to evaluate how this literature has informed our understanding of youth AB, 2. to evaluate current neuroimaging studies of youth AB from a developmental psychopathology perspective with a focus on integrating research from neuroscience and developmental psychopathology, as well as placing this research in the context of other related areas (e.g., psychopathy, molecular genetics), and 3. to examine strengths and weaknesses of neuroimaging and behavioral studies of youth AB to suggest how future studies can develop a more informed and integrated understanding of youth AB. PMID:24273368

  17. Developmental changes in the transcriptome of human cerebral cortex tissue: long noncoding RNA transcripts.

    PubMed

    Lipovich, Leonard; Tarca, Adi L; Cai, Juan; Jia, Hui; Chugani, Harry T; Sterner, Kirstin N; Grossman, Lawrence I; Uddin, Monica; Hof, Patrick R; Sherwood, Chet C; Kuzawa, Christopher W; Goodman, Morris; Wildman, Derek E

    2014-06-01

    The human neocortex is characterized by protracted developmental intervals of synaptogenesis and myelination, which allow for an extended period of learning. The molecular basis of these and other postnatal developmental changes in the human cerebral cortex remain incompletely understood. Recently, a new large class of mammalian genes, encoding nonmessenger, long nonprotein-coding ribonucleic acid (lncRNA) molecules has been discovered. Although their function remains uncertain, numerous lncRNAs have primate-specific sequences and/or show evidence of rapid, lineage-specific evolution, making them potentially relevant to the evolution of unique human neural properties. To examine the hypothesis that lncRNA expression varies with age, potentially paralleling known developmental trends in synaptogenesis, myelination, and energetics, we quantified levels of nearly 6000 lncRNAs in 36 surgically resected human neocortical samples (primarily derived from temporal cortex) spanning infancy to adulthood. Our analysis identified 8 lncRNA genes with distinct developmental expression patterns. These lncRNA genes contained anthropoid-specific exons, as well as splice sites and polyadenylation signals that resided in primate-specific sequences. To our knowledge, our study is the first to describe developmental expression profiles of lncRNA in surgically resected in vivo human brain tissue. Future analysis of the functional relevance of these transcripts to neural development and energy metabolism is warranted. PMID:23377288

  18. [Human nature--understanding psychology in Nietzsche].

    PubMed

    Dieckhöfer, K

    1980-01-01

    It was tried to show some decisive and essential points of the psychological analyses contained in the complex work of the philosopher Nietzsche. The extent of his knowledge of man and his changeability constitutes here the field of an understanding, "unmasking" psychology with a sociological-historical touch. The thorough, slow ("lento") study of the original sources on the part of the master of a "connaisseurship of the word" seems to be indispensable for any reader trying to occupy himself with Nietzsche in a work of his own and the questions arising therefrom. PMID:7003939

  19. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    SciTech Connect

    Kleinstreuer, N.C.; Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R.; Weir-Hauptman, A.M.; Palmer, J.A.; Knudsen, T.B.; Dix, D.J.; Donley, E.L.R.; Cezar, G.G.

    2011-11-15

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal development and

  20. Understanding the origins of human cancer

    SciTech Connect

    Alexandrov, L. B.

    2015-12-04

    All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on the genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).

  1. Understanding the origins of human cancer

    DOE PAGESBeta

    Alexandrov, L. B.

    2015-12-04

    All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on themore » genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).« less

  2. Understanding African American Adolescents' Identity Development: A Relational Developmental Systems Perspective

    ERIC Educational Resources Information Center

    Brittian, Aerika S.

    2012-01-01

    This article examines the development of African American adolescents' identity using a relational developmental systems theory framework, which led to the expectation that identity development is linked to both the reduction of risk behaviors and the promotion of African American adolescents' healthy development. Different personological theories…

  3. Developmental Relational Counseling: A Model for Self-Understanding in Relation to Others

    ERIC Educational Resources Information Center

    Duffey, Thelma; Haberstroh, Shane

    2012-01-01

    Developmental relational counseling (DRC) is an integrative framework designed to help clients develop personal awareness and relational functioning and conceptualize personal growth. DRC emerged from both authors' clinical work and was significantly influenced by relational-cultural theory and guided by the Enneagram personality typology and…

  4. A MODE-OF-ACTION-BASED QSAR APPROACH TO IMPROVE UNDERSTANDING OF DEVELOPMENTAL TOXICITY

    EPA Science Inventory

    QSAR models of developmental toxicity (devtox) have met with limited regulatory acceptance due to the use of ill-defined endpoints, lack of biological interpretability, and poor model performance. More generally, the lack of biological inference of many QSAR models is often due t...

  5. Understanding complexity in the human brain

    PubMed Central

    Bassett, Danielle S.; Gazzaniga, Michael S.

    2011-01-01

    Although the ultimate aim of neuroscientific enquiry is to gain an understanding of the brain and how its workings relate to the mind, the majority of current efforts are largely focused on small questions using increasingly detailed data. However, it might be possible to successfully address the larger question of mind–brain mechanisms if the cumulative findings from these neuroscientific studies are coupled with complementary approaches from physics and philosophy. The brain, we argue, can be understood as a complex system or network, in which mental states emerge from the interaction between multiple physical and functional levels. Achieving further conceptual progress will crucially depend on broad-scale discussions regarding the properties of cognition and the tools that are currently available or must be developed in order to study mind–brain mechanisms. PMID:21497128

  6. Human-Machine CRFs for Identifying Bottlenecks in Scene Understanding.

    PubMed

    Mottaghi, Roozbeh; Fidler, Sanja; Yuille, Alan; Urtasun, Raquel; Parikh, Devi

    2016-01-01

    Recent trends in image understanding have pushed for scene understanding models that jointly reason about various tasks such as object detection, scene recognition, shape analysis, contextual reasoning, and local appearance based classifiers. In this work, we are interested in understanding the roles of these different tasks in improved scene understanding, in particular semantic segmentation, object detection and scene recognition. Towards this goal, we "plug-in" human subjects for each of the various components in a conditional random field model. Comparisons among various hybrid human-machine CRFs give us indications of how much "head room" there is to improve scene understanding by focusing research efforts on various individual tasks. PMID:26656579

  7. Understanding the complexity of human gait dynamics

    NASA Astrophysics Data System (ADS)

    Scafetta, Nicola; Marchi, Damiano; West, Bruce J.

    2009-06-01

    Time series of human gait stride intervals exhibit fractal and multifractal properties under several conditions. Records from subjects walking at normal, slow, and fast pace speed are analyzed to determine changes in the fractal scalings as a function of the stress condition of the system. Records from subjects with different age from children to elderly and patients suffering from neurodegenerative disease are analyzed to determine changes in the fractal scalings as a function of the physical maturation or degeneration of the system. A supercentral pattern generator model is presented to simulate the above two properties that are typically found in dynamical network performance: that is, how a dynamical network responds to stress and to evolution.

  8. Making Human Beings Human: Bioecological Perspectives on Human Development. The SAGE Program on Applied Developmental Science

    ERIC Educational Resources Information Center

    Bronfenbrenner, Urie, Ed.

    2004-01-01

    To a greater extent than any other species, human beings create the environments that, in turn, shape their own development. This book endeavors to demonstrate that human beings can also develop those environments to optimize their most constructive genetic potentials. What makes human beings human, therefore, is both the potential to shape their…

  9. Understanding African American Adolescents’ Identity Development: A Relational Developmental Systems Perspective

    PubMed Central

    Brittian, Aerika S.

    2012-01-01

    This article examines the development of African American adolescents’ identity using a relational developmental systems theory framework, which led to the expectation that identity development is linked to both the reduction of risk behaviors and the promotion of African American adolescents’ healthy development. Different personological theories of identity development were discussed, including Erikson’s theory of psychosocial development and Marcia’s theory of identity statuses. Developmental systems theory was used to further the literature on African American adolescents’ identity development, by integrating various views of identity development as they pertain to these youth. Furthermore, the formation of many aspects of identity may be an important coping and resilience process for such youth. In addition, directions for future research are discussed, including a consideration of the complexity of diversity that exists within the African American adolescent population, and a call for more longitudinal assessments of identity development is presented. PMID:23243325

  10. Social anxiety disorder in adolescence: How developmental cognitive neuroscience findings may shape understanding and interventions for psychopathology.

    PubMed

    Haller, Simone P W; Cohen Kadosh, Kathrin; Scerif, Gaia; Lau, Jennifer Y F

    2015-06-01

    Social anxiety disorder represents a debilitating condition that has large adverse effects on the quality of social connections, educational achievement and wellbeing. Age-of-onset data suggests that early adolescence is a developmentally sensitive juncture for the onset of social anxiety. In this review, we highlight the potential of using a developmental cognitive neuroscience approach to understand (i) why there are normative increases in social worries in adolescence and (ii) how adolescence-associated changes may 'bring out' neuro-cognitive risk factors for social anxiety in a subset of individuals during this developmental period. We also speculate on how changes that occur in learning and plasticity may allow for optimal acquisition of more adaptive neurocognitive strategies through external interventions. Hence, for the minority of individuals who require external interventions to target their social fears, this enhanced flexibility could result in more powerful and longer-lasting therapeutic effects. We will review two novel interventions that target information-processing biases and their neural substrates via cognitive training and visual feedback of neural activity measured through functional magnetic resonance imaging. PMID:25818181

  11. Triclosan Decreases Rat Thyroxine: Mode-of-Action, Developmental Susceptibility and Human Relevance

    EPA Science Inventory

    Triclosan (TCS) decreases serum thyroxine (T4) in the rat. In vivo and in vitro approaches were used to address three uncertainties: by what mode-of-action (MOA) does TCS decrease T4; does TCS decrease T4 developmentally; and, are effects observed in rats relevant to humans? To t...

  12. Neutral versus Emotional Human Stimuli Processing in Children with Pervasive Developmental Disorders not Otherwise Specified

    ERIC Educational Resources Information Center

    Vannetzel, Leonard; Chaby, Laurence; Cautru, Fabienne; Cohen, David; Plaza, Monique

    2011-01-01

    Pervasive developmental disorder not otherwise specified (PDD-NOS) represents up to two-thirds of autism spectrum disorders; however, it is usually described in terms of the symptoms not shared by autism. The study explores processing of neutral and emotional human stimuli (by auditory, visual and multimodal channels) in children with PDD-NOS (n =…

  13. Characterization of Human Neural Progenitor Cell Models for Developmental Neurotoxicity Screening

    EPA Science Inventory

    Current testing methods for developmental neurotoxicity (DNT) make evaluation of the effects of large numbers of chemicals impractical and prohibitively expensive. As such, we are evaluating two different human neural progenitor cell (hNPC) models for their utility in screens for...

  14. WORKSHOP ON THE QUALITATIVE AND QUANTITATIVE COMPARABILITY OF HUMAN AND ANIMAL DEVELOPMENTAL NEUROTOXICITY: SUMMARY AND IMPLICATIONS

    EPA Science Inventory

    The Workshop on the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity was convened by the U.S. Environmental Protection Agency (EPA) and the National Institute on Drug Abuse to address issues related to when testing should be required, wha...

  15. Linking Social Change and Developmental Change: Shifting Pathways of Human Development

    ERIC Educational Resources Information Center

    Greenfield, Patricia M.

    2009-01-01

    P. M. Greenfield's new theory of social change and human development aims to show how changing sociodemographic ecologies alter cultural values and learning environments and thereby shift developmental pathways. Worldwide sociodemographic trends include movement from rural residence, informal education at home, subsistence economy, and…

  16. The Juvenile Transition: A Developmental Switch Point in Human Life History

    ERIC Educational Resources Information Center

    Del Giudice, Marco; Angeleri, Romina; Manera, Valeria

    2009-01-01

    This paper presents a new perspective on the transition from early to middle childhood (i.e., human juvenility), investigated in an integrative evolutionary framework. Juvenility is a crucial life history stage, when social learning and interaction with peers become central developmental functions; here it is argued that the "juvenile transition"…

  17. Inferring Developmental Stage Composition from Gene Expression in Human Malaria

    PubMed Central

    Montgomery, Jacqui; Sidhu, Amar Bir; Oh, Keunyoung; Meyer, Evan; Pierre-Louis, Willythssa; Seydel, Karl; Milner, Danny; Williamson, Kim; Wiegand, Roger; Ndiaye, Daouda; Daily, Johanna; Wirth, Dyann; Taylor, Terrie; Huttenhower, Curtis; Marti, Matthias

    2013-01-01

    In the current era of malaria eradication, reducing transmission is critical. Assessment of transmissibility requires tools that can accurately identify the various developmental stages of the malaria parasite, particularly those required for transmission (sexual stages). Here, we present a method for estimating relative amounts of Plasmodium falciparum asexual and sexual stages from gene expression measurements. These are modeled using constrained linear regression to characterize stage-specific expression profiles within mixed-stage populations. The resulting profiles were analyzed functionally by gene set enrichment analysis (GSEA), confirming differentially active pathways such as increased mitochondrial activity and lipid metabolism during sexual development. We validated model predictions both from microarrays and from quantitative RT-PCR (qRT-PCR) measurements, based on the expression of a small set of key transcriptional markers. This sufficient marker set was identified by backward selection from the whole genome as available from expression arrays, targeting one sentinel marker per stage. The model as learned can be applied to any new microarray or qRT-PCR transcriptional measurement. We illustrate its use in vitro in inferring changes in stage distribution following stress and drug treatment and in vivo in identifying immature and mature sexual stage carriers within patient cohorts. We believe this approach will be a valuable resource for staging lab and field samples alike and will have wide applicability in epidemiological studies of malaria transmission. PMID:24348235

  18. "Unwilling" versus "Unable": Chimpanzees' Understanding of Human Intentional Action

    ERIC Educational Resources Information Center

    Call, Josep; Hare, Brian; Carpenter, Malinda; Tomasello, Michael

    2004-01-01

    Understanding the intentional actions of others is a fundamental part of human social cognition and behavior. An important question is therefore whether other animal species, especially our nearest relatives the chimpanzees, also understand the intentional actions of others. Here we show that chimpanzees spontaneously (without training) behave…

  19. Statistical analyses in trials for the comprehensive understanding of organogenesis and histogenesis in humans and mice.

    PubMed

    Otani, Hiroki; Udagawa, Jun; Naito, Kanta

    2016-06-01

    Statistical analyses based on the quantitative data from real multicellular organisms are useful as inductive-type studies to analyse complex morphogenetic events in addition to deductive-type analyses using mathematical models. Here, we introduce several of our trials for the statistical analysis of organogenesis and histogenesis of human and mouse embryos and foetuses. Multidimensional scaling has been applied to prove the existence and examine the mode of interkinetic nuclear migration, a regulatory mechanism of stem cell proliferation/differentiation in epithelial tubular tissues. Several statistical methods were used on morphometric data from human foetuses to establish the multidimensional standard growth curve and to describe the relation among the developing organs and body parts. Although the results are still limited, we show that these analyses are not only useful to understand the normal and abnormal morphogenesis in humans and mice but also to provide clues that could correlate aspects of prenatal developmental events with postnatal diseases. PMID:26935132

  20. Methods to identify and characterize developmental neurotoxicity for human health risk assessment. II: neuropathology.

    PubMed Central

    Garman, R H; Fix, A S; Jortner, B S; Jensen, K F; Hardisty, J F; Claudio, L; Ferenc, S

    2001-01-01

    Neuropathologic assessment of chemically induced developmental alterations in the nervous system for regulatory purposes is a multifactorial, complex process. This calls for careful qualitative and quantitative morphologic study of numerous brains at several developmental stages in rats. Quantitative evaluation may include such basic methods as determination of brain weight and dimensions as well as the progressively more complex approaches of linear, areal, or stereologic measurement of brain sections. Histologic evaluation employs routine stains (such as hematoxylin and eosin), which can be complemented by a variety of special and immunohistochemical procedures. These brain studies are augmented by morphologic assessment of selected peripheral nervous system structures. Studies of this nature require a high level of technical skill as well as special training on the part of the pathologist. The pathologist should have knowledge of normal microscopic neuroanatomy/neuronal circuitry and an understanding of basic principles of developmental neurobiology, such as familiarity with the patterns of physiologic or programmed cell de PMID:11250809

  1. Increase developmental plasticity of human keratinocytes with gene suppression.

    PubMed

    Li, Shengwen Calvin; Jin, Yangsun; Loudon, William G; Song, Yahui; Ma, Zhiwei; Weiner, Leslie P; Zhong, Jiang F

    2011-08-01

    Recent evidence indicates that p53 suppression increased the efficiency of induced pluripotent stem cell (iPSC) generation. This occurred even with the enforced expression of as few as two canonical transcription factors, Oct4 and Sox2. In this study, primary human keratinocytes were successfully induced into a stage of plasticity by transient inactivation of p53, without enforced expression of any of the transcription factors previously used in iPSC generation. These cells were later redifferentiated into neural lineages. The gene suppression plastic cells were morphologically indistinguishable from human ES cells. Gene suppression plastic cells were alkaline phosphatase-positive, had normal karyotypes, and expressed p53. Together with the accumulating evidence of similarities and overlapping mechanisms between iPSC generation and cancer formation, this finding sheds light on the emerging picture of p53 sitting at the crossroads between two intricate cellular potentials: stem cell vs. cancer cell generation. This finding further supports the crucial role played by p53 in cellular reprogramming and suggests an alternative method to switch the lineage identity of human cells. This reported method offers the potential for directed lineage switching with the goal of generating autologous cell populations for novel clinical applications for neurodegenerative diseases. PMID:21768375

  2. Music, empathy and cultural understanding: The need for developmental research. Comment on "Music, empathy and cultural understanding" by E. Clarke et al.

    NASA Astrophysics Data System (ADS)

    Rabinowitch, Tal-Chen

    2015-12-01

    Clarke, DeNora and Vuoskoski have carried out a formidable task of preparing a profound and encompassing review [3] that brings together two highly complex and multifaceted concepts, empathy and music, as well as a specific aspect of empathy that is highly relevant to society, cultural understanding. They have done an extraordinary service in synthesizing the growing, but still highly fragmented body of work in this area. At the heart of this review lies an intricate model that the authors develop, which accounts for a variety of mechanisms and cognitive processes underlying musical empathic engagement. In what follows I would like to first point out what I think is unique about this model. Then, I will briefly describe the need for including in any such model a developmental angle.

  3. Understanding the relationships between air quality and human health

    SciTech Connect

    S.T. Rao

    2006-09-15

    Although there has been substantial progress in improving ambient air quality in the United States, atmospheric concentrations of ozone and fine particulate matter (PM2.5) continue to exceed the National Ambient Air Quality Standards in many locations. Consequently, a large portion of the U.S. population continues to be exposed to unhealthful levels of ozone and fine particles. This issue of EM, entitled 'Understanding the relationships between air quality and human health' presents a series of articles that focus on the relationships between air quality and human health - what we know so far and the challenges that remain. Their titles are: Understanding the effects of air pollution on human health; Assessing population exposures in studies of human health effects of PM2.5; Establishing a national environmental public health tracking network; Linking air quality and exposure models; and On alert: air quality forecasting and health advisory warnings.

  4. The Developmental Progression of Understanding of Mind during a Hiding Game

    ERIC Educational Resources Information Center

    Nelson, P. Brooke; Adamson, Lauren B.; Bakeman, Roger

    2012-01-01

    In this longitudinal study, 52 typically developing preschoolers engaged in a hiding game with their mothers when children were 42-, 54-, and 66-months old. Children's understanding of mind, positive affect, and engagement with the task were rated, and mothers' utterances were coded for role and content. Analyses confirmed that some facets of…

  5. Understanding the Law: An Advocate's Guide to the Law and Developmental Disabilities.

    ERIC Educational Resources Information Center

    Taylor, Steven J.; Biklen, Douglas

    This handbook, designed for advocates for disabled persons, focuses on understanding and researching the law. It is presented in seven chapters. Following the introduction (Chapter I), Chapter II provides a glossary of legal terms. The authors point out that in order for the law to serve as a tool for change, its language must be understood by…

  6. When Young Children Need Help: Understanding and Addressing Emotional, Behavioral, and Developmental Challenges

    ERIC Educational Resources Information Center

    Hirschland, Deborah

    2015-01-01

    You know what it's like to spend time with youngsters who are particularly puzzling or hard to help. "When Young Children Need Help" helps early childhood educators make sense of what is going on for such children and use that understanding to promote growth and mastery. Written for child care center staff, family child care providers,…

  7. Developmental stages in human embryos: revised and new measurements.

    PubMed

    O'Rahilly, Ronan; Müller, Fabiola

    2010-01-01

    The staging of human embryos, as distinct from seriation, depends on a morphological scheme devised by Streeter and completed by O'Rahilly, who proposed the term Carnegie stages. To avoid misconceptions and errors, and to place new findings in perspective, it is necessary to summarize the essentials of the Carnegie system: (1) Twenty-three stages cover the embryonic period, i. e. the first 8 postfertilizational weeks of development. (2) The system is based on internal as well as external features, and the use of only external criteria is subject to serious limitations. For example, precise delineation of stages 19-23 and of the embryonic-fetal transition depends on histological examination. (3) Prenatal measurements are not an integral component of the staging system, and hence a stage should never be assigned merely on the basis of embryonic length. A 20-mm embryo, for example, could belong to any of three stages. Measurements, however, are important for the assessment of age, and very few measurements are available for staged embryos. Presented here and based on accurate staging are the maximum diameter of the chorionic sac, the crown-heel length, the greatest length exclusive of the lower limbs, the biparietal diameter, the head circumference, the length of the hindbrain, the total length of the brain, and the lengths of the limbs as well as of their segments, including the foot length. (4) Prenatal ages are also not an integral part of the staging system and hence a stage should never be assigned merely on the basis of prenatal age. Ages, however, are of clinical importance and their estimate has been rendered more precise by accurate timing of fertilization followed by ultrasonography. Prenatal age is postfertilizational and hence some 2 weeks less than the postmenstrual interval. The term gestational age is ambiguous and should be discarded. Presented here is a new graph showing proposed estimates of age in relation to stages and based on current information

  8. Developmental potential of human oocytes reconstructed by transferring somatic cell nuclei into polyspermic zygote cytoplasm

    SciTech Connect

    Fan, Yong; Chen, Xinjie; Luo, Yumei; Chen, Xiaolin; Li, Shaoying; Huang, Yulin; Sun, Xiaofang

    2009-04-24

    The generation of patient-specific nuclear transfer embryonic stem cells holds huge promise in modern regenerative medicine and cell-based drug discovery. Since human in vivo matured oocytes are not readily available, human therapeutic cloning is developing slowly. Here, we investigated for the first time whether human polyspermic zygotes could support preimplantation development of cloned embryos. Our results showed that polyspermic zygotes could be used as recipients for human somatic cell nuclear transfer (SCNT). The preimplantation developmental potential of SCNT embryos from polyspermic zygotes was limited to the 8-cell stage. Since ES cell lines can be derived from single blastomeres, these results may have important significance for human ES cells derived by SCNT. In addition, confocal images demonstrated that all of the SCNT embryos that failed to cleave showed abnormal microtubule organization. The results of the present study suggest that polyspermic human zygotes could be used as a potential source of recipient cytoplasm for SCNT.

  9. Mental Retardation Genes in Drosophila: New Approaches to Understanding and Treating Developmental Brain Disorders

    ERIC Educational Resources Information Center

    Restifo, Linda L.

    2005-01-01

    "Drosophila melanogaster" is emerging as a valuable genetic model system for the study of mental retardation (MR). MR genes are remarkably similar between humans and fruit flies. Cognitive behavioral assays can detect reductions in learning and memory in flies with mutations in MR genes. Neuroanatomical methods, including some at single-neuron…

  10. The Various Roles of Animal Models in Understanding Human Development

    ERIC Educational Resources Information Center

    Gottlieb, Gilbert; Lickliter, Robert

    2004-01-01

    In this article, the authors take a very conservative view of the contribution of animal models to an understanding of human development. We do not think that homologies can be readily documented with even our most closely related relatives' behavior and psychological functioning. The major contribution of animal models is their provision of food…

  11. 1970 Project Understanding: A Community Education Project on Human Survival.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Milwaukee.

    The purposes of Project Understanding were to help participants to: obtain accurate information of human survival issues relating to people, poverty, pollution, and politics; think through the implications of these issues and examine their opinions about them; change their own opinions, attitudes, and behavior; and take effective citizen action.…

  12. Computer and Human Understanding in Intelligent Retrieval Assistance.

    ERIC Educational Resources Information Center

    Marcus, Richard S.

    1991-01-01

    Discusses general issues of computer and human understanding; contrasts three paradigms of information retrieval methodology, including statistical, deep semantic or natural language, and smart Boolean; describes CONIT, a knowledge-based intermediary retrieval assistance system; and examines system evaluation procedures, including a…

  13. Using Mouse and Zebrafish Models to Understand the Etiology of Developmental Defects in Cornelia de Lange Syndrome

    PubMed Central

    KAWAUCHI, SHIMAKO; SANTOS, ROSAYSELA; MUTO, AKIHIKO; LOPEZ-BURKS, MARTHA E.; SCHILLING, THOMAS F.; LANDER, ARTHUR D.; CALOF, ANNE L.

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a multisystem birth defects disorder that affects every tissue and organ system in the body. Understanding the factors that contribute to the origins, prevalence, and severity of these developmental defects provides the most direct approach for developing screens and potential treatments for individuals with CdLS. Since the majority of cases of CdLS are caused by haploinsufficiency for NIPBL (Nipped-B-like, which encodes a cohesin-associated protein), we have developed mouse and zebrafish models of CdLS by using molecular genetic tools to create Nipbl-deficient mice and zebrafish (Nipbl+/− mice, zebrafish nipbl morphants). Studies of these vertebrate animal models have yielded novel insights into the developmental etiology and genes/gene pathways that contribute to CdLS-associated birth defects, particularly defects of the gut, heart, craniofacial structures, nervous system, and limbs. Studies of these mouse and zebrafish CdLS models have helped clarify how deficiency for NIPBL, a protein that associates with cohesin and other transcriptional regulators in the nucleus, affects processes important to the emergence of the structural and physiological birth defects observed in CdLS: NIPBL exerts chromosome position-specific effects on gene expression; it influences long-range interactions between different regulatory elements of genes; and it regulates combinatorial and synergistic actions of genes in developing tissues. Our current understanding is that CdLS should be considered as not only a cohesinopathy, but also a “transcriptomopathy,” that is, a disease whose underlying etiology is the global dysregulation of gene expression throughout the organism. PMID:27120001

  14. Using mouse and zebrafish models to understand the etiology of developmental defects in Cornelia de Lange Syndrome.

    PubMed

    Kawauchi, Shimako; Santos, Rosaysela; Muto, Akihiko; Lopez-Burks, Martha E; Schilling, Thomas F; Lander, Arthur D; Calof, Anne L

    2016-06-01

    Cornelia de Lange Syndrome (CdLS) is a multisystem birth defects disorder that affects every tissue and organ system in the body. Understanding the factors that contribute to the origins, prevalence, and severity of these developmental defects provides the most direct approach for developing screens and potential treatments for individuals with CdLS. Since the majority of cases of CdLS are caused by haploinsufficiency for NIPBL (Nipped-B-like, which encodes a cohesin-associated protein), we have developed mouse and zebrafish models of CdLS by using molecular genetic tools to create Nipbl-deficient mice and zebrafish (Nipbl(+/-) mice, zebrafish nipbl morphants). Studies of these vertebrate animal models have yielded novel insights into the developmental etiology and genes/gene pathways that contribute to CdLS-associated birth defects, particularly defects of the gut, heart, craniofacial structures, nervous system, and limbs. Studies of these mouse and zebrafish CdLS models have helped clarify how deficiency for NIPBL, a protein that associates with cohesin and other transcriptional regulators in the nucleus, affects processes important to the emergence of the structural and physiological birth defects observed in CdLS: NIPBL exerts chromosome position-specific effects on gene expression; it influences long-range interactions between different regulatory elements of genes; and it regulates combinatorial and synergistic actions of genes in developing tissues. Our current understanding is that CdLS should be considered as not only a cohesinopathy, but also a "transcriptomopathy," that is, a disease whose underlying etiology is the global dysregulation of gene expression throughout the organism. © 2016 Wiley Periodicals, Inc. PMID:27120001

  15. Understanding the behavior of floodplains as human-water systems

    NASA Astrophysics Data System (ADS)

    Di Baldassarre, G.; Brandimarte, L.

    2012-12-01

    Floodplains are among the most valuable ecosystems for supporting biodiversity and providing services to the environment. Moreover, they are home of approximately one-sixth of the world population as they offer favorable conditions for economic development. As a result, flood disasters currently affect more than 100 million people a year. Sadly, flood losses and fatalities are expected to increase further in many countries because of population growth as well as changes in land use and climate. Given the relevance of floodplain systems, a number of social scientists have examined how the frequency and severity of flooding often determine whether human development in floodplains is desirable or not. Meanwhile, many earth scientists have investigated the impact of human activities (e.g. land-use changes, urbanization, river training) on the frequency and magnitude of floods. In fact, as human activities change the frequency of flooding, the frequency of flooding affects human developments in floodplain areas. Yet, these dynamic interactions between floods and societies and the associated feedback mechanisms remain largely unexplored and poorly understood. As a result, we typically consider humans as external forcing (or boundary condition) without representing the feedback loops and our prediction of future trajectories are therefore extremely limited. This presentation shows a first attempt to understand the behavior of floodplains as coupled human-water systems. In particular, we analyzed a number of long time series of hydrological and population data in the Po River Basin (Italy) to explore the feedback mechanisms, reciprocal effects, surprises, and threshold mechanisms, taking place in floodplain systems. The outcomes of the study enable a better understanding of how the occurrences of floods shape human developments while, at the same time, human activities shape the magnitude and frequency of floods. The presentation also discusses the opportunities offered by

  16. NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines.

    PubMed

    2005-07-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for amphetamines to cause adverse effects on reproduction and development in humans. Amphetamines evaluated were D- and D,L-amphetamine and methamphetamine. Amphetamine is approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons over 3 years of age and narcolepsy; methamphetamine is approved for the treatment of ADHD in persons 6 years of age and older and for short-term treatment of obesity. Amphetamines were selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. The results of this evaluation on amphetamines are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is some concern for developmental effects, specifically for potential neurobehavioral alterations, from prenatal amphetamine exposure in humans both in therapeutic and non-therapeutic settings. After prenatal exposure to therapeutic doses of amphetamine, rat pups demonstrated neurobehavioral alterations. Data from human and animal studies were judged insufficient for an evaluation of the effect of amphetamine exposure on growth and other related developmental effects. Second, there is concern for methamphetamine-induced adverse developmental effects, specifically on growth and neurobehavioral development, in therapeutic and non-therapeutic settings. This conclusion is based

  17. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Fluoxetine.

    PubMed

    2004-11-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for fluoxetine to cause adverse effects on reproduction and development in humans. Fluoxetine (Prozac(R); Serafemtrade mark) was selected for evaluation because of 1) sufficient reproductive and developmental studies, 2) human exposure information, 3) changing prescription patterns, and 4) public concern about potential reproductive and/or developmental hazards associated with exposure. Fluoxetine, an antidepressant, is also prescribed to treat premenstrual dysphoric disorder and has recently been approved for use in 7-17 year-olds. The results of this evaluation on fluoxetine are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Fluoxetine, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to fluoxetine on human development and reproduction. First, there is some concern for developmental effects, specifically shortened gestation and poor neonatal adaptation at therapeutic doses (20-80 mg/day). This conclusion is based on evidence from human studies that fluoxetine produces an increased rate of poor neonatal adaptation and that fluoxetine exposure during pregnancy can result in a shortened gestation and reduced birth weight at term. Second, there is minimal concern for adverse reproductive effects in fluoxetine-exposed adults. Evidence from human studies show that therapeutic doses of fluoxetine may, in both men and women, result in reversible, impaired sexual function, specifically a delay in or an inability to achieve orgasm. Finally, there are insufficient data to draw conclusions on 1) an association between fluoxetine therapy in pregnant women and pregnancy loss; and 2) on how breast milk or therapeutic

  18. Developmental growth trajectories in understanding of fraction magnitude from fourth through sixth grade.

    PubMed

    Resnick, Ilyse; Jordan, Nancy C; Hansen, Nicole; Rajan, Vinaya; Rodrigues, Jessica; Siegler, Robert S; Fuchs, Lynn S

    2016-05-01

    Development of fraction number line estimation was assessed longitudinally over 5 time points between 4th and 6th grades. Although students showed positive linear growth overall, latent class growth analyses revealed 3 distinct growth trajectory classes: Students who were highly accurate from the start and became even more accurate (n = 154); students who started inaccurate but showed steep growth (n = 121); and students who started inaccurate and showed minimal growth (n = 197). Younger and minimal growth students typically estimated both proper and improper fractions as being less than 1, failing to base estimates on the relation between the numerator and denominator. Class membership was highly predictive of performance on a statewide-standardized mathematics test as well as on a general fraction knowledge measure at the end of 6th grade, even after controlling for mathematic-specific abilities, domain-general cognitive abilities, and demographic variables. Multiplication fluency, classroom attention, and whole number line estimation acuity at the start of the study predicted class membership. The findings reveal that fraction magnitude understanding is central to mathematical development. (PsycINFO Database Record PMID:26914215

  19. Developmental Origins of Health and Disease: A Paradigm for Understanding Disease Etiology and Prevention

    PubMed Central

    Heindel, Jerrold J.; Vandenberg, Laura N.

    2015-01-01

    Purpose of Review While diseases may appear clinically throughout the lifespan, it is clear that many diseases have origins during development. Altered nutrition, as well as exposure to environmental chemicals, drugs, infections, or stress during specific times of development can lead to functional changes in tissues, predisposing those tissues to diseases that manifest later in life. This review will focus on the role of altered nutrition and exposures to environmental chemicals during development in the role of disease/dysfunctions. Recent Findings Effects of altered nutrition or exposure to environmental chemicals during development are likely due to altered programming of epigenetic marks which persist across the lifespan. Indeed some changes can be transmitted to future generations. Summary Evidence in support of the DOHaD paradigm is sufficiently robust and repeatable across species including humans, suggesting a need for greater emphasis in the clinical area. Because of these data, obesity, diabetes, cardiovascular morbidity, and neuropsychiatric diseases can all be considered pediatric diseases. Disease prevention must start with improved nutrition and reduced exposures to environmental chemicals during development. PMID:25635586

  20. Embodied artificial agents for understanding human social cognition.

    PubMed

    Wykowska, Agnieszka; Chaminade, Thierry; Cheng, Gordon

    2016-05-01

    In this paper, we propose that experimental protocols involving artificial agents, in particular the embodied humanoid robots, provide insightful information regarding social cognitive mechanisms in the human brain. Using artificial agents allows for manipulation and control of various parameters of behaviour, appearance and expressiveness in one of the interaction partners (the artificial agent), and for examining effect of these parameters on the other interaction partner (the human). At the same time, using artificial agents means introducing the presence of artificial, yet human-like, systems into the human social sphere. This allows for testing in a controlled, but ecologically valid, manner human fundamental mechanisms of social cognition both at the behavioural and at the neural level. This paper will review existing literature that reports studies in which artificial embodied agents have been used to study social cognition and will address the question of whether various mechanisms of social cognition (ranging from lower- to higher-order cognitive processes) are evoked by artificial agents to the same extent as by natural agents, humans in particular. Increasing the understanding of how behavioural and neural mechanisms of social cognition respond to artificial anthropomorphic agents provides empirical answers to the conundrum 'What is a social agent?' PMID:27069052

  1. Embodied artificial agents for understanding human social cognition

    PubMed Central

    Wykowska, Agnieszka; Chaminade, Thierry; Cheng, Gordon

    2016-01-01

    In this paper, we propose that experimental protocols involving artificial agents, in particular the embodied humanoid robots, provide insightful information regarding social cognitive mechanisms in the human brain. Using artificial agents allows for manipulation and control of various parameters of behaviour, appearance and expressiveness in one of the interaction partners (the artificial agent), and for examining effect of these parameters on the other interaction partner (the human). At the same time, using artificial agents means introducing the presence of artificial, yet human-like, systems into the human social sphere. This allows for testing in a controlled, but ecologically valid, manner human fundamental mechanisms of social cognition both at the behavioural and at the neural level. This paper will review existing literature that reports studies in which artificial embodied agents have been used to study social cognition and will address the question of whether various mechanisms of social cognition (ranging from lower- to higher-order cognitive processes) are evoked by artificial agents to the same extent as by natural agents, humans in particular. Increasing the understanding of how behavioural and neural mechanisms of social cognition respond to artificial anthropomorphic agents provides empirical answers to the conundrum ‘What is a social agent?’ PMID:27069052

  2. Current understanding of mdig/MINA in human cancers

    PubMed Central

    Thakur, Chitra; Chen, Fei

    2015-01-01

    Mineral dust-induced gene, mdig has recently been identified and is known to be overexpressed in a majority of human cancers and holds predictive power in the poor prognosis of the disease. Mdig is an environmentally expressed gene that is involved in cell proliferation, neoplastic transformation and immune regulation. With the advancement in deciphering the prognostic role of mdig in human cancers, our understanding on how mdig renders a normal cell to undergo malignant transformation is still very limited. This article reviews the current knowledge of the mdig gene in context to human neoplasias and its relation to the clinico-pathologic factors predicting the outcome of the disease in patients. It also emphasizes on the promising role of mdig that can serve as a potential candidate for biomarker discovery and as a therapeutic target in inflammation and cancers. Considering the recent advances in understanding the underlying mechanisms of tumor formation, more preclinical and clinical research is required to validate the potential of using mdig as a novel biological target of therapeutic and diagnostic value. Summary Expression level of mdig influences the prognosis of several human cancers especially cancers of the breast and lung. Evaluation of mdig in cancers can offer novel biomarker with potential therapeutic interventions for the early assessment of cancer development in patients. PMID:26413213

  3. Human DNA quantification and sample quality assessment: Developmental validation of the PowerQuant(®) system.

    PubMed

    Ewing, Margaret M; Thompson, Jonelle M; McLaren, Robert S; Purpero, Vincent M; Thomas, Kelli J; Dobrowski, Patricia A; DeGroot, Gretchen A; Romsos, Erica L; Storts, Douglas R

    2016-07-01

    Quantification of the total amount of human DNA isolated from a forensic evidence item is crucial for DNA normalization prior to short tandem repeat (STR) DNA analysis and a federal quality assurance standard requirement. Previous commercial quantification methods determine the total human DNA and total human male DNA concentrations, but provide limited information about the condition of the DNA sample. The PowerQuant(®) System includes targets for quantification of total human and total human male DNA as well as targets for evaluating whether the human DNA is degraded and/or PCR inhibitors are present in the sample. A developmental validation of the PowerQuant(®) System was completed, following SWGDAM Validation Guidelines, to evaluate the assay's specificity, sensitivity, precision and accuracy, as well as the ability to detect degraded DNA or PCR inhibitors. In addition to the total human DNA and total human male DNA concentrations in a sample, data from the degradation target and internal PCR control (IPC) provide a forensic DNA analyst meaningful information about the quality of the isolated human DNA and the presence of PCR inhibitors in the sample that can be used to determine the most effective workflow and assist downstream interpretation. PMID:27206225

  4. Can we understand modern humans without considering pathogens?

    PubMed Central

    Thomas, Frédéric; Daoust, Simon P; Raymond, Michel

    2012-01-01

    Throughout our evolutionary history, humankind has always lived in contact with large numbers of pathogens. Some cultural traits, such as sedentarization and animal domestication, have considerably increased new parasitic contacts and epidemic transitions. Here, we review the various phenotypic traits that have been proposed to be affected by the highly parasitic human environment, including fertility, birth weight, fluctuating asymmetry, body odours, food recipes, sexual behaviour, pregnancy sickness, language, religion and intellectual quotient. We also discuss how such knowledge is important to understanding several aspects of the current problems faced by humanity in our changing world and to predicting the long-term consequences of parasite eradication policies on our health and well-being. The study of the evolutionary interactions between humans and parasites is a burgeoning and most promising field, as demonstrated by the recent increasing popularity of Darwinian medicine. PMID:25568057

  5. Understanding the immunological impact of the human mutation explosion.

    PubMed

    Andrews, T D; Sjollema, G; Goodnow, C C

    2013-03-01

    The recent development of human exome sequencing technology has revealed that our immune system is riddled with more genetic defects than anyone imagined. As a legacy of the recent human population explosion, we each inherit hundreds of rare mutations that alter the sequence of proteins. This mutation load is ten times higher than that induced by experimental treatment of mice by ethylnitrosourea; a high fraction of which has substantial effects on immune function. This mutation burden is likely to be a major factor in the incidence of many human immune disorders, but understanding this at the level of individual patients will require new bioinformatics and experimental strategies to assess the impact of individual and combined mutations on immune response pathways. PMID:23333204

  6. Understanding Dyslexia in Children through Human Development Theories.

    PubMed

    Al-Shidhani, Thuraya Ahmed; Arora, Vinita

    2012-08-01

    Dyslexia is a specific learning disability that is neurological in origin, with an estimated overall worldwide prevalence of 5-10% of the population. It is characterised by difficulties in reading, accuracy, fluency, spelling and decoding abilities. The majority of publications reviewed indicated that screening is performed at the preschool level. Screening can also be conducted at birth or the first year of life. Understanding human development theory, for example, Piaget's human development theory, may help determine at which stage of childhood development dyslexia is more detectable, and therefore guide the management of this disability. The objective of this review is to provide a brief and updated overview of dyslexia and its management in children through human development issues. PMID:23269949

  7. Understanding Dyslexia in Children through Human Development Theories

    PubMed Central

    Al-Shidhani, Thuraya Ahmed; Arora, Vinita

    2012-01-01

    Dyslexia is a specific learning disability that is neurological in origin, with an estimated overall worldwide prevalence of 5–10% of the population. It is characterised by difficulties in reading, accuracy, fluency, spelling and decoding abilities. The majority of publications reviewed indicated that screening is performed at the preschool level. Screening can also be conducted at birth or the first year of life. Understanding human development theory, for example, Piaget’s human development theory, may help determine at which stage of childhood development dyslexia is more detectable, and therefore guide the management of this disability. The objective of this review is to provide a brief and updated overview of dyslexia and its management in children through human development issues. PMID:23269949

  8. "Unwilling" versus "Unable": Capuchin Monkeys' ("Cebus Apella") Understanding of Human Intentional Action

    ERIC Educational Resources Information Center

    Phillips, Webb; Barnes, Jennifer L.; Mahajan, Neha; Yamaguchi, Mariko; Santos, Laurie R.

    2009-01-01

    A sensitivity to the intentions behind human action is a crucial developmental achievement in infants. Is this intention reading ability a unique and relatively recent product of human evolution and culture, or does this capacity instead have roots in our non-human primate ancestors? Recent work by Call and colleagues (2004) lends credence to the…

  9. Methods to identify and characterize developmental neurotoxicity for human health risk assessment. I: behavioral effects.

    PubMed Central

    Cory-Slechta, D A; Crofton, K M; Foran, J A; Ross, J F; Sheets, L P; Weiss, B; Mileson, B

    2001-01-01

    Alterations in nervous system function after exposure to a developmental neurotoxicant may be identified and characterized using neurobehavioral methods. A number of methods can evaluate alterations in sensory, motor, and cognitive functions in laboratory animals exposed to toxicants during nervous system development. Fundamental issues underlying proper use and interpretation of these methods include a) consideration of the scientific goal in experimental design, b) selection of an appropriate animal model, c) expertise of the investigator, d) adequate statistical analysis, and e) proper data interpretation. Strengths and weaknesses of the assessment methods include sensitivity, selectivity, practicality, and variability. Research could improve current behavioral methods by providing a better understanding of the relationship between alterations in motor function and changes in the underlying structure of these systems. Research is also needed to develop simple and sensitive assays for use in screening assessments of sensory and cognitive function. Assessment methods are being developed to examine other nervous system functions, including social behavior, autonomic processes, and biologic rhythms. Social behaviors are modified by many classes of developmental neurotoxicants and hormonally active compounds that may act either through neuroendocrine mechanisms or by directly influencing brain morphology or neurochemistry. Autonomic and thermoregulatory functions have been the province of physiologists and neurobiologists rather than toxicologists, but this may change as developmental neurotoxicology progresses and toxicologists apply techniques developed by other disciplines to examine changes in function after toxicant exposure. PMID:11250808

  10. Sex Biased Gene Expression Profiling of Human Brains at Major Developmental Stages.

    PubMed

    Shi, Lei; Zhang, Zhe; Su, Bing

    2016-01-01

    There are many differences in brain structure and function between males and females. However, how these differences were manifested during development and maintained through adulthood are still unclear. Here we present a time series analyses of genome-wide transcription profiles of the human brain, and we identified genes showing sex biased expression at major developmental stages (prenatal time, early childhood, puberty time and adulthood). We observed a great number of genes (>2,000 genes) showing between-sex expression divergence at all developmental stages with the greatest number (4,164 genes) at puberty time. However, there are little overlap of sex-biased genes among the major developmental stages, an indication of dynamic expression regulation of the sex-biased genes in the brain during development. Notably, the male biased genes are highly enriched for genes involved in neurological and psychiatric disorders like schizophrenia, bipolar disorder, Alzheimer's disease and autism, while no such pattern was seen for the female-biased genes, suggesting that the differences in brain disorder susceptibility between males and females are likely rooted from the sex-biased gene expression regulation during brain development. Collectively, these analyses reveal an important role of sex biased genes in brain development and neurodevelopmental disorders. PMID:26880485

  11. Sex Biased Gene Expression Profiling of Human Brains at Major Developmental Stages

    PubMed Central

    Shi, Lei; Zhang, Zhe; Su, Bing

    2016-01-01

    There are many differences in brain structure and function between males and females. However, how these differences were manifested during development and maintained through adulthood are still unclear. Here we present a time series analyses of genome-wide transcription profiles of the human brain, and we identified genes showing sex biased expression at major developmental stages (prenatal time, early childhood, puberty time and adulthood). We observed a great number of genes (>2,000 genes) showing between-sex expression divergence at all developmental stages with the greatest number (4,164 genes) at puberty time. However, there are little overlap of sex-biased genes among the major developmental stages, an indication of dynamic expression regulation of the sex-biased genes in the brain during development. Notably, the male biased genes are highly enriched for genes involved in neurological and psychiatric disorders like schizophrenia, bipolar disorder, Alzheimer’s disease and autism, while no such pattern was seen for the female-biased genes, suggesting that the differences in brain disorder susceptibility between males and females are likely rooted from the sex-biased gene expression regulation during brain development. Collectively, these analyses reveal an important role of sex biased genes in brain development and neurodevelopmental disorders. PMID:26880485

  12. Evaluation of a human neurite growth assay as specific screen for developmental neurotoxicants.

    PubMed

    Krug, Anne K; Balmer, Nina V; Matt, Florian; Schönenberger, Felix; Merhof, Dorit; Leist, Marcel

    2013-12-01

    Organ-specific in vitro toxicity assays are often highly sensitive, but they lack specificity. We evaluated here examples of assay features that can affect test specificity, and some general procedures are suggested on how positive hits in complex biological assays may be defined. Differentiating human LUHMES cells were used as potential model for developmental neurotoxicity testing. Forty candidate toxicants were screened, and several hits were obtained and confirmed. Although the cells had a definitive neuronal phenotype, the use of a general cell death endpoint in these cultures did not allow specific identification of neurotoxicants. As alternative approach, neurite growth was measured as an organ-specific functional endpoint. We found that neurite extension of developing LUHMES was specifically inhibited by diverse compounds such as colchicine, vincristine, narciclasine, rotenone, cycloheximide, or diquat. These compounds reduced neurite growth at concentrations that did not compromise cell viability, and neurite growth was affected more potently than the integrity of developed neurites of mature neurons. A ratio of the EC50 values of neurite growth inhibition and cell death of >4 provided a robust classifier for compounds associated with a developmental neurotoxic hazard. Screening of unspecific toxicants in the test system always yielded ratios <4. The assay identified also compounds that accelerated neurite growth, such as the rho kinase pathway modifiers blebbistatin or thiazovivin. The negative effects of colchicine or rotenone were completely inhibited by a rho kinase inhibitor. In summary, we suggest that assays using functional endpoints (neurite growth) can specifically identify and characterize (developmental) neurotoxicants. PMID:23670202

  13. Human Inspired Self-developmental Model of Neural Network (HIM): Introducing Content/Form Computing

    NASA Astrophysics Data System (ADS)

    Krajíček, Jiří

    This paper presents cross-disciplinary research between medical/psychological evidence on human abilities and informatics needs to update current models in computer science to support alternative methods for computation and communication. In [10] we have already proposed hypothesis introducing concept of human information model (HIM) as cooperative system. Here we continue on HIM design in detail. In our design, first we introduce Content/Form computing system which is new principle of present methods in evolutionary computing (genetic algorithms, genetic programming). Then we apply this system on HIM (type of artificial neural network) model as basic network self-developmental paradigm. Main inspiration of our natural/human design comes from well known concept of artificial neural networks, medical/psychological evidence and Sheldrake theory of "Nature as Alive" [22].

  14. Human developmental chondrogenesis as a basis for engineering chondrocytes from pluripotent stem cells.

    PubMed

    Wu, Ling; Bluguermann, Carolina; Kyupelyan, Levon; Latour, Brooke; Gonzalez, Stephanie; Shah, Saumya; Galic, Zoran; Ge, Sundi; Zhu, Yuhua; Petrigliano, Frank A; Nsair, Ali; Miriuka, Santiago G; Li, Xinmin; Lyons, Karen M; Crooks, Gay M; McAllister, David R; Van Handel, Ben; Adams, John S; Evseenko, Denis

    2013-01-01

    Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166(low/neg)CD146(low/neg)CD73(+)CD44(low)BMPR1B(+)) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5-6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166(low/neg)BMPR1B(+) putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering. PMID:24371811

  15. Human Developmental Chondrogenesis as a Basis for Engineering Chondrocytes from Pluripotent Stem Cells

    PubMed Central

    Wu, Ling; Bluguermann, Carolina; Kyupelyan, Levon; Latour, Brooke; Gonzalez, Stephanie; Shah, Saumya; Galic, Zoran; Ge, Sundi; Zhu, Yuhua; Petrigliano, Frank A.; Nsair, Ali; Miriuka, Santiago G.; Li, Xinmin; Lyons, Karen M.; Crooks, Gay M.; McAllister, David R.; Van Handel, Ben; Adams, John S.; Evseenko, Denis

    2013-01-01

    Summary Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166low/negCD146low/negCD73+CD44lowBMPR1B+) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5–6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166low/negBMPR1B+ putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering. PMID:24371811

  16. Accepting, understanding, teaching, and learning (human) evolution: Obstacles and opportunities.

    PubMed

    Pobiner, Briana

    2016-01-01

    Questions about our origin as a species are universal and compelling. Evolution-and in particular human evolution-is a subject that generates intense interest across the world, evidenced by the fact that fossil and DNA discoveries grace the covers of major science journals and magazines as well as other popular print and online media. However, virtually all national polls indicate that the majority of Americans strongly reject biological evolution as a fact-based, well-tested, and robust understanding of the history of life. In the popular mind, no topic in all of science is more contentious or polarizing than evolution and media sources often only serve to magnify this polarization by covering challenges to the teaching of evolution. In the realm of teaching, debates about evolution have shaped textbooks, curricula, standards, and policy. Challenges to accepting and understanding evolution include mistrust and denial of science, cognitive obstacles and misconceptions, language and terminology, and a religious worldview, among others. Teachers, who are on the front lines of these challenges, must be armed with the tools and techniques to teach evolution in formal education settings across grades K-16 in a straightforward, thorough, and sensitive way. Despite the potentially controversial topic of human evolution, growing research is demonstrating that a pedagogical focus on human examples is an effective and engaging way to teach core concepts of evolutionary biology. PMID:26808108

  17. Use of NOD Mice to Understand Human Type 1 Diabetes

    PubMed Central

    Thayer, Terri C.; Wilson, Brian S.; Mathews, Clayton E.

    2010-01-01

    Synopsis In 1922, Leonard Thompson received the first injections of insulin prepared from the pancreas of canine test subjects. From pancreatectomized dogs to the more recent development of animal models that spontaneously develop autoimmune syndromes, animal models have played a meaningful role in furthering diabetes research. Of these animals the non-obese diabetic (NOD) mouse is the most widely used for research in Type 1 Diabetes (T1D) as the NOD shares a number of genetic and immunologic traits with the human form of the disease. In this chapter, we review both similarities and differences in NOD and human T1D and discuss the potential role of NOD mice in future pre-clinical studies aiming to provide a better understanding of the genetic and immune defects that lead to T1D. PMID:20723819

  18. An Overview on Human Umbilical Cord Blood Stem Cell-Based Alternative In Vitro Models for Developmental Neurotoxicity Assessment.

    PubMed

    Singh, Abhishek Kumar; Kashyap, Mahendra Pratap

    2016-07-01

    The developing brain is found highly vulnerable towards the exposure of different environmental chemicals/drugs, even at concentrations, those are generally considered safe in mature brain. The brain development is a very complex phenomenon which involves several processes running in parallel such as cell proliferation, migration, differentiation, maturation and synaptogenesis. If any step of these cellular processes hampered due to exposure of any xenobiotic/drug, there is almost no chance of recovery which could finally result in a life-long disability. Therefore, the developmental neurotoxicity (DNT) assessment of newly discovered drugs/molecules is a very serious concern among the neurologists. Animal-based DNT models have their own limitations such as ethical concerns and lower sensitivity with less predictive values in humans. Furthermore, non-availability of human foetal brain tissues/cells makes job more difficult to understand about mechanisms involve in DNT in human beings. Although, the use of cell culture have been proven as a powerful tool for DNT assessment, but many in vitro models are currently utilizing genetically unstable cell lines. The interpretation of data generated using such terminally differentiated cells is hard to extrapolate with in vivo situations. However, human umbilical cord blood stem cells (hUCBSCs) have been proposed as an excellent tool for alternative DNT testing because neuronal development from undifferentiated state could exactly mimic the original pattern of neuronal development in foetus when hUCBSCs differentiated into neuronal cells. Additionally, less ethical concern, easy availability and high plasticity make them an attractive source for establishing in vitro model of DNT assessment. In this review, we are focusing towards recent advancements on hUCBSCs-based in vitro model to understand DNTs. PMID:26041658

  19. Developmental potential of clinically discarded human embryos and associated chromosomal analysis

    PubMed Central

    Yao, Guidong; Xu, Jiawei; Xin, Zhimin; Niu, Wenbin; Shi, Senlin; Jin, Haixia; Song, Wenyan; Wang, Enyin; Yang, Qingling; Chen, Lei; Sun, Yingpu

    2016-01-01

    Clinically discarded human embryos, which are generated from both normal and abnormal fertilizations, have the potential of developing into blastocysts. A total of 1,649 discarded human embryos, including zygotes containing normal (2PN) and abnormal (0PN, 1PN, 3PN and ≥4PN) pronuclei and prematurely cleaved embryos (2Cell), were collected for in vitro culture to investigate their developmental potential and chromosomal constitution using an SNP array-based chromosomal analysis. We found that blastocyst formation rates were 63.8% (for 2Cell embryos), 22.6% (2PN), 16.7% (0PN), 11.2% (3PN) and 3.6% (1PN). SNP array-based chromosomal analysis of the resultant blastocysts revealed that the percentages of normal chromosomes were 55.2% (2Cell), 60.7% (2PN), 44.4% (0PN) and 47.4% (0PN). Compared with clinical preimplantation genetic diagnosis (PGD) data generated with clinically acceptable embryos, results of the SNP array-based chromosome analysis on blastocysts from clinically discarded embryos showed similar values for the frequency of abnormal chromosome occurrence, aberrant signal classification and chromosomal distribution. The present study is perhaps the first systematic analysis of the developmental potential of clinically discarded embryos and provides a basis for future studies. PMID:27045374

  20. The progeny of Legionella pneumophila in human macrophages shows unique developmental traits.

    PubMed

    Abdelhady, Hany; Garduño, Rafael A

    2013-12-01

    The Gram-negative bacterium Legionella pneumophila is an intracellular parasite of amoebae and an accidental human pathogen that causes a noncommunicable atypical pneumonia known as Legionnaires' disease (LD). In some mammalian cells (e.g. HeLa), L. pneumophila follows a biphasic developmental cycle, differentiating between a replicative form that actively multiplies intracellularly, and a mature infectious form (MIF) that emerges as progeny. To date, it is not known whether the L. pneumophila progenies that emerge from amoebae and human macrophages reach similar developmental stages. Here, we demonstrate that in relation to the fully differentiated and highly infectious MIFs that emerge from amoebae, the L. pneumophila progeny that emerges from macrophages is morphologically undifferentiated, less resistant to antibiotics and less able to initiate infections. However, the L. pneumophila progeny from macrophages did not show any defects in intracellular growth. We thus concluded that macrophage infection with L. pneumophila yields a low number of bona fide MIFs. Because MIFs are the transmissive forms of L. pneumophila produced in vivo, our results showing that they are not efficiently produced in cultured macrophages provide an initial insight into why LD is not communicable. PMID:24206397

  1. Cleavage pattern predicts developmental potential of day 3 human embryos produced by IVF.

    PubMed

    Yang, S T; Shi, J X; Gong, F; Zhang, S P; Lu, C F; Tan, K; Leng, L Z; Hao, M; He, H; Gu, Y F; Lu, G X; Lin, G

    2015-06-01

    Time-lapse technique provides opportunities to observe the dynamic process of human early development. Previous studies have suggested several abnormal division patterns were associated with decreased developmental potential, but no systematic results are currently available. In this study, seven abnormal division patterns were observed during early cleavage, and these had different effects on the further development potential of daughter blastomeres. According to the severity and occurrence of abnormal division patterns during the initial three cleavages, an embryo hierarchical classification model was developed and day 3 embryos were classified into six grades (from A to F). The good-quality blastocyst formation rate for these grades decreased from 70.8-3.8% (P < 0.001). In a prospective observational study, 139 IVF cycles were recruited to assess the efficiency of this classification model. In the embryos that had confirmed implantation results, the implantation rate decreased from 67.0% (Grade A) to 0% (Grade D;P < 0.001). These results indicated that cleavage patterns can predict the developmental potential of day 3 human embryos. PMID:25892500

  2. Developmental Immunotoxicity, Perinatal Programming, and Noncommunicable Diseases: Focus on Human Studies.

    PubMed

    Dietert, Rodney R

    2014-01-01

    Developmental immunotoxicity (DIT) is a term given to encompass the environmentally induced disruption of normal immune development resulting in adverse outcomes. A myriad of chemical, physical, and psychological factors can all contribute to DIT. As a core component of the developmental origins of adult disease, DIT is interlinked with three important concepts surrounding health risks across a lifetime: (1) the Barker Hypothesis, which connects prenatal development to later-life diseases, (2) the hygiene hypothesis, which connects newborns and infants to risk of later-life diseases and, (3) fetal programming and epigenetic alterations, which may exert effects both in later life and across future generations. This review of DIT considers: (1) the history and context of DIT research, (2) the fundamental features of DIT, (3) the emerging role of DIT in risk of noncommunicable diseases (NCDs) and (4) the range of risk factors that have been investigated through human research. The emphasis on the human DIT-related literature is significant since most prior reviews of DIT have largely focused on animal research and considerations of specific categories of risk factors (e.g., heavy metals). Risk factors considered in this review include air pollution, aluminum, antibiotics, arsenic, bisphenol A, ethanol, lead (Pb), maternal smoking and environmental tobacco smoke, paracetamol (acetaminophen), pesticides, polychlorinated biphenyls, and polyfluorinated compounds. PMID:26556429

  3. Developmental Immunotoxicity, Perinatal Programming, and Noncommunicable Diseases: Focus on Human Studies

    PubMed Central

    Dietert, Rodney R.

    2014-01-01

    Developmental immunotoxicity (DIT) is a term given to encompass the environmentally induced disruption of normal immune development resulting in adverse outcomes. A myriad of chemical, physical, and psychological factors can all contribute to DIT. As a core component of the developmental origins of adult disease, DIT is interlinked with three important concepts surrounding health risks across a lifetime: (1) the Barker Hypothesis, which connects prenatal development to later-life diseases, (2) the hygiene hypothesis, which connects newborns and infants to risk of later-life diseases and, (3) fetal programming and epigenetic alterations, which may exert effects both in later life and across future generations. This review of DIT considers: (1) the history and context of DIT research, (2) the fundamental features of DIT, (3) the emerging role of DIT in risk of noncommunicable diseases (NCDs) and (4) the range of risk factors that have been investigated through human research. The emphasis on the human DIT-related literature is significant since most prior reviews of DIT have largely focused on animal research and considerations of specific categories of risk factors (e.g., heavy metals). Risk factors considered in this review include air pollution, aluminum, antibiotics, arsenic, bisphenol A, ethanol, lead (Pb), maternal smoking and environmental tobacco smoke, paracetamol (acetaminophen), pesticides, polychlorinated biphenyls, and polyfluorinated compounds. PMID:26556429

  4. Developmental potential of clinically discarded human embryos and associated chromosomal analysis.

    PubMed

    Yao, Guidong; Xu, Jiawei; Xin, Zhimin; Niu, Wenbin; Shi, Senlin; Jin, Haixia; Song, Wenyan; Wang, Enyin; Yang, Qingling; Chen, Lei; Sun, Yingpu

    2016-01-01

    Clinically discarded human embryos, which are generated from both normal and abnormal fertilizations, have the potential of developing into blastocysts. A total of 1,649 discarded human embryos, including zygotes containing normal (2PN) and abnormal (0PN, 1PN, 3PN and ≥4PN) pronuclei and prematurely cleaved embryos (2Cell), were collected for in vitro culture to investigate their developmental potential and chromosomal constitution using an SNP array-based chromosomal analysis. We found that blastocyst formation rates were 63.8% (for 2Cell embryos), 22.6% (2PN), 16.7% (0PN), 11.2% (3PN) and 3.6% (1PN). SNP array-based chromosomal analysis of the resultant blastocysts revealed that the percentages of normal chromosomes were 55.2% (2Cell), 60.7% (2PN), 44.4% (0PN) and 47.4% (0PN). Compared with clinical preimplantation genetic diagnosis (PGD) data generated with clinically acceptable embryos, results of the SNP array-based chromosome analysis on blastocysts from clinically discarded embryos showed similar values for the frequency of abnormal chromosome occurrence, aberrant signal classification and chromosomal distribution. The present study is perhaps the first systematic analysis of the developmental potential of clinically discarded embryos and provides a basis for future studies. PMID:27045374

  5. Safety and side effects of ayahuasca in humans--an overview focusing on developmental toxicology.

    PubMed

    dos Santos, Rafael Guimarães

    2013-01-01

    Despite being relatively well studied from a botanical, chemical, and (acute) pharmacological perspective, little is known about the possible toxic effects of ayahuasca (an hallucinogenic brew used for magico-ritual purposes) in pregnant women and in their children, and the potential toxicity of long-term ayahuasca consumption. It is the main objective of the present text to do an overview of the risks and possible toxic effects of ayahuasca in humans, reviewing studies on the acute ayahuasca administration to humans, on the possible risks associated with long-term consumption by adults and adolescents, and on the possible toxic effects on pregnant animals and in their offspring. Acute ayahuasca administration, as well as long-term consumption of this beverage, does not seem to be seriously toxic to humans. Although some nonhuman developmental studies suggested possible toxic effects of ayahuasca or of some of its alkaloids, the limited human literature on adolescents exposed to ayahuasca as early as in the uterus reports no serious toxic effects of the ritual consumption of the brew. Researchers must take caution when extrapolating nonhuman data to humans and more data are needed in basic and human research before a definite opinion can be made regarding the possible toxic effects of ayahuasca in pregnant women and in their children. PMID:23662333

  6. Chromodomain Helicase DNA-Binding Proteins in Stem Cells and Human Developmental Diseases

    PubMed Central

    Micucci, Joseph A.; Sperry, Ethan D.

    2015-01-01

    Dynamic regulation of gene expression is vital for proper cellular development and maintenance of differentiated states. Over the past 20 years, chromatin remodeling and epigenetic modifications of histones have emerged as key controllers of rapid reversible changes in gene expression. Mutations in genes encoding enzymes that modify chromatin have also been identified in a variety of human neurodevelopmental disorders, ranging from isolated intellectual disability and autism spectrum disorder to multiple congenital anomaly conditions that affect major organ systems and cause severe morbidity and mortality. In this study, we review recent evidence that chromodomain helicase DNA-binding (CHD) proteins regulate stem cell proliferation, fate, and differentiation in a wide variety of tissues and organs. We also highlight known roles of CHD proteins in human developmental diseases and present current unanswered questions about the pleiotropic effects of CHD protein complexes, their genetic targets, nucleosome sliding functions, and enzymatic effects in cells and tissues. PMID:25567374

  7. Do Domestic Dogs Understand Human Actions as Goal-Directed?

    PubMed Central

    Marshall-Pescini, Sarah; Ceretta, Maria; Prato-Previde, Emanuela

    2014-01-01

    Understanding of other’s actions as goal-directed is considered a fundamental ability underlying cognitive and social development in human infants. A number of studies using the habituation-dishabituation paradigm have shown that the ability to discern intentional relations, in terms of goal-directedness of an action towards an object, appears around 5 months of age. The question of whether non-human species can perceive other’s actions as goal-directed has been more controversial, however there is mounting evidence that at least some primates species do. Recently domestic dogs have been shown to be particularly sensitive to human communicative cues and more so in cooperative and intentional contexts. Furthermore, they have been shown to imitate selectively. Taken together these results suggest that dogs may perceive others' actions as goal-directed, however no study has investigated this issue directly. In the current study, adopting an infant habituation-dishabituation paradigm, we investigated whether dogs attribute intentions to an animate (a human) but not an inanimate (a black box) agent interacting with an object. Following an habituation phase in which the agent interacted always with one of two objects, two sets of 3 trials were presented: new side trials (in which the agent interacted with the same object as in the habituation trial but placed in a novel location) and new goal trials (in which the agent interacted with the other object placed in the old location). Dogs showed a similar pattern of response to that shown in infants, looking longer in the new goal than new side trials when they saw the human agent interact with the object. No such difference emerging with the inanimate agent (the black box). Results provide the first evidence that a non-primate species can perceive another individual’s actions as goal-directed. We discuss results in terms of the prevailing mentalisitic and non-mentalistic hypotheses regarding goal-attribution. PMID

  8. NTP-CERHR monograph on the potential human reproductive and developmental effects of methylphenidate.

    PubMed

    2005-08-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for methylphenidate to cause adverse effects on reproduction and development in humans. Methylphenidate was selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. Methylphenidate is a central nervous system stimulant approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons 6 years of age and older and for narcolepsy. The results of this evaluation on methylphenidate are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is negligible concern for methylphenidate-induced tics and movement disorders. This conclusion is based on studies showing that children treated with therapeutic doses of methylphenidate have no evidence of movement disorders or tics due to the medication. Second, there is minimal concern for methylphenidate-induced growth restriction. This conclusion is based on growth restriction being observed in animal studies only at high doses of methylphenidate using a non-therapeutic route of exposure. The effect on growth was reversible. Finally, there are insufficient data to draw conclusions on 1) an association between methylphenidate therapy in pregnant women and pregnancy loss and 2) possible reproductive effects of methylphenidate in humans. NTP-CERHR monographs are transmitted to federal and state agencies, interested

  9. Key concepts in human genetics: understanding the complex phenotype.

    PubMed

    Gibson, William T

    2009-01-01

    The recent sequencing of a reference human genome has generated a large number of DNA-based tools, which are being used to locate genes that contribute to disease. These tools have also enabled studies of the genetics of non-disease traits such as athletic fitness. Sport scientists should keep in mind three major factors when designing such studies and interpreting the literature. First of all, the methods used to assign a biological trait (be it performance related or disease related) to a specific gene are not as powerful as is commonly believed. Second, the methods used are thought to be more robust for disease-related traits than for normal physical characteristics, likely because there are many more biological factors contributing to the latter. Third, additional levels of variability continue to be uncovered in the human genome; these may ultimately contribute more to physical differences between human beings than the levels studied over the past decade. This introductory chapter will aim to equip the reader with the necessary vocabulary to understand and interpret genetic studies targeted to sport fitness and sport-related injury. PMID:19696504

  10. Human Science for Human Freedom? Piaget's Developmental Research and Foucault's Ethical Truth Games

    ERIC Educational Resources Information Center

    Zhao, Guoping

    2012-01-01

    The construction of the modern subject and the pursuit of human freedom and autonomy, as well as the practice of human science has been pivotal in the development of modern education. But for Foucault, the subject is only the effect of discourses and power-knowledge arrangements, and modern human science is part of the very arrangement that has…

  11. Understanding and managing human threats to the coastal marine environment.

    PubMed

    Crain, Caitlin M; Halpern, Benjamin S; Beck, Mike W; Kappel, Carrie V

    2009-04-01

    Coastal marine habitats at the interface of land and sea are subject to threats from human activities in both realms. Researchers have attempted to quantify how these various threats impact different coastal ecosystems, and more recently have focused on understanding the cumulative impact from multiple threats. Here, the top threats to coastal marine ecosystems and recent efforts to understand their relative importance, ecosystem-level impacts, cumulative effects, and how they can best be managed and mitigated, are briefly reviewed. Results of threat analysis and rankings will differ depending on the conservation target (e.g., vulnerable species, pristine ecosystems, mitigatable threats), scale of interest (local, regional, or global), whether externalities are considered, and the types of management tools available (e.g., marine-protected areas versus ecosystem-based management). Considering the cumulative effect of multiple threats has only just begun and depends on spatial analysis to predict overlapping threats and a better understanding of multiple-stressor effects and interactions. Emerging conservation practices that hold substantial promise for protecting coastal marine systems include multisector approaches, such as ecosystem-based management (EBM), that account for ecosystem service valuation; comprehensive spatial management, such as ocean zoning; and regulatory mechanisms that encourage or require cross-sector goal setting and evaluation. In all cases, these efforts require a combination of public and private initiatives for success. The state of our ecological understanding, public awareness, and policy initiatives make the time ripe for advancing coastal marine management and improving our stewardship of coastal and marine ecosystems. PMID:19432644

  12. Understanding the human dimensions of a sustainable energy transition.

    PubMed

    Steg, Linda; Perlaviciute, Goda; van der Werff, Ellen

    2015-01-01

    Global climate change threatens the health, economic prospects, and basic food and water sources of people. A wide range of changes in household energy behavior is needed to realize a sustainable energy transition. We propose a general framework to understand and encourage sustainable energy behaviors, comprising four key issues. First, we need to identify which behaviors need to be changed. A sustainable energy transition involves changes in a wide range of energy behaviors, including the adoption of sustainable energy sources and energy-efficient technology, investments in energy efficiency measures in buildings, and changes in direct and indirect energy use behavior. Second, we need to understand which factors underlie these different types of sustainable energy behaviors. We discuss three main factors that influence sustainable energy behaviors: knowledge, motivations, and contextual factors. Third, we need to test the effects of interventions aimed to promote sustainable energy behaviors. Interventions can be aimed at changing the actual costs and benefits of behavior, or at changing people's perceptions and evaluations of different costs and benefits of behavioral options. Fourth, it is important to understand which factors affect the acceptability of energy policies and energy systems changes. We discuss important findings from psychological studies on these four topics, and propose a research agenda to further explore these topics. We emphasize the need of an integrated approach in studying the human dimensions of a sustainable energy transition that increases our understanding of which general factors affect a wide range of energy behaviors as well as the acceptability of different energy policies and energy system changes. PMID:26136705

  13. Understanding the human dimensions of a sustainable energy transition

    PubMed Central

    Steg, Linda; Perlaviciute, Goda; van der Werff, Ellen

    2015-01-01

    Global climate change threatens the health, economic prospects, and basic food and water sources of people. A wide range of changes in household energy behavior is needed to realize a sustainable energy transition. We propose a general framework to understand and encourage sustainable energy behaviors, comprising four key issues. First, we need to identify which behaviors need to be changed. A sustainable energy transition involves changes in a wide range of energy behaviors, including the adoption of sustainable energy sources and energy-efficient technology, investments in energy efficiency measures in buildings, and changes in direct and indirect energy use behavior. Second, we need to understand which factors underlie these different types of sustainable energy behaviors. We discuss three main factors that influence sustainable energy behaviors: knowledge, motivations, and contextual factors. Third, we need to test the effects of interventions aimed to promote sustainable energy behaviors. Interventions can be aimed at changing the actual costs and benefits of behavior, or at changing people’s perceptions and evaluations of different costs and benefits of behavioral options. Fourth, it is important to understand which factors affect the acceptability of energy policies and energy systems changes. We discuss important findings from psychological studies on these four topics, and propose a research agenda to further explore these topics. We emphasize the need of an integrated approach in studying the human dimensions of a sustainable energy transition that increases our understanding of which general factors affect a wide range of energy behaviors as well as the acceptability of different energy policies and energy system changes. PMID:26136705

  14. Developmental- and differentiation-specific patterns of human gamma- and beta-globin promoter DNA methylation.

    PubMed

    Mabaera, Rodwell; Richardson, Christine A; Johnson, Kristin; Hsu, Mei; Fiering, Steven; Lowrey, Christopher H

    2007-08-15

    The mechanisms underlying the human fetal-to-adult beta-globin gene switch remain to be determined. While there is substantial experimental evidence to suggest that promoter DNA methylation is involved in this process, most data come from studies in nonhuman systems. We have evaluated human gamma- and beta-globin promoter methylation in primary human fetal liver (FL) and adult bone marrow (ABM) erythroid cells. Our results show that, in general, promoter methylation and gene expression are inversely related. However, CpGs at -162 of the gamma promoter and -126 of the beta promoter are hypomethylated in ABM and FL, respectively. We also studied gamma-globin promoter methylation during in vitro differentiation of erythroid cells. The gamma promoters are initially hypermethylated in CD34(+) cells. The upstream gamma promoter CpGs become hypomethylated during the preerythroid phase of differentiation and are then remethylated later, during erythropoiesis. The period of promoter hypomethylation correlates with transient gamma-globin gene expression and may explain the previously observed fetal hemoglobin production that occurs during early adult erythropoiesis. These results provide the first comprehensive survey of developmental changes in human gamma- and beta-globin promoter methylation and support the hypothesis that promoter methylation plays a role in human beta-globin locus gene switching. PMID:17456718

  15. Our Complex Universe: A Human Understanding through Art

    NASA Astrophysics Data System (ADS)

    Kaler, J. B.

    2013-04-01

    Nature, in all its aspects, provides us with a foundation for creating art in all its forms. Among the most inspirational of these aspects are those of the sky, from sunsets to stars to galaxies. But it works both ways. While we can strive to know the Universe through physics and mathematics, the unending complexity of the structures we examine overwhelms the senses and hinders our ability to appreciate the beauty and meaning of our surroundings. The arts provide avenues for understanding and interpreting the complexity of nature in human terms. In doing so, they reveal more of nature's aesthetics and thereby have the power to inspire scientists to look ever deeper into our Universe.

  16. Utilising proteomic approaches to understand oncogenic human herpesviruses (Review)

    PubMed Central

    OWEN, CHRISTOPHER B.; HUGHES, DAVID J.; BAQUERO-PEREZ, BELINDA; BERNDT, ANJA; SCHUMANN, SOPHIE; JACKSON, BRIAN R.; WHITEHOUSE, ADRIAN

    2014-01-01

    The γ-herpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus are successful pathogens, each infecting a large proportion of the human population. These viruses persist for the life of the host and may each contribute to a number of malignancies, for which there are currently no cures. Large-scale proteomic-based approaches provide an excellent means of increasing the collective understanding of the proteomes of these complex viruses and elucidating their numerous interactions within the infected host cell. These large-scale studies are important for the identification of the intricacies of viral infection and the development of novel therapeutics against these two important pathogens. PMID:25279171

  17. Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human

    PubMed Central

    Kushwah, Rahul; Guezguez, Borhane; Lee, Jung Bok; Hopkins, Claudia I; Bhatia, Mickie

    2014-01-01

    The Notch signaling pathway is evolutionarily conserved across species and plays an important role in regulating cell differentiation, proliferation, and survival. It has been implicated in several different hematopoietic processes including early hematopoietic development as well as adult hematological malignancies in humans. This review focuses on recent developments in understanding the role of Notch signaling in the human hematopoietic system with an emphasis on hematopoietic initiation from human pluripotent stem cells and regulation within the bone marrow. Based on recent insights, we summarize potential strategies for treatment of human hematological malignancies toward the concept of targeting Notch signaling for fate regulation. PMID:25252682

  18. Cellular reprogramming for understanding and treating human disease.

    PubMed

    Kanherkar, Riya R; Bhatia-Dey, Naina; Makarev, Evgeny; Csoka, Antonei B

    2014-01-01

    In the last two decades we have witnessed a paradigm shift in our understanding of cells so radical that it has rewritten the rules of biology. The study of cellular reprogramming has gone from little more than a hypothesis, to applied bioengineering, with the creation of a variety of important cell types. By way of metaphor, we can compare the discovery of reprogramming with the archeological discovery of the Rosetta stone. This stone slab made possible the initial decipherment of Egyptian hieroglyphics because it allowed us to see this language in a way that was previously impossible. We propose that cellular reprogramming will have an equally profound impact on understanding and curing human disease, because it allows us to perceive and study molecular biological processes such as differentiation, epigenetics, and chromatin in ways that were likewise previously impossible. Stem cells could be called "cellular Rosetta stones" because they allow also us to perceive the connections between development, disease, cancer, aging, and regeneration in novel ways. Here we present a comprehensive historical review of stem cells and cellular reprogramming, and illustrate the developing synergy between many previously unconnected fields. We show how stem cells can be used to create in vitro models of human disease and provide examples of how reprogramming is being used to study and treat such diverse diseases as cancer, aging, and accelerated aging syndromes, infectious diseases such as AIDS, and epigenetic diseases such as polycystic ovary syndrome. While the technology of reprogramming is being developed and refined there have also been significant ongoing developments in other complementary technologies such as gene editing, progenitor cell production, and tissue engineering. These technologies are the foundations of what is becoming a fully-functional field of regenerative medicine and are converging to a point that will allow us to treat almost any disease. PMID

  19. Cellular reprogramming for understanding and treating human disease

    PubMed Central

    Kanherkar, Riya R.; Bhatia-Dey, Naina; Makarev, Evgeny; Csoka, Antonei B.

    2014-01-01

    In the last two decades we have witnessed a paradigm shift in our understanding of cells so radical that it has rewritten the rules of biology. The study of cellular reprogramming has gone from little more than a hypothesis, to applied bioengineering, with the creation of a variety of important cell types. By way of metaphor, we can compare the discovery of reprogramming with the archeological discovery of the Rosetta stone. This stone slab made possible the initial decipherment of Egyptian hieroglyphics because it allowed us to see this language in a way that was previously impossible. We propose that cellular reprogramming will have an equally profound impact on understanding and curing human disease, because it allows us to perceive and study molecular biological processes such as differentiation, epigenetics, and chromatin in ways that were likewise previously impossible. Stem cells could be called “cellular Rosetta stones” because they allow also us to perceive the connections between development, disease, cancer, aging, and regeneration in novel ways. Here we present a comprehensive historical review of stem cells and cellular reprogramming, and illustrate the developing synergy between many previously unconnected fields. We show how stem cells can be used to create in vitro models of human disease and provide examples of how reprogramming is being used to study and treat such diverse diseases as cancer, aging, and accelerated aging syndromes, infectious diseases such as AIDS, and epigenetic diseases such as polycystic ovary syndrome. While the technology of reprogramming is being developed and refined there have also been significant ongoing developments in other complementary technologies such as gene editing, progenitor cell production, and tissue engineering. These technologies are the foundations of what is becoming a fully-functional field of regenerative medicine and are converging to a point that will allow us to treat almost any disease. PMID

  20. How evolutionary principles improve the understanding of human health and disease

    PubMed Central

    Gluckman, Peter D; Low, Felicia M; Buklijas, Tatjana; Hanson, Mark A; Beedle, Alan S

    2011-01-01

    An appreciation of the fundamental principles of evolutionary biology provides new insights into major diseases and enables an integrated understanding of human biology and medicine. However, there is a lack of awareness of their importance amongst physicians, medical researchers, and educators, all of whom tend to focus on the mechanistic (proximate) basis for disease, excluding consideration of evolutionary (ultimate) reasons. The key principles of evolutionary medicine are that selection acts on fitness, not health or longevity; that our evolutionary history does not cause disease, but rather impacts on our risk of disease in particular environments; and that we are now living in novel environments compared to those in which we evolved. We consider these evolutionary principles in conjunction with population genetics and describe several pathways by which evolutionary processes can affect disease risk. These perspectives provide a more cohesive framework for gaining insights into the determinants of health and disease. Coupled with complementary insights offered by advances in genomic, epigenetic, and developmental biology research, evolutionary perspectives offer an important addition to understanding disease. Further, there are a number of aspects of evolutionary medicine that can add considerably to studies in other domains of contemporary evolutionary studies. PMID:25567971

  1. Recent progress towards understanding the role of DNA methylation in human placental development.

    PubMed

    Bianco-Miotto, Tina; Mayne, Benjamin T; Buckberry, Sam; Breen, James; Rodriguez Lopez, Carlos M; Roberts, Claire T

    2016-07-01

    Epigenetic modifications, and particularly DNA methylation, have been studied in many tissues, both healthy and diseased, and across numerous developmental stages. The placenta is the only organ that has a transient life of 9 months and undergoes rapid growth and dynamic structural and functional changes across gestation. Additionally, the placenta is unique because although developing within the mother, its genome is identical to that of the foetus. Given these distinctive characteristics, it is not surprising that the epigenetic landscape affecting placental gene expression may be different to that in other healthy tissues. However, the role of epigenetic modifications, and particularly DNA methylation, in placental development remains largely unknown. Of particular interest is the fact that the placenta is the most hypomethylated human tissue and is characterized by the presence of large partially methylated domains (PMDs) containing silenced genes. Moreover, how and why the placenta is hypomethylated and what role DNA methylation plays in regulating placental gene expression across gestation are poorly understood. We review genome-wide DNA methylation studies in the human placenta and highlight that the different cell types that make up the placenta have very different DNA methylation profiles. Summarizing studies on DNA methylation in the placenta and its relationship with pregnancy complications are difficult due to the limited number of studies available for comparison. To understand the key steps in placental development and hence what may be perturbed in pregnancy complications requires large-scale genome-wide DNA methylation studies coupled with transcriptome analyses. PMID:27026712

  2. Understanding and Predicting Human Behavior for Social Communities

    NASA Astrophysics Data System (ADS)

    Simoes, Jose; Magedanz, Thomas

    Over the last years, with the rapid advance in technology, it is becoming increasingly feasible for people to take advantage of the devices and services in the surrounding environment to remain "connected" and continuously enjoy the activity they are engaged in, be it sports, entertainment, or work. Such a ubiquitous computing environment will allow everyone permanent access to the Internet anytime, anywhere and anyhow [1]. Nevertheless, despite the evolution of services, social aspects remain in the roots of every human behavior and activities. Great examples of such phenomena are online social networks, which engage users in a way never seen before in the online world. At the same time, being aware and communicating context is a key part of human interaction and is a particularly powerful concept when applied to a community of users where services can be made more personalized and useful. Altogether, harvesting context to reason and learn about user behavior will further enhance the future multimedia vision where services can be composed and customized according to user context. Moreover, it will help us to understand users in a better way.

  3. Building a Database of Developmental Neurotoxitants: Evidence from Human and Animal Studies

    EPA Science Inventory

    EPA’s program for the screening and prioritization of chemicals for developmental neurotoxicity (DNT) necessitates the generation of a list of chemicals that are known mammalian developmental neurotoxicants. This chemical list will be used to evaluate the sensitivity, reliability...

  4. Understanding Human Motion Skill with Peak Timing Synergy

    NASA Astrophysics Data System (ADS)

    Ueno, Ken; Furukawa, Koichi

    The careful observation of motion phenomena is important in understanding the skillful human motion. However, this is a difficult task due to the complexities in timing when dealing with the skilful control of anatomical structures. To investigate the dexterity of human motion, we decided to concentrate on timing with respect to motion, and we have proposed a method to extract the peak timing synergy from multivariate motion data. The peak timing synergy is defined as a frequent ordered graph with time stamps, which has nodes consisting of turning points in motion waveforms. A proposed algorithm, PRESTO automatically extracts the peak timing synergy. PRESTO comprises the following 3 processes: (1) detecting peak sequences with polygonal approximation; (2) generating peak-event sequences; and (3) finding frequent peak-event sequences using a sequential pattern mining method, generalized sequential patterns (GSP). Here, we measured right arm motion during the task of cello bowing and prepared a data set of the right shoulder and arm motion. We successfully extracted the peak timing synergy on cello bowing data set using the PRESTO algorithm, which consisted of common skills among cellists and personal skill differences. To evaluate the sequential pattern mining algorithm GSP in PRESTO, we compared the peak timing synergy by using GSP algorithm and the one by using filtering by reciprocal voting (FRV) algorithm as a non time-series method. We found that the support is 95 - 100% in GSP, while 83 - 96% in FRV and that the results by GSP are better than the one by FRV in the reproducibility of human motion. Therefore we show that sequential pattern mining approach is more effective to extract the peak timing synergy than non-time series analysis approach.

  5. A Structural Biology Approach to Understand Human Lymphatic Filarial Infection

    PubMed Central

    Nagampalli, Raghavendra Sashi Krishna; Gunasekaran, Krishnasamy; Narayanan, Rangarajan Badri; Peters, Angela; Bhaskaran, Rajagopalan

    2014-01-01

    The presence of aspartic protease inhibitor in filarial parasite Brugia malayi (Bm-Aspin) makes it interesting to study because of the fact that the filarial parasite never encounters the host digestive system. Here, the aspartic protease inhibition kinetics of Bm-Aspin and its NMR structural characteristics have been investigated. The overall aim of this study is to explain the inhibition and binding properties of Bm-Aspin from its structural point of view. UV-spectroscopy and multi-dimensional NMR are the experiments that have been performed to understand the kinetic and structural properties of Bm-Aspin respectively. The human aspartic proteases that are considered for this study are pepsin, renin, cathepsin-E and cathepsin-D. The results of this analysis performed with the specific substrate [Phe-Ala-Ala-Phe (4-NO2)-Phe-Val-Leu (4-pyridylmethyl) ester] against aspartic proteases suggest that Bm-Aspin inhibits the activities of all four human aspartic proteases. The kinetics studies indicate that Bm-Aspin follows a competitive mode of inhibition for pepsin and cathepsin-E, non-competitive for renin and mixed mode for cathepsin-D. The triple resonance NMR experiments on Bm-Aspin suggested the feasibility of carrying out NMR studies to obtain its solution structure. The NMR titration studies on the interactions of Bm-Aspin with the proteases indicate that it undergoes fast-exchange phenomena among themselves. In addition to this, the chemical shift perturbations for some of the residues of Bm-Aspin observed from 15N-HSQC spectra upon the addition of saturated amounts of aspartic proteases suggest the binding between Bm-Aspin and human aspartic proteases. They also provide information on the variations in the intensities and mode of binding between the proteases duly corroborating with the results from the protease inhibition assay method. PMID:24516678

  6. Molecular signature in human cumulus cells related to embryonic developmental potential.

    PubMed

    Xu, Xiaofeng; Chen, Dawei; Zhang, Zhiguo; Wei, Zhaolian; Cao, Yunxia

    2015-02-01

    Identification of criteria for embryo quality is required to improve the clinical outcome of in vitro fertilization. The aim of this study was to determine the gene expression profile of cumulus cells (CC) surrounding the oocyte as biomarkers for embryonic developmental potential. CCs from single oocytes were analysed using DNA microarrays. Gene expression profiles of CC surrounding the oocyte associated with good embryonic quality were analyzed. We observed that CCs issued from oocytes that developed into embryos with a good morphology had significantly different gene expression profile from those with bad morphology. These results were confirmed by quantitative RT-PCR. The gene expression profiling of human CC correlates with embryo potential. Our findings suggest anon-invasive approach, offering a new potential strategy for competent embryo selection. PMID:24899471

  7. Developmental analysis of human figure drawings in adolescence, young adulthood, and middle age.

    PubMed

    Saarni, C; Azara, V

    1977-02-01

    Analyzed 195 human figure drawings (HFDs) of adolescents, young adults, and middle-aged adults in terms of developmental differences in anxiety signs, grouped into aggressive-hostile and insecure-labile categories, and according to sex-role stereotype, as measured by the Broverman Sex-role Stereotype Scale. Adolescent males and females were significantly more likely to obtain more anxiety signs than the two adult groups, although young adults and middle-aged adults did not differ from one another in HFD performance. The most reliable sex difference was that males reveal significantly more aggressive-hostile indices in the HFDs relative to females; no significant sex differences were obtained for number of insecure-labile indices. The degree to which one has adopted a conventional sex-role stereotype was not predictive of anxiety sign differences in HFD performance for either sex or for any age group. PMID:321746

  8. Developmental trajectories during adolescence in males and females: a cross-species understanding of underlying brain changes

    PubMed Central

    Brenhouse, Heather C.; Andersen, Susan L.

    2011-01-01

    Adolescence is a transitional period between childhood and adulthood that encompasses vast changes within brain systems that parallel some, but not all, behavioral changes. Elevations in emotional reactivity and reward processing follow an inverted U shape in terms of onset and remission, with the peak occurring during adolescence. However, cognitive processing follows a more linear course of development. This review will focus on changes within key structures and will highlight the relationships between brain changes and behavior, with evidence spanning from functional magnetic resonance imaging (fMRI) in humans to molecular studies of receptor and signaling factors in animals. Adolescent changes in neuronal substrates will be used to understand how typical and atypical behaviors arise during adolescence. We draw upon clinical and preclinical studies to provide a neural framework for defining adolescence and its role in the transition to adulthood. PMID:21600919

  9. Understanding the Diversity: A Taxonomy for Postsecondary Education Programs and Services for Students with Intellectual and Developmental Disabilities

    ERIC Educational Resources Information Center

    McEathron, Mary A.; Beuhring, Trisha; Maynard, Amelia; Mavis, Ann

    2013-01-01

    The number of postsecondary education (PSE) programs for individuals with intellectual and developmental disabilities (IDD) has been steadily growing over the last few decades. There has been little public information regarding these programs and schools. Consequently, students, families, and researchers alike lack details about the various…

  10. Improving Social Understanding of Individuals of Intellectual and Developmental disabilities through a 3D-Facial Expression Intervention Program

    ERIC Educational Resources Information Center

    Cheng, Yufang; Chen, Shuhui

    2010-01-01

    Individuals with intellectual and developmental disabilities (IDD) have specific difficulties in cognitive social-emotional capability, which affect numerous aspects of social competence. This study evaluated the learning effects of using 3D-emotion system intervention program for individuals with IDD in learning socially based-emotions capability…

  11. The Contribution of Novel Brain Imaging Techniques to Understanding the Neurobiology of Mental Retardation and Developmental Disabilities

    ERIC Educational Resources Information Center

    Gothelf, Doron; Furfaro, Joyce A.; Penniman, Lauren C.; Glover, Gary H.; Reiss, Allan L.

    2005-01-01

    Studying the biological mechanisms underlying mental retardation and developmental disabilities (MR/DD) is a very complex task. This is due to the wide heterogeneity of etiologies and pathways that lead to MR/DD. Breakthroughs in genetics and molecular biology and the development of sophisticated brain imaging techniques during the last decades…

  12. Mental Retardation and Developmental Disabilities: 1981 Research Programs of the National Institute of Child Health and Human Development.

    ERIC Educational Resources Information Center

    National Inst. of Child Health and Human Development (NIH), Bethesda, MD.

    The monograph reviews federal research activities and progress in biomedical and behavioral/social science research in mental retardation. Activities represent the National Institute of Child Health and Human Development and the Mental Retardation and Developmental Disabilities branch. The following categories are addressed in terms of biomedical…

  13. Impairments in Monkey and Human Face Recognition in 2-Year-Old Toddlers with Autism Spectrum Disorder and Developmental Delay

    ERIC Educational Resources Information Center

    Chawarska, Katarzyna; Volkmar, Fred

    2007-01-01

    Face recognition impairments are well documented in older children with Autism Spectrum Disorders (ASD); however, the developmental course of the deficit is not clear. This study investigates the progressive specialization of face recognition skills in children with and without ASD. Experiment 1 examines human and monkey face recognition in…

  14. Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity

    EPA Science Inventory

    Induced pluripotent stem cell-derived neurons as a human model for testing environmentally induced developmental neurotoxicity Ingrid L. Druwe1, Timothy J. Shafer2, Kathleen Wallace2, Pablo Valdivia3 ,and William R. Mundy2. 1University of North Carolina, Curriculum in Toxicology...

  15. EVALUATION OF HUMAN NEURAL PROGENITOR CELLS FOR DEVELOPMENTAL NEUROTOXICITY SCREENING: TIME COURSE OF EFFECTS ON CELL PROLIFERATION AND VIABILITY.

    EPA Science Inventory

    Current testing methods for developmental neurotoxicity (DNT) make evaluation of the effects of large numbers of chemicals impractical and prohibitively expensive. As such, we are evaluating human neural progenitor cells (NPCs) as a screen for DNT. ReNcell CX (ReN CX) cells are a...

  16. Evaluation of 1066 ToxCast Chemicals in a human stem cell assay for developmental toxicity (SOT)

    EPA Science Inventory

    To increase the diversity of assays used to assess potential developmental toxicity, the ToxCast chemical library was screened in the Stemina devTOX quickPREDICT assay using human embryonic stem (hES) cells. A model for predicting teratogenicity was based on a training set of 23 ...

  17. Advancing our understanding of the human microbiome using QIIME

    PubMed Central

    Navas-Molina, José A.; Peralta-Sánchez, Juan M.; González, Antonio; McMurdie, Paul J.; Vázquez-Baeza, Yoshiki; Xu, Zhenjiang; Ursell, Luke K.; Lauber, Christian; Zhou, Hongwei; Song, Se Jin; Huntley, James; Ackermann, Gail L.; Berg-Lyons, Donna; Holmes, Susan; Caporaso, J. Gregory; Knight, Rob

    2014-01-01

    High-throughput DNA sequencing technologies, coupled with advanced bioinformatics tools, have enabled rapid advances in microbial ecology and our understanding of the human microbiome. QIIME (Quantitative Insights Into Microbial Ecology) is an open-source bioinformatics software package designed for microbial community analysis based on DNA sequence data, which provides a single analysis framework for analysis of raw sequence data through publication quality statistical analyses and interactive visualizations. In this paper, we demonstrate the use of the QIIME pipeline to analyze microbial communities obtained from several sites on the bodies of transgenic and wild-type mice, as assessed using 16S rRNA gene sequences generated on the Illumina MiSeq platform. We present our recommended pipeline for performing microbial community analysis, and provide guidelines for making critical choices in the process. We present examples of some of the types of analyses that are enabled by QIIME, and discuss how other tools, such as phyloseq and R, can be applied to expand upon these analyses. PMID:24060131

  18. Measuring and Understanding Public Opinion on Human Evolution

    NASA Astrophysics Data System (ADS)

    Gwon, Misook

    The theory of evolution has long generated controversy in American society, but Americans' attitudes about human evolution are often neglected in studies of "culture wars" and the nature of mass belief systems more generally (Berkman and Plutzer 2010; Freeland and Houston 2009). Gallup and other survey organizations have polled about evolution, but offered limited response categories that mask complexity in public opinion (Bishop 2006; Moore 2008). The main problems concerning the leading survey questions about evolution are: first, questions measure only a single dimension, thus they ignore the potential for multidimensionality in people's attitudes. Second, depending on question wording and response options, the results of public opinion surveys vary by polling groups. This is an example of measurement error which misleads the interpretation and impression of American public opinion on the origin of humankind. A number of studies have analyzed Americans' beliefs about evolution and hypothesized about the influential effects of several factors (Deckman 2002; Mazur 2005; Mooney 2005; Miller et al. 2006; Newport 2006; Forrest 2007;Nisbet and Goidel 2007;Scott 2009). However, there remains a lack of complete understanding of what Americans know and believe about human evolution. Given the salience of this issue and the significant influence of public opinion on policy-making in America (Page and Shapiro 1992; Stimson 2004; Newport 2004), the measurement error and explanation of polling results on controversial issues related to this topic are in need of clarification. In this study, I address these deficiencies with analyses of data from a 2008 national survey by Harris Interactive (n= 4,626) that included numerous measures of factual knowledge and beliefs about evolution. The items offer more nuanced response options than the standard three-category question asked for decades by the Gallup poll. The Harris survey also had multiple measures of religiosity and the

  19. Early developmental exposures shape trade-offs between acquired and innate immunity in humans

    PubMed Central

    Georgiev, Alexander V.; Kuzawa, Christopher W.; McDade, Thomas W.

    2016-01-01

    Background and objectives Life history theory predicts resource allocation trade-offs between competing functions and processes. We test the hypothesis that relative investment towards innate versus acquired immunity in humans is subject to such trade-offs and that three types of early developmental exposures are particularly salient in shaping adult immunophenotype: (i) pathogen exposure, (ii) nutritional resources; and (iii) extrinsic mortality cues. Methodology We quantified one aspect each of innate and acquired immune function, via C-reactive protein and Epstein–Barr virus antibodies, respectively, in a sample of 1248 men and women from the Philippines (ca. 21.5 years old). Early developmental exposures were assessed via long-term data collected prospectively since participants’ birth (1983–4). We calculated a standardized ratio to assess relative bias towards acquired versus innate immune function and examined its relationship to a suite of predictors via multiple regression. Results In partial support of our predictions, some of the measures of higher pathogen exposure, greater availability of nutritional resources, and lower extrinsic mortality cues in early life were associated with a bias toward acquired immunity in both men and women. The immune profile of women, in particular, appeared to be more sensitive to early life pathogen exposures than those of men. Finally, contrary to prediction, women exhibited a greater relative investment toward innate, not acquired, immunity. Conclusions and implications Early environments can exert considerable influence on the development of immunity. They affect trade-offs between innate and acquired immunity, which show adaptive plasticity and may differ in their influence in men and women. PMID:27530543

  20. NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A.

    PubMed

    Shelby, Michael D

    2008-09-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans. The CERHR Expert Panel on Bisphenol A completed its evaluation in August 2007. CERHR selected bisphenol A for evaluation because of the: widespread human exposure; public concern for possible health effects from human exposures; high production volume; evidence of reproductive and developmental toxicity in laboratory animal studies Bisphenol A (CAS RN: 80-05-7) is a high production volume chemical used primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics are used in some food and drink containers; the resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. To a lesser extent bisphenol A is used in the production of polyester resins, polysulfone resins, polyacrylate resins, and flame retardants. In addition, bisphenol A is used in the processing of polyvinyl chloride plastic and in the recycling of thermal paper. Some polymers used in dental sealants and tooth coatings contain bisphenol A. The primary source of exposure to bisphenol A for most people is assumed to occur through the diet. While air, dust, and water (including skin contact during bathing and swimming) are other possible sources of exposure, bisphenol A in food and beverages accounts for the majority of daily human exposure. The highest estimated daily intakes of bisphenol A in the general population occur in infants and children. The results of this bisphenol A evaluation are published in an NTP-CERHR Monograph that includes the (1) NTP Brief and (2) Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A. Additional information related to the evaluation process, including the peer review report for the NTP Brief and public comments received on the draft NTP

  1. Morphological and Molecular Descriptors of the Developmental Cycle of Babesia divergens Parasites in Human Erythrocytes

    PubMed Central

    Rossouw, Ingrid; Maritz-Olivier, Christine; Niemand, Jandeli; van Biljon, Riette; Smit, Annel; Olivier, Nicholas A.; Birkholtz, Lyn-Marie

    2015-01-01

    Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites, information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries. PMID:25955414

  2. Morphological and Molecular Descriptors of the Developmental Cycle of Babesia divergens Parasites in Human Erythrocytes.

    PubMed

    Rossouw, Ingrid; Maritz-Olivier, Christine; Niemand, Jandeli; van Biljon, Riette; Smit, Annel; Olivier, Nicholas A; Birkholtz, Lyn-Marie

    2015-05-01

    Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites, information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries. PMID:25955414

  3. Infant Formula Fat Analogs and Human Milk Fat: New Focus on Infant Developmental Needs.

    PubMed

    Zou, Long; Pande, Garima; Akoh, Casimir C

    2016-01-01

    Human breast milk is generally and universally recognized as the optimal choice for nutrition during the first year of life. In certain cases in which it is not feasible to breast-feed the infant or the breast milk is not sufficient, especially in the case of preterm infants, infant formula is the next best alternative to provide nutrition to nurture the infant. Therefore, it is highly important that the nutrient composition of the infant formula is as close to breast milk as possible for proper growth and development of the infant. However, human milk is a complex dynamic matrix, and therefore significant research has been done and is still ongoing to fully understand and mimic human breast milk, particularly its fat composition. Lipids play a critical role in infant nutrition. A number of advances have been made in infant formula lipid content and composition so that formula can better simulate or mimic the nutritional functions of human maternal milk. PMID:26934172

  4. Relationship of Bender Gestalt Developmental Scores and Human Drawing Developmental Scores in a Sample of Turkish Preschool Children

    ERIC Educational Resources Information Center

    Ozer, Serap

    2009-01-01

    The Bender Gestalt test and Human Drawings are frequently utilized tests in assessing school readiness in children. This study was a pilot attempt to evaluate these two tests in a Turkish sample as they relate to first grade behaviour as measured by teacher ratings. One hundred and five children were evaluated at the end of kindergarten using the…

  5. The Developmental Perspective in Integral Counseling

    ERIC Educational Resources Information Center

    Cook-Greuter, Susanne R.; Soulen, Jeffrey

    2007-01-01

    The process of making meaning is a core determinant of human experience. Understanding this process, developmentally, is a vital part of integral counseling. In this article, the authors introduce the concept of ego development stages as increasingly complex and flexible systems of meaning making. An understanding of ego development stages can…

  6. Developmental hyperbilirubinemia and CNS toxicity in mice humanized with the UDP glucuronosyltransferase 1 (UGT1) locus.

    PubMed

    Fujiwara, Ryoichi; Nguyen, Nghia; Chen, Shujuan; Tukey, Robert H

    2010-03-16

    High levels of unconjugated bilirubin (UCB) in newborn children is associated with a reduction in hepatic UDP glucuronosyltransferase (UGT) 1A1 activity that can lead to CNS toxicity, brain damage, and even death. Little is known regarding those events that lead to UCB accumulation in brain tissue, and therefore, we sought to duplicate this condition in mice. The human UGT1 locus, encoding all 9-UGT1A genes including UGT1A1, was expressed in Ugt1(-/-) mice. Because the most common clinical condition associated with jaundice in adults is Gilbert's syndrome, which is characterized by an allelic polymorphism in the UGT1A1 promoter, hyperbilirubinemia was monitored in humanized UGT1 mice that expressed either the Gilbert's UGT1A1*28 allele [Tg(UGT1(A1*28))Ugt1(-/-) mice] or the normal UGT1A1*1 allele [Tg(UGT1(A1*1))Ugt1(-/-) mice]. Adult Tg(UGT1(A1*28))Ugt1(-/-) mice expressed elevated levels of total bilirubin (TB) compared with Tg(UGT1(A1*1))Ugt1(-/-) mice, confirming that the promoter polymorphism associated with the UGT1A1*28 allele contributes to hyperbilirubinemia in mice. However, TB accumulated to near toxic levels during neonatal development, a finding that is independent of the Gilbert's UGT1A1*28 promoter polymorphism. Whereas serum TB levels eventually returned to adult levels, TB clearance in neonatal mice was not associated with hepatic UGT1A1 expression. In approximately 10% of the humanized UGT1 mice, peak TB levels culminated in seizures followed by death. UCB deposition in brain tissue and the ensuing seizures were associated with developmental milestones and can be prevented by enhancing regulation of the UGT1A1 gene in neonatal mice. PMID:20194756

  7. Human enhancement and communication: on meaning and shared understanding.

    PubMed

    Cabrera, Laura; Weckert, John

    2013-09-01

    Our technologies have enabled us to change both the world and our perceptions of the world, as well as to change ourselves and to find new ways to fulfil the human desire for improvement and for having new capacities. The debate around using technology for human enhancement has already raised many ethical concerns, however little research has been done in how human enhancement can affect human communication. The purpose of this paper is to explore whether some human enhancements could change our shared lifeworld so radically that human communication as we know it would not be possible any longer. After exploring the kinds of communication problems we are concerned with as well as mentioning some possible enhancement interventions that could bring about such problems, we will address some of the ethical implications that follow from these potential communication problems. We argue that because of the role that communication plays in human society, this issue deserves attention. PMID:23054673

  8. [Understanding and support for children with autism spectrum and developmental disorders--looking steadily at peaceful lives in adolescence].

    PubMed

    Sasaki, Masami

    2010-05-01

    For a long time autism spectrum and developmental disorders have not been well understood. Treatment and education for children with this disorders have been inappropriate in many ways. Although this fact was not obvious until many such children began to demonstrate secondary emotional disturbances including social withdrawal, social aggression, delinquency, domestic violence and momicide. This discourse describes advances in research and practice of clinical and psycho-neurological for autism spectrum in recent years. In addition, I suggest policies and measures for therapeutic education that will avoid secondary symptoms allowing these individuals to conduct their lives in socially independent directions. PMID:23858573

  9. Executive functioning - a key construct for understanding developmental psychopathology or a 'catch-all' term in need of some rethinking?

    PubMed

    Halperin, Jeffrey M

    2016-04-01

    For the past few decades, the role of executive functions in developmental psychopathology has been the focus of considerable research and a feature of conceptual models for a range of conditions including, but not limited to, ADHD, autism, schizophrenia, bipolar disorder, learning disorders, and aggression/conduct problems. Consistent with its prominence throughout the field, executive functioning plays a central role in approximately a third of the papers in this issue of JCPP, and notably, with foci largely on different conditions. These papers, all of which make valuable contributions to the field, propose or test the possibility of a causal role for executive functions in the emergence of psychopathology. PMID:26968313

  10. Students' Understandings of Human Organs and Organ Systems.

    ERIC Educational Resources Information Center

    Reiss, Michael J.; Tunnicliffe, Sue Dale

    2001-01-01

    Discusses students' understandings of their own internal structure. Analysis shows the extent to which student understanding increases with age and the degree to which students know more about some organs and organ systems than others. Gender differences in the drawings were generally not large and there were some intriguing differences in the…

  11. UNDERSTANDING THE RELATIONSHIPS BETWEEN AIR QUALITY AND HUMAN HEALTH

    EPA Science Inventory

    This issue of EM presents a series of articles that focus on air quality and human health--what we know so far and the challenges that remain. The first article provides an overview of the problem at hand and approaches to properly address air quality and human health issues. Fo...

  12. High School Students' Understanding of the Human Body System

    ERIC Educational Resources Information Center

    Assaraf, Orit Ben-Zvi; Dodick, Jeff; Tripto, Jaklin

    2013-01-01

    In this study, 120 tenth-grade students from 8 schools were examined to determine the extent of their ability to perceive the human body as a system after completing the first stage in their biology curriculum--"The human body, emphasizing homeostasis". The students' systems thinking was analyzed according to the STH thinking model, which roughly…

  13. Understanding Movement: A Sociocultural Approach to Exploring Moving Humans

    ERIC Educational Resources Information Center

    Larsson, Hakan; Quennerstedt, Mikael

    2012-01-01

    The purpose of the article is to outline a sociocultural way of exploring human movement. Our ambition is to develop an analytical framework where moving humans are explored in terms of what it means to move as movements are performed by somebody, for a certain purpose, and in a certain situation. We find this approach in poststructural…

  14. Understanding 3D human torso shape via manifold clustering

    NASA Astrophysics Data System (ADS)

    Li, Sheng; Li, Peng; Fu, Yun

    2013-05-01

    Discovering the variations in human torso shape plays a key role in many design-oriented applications, such as suit designing. With recent advances in 3D surface imaging technologies, people can obtain 3D human torso data that provide more information than traditional measurements. However, how to find different human shapes from 3D torso data is still an open problem. In this paper, we propose to use spectral clustering approach on torso manifold to address this problem. We first represent high-dimensional torso data in a low-dimensional space using manifold learning algorithm. Then the spectral clustering method is performed to get several disjoint clusters. Experimental results show that the clusters discovered by our approach can describe the discrepancies in both genders and human shapes, and our approach achieves better performance than the compared clustering method.

  15. Robotic Billiards: Understanding Humans in Order to Counter Them.

    PubMed

    Nierhoff, Thomas; Leibrandt, Konrad; Lorenz, Tamara; Hirche, Sandra

    2016-08-01

    Ongoing technological advances in the areas of computation, sensing, and mechatronics enable robotic-based systems to interact with humans in the real world. To succeed against a human in a competitive scenario, a robot must anticipate the human behavior and include it in its own planning framework. Then it can predict the next human move and counter it accordingly, thus not only achieving overall better performance but also systematically exploiting the opponent's weak spots. Pool is used as a representative scenario to derive a model-based planning and control framework where not only the physics of the environment but also a model of the opponent is considered. By representing the game of pool as a Markov decision process and incorporating a model of the human decision-making based on studies, an optimized policy is derived. This enables the robot to include the opponent's typical game style into its tactical considerations when planning a stroke. The results are validated in simulations and real-life experiments with an anthropomorphic robot playing pool against a human. PMID:26292355

  16. Improving social understanding of individuals of intellectual and developmental disabilities through a 3D-facail expression intervention program.

    PubMed

    Cheng, Yufang; Chen, Shuhui

    2010-01-01

    Individuals with intellectual and developmental disabilities (IDD) have specific difficulties in cognitive social-emotional capability, which affect numerous aspects of social competence. This study evaluated the learning effects of using 3D-emotion system intervention program for individuals with IDD in learning socially based-emotions capability in social contexts. The 3D-emotion system involves three stages with 24 questions with designed different social events. The experimental study was to evaluate using a single subject design on three participants with IDD for identifying the effects of 3D-emotion system intervention program; and the collected data of using this system and informal interview with the participants' were involved. The results showed that three participants had significant positive effects on using of the 3D-emotion system intervention program, and in terms of follow-up learning have been discussed in this paper. PMID:20674267

  17. Students' Understandings of Human Organs and Organ Systems

    NASA Astrophysics Data System (ADS)

    Reiss, Michael J.; Tunnicliffe, Sue Dale

    2001-06-01

    How do people develop their understanding of what is inside them? This study looks at students' understandings of their internal structure. A cross-sectional approach was used involving a total of 158 students in England from six different age groups (ranging from four year old students to first year undergraduates). Students were given a blank piece of A4-sized paper and asked to draw what they thought was inside themselves. Repeated inspections of the completed drawings allowed us to construct a seven point scale of these representations. Our analysis shows the extent to which student understanding increases with age and the degree to which students know more about some organs and organ systems than others. While gender differences in the drawings were generally not large there were some intriguing differences in the ways males and females drew reproductive organs.

  18. Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

    PubMed Central

    Dorman, D C; Allen, S L; Byczkowski, J Z; Claudio, L; Fisher, J E; Fisher, J W; Harry, G J; Li, A A; Makris, S L; Padilla, S; Sultatos, L G; Mileson, B E

    2001-01-01

    We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. In addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood--brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose--response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the test chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic. PMID:11250810

  19. Developmental Changes of Prefrontal Activation in Humans: A Near-Infrared Spectroscopy Study of Preschool Children and Adults

    PubMed Central

    Kawakubo, Yuki; Kono, Toshiaki; Takizawa, Ryu; Kuwabara, Hitoshi; Ishii-Takahashi, Ayaka; Kasai, Kiyoto

    2011-01-01

    Previous morphological studies indicated that development of the human prefrontal cortex (PFC) appears to continue into late adolescence. Although functional brain imaging studies have sought to determine the time course of functional development of the PFC, it is unclear whether the developmental change occurs after adolescence to adulthood and when it achieves a peak because of the narrow or discontinuous range in the participant's age. Moreover, previous functional studies have not focused on the anterior frontal region, that is, the frontopolar regions (BA9/10). Thus, the present study investigated the developmental change in frontopolar PFC activation associated with letter fluency task by using near-infrared spectroscopy (NIRS), in subjects from preschool children to adults. We analyzed the relative concentration of hemoglobin (ΔHb) in the prefrontal cortex measured during the activation task in 48 typically-developing children and adolescents and 22 healthy adults. Consistent with prior morphological studies, we found developmental change with age in the children/adolescents. Moreover, the average Δoxy-Hb in adult males was significantly larger than that in child/adolescent males, but was not true for females. These data suggested that functional development of the PFC continues into late adolescence. Although the developmental change of the frontopolar PFC was independent of gender from childhood to adolescence, in adulthood a gender difference was shown. PMID:22022479

  20. 75 FR 386 - Memorandum of Understanding Between the United States Department of Health and Human Services...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-05

    ... HUMAN SERVICES Food and Drug Administration Memorandum of Understanding Between the United States Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research and Northeastern University AGENCY: Food and Drug Administration, HHS. ACTION: Notice....

  1. Understanding the Human Genome Project — A Fact Sheet | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Javascript on. Feature: Genetics 101 Understanding the Human Genome Project — A Fact Sheet Past Issues / Summer 2013 ... billion letters, or base pairs, in the human genome, which is the complete set of DNA in ...

  2. Ontogeny and social dominance: a developmental view of human power patterns.

    PubMed

    Hawley, Patricia H

    2014-01-01

    Developmental science has long evolutionary roots and has historically focused on individual differences. Accordingly, developmental models can inform conversations about phylogeny and personality. The present paper evokes life history theory to describe a theoretical model of competitive behavior that applies to both children and adults (resource control theory: RCT). The model suggests that prosocial and coercive behavior, though different in manifest form, serve similar evolutionary functions. Accordingly, RCT presents a view on social dominance that gives primacy to function over form that contrasts sharply from traditional views. This reformulation gives rise to novel questions (both developmental and non-developmental) and challenges long accepted views on prosociality (e.g., that it is altruistic) and aggression (e.g., that it is maladaptive). Similarly, RCT gives rise to a minority perspective that aligns aggression with social competence. PMID:25299882

  3. Pyrosequencing as a tool for better understanding of human microbiomes.

    PubMed

    Siqueira, José F; Fouad, Ashraf F; Rôças, Isabela N

    2012-01-01

    Next-generation sequencing technologies have revolutionized the analysis of microbial communities in diverse environments, including the human body. This article reviews several aspects of one of these technologies, the pyrosequencing technique, including its principles, applications, and significant contribution to the study of the human microbiome, with especial emphasis on the oral microbiome. The results brought about by pyrosequencing studies have significantly contributed to refining and augmenting the knowledge of the community membership and structure in and on the human body in healthy and diseased conditions. Because most oral infectious diseases are currently regarded as biofilm-related polymicrobial infections, high-throughput sequencing technologies have the potential to disclose specific patterns related to health or disease. Further advances in technology hold the perspective to have important implications in terms of accurate diagnosis and more effective preventive and therapeutic measures for common oral diseases. PMID:22279602

  4. Pyrosequencing as a tool for better understanding of human microbiomes

    PubMed Central

    Siqueira, José F.; Fouad, Ashraf F.; Rôças, Isabela N.

    2012-01-01

    Next-generation sequencing technologies have revolutionized the analysis of microbial communities in diverse environments, including the human body. This article reviews several aspects of one of these technologies, the pyrosequencing technique, including its principles, applications, and significant contribution to the study of the human microbiome, with especial emphasis on the oral microbiome. The results brought about by pyrosequencing studies have significantly contributed to refining and augmenting the knowledge of the community membership and structure in and on the human body in healthy and diseased conditions. Because most oral infectious diseases are currently regarded as biofilm-related polymicrobial infections, high-throughput sequencing technologies have the potential to disclose specific patterns related to health or disease. Further advances in technology hold the perspective to have important implications in terms of accurate diagnosis and more effective preventive and therapeutic measures for common oral diseases. PMID:22279602

  5. Understanding mutagenesis through delineation of mutational signatures in human cancer

    DOE PAGESBeta

    Petljak, Mia; Alexandrov, Ludmil B.

    2016-06-01

    Each individual cell within a human body acquires a certain number of somatic mutations during a course of its lifetime. These mutations originate from a wide spectra of both endogenous and exogenous mutational processes that leave distinct patterns of mutations, termed mutational signatures, embedded within the genomes of all cells. In recent years, the vast amount of data produced by sequencing of cancer genomes was coupled with novel mathematical models and computational tools to generate the first comprehensive map of mutational signatures in human cancer. Up to date, >30 distinct mutational signatures have been identified, and etiologies have been proposedmore » for many of them. This paper provides a brief historical background on examination of mutational patterns in human cancer, summarizes the knowledge accumulated since introducing the concept of mutational signatures and discusses their future potential applications and perspectives within the field.« less

  6. Understanding mutagenesis through delineation of mutational signatures in human cancer.

    PubMed

    Petljak, Mia; Alexandrov, Ludmil B

    2016-06-01

    Each individual cell within a human body acquires a certain number of somatic mutations during a course of its lifetime. These mutations originate from a wide spectra of both endogenous and exogenous mutational processes that leave distinct patterns of mutations, termed mutational signatures, embedded within the genomes of all cells. In recent years, the vast amount of data produced by sequencing of cancer genomes was coupled with novel mathematical models and computational tools to generate the first comprehensive map of mutational signatures in human cancer. Up to date, >30 distinct mutational signatures have been identified, and etiologies have been proposed for many of them. This review provides a brief historical background on examination of mutational patterns in human cancer, summarizes the knowledge accumulated since introducing the concept of mutational signatures and discusses their future potential applications and perspectives within the field. PMID:27207657

  7. Classic and Golli Myelin Basic Protein have distinct developmental trajectories in human visual cortex

    PubMed Central

    Siu, Caitlin R.; Balsor, Justin L.; Jones, David G.; Murphy, Kathryn M.

    2015-01-01

    Traditionally, myelin is viewed as insulation around axons, however, more recent studies have shown it also plays an important role in plasticity, axonal metabolism, and neuroimmune signaling. Myelin is a complex multi-protein structure composed of hundreds of proteins, with Myelin Basic Protein (MBP) being the most studied. MBP has two families: Classic-MBP that is necessary for activity driven compaction of myelin around axons, and Golli-MBP that is found in neurons, oligodendrocytes, and T-cells. Furthermore, Golli-MBP has been called a “molecular link” between the nervous and immune systems. In visual cortex specifically, myelin proteins interact with immune processes to affect experience-dependent plasticity. We studied myelin in human visual cortex using Western blotting to quantify Classic- and Golli-MBP expression in post-mortem tissue samples ranging in age from 20 days to 80 years. We found that Classic- and Golli-MBP have different patterns of change across the lifespan. Classic-MBP gradually increases to 42 years and then declines into aging. Golli-MBP has early developmental changes that are coincident with milestones in visual system sensitive period, and gradually increases into aging. There are three stages in the balance between Classic- and Golli-MBP expression, with Golli-MBP dominating early, then shifting to Classic-MBP, and back to Golli-MBP in aging. Also Golli-MBP has a wave of high inter-individual variability during childhood. These results about cortical MBP expression are timely because they compliment recent advances in MRI techniques that produce high resolution maps of cortical myelin in normal and diseased brain. In addition, the unique pattern of Golli-MBP expression across the lifespan suggests that it supports high levels of neuroimmune interaction in cortical development and in aging. PMID:25964736

  8. Understanding Human-Landscape Interactions in the "Anthropocene"

    NASA Astrophysics Data System (ADS)

    Harden, Carol P.; Chin, Anne; English, Mary R.; Fu, Rong; Galvin, Kathleen A.; Gerlak, Andrea K.; McDowell, Patricia F.; McNamara, Dylan E.; Peterson, Jeffrey M.; Poff, N. LeRoy; Rosa, Eugene A.; Solecki, William D.; Wohl, Ellen E.

    2014-01-01

    This article summarizes the primary outcomes of an interdisciplinary workshop in 2010, sponsored by the U.S. National Science Foundation, focused on developing key questions and integrative themes for advancing the science of human-landscape systems. The workshop was a response to a grand challenge identified recently by the U.S. National Research Council (2010a)—"How will Earth's surface evolve in the "Anthropocene?"—suggesting that new theories and methodological approaches are needed to tackle increasingly complex human-landscape interactions in the new era. A new science of human-landscape systems recognizes the interdependence of hydro-geomorphological, ecological, and human processes and functions. Advances within a range of disciplines spanning the physical, biological, and social sciences are therefore needed to contribute toward interdisciplinary research that lies at the heart of the science. Four integrative research themes were identified—thresholds/tipping points, time scales and time lags, spatial scales and boundaries, and feedback loops—serving as potential focal points around which theory can be built for human-landscape systems. Implementing the integrative themes requires that the research communities: (1) establish common metrics to describe and quantify human, biological, and geomorphological systems; (2) develop new ways to integrate diverse data and methods; and (3) focus on synthesis, generalization, and meta-analyses, as individual case studies continue to accumulate. Challenges to meeting these needs center on effective communication and collaboration across diverse disciplines spanning the natural and social scientific divide. Creating venues and mechanisms for sustained focused interdisciplinary collaborations, such as synthesis centers, becomes extraordinarily important for advancing the science.

  9. Understanding human-landscape interactions in the "Anthropocene".

    PubMed

    Harden, Carol P; Chin, Anne; English, Mary R; Fu, Rong; Galvin, Kathleen A; Gerlak, Andrea K; McDowell, Patricia F; McNamara, Dylan E; Peterson, Jeffrey M; Poff, N LeRoy; Rosa, Eugene A; Solecki, William D; Wohl, Ellen E

    2014-01-01

    This article summarizes the primary outcomes of an interdisciplinary workshop in 2010, sponsored by the U.S. National Science Foundation, focused on developing key questions and integrative themes for advancing the science of human-landscape systems. The workshop was a response to a grand challenge identified recently by the U.S. National Research Council (2010a)--"How will Earth's surface evolve in the "Anthropocene?"--suggesting that new theories and methodological approaches are needed to tackle increasingly complex human-landscape interactions in the new era. A new science of human-landscape systems recognizes the interdependence of hydro-geomorphological, ecological, and human processes and functions. Advances within a range of disciplines spanning the physical, biological, and social sciences are therefore needed to contribute toward interdisciplinary research that lies at the heart of the science. Four integrative research themes were identified--thresholds/tipping points, time scales and time lags, spatial scales and boundaries, and feedback loops--serving as potential focal points around which theory can be built for human-landscape systems. Implementing the integrative themes requires that the research communities: (1) establish common metrics to describe and quantify human, biological, and geomorphological systems; (2) develop new ways to integrate diverse data and methods; and (3) focus on synthesis, generalization, and meta-analyses, as individual case studies continue to accumulate. Challenges to meeting these needs center on effective communication and collaboration across diverse disciplines spanning the natural and social scientific divide. Creating venues and mechanisms for sustained focused interdisciplinary collaborations, such as synthesis centers, becomes extraordinarily important for advancing the science. PMID:23793544

  10. Understanding What We Do: Emerging Models for Human Rights Education

    NASA Astrophysics Data System (ADS)

    Tibbitts, Felisa

    2002-07-01

    The author presents three approaches to contemporary human rights education practice: the Values and Awareness Model, the Accountability Model and the Transformational Model. Each model is associated with particular target groups, contents and strategies. The author suggests that these models can lend themselves to theory development and research in what might be considered an emerging educational field. Human rights education can be further strengthened through the appropriate use oflearning theory, as well as through the setting of standards for trainer preparation and program content, and through evaluating the impact of programs in terms of reaching learner goals (knowledge, values and skills) and contributing to social change.

  11. Increasing our Understanding of Human Cognition Through the Study of Fragile X Syndrome

    PubMed Central

    Denise, Cook; Erin, Nuro; Keith, K. Murai

    2014-01-01

    Fragile X Syndrome (FXS) is considered the most common form of inherited intellectual disability. It is caused by reductions in the expression level or function of a single protein, the Fragile X Mental Retardation Protein (FMRP), a translational regulator which binds to approximately 4% of brain messenger RNAs. Accumulating evidence suggests that FXS is a complex disorder of cognition, involving interactions between genetic and environmental influences, leading to difficulties in acquiring key life skills including motor skills, language, and proper social behaviors. Since many FXS patients also present with one or more features of autism spectrum disorders (ASDs), insights gained from studying the monogenic basis of FXS could pave the way to a greater understanding of underlying features of multigenic ASDs. Here we present an overview of the FXS and FMRP field with the goal of demonstrating how loss of a single protein involved in translational control affects multiple stages of brain development and leads to debilitating consequences on human cognition. We also focus on studies which have rescued or improved FXS symptoms in mice using genetic or therapeutic approaches to reduce protein expression. We end with a brief description of how deficits in translational control are implicated in FXS and certain cases of ASDs, with many recent studies demonstrating that ASDs are likely caused by increases or decreases in the levels of certain key synaptic proteins. The study of FXS and its underlying single genetic cause offers an invaluable opportunity to study how a single gene influences brain development and behavior. © 2013 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 74: 147–177, 2014 PMID:23723176

  12. Measuring and Understanding Public Opinion on Human Evolution

    ERIC Educational Resources Information Center

    Gwon, Misook

    2012-01-01

    The theory of evolution has long generated controversy in American society, but Americans' attitudes about human evolution are often neglected in studies of "culture wars" and the nature of mass belief systems more generally (Berkman and Plutzer 2010; Freeland and Houston 2009). Gallup and other survey organizations have polled…

  13. UNDERSTANDING THE EFFECTS OF AIR POLLUTION ON HUMAN HEALTH

    EPA Science Inventory

    Modern air pollution regulation is first and foremost motivated by concerns about the effects of air pollutants on human health and secondarily by concerns about its effects on ecosystems, cultural artifacts, and quality of life values such as visibility. This order of priority ...

  14. Genital Measures: Comments on Their Role in Understanding Human Sexuality

    ERIC Educational Resources Information Center

    Geer, James H.

    1976-01-01

    This paper discusses the use of genital measures in the study of both applied and basic work in human sexuality. Some of the advantages of psychophysiological measures are considered along with cautions concerning unwarranted assumptions. Some of the advances that are possible in both applied and basic work are examined. (Author)

  15. Understanding the heavy-tailed dynamics in human behavior.

    PubMed

    Ross, Gordon J; Jones, Tim

    2015-06-01

    The recent availability of electronic data sets containing large volumes of communication data has made it possible to study human behavior on a larger scale than ever before. From this, it has been discovered that across a diverse range of data sets, the interevent times between consecutive communication events obey heavy-tailed power law dynamics. Explaining this has proved controversial, and two distinct hypotheses have emerged. The first holds that these power laws are fundamental, and arise from the mechanisms such as priority queuing that humans use to schedule tasks. The second holds that they are statistical artifacts which only occur in aggregated data when features such as circadian rhythms and burstiness are ignored. We use a large social media data set to test these hypotheses, and find that although models that incorporate circadian rhythms and burstiness do explain part of the observed heavy tails, there is residual unexplained heavy-tail behavior which suggests a more fundamental cause. Based on this, we develop a quantitative model of human behavior which improves on existing approaches and gives insight into the mechanisms underlying human interactions. PMID:26172756

  16. Understanding the heavy-tailed dynamics in human behavior

    NASA Astrophysics Data System (ADS)

    Ross, Gordon J.; Jones, Tim

    2015-06-01

    The recent availability of electronic data sets containing large volumes of communication data has made it possible to study human behavior on a larger scale than ever before. From this, it has been discovered that across a diverse range of data sets, the interevent times between consecutive communication events obey heavy-tailed power law dynamics. Explaining this has proved controversial, and two distinct hypotheses have emerged. The first holds that these power laws are fundamental, and arise from the mechanisms such as priority queuing that humans use to schedule tasks. The second holds that they are statistical artifacts which only occur in aggregated data when features such as circadian rhythms and burstiness are ignored. We use a large social media data set to test these hypotheses, and find that although models that incorporate circadian rhythms and burstiness do explain part of the observed heavy tails, there is residual unexplained heavy-tail behavior which suggests a more fundamental cause. Based on this, we develop a quantitative model of human behavior which improves on existing approaches and gives insight into the mechanisms underlying human interactions.

  17. Understanding the Human Volcano: What Teens Can Do about Violence.

    ERIC Educational Resources Information Center

    Hipp, Earl

    Anger and violence among children has moved from the streets to the schools, with tragic, and well-documented, results. This book addresses anger and violence among children and is, in essence, an anger-management course for teens, written at about an eighth-grade level. Part 1, "The Problems of Violence in Our World," explores human violence. It…

  18. Understanding Arts and Humanities Students' Experiences of Assessment and Feedback

    ERIC Educational Resources Information Center

    Adams, Joelle; McNab, Nicole

    2013-01-01

    This article examines how undergraduate students on arts and humanities courses experience assessment and feedback. The research uses a detailed audit, a specially devised questionnaire (the Assessment Experience Questionnaire), and student focus group data, and the article examines results from 19 programmes, comparing those from "arts and…

  19. Humanities in Dental Education: A Focus on Understanding the Child.

    ERIC Educational Resources Information Center

    Balis, Sophia A.; Rule, James T.

    1999-01-01

    Describes a seminar program at the University of Maryland Dental School, which uses books, short stories, and films that integrate human values into dental education, specifically in pediatric dentistry, for residents, clerks, and faculty. Results of initial evaluation and changes in the program over time are detailed. (DB)

  20. Applying artificial vision models to human scene understanding

    PubMed Central

    Aminoff, Elissa M.; Toneva, Mariya; Shrivastava, Abhinav; Chen, Xinlei; Misra, Ishan; Gupta, Abhinav; Tarr, Michael J.

    2015-01-01

    How do we understand the complex patterns of neural responses that underlie scene understanding? Studies of the network of brain regions held to be scene-selective—the parahippocampal/lingual region (PPA), the retrosplenial complex (RSC), and the occipital place area (TOS)—have typically focused on single visual dimensions (e.g., size), rather than the high-dimensional feature space in which scenes are likely to be neurally represented. Here we leverage well-specified artificial vision systems to explicate a more complex understanding of how scenes are encoded in this functional network. We correlated similarity matrices within three different scene-spaces arising from: (1) BOLD activity in scene-selective brain regions; (2) behavioral measured judgments of visually-perceived scene similarity; and (3) several different computer vision models. These correlations revealed: (1) models that relied on mid- and high-level scene attributes showed the highest correlations with the patterns of neural activity within the scene-selective network; (2) NEIL and SUN—the models that best accounted for the patterns obtained from PPA and TOS—were different from the GIST model that best accounted for the pattern obtained from RSC; (3) The best performing models outperformed behaviorally-measured judgments of scene similarity in accounting for neural data. One computer vision method—NEIL (“Never-Ending-Image-Learner”), which incorporates visual features learned as statistical regularities across web-scale numbers of scenes—showed significant correlations with neural activity in all three scene-selective regions and was one of the two models best able to account for variance in the PPA and TOS. We suggest that these results are a promising first step in explicating more fine-grained models of neural scene understanding, including developing a clearer picture of the division of labor among the components of the functional scene-selective brain network. PMID:25698964

  1. Applying artificial vision models to human scene understanding.

    PubMed

    Aminoff, Elissa M; Toneva, Mariya; Shrivastava, Abhinav; Chen, Xinlei; Misra, Ishan; Gupta, Abhinav; Tarr, Michael J

    2015-01-01

    How do we understand the complex patterns of neural responses that underlie scene understanding? Studies of the network of brain regions held to be scene-selective-the parahippocampal/lingual region (PPA), the retrosplenial complex (RSC), and the occipital place area (TOS)-have typically focused on single visual dimensions (e.g., size), rather than the high-dimensional feature space in which scenes are likely to be neurally represented. Here we leverage well-specified artificial vision systems to explicate a more complex understanding of how scenes are encoded in this functional network. We correlated similarity matrices within three different scene-spaces arising from: (1) BOLD activity in scene-selective brain regions; (2) behavioral measured judgments of visually-perceived scene similarity; and (3) several different computer vision models. These correlations revealed: (1) models that relied on mid- and high-level scene attributes showed the highest correlations with the patterns of neural activity within the scene-selective network; (2) NEIL and SUN-the models that best accounted for the patterns obtained from PPA and TOS-were different from the GIST model that best accounted for the pattern obtained from RSC; (3) The best performing models outperformed behaviorally-measured judgments of scene similarity in accounting for neural data. One computer vision method-NEIL ("Never-Ending-Image-Learner"), which incorporates visual features learned as statistical regularities across web-scale numbers of scenes-showed significant correlations with neural activity in all three scene-selective regions and was one of the two models best able to account for variance in the PPA and TOS. We suggest that these results are a promising first step in explicating more fine-grained models of neural scene understanding, including developing a clearer picture of the division of labor among the components of the functional scene-selective brain network. PMID:25698964

  2. High School Students' Understanding of the Human Body System

    NASA Astrophysics Data System (ADS)

    Assaraf, Orit Ben-Zvi; Dodick, Jeff; Tripto, Jaklin

    2013-02-01

    In this study, 120 tenth-grade students from 8 schools were examined to determine the extent of their ability to perceive the human body as a system after completing the first stage in their biology curriculum - "The human body, emphasizing homeostasis". The students' systems thinking was analyzed according to the STH thinking model, which roughly divides it into three main levels that are arranged "pyramid" style, in an ascending order of difficulty: 1. Analysis of system components—the ability to identify the components and processes existing in the human body system; 2. Synthesis of system components—ability to identify dynamic relations within the system; 3. Implementation—ability to generalize and identify patterns in the system, and to identify its hidden dimensions. The students in this study proved largely incapable of achieving systems thinking beyond the primary STH level of identifying components. An overwhelming majority if their responses corresponded to this level of the STH model, further indicating a pronounced favoring of structure over process, and of larger, macro elements over microscopic ones.

  3. Developmental Progression of the Coronary Vasculature in Human Embryos and Fetuses.

    PubMed

    Tomanek, Robert J

    2016-01-01

    Although considerable advances in our understanding of mammalian and avian embryonic coronary development have occurred during the last decade, our current knowledge of this topic in humans is limited. Accordingly, the aim of this study was to determine if the development of the human coronary vasculature in humans is like that of other mammals and avians. The data document a progression of events involving mesenchymal cell-containing villi from the proepicardium, establishment of blood islands and a capillary network. The major finding of the study is direct evidence that the capillary plexus associated with spindle cells and erythroblasts invades the base of the aorta to form coronary ostia. A role for the dorsal mesocardium is also indicated by the finding that cells from this region are continuous with the aorta and pulmonary artery. The development of the tunica media of the coronary arteries follows the same base-apex progression as in other species, with the development of branches occurring late in the embryonic period. The fetal period is characterized by 1) growth and a numerical increase in the smallest arterial branches, veins, and venules, 2) innervation of arteries, and 3) inclusion of elastic fibers in the tunica media of the coronary arteries and development of the tunica adventitia. In conclusion, the data demonstrate that the development of the coronary system in humans is similar to that of other mammalian and avian species, and for the first time documents that the formation of the ostia and coronary stems in humans occurs by ingrowth of a vascular plexus and associated cells from the epicardium. PMID:26475042

  4. Away from ethnocentrism and anthropocentrism: towards a scientific understanding of "what makes us human".

    PubMed

    Boesch, Christophe

    2010-06-01

    The quest to understand "what makes us human" has been heading towards an impasse, when comparative psychology compares primarily individuals that are not representative of their species. Captives experience such divergent socioecological niches that they cannot stand for their wild counterparts. Only after removing ethnocentrism and anthropocentrism will we be able to progress in our understanding of "what makes us human." PMID:20550734

  5. Use of a mouse in vitro fertilization model to understand the developmental origins of health and disease hypothesis.

    PubMed

    Feuer, Sky K; Liu, Xiaowei; Donjacour, Annemarie; Lin, Wingka; Simbulan, Rhodel K; Giritharan, Gnanaratnam; Piane, Luisa Delle; Kolahi, Kevin; Ameri, Kurosh; Maltepe, Emin; Rinaudo, Paolo F

    2014-05-01

    The Developmental Origins of Health and Disease hypothesis holds that alterations to homeostasis during critical periods of development can predispose individuals to adult-onset chronic diseases such as diabetes and metabolic syndrome. It remains controversial whether preimplantation embryo manipulation, clinically used to treat patients with infertility, disturbs homeostasis and affects long-term growth and metabolism. To address this controversy, we have assessed the effects of in vitro fertilization (IVF) on postnatal physiology in mice. We demonstrate that IVF and embryo culture, even under conditions considered optimal for mouse embryo culture, alter postnatal growth trajectory, fat accumulation, and glucose metabolism in adult mice. Unbiased metabolic profiling in serum and microarray analysis of pancreatic islets and insulin sensitive tissues (liver, skeletal muscle, and adipose tissue) revealed broad changes in metabolic homeostasis, characterized by systemic oxidative stress and mitochondrial dysfunction. Adopting a candidate approach, we identify thioredoxin-interacting protein (TXNIP), a key molecule involved in integrating cellular nutritional and oxidative states with metabolic response, as a marker for preimplantation stress and demonstrate tissue-specific epigenetic and transcriptional TXNIP misregulation in selected adult tissues. Importantly, dysregulation of TXNIP expression is associated with enrichment for H4 acetylation at the Txnip promoter that persists from the blastocyst stage through adulthood in adipose tissue. Our data support the vulnerability of preimplantation embryos to environmental disturbance and demonstrate that conception by IVF can reprogram metabolic homeostasis through metabolic, transcriptional, and epigenetic mechanisms with lasting effects for adult growth and fitness. This study has wide clinical relevance and underscores the importance of continued follow-up of IVF-conceived offspring. PMID:24684304

  6. A chronology of human understanding of the nitrogen cycle†

    PubMed Central

    Galloway, James N.; Leach, Allison M.; Bleeker, Albert; Erisman, Jan Willem

    2013-01-01

    Nitrogen over the ages! It was discovered in the eighteenth century. The following century, its importance in agriculture was documented and the basic components of its cycle were elucidated. In the twentieth century, a process to provide an inexhaustible supply of reactive N (Nr; all N species except N2) for agricultural, industrial and military uses was invented. This discovery and the extensive burning of fossil fuels meant that by the beginning of the twenty-first century, anthropogenic sources of newly created Nr were two to three times that of natural terrestrial sources. This caused a fundamental change in the nitrogen cycle; for the first time, there was the potential for enough food to sustain growing populations and changing dietary patterns. However, most Nr created by humans is lost to the environment, resulting in a cascade of negative earth systems impacts—including enhanced acid rain, smog, eutrophication, greenhouse effect and stratospheric ozone depletion, with associated impacts on human and ecosystem health. The impacts continue and will be magnified, as Nr is lost to the environment at an even greater rate. Thus, the challenge for the current century is how to optimize the uses of N while minimizing the negative impacts. PMID:23713118

  7. A chronology of human understanding of the nitrogen cycle.

    PubMed

    Galloway, James N; Leach, Allison M; Bleeker, Albert; Erisman, Jan Willem

    2013-07-01

    Nitrogen over the ages! It was discovered in the eighteenth century. The following century, its importance in agriculture was documented and the basic components of its cycle were elucidated. In the twentieth century, a process to provide an inexhaustible supply of reactive N (Nr; all N species except N2) for agricultural, industrial and military uses was invented. This discovery and the extensive burning of fossil fuels meant that by the beginning of the twenty-first century, anthropogenic sources of newly created Nr were two to three times that of natural terrestrial sources. This caused a fundamental change in the nitrogen cycle; for the first time, there was the potential for enough food to sustain growing populations and changing dietary patterns. However, most Nr created by humans is lost to the environment, resulting in a cascade of negative earth systems impacts-including enhanced acid rain, smog, eutrophication, greenhouse effect and stratospheric ozone depletion, with associated impacts on human and ecosystem health. The impacts continue and will be magnified, as Nr is lost to the environment at an even greater rate. Thus, the challenge for the current century is how to optimize the uses of N while minimizing the negative impacts. PMID:23713118

  8. Social Understanding and Social Lives: From Toddlerhood through to the Transition to School. Essays in Developmental Psychology

    ERIC Educational Resources Information Center

    Hughes, Claire

    2011-01-01

    Over the past thirty years, researchers have documented a remarkable growth in children's social understanding between toddlerhood and the early school years. However, it is still unclear why some children's awareness of others' thoughts and feelings lags so far behind that of their peers. Based on research that spans an extended developmental…

  9. Putting the Mind in the Brain: Promoting an Appreciation of the Biological Basis to Understanding Human Behavior

    ERIC Educational Resources Information Center

    Neumann, David L.

    2010-01-01

    A surprising number of students in psychology, behavioral science, and related social science classes fail to appreciate the importance of biological mechanisms to understanding behavior. To help teachers promote this understanding, this paper outlines six sources of evidence. These are (a) phylogenetic, (b) genetic/developmental, (c) clinical,…

  10. Bootstrapping Q Methodology to Improve the Understanding of Human Perspectives

    PubMed Central

    Zabala, Aiora; Pascual, Unai

    2016-01-01

    Q is a semi-qualitative methodology to identify typologies of perspectives. It is appropriate to address questions concerning diverse viewpoints, plurality of discourses, or participation processes across disciplines. Perspectives are interpreted based on rankings of a set of statements. These rankings are analysed using multivariate data reduction techniques in order to find similarities between respondents. Discussing the analytical process and looking for progress in Q methodology is becoming increasingly relevant. While its use is growing in social, health and environmental studies, the analytical process has received little attention in the last decades and it has not benefited from recent statistical and computational advances. Specifically, the standard procedure provides overall and arguably simplistic variability measures for perspectives and none of these measures are associated to individual statements, on which the interpretation is based. This paper presents an innovative approach of bootstrapping Q to obtain additional and more detailed measures of variability, which helps researchers understand better their data and the perspectives therein. This approach provides measures of variability that are specific to each statement and perspective, and additional measures that indicate the degree of certainty with which each respondent relates to each perspective. This supplementary information may add or subtract strength to particular arguments used to describe the perspectives. We illustrate and show the usefulness of this approach with an empirical example. The paper provides full details for other researchers to implement the bootstrap in Q studies with any data collection design. PMID:26845694

  11. Specializations of the human upper respiratory and upper digestive systems as seen through comparative and developmental anatomy.

    PubMed

    Laitman, J T; Reidenberg, J S

    1993-01-01

    The human upper respiratory, or aerodigestive, tract serves as the crossroads of our breathing, swallowing and vocalizing pathways. Accordingly, developmental or evolutionary change in any of these functions will, of necessity, affect the others. Our studies have shown that the position in the neck of the mammalian larynx is a major factor in determining function in this region. Most mammals, such as our closest relatives the nonhuman primates, exhibit a larynx positioned high in the neck. This permits an intranarial larynx to be present and creates largely separate respiratory and digestive routes. While infant humans retain this basic mammalian pattern, developmental descent of the larynx considerably alters this configuration. Adult humans have, accordingly, lost separation of the respiratory and digestive routes, but have gained an increased supralaryngeal region of the pharynx which allows for the production of the varied sounds of human speech. How this region has changed during human evolution has been difficult to assess due to the absence of preserved soft-tissue structures. Our studies have shown that the relationship between basicranial shape and laryngeal position in living mammals can be a valuable guide to reconstruct the region in ancestral humans. Based on these findings we have examined the basicrania of fossil ancestors--from over two million years ago to near recent times--and have reconstructed the position of the larynx and pharyngeal region in these early forms. This has allowed us insight into how our ancestors may have breathed and swallowed, and when the anatomy necessary for human speech evolved. PMID:8269722

  12. SUPERNUMERARY RIBS IN DEVELOPMENTAL TOXICITY BIOASSAYS AND IN HUMAN POPULATIONS: INCIDENCE AND BIOLOGICAL SIGNIFICANCE

    EPA Science Inventory

    Abstract
    Supernumerary or accessory ribs (SNR), either lumbar (LSNR) or cervical (CSNR) are a common finding in standard developmental toxicology bioassays. The biological significance of these anomalies within the regulatory arena has been problematic and the subject of some...

  13. The Developmental Cycle: Teachings on the Eight Stages of Growth of a Human Being.

    ERIC Educational Resources Information Center

    Coyhis, Don

    1997-01-01

    Ties Native American Medicine Wheel teachings on the cycle of life to Eric Erickson's work on the eight developmental stages: trust, autonomy, initiative, accomplishment, identity, intimacy, generativity, and integrity. To have healthy communities, people need to move successfully through these stages. Knowing about these stages can help a person…

  14. Genome-Wide Reprogramming of Transcript Architecture by Temperature Specifies the Developmental States of the Human Pathogen Histoplasma

    PubMed Central

    Gilmore, Sarah A.; Voorhies, Mark; Gebhart, Dana; Sil, Anita

    2015-01-01

    Eukaryotic cells integrate layers of gene regulation to coordinate complex cellular processes; however, mechanisms of post-transcriptional gene regulation remain poorly studied. The human fungal pathogen Histoplasma capsulatum (Hc) responds to environmental or host temperature by initiating unique transcriptional programs to specify multicellular (hyphae) or unicellular (yeast) developmental states that function in infectivity or pathogenesis, respectively. Here we used recent advances in next-generation sequencing to uncover a novel re-programming of transcript length between Hc developmental cell types. We found that ~2% percent of Hc transcripts exhibit 5’ leader sequences that differ markedly in length between morphogenetic states. Ribosome density and mRNA abundance measurements of differential leader transcripts revealed nuanced transcriptional and translational regulation. One such class of regulated longer leader transcripts exhibited tight transcriptional and translational repression. Further examination of these dually repressed genes revealed that some control Hc morphology and that their strict regulation is necessary for the pathogen to make appropriate developmental decisions in response to temperature. PMID:26177267

  15. Non-Mendelian developmental defects: animal models and implications for research into human disease*

    PubMed Central

    1977-01-01

    The major groups of malformations in man are polygenic in origin but this review deals only with defects due to non-Mendelian factors. Animal models that help in identifying the causes and in understanding the numerous and often subtle mechanisms of human malformations are of particular value. Many chemicals, physical agents, and nutritional deficiencies affect experimental species but few are teratogenic for domestic animals and even fewer for man. The known fetopathic viruses of animals and man cross the placenta to cause chronic, nonlethal fetal damage without harm to the mother. Ionizing radiations are teratogenic for all species and hyperthermia for many, but the role of the latter in human development is uncertain. The identification of more animal species with spontaneous or induced defects comparable to those found in man and of additional causative teratogens will increase the resources available for research into the causes and mechanisms of abnormal development in man. No animal species is ideal in teratological research but each has its virtues. This report comments on the present status of research in teratology and the trends that might profitably be followed in the future. PMID:413638

  16. Understanding the human health effects of chemical mixtures.

    PubMed Central

    Carpenter, David O; Arcaro, Kathleen; Spink, David C

    2002-01-01

    Most research on the effects of chemicals on biologic systems is conducted on one chemical at a time. However, in the real world people are exposed to mixtures, not single chemicals. Although various substances may have totally independent actions, in many cases two substances may act at the same site in ways that can be either additive or nonadditive. Many even more complex interactions may occur if two chemicals act at different but related targets. In the extreme case there may be synergistic effects, in which case the effects of two substances together are greater than the sum of either effect alone. In reality, most persons are exposed to many chemicals, not just one or two, and therefore the effects of a chemical mixture are extremely complex and may differ for each mixture depending on the chemical composition. This complexity is a major reason why mixtures have not been well studied. In this review we attempt to illustrate some of the principles and approaches that can be used to study effects of mixtures. By the nature of the state of the science, this discussion is more a presentation of what we do not know than of what we do know about mixtures. We approach the study of mixtures at three levels, using specific examples. First, we discuss several human diseases in relation to a variety of environmental agents believed to influence the development and progression of the disease. We present results of selected cellular and animal studies in which simple mixtures have been investigated. Finally, we discuss some of the effects of mixtures at a molecular level. PMID:11834461

  17. The Dynamic Lift of Developmental Process

    ERIC Educational Resources Information Center

    Smith, Linda B.; Breazeal, Cynthia

    2007-01-01

    What are the essential properties of human intelligence, currently unparalleled in its power relative to other biological forms and relative to artificial forms of intelligence? We suggest that answering this question depends critically on understanding developmental process. This paper considers three principles potentially essential to building…

  18. Developmental decisions

    PubMed Central

    Tobin, David V.; Saito, Richard Mako

    2012-01-01

    The small nematode C. elegans is characterized by developing through a highly coordinated, reproducible cell lineage that serves as the basis of many studies focusing on the development of multi-lineage organisms. Indeed, the reproducible cell lineage enables discovery of developmental defects that occur in even a single cell. Only recently has attention been focused on how these animals modify their genetically programmed cell lineages to adapt to altered environments. Here, we summarize the current understanding of how C. elegans responds to food deprivation by adapting their developmental program in order to conserve energy. In particular, we highlight the AMPK-mediated and insulin-like growth factor signaling pathways that are the principal regulators of induced cell cycle quiescence. PMID:22510569

  19. The Relationship between Cell Number, Division Behavior and Developmental Potential of Cleavage Stage Human Embryos: A Time-Lapse Study

    PubMed Central

    Gong, Fei; Lu, Changfu; Zhang, Shuoping; Lu, Guangxiu; Lin, Ge

    2016-01-01

    Day 3 cleavage embryo transfer is routine in many assisted reproductive technology centers today. Embryos are usually selected according to cell number, cell symmetry and fragmentation for transfer. Many studies have showed the relationship between cell number and embryo developmental potential. However, there is limited understanding of embryo division behavior and their association with embryo cell number and developmental potential. A retrospective and observational study was conducted to investigate how different division behaviors affect cell number and developmental potential of day 3 embryos by time-lapse imaging. Based on cell number at day 3, the embryos (from 104 IVF/intracytoplasmic sperm injection (ICSI) treatment cycles, n = 799) were classified as follows: less than 5 cells (< 5C; n = 111); 5–6 cells (5–6C; n = 97); 7–8 cells (7–8C; n = 442), 9–10 cells (9–10C; n = 107) and more than 10 cells (>10C; n = 42). Division behavior, morphokinetic parameters and blastocyst formation rate were analyzed in 5 groups of day 3 embryos with different cell numbers. In <5C and 5–6C embryos, fragmentation (FR; 62.2% and 30.9%, respectively) was the main cause for low cell number. The majority of 7–8C embryos exhibited obvious normal behaviors (NB; 85.7%) during development. However, the incidence of DC in 9–10C and >10C embryos increased compared to 7–8C embryos (45.8%, 33.3% vs. 11.1%, respectively). In ≥5C embryos, FR and DC significantly reduced developmental potential, whereas <5C embryos showed little potential irrespective of division behaviors. In NB embryos, the blastocyst formation rate increased with cell number from 7.4% (<5C) to 89.3% (>10C). In NB embryos, the cell cycle elongation or shortening was the main cause for abnormally low or high cell number, respectively. After excluding embryos with abnormal division behaviors, the developmental potential, implantation rate and live birth rate of day 3 embryos increased with cell number

  20. Simplified ontologies allowing comparison of developmental mammalian gene expression

    PubMed Central

    Kruger, Adele; Hofmann, Oliver; Carninci, Piero; Hayashizaki, Yoshihide; Hide, Winston

    2007-01-01

    Model organisms represent an important resource for understanding the fundamental aspects of mammalian biology. Mapping of biological phenomena between model organisms is complex and if it is to be meaningful, a simplified representation can be a powerful means for comparison. The Developmental eVOC ontologies presented here are simplified orthogonal ontologies describing the temporal and spatial distribution of developmental human and mouse anatomy. We demonstrate the ontologies by identifying genes showing a bias for developmental brain expression in human and mouse. PMID:17961239

  1. Developmental changes in intralimb coordination during spontaneous movements of human infants from 2 to 3 months of age.

    PubMed

    Ohmura, Yoshiyuki; Gima, Hirotaka; Watanabe, Hama; Taga, Gentaro; Kuniyoshi, Yasuo

    2016-08-01

    Human infants show a variety of spontaneous movements in the first few months of life. Although the pattern of spontaneous movements changes at approximately 2 months of age, the precise mechanism that governs the developmental changes in intralimb coordination remains unclear. In the present study, we focused on knee-ankle coordination during spontaneous movements of human infants from 2 to 3 months of age. Multiple attitude sensors were used to measure three-dimensional angular motion of knee and ankle joint motions. We acquired a one-dimensional time series of the knee joint angle around the putative hinge joint and a two-dimensional time series of ankle motions on the putative sagittal and frontal plane. First, we found that 3-month-old infants show a significant predominance to extend their knee joints, remarkably so on the left side. To quantify dissociated motions of the knee and ankle, we calculated the temporal correlation and the regression slope between them. We observed that 3-month-old infants moved their ankle joints more independently of knee motions than 2-month-old infants. Finally, we found that dissociated motions of the knee and ankle simultaneously develop with knee extension predominance. The developmental change from synchronization to dissociation of intralimb joint movements during spontaneous movements suggests that the development of the cortical and/or subcortical mechanism may mediate selective activation and inhibition of joint motions at approximately 2 months of age. PMID:27010721

  2. RNA Sequence Analysis of Human Huntington Disease Brain Reveals an Extensive Increase in Inflammatory and Developmental Gene Expression

    PubMed Central

    Labadorf, Adam; Hoss, Andrew G.; Lagomarsino, Valentina; Latourelle, Jeanne C.; Hadzi, Tiffany C.; Bregu, Joli; MacDonald, Marcy E.; Gusella, James F.; Chen, Jiang-Fan; Akbarian, Schahram; Weng, Zhiping; Myers, Richard H.

    2015-01-01

    Huntington’s Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently detected genes are differentially expressed (FDR<0.05) and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes), that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD. PMID:26636579

  3. Can stem cells really regenerate the human heart? Use your noggin, dickkopf! Lessons from developmental biology.

    PubMed

    Sommer, Paula

    2013-06-01

    The human heart is the first organ to develop and its development is fairly well characterised. In theory, the heart has the capacity to regenerate, as its cardiomyocytes may be capable of cell division and the adult heart contains a cardiac stem cell niche, presumably capable of differentiating into cardiomyocytes and other cardiac-associated cell types. However, as with most other organs, these mechanisms are not activated upon serious injury. Several experimental options to induce regeneration of the damaged heart tissue are available: activate the endogenous cardiomyocytes to divide, coax the endogenous population of stem cells to divide and differentiate, or add exogenous cell-based therapy to replace the lost cardiac tissue. This review is a summary of the recent research into all these avenues, discussing the reasons for the limited successes of clinical trials using stem cells after cardiac injury and explaining new advances in basic science. It concludes with a reiteration that chances of successful regeneration would be improved by understanding and implementing the basics of heart development and stem cell biology. PMID:24217168

  4. Educational Cooperation between Thailand and Cambodia: Outcomes on Human Development, International Understanding and Future Prospect

    ERIC Educational Resources Information Center

    Kijtorntham, Wichuda; Ruangdej, Phumjit; Saisuwan, Chatchanog

    2015-01-01

    Thailand and Cambodia set up educational cooperation since 1996, before signed a Memorandum of Understanding on Cooperation in the Promotion of Education in 2003. This research aimed to investigate outcomes of educational cooperation projects on Cambodia human development and international understanding, process of participatory learning and…

  5. Facilitating Conceptual Change in Ninth Grade Students' Understanding of Human Circulatory System Concepts

    ERIC Educational Resources Information Center

    Alkhawaldeh, Salem A.

    2007-01-01

    The purpose of this study was to investigate the effectiveness of the conceptual change text oriented instruction over traditionally designed instruction on ninth grade students' understanding of the human circulatory system concepts, and their retention of this understanding. The subjects of this study consist of 73 ninth grade female students…

  6. Developmental Toxicology##

    EPA Science Inventory

    Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

  7. The International Space Station: A Research Platform to Understand Environmental and Human Microbiomes

    NASA Technical Reports Server (NTRS)

    Ott, C. Mark

    2016-01-01

    ISS microbiological operations and research are a key part of protect the astronauts and their vehicles. These studies are also providing novel findings that can translate into benefits for the general public on Earth. Understanding the environmental and human microbiomes is especially critical as we leave Earth's orbit on our future exploration efforts. ISS Platform Advantages Remarkable correlation potential for crew and environmental metadata Almost closed environment enables a baseline understanding of humans with their environment ISS Platform Disadvantages Sample number for human microbiome studies is very low Most of the samples must be returned for a full analysis.

  8. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890892

  9. The Emergence of Autobiographical Memory: A Social Cultural Developmental Theory

    ERIC Educational Resources Information Center

    Nelson, Katherine; Fivush, Robyn

    2004-01-01

    The authors present a multicomponent dynamic developmental theory of human autobiographical memory that emerges gradually across the preschool years. The components that contribute to the process of emergence include basic memory abilities, language and narrative, adult memory talk, temporal understanding, and understanding of self and others. The…

  10. NTP-CERHR monograph on the potential human reproductive and developmental effects of acrylamide.

    PubMed

    2005-02-01

    Acrylamide, used in the manufacture of polyacrylamide and grouting agents, is produced during the cooking of foods. Workplace exposure to acrylamide can occur through the dermal and inhalation routes. The objectives of this study were to evaluate the metabolism of acrylamide in humans following oral administration, to compare hemoglobin adduct formation on oral and dermal administration, to measure hormone levels, and to monitor the safety of acrylamide in people exposed under controlled conditions. Prior to conducting exposures in humans, a low-dose study was conducted in rats administered 3 mg/kg 1,2,3-¹³C₃acrylamide by gavage. The study protocol was reviewed and approved by Institute Review Boards both at RTI which performed the sample analysis, and the clinical research center conducting the study. 1,2,3-¹³C₃Acrylamide (AM) was administered in an aqueous solution orally (single dose of 0.5, 1.0,or 3.0 mg/kg) or dermally (3 daily doses of 3.0 mg/kg) to sterile male volunteers. Urine samples (3 mg/kg oral dose) were analyzed for AM metabolites using 13C NMR spectroscopy. Approximately 86 % of the urinary metabolites were derived from GSH conjugation, and excreted as N-acetyl-S-(3-amino-3-oxopropyl)cysteine and its S-oxide.Glycidamide, glycer amide, and low levels of N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)cysteine were detected in urine. On oral administration, a linear dose response was observed for N-(2-carbamoylethyl)valine (AAVal) and N-(2-carbamoyl-2-hydroxyethyl)valine (GAVal) in hemoglobin. Dermal administration resulted in lower levels of AAVal and GAVal. This study indicated that humans metabolize acrylamide via glycidamide to a lesser extent than rodents, and dermal uptake was approximately 5%of that observed with oral uptake. Acrylamide is used in the manufacture of water- soluble polymers (European Union,2002). These polymers are then used for wastewater and sludge treatment, paper manufacture, soil stabilization, mining and many other uses

  11. Understanding and Choosing Assessments and Developmental Screeners for Young Children Ages 3-5: Profiles of Selected Measures. OPRE Report #2011-23

    ERIC Educational Resources Information Center

    Halle, Tamara; Zaslow, Martha; Wessel, Julia; Moodie, Shannon; Darling-Churchill, Kristen

    2011-01-01

    The 2007 reauthorization of Head Start requires Head Start programs to use child assessments and developmental screeners that are developmentally, linguistically, and culturally appropriate, as well as valid and reliable in the language in which they are used. This can be a challenge, since very few child assessment tools are developed or tested…

  12. Critical review of the developmental toxicity and teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Recent advances toward understanding the mechanism

    SciTech Connect

    Couture, L.A.; Abbott, B.D.; Birnbaum, L.S.

    1990-01-01

    A specific teratogenic response is elicited in the mouse as a result of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin). The characteristic spectrum of structural malformations induced in mice following exposure to TCDD and structurally-related congeners is highly reproducible and includes both hydronephrosis and cleft palate. In addition, prenatal exposure to TCDD has been shown to induce thymic hypoplasia. The three abnormalities occur at doses well below those producing maternal or embryo/fetal toxicity, and are among the most sensitive indicators of dioxin toxicity. In all other laboratory species tested, TCDD causes maternal and embryo/fetal toxicity, but does not induce a significant increase in the incidence of structural abnormalities even at toxic dose levels. Developmental toxicity occurs in a similar dose range across species, however, mice are particularly susceptible to development of TCDD-induced terata. Recent experiments using an organ culture were an attempt to address the issue of species and organ differences in sensitivity to TCDD. Human palatal shelves were examined in this in vitro system, and were found to approximate the rat in terms of sensitivity for induction of cleft palate.

  13. Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

    PubMed

    Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios

    2015-01-01

    Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically. PMID:26132533

  14. The effect of human follicular fluid on bovine oocyte developmental competence and embryo quality.

    PubMed

    Valckx, Sara D M; De Bie, Jessie; Michiels, Ellen D; Goovaerts, Ilse G; Punjabi, Usha; Ramos-Ibeas, Priscila; Gutierrez-Adan, Alfonso; Bols, Peter E; Leroy, Jo L

    2015-02-01

    In this study, the hypothesis that embryo development during routine IVF procedures is determined by the pre-ovulatory follicular fluid composition was tested. Follicular fluid from women with obesity ('obese') and a 'positive' or 'negative' IVF outcome was added during the in-vitro maturation of bovine oocytes. 'Negative' and 'obese' follicular fluid reduced bovine embryo development, compared with laboratory control embryo development (P < 0.05 or P < 0.1). The addition of follicular fluid also altered bovine blastocyst gene expression. Furthermore, LDHA and PPARGC1B gene expression differed between follicular fluid groups. Data suggest that pre-ovulatory follicular fluid can potentially affect oocyte developmental competence and embryo quality. Furthermore, the bovine model may be used as a screening tool. PMID:25498595

  15. Developmental Toxicity and Fertility Assessment in Rabbits with Tabalumab: A Human IgG4 Monoclonal Antibody.

    PubMed

    Breslin, William J; Hilbish, Kim G; Martin, Jennifer A; Halstead, Carolyn A; Edwards, Tammy L

    2015-06-01

    Tabalumab is a human immunoglobulin G subclass 4 monoclonal antibody that has been under development for autoimmune disorders. Tabalumab has full neutralizing activity against both soluble and membrane B-cell activating factor, a B-cell survival factor. The objectives of these studies were to assess the effects of tabalumab on embryo-fetal development and on male (M) and female (F) fertility in rabbits, a pharmacologically relevant species. Doses were administered at 0 (vehicle control), 0.3 (embryo-fetal study only), 1.0, and 30 mg/kg. In the embryo-fetal study, pregnant rabbits does were given a single dose by intravenous injection on gestation day (GD) 7. In the fertility studies, tabalumab was administered by intravenous injection every 7 days starting 2 (F) or 4 (M) weeks before mating, during cohabitation, and until necropsy (M) or through GD 18 (F). Treated animals were mated with untreated partners. Parental clinical signs, body weight, food consumption, blood lymphocyte phenotyping, organ weights, morphologic pathology, ovarian and uterine observations, sperm parameters, and fertility indices were evaluated along with conceptus viability, weight, and morphology. Exposure assessments were made in all main study animals and satellite animals. No adverse parental, reproductive, or developmental effects were observed in any study at any dose. A pharmacodynamic response consisting of dose-dependent decreases in the percent and number of total B lymphocytes and increases in the percent and/or number of total T lymphocytes was observed in parental rabbits at 1.0 and 30 mg/kg. In conclusion, no adverse reproductive or developmental effects were observed in rabbits following exposure to tabalumab at doses as high as 30 mg/kg and exposures at least 14-fold greater than human exposure levels. PMID:26195315

  16. Continuing harmonization of terminology and innovations for methodologies in developmental toxicology: Report of the 8th Berlin Workshop on Developmental Toxicity, 14-16 May 2014.

    PubMed

    Solecki, Roland; Rauch, Martina; Gall, Andrea; Buschmann, Jochen; Clark, Ruth; Fuchs, Antje; Kan, Haidong; Heinrich, Verena; Kellner, Rupert; Knudsen, Thomas B; Li, Weihua; Makris, Susan L; Ooshima, Yojiro; Paumgartten, Francisco; Piersma, Aldert H; Schönfelder, Gilbert; Oelgeschläger, Michael; Schaefer, Christof; Shiota, Kohei; Ulbrich, Beate; Ding, Xuncheng; Chahoud, Ibrahim

    2015-11-01

    This article is a report of the 8th Berlin Workshop on Developmental Toxicity held in May 2014. The main aim of the workshop was the continuing harmonization of terminology and innovations for methodologies used in the assessment of embryo- and fetotoxic findings. The following main topics were discussed: harmonized categorization of external, skeletal, visceral and materno-fetal findings into malformations, variations and grey zone anomalies, aspects of developmental anomalies in humans and laboratory animals, and innovations for new methodologies in developmental toxicology. The application of Version 2 terminology in the DevTox database was considered as a useful improvement in the categorization of developmental anomalies. Participants concluded that initiation of a project for comparative assessments of developmental anomalies in humans and laboratory animals could support regulatory risk assessment and university-based training. Improvement of new methodological approaches for alternatives to animal testing should be triggered for a better understanding of developmental outcomes. PMID:26073002

  17. The Role of Human Intelligence in the USAs 1960s Efforts to Understand Soviet Space Activities

    NASA Astrophysics Data System (ADS)

    Pesavento, P.

    Recent declassification of material from the Interagency Security Classification Appeals Panel (ISCAP) and the archives of the US State Department provide several new insights into US intelligence's knowledge of Soviet Space Activities and sources of that knowledge. It is apparent that there was a significant human intelligence source providing information on subjects such as the USSR's Voskhod 3 mission and manned lunar program activities. This new understanding shows that US intelligence was employing the complete panoply of intelligence tools and that human intelligence appears to have provided many key understandings

  18. The Importance of Human Reliability Analysis in Human Space Flight: Understanding the Risks

    NASA Technical Reports Server (NTRS)

    Hamlin, Teri L.

    2010-01-01

    HRA is a method used to describe, qualitatively and quantitatively, the occurrence of human failures in the operation of complex systems that affect availability and reliability. Modeling human actions with their corresponding failure in a PRA (Probabilistic Risk Assessment) provides a more complete picture of the risk and risk contributions. A high quality HRA can provide valuable information on potential areas for improvement, including training, procedural, equipment design and need for automation.

  19. The early origins of human charity: developmental changes in preschoolers’ sharing with poor and wealthy individuals

    PubMed Central

    Paulus, Markus

    2014-01-01

    Recent studies have provided evidence that young children already engage in sharing behavior. The underlying social-cognitive mechanisms, however, are still under debate. In particular, it is unclear whether or not young children’s sharing is motivated by an appreciation of others’ wealth. Manipulating the material needs of recipients in a sharing task (Experiment 1) and a resource allocation task (Experiment 2), we show that 5- but not 3-year-old children share more with poor than wealthy individuals. The 3-year-old children even showed a tendency to behave less selfishly towards the rich, yet not the poor recipient. This suggests that very early instances of sharing behavior are not motivated by a consideration of others’ material needs. Moreover, the results show that 5-year-old children were rather inclined to give more to the poor individual than distributing the resources equally, demonstrating that their wish to support the poor overruled the otherwise very prominent inclination to share resources equally. This indicates that charity has strong developmental roots in preschool children. PMID:25018735

  20. Adult human neural stem cell therapeutics: Current developmental status and prospect

    PubMed Central

    Nam, Hyun; Lee, Kee-Hang; Nam, Do-Hyun; Joo, Kyeung Min

    2015-01-01

    Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as cell therapeutics for neurological disease. Compared with other types of stem cells, aNSCs have clinical advantages, such as limited proliferation, inborn differentiation potential into functional neural cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in the isolation from the normal brain, and in the in vitro expansion, have blocked preclinical and clinical study using aNSCs. However, several groups have recently developed novel techniques to isolate and expand aNSCs from normal adult brains, and showed successful applications of aNSCs to neurological diseases. With new technologies for aNSCs and their clinical strengths, previous hurdles in stem cell therapies for neurological diseases could be overcome, to realize clinically efficacious regenerative stem cell therapeutics. PMID:25621112

  1. Global Developmental Gene Expression and Pathway Analysis of Normal Brain Development and Mouse Models of Human Neuronal Migration Defects

    PubMed Central

    Pramparo, Tiziano; Libiger, Ondrej; Jain, Sonia; Li, Hong; Youn, Yong Ha; Hirotsune, Shinji; Schork, Nicholas J.; Wynshaw-Boris, Anthony

    2011-01-01

    Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε), and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define

  2. Contributions of in vitro transcription to the understanding of human RNA polymerase III transcription

    PubMed Central

    Dumay-Odelot, Hélène; Durrieu-Gaillard, Stéphanie; El Ayoubi, Leyla; Parrot, Camila; Teichmann, Martin

    2014-01-01

    Human RNA polymerase III transcribes small untranslated RNAs that contribute to the regulation of essential cellular processes, including transcription, RNA processing and translation. Analysis of this transcription system by in vitro transcription techniques has largely contributed to the discovery of its transcription factors and to the understanding of the regulation of human RNA polymerase III transcription. Here we review some of the key steps that led to the identification of transcription factors and to the definition of minimal promoter sequences for human RNA polymerase III transcription. PMID:25764111

  3. Deconstructing Pancreas Developmental Biology

    PubMed Central

    Benitez, Cecil M.; Goodyer, William R.

    2012-01-01

    The relentless nature and increasing prevalence of human pancreatic diseases, in particular, diabetes mellitus and adenocarcinoma, has motivated further understanding of pancreas organogenesis. The pancreas is a multifunctional organ whose epithelial cells govern a diversity of physiologically vital endocrine and exocrine functions. The mechanisms governing the birth, differentiation, morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine components in the pancreas have been discovered recently with increasing tempo. This includes recent studies unveiling mechanisms permitting unexpected flexibility in the developmental potential of immature and mature pancreatic cell subsets, including the ability to interconvert fates. In this article, we describe how classical cell biology, genetic analysis, lineage tracing, and embryological investigations are being complemented by powerful modern methods including epigenetic analysis, time-lapse imaging, and flow cytometry-based cell purification to dissect fundamental processes of pancreas development. PMID:22587935

  4. (Mis)Understanding Human Beings: Theory, Value, and Progress in Education Research

    ERIC Educational Resources Information Center

    Hostetler, Karl

    2010-01-01

    There is renewed interest in what can be called an "experimentist" approach to education research. The claim is that if researchers would focus on experiments and "evidence-based" policies and practices, irreversible progress in education can be achieved. This experimentist approach cannot provide the understanding of knowledge and human beings…

  5. The Psychology of Isolated and Confined Environments: Understanding Human Behavior in Antarctica.

    ERIC Educational Resources Information Center

    Palinkas, Lawrence A.

    2003-01-01

    Reviews lessons learned from research in Antarctica with relevance to understanding human behavior in other isolated and confined environments. Outlines four distinct characteristics of psychosocial adaptation to such environments and discusses some of the benefits for individuals seeking challenging experiences. (Contains references.) (SLD)

  6. Communicating Numerical Risk: Human Factors That Aid Understanding in Health Care

    PubMed Central

    Brust-Renck, Priscila G.; Royer, Caisa E.; Reyna, Valerie F.

    2014-01-01

    In this chapter, we review evidence from the human factors literature that verbal and visual formats can help increase the understanding of numerical risk information in health care. These visual representations of risk are grounded in empirically supported theory. As background, we first review research showing that people often have difficulty understanding numerical risks and benefits in health information. In particular, we discuss how understanding the meanings of numbers results in healthier decisions. Then, we discuss the processes that determine how communication of numerical risks can enhance (or degrade) health judgments and decisions. Specifically, we examine two different approaches to risk communication: a traditional approach and fuzzy-trace theory. Applying research on the complications of understanding and communicating risks, we then highlight how different visual representations are best suited to communicating different risk messages (i.e., their gist). In particular, we review verbal and visual messages that highlight gist representations that can better communicate health information and improve informed decision making. This discussion is informed by human factors theories and methods, which involve the study of how to maximize the interaction between humans and the tools they use. Finally, we present implications and recommendations for future research on human factors in health care. PMID:24999307

  7. X Chromosome Abnormalities and Cognitive Development: Implications for Understanding Normal Human Development.

    ERIC Educational Resources Information Center

    Walzer, Stanley

    1985-01-01

    Argues that knowledge from studies of individuals with sex chromosome abnormalities can further understanding of aspects of normal human development. Studies of XO girls, XXY boys, XXX girls, and males with a fragile X chromosome are summarized to demonstrate how results contribute to knowledge about normal cognitive development and about…

  8. Effects of a Co-operative Learning Strategy on Ninth-Graders' Understanding of Human Nutrition.

    ERIC Educational Resources Information Center

    Soyibo, Kola; Evans, Hermel G.

    2002-01-01

    Looks at the effect of teaching strategies on a group's attitude toward biology and understanding human nutrition. Used an experimental group that participated in co-operative learning and a control group taught using the lecture method. Involves ninth graders (n=156) from two high schools in Jamaica. (Author/YDS)

  9. UNESCO and the Associated Schools Project: Symbolic Affirmation of World Community, International Understanding, and Human Rights

    ERIC Educational Resources Information Center

    Suarez, David F.; Ramirez, Francisco O.; Koo, Jeong-Woo

    2009-01-01

    The UNESCO Associated Schools Project emphasizes world community, human rights, and international understanding. This article investigates the emergence and global diffusion of the project from 1953 to 2001, estimating the influence of national, regional, and world characteristics on the likelihood of a country adopting a UNESCO school. It also…

  10. Global and regional cortical connectivity maturation index (CCMI) of developmental human brain with quantification of short-range association tracts

    PubMed Central

    Ouyang, Minhui; Jeon, Tina; Mishra, Virendra; Du, Haixiao; Wang, Yu; Peng, Yun; Huang, Hao

    2016-01-01

    From early childhood to adulthood, synaptogenesis and synaptic pruning continuously reshape the structural architecture and neural connection in developmental human brains. Disturbance of the precisely balanced strengthening of certain axons and pruning of others may cause mental disorders such as autism and schizophrenia. To characterize this balance, we proposed a novel measurement based on cortical parcellation and diffusion MRI (dMRI) tractography, a cortical connectivity maturation index (CCMI). To evaluate the spatiotemporal sensitivity of CCMI as a potential biomarker, dMRI and T1 weighted datasets of 21 healthy subjects 2–25 years were acquired. Brain cortex was parcellated into 68 gyral labels using T1 weighted images, then transformed into dMRI space to serve as the seed region of interest for dMRI-based tractography. Cortico-cortical association fibers initiated from each gyrus were categorized into long- and short-range ones, based on the other end of fiber terminating in non-adjacent or adjacent gyri of the seed gyrus, respectively. The regional CCMI was defined as the ratio between number of short-range association tracts and that of all association tracts traced from one of 68 parcellated gyri. The developmental trajectory of the whole brain CCMI follows a quadratic model with initial decreases from 2 to 16 years followed by later increases after 16 years. Regional CCMI is heterogeneous among different cortical gyri with CCMI dropping to the lowest value earlier in primary somatosensory cortex and visual cortex while later in the prefrontal cortex. The proposed CCMI may serve as sensitive biomarker for brain development under normal or pathological conditions. PMID:27076697

  11. Global and regional cortical connectivity maturation index (CCMI) of developmental human brain with quantification of short-range association tracts

    NASA Astrophysics Data System (ADS)

    Ouyang, Minhui; Jeon, Tina; Mishra, Virendra; Du, Haixiao; Wang, Yu; Peng, Yun; Huang, Hao

    2016-03-01

    From early childhood to adulthood, synaptogenesis and synaptic pruning continuously reshape the structural architecture and neural connection in developmental human brains. Disturbance of the precisely balanced strengthening of certain axons and pruning of others may cause mental disorders such as autism and schizophrenia. To characterize this balance, we proposed a novel measurement based on cortical parcellation and diffusion MRI (dMRI) tractography, a cortical connectivity maturation index (CCMI). To evaluate the spatiotemporal sensitivity of CCMI as a potential biomarker, dMRI and T1 weighted datasets of 21 healthy subjects 2-25 years were acquired. Brain cortex was parcellated into 68 gyral labels using T1 weighted images, then transformed into dMRI space to serve as the seed region of interest for dMRI-based tractography. Cortico-cortical association fibers initiated from each gyrus were categorized into long- and short-range ones, based on the other end of fiber terminating in non-adjacent or adjacent gyri of the seed gyrus, respectively. The regional CCMI was defined as the ratio between number of short-range association tracts and that of all association tracts traced from one of 68 parcellated gyri. The developmental trajectory of the whole brain CCMI follows a quadratic model with initial decreases from 2 to 16 years followed by later increases after 16 years. Regional CCMI is heterogeneous among different cortical gyri with CCMI dropping to the lowest value earlier in primary somatosensory cortex and visual cortex while later in the prefrontal cortex. The proposed CCMI may serve as sensitive biomarker for brain development under normal or pathological conditions.

  12. Structure and Sequence of the Human Fast Skeletal Troponin T (TNNT3) Gene: Insight Into the Evolution of the Gene and the Origin of the Developmentally Regulated Isoforms

    PubMed Central

    Stefancsik, Raymund; Randall, Jeffrey D.; Mao, Chengjian

    2003-01-01

    We describe the cloning, sequencing and structure of the human fast skeletal troponin T (TNNT3) gene located on chromosome 11p15.5. The single-copy gene encodes 19 exons and 18 introns. Eleven of these exons, 1–3, 9–15 and 18, are constitutively spliced, whereas exons 4–8 are alternatively spliced. The gene contains an additional subset of developmentally regulated and alternatively spliced exons, including a foetal exon located between exon 8 and 9 and exon 16 or α (adult) and 17 or β (foetal and neonatal). Exon phasing suggests that the majority of the alternatively spliced exons located at the 5′ end of the gene may have evolved as a result of exon shuffling, because they are of the same phase class. In contrast, the 3′ exons encoding an evolutionarily conserved heptad repeat domain, shared by both TnT and troponin I (TnI), may be remnants of an ancient ancestral gene. The sequence of the 5′ flanking region shows that the putative promoter contains motifs including binding sites for MyoD, MEF-2 and several transcription factors which may play a role in transcriptional regulation and tissue-specific expression of TnT. The coding region of TNNT3 exhibits strong similarity to the corresponding rat sequence. However, unlike the rat TnT gene, TNNT3 possesses two repeat regions of CCA and TC. The exclusive presence of these repetitive elements in the human gene indicates divergence in the evolutionary dynamics of mammalian TnT genes. Homologous muscle-specific splicing enhancer motifs are present in the introns upstream and downstream of the foetal exon, and may play a role in the developmental pattern of alternative splicing of the gene. The genomic correlates of TNNT3 are relevant to our understanding of the evolution and regulation of expression of the gene, as well as the structure and function of the protein isoforms. The nucleotide sequence of TNNT3 has been submitted to EMBL/GenBank under Accession No. AF026276. PMID:18629027

  13. Non-Verbal Information Storage in Humans and Developmental Information Processing Channel Capacity.

    ERIC Educational Resources Information Center

    Randhawa, Bikkar S.

    This study was designed to ascertain the nature of information storage in humans and to determine the channel capacity of Ss at various stages of development. A 3 x 2 x 2 multivariate complete factorial design was employed: the three levels of the first factor (Age) were 5, 8, and 12 years; the two levels of the second factor were Visual and…

  14. Developmental and Cognitive Perspectives on Humans' Sense of the Times of Past and Future Events

    ERIC Educational Resources Information Center

    Friedman, W.J.

    2005-01-01

    Mental time travel in human adults includes a sense of when past events occurred and future events are expected to occur. Studies with adults and children reveal that a number of distinct psychological processes contribute to a temporally differentiated sense of the past and future. Adults possess representations of multiple time patterns, and…

  15. Testing the relationship between human occupancy in the landscape and tadpole developmental stress.

    PubMed

    Eterovick, Paula C; Bar, Luís F F; Souza, Jorge B; Castro, José F M; Leite, Felipe S F; Alford, Ross A

    2015-01-01

    Amphibian population declines are widespread; the main causal factors are human related and include habitat fragmentation due to agriculture, mining, fires, and urban development. Brazil is the richest country in species of amphibians, and the Brazilian regions with the greatest amphibian diversity are experiencing relatively high rates of habitat destruction, but there are presently relatively few reports of amphibian declines. It is thus important to develop research methods that will detect deterioration in population health before severe declines occur. We tested the use of measurements of fluctuating asymmetry (FA) taken on amphibian larvae to detect anthropogenic stress. We hypothesized that greater human occupancy in the landscape might result in more stressful conditions for amphibians. We conducted this study at the Espinhaço mountain range in southeastern Brazil, using as a model an endemic species (Bokermannohyla saxicola, Hylidae). We chose two tadpole denticle rows and eye-nostril distance as traits for FA measurement. We measured percent cover of human-altered habitats in the landscape around tadpole sampling points and measured FA levels in sampled tadpoles. We found FA levels to differ among localities but found no relationship between human modification of the landscape and tadpole FA levels. Levels of FA in the traits we examined may not be strongly affected by environmental conditions, or may be affected by local variables that were not captured by our landscape-scale measures. Alternatively, populations may be genetically differentiated, affecting how FA levels respond to stress and obscuring the effects of anthropogenic disturbance. PMID:25793699

  16. Developmental Changes in the Discrimination of Dynamic Human Actions in Infancy

    ERIC Educational Resources Information Center

    Loucks, Jeff; Sommerville, Jessica A.

    2012-01-01

    Recent evidence suggests that adults selectively attend to features of action, such as how a hand contacts an object, and less to configural properties of action, such as spatial trajectory, when observing human actions. The current research investigated whether this bias develops in infancy. We utilized a habituation paradigm to assess…

  17. Deletion of the c-kit protooncogene in the human developmental defect piebald trait.

    PubMed

    Fleischman, R A; Saltman, D L; Stastny, V; Zneimer, S

    1991-12-01

    The protooncogene c-kit is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. Homozygous mutations of this gene in the mouse cause anemia, infertility, and albinism, whereas heterozygous mutant mice usually exhibit only a white forehead blaze and depigmentation of the ventral body, tail, and feet. The heterozygous mouse phenotype is very similar to human piebald trait, which is characterized by a congenital white hair forelock and ventral and extremity depigmentation. To investigate the possibility that alterations in the human c-kit gene may be a cause of piebald trait, DNA from seven unrelated affected individuals was examined by Southern blot analysis. One subject, although cytogenetically normal, has a heterozygous deletion of the c-kit protooncogene. This deletion encompasses the entire coding region for c-kit and also involves the closely linked gene for platelet-derived growth factor receptor alpha. Fluorescence in situ hybridization of genomic c-kit probes to metaphase chromosomes independently confirmed the deletion in this case. These findings provide molecular evidence mapping piebald trait to the c-kit locus on chromosome 4. Although we cannot exclude the involvement of other closely linked genes, the demonstration of a genomic c-kit deletion in one subject with piebald trait and the marked concordance of the human and mouse phenotypes provide strong evidence for the role of c-kit in the development of human melanocytes and in the pathogenesis of piebald trait. PMID:1720553

  18. Deletion of the c-kit protooncogene in the human developmental defect piebald trait

    SciTech Connect

    Fleischman, R.A.; Stastny, V.; Zneimer, S. ); Saltman, D.L. )

    1991-12-01

    The protooncogene c-kit is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. Homozygous mutations of this gene in the mouse cause anemia, infertility, and albinism, whereas heterozygous mutant mice usually exhibit only a white forehead blaze and depigmentation of the ventral body, tail, and feet. The heterozygous mouse phenotype is very similar to human piebald trait, which is characterized by a congenital white hair forelock and ventral and extremity depigmentation. To investigate the possibility that alterations in the human c-kit gene may be a cause of piebald trait, DNA from seven unrelated affected individuals was examined by Southern blot analysis. One subject, although cytogenetically normal, has a heterozygous deletion of the c-kit protooncogene. This deletion encompasses the entire coding region for c-kit and also involves the closely linked gene for platelet-derived growth factor receptor {alpha}. These findings provide molecular evidence mapping piebald trait to the c-kit locus on chromosome 4. Although the authors cannot exclude the involvement of other closely linked genes, the demonstration of a genomic c-kit deletion in one subject with piebald trait and the marked concordance of the human and mouse phenotypes provide strong evidence for the role of c-kit in the development of human melanocytes and in the pathogenesis of piebald trait.

  19. Testing the Relationship between Human Occupancy in the Landscape and Tadpole Developmental Stress

    PubMed Central

    Eterovick, Paula C.; Bar, Luís F. F.; Souza, Jorge B.; Castro, José F. M.; Leite, Felipe S. F.; Alford, Ross A.

    2015-01-01

    Amphibian population declines are widespread; the main causal factors are human related and include habitat fragmentation due to agriculture, mining, fires, and urban development. Brazil is the richest country in species of amphibians, and the Brazilian regions with the greatest amphibian diversity are experiencing relatively high rates of habitat destruction, but there are presently relatively few reports of amphibian declines. It is thus important to develop research methods that will detect deterioration in population health before severe declines occur. We tested the use of measurements of fluctuating asymmetry (FA) taken on amphibian larvae to detect anthropogenic stress. We hypothesized that greater human occupancy in the landscape might result in more stressful conditions for amphibians. We conducted this study at the Espinhaço mountain range in southeastern Brazil, using as a model an endemic species (Bokermannohyla saxicola, Hylidae). We chose two tadpole denticle rows and eye-nostril distance as traits for FA measurement. We measured percent cover of human-altered habitats in the landscape around tadpole sampling points and measured FA levels in sampled tadpoles. We found FA levels to differ among localities but found no relationship between human modification of the landscape and tadpole FA levels. Levels of FA in the traits we examined may not be strongly affected by environmental conditions, or may be affected by local variables that were not captured by our landscape-scale measures. Alternatively, populations may be genetically differentiated, affecting how FA levels respond to stress and obscuring the effects of anthropogenic disturbance. PMID:25793699

  20. Gene expression profiles in the cerebellum and hippocampus following exposure to a neurotoxicant, Aroclor 1254: Developmental effects.

    EPA Science Inventory

    The developmental consequences of exposure to the polychlorinated biphenyls (PCBs) have been widely studied, making PCBs a unique model to understand issues related to environmental mixture of persistent chemicals. PCB exposure in humans adversely affects neurocognitive developm...

  1. Developmental Testing of Habitability and Human Factors Tools and Methods During Neemo 15

    NASA Technical Reports Server (NTRS)

    Thaxton, S. S.; Litaker, H. L., Jr.; Holden, K. L.; Adolf, J. A.; Pace, J.; Morency, R. M.

    2011-01-01

    Currently, no established methods exist to collect real-time human factors and habitability data while crewmembers are living aboard the International Space Station (ISS), traveling aboard other space vehicles, or living in remote habitats. Currently, human factors and habitability data regarding space vehicles and habitats are acquired at the end of missions during postflight crew debriefs. These debriefs occur weeks or often longer after events have occurred, which forces a significant reliance on incomplete human memory, which is imperfect. Without a means to collect real-time data, small issues may have a cumulative effect and continue to cause crew frustration and inefficiencies. Without timely and appropriate reporting methodologies, issues may be repeated or lost. TOOL DEVELOPMENT AND EVALUATION: As part of a directed research project (DRP) aiming to develop and validate tools and methods for collecting near real-time human factors and habitability data, a preliminary set of tools and methods was developed. These tools and methods were evaluated during the NASA Extreme Environments Mission Operations (NEEMO) 15 mission in October 2011. Two versions of a software tool were used to collect observational data from NEEMO crewmembers that also used targeted strategies for using video cameras to collect observations. Space habitability observation reporting tool (SHORT) was created based on a tool previously developed by NASA to capture human factors and habitability issues during spaceflight. SHORT uses a web-based interface that allows users to enter a text description of any observations they wish to report and assign a priority level if changes are needed. In addition to the web-based format, a mobile Apple (iOS) format was implemented, referred to as iSHORT. iSHORT allows users to provide text, audio, photograph, and video data to report observations. iSHORT can be deployed on an iPod Touch, iPhone, or iPad; for NEEMO 15, the app was provided on an iPad2.

  2. Developmental dyslexia.

    PubMed

    Peterson, Robin L; Pennington, Bruce F

    2015-01-01

    This review uses a levels-of-analysis framework to summarize the current understanding of developmental dyslexia's etiology, brain bases, neuropsychology, and social context. Dyslexia is caused by multiple genetic and environmental risk factors as well as their interplay. Several candidate genes have been identified in the past decade. At the brain level, dyslexia is associated with aberrant structure and function, particularly in left hemisphere reading/language networks. The neurocognitive influences on dyslexia are also multifactorial and involve phonological processing deficits as well as weaknesses in other oral language skills and processing speed. We address contextual issues such as how dyslexia manifests across languages and social classes as well as what treatments are best supported. Throughout the review, we highlight exciting new research that cuts across levels of analysis. Such work promises eventually to provide a comprehensive explanation of the disorder as well as its prevention and remediation. PMID:25594880

  3. Using Big Data to Understand the Human Condition: The Kavli HUMAN Project

    PubMed Central

    Azmak, Okan; Bayer, Hannah; Caplin, Andrew; Chun, Miyoung; Glimcher, Paul; Koonin, Steven; Patrinos, Aristides

    2015-01-01

    Abstract Until now, most large-scale studies of humans have either focused on very specific domains of inquiry or have relied on between-subjects approaches. While these previous studies have been invaluable for revealing important biological factors in cardiac health or social factors in retirement choices, no single repository contains anything like a complete record of the health, education, genetics, environmental, and lifestyle profiles of a large group of individuals at the within-subject level. This seems critical today because emerging evidence about the dynamic interplay between biology, behavior, and the environment point to a pressing need for just the kind of large-scale, long-term synoptic dataset that does not yet exist at the within-subject level. At the same time that the need for such a dataset is becoming clear, there is also growing evidence that just such a synoptic dataset may now be obtainable—at least at moderate scale—using contemporary big data approaches. To this end, we introduce the Kavli HUMAN Project (KHP), an effort to aggregate data from 2,500 New York City households in all five boroughs (roughly 10,000 individuals) whose biology and behavior will be measured using an unprecedented array of modalities over 20 years. It will also richly measure environmental conditions and events that KHP members experience using a geographic information system database of unparalleled scale, currently under construction in New York. In this manner, KHP will offer both synoptic and granular views of how human health and behavior coevolve over the life cycle and why they evolve differently for different people. In turn, we argue that this will allow for new discovery-based scientific approaches, rooted in big data analytics, to improving the health and quality of human life, particularly in urban contexts. PMID:26487987

  4. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  5. Developmental Screening

    MedlinePlus

    Learn More about Your Child’s Development: Developmental Monitoring and Screening Taking a first step, waving “bye-bye,” and pointing to something interesting are all developmental milestones, ...

  6. Developmental Disabilities

    MedlinePlus

    Developmental disabilities are severe, long-term problems. They may be physical, such as blindness. They may affect mental ability, ... everyday living. There are many causes of developmental disabilities, including Genetic or chromosome abnormalities. These cause conditions ...

  7. Developmental origins of adult diseases.

    PubMed

    Mathew, Vivek; Ayyar, S Vageesh

    2012-07-01

    There is considerable evidence for the fact that early life environment in human beings are associated with future development of various metabolic diseases. Fetal programming and perinatal events appear to exert effects on later life that are independent of environmental risk factors in adults. Our understanding of the underlying mechanisms are limited and remains unclear. However several animal models and epidemiological studies have shown this association, and it is assumed secondary to the penalties of developmental plasticity. In this review, we amalgamate facts from several disciplines to support this hypothesis. PMID:22837912

  8. An automated statistical shape model developmental pipeline: application to the human scapula and humerus.

    PubMed

    Mutsvangwa, Tinashe; Burdin, Valérie; Schwartz, Cédric; Roux, Christian

    2015-04-01

    This paper presents development of statistical shape models based on robust and rigid-groupwise registration followed by pointset nonrigid registration. The main advantages of the pipeline include automation in that the method does not rely on manual landmarks or a regionalization step; there is no bias in the choice of reference during the correspondence steps and the use of the probabilistic principal component analysis framework increases the domain of the shape variability. A comparison between the widely used expectation maximization-iterative closest point algorithm and a recently reported groupwise method on publicly available data (hippocampus) using the well-known criteria of generality, specificity, and compactness is also presented. The proposed method gives similar values but the curves of generality and specificity are superior to those of the other two methods. Finally, the method is applied to the human scapula, which is a known difficult structure, and the human humerus. PMID:25389238

  9. Recent Advances in Understanding the Role of Nutrition in Human Genome Evolution12

    PubMed Central

    Ye, Kaixiong; Gu, Zhenglong

    2011-01-01

    Dietary transitions in human history have been suggested to play important roles in the evolution of mankind. Genetic variations caused by adaptation to diet during human evolution could have important health consequences in current society. The advance of sequencing technologies and the rapid accumulation of genome information provide an unprecedented opportunity to comprehensively characterize genetic variations in human populations and unravel the genetic basis of human evolution. Series of selection detection methods, based on various theoretical models and exploiting different aspects of selection signatures, have been developed. Their applications at the species and population levels have respectively led to the identification of human specific selection events that distinguish human from nonhuman primates and local adaptation events that contribute to human diversity. Scrutiny of candidate genes has revealed paradigms of adaptations to specific nutritional components and genome-wide selection scans have verified the prevalence of diet-related selection events and provided many more candidates awaiting further investigation. Understanding the role of diet in human evolution is fundamental for the development of evidence-based, genome-informed nutritional practices in the era of personal genomics. PMID:22332091

  10. Species-Specific Differential AhR Expression Protects Human Neural Progenitor Cells against Developmental Neurotoxicity of PAHs

    PubMed Central

    Gassmann, Kathrin; Abel, Josef; Bothe, Hanno; Haarmann-Stemmann, Thomas; Merk, Hans F.; Quasthoff, Kim N.; Rockel, Thomas Dino; Schreiber, Timm; Fritsche, Ellen

    2010-01-01

    Background Because of their lipophilicity, persistent organic pollutants (POPs) cross the human placenta, possibly affecting central nervous system development. Most POPs are known aryl hydrocarbon receptor (AhR) ligands and activators of AhR signaling. Therefore, AhR activation has been suggested to cause developmental neurotoxicity (DNT). Objective We studied the effects of AhR ligands on basic processes of brain development in two comparative in vitro systems to determine whether AhR-activation is the underlying mechanism for reported DNT of POPs in humans. Methods We employed neurosphere cultures based on human neural progenitor cells (hNPCs) and wild-type and AhR-deficient mouse NPCs (mNPCs) and studied the effects of different AhR agonists [3-methylcholanthrene (3-MC), benzo(a)pyrene [B(a)P], and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] and an antagonist [3′-methoxy-4′-nitroflavone (MNF)] on neurosphere development. Moreover, we analyzed expression of AhR and genes involved in AhR signaling. Results In contrast to wild-type mNPCs, hNPCs and AhR-deficient mNPCs were insensitive to AhR agonism or antagonism. Although AhR modulation attenuated wild-type mNPC proliferation and migration, hNPCs and AhR-deficient mNPCs remained unaffected. Results also suggest that species-specific differences resulted from nonfunctional AhR signaling in hNPCs. Conclusion Our findings suggest that in contrast to wild-type mNPCs, hNPCs were protected against polycyclic aromatic hydrocarbon–induced DNT because of an absence of AhR. This difference may contribute to species-specific differences in sensitivity to POPs. PMID:20570779

  11. From Caenorhabditis elegans to the human connectome: a specific modular organization increases metabolic, functional and developmental efficiency

    PubMed Central

    Kim, Jinseop S.; Kaiser, Marcus

    2014-01-01

    The connectome, or the entire connectivity of a neural system represented by a network, ranges across various scales from synaptic connections between individual neurons to fibre tract connections between brain regions. Although the modularity they commonly show has been extensively studied, it is unclear whether the connection specificity of such networks can already be fully explained by the modularity alone. To answer this question, we study two networks, the neuronal network of Caenorhabditis elegans and the fibre tract network of human brains obtained through diffusion spectrum imaging. We compare them to their respective benchmark networks with varying modularities, which are generated by link swapping to have desired modularity values. We find several network properties that are specific to the neural networks and cannot be fully explained by the modularity alone. First, the clustering coefficient and the characteristic path length of both C. elegans and human connectomes are higher than those of the benchmark networks with similar modularity. High clustering coefficient indicates efficient local information distribution, and high characteristic path length suggests reduced global integration. Second, the total wiring length is smaller than for the alternative configurations with similar modularity. This is due to lower dispersion of connections, which means each neuron in the C. elegans connectome or each region of interest in the human connectome reaches fewer ganglia or cortical areas, respectively. Third, both neural networks show lower algorithmic entropy compared with the alternative arrangements. This implies that fewer genes are needed to encode for the organization of neural systems. While the first two findings show that the neural topologies are efficient in information processing, this suggests that they are also efficient from a developmental point of view. Together, these results show that neural systems are organized in such a way as to yield

  12. Are animal models useful or confusing in understanding the human feto-maternal relationship? A debate.

    PubMed

    Chaouat, Gérard; Clark, David A

    2015-04-01

    The proposition "This house agrees that the proper study of man is woman" was debated. For those negating the proposition, the alternative was that "animal models are useful in understanding the human feto-maternal relationship." Evidence for the proposition emphasized molecular and structural differences between the human and animal placenta and placentation. Evidence against the proposition and in favor of the alternative focused on functional and structural homologies, emphasizing that different molecules could be used in humans to achieve similar functional effects seen in animal (e.g., mouse) models. It was agreed that one always needed to test the validity of animal data by studying humans. The advantages and limitations of animal models were discussed. PMID:25534633

  13. Developmental Exposure to Estrogen Alters Differentiation and Epigenetic Programming in a Human Fetal Prostate Xenograft Model

    PubMed Central

    Saffarini, Camelia M.; McDonnell-Clark, Elizabeth V.; Amin, Ali; Huse, Susan M.; Boekelheide, Kim

    2015-01-01

    Prostate cancer is the most frequent non-cutaneous malignancy in men. There is strong evidence in rodents that neonatal estrogen exposure plays a role in the development of this disease. However, there is little information regarding the effects of estrogen in human fetal prostate tissue. This study explored early life estrogen exposure, with and without a secondary estrogen and testosterone treatment in a human fetal prostate xenograft model. Histopathological lesions, proliferation, and serum hormone levels were evaluated at 7, 30, 90, and 200-day time-points after xenografting. The expression of 40 key genes involved in prostatic glandular and stromal growth, cell-cycle progression, apoptosis, hormone receptors and tumor suppressors was evaluated using a custom PCR array. Epigenome-wide analysis of DNA methylation was performed on whole tissue, and laser capture-microdissection (LCM) isolated epithelial and stromal compartments of 200-day prostate xenografts. Combined initial plus secondary estrogenic exposures had the most severe tissue changes as revealed by the presence of hyperplastic glands at day 200. Gene expression changes corresponded with the cellular events in the KEGG prostate cancer pathway, indicating that initial plus secondary exposure to estrogen altered the PI3K-Akt signaling pathway, ultimately resulting in apoptosis inhibition and an increase in cell cycle progression. DNA methylation revealed that differentially methylated CpG sites significantly predominate in the stromal compartment as a result of estrogen-treatment, thereby providing new targets for future investigation. By using human fetal prostate tissue and eliminating the need for species extrapolation, this study provides novel insights into the gene expression and epigenetic effects related to prostate carcinogenesis following early life estrogen exposure. PMID:25799167

  14. Toward an understanding of the protein interaction network of the human liver

    PubMed Central

    Wang, Jian; Huo, Keke; Ma, Lixin; Tang, Liujun; Li, Dong; Huang, Xiaobi; Yuan, Yanzhi; Li, Chunhua; Wang, Wei; Guan, Wei; Chen, Hui; Jin, Chaozhi; Wei, Junchen; Zhang, Wanqiao; Yang, Yongsheng; Liu, Qiongming; Zhou, Ying; Zhang, Cuili; Wu, Zhihao; Xu, Wangxiang; Zhang, Ying; Liu, Tao; Yu, Donghui; Zhang, Yaping; Chen, Liang; Zhu, Dewu; Zhong, Xing; Kang, Lixin; Gan, Xiang; Yu, Xiaolan; Ma, Qi; Yan, Jing; Zhou, Li; Liu, Zhongyang; Zhu, Yunping; Zhou, Tao; He, Fuchu; Yang, Xiaoming

    2011-01-01

    Proteome-scale protein interaction maps are available for many organisms, ranging from bacteria, yeast, worms and flies to humans. These maps provide substantial new insights into systems biology, disease research and drug discovery. However, only a small fraction of the total number of human protein–protein interactions has been identified. In this study, we map the interactions of an unbiased selection of 5026 human liver expression proteins by yeast two-hybrid technology and establish a human liver protein interaction network (HLPN) composed of 3484 interactions among 2582 proteins. The data set has a validation rate of over 72% as determined by three independent biochemical or cellular assays. The network includes metabolic enzymes and liver-specific, liver-phenotype and liver-disease proteins that are individually critical for the maintenance of liver functions. The liver enriched proteins had significantly different topological properties and increased our understanding of the functional relationships among proteins in a liver-specific manner. Our data represent the first comprehensive description of a HLPN, which could be a valuable tool for understanding the functioning of the protein interaction network of the human liver. PMID:21988832

  15. Gut microbiota: next frontier in understanding human health and development of biotherapeutics

    PubMed Central

    Prakash, Satya; Rodes, Laetitia; Coussa-Charley, Michael; Tomaro-Duchesneau, Catherine

    2011-01-01

    The gut microbiota is a remarkable asset for human health. As a key element in the development and prevention of specific diseases, its study has yielded a new field of promising biotherapeutics. This review provides comprehensive and updated knowledge of the human gut microbiota, its implications in health and disease, and the potentials and limitations of its modification by currently available biotherapeutics to treat, prevent and/or restore human health, and future directions. Homeostasis of the gut microbiota maintains various functions which are vital to the maintenance of human health. Disruption of the intestinal ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human diseases, including autoimmune and allergic diseases, colorectal cancer, metabolic diseases, and bacterial infections. Relevant underlying mechanisms by which specific intestinal bacteria populations might trigger the development of disease in susceptible hosts are being explored across the globe. Beneficial modulation of the gut microbiota using biotherapeutics, such as prebiotics, probiotics, and antibiotics, may favor health-promoting populations of bacteria and can be exploited in development of biotherapeutics. Other technologies, such as development of human gut models, bacterial screening, and delivery formulations eg, microencapsulated probiotics, may contribute significantly in the near future. Therefore, the human gut microbiota is a legitimate therapeutic target to treat and/or prevent various diseases. Development of a clear understanding of the technologies needed to exploit the gut microbiota is urgently required. PMID:21847343

  16. Understanding Substrate Selectivity of Human UDP-glucuronosyltransferases through QSAR modeling and analysis of homologous enzymes

    PubMed Central

    Dong, Dong; Ako, Roland; Hu, Ming; Wu, Baojian

    2015-01-01

    The UDP-glucuronosyltransferase (UGT) enzyme catalyzes the glucuronidation reaction which is a major metabolic and detoxification pathway in humans. Understanding the mechanisms for substrate recognition by UGT assumes great importance in an attempt to predict its contribution to xenobiotic/drug disposition in vivo. Spurred on by this interest, 2D/3D-quantitative structure activity relationships (QSAR) and pharmacophore models have been established in the absence of a complete mammalian UGT crystal structure. This review discusses the recent progress in modeling human UGT substrates including those with multiple sites of glucuronidation. A better understanding of UGT active site contributing to substrate selectivity (and regioselectivity) from the homologous enzymes (i.e., plant and bacterial UGTs, all belong to family 1 of glycosyltransferase (GT1)) is also highlighted, as these enzymes share a common catalytic mechanism and/or overlapping substrate selectivity. PMID:22385482

  17. Genetic and Developmental Perspective of Language Abnormality in Autism and Schizophrenia: One Disease Occurring at Different Ages in Humans?

    PubMed

    Wang, Haoran George; Jeffries, Joseph Joel; Wang, Tianren Frank

    2016-04-01

    Language and communication through it are two of the defining features of normally developed human beings. However, both these functions are often impaired in autism and schizophrenia. In the former disorder, the problem usually emerges in early childhood (~2 years old) and typically includes a lack of communication. In the latter condition, the language problems usually occur in adolescence and adulthood and presents as disorganized speech. What are the fundamental mechanisms underlying these two disorders? Is there a shared genetic basis? Are the traditional beliefs about them true? Are there any common strategies for their prevention and management? To answer these questions, we searched PubMed by using autism, schizophrenia, gene, and language abnormality as keywords, and we reconsidered the basic concepts about these two diseases or syndromes. We found many functional genes, for example, FOXP2, COMT, GABRB3, and DISC1, are actually implicated in both of them. After observing the symptoms, genetic correlates, and temporal progression of these two disorders as well as their relationships more carefully, we now infer that the occurrence of these two diseases is likely developmentally regulated via interaction between the genome and the environment. Furthermore, we propose a unified view of autism and schizophrenia: a single age-dependently occurred disease that is newly named as Systemic Integral Disorder: if occurring in children before age 2, it is called autism; if in adolescence or a later age, it is called schizophrenia. PMID:25686622

  18. Developmental insights from early mammalian embryos and core signaling pathways that influence human pluripotent cell growth and differentiation

    PubMed Central

    Chen, Kevin G.; Mallon, Barbara S.; Johnson, Kory R.; Hamilton, Rebecca S.; McKay, Ronald D.G.; Robey, Pamela G.

    2014-01-01

    Human pluripotent stem cells (hPSCs) have two potentially attractive applications: cell replacement-based therapies and drug discovery. Both require the efficient generation of large quantities of clinical-grade stem cells that are free from harmful genomic alterations. The currently employed colony-type culture methods often result in low cell yields, unavoidably heterogeneous cell populations, and substantial chromosomal abnormalities. Here, we shed light on the structural relationship between hPSC colonies/embryoid bodies and early-stage embryos in order to optimize current culture methods based on the insights from developmental biology. We further highlight core signaling pathways that underlie multiple epithelial-to-mesenchymal transitions (EMTs), cellular heterogeneity, and chromosomal instability in hPSCs. We also analyze emerging methods such as non-colony type monolayer (NCM) and suspension culture, which provide alternative growth models for hPSC expansion and differentiation. Furthermore, based on the influence of cell-cell interactions and signaling pathways, we propose concepts, strategies, and solutions for production of clinical-grade hPSCs, stem cell precursors, and miniorganoids, which are pivotal steps needed for future clinical applications. PMID:24603366

  19. Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization

    PubMed Central

    Yanez, Livia Z.; Han, Jinnuo; Behr, Barry B.; Pera, Renee A. Reijo; Camarillo, David B.

    2016-01-01

    The causes of embryonic arrest during pre-implantation development are poorly understood. Attempts to correlate patterns of oocyte gene expression with successful embryo development have been hampered by the lack of reliable and nondestructive predictors of viability at such an early stage. Here we report that zygote viscoelastic properties can predict blastocyst formation in humans and mice within hours after fertilization, with >90% precision, 95% specificity and 75% sensitivity. We demonstrate that there are significant differences between the transcriptomes of viable and non-viable zygotes, especially in expression of genes important for oocyte maturation. In addition, we show that low-quality oocytes may undergo insufficient cortical granule release and zona-hardening, causing altered mechanics after fertilization. Our results suggest that embryo potential is largely determined by the quality and maturation of the oocyte before fertilization, and can be predicted through a minimally invasive mechanical measurement at the zygote stage. PMID:26904963

  20. Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization.

    PubMed

    Yanez, Livia Z; Han, Jinnuo; Behr, Barry B; Reijo Pera, Renee A; Camarillo, David B

    2016-01-01

    The causes of embryonic arrest during pre-implantation development are poorly understood. Attempts to correlate patterns of oocyte gene expression with successful embryo development have been hampered by the lack of reliable and nondestructive predictors of viability at such an early stage. Here we report that zygote viscoelastic properties can predict blastocyst formation in humans and mice within hours after fertilization, with >90% precision, 95% specificity and 75% sensitivity. We demonstrate that there are significant differences between the transcriptomes of viable and non-viable zygotes, especially in expression of genes important for oocyte maturation. In addition, we show that low-quality oocytes may undergo insufficient cortical granule release and zona-hardening, causing altered mechanics after fertilization. Our results suggest that embryo potential is largely determined by the quality and maturation of the oocyte before fertilization, and can be predicted through a minimally invasive mechanical measurement at the zygote stage. PMID:26904963

  1. Developmental effects of endocrine-disrupting chemicals in wildlife and humans.

    PubMed Central

    Colborn, T; vom Saal, F S; Soto, A M

    1993-01-01

    Large numbers and large quantities of endocrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, transgenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistence of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans. PMID:8080506

  2. Developmental effects of endocrine-disrupting chemicals in wildlife and humans

    SciTech Connect

    Colborn, T. ); vom Saal, F.S. ); Soto, A.M. )

    1993-10-01

    Large numbers and large quantities of endoncrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, trangenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistent of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans.

  3. Developmental changes of BOLD signal correlations with global human EEG power and synchronization during working memory.

    PubMed

    Michels, Lars; Lüchinger, Rafael; Koenig, Thomas; Martin, Ernst; Brandeis, Daniel

    2012-01-01

    In humans, theta band (5-7 Hz) power typically increases when performing cognitively demanding working memory (WM) tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent) signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-)dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was--in contrast to EEG power--positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and synchronization and that

  4. Instead of Erklären and Verstehen: William James on Human Understanding

    NASA Astrophysics Data System (ADS)

    Leary, David E.

    Perhaps more than any other American psychologist and philosopher, William James (1842-1910) was intimately familiar with contemporary European thought and debate, including the discussion of Erklären and Verstehen advanced by Wilhelm Dilthey (1833-1911) and others around the turn of the twentieth century. Even before this discussion was initiated, James had been dealing with related issues, pondering alternative solutions, and formulating his own original views on human understanding. These views coalesced in a distinctive approach to cognition. Fundamental to this approach was a belief in possibility and probability as innate features of the physical as well as mental manifestations of the universe. Also fundamental was a conviction that understanding is understanding, regardless of its viewpoint, object, or label as either "descriptive" or "explanatory."

  5. Prediction of developmental chemical toxicity based on gene networks of human embryonic stem cells

    PubMed Central

    Yamane, Junko; Aburatani, Sachiyo; Imanishi, Satoshi; Akanuma, Hiromi; Nagano, Reiko; Kato, Tsuyoshi; Sone, Hideko; Ohsako, Seiichiroh; Fujibuchi, Wataru

    2016-01-01

    Predictive toxicology using stem cells or their derived tissues has gained increasing importance in biomedical and pharmaceutical research. Here, we show that toxicity category prediction by support vector machines (SVMs), which uses qRT-PCR data from 20 categorized chemicals based on a human embryonic stem cell (hESC) system, is improved by the adoption of gene networks, in which network edge weights are added as feature vectors when noisy qRT-PCR data fail to make accurate predictions. The accuracies of our system were 97.5–100% for three toxicity categories: neurotoxins (NTs), genotoxic carcinogens (GCs) and non-genotoxic carcinogens (NGCs). For two uncategorized chemicals, bisphenol-A and permethrin, our system yielded reasonable results: bisphenol-A was categorized as an NGC, and permethrin was categorized as an NT; both predictions were supported by recently published papers. Our study has two important features: (i) as the first study to employ gene networks without using conventional quantitative structure-activity relationships (QSARs) as input data for SVMs to analyze toxicogenomics data in an hESC validation system, it uses additional information of gene-to-gene interactions to significantly increase prediction accuracies for noisy gene expression data; and (ii) using only undifferentiated hESCs, our study has considerable potential to predict late-onset chemical toxicities, including abnormalities that occur during embryonic development. PMID:27207879

  6. The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis.

    PubMed

    Cimadomo, Danilo; Capalbo, Antonio; Ubaldi, Filippo Maria; Scarica, Catello; Palagiano, Antonio; Canipari, Rita; Rienzi, Laura

    2016-01-01

    Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential. PMID:26942198

  7. The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis

    PubMed Central

    Cimadomo, Danilo; Capalbo, Antonio; Ubaldi, Filippo Maria; Scarica, Catello; Palagiano, Antonio; Canipari, Rita; Rienzi, Laura

    2016-01-01

    Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential. PMID:26942198

  8. Early developmental emergence of human amygdala–prefrontal connectivity after maternal deprivation

    PubMed Central

    Gee, Dylan G.; Gabard-Durnam, Laurel J.; Flannery, Jessica; Goff, Bonnie; Humphreys, Kathryn L.; Telzer, Eva H.; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim

    2013-01-01

    Under typical conditions, medial prefrontal cortex (mPFC) connections with the amygdala are immature during childhood and become adult-like during adolescence. Rodent models show that maternal deprivation accelerates this development, prompting examination of human amygdala–mPFC phenotypes following maternal deprivation. Previously institutionalized youths, who experienced early maternal deprivation, exhibited atypical amygdala–mPFC connectivity. Specifically, unlike the immature connectivity (positive amygdala–mPFC coupling) of comparison children, children with a history of early adversity evidenced mature connectivity (negative amygdala–mPFC coupling) and thus, resembled the adolescent phenotype. This connectivity pattern was mediated by the hormone cortisol, suggesting that stress-induced modifications of the hypothalamic–pituitary–adrenal axis shape amygdala–mPFC circuitry. Despite being age-atypical, negative amygdala–mPFC coupling conferred some degree of reduced anxiety, although anxiety was still significantly higher in the previously institutionalized group. These findings suggest that accelerated amygdala–mPFC development is an ontogenetic adaptation in response to early adversity. PMID:24019460

  9. Prediction of developmental chemical toxicity based on gene networks of human embryonic stem cells.

    PubMed

    Yamane, Junko; Aburatani, Sachiyo; Imanishi, Satoshi; Akanuma, Hiromi; Nagano, Reiko; Kato, Tsuyoshi; Sone, Hideko; Ohsako, Seiichiroh; Fujibuchi, Wataru

    2016-07-01

    Predictive toxicology using stem cells or their derived tissues has gained increasing importance in biomedical and pharmaceutical research. Here, we show that toxicity category prediction by support vector machines (SVMs), which uses qRT-PCR data from 20 categorized chemicals based on a human embryonic stem cell (hESC) system, is improved by the adoption of gene networks, in which network edge weights are added as feature vectors when noisy qRT-PCR data fail to make accurate predictions. The accuracies of our system were 97.5-100% for three toxicity categories: neurotoxins (NTs), genotoxic carcinogens (GCs) and non-genotoxic carcinogens (NGCs). For two uncategorized chemicals, bisphenol-A and permethrin, our system yielded reasonable results: bisphenol-A was categorized as an NGC, and permethrin was categorized as an NT; both predictions were supported by recently published papers. Our study has two important features: (i) as the first study to employ gene networks without using conventional quantitative structure-activity relationships (QSARs) as input data for SVMs to analyze toxicogenomics data in an hESC validation system, it uses additional information of gene-to-gene interactions to significantly increase prediction accuracies for noisy gene expression data; and (ii) using only undifferentiated hESCs, our study has considerable potential to predict late-onset chemical toxicities, including abnormalities that occur during embryonic development. PMID:27207879

  10. Developmental neurotoxicity of ortho-phthalate diesters: review of human and experimental evidence.

    PubMed

    Miodovnik, Amir; Edwards, Andrea; Bellinger, David C; Hauser, Russ

    2014-03-01

    Ortho-phthalate diesters, or phthalates, are widely used synthetic chemicals found primarily in consumer products and polyvinyl chloride plastics. Experimental evidence suggests that several phthalates possess antiandrogenic properties and may disrupt endocrine pathways resulting in abnormal reproductive outcomes. Low-level exposure to phthalates has been well documented in humans, with higher levels found in children and women of childbearing age. Recent epidemiologic studies postulate that prenatal exposure to measurable urine phthalate concentrations may be associated with altered genital and pubertal development in infants and children. This review addresses the emerging evidence that some phthalates may have an adverse impact on the developing brain. The supporting animal studies and proposed mechanisms underlying the deleterious properties of phthalates in relation to neurodevelopmental outcomes are also discussed. While the observed associations are based on limited studies with a broad range of endpoints, the implications of such outcomes are of concern from a public health standpoint and merit further investigation given the widespread nature of the exposure. PMID:24486776

  11. Understanding specificity in metabolic pathways-Structural biology of human nucleotide metabolism

    SciTech Connect

    Welin, Martin; Nordlund, Paer

    2010-05-21

    Interactions are the foundation of life at the molecular level. In the plethora of activities in the cell, the evolution of enzyme specificity requires the balancing of appropriate substrate affinity with a negative selection, in order to minimize interactions with other potential substrates in the cell. To understand the structural basis for enzyme specificity, the comparison of structural and biochemical data between enzymes within pathways using similar substrates and effectors is valuable. Nucleotide metabolism is one of the largest metabolic pathways in the human cell and is of outstanding therapeutic importance since it activates and catabolises nucleoside based anti-proliferative drugs and serves as a direct target for anti-proliferative drugs. In recent years the structural coverage of the enzymes involved in human nucleotide metabolism has been dramatically improved and is approaching completion. An important factor has been the contribution from the Structural Genomics Consortium (SGC) at Karolinska Institutet, which recently has solved 33 novel structures of enzymes and enzyme domains in human nucleotide metabolism pathways and homologs thereof. In this review we will discuss some of the principles for substrate specificity of enzymes in human nucleotide metabolism illustrated by a selected set of enzyme families where a detailed understanding of the structural determinants for specificity is now emerging.

  12. Three-Dimensional Human Skin Models to Understand Staphylococcus aureus Skin Colonization and Infection

    PubMed Central

    Popov, Lauren; Kovalski, Joanna; Grandi, Guido; Bagnoli, Fabio; Amieva, Manuel R.

    2014-01-01

    Staphylococcus aureus is both a major bacterial pathogen as well as a common member of the human skin microbiota. Due to its widespread prevalence as an asymptomatic skin colonizer and its importance as a source of skin and soft tissue infections, an improved understanding of how S. aureus attaches to, grows within, and breaches the stratified layers of the epidermis is of critical importance. Three-dimensional organotypic human skin culture models are informative and tractable experimental systems for future investigations of the interactions between S. aureus and the multi-faceted skin tissue. We propose that S. aureus virulence factors, primarily appreciated for their role in pathogenesis of invasive infections, play alternative roles in promoting asymptomatic bacterial growth within the skin. Experimental manipulations of these cultures will provide insight into the many poorly understood molecular interactions occurring at the interface between S. aureus and stratified human skin tissue. PMID:24567733

  13. Three-Dimensional Human Skin Models to Understand Staphylococcus aureus Skin Colonization and Infection.

    PubMed

    Popov, Lauren; Kovalski, Joanna; Grandi, Guido; Bagnoli, Fabio; Amieva, Manuel R

    2014-01-01

    Staphylococcus aureus is both a major bacterial pathogen as well as a common member of the human skin microbiota. Due to its widespread prevalence as an asymptomatic skin colonizer and its importance as a source of skin and soft tissue infections, an improved understanding of how S. aureus attaches to, grows within, and breaches the stratified layers of the epidermis is of critical importance. Three-dimensional organotypic human skin culture models are informative and tractable experimental systems for future investigations of the interactions between S. aureus and the multi-faceted skin tissue. We propose that S. aureus virulence factors, primarily appreciated for their role in pathogenesis of invasive infections, play alternative roles in promoting asymptomatic bacterial growth within the skin. Experimental manipulations of these cultures will provide insight into the many poorly understood molecular interactions occurring at the interface between S. aureus and stratified human skin tissue. PMID:24567733

  14. The Ecological and Developmental Role of Recovery High Schools

    ERIC Educational Resources Information Center

    Finch, Andrew J.; Frieden, Gina

    2014-01-01

    Recovery high schools are secondary schools designed specifically for students recovering from substance use or co-occurring disorders. Studies have affirmed the chronic nature of substance use disorders and the developmental value of social supports for adolescents. As part of understanding human growth and development, training programs for…

  15. The search for biomarkers of human embryo developmental potential in IVF: a comprehensive proteomic approach.

    PubMed

    Nyalwidhe, Julius; Burch, Tanya; Bocca, Silvina; Cazares, Lisa; Green-Mitchell, Shamina; Cooke, Marissa; Birdsall, Paige; Basu, Gaurav; Semmes, O John; Oehninger, Sergio

    2013-04-01

    The objective of these studies was to identify differentially expressed peptides/proteins in the culture media of embryos grown during in vitro fertilization (IVF) treatment to establish their value as biomarkers predictive of implantation potential and live birth. Micro-droplets of embryo culture media from IVF patients (conditioned) and control media maintained under identical culture conditions were collected and frozen at -80°C on Days 2-3 of in vitro development prior to analysis. The embryos were transferred on Day 3. The peptides were affinity purified based on their physico-chemical properties and profiled by mass spectrometry for differential expression. The identified proteins were further characterized by western blot and ELISA, and absolute quantification was achieved by multiple reaction monitoring (MRM). We identified up to 14 differentially regulated peptides after capture using paramagnetic beads with different affinities. These differentially expressed peptides were used to generate genetic algorithms (GAs) with a recognition capability of 71-84% for embryo transfer cycles resulting in pregnancy and 75-89% for those with failed implantation. Several peptides were further identified as fragments of Apolipoprotein A-1, which showed consistent and significantly reduced expression in the embryo media samples from embryo transfer cycles resulting in viable pregnancies. Western blot and ELISA, as well as quantitative MRM results, were confirmatory. These results demonstrated that peptide/protein profiles from the culture medium during early human in vitro development can discriminate embryos with highest and lowest implantation competence following uterine transfer. Further prospective studies are needed to establish validated thresholds for clinical application. PMID:23247814

  16. Developmental changes in expression of contractile and cytoskeletal proteins in human aortic smooth muscle.

    PubMed

    Glukhova, M A; Frid, M G; Koteliansky, V E

    1990-08-01

    To describe phenotypic changes of human aortic smooth muscle cells (SMCs), proportion of smooth muscle and nonmuscle variants of actin, myosin heavy chains (MHCs), vinculin, and caldesmon, during prenatal and several months of postnatal development was determined. In aortic SMCs from 9-10-week-old fetus, both nonmuscle and smooth muscle-specific variants of all four proteins were present, however, the nonmuscle forms were more abundant. During development, a shift towards the expression of muscle-specific variants was observed, although the time course of changes in protein variant content was not similar for all the proteins studied. By the 24th week of gestation, fractional content of alpha-smooth muscle actin and smooth muscle MHCs was rather close to that in the mature SMCs, and comprised approximately 80 and 90%, respectively, of the levels characteristic of SMCs from adult aortic media. On the contrary, fractional ratio of meta-vinculin and 150-kDa caldesmon was still rather low in the aorta from the 24-week-old fetus, did not increase in a 2-month-old child aorta, and did not reach the level characteristic of mature SMCs even in the 6-month-old child aorta. Thus changes in alpha-smooth muscle actin and smooth muscle MHC fractional content occur mainly during the prenatal period of development, before the 24th week of gestation; while meta-vinculin and the 150-kDa caldesmon proportion increases mainly in the postnatal period, during several months after birth. In the "Discussion," phenotypes of SMCs from developing aorta were compared to those from different layers of the adult aortic wall. PMID:2376586

  17. The domain of developmental psychopathology.

    PubMed

    Sroufe, L A; Rutter, M

    1984-02-01

    It is the "developmental" component of developmental psychopathology that distinguishes this discipline from abnormal psychology, psychiatry, and even clinical child psychology. At the same time, the focus on individual patterns of adaptation and maladaptation distinguishes this field from the larger discipline of developmental psychology. In this essay a developmental perspective is presented, and the implications of this perspective for research in developmental psychopathology are discussed. A primary consideration is the complexity of the adaptational process, with developmental transformation being the rule. Thus, links between earlier adaptation and later pathology generally will not be simple or direct. It will be necessary to understand both individual patterns of adaptation with respect to salient issues of a given developmental period and the transaction between prior adaptation, maturational change, and subsequent environmental challenges. Some examples are discussed, with special attention to the case of depression. PMID:6705619

  18. Understanding the interplay of individual and social-developmental factors in the progression of substance use and mental health from childhood to adulthood.

    PubMed

    Jones, Tiffany M; Hill, Karl G; Epstein, Marina; Lee, Jungeun Olivia; Hawkins, J David; Catalano, Richard F

    2016-08-01

    This study examines the interplay between individual and social-developmental factors in the development of positive functioning, substance use problems, and mental health problems. This interplay is nested within positive and negative developmental cascades that span childhood, adolescence, the transition to adulthood, and adulthood. Data are drawn from the Seattle Social Development Project, a gender-balanced, ethnically diverse community sample of 808 participants interviewed 12 times from ages 10 to 33. Path modeling showed short- and long-term cascading effects of positive social environments, family history of depression, and substance-using social environments throughout development. Positive family social environments set a template for future partner social environment interaction and had positive influences on proximal individual functioning, both in the next developmental period and long term. Family history of depression adversely affected mental health functioning throughout adulthood. Family substance use began a cascade of substance-specific social environments across development, which was the pathway through which increasing severity of substance use problems flowed. The model also indicated that adolescent, but not adult, individual functioning influenced selection into positive social environments, and significant cross-domain effects were found in which substance-using social environments affected subsequent mental health. PMID:27427802

  19. Understanding the Interplay of Individual and Social-Developmental Factors in the Progression of Substance Use and Mental Health from Childhood to Adulthood

    PubMed Central

    Jones, Tiffany M.; Hill, Karl G.; Epstein, Marina; Lee, Jungeun Olivia; Hawkins, J. David; Catalano, Richard F.

    2016-01-01

    This study examines the interplay between individual and social-developmental factors in the development of positive functioning, substance use problems, and mental health problems. This interplay is nested within positive and negative developmental cascades that span childhood, adolescence, the transition to adulthood, and adulthood. Data are drawn from the Seattle Social Development Project, a gender-balanced, ethnically diverse community sample of 808 participants interviewed 12 times from ages 10 to 33. Path modeling showed short- and long-term cascading effects of positive social environments, family history of depression, and substance using social environments throughout development. Positive family social environments set a template for future partner social environment interaction and had positive influences on proximal individual functioning, both in the next developmental period and long term. Family history of depression adversely affected mental health functioning throughout adulthood. Family substance use began a cascade of substance-specific social environments across development, which was the pathway through which increasing severity of substance use problems flowed. The model also indicated that adolescent, but not adult, individual functioning influenced selection into positive social environments, and significant cross-domain effects were found in which substance using social environments affected subsequent mental health. PMID:27427802

  20. ASSESSMENT OF LITHIUM USING THE IEHR EVALUATIVE PROCESS FOR ASSESSING HUMAN DEVELOPMENTAL AND REPRODUCTIVE TOXICITY OF AGENTS

    EPA Science Inventory

    This document presents an evaluation of the reproductive and developmental effects of lithium and reviews toxicologic information on several specific lithium salts: ithium carbonate, lithium chloride, lithium citrate, and lithium hypochlorite. ithium (Li), an alkali metal, is a n...

  1. Understanding Challenges in the Front Lines of Home Health Care: A Human-Systems Approach

    PubMed Central

    Beer, Jenay M.; McBride, Sara E.; Mitzner, Tracy L.; Rogers, Wendy A.

    2014-01-01

    A human-systems perspective is a fruitful approach to understanding home health care because it emphasizes major individual components of the system – persons, equipment/technology, tasks, and environments –as well as the interaction between these components. The goal of this research was to apply a human-system perspective to consider the capabilities and limitations of the persons, in relation to the demands of the tasks and equipment/technology in home health care. Identification of challenges and mismatches between the person(s) capabilities and the demands of providing care provide guidance for human factors interventions. A qualitative study was conducted with 8 home health Certified Nursing Assistants and 8 home health Registered Nurses interviewed about challenges they encounter in their jobs. A systematic categorization of the challenges the care providers reported was conducted and human factors recommendations were proposed in response, to improve home health. The challenges inform a human-systems model of home health care. PMID:24958610

  2. A breakdown in communication? Understanding the effects of aging on the human small intestine epithelium

    PubMed Central

    2015-01-01

    In the intestine, a single layer of epithelial cells sealed together at their apical surfaces by tight junctions helps to prevent the luminal commensal and pathogenic micro-organisms and their toxins from entering host tissues. The intestinal epithelium also helps to maintain homoeostasis in the mucosal immune system by expressing anti-inflammatory cytokines in the steady state and inflammatory cytokines in response to pathogens. Although the function of the mucosal immune system is impaired in elderly humans, the molecular mechanisms which cause this dramatic functional decline are poorly understood. Our current understanding of the effects of aging on the physical and immunological properties of the intestinal epithelial barrier is also very limited. In this issue of Clinical Science, Man et al. provide further insight into the effects of aging on small intestinal barrier function in humans and the influence that gut luminal micro-organisms may have on it. Using human terminal ileal biopsy tissues they show that intestinal permeability to solutes, but not macromolecules, was significantly increased in the intestines of elderly humans. This was accompanied by elevated expression of the pro-inflammatory cytokine interleukin (IL)-6 which appeared to modulate claudin-2 expression and solute permeability in the epithelium. Conversely, IL-8 synthesis in response to flagellin stimulation was reduced in intestines of the elderly subjects, but was not associated with effects on Toll-like receptor 5 (TLR5) expression. These data provide an important advance in our understanding on the effects of aging on intestinal permeability and innate mucosal immune responsiveness in elderly humans. PMID:26186738

  3. Human behavior understanding for assisted living by means of hierarchical context free grammars

    NASA Astrophysics Data System (ADS)

    Rosani, A.; Conci, N.; De Natale, F. G. B.

    2014-03-01

    Human behavior understanding has attracted the attention of researchers in various fields over the last years. Recognizing behaviors with sufficient accuracy from sensors analysis is still an unsolved problem, because of many reasons, including the low accuracy of the data, differences in the human behaviors as well as the gap between low-level sensors data and high-level scene semantics. In this context, an application that is attracting the interest of both public and industrial entities is the possibility to allow elderly or physically impaired people conducting a normal life at home. Ambient intelligence (AmI) technologies, intended as the possibility of automatically detecting and reacting to the status of the environment and of the persons, is probably the major enabling factor for the achievement of such an ambitious objective. AmI technologies require suitable networks of sensors and actuators, as well as adequate processing and communication technologies. In this paper we propose a solution based on context free grammars for human behavior understanding with an application to assisted living. First, the grammars of the different actions performed by a person in his/her daily life are discovered. Then, a longterm analysis of the behavior is used to generate a control grammar, taking care of the context when an action is performed, and adding semantics. The proposed framework is tested on a dataset acquired in a real environment and compared with state of the art methods already available for the problem considered.

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

    PubMed Central

    Sear, Rebecca; Lawson, David W.; Kaplan, Hillard

    2016-01-01

    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. PMID:27022071

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

    PubMed

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

    2016-04-19

    Decades of research on human fertility has presented a clear picture ofhowfertility varies, including its dramatic decline over the last two centuries in most parts of the world.Whyfertility 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. PMID:27022071

  6. Understanding the Basis of Auriculocondylar Syndrome: Insights From Human and Mouse Genetic Studies

    PubMed Central

    Clouthier, David E.; Passos Bueno, Maria Rita; Tavares, Andre L.P.; Lyonnet, Stanislas; Amiel, Jeanne; Gordon, Christopher T.

    2014-01-01

    Among human birth defect syndromes, malformations affecting the face are perhaps the most striking due to cultural and psychological expectations of facial shape. One such syndrome is auriculocondylar syndrome (ACS), in which patients present with defects in ear and mandible development. Affected structures arise from cranial neural crest cells, a population of cells in the embryo that reside in the pharyngeal arches and give rise to most of the bone, cartilage and connective tissue of the face. Recent studies have found that most cases of ACS arise from defects in signaling molecules associated with the endothelin signaling pathway. Disruption of this signaling pathway in both mouse and zebrafish results in loss of identity of neural crest cells of the mandibular portion of the first pharyngeal arch and the subsequent repatterning of these cells, leading to homeosis of lower jaw structures into more maxillary-like structures. These findings illustrate the importance of endothelin signaling in normal human craniofacial development and illustrate how clinical and basic science approaches can coalesce to improve our understanding of the genetic basis of human birth syndromes. Further, understanding the genetic basis for ACS that lies outside of known endothelin signaling components may help elucidate unknown aspects critical to the establishment of neural crest cell patterning during facial morphogenesis. PMID:24123988

  7. Chromosomal meiotic segregation, embryonic developmental kinetics and DNA (hydroxy)methylation analysis consolidate the safety of human oocyte vitrification.

    PubMed

    De Munck, N; Petrussa, L; Verheyen, G; Staessen, C; Vandeskelde, Y; Sterckx, J; Bocken, G; Jacobs, K; Stoop, D; De Rycke, M; Van de Velde, H

    2015-06-01

    Oocyte vitrification has been introduced into clinical settings without extensive pre-clinical safety testing. In this study, we analysed major safety aspects of human oocyte vitrification in a high security closed system: (i) chromosomal meiotic segregation, (ii) embryonic developmental kinetics and (iii) DNA (hydroxy)methylation status. Fresh and vitrified sibling oocytes from young donors after intracytoplasmic sperm injection (ICSI) were compared in three different assays. Firstly, the chromosomal constitution of the fertilized zygotes was deduced from array comparative genomic hybridization results obtained from both polar bodies biopsied at Day 1. Secondly, embryo development up to Day 3 was analysed by time-lapse imaging. Ten specific time points, six morphokinetic time intervals and the average cell number on Day 3 were recorded. Thirdly, global DNA methylation and hydroxymethylation patterns were analysed by immunostaining on Day 3 embryos. The nuclear fluorescence intensity was measured by Volocity imaging software. Comprehensive chromosomal screening of the polar bodies demonstrated that at least half of the zygotes obtained after ICSI of fresh and vitrified oocytes were euploid. Time-lapse analysis showed that there was no significant difference in cleavage timings, the predictive morphokinetic time intervals nor the average cell number between embryos developed from fresh and vitrified oocytes. Finally, global DNA (hydroxy)methylation patterns were not significantly different between Day 3 embryos obtained from fresh and from vitrified oocytes. Our data further consolidate the safety of the oocyte vitrification technique. Nevertheless, additional testing in young and older sub-fertile/infertile patients and sound follow-up studies of children born after oocyte cryopreservation remain mandatory. PMID:25833840

  8. Current and future needs for developmental toxicity testing.

    PubMed

    Makris, Susan L; Kim, James H; Ellis, Amy; Faber, Willem; Harrouk, Wafa; Lewis, Joseph M; Paule, Merle G; Seed, Jennifer; Tassinari, Melissa; Tyl, Rochelle

    2011-10-01

    A review is presented of the use of developmental toxicity testing in the United States and international regulatory assessment of human health risks associated with exposures to pharmaceuticals (human and veterinary), chemicals (agricultural, industrial, and environmental), food additives, cosmetics, and consumer products. Developmental toxicology data are used for prioritization and screening of pharmaceuticals and chemicals, for evaluating and labeling of pharmaceuticals, and for characterizing hazards and risk of exposures to industrial and environmental chemicals. The in vivo study designs utilized in hazard characterization and dose-response assessment for developmental outcomes have not changed substantially over the past 30 years and have served the process well. Now there are opportunities to incorporate new technologies and approaches to testing into the existing assessment paradigm, or to apply innovative approaches to various aspects of risk assessment. Developmental toxicology testing can be enhanced by the refinement or replacement of traditional in vivo protocols, including through the use of in vitro assays, studies conducted in alternative nonmammalian species, the application of new technologies, and the use of in silico models. Potential benefits to the current regulatory process include the ability to screen large numbers of chemicals quickly, with the commitment of fewer resources than traditional toxicology studies, and to refine the risk assessment process through an enhanced understanding of the mechanisms of developmental toxicity and their relevance to potential human risk. As the testing paradigm evolves, the ability to use developmental toxicology data to meet diverse critical regulatory needs must be retained. PMID:21922641

  9. Toward Understanding the Catalytic Mechanism of Human Paraoxonase 1: Site-Specific Mutagenesis at Position 192

    PubMed Central

    Aggarwal, Geetika; Prajapati, Rameshwar; Tripathy, Rajan K.; Bajaj, Priyanka; Iyengar, A. R. Satvik; Sangamwar, Abhay T.; Pande, Abhay H.

    2016-01-01

    Human paraoxonase 1 (h-PON1) is a serum enzyme that can hydrolyze a variety of substrates. The enzyme exhibits anti-inflammatory, anti-oxidative, anti-atherogenic, anti-diabetic, anti-microbial and organophosphate-hydrolyzing activities. Thus, h-PON1 is a strong candidate for the development of therapeutic intervention against a variety conditions in human. However, the crystal structure of h-PON1 is not solved and the molecular details of how the enzyme hydrolyzes different substrates are not clear yet. Understanding the catalytic mechanism(s) of h-PON1 is important in developing the enzyme for therapeutic use. Literature suggests that R/Q polymorphism at position 192 in h-PON1 dramatically modulates the substrate specificity of the enzyme. In order to understand the role of the amino acid residue at position 192 of h-PON1 in its various hydrolytic activities, site-specific mutagenesis at position 192 was done in this study. The mutant enzymes were produced using Escherichia coli expression system and their hydrolytic activities were compared against a panel of substrates. Molecular dynamics simulation studies were employed on selected recombinant h-PON1 (rh-PON1) mutants to understand the effect of amino acid substitutions at position 192 on the structural features of the active site of the enzyme. Our results suggest that, depending on the type of substrate, presence of a particular amino acid residue at position 192 differentially alters the micro-environment of the active site of the enzyme resulting in the engagement of different subsets of amino acid residues in the binding and the processing of substrates. The result advances our understanding of the catalytic mechanism of h-PON1. PMID:26829396

  10. An essay concerning human understanding: how the cerebri anatome of Thomas Willis influenced John Locke.

    PubMed

    Lega, Bradley C

    2006-03-01

    Neurosurgeons are familiar with the anatomic investigations of Thomas Willis, but his intellectual legacy actually extends into the arena of philosophy. John Locke was a student of Willis while at Oxford, and this essay explores how some of Willis's anatomic discoveries might have influenced the ideas Locke expressed in his Essay Concerning Human Understanding. It also includes historical information about 17th century England and the group of men (including Christopher Wren and Robert Boyle) who worked with Willis and founded the Oxford Experimental Philosophy Club, which became the Royal Society. PMID:16528199

  11. Cultural evolution: implications for understanding the human language faculty and its evolution.

    PubMed

    Smith, Kenny; Kirby, Simon

    2008-11-12

    Human language is unique among the communication systems of the natural world: it is socially learned and, as a consequence of its recursively compositional structure, offers open-ended communicative potential. The structure of this communication system can be explained as a consequence of the evolution of the human biological capacity for language or the cultural evolution of language itself. We argue, supported by a formal model, that an explanatory account that involves some role for cultural evolution has profound implications for our understanding of the biological evolution of the language faculty: under a number of reasonable scenarios, cultural evolution can shield the language faculty from selection, such that strongly constraining language-specific learning biases are unlikely to evolve. We therefore argue that language is best seen as a consequence of cultural evolution in populations with a weak and/or domain-general language faculty. PMID:18801718

  12. Understanding and Re-engineering Nucleoprotein Machines to Cure Human Disease

    PubMed Central

    Dynan, William; Takeda, Yoshihiko; Roth, David; Bao, Gang

    2009-01-01

    Summary The mammalian nucleus is filled with self-organizing, nanometer-scale nucleoprotein machines that carry out DNA replication, RNA biogenesis, and DNA repair. We discuss, as a model, the nonhomologous end-joining (NHEJ) machine, which repairs DNA double-strand breaks. The NHEJ machine consists of six core polypeptides and 10–20 ancillary polypeptides. A full understanding of its design principles will require measuring the behavior of single NHEJ complexes in living cells, using a Nano Toolbox that includes bright, stable, biocompatible fluorophores, efficient protein and nucleic acid tagging strategies, and sensitive, high-resolution imaging methods. Taking inspiration from natural examples, it may be possible to adapt and redesign the NHEJ machine to precisely correct mutations responsible for common human diseases, such as K-ras in lung cancer, or human papillomavirus E6 and E7 genes in cervical and oral cancers. PMID:18393669

  13. Understanding Human Perception of Building Categories in Virtual 3d Cities - a User Study

    NASA Astrophysics Data System (ADS)

    Tutzauer, P.; Becker, S.; Niese, T.; Deussen, O.; Fritsch, D.

    2016-06-01

    Virtual 3D cities are becoming increasingly important as a means of visually communicating diverse urban-related information. To get a deeper understanding of a human's cognitive experience of virtual 3D cities, this paper presents a user study on the human ability to perceive building categories (e.g. residential home, office building, building with shops etc.) from geometric 3D building representations. The study reveals various dependencies between geometric properties of the 3D representations and the perceptibility of the building categories. Knowledge about which geometries are relevant, helpful or obstructive for perceiving a specific building category is derived. The importance and usability of such knowledge is demonstrated based on a perception-guided 3D building abstraction process.

  14. NTP-CERHR monograph on the potential human reproductive and developmental effects of di (2-ethylhexyl) phthalate (DEHP).

    PubMed

    Shelby, Michael D

    2006-11-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an updated evaluation of the potential for DEHP to cause adverse effects on reproduction and development in humans. The first CERHR expert panel evaluation of DEHP was completed in 2000 by the Phthalates Expert Panel. CERHR selected DEHP for an updated evaluation because of: (1) widespread human exposure, (2) public and government interest in adverse health effects, (3) recently available human exposure studies, and (4) the large number of relevant toxicity papers published since the earlier evaluation. DEHP (CAS RN: 117-81-7) is a high production volume chemical used as a plasticizer of polyvinyl chloride in the manufacture of a wide variety of consumer goods, such as building products, car products, clothing, food packaging, children's products (but not in toys intended for mouthing), and in medical devices made of polyvinyl chloride. The public can be exposed to DEHP by ingesting food, drink or dust that has been in contact with DEHP-containing materials, by inhaling contaminated air or dust, or by undergoing a medical procedure that uses polyvinyl chloride medical tubing or storage bags. It is estimated that the general population of the United States is exposed to DEHP levels ranging from 1 to 30 microg/kg bw/day (micrograms per kilogram body weight per day). The results of this DEHP update evaluation are published in an NTP-CERHR monograph that includes: (1) the NTP Brief, (2) the Expert Panel Update on the Reproductive and Developmental Toxicity of DEHP, and (3) public comments on the expert panel report. The NTP reached the following conclusions on the possible effects of exposure to DEHP on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. There is serious concern that certain intensive medical treatments of

  15. METROPOLITAN ATLANTA DEVELOPMENTAL DISABILITIES PROGRAM (MADDSP)

    EPA Science Inventory

    To address the problem of developmental disabilities among children, CDC, the former Division of Birth Defects and Developmental Disabilities, which was funded by the Agency for Toxic Substances and Disease Registry (ATSDR), and the Georgia Department of Human Resources, initiate...

  16. Understanding the influence of watershed storage caused by human interferences on ET variance

    NASA Astrophysics Data System (ADS)

    Zeng, R.; Cai, X.

    2014-12-01

    Understanding the temporal variance of evapotranspiration (ET) at the watershed scale remains a challenging task, because it is affected by complex climate conditions, soil properties, vegetation, groundwater and human activities. In a changing environment with extensive and intensive human interferences, understanding ET variance and its factors is important for sustainable water resources management. This study presents an analysis of the effect of storage change caused by human activities on ET variance Irrigation usually filters ET variance through the use of surface and groundwater; however, over-amount irrigation may cause the depletion of watershed storage, which changes the coincidence of water availability and energy supply for ET. This study develops a framework by incorporating the water balance and the Budyko Hypothesis. It decomposes the ET variance to the variances of precipitation, potential ET, catchment storage change, and their covariances. The contributions of ET variance from the various components are scaled by some weighting functions, expressed as long-term climate conditions and catchment properties. ET variance is assessed by records from 32 major river basins across the world. It is found that ET variance is dominated by precipitation variance under hot-dry condition and by evaporative demand variance under cool-wet condition; while the coincidence of water and energy supply controls ET variance under moderate climate condition. Watershed storage change plays an increasing important role in determining ET variance with relatively shorter time scale. By incorporating storage change caused by human interferences, this framework corrects the over-estimation of ET variance in hot-dry climate and under-estimation of ET variance in cool-wet climate. Furthermore, classification of dominant factors on ET variance shows similar patterns as geographic zonation.

  17. Towards understanding the dynamic behaviour of floodplains as human-water systems

    NASA Astrophysics Data System (ADS)

    Di Baldassarre, G.; Kooy, M.; Kemerink, J. S.; Brandimarte, L.

    2013-03-01

    This paper offers a conceptual approach to explore the complex dynamics of floodplains as fully coupled human-water systems. A number of hydrologists have recently investigated the impact of human activities (such as flood control measures, land-use changes, and settlement patterns) on the frequency and severity of floods. Meanwhile, social scientists have shown how interactions between society and waters in floodplain areas, including the frequency and severity of floods, have an impact on the ways in which social relations unfold (in terms of governance processes, policies, and institutions) and societies are organised (spatially, politically, and socially). However, we argue that the interactions and associated feedback mechanisms between hydrological and social processes remain largely unexplored and poorly understood. Thus, there is a need to better understand how the institutions and governance processes interact with hydrological processes in floodplains to influence the frequency and severity of floods, while (in turn) hydrological processes co-constitute the social realm and make a difference for how social relations unfold to shape governance processes and institutions. Our research goal, therefore, is not in identifying one or the other side of the cycle (hydrological or social), but in explaining the relationship between them: how, when, where, and why they interact, and to what result for both social relations and hydrological processes? We argue that long time series of hydrological and social data, along with remote sensing data, can be used to observe floodplain dynamics from unconventional approaches, and understand the complex interactions between water and human systems taking place in floodplain areas, across scales and levels of human impacts, and within different hydro-climatic conditions, socio-cultural settings, and modes of governance.

  18. Towards understanding the dynamic behaviour of floodplains as human-water systems

    NASA Astrophysics Data System (ADS)

    Di Baldassarre, G.; Kooy, M.; Kemerink, J. S.; Brandimarte, L.

    2013-08-01

    This paper offers a conceptual approach to explore the complex dynamics of floodplains as fully coupled human-water systems. A number of hydrologists have recently investigated the impact of human activities (such as flood control measures, land-use changes, and settlement patterns) on the frequency and severity of floods. Meanwhile, social scientists have shown how interactions between society and waters in deltas and floodplain areas, including the frequency and severity of floods, have an impact on the ways in which social relations unfold (in terms of governance processes, policies, and institutions) and societies are organised (spatially, politically, and socially). However, we argue that the interactions and associated feedback mechanisms between hydrological and social processes remain largely unexplored and poorly understood. Thus, there is a need to better understand how the institutions and governance processes interact with hydrological processes in deltas and floodplains to influence the frequency and severity of floods, while (in turn) hydrological processes co-constitute the social realm and make a difference for how social relations unfold to shape governance processes and institutions. Our research goal, therefore, is not in identifying one or the other side of the cycle (hydrological or social), but in explaining the relationship between them: how, when, where, and why they interact, and to what result for both social relations and hydrological processes? We argue that long time series of hydrological and social data, along with remote sensing data, can be used to observe floodplain dynamics from unconventional approaches, and understand the complex interactions between water and human systems taking place in floodplain areas, across scales and levels of human impacts, and within different hydro-climatic conditions, socio-cultural settings, and modes of governance.

  19. Explaining human movements and actions: children's understanding of the limits of psychological explanation.

    PubMed

    Schult, C A; Wellman, H M

    1997-03-01

    Human actions and movements can be caused by psychological states (e.g. beliefs and desires), physical forces (e.g. gravity) and biological processes (e.g. reflexes). In three studies we explored young children's understanding of the causes of human movements in order to examine their ability to differentiate and coordinate psychological, physical and biological reasoning to account for the activities of one single entity--a human being. In Study 1, 4-year-olds explained characters' voluntary actions, mistakes, physically-caused and biologically-caused behaviors and movements. Children gave psychological explanations for the intended actions and mistakes, but biological and physical explanations for the biologically-caused and physically-caused movements. Studies 2 and 3 extended the investigation to younger children (3-year-olds), encompassed a greater variety of items, and used several converging methods in order to examine children's judgments and explanations. Consistently, 3- and 4-year-olds gave appropriately different responses and explanations to the different item types. These findings show that far from viewing people in strictly psychological terms, young children evidence multiple causal-explanatory construals of human behavior. We discuss the implications of these findings for children's everyday psychological, physical, and biological theories. One implication of the findings is that young children do not assume a match between entities and theories (persons-psychology, objects-physics). If they do not, this raises the question of what information they use to decide which explanatory system fits which events. PMID:9187061

  20. Symmetry States of the physical space: an expanded reference frame for understanding human consciousness.

    PubMed

    Manek, Nisha J

    2012-01-01

    A remarkable phenomenon is taking place around the globe, one that I have been fortunate enough to witness and in which to participate. The relics of the historical Buddha, also known as Siddhartha or Shakyamuni Buddha, still survive today over 2500 years since his enlightenment, and, for the first time in history, are traveling throughout the world. In common Buddhist practice, relics are highly venerated and treasured remains of realized Masters. It is very rare for relics to travel from city to city and be available for viewing by the general public. The Buddha relic tour is demonstrating that a direct experience of the spiritual state is not mysterious, nor is it for a select few. The spiritual state, here defined as a universal theme of unconditional love, is a component of human evolutionary unfoldment, a process through which thousands of human beings have passed, and through which thousands more will pass. We are "waking up" as a species. Consequently, more information is required about this transformation of human consciousness. The Buddha relics offer us a priceless means by which we can obtain a richer perspective about the nature of human consciousness, spiritual realities such as love, and ultimately understanding ourselves. PMID:22106870

  1. Understanding multicellular function and disease with human tissue-specific networks

    PubMed Central

    Greene, Casey S.; Krishnan, Arjun; Wong, Aaron K.; Ricciotti, Emanuela; Zelaya, Rene A.; Himmelstein, Daniel S.; Zhang, Ran; Hartmann, Boris M.; Zaslavsky, Elena; Sealfon, Stuart C.; Chasman, Daniel I.; FitzGerald, Garret A.; Dolinski, Kara; Grosser, Tilo; Troyanskaya, Olga G.

    2016-01-01

    Tissue and cell-type identity lie at the core of human physiology and disease. Understanding the genetic underpinnings of complex tissues and individual cell lineages is crucial for developing improved diagnostics and therapeutics. We present genome-wide functional interaction networks for 144 human tissues and cell types developed using a data-driven Bayesian methodology that integrates thousands of diverse experiments spanning tissue and disease states. Tissue-specific networks predict lineage-specific responses to perturbation, reveal genes’ changing functional roles across tissues, and illuminate disease-disease relationships. We introduce NetWAS, which combines genes with nominally significant GWAS p-values and tissue-specific networks to identify disease-gene associations more accurately than GWAS alone. Our webserver, GIANT, provides an interface to human tissue networks through multi-gene queries, network visualization, analysis tools including NetWAS, and downloadable networks. GIANT enables systematic exploration of the landscape of interacting genes that shape specialized cellular functions across more than one hundred human tissues and cell types. PMID:25915600

  2. Developmental regulation of the human embryonic beta-like globin gene is mediated by synergistic interactions among multiple tissue- and stage-specific elements.

    PubMed Central

    Trepicchio, W L; Dyer, M A; Baron, M H

    1993-01-01

    The stage-specific regulation of mammalian embryonic globin genes has been an experimentally elusive problem, in part because of the developmentally early timing of their expression. We have carried out a systematic analysis of truncation and internal deletion mutations within the 5'-flanking region of the human embryonic beta-like globin gene (epsilon) in erythroid and nonerythroid cell lines. Within a 670-bp region upstream from the constitutive promoter are multiple positive and negative control elements. Of these, a positive regulatory element (epsilon-PRE II) which is active only in embryonic erythroid cells is of particular interest. Remarkably, although it is inactive on its own, in the presence of other sequences located further upstream, it confers tissue- and developmental stage-specific expression on a constitutive epsilon-globin or heterologous promoter. The activity of epsilon-PRE II is also modulated by another positive regulatory domain located further downstream to direct erythroid cell-specific, but little or no embryonic stage-specific, transcription. A nuclear factor highly enriched in embryonic erythroid cells binds specifically within a 19-bp region of epsilon-PRE II. Nuclei from adult erythroid cells also contain a factor that binds to this region but forms a complex of faster electrophoretic mobility. We speculate that interactions between epsilon-PRE II and other upstream control elements play an important role in the developmental regulation of the human embryonic beta-like globin gene. Images PMID:8246963

  3. Developmental intervention: a pediatric clinical review.

    PubMed

    Casey, P H; Bradley, R H; Caldwell, B M; Edwards, D R

    1986-08-01

    's understanding of the individual developmental characteristics and temperamental style of their child. Promote parental sensitivity to the social nature of infant behaviors. Encourage parent responsiveness to the social behaviors. Improve parental feelings of confidence and competence to affect their child's development. Pediatricians can be influential in supporting structural changes that can have beneficial effects on children's development. Support of humanization of obstetric and nursery practices, and the increased use of child health supervision to parents in groups are examples of such efforts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2426651

  4. Solving Water Crisis through Understanding of Hydrology and Human Systems: a Possible Target

    NASA Astrophysics Data System (ADS)

    Montanari, A.

    2014-12-01

    While the majority of the Earth surface is still in pristine conditions, the totality of the hydrological systems that are relevant to humans are human impacted, with the only exception of small headwater catchments. In fact, the limited transferability of water in space and time implies that water withdrawals from natural resources take place where and when water is needed. Therefore, hydrological systems are impacted where and when humans are, thereby causing a direct perturbation of all water bodies that are relevant to society. The current trend of population dynamics and the current status of water systems are such that the above impact will be not sustainable in the near future, therefore causing a water emergency that will be extended to all intensively populated regions of the world, with relevant implications on migration fluxes, political status and social security. Therefore mitigation actions are urgently needed, whose planning needs to be based on improved interpretations of the above impact. Up to recent times, hydrologists mainly concentrated their research on catchments where the human perturbation is limited, to improve our understanding of pristine hydrology. There were good motivations for this focus: given the relevant uncertainty affecting hydrological modeling, and the even greater uncertainty involved in societal modeling, hydrologists made an effort to separate hydrological and human dynamics. Nowadays, the urgency of the above need to mitigate the global water crisis through improved water resources management calls for a research attempt to bridge water and social sciences. The relevant research question is how to build operational models in order to fully account for the interactions and feedbacks between water resources systems and society. Given that uncertainty estimation is necessary for the operational application of model results, one of the crucial issues is how to quantify uncertainty by means of suitable assumptions. This talk

  5. Context-dependent encoding in the human auditory brainstem relates to hearing speech in noise: Implications for developmental dyslexia

    PubMed Central

    Chandrasekaran, Bharath; Hornickel, Jane; Skoe, Erika; Nicol, Trent; Kraus, Nina

    2009-01-01

    SUMMARY We examined context-dependent encoding of speech in children with and without developmental dyslexia by measuring auditory brainstem responses to a speech syllable presented in a repetitive or variable context. Typically developing children showed enhanced brainstem representation of features related to voice pitch in the repetitive context, relative to the variable context. In contrast, children with developmental dyslexia exhibited impairment in their ability to modify representation in predictable contexts. From a functional perspective, we found that the extent of context-dependent encoding in the auditory brainstem positively correlated with behavioral indices of speech perception in noise. The ability to sharpen representation of repeating elements is crucial to speech perception in noise, since it allows superior ‘tagging’ of voice pitch, an important cue for segregating sound streams in background noise. The disruption of this mechanism contributes to a critical deficit in noise-exclusion, a hallmark symptom in developmental dyslexia. PMID:19914180

  6. A human pluripotent carcinoma stem cell-based model for in vitro developmental neurotoxicity testing: effects of methylmercury, lead and aluminum evaluated by gene expression studies.

    PubMed

    Laurenza, Incoronata; Pallocca, Giorgia; Mennecozzi, Milena; Scelfo, Bibiana; Pamies, David; Bal-Price, Anna

    2013-11-01

    The major advantage of the neuronal cell culture models derived from human stem cells is their ability to replicate the crucial stages of neurodevelopment such as the commitment of human stem cells to the neuronal lineage and their subsequent stages of differentiation into neuronal and glial-like cell. In these studies we used mixed neuronal/glial culture derived from the NTERA-2 (NT-2) cell line, which has been established from human pluripotent testicular embryonal carcinoma cells. After characterization of the different stages of cell differentiation into neuronal- and glial-like phenotype toxicity studies were performed to evaluate whether this model would be suitable for developmental neurotoxicity studies. The cells were exposed during the differentiation process to non-cytotoxic concentrations of methylmercury chloride, lead chloride and aluminum nitrate for two weeks. The toxicity was then evaluated by measuring the mRNA levels of cell specific markers (neuronal and glial). The results obtained suggest that lead chloride and aluminum nitrate at low concentrations were toxic primarily to astrocytes and at the higher concentrations it also induced neurotoxicity. In contrast, MetHgCl was toxic for both cell types, neuronal and glial, as mRNA specific for astrocytes and neuronal markers were affected. The results obtained suggest that a neuronal mixed culture derived from human NT2 precursor cells is a suitable model for developmental neurotoxicity studies and gene expression could be used as a sensitive endpoint for initial screening of potential neurotoxic compounds. PMID:23501475

  7. Aspects of Ancient Mitochondrial DNA Analysis in Different Populations for Understanding Human Evolution

    PubMed Central

    Nesheva, DV

    2014-01-01

    The evolution of modern humans is a long and difficult process which started from their first appearance and continues to the present day. The study of the genetic origin of populations can help to determine population kinship and to better understand the gradual changes of the gene pool in space and time. Mitochondrial DNA (mtDNA) is a proper tool for the determination of the origin of populations due to its high evolutionary importance. Ancient mitochondrial DNA retrieved from museum specimens, archaeological finds and fossil remains can provide direct evidence for population origins and migration processes. Despite the problems with contaminations and authenticity of ancient mitochondrial DNA, there is a developed set of criteria and platforms for obtaining authentic ancient DNA. During the last two decades, the application of different methods and techniques for analysis of ancient mitochondrial DNA gave promising results. Still, the literature is relatively poor with information for the origin of human populations. Using comprehensive phylogeographic and population analyses we can observe the development and formation of the contemporary populations. The aim of this study was to shed light on human migratory processes and the formation of populations based on available ancient mtDNA data. PMID:25741209

  8. Developmental Algorithms Have Meaning!

    ERIC Educational Resources Information Center

    Green, John

    1997-01-01

    Adapts Stanic and McKillip's ideas for the use of developmental algorithms to propose that the present emphasis on symbolic manipulation should be tempered with an emphasis on the conceptual understanding of the mathematics underlying the algorithm. Uses examples from the areas of numeric computation, algebraic manipulation, and equation solving…

  9. Four decades of teaching developmental biology in Germany.

    PubMed

    Grunz, Horst

    2003-01-01

    I have taught developmental biology in Essen for 30 years. Since my department is named Zoophysiologie (Zoophysiology), besides Developmental Biology, I also have to teach General Animal Physiology. This explains why the time for teaching developmental biology is restricted to a lecture course, a laboratory course and several seminar courses. However, I also try to demonstrate in the lecture courses on General Physiology the close relationship between developmental biology, physiology, morphology, anatomy, teratology, carcinogenesis, evolution and ecology (importance of environmental factors on embryogenesis). Students are informed that developmental biology is a core discipline of biology. In the last decade, knowledge about molecular mechanisms in different organisms has exponentially increased. The students are trained to understand the close relationship between conserved gene structure, gene function and signaling pathways, in addition to or as an extension of, classical concepts. Public reports about the human genome project and stem cell research (especially therapeutic and reproductive cloning) have shown that developmental biology, both in traditional view and at the molecular level, is essential for the understanding of these complex topics and for serious and non-emotional debate. PMID:12705670

  10. Male-mediated developmental toxicity.

    PubMed

    Anderson, Diana; Schmid, Thomas E; Baumgartner, Adolf

    2014-01-01

    Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components. PMID:24369136

  11. Male-mediated developmental toxicity

    PubMed Central

    Anderson, Diana; Schmid, Thomas E; Baumgartner, Adolf

    2014-01-01

    Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components. PMID:24369136

  12. Vitamin D signaling in the bovine immune system: a model for understanding human vitamin D requirements.

    PubMed

    Nelson, Corwin D; Reinhardt, Timothy A; Lippolis, John D; Sacco, Randy E; Nonnecke, Brian J

    2012-03-01

    The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance. PMID:22666545

  13. Predicting Developmental Toxicity of ToxCast Phase I Chemicals Using Human Embryonic Stem Cells and Metabolomics

    EPA Science Inventory

    EPA’s ToxRefDB contains prenatal guideline study data from rats and rabbits for over 240 chemicals that overlap with the ToxCast in vitro high throughput screening project. A subset of these compounds were tested in Stemina Biomarker Discovery's developmental toxicity platform, a...

  14. The Significance of Human-Animal Relationships as Modulators of Trauma Effects in Children: A Developmental Neurobiological Perspective

    ERIC Educational Resources Information Center

    Yorke, Jan

    2010-01-01

    Emotional stress and trauma impacts the neurobiology of children. They are especially vulnerable given the developmental plasticity of the brain. The neural synaptic circular processes between the anterior cingulated cortex, prefrontal cortex, amygdala and the hypothalamus are altered. Trauma results in the release of the peptide glucocortisoid,…

  15. Standing between Two Worlds in Harlem: A Developmental Psychopathology Perspective of Perinatally Acquired Human Immunodeficiency Virus and Adolescence

    ERIC Educational Resources Information Center

    Kang, Ezer; Mellins, Claude Ann; Ng, Warren Yiu Kee; Robinson, Lisa-Gaye; Abrams, Elaine J.

    2008-01-01

    Perinatal HIV infection in the US continues to evolve from a fatal pediatric illness to a chronic medical condition of childhood and adolescence. Although navigating this period is influenced by multi-leveled deprivations commonly experienced by low-income minority families, HIV alters the timing and experience of developmental milestones for many…

  16. Cognitive and Behavioral Distribution of Rewards: Developmental and Instructional Tests of Young Children's Understanding and Application of Some Principles of Equity. Final Report.

    ERIC Educational Resources Information Center

    Vance, Barbara

    Two studies attempted to determine: (1) at what age children understand and apply the principle of equity; and (2) whether theory based instruction is effective in helping young children understand the principle of equity. Further, do children exposed to such instruction perform better on a behavioral test than children not exposed to such…

  17. Advanced simulation technology used to reduce accident rates through a better understanding of human behaviors and human perception

    NASA Astrophysics Data System (ADS)

    Manser, Michael P.; Hancock, Peter A.

    1996-06-01

    Human beings and technology have attained a mutually dependent and symbiotic relationship. It is easy to recognize how each depends on the other for survival. It is also easy to see how technology advances due to human activities. However, the role technology plays in advancing humankind is seldom examined. This presentation examines two research areas where the role of advanced visual simulation systems play an integral and essential role in understanding human perception and behavior. The ultimate goal of this research is the betterment of humankind through reduced accident and death rates in transportation environments. The first research area examined involved the estimation of time-to-contact. A high-fidelity wrap-around simulator (RAS) was used to examine people's ability to estimate time-to- contact. The ability of people to estimate the amount of time before an oncoming vehicle will collide with them is a necessary skill for avoiding collisions. A vehicle approached participants at one of three velocities, and while en route to the participant, the vehicle disappeared. The participants' task was to respond when they felt the accuracy of time-to-contact estimates and the practical applications of the result. The second area of research investigates the effects of various visual stimuli on underground transportation tunnel walls for the perception of vehicle speed. A RAS is paramount in creating visual patterns in peripheral vision. Flat-screen or front-screen simulators do not have this ability. Results are discussed in terms of speed perception and the application of these results to real world environments.

  18. Evolutionary Developmental Psychology.

    ERIC Educational Resources Information Center

    Geary, David C.; Bjorklund, David F.

    2000-01-01

    Describes evolutionary developmental psychology as the study of the genetic and ecological mechanisms that govern the development of social and cognitive competencies common to all human beings and the epigenetic (gene-environment interactions) processes that adapt these competencies to local conditions. Outlines basic assumptions and domains of…

  19. Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression.

    PubMed

    Jackson, Stephen M; Harp, Natessa; Patel, Darshna; Wulf, Jordan; Spaeth, Erich D; Dike, Uzoamaka K; James, Judith A; Capra, J Donald

    2009-04-23

    We previously reported that RO(+) expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells. Here, we subdivided human tonsillar B cells, including IgD(-)CD38(+) GC B cells, into different fractions based on RB expression. Although each subset contained RB(+) cells, when used as an intrasubset marker, differential RB expression effectively discriminated between phenotypically distinct cells. For example, RB(+) GC B cells were enriched for activated cells with lower AID expression. RB inversely correlated with mutation frequency, demonstrating a key difference between RB- and RO-expressing GC B cells. Reduced RB expression during the transition from pre-GC (IgM(+)IgD(+)CD38(+)CD27(-)) to GCB cells was followed by a dramatic increase during the GC-to-plasmablast (IgD(-)CD38(++)CD27(+)) and memory (IgD(-)CD38(-)CD27(+)) transition. Interestingly, RB(+) GC B cells showed increased signs of terminal differentiation toward CD27(+) post-GC early plasmablast (increased CD38 and RO) or early memory (decreased CD38 and RO) B cells. We propose that as in T cells, differential RB expression directly correlates with development- and function-based transitions in tonsillar B cells. Application of this RB:RO system should advance our understanding of normal B-cell development and facilitate the isolation of more discrete B-cell populations with potentially different propensities in disease pathogenesis. PMID:19059880

  20. Expected Satiety: Application to Weight Management and Understanding Energy Selection in Humans

    PubMed Central

    Forde, Ciarán G.; Almiron-Roig, Eva; Brunstrom, Jeffrey M.

    2016-01-01

    Recent advances in the approaches used to quantify expectations of satiation and satiety have led to a better understanding of how humans select and consume food, and the associated links to energy intake regulation. When compared calorie for calorie some foods are expected to deliver several times more satiety than others, and multiple studies have demonstrated that people are able to discriminate between similar foods reliably and with considerable sensitivity. These findings have implications for the control of meal size and the design of foods that can be used to lower the energy density of diets. These methods and findings are discussed in terms of their implications for weight management. The current paper also highlights why expected satiety may also play an important role beyond energy selection, in moderating appetite sensations after a meal has been consumed, through memory for recent eating and the selection of foods across future meals. PMID:26627096

  1. Systematically labeling developmental stage-specific genes for the study of pancreatic β-cell differentiation from human embryonic stem cells

    PubMed Central

    Liu, Haisong; Yang, Huan; Zhu, Dicong; Sui, Xin; Li, Juan; Liang, Zhen; Xu, Lei; Chen, Zeyu; Yao, Anzhi; Zhang, Long; Zhang, Xi; Yi, Xing; Liu, Meng; Xu, Shiqing; Zhang, Wenjian; Lin, Hua; Xie, Lan; Lou, Jinning; Zhang, Yong; Xi, Jianzhong; Deng, Hongkui

    2014-01-01

    The applications of human pluripotent stem cell (hPSC)-derived cells in regenerative medicine has encountered a long-standing challenge: how can we efficiently obtain mature cell types from hPSCs? Attempts to address this problem are hindered by the complexity of controlling cell fate commitment and the lack of sufficient developmental knowledge for guiding hPSC differentiation. Here, we developed a systematic strategy to study hPSC differentiation by labeling sequential developmental genes to encompass the major developmental stages, using the directed differentiation of pancreatic β cells from hPSCs as a model. We therefore generated a large panel of pancreas-specific mono- and dual-reporter cell lines. With this unique platform, we visualized the kinetics of the entire differentiation process in real time for the first time by monitoring the expression dynamics of the reporter genes, identified desired cell populations at each differentiation stage and demonstrated the ability to isolate these cell populations for further characterization. We further revealed the expression profiles of isolated NGN3-eGFP+ cells by RNA sequencing and identified sushi domain-containing 2 (SUSD2) as a novel surface protein that enriches for pancreatic endocrine progenitors and early endocrine cells both in human embryonic stem cells (hESC)-derived pancreatic cells and in the developing human pancreas. Moreover, we captured a series of cell fate transition events in real time, identified multiple cell subpopulations and unveiled their distinct gene expression profiles, among heterogeneous progenitors for the first time using our dual reporter hESC lines. The exploration of this platform and our new findings will pave the way to obtain mature β cells in vitro. PMID:25190258

  2. Systematically labeling developmental stage-specific genes for the study of pancreatic β-cell differentiation from human embryonic stem cells.

    PubMed

    Liu, Haisong; Yang, Huan; Zhu, Dicong; Sui, Xin; Li, Juan; Liang, Zhen; Xu, Lei; Chen, Zeyu; Yao, Anzhi; Zhang, Long; Zhang, Xi; Yi, Xing; Liu, Meng; Xu, Shiqing; Zhang, Wenjian; Lin, Hua; Xie, Lan; Lou, Jinning; Zhang, Yong; Xi, Jianzhong; Deng, Hongkui

    2014-10-01

    The applications of human pluripotent stem cell (hPSC)-derived cells in regenerative medicine has encountered a long-standing challenge: how can we efficiently obtain mature cell types from hPSCs? Attempts to address this problem are hindered by the complexity of controlling cell fate commitment and the lack of sufficient developmental knowledge for guiding hPSC differentiation. Here, we developed a systematic strategy to study hPSC differentiation by labeling sequential developmental genes to encompass the major developmental stages, using the directed differentiation of pancreatic β cells from hPSCs as a model. We therefore generated a large panel of pancreas-specific mono- and dual-reporter cell lines. With this unique platform, we visualized the kinetics of the entire differentiation process in real time for the first time by monitoring the expression dynamics of the reporter genes, identified desired cell populations at each differentiation stage and demonstrated the ability to isolate these cell populations for further characterization. We further revealed the expression profiles of isolated NGN3-eGFP(+) cells by RNA sequencing and identified sushi domain-containing 2 (SUSD2) as a novel surface protein that enriches for pancreatic endocrine progenitors and early endocrine cells both in human embryonic stem cells (hESC)-derived pancreatic cells and in the developing human pancreas. Moreover, we captured a series of cell fate transition events in real time, identified multiple cell subpopulations and unveiled their distinct gene expression profiles, among heterogeneous progenitors for the first time using our dual reporter hESC lines. The exploration of this platform and our new findings will pave the way to obtain mature β cells in vitro. PMID:25190258

  3. DEVELOPMENTAL LEVEL AND VOCATIONAL INTERESTS (SVIB).

    ERIC Educational Resources Information Center

    SAGE, ELLIS H.

    DEVELOPMENTAL TASKS OF IMPLEMENTING A VOCATIONAL ROLE IN LATE ADOLESCENCE WERE UNRELATED TO A DEVELOPMENTAL SCALE (DS) FOR COLLEGE FRESHMENT (N=107 MALES). THE DEVELOPMENTAL TASKS CORRELATED SIGNIFICANTLY WITH SOME JACKSON PERSONALITY RESEARCH FORM NEEDS (PRF)--(1) INTEREST PATTERNING CORRELATED WITH UNDERSTANDING (.31) AND AFFILIATION (-.22),…

  4. Cord Blood Cells for Developmental Toxicology and Environmental Health

    PubMed Central

    Il’yasova, Dora; Kloc, Noreen; Kinev, Alexander

    2015-01-01

    The Tox21 program initiated a shift in toxicology toward in vitro testing with a focus on the biological mechanisms responsible for toxicological response. We discuss the applications of these initiatives to developmental toxicology. Specifically, we briefly review current approaches that are widely used in developmental toxicology to demonstrate the gap in relevance to human populations. An important aspect of human relevance is the wide variability of cellular responses to toxicants. We discuss how this gap can be addressed by using cells isolated from umbilical cord blood, an entirely non-invasive source of fetal/newborn cells. Extension of toxicological testing to collections of human fetal/newborn cells would be useful for better understanding the effect of toxicants on fetal development in human populations. By presenting this perspective, we aim to initiate a discussion about the use of cord blood donor-specific cells to capture the variability of cellular toxicological responses during this vulnerable stage of human development. PMID:26697419

  5. Mechanistic understanding of human-wildlife conflict through a novel application of dynamic occupancy models.

    PubMed

    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

  6. The role of particular tick developmental stages in the circulation of tick-borne pathogens affecting humans in Central Europe. 2. Tick-borne encephalitis virus.

    PubMed

    Karbowiak, Grzegorz; Biernat, Beata

    2016-01-01

    Hard-bodied ticks transmit various pathogens, such as Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Rickettsia spp., Babesia spp., and carry numerous other microorganisms with an unknown pathogenic potential. Among them, tick-borne encephalitis virus has great importance. In Central European conditions all developmental stages of ticks participate in the zoonotic cycle of the TBE virus. According to pathogen and tick biology, the roles of larvae, nymphs and adults are different. Larvae and nymphs of Ixodes ricinus ticks are responsible for circulation in rodents and medium sized mammals; adults transfer the infection to ruminants and to next generations via transovarial transmission. All active developmental stages of I. ricinus can play role of the bridge vector, transmitting the infection to humans apart males which don't feed. The late summer peak of human infectivity is caused by the summer peak of I. ricinus nymphs' activity. The Dermacentor reticulatus tick attacks humans infrequently, but does participate in the circulation of the virus in the zoonotic foci; larvae and nymphs of the D. reticulatus ticks are responsible for circulation in rodents, mainly Microtinae, while adults transmit the infection to ruminants. PMID:27262951

  7. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Hexyl Phthalate (DnHP).

    PubMed

    2003-05-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-hexyl phthalate (DnHP) to cause adverse effects on reproduction and development in humans. DnHP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of reproductive or developmental toxicity. Available information indicates that DnHP is manufactured in relatively small amounts but occurs in a variety of commercial products including dip-molded products such as tool handles or dishwasher baskets, flooring, vinyl gloves, flea collars, and conveyer belts used in food processing. The results of this evaluation on DnHP are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of DnHP, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DnHP on human development and reproduction. The scientific evidence was insufficient to reach a conclusion regarding the potential for DnHP to adversely affect human development or reproduction. There was very limited information on developmental and reproductive toxicity available to the panel. The panel evaluated only a single developmental toxicity study using a high dose (9,900 mg/kg body weight/day on gestational days 6-13) of DnHP. No live pups were delivered. In a reproductive study, effects on fertility were noted in all treatment groups (380-1,670 mg/ kg body weight/day). These studies provided sufficient information in experimental animals to conclude that DnHP is a reproductive and developmental toxicant at the doses tested. However, the treatment doses were high and these

  8. The Contribution of Conceptual Change Texts Accompanied by Concept Mapping to Students' Understanding of the Human Circulatory System.

    ERIC Educational Resources Information Center

    Sungur, Semra; Tekkaya, Ceren; Geban, Omer

    2001-01-01

    Investigates the contribution of conceptual change texts accompanied by concept mapping instruction to 10th-grade students' understanding of the human circulatory system. Indicates that the conceptual change texts accompanied by concept mapping instruction produced a positive effect on students' understanding of concepts. Concludes that students…

  9. Developmental psychopathology: recent advances and future challenges

    PubMed Central

    Pollak, Seth D

    2015-01-01

    The integrative field of developmental psychopathology is having a huge impact on our understanding of human health and behavior. In this paper, I use the example of children’s early stress exposure to illustrate how developmental psychopathologists now tend to deemphasize diagnostic categories and, instead, emphasize the social and biological contexts, events and circumstances that have created opportunities for maladaptive responses and health problems in youth. This example shows that developmental psychopathology is increasing understanding of how children develop the abilities that allow them to cope effectively with challenges and what leads to failures in development of these abilities. Integrating research about the neurobiology of learning may prove to be a powerful future direction to understand how the environment regulates behavior. Learning processes become increasingly intricate and fine-tuned as relevant neuroanatomical systems develop, and as the range, complexity and amount of environmental information increases for the developing child. A focus on these processes allows psychopathologists to formulate questions about which neural mechanisms children use to process information, how these mechanisms are themselves shaped by social context, why adverse social environments confer risk for children, and, perhaps, what sorts of neutrally informed interventions might remediate the deficits in self-regulation that underlie common psychopathologies. PMID:26407771

  10. Developmental exposure to lead (Pb) alters the expression of the human tau gene and its products in a transgenic animal model.

    PubMed

    Dash, M; Eid, A; Subaiea, G; Chang, J; Deeb, R; Masoud, A; Renehan, W E; Adem, A; Zawia, N H

    2016-07-01

    Tauopathies are a class of neurodegenerative diseases associated with the pathological aggregation of the tau protein in the human brain. The best known of these illnesses is Alzheimer's disease (AD); a disease where the microtubule associated protein tau (MAPT) becomes hyperphosphorylated (lowering its binding affinity to microtubules) and aggregates within neurons in the form of neurofibrillary tangles (NFTs). In this paper we examine whether environmental factors play a significant role in tau pathogenesis. Our studies were conducted in a double mutant mouse model that expressed the human tau gene and lacked the gene for murine tau. The human tau mouse model was tested for the transgene's ability to respond to an environmental toxicant. Pups were developmentally exposed to lead (Pb) from postnatal day (PND) 1-20 with 0.2% Pb acetate. Mice were then sacrificed at PND 20, 30, 40 and 60. Protein and mRNA levels for tau and CDK5 as well as tau phosphorylation at Ser396 were determined. In addition, the potential role of miRNA in tau expression was investigated by measuring levels of miR-34c, a miRNA that targets the mRNA for human tau, at PND20 and 50. The expression of the human tau transgene was altered by developmental exposure to Pb. This exposure also altered the expression of miR-34c. Our findings are the first of their kind to test the responsiveness of the human tau gene to an environmental toxicant and to examine an epigenetic mechanism that may be involved in the regulation of this gene's expression. PMID:27293183

  11. Toward Human-Carnivore Coexistence: Understanding Tolerance for Tigers in Bangladesh.

    PubMed

    Inskip, Chloe; Carter, Neil; Riley, Shawn; Roberts, Thomas; MacMillan, Douglas

    2016-01-01

    Fostering local community tolerance for endangered carnivores, such as tigers (Panthera tigris), is a core component of many conservation strategies. Identification of antecedents of tolerance will facilitate the development of effective tolerance-building conservation action and secure local community support for, and involvement in, conservation initiatives. We use a stated preference approach for measuring tolerance, based on the 'Wildlife Stakeholder Acceptance Capacity' concept, to explore villagers' tolerance levels for tigers in the Bangladesh Sundarbans, an area where, at the time of the research, human-tiger conflict was severe. We apply structural equation modeling to test an a priori defined theoretical model of tolerance and identify the experiential and psychological basis of tolerance in this community. Our results indicate that beliefs about tigers and about the perceived current tiger population trend are predictors of tolerance for tigers. Positive beliefs about tigers and a belief that the tiger population is not currently increasing are both associated with greater stated tolerance for the species. Contrary to commonly-held notions, negative experiences with tigers do not directly affect tolerance levels; instead, their effect is mediated by villagers' beliefs about tigers and risk perceptions concerning human-tiger conflict incidents. These findings highlight a need to explore and understand the socio-psychological factors that encourage tolerance towards endangered species. Our research also demonstrates the applicability of this approach to tolerance research to a wide range of socio-economic and cultural contexts and reveals its capacity to enhance carnivore conservation efforts worldwide. PMID:26760035

  12. Toward Human-Carnivore Coexistence: Understanding Tolerance for Tigers in Bangladesh

    PubMed Central

    Inskip, Chloe; Roberts, Thomas; MacMillan, Douglas

    2016-01-01

    Fostering local community tolerance for endangered carnivores, such as tigers (Panthera tigris), is a core component of many conservation strategies. Identification of antecedents of tolerance will facilitate the development of effective tolerance-building conservation action and secure local community support for, and involvement in, conservation initiatives. We use a stated preference approach for measuring tolerance, based on the ‘Wildlife Stakeholder Acceptance Capacity’ concept, to explore villagers’ tolerance levels for tigers in the Bangladesh Sundarbans, an area where, at the time of the research, human-tiger conflict was severe. We apply structural equation modeling to test an a priori defined theoretical model of tolerance and identify the experiential and psychological basis of tolerance in this community. Our results indicate that beliefs about tigers and about the perceived current tiger population trend are predictors of tolerance for tigers. Positive beliefs about tigers and a belief that the tiger population is not currently increasing are both associated with greater stated tolerance for the species. Contrary to commonly-held notions, negative experiences with tigers do not directly affect tolerance levels; instead, their effect is mediated by villagers’ beliefs about tigers and risk perceptions concerning human-tiger conflict incidents. These findings highlight a need to explore and understand the socio-psychological factors that encourage tolerance towards endangered species. Our research also demonstrates the applicability of this approach to tolerance research to a wide range of socio-economic and cultural contexts and reveals its capacity to enhance carnivore conservation efforts worldwide. PMID:26760035

  13. Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy.

    PubMed

    Majewski, Tadeusz; Lee, Sangkyou; Jeong, Joon; Yoon, Dong-Sup; Kram, Andrzej; Kim, Mi-Sook; Tuziak, Tomasz; Bondaruk, Jolanta; Lee, Sooyong; Park, Weon-Seo; Tang, Kuang S; Chung, Woonbok; Shen, Lanlan; Ahmed, Saira S; Johnston, Dennis A; Grossman, H Barton; Dinney, Colin P; Zhou, Jain-Hua; Harris, R Alan; Snyder, Carrie; Filipek, Slawomir; Narod, Steven A; Watson, Patrice; Lynch, Henry T; Gazdar, Adi; Bar-Eli, Menashe; Wu, Xifeng F; McConkey, David J; Baggerly, Keith; Issa, Jean-Pierre; Benedict, William F; Scherer, Steven E; Czerniak, Bogdan

    2008-07-01

    The search for the genomic sequences involved in human cancers can be greatly facilitated by maps of genomic imbalances identifying the involved chromosomal regions, particularly those that participate in the development of occult preneoplastic conditions that progress to clinically aggressive invasive cancer. The integration of such regions with human genome sequence variation may provide valuable clues about their overall structure and gene content. By extension, such knowledge may help us understand the underlying genetic components involved in the initiation and progression of these cancers. We describe the development of a genome-wide map of human bladder cancer that tracks its progression from in situ precursor conditions to invasive disease. Testing for allelic losses using a genome-wide panel of 787 microsatellite markers was performed on multiple DNA samples, extracted from the entire mucosal surface of the bladder and corresponding to normal urothelium, in situ preneoplastic lesions, and invasive carcinoma. Using this approach, we matched the clonal allelic losses in distinct chromosomal regions to specific phases of bladder neoplasia and produced a detailed genetic map of bladder cancer development. These analyses revealed three major waves of genetic changes associated with growth advantages of successive clones and reflecting a stepwise conversion of normal urothelial cells into cancer cells. The genetic changes map to six regions at 3q22-q24, 5q22-q31, 9q21-q22, 10q26, 13q14, and 17p13, which may represent critical hits driving the development of bladder cancer. Finally, we performed high-resolution mapping using single nucleotide polymorphism markers within one region on chromosome 13q14, containing the model tumor suppressor gene RB1, and defined a minimal deleted region associated with clonal expansion of in situ neoplasia. These analyses provided new insights on the involvement of several non-coding sequences mapping to the region and identified

  14. Understanding and Evaluating Human Thermal Comfort at Tertiary Level Using a Computer-Based Laboratory Teaching Tool

    ERIC Educational Resources Information Center

    Pellegrini, Marco

    2014-01-01

    Phase changes in water are experienced in everyday life but students often struggle to understand mechanisms that regulate them. Human thermal comfort is closely related to humidity, evaporative heat loss and heat transfer. The purpose of the present study is to assist students in the evaluation of human thermal comfort. Such a goal is achievable…

  15. On the Importance of Comparative Research for the Understanding of Human Behavior and Development: A Reply to Gottlieb & Lickliter (2004)

    ERIC Educational Resources Information Center

    Maestripieri, Dario

    2005-01-01

    Comparative behavioral research is important for a number of reasons and can contribute to the understanding of human behavior and development in many different ways. Research with animal models of human behavior and development can be a source not only of general principles and testable hypotheses but also of empirical information that may be…

  16. Proteomic Analysis of the Developmental Trajectory of Human Hepatic Membrane Transporter Proteins in the First Three Months of Life.

    PubMed

    Mooij, Miriam G; van de Steeg, Evita; van Rosmalen, Joost; Windster, Jonathan D; de Koning, Barbara A E; Vaes, Wouter H J; van Groen, Bianca D; Tibboel, Dick; Wortelboer, Heleen M; de Wildt, Saskia N

    2016-07-01

    Human hepatic membrane-embedded transporter proteins are involved in trafficking endogenous and exogenous substrates. Even though impact of transporters on pharmacokinetics is recognized, little is known on maturation of transporter protein expression levels, especially during early life. We aimed to study the protein expression of 10 transporters in liver tissue from fetuses, infants, and adults. Transporter protein expression levels [ATP-binding cassette transporter (ABC)B1, ABCG2, ABCC2, ABCC3, bile salt efflux pump, glucose transporter 1, monocarboxylate transporter 1, organic anion transporter polypeptide (OATP)1B1, OATP2B1, and organic cation/carnitine transporter 2) were quantified using ultraperformance liquid chromatography tandem mass spectrometry in snap-frozen postmortem fetal, infant, and adult liver samples. Protein expression was quantified in isolated crude membrane fractions. The possible association between postnatal and postmenstrual age versus protein expression was studied. We studied 25 liver samples, as follows: 10 fetal [median gestational age 23.2 wk (range 16.4-37.9)], 12 infantile [gestational age at birth 35.1 wk (27.1-41.0), postnatal age 1 wk (0-11.4)], and 3 adult. The relationship of protein expression with age was explored by comparing age groups. Correlating age within the fetal/infant age group suggested four specific protein expression patterns, as follows: stable, low to high, high to low, and low-high-low. The impact of growth and development on human membrane transporter protein expression is transporter-dependent. The suggested age-related differences in transporter protein expression may aid our understanding of normal growth and development, and also may impact the disposition of substrate drugs in neonates and young infants. PMID:27103634

  17. Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors.

    PubMed

    Eberhardt, Esther; Havlicek, Steven; Schmidt, Diana; Link, Andrea S; Neacsu, Cristian; Kohl, Zacharias; Hampl, Martin; Kist, Andreas M; Klinger, Alexandra; Nau, Carla; Schüttler, Jürgen; Alzheimer, Christian; Winkler, Jürgen; Namer, Barbara; Winner, Beate; Lampert, Angelika

    2015-09-01

    Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain. PMID:26321143

  18. Understanding Human Decision Making as a Driver for Carbon Sequestration on Land

    NASA Astrophysics Data System (ADS)

    Failey, E. L.; Dilling, L.

    2008-12-01

    As society begins to grapple with reducing the concentration of carbon dioxide and other greenhouse gases in the atmosphere in order to address climate change, policy discussions have emerged on the role of land use as a means to sequester carbon. Land use is already a key player in the global carbon budget through manipulations of vegetation and soils for agriculture and forestry. At the heart of land use is human decision making. The land use pattern and its attendant carbon impacts are a manifestation of a complex set of policy, economic, and cultural drivers that are channeled and expressed through individuals making decisions about land use. In order to understand the current pattern of carbon fluxes on managed land, and any future potential for land use to play a greater role in sequestering carbon, it is essential to understand the drivers of land use decision making at different scales, and their intersection with new imperatives and opportunities coming from climate mitigation goals. To this end, we have conducted a case study on land use decision making in the U.S. state of Colorado, a western state with significant portions of land managed by U.S. Federal governmental agencies in addition to privately-owned agricultural, grazing and forested lands. Our main goal was to put together a first-order look at the types of decision makers involved in managing land, what influences their decisions, and how the potential for storage of additional carbon on land might vary according to ownership category and land vegetation type. Our study has three significant components: 1. examining ownership patterns; 2. calculating the flux and carbon storage by land ownership category; and 3. illuminating the influences on land use decisions at different scales. In this paper, we will report the preliminary results of GIS work examining carbon fluxes by ownership category and the potential for additional storage of carbon based on policy and economic incentives.

  19. Towards an understanding and application of environmental flow requirements for human welfare in East African Rivers

    NASA Astrophysics Data System (ADS)

    McClain, Michael

    2013-04-01

    lands. Environmental flow recommendations have been made at six locations along the river, including three sites destined for the construction of new dams and multipurpose reservoirs. Flow recommendations consist of variable mean monthly base flows during normal and drought years and medium to large floods timed to achieve specific ecological objectives. The objective of water authorities, and thus of environmental flow recommendations, is to conserve the current good ecological status of the river and the many services it provides to people living along its margins. Complimentary research on the interrelationships between flow variability, ecosystem function, and human welfare is turning the Mara into a model system for better understanding these dynamics in an African development context.

  20. Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment

    PubMed Central

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

    2012-01-01

    Benzene causes acute myeloid leukemia and probably other hematological malignancies. As benzene also causes hematotoxicity even in workers exposed to levels below the US permissible occupational exposure limit of 1 part per million, further assessment of the health risks associated with its exposure, particularly at low levels, is needed. Here, we describe the probable mechanism by which benzene induces leukemia involving the targeting of critical genes and pathways through the induction of genetic, chromosomal or epigenetic abnormalities and genomic instability, in a hematopoietic stem cell (HSC); stromal cell dysregulation; apoptosis of HSCs and stromal cells and altered proliferation and differentiation of HSCs. These effects modulated by benzene-induced oxidative stress, aryl hydrocarbon receptor dysregulation and reduced immunosurveillance, lead to the generation of leukemic stem cells and subsequent clonal evolution to leukemia. A mode of action (MOA) approach to the risk assessment of benzene was recently proposed. This approach is limited, however, by the challenges of defining a simple stochastic MOA of benzene-induced leukemogenesis and of identifying relevant and quantifiable parameters associated with potential key events. An alternative risk assessment approach is the application of toxicogenomics and systems biology in human populations, animals and in vitro models of the HSC stem cell niche, exposed to a range of levels of benzene. These approaches will inform our understanding of the mechanisms of benzene toxicity and identify additional biomarkers of exposure, early effect and susceptibility useful for risk assessment. PMID:22166497

  1. Understanding Social Complexity Within the Wildland-Urban Interface: A New Species of Human Habitation?

    NASA Astrophysics Data System (ADS)

    Paveglio, Travis B.; Jakes, Pamela J.; Carroll, Matthew S.; Williams, Daniel R.

    2009-06-01

    The lack of knowledge regarding social diversity in the Wildland Urban Interface (WUI) or an in-depth understanding of the ways people living there interact to address common problems is concerning, perhaps even dangerous, given that community action is necessary for successful wildland fire preparedness and natural resource management activities. In this article, we lay out the knowledge and preliminary case study evidence needed to begin systematically documenting the differing levels and types of adaptive capacity WUI communities have for addressing collective problems such as wildland fire hazard. In order to achieve this end, we draw from two theoretical perspectives encompassing humans' interactions with their environment, including (1) Kenneth Wilkinson's interactional approach to community, (2) and certain elements of place literature. We also present case study research on wildfire protection planning in two drastically different California communities to illustrate how social diversity influences adaptive capacity to deal with hazards such as wildland fire. These perspectives promote an image of the WUI not as a monolithic entity but a complex mosaic of communities with different needs and existing capacities for wildland fire and natural resource management.

  2. Understanding customers' holistic perception of switches in automotive human-machine interfaces.

    PubMed

    Wellings, Tom; Williams, Mark; Tennant, Charles

    2010-01-01

    For successful new product development, it is necessary to understand the customers' holistic experience of the product beyond traditional task completion, and acceptance measures. This paper describes research in which ninety-eight UK owners of luxury saloons assessed the feel of push-switches in five luxury saloon cars both in context (in-car) and out of context (on a bench). A combination of hedonic data (i.e. a measure of 'liking'), qualitative data and semantic differential data was collected. It was found that customers are clearly able to differentiate between switches based on the degree of liking for the samples' perceived haptic qualities, and that the assessment environment had a statistically significant effect, but that it was not universal. A factor analysis has shown that perceived characteristics of switch haptics can be explained by three independent factors defined as 'Image', 'Build Quality', and 'Clickiness'. Preliminary steps have also been taken towards identifying whether existing theoretical frameworks for user experience may be applicable to automotive human-machine interfaces. PMID:19375691

  3. Ad cerebrum per scientia: Ira Hirsh, psychoacoustics, and new approaches to understanding the human brain

    NASA Astrophysics Data System (ADS)

    Lauter, Judith

    2002-05-01

    As Research Director of CID, Ira emphasized the importance of combining information from biology with rigorous studies of behavior, such as psychophysics, to better understand how the brain and body accomplish the goals of everyday life. In line with this philosophy, my doctoral dissertation sought to explain brain functional asymmetries (studied with dichotic listening) in terms of the physical dimensions of a library of test sounds designed to represent a speech-music continuum. Results highlighted individual differences plus similarities in terms of patterns of relative ear advantages, suggesting an organizational basis for brain asymmetries depending on physical dimensions of stimulus and gesture with analogs in auditory, visual, somatosensory, and motor systems. My subsequent work has employed a number of noninvasive methods (OAEs, EPs, qEEG, PET, MRI) to explore the neurobiological bases of individual differences in general and functional asymmetries in particular. This research has led to (1) the AXS test battery for assessing the neurobiology of human sensory-motor function; (2) the handshaking model of brain function, describing dynamic relations along all three body/brain axes; (3) the four-domain EPIC model of functional asymmetries; and (4) the trimodal brain, a new model of individual differences based on psychoimmunoneuroendocrinology.

  4. Understanding social complexity within the wildland-urban interface: a new species of human habitation?

    PubMed

    Paveglio, Travis B; Jakes, Pamela J; Carroll, Matthew S; Williams, Daniel R

    2009-06-01

    The lack of knowledge regarding social diversity in the Wildland Urban Interface (WUI) or an in-depth understanding of the ways people living there interact to address common problems is concerning, perhaps even dangerous, given that community action is necessary for successful wildland fire preparedness and natural resource management activities. In this article, we lay out the knowledge and preliminary case study evidence needed to begin systematically documenting the differing levels and types of adaptive capacity WUI communities have for addressing collective problems such as wildland fire hazard. In order to achieve this end, we draw from two theoretical perspectives encompassing humans' interactions with their environment, including (1) Kenneth Wilkinson's interactional approach to community, (2) and certain elements of place literature. We also present case study research on wildfire protection planning in two drastically different California communities to illustrate how social diversity influences adaptive capacity to deal with hazards such as wildland fire. These perspectives promote an image of the WUI not as a monolithic entity but a complex mosaic of communities with different needs and existing capacities for wildland fire and natural resource management. PMID:19238478

  5. Current understanding of dysbiosis in disease in human and animal models

    PubMed Central

    DeGruttola, Arianna K.; Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2016-01-01

    Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects over two million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed “dysbiosis”. In spite of the extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, we have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments in order to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases. PMID:27070911

  6. Current Understanding of Dysbiosis in Disease in Human and Animal Models.

    PubMed

    DeGruttola, Arianna K; Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2016-05-01

    Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed "dysbiosis." Despite extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in patients with IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, the authors have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases. PMID:27070911

  7. From competencies to human interests: ways of knowing and understanding in medical education.

    PubMed

    Kumagai, Arno K

    2014-07-01

    When considering the teaching and learning of topics of social relevance in medicine, such as professionalism, medical ethics, the doctor-patient relationship, and issues of diversity and social justice, one is tempted to ask, are the ways of knowing in these fields different from that in the biomedical and clinical sciences? Furthermore, given that the competency approach is dominant in medical education, one might also ask, is the competency model truly appropriate for all of the types of knowledge necessary to become a good physician? These questions are not merely academic, for they are at the core of how these subjects are taught, learned, and assessed.The goal of this article is threefold: first, to explore the nature of knowing and the educational goals in different areas of medicine and, in particular, those areas that have social relevance; second, to critically review the concept of competencies when applied to education in these areas; and third, to explore alternative strategies for teaching, learning, and assessment. This discussion reflects a view that the goal of education in areas of social relevance in medicine should be the enhancement of an understanding of-a deep and abiding connection with-the social responsibilities of the physician. Moving beyond competencies, this approach aspires toward the development of practical wisdom (phronesis) which, when embodied in the physician, links the knowledge and skills of the biomedical and clinical sciences with a moral orientation and call to action that addresses human interests in the practice of medicine. PMID:24662200

  8. Sleep in Korea: a developmental perspective.

    PubMed

    Jeong, D U

    1995-05-01

    Sleep is an ubiquitous phenomenon. It is a developmental product, being subjected to the vicissitudes of human behavior and culture. The author will attempt to elaborate on sleep, sleep disorders, and sleep medicine in Korea from various developmental perspectives (i.e. personal, national and scientific). Korea is a rapidly developing industrialized nation and is now experiencing immense cultural changes which force individuals to change their behavior and value systems. For example, shift working is becoming increasingly popular and early working hours are being adopted by more companies as a measure to win competitions in the international market. In the clinical setting it is observed very easily that patients develop and maintain disturbed sleep-wake rhythm and its consequences. More obstructive sleep apnea, presumably due to obesity, are observed and studied in sleep clinics. The nuclear family system, an inevitable outcome of industrialization, produces some profound difference in sleeping arrangement such as children's earlier separation from parental or grandparental sleeping environment. The question is how these and other industrialization-related changes may affect the incidence and the manifestation of sleep and sleep disorders. In the background there is emerging interest in healthy sleep and sleep disorders, exemplified by increasing coverage of the topics in the mass media and the publication business. Development of sleep medicine/research per se also involves a developmental perspective. Interests in sleep and sleep disorders began sporadically decades ago in Korea and are now actively being organized mainly by the Korean Association of Sleep Medicine and Psychophysiology as a unified developing force. Understanding of sleep and of sleep disorders is not complete without in-depth understanding of culture, philosophy, and tradition from developmental perspectives. Traditional ideas and wisdom from the past are the unavoidable resources for further

  9. Developmental delay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrition support is essential for the care of the child with developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the child’s nutrition status, feeding ability, and medical condition may be determined. Nutrition assessments may be performed at leas...

  10. Developmental dyscalculia.

    PubMed

    Shalev, Ruth S

    2004-10-01

    Developmental dyscalculia is a specific learning disability affecting the normal acquisition of arithmetic skills. Genetic, neurobiologic, and epidemiologic evidence indicates that dyscalculia, like other learning disabilities, is a brain-based disorder. However, poor teaching and environmental deprivation have also been implicated in its etiology. Because the neural network of both hemispheres comprises the substrate of normal arithmetic skills, dyscalculia can result from dysfunction of either hemisphere, although the left parietotemporal area is of particular significance. The prevalence of developmental dyscalculia is 5 to 6% in the school-aged population and is as common in girls as in boys. Dyscalculia can occur as a consequence of prematurity and low birthweight and is frequently encountered in a variety of neurologic disorders, such as attention-deficit hyperactivity disorder (ADHD), developmental language disorder, epilepsy, and fragile X syndrome. Developmental dyscalculia has proven to be a persisting learning disability, at least for the short term, in about half of affected preteen pupils. Educational interventions for dyscalculia range from rote learning of arithmetic facts to developing strategies for solving arithmetic exercises. The long-term prognosis of dyscalculia and the role of remediation in its outcome are yet to be determined. PMID:15559892

  11. [Developmental Assessment.

    ERIC Educational Resources Information Center

    Fenichel, Emily, Ed.

    1994-01-01

    This newsletter theme issue contains contributions by parents, practitioners, researchers, administrators, and providers of technical assistance, which explore aspects of the complex process of developmental assessment of infants and young children. They describe what is helpful and what can be harmful in current assessment practice. They offer…

  12. Use of Both Cumulus Cells’ Transcriptomic Markers and Zona Pellucida Birefringence to Select Developmentally Competent Oocytes in Human Assisted Reproductive Technologies

    PubMed Central

    2015-01-01

    Background Selection of the best oocyte for subsequent steps of fertilization and embryo transfer was shown to be the crucial step in human infertility treatment procedure. Oocyte selection using morphological criteria mainly Zona pellucida (ZP) has been the gold standard method in assisted reproductive technologies (ART) clinics, but this selection approach has limitations in terms of accuracy, objectivity and constancy. Recent studies using OMICs-based approaches have allowed the identification of key molecular markers that quantitatively and non-invasively predict the oocyte quality for higher pregnancy rates and efficient infertility treatment. These biomarkers are a valuable reinforcement of the morphological selection criteria widely used in in vitro fertilization (IVF) clinics. In this context, this study was designed to investigate the relationship between transcriptomic predictors of oocyte quality found by our group and the conventional morphological parameters of oocyte quality mainly the ZP birefringence. Results Microarray data revealed that 48 and 27 differentially expressed candidate genes in cumulus cells (CCs) were respectively overexpressed and underexpressed in the ZGP (Zona Good Pregnant) versus ZBNP (Zona Bad Non Pregnant) groups. More than 70% of previously reported transcriptomic biomarkers of oocyte developmental competence were confirmed in this study. The analysis of possible association between ZP birefringence versus molecular markers approach showed an absence of correlation between them using the current set of markers. Conclusions This study suggested a new integrative approach that matches morphological and molecular approaches used to select developmentally competent oocytes able to lead to successful pregnancy and the delivery of healthy baby. For each ZP birefringence score, oocytes displayed a particular CCs' gene expression pattern. However, no correlations were found between the 7 gene biomarkers of oocyte developmental

  13. ST8SIA4-Dependent Polysialylation is Part of a Developmental Program Required for Germ Layer Formation from Human Pluripotent Stem Cells.

    PubMed

    Berger, Ryan P; Sun, Yu Hua; Kulik, Michael; Lee, Jin Kyu; Nairn, Alison V; Moremen, Kelley W; Pierce, Michael; Dalton, Stephen

    2016-07-01

    Polysialic acid (PSA) is a carbohydrate polymer of repeating α-2,8 sialic acid residues that decorates multiple targets, including neural cell adhesion molecule (NCAM). PST and STX encode the two enzymes responsible for PSA modification of target proteins in mammalian cells, but despite widespread polysialylation in embryonic development, the majority of studies have focused strictly on the role of PSA in neurogenesis. Using human pluripotent stem cells (hPSCs), we have revisited the developmental role of PST and STX and show that early progenitors of the three embryonic germ layers are polysialylated on their cell surface. Changes in polysialylation can be attributed to lineage-specific expression of polysialyltransferase genes; PST is elevated in endoderm and mesoderm, while STX is elevated in ectoderm. In hPSCs, PST and STX genes are epigenetically marked by overlapping domains of H3K27 and H3K4 trimethylation, indicating that they are held in a "developmentally-primed" state. Activation of PST transcription during early mesendoderm differentiation is under control of the T-Goosecoid transcription factor network, a key regulatory axis required for early cell fate decisions in the vertebrate embryo. This establishes polysialyltransferase genes as part of a developmental program associated with germ layer establishment. Finally, we show by shRNA knockdown and CRISPR-Cas9 genome editing that PST-dependent cell surface polysialylation is essential for endoderm specification. This is the first report to demonstrate a role for a glycosyltransferase in hPSC lineage specification. Stem Cells 2016;34:1742-1752. PMID:27074314

  14. Effect of aspiration vacuum on the developmental competence of immature human oocytes retrieved using a 20-gauge needle.

    PubMed

    Hashimoto, Shu; Fukuda, Aisaku; Murata, Yasutaka; Kikkawa, Miho; Oku, Hirotsugu; Kanaya, Hiroyuki; Sonoda, Momoyo; Sugihara, Kengo; Murata, Tomoko; Nagata, Fumie; Nakaoaka, Yoshiharu; Morimoto, Yoshiharu

    2007-04-01

    In-vitro maturation (IVM) of immature oocytes has been proposed as a potential alternative to conventional IVF treatment following ovarian stimulation. However, the effects of the oocyte retrieval conditions on subsequent development have not been well understood. This study assessed the effects of different aspiration vacuums during oocyte retrieval on the developmental competence of immature oocytes following IVM, IVF and embryo transfer, retrospectively. Immature oocytes were aspirated with 20-gauge needles with a vacuum of 180 or 300 mmHg. Immature oocytes were cultured in IVM medium for 26 h. All mature oocytes were inseminated by intracytoplasmic sperm injection (ICSI). Embryo transfer was carried out 2 or 3 days after ICSI. The percentage of cumulus-cell enclosed oocytes and of transferable embryos per retrieved oocytes in 180 mmHg (69.7% and 23.8%, respectively) were significantly higher (P < 0.01) than those in 300 mmHg (46.2% and 12.8%, respectively). The ongoing pregnancy rate per retrieval cycle in 180 mmHg (30%) was higher (P < 0.01) than that in 300 mmHg (4.3%). The data indicate that lower pressure of vacuum aspiration with a 20-gauge needle improves the developmental competence of immature oocytes following IVM, IVF and embryo transfer. PMID:17425825

  15. Understanding the links between humans, climate change, water and carbon and in a Corn Belt Watershed

    NASA Astrophysics Data System (ADS)

    Secchi, S.; Perez Lapena, B.; Teshager, A. D.; Bhattarai, M. D.; Schoof, J. T.

    2014-12-01

    Accounting for the value of ecosystem services is difficult for several reasons: we need to understand and model the behavior of humans, and how they respond to changes in policies, we need to quantify the changes in material fluxes or ecological responses resulting from their behavior, and finally we need to monetize the value of those material fluxes. Since coupled human-natural systems are highly idiosyncratic, integrated modeling can be challenging because it is not easy to transfer results from one system to another. Moreover, modeling changes in multiple ecosystem services often requires the simultaneous coordination of several biophysical models. In a non-static world, climate change models are also often necessary to identify future challenges and opportunities for better policy-making. We will discuss results from an integrated modeling perspective for the Raccoon River watershed in central Iowa. The watershed is in the heart of the Corn Belt, and it is under very intensive agricultural production which results in nitrate levels so high that a Total Maximum Daily Load has been put in place. The Des Moines Water Works that provides water to Iowa's capital either from the Raccoon or the Des Moines River has had to build several layers of treatment to ensure the water is safe to drink. We will present results from the integration of an agent-based model with a surface water quality model (the Soil and Water Assessment Tool) and an edge of field environmental model (the Environmental Policy Integrated Climate). The integration can simultaneously provide changes in water quality indicators - particularly nitrates, which can be monetized using the avoided cost method - and carbon sequestration - for which monetary values are readily available in the literature. This integrated system is linked to regional climate change models to help assess changes in agricultural productivity and farmers' behavior in the future. We will discuss the importance of quantifying

  16. Developmental psychopathology: concepts and challenges.

    PubMed

    Rutter, M; Sroufe, L A

    2000-01-01

    The defining features of developmental psychopathology concepts include attention to the understanding of causal processes, appreciation of the role of developmental mechanisms, and consideration of continuities and discontinuities between normality and psychopathology. Accomplishments with respect to these issues are reviewed in relation to attachment disorders, antisocial behavior, autism, depressive disorder, schizophrenia, and intellectual development. Major research challenges remain in relation to measurement issues, comorbidity, gender differences, cognitive processing, nature-nurture interplay, heterotypic continuity, continuities between normal variations and disorders, developmental programming, and therapeutic mechanisms in effective treatments. PMID:11014739

  17. Combining metagenomics, metatranscriptomics and viromics to explore novel microbial interactions: towards a systems-level understanding of human microbiome

    PubMed Central

    Bikel, Shirley; Valdez-Lara, Alejandra; Cornejo-Granados, Fernanda; Rico, Karina; Canizales-Quinteros, Samuel; Soberón, Xavier; Del Pozo-Yauner, Luis; Ochoa-Leyva, Adrián

    2015-01-01

    The advances in experimental methods and the development of high performance bioinformatic tools have substantially improved our understanding of microbial communities associated with human niches. Many studies have documented that changes in microbial abundance and composition of the human microbiome is associated with human health and diseased state. The majority of research on human microbiome is typically focused in the analysis of one level of biological information, i.e., metagenomics or metatranscriptomics. In this review, we describe some of the different experimental and bioinformatic strategies applied to analyze the 16S rRNA gene profiling and shotgun sequencing data of the human microbiome. We also discuss how some of the recent insights in the combination of metagenomics, metatranscriptomics and viromics can provide more detailed description on the interactions between microorganisms and viruses in oral and gut microbiomes. Recent studies on viromics have begun to gain importance due to the potential involvement of viruses in microbial dysbiosis. In addition, metatranscriptomic combined with metagenomic analysis have shown that a substantial fraction of microbial transcripts can be differentially regulated relative to their microbial genomic abundances. Thus, understanding the molecular interactions in the microbiome using the combination of metagenomics, metatranscriptomics and viromics is one of the main challenges towards a system level understanding of human microbiome. PMID:26137199

  18. Developmental changes in the expression of somatostatin receptors (1-5) in the brain, hypothalamus, pituitary and spinal cord of the human fetus.

    PubMed

    Goodyer, C G; Grigorakis, S I; Patel, Y C; Kumar, U

    2004-01-01

    The actions of somatostatin (SST) in the nervous system are mediated by specific high affinity SST receptors (SSTR1-5). However, the role of this hormone and the distribution of its receptor subtypes have not yet been defined in neural structures of the human fetus. We have analyzed four neural tissues (CNS, hypothalamus, pituitary and spinal cord) from early to midgestation for the expression of five human SSTR mRNAs, using a reverse transcription-polymerase chain reaction and Southern blot approach. These fetal neural tissues all express mRNA for multiple SSTR subtypes from as early as 16 weeks of fetal life but the developmental patterns of expression vary considerably. Transcripts for SSTR1 and SSTR2A are the most widely distributed, being expressed in all four neural tissues. SSTR2A is often the earliest transcript to be detected (7.5 weeks in CNS). SSTR3 mRNA is confined to the pituitary, hypothalamus, and spinal cord. SSTR4 is expressed in fetal brain, hypothalamus and spinal cord but not pituitary. SSTR5 mRNA is detectable in the pituitary and spinal cord by 14-16 weeks of fetal life. This mapping of SSTR mRNA expression patterns in human fetal neural tissues is an important first step toward our goal of determining the role of SST in the nervous system during early stages in human development. PMID:15062986

  19. Assessment of boric acid and borax using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents

    SciTech Connect

    Moore, J.A.

    1995-03-01

    This document presents an evaluation of the reproductive and developmental effects of boric acid, H3BO3 (CAS Registry No. 10043-35-3) and disodium tetraborate decahydrate or borax, Na2B4O2O(CAS Registry No. 1303-96-4). The element, boron, does not exist naturally. In dilute aqueous solution and at physiological pH (7.4), the predominant species in undissociated boric acid (greater than 98%), irrespective of whether the initial material was boric acid of borax. Therefore, it is both useful and correct to compare exposures and dosages to boric acid and borax in terms of `boron equivalents`, since both materials form equivalent species in dilute aqueous solution with similar systemic effects. In order to be clear in this document, the term `boron` will refer to `boron equivalents` or percent boron in boric acid and borax.

  20. Analysis of splice variants for the C. elegans orthologue of human neuroligin reveals a developmentally regulated transcript.

    PubMed

    Calahorro, Fernando; Holden-Dye, Lindy; O'Connor, Vincent

    2015-03-01

    Neuroligins are synaptic adhesion molecules and important determinants of synaptic function. They are expressed at postsynaptic sites and involved in synaptic organization through key extracellular and intracellular protein interactions. They undergo trans-synaptic interaction with presynaptic neurexins. Distinct neuroligins use differences in their intracellular domains to selectively recruit synaptic scaffolds and this plays an important role in how they encode specialization of synaptic function. Several levels of regulation including gene expression, splicing, protein translation and processing regulate the expression of neuroligin function. We have used in silico and cDNA analyses to investigate the mRNA splicing of the Caenorhabditis elegans orthologue nlg-1. Transcript analysis highlights the potential for gene regulation with respect to both temporal expression and splicing. We found nlg-1 splice variants with all the predicted exons are a minor species relative to major splice variants lacking exons 13 and 14, or 14 alone. These major alternatively spliced variants change the intracellular domain of the gene product NLG-1. Interestingly, exon 14 encodes a cassette with two distinct potential functional domains. One is a polyproline SH3 binding domain and the other has homology to a region encoding the binding site for the scaffolding protein gephyrin in mammalian neuroligins. This suggests differential splicing impacts on NLG-1 competence to recruit intracellular binding partners. This may have developmental relevance as nlg-1 exon 14 containing transcripts are selectively expressed in L2-L3 larvae. These results highlight a developmental regulation of C. elegans nlg-1 that could play a key role in the assembly of synaptic protein complexes during the early stages of nervous system development. PMID:25726726

  1. The rise of developmental genetics - a historical account of the fusion of embryology and cell biology with human genetics and the emergence of the Stem Cell Initiative.

    PubMed

    Kidson, S H; Ballo, R; Greenberg, L J

    2016-01-01

    Genetics and cell biology are very prominent areas of biological research with rapid advances being driven by a flood of theoretical, technological and informational knowledge. Big biology and small biology continue to feed off each other. In this paper, we provide a brief overview of the productive interactions that have taken place between human geneticists and cell biologists at UCT, and credit is given to the enabling environment created led by Prof. Peter Beighton. The growth of new disciplines and disciplinary mergers that have swept away division of the past to make new exciting syntheses are discussed. We show how our joint research has benefitted from worldwide advances in developmental genetics, cloning and stem cell technologies, genomics, bioinformatics and imaging. We conclude by describing the role of the UCT Stem Cell Initiative and show how we are using induced pluripotent cells to carry out disease-in-the- dish studies on retinal degeneration and fibrosis. PMID:27245528

  2. Understanding Historical Human Migration Patterns and Interbreeding (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

    ScienceCinema

    Willerslev, Eske [University of Copenhagen

    2013-01-15

    Eske Willerslev from the University of Copenhagen on "Understanding Historical Human Migration Patterns and Interbreeding Using the Ancient Genomes of a Palaeo-Eskimo and an Aboriginal Australian" at the 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, California.

  3. Understanding Historical Human Migration Patterns and Interbreeding (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

    SciTech Connect

    Willerslev, Eske

    2012-03-21

    Eske Willerslev from the University of Copenhagen on "Understanding Historical Human Migration Patterns and Interbreeding Using the Ancient Genomes of a Palaeo-Eskimo and an Aboriginal Australian" at the 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, California.

  4. Evo-Devo insights from pathological networks: exploring craniosynostosis as a developmental mechanism for modularity and complexity in the human skull.

    PubMed

    Esteve-Altava, Borja; Rasskin-Gutman, Diego

    2015-07-20

    Bone fusion has occurred repeatedly during skull evolution in all tetrapod lineages, leading to a reduction in the number of bones and an increase in their morphological complexity. The ontogeny of the human skull includes also bone fusions as part of its normal developmental process. However, several disruptions might cause premature closure of cranial sutures (craniosynostosis), reducing the number of bones and producing new skull growth patterns that causes shape changes. Here, we compare skull network models of a normal newborn with different craniosynostosis conditions, the normal adult stage, and phylogenetically reconstructed forms of a primitive tetrapod, a synapsid, and a placental mammal. Changes in morphological complexity of newborn-to-synostosed skulls are two to three times less than in newborn-to-adult; and even smaller when we compare them to the increases among the reconstructed ancestors in the evolutionary transitions. In addition, normal, synostosed, and adult human skulls show the same connectivity modules: facial and cranial. Differences arise in the internal structure of these modules. In the adult skull the facial module has an internal hierarchical organization, whereas the cranial module has a regular network organization. However, all newborn forms, normal and synostosed, do not reach such kind of internal organization. We conclude that the subtle changes in skull complexity at the developmental scale can change the modular substructure of the newborn skull to more integrated modules in the adult skull, but is not enough to generate radical changes as it occurs at a macroevolutionary scale. The timing of closure of craniofacial sutures, together with the conserved patterns of morphological modularity, highlights a potential relation between the premature fusion of bones and the evolution of the shape of the skull in hominids. PMID:25324462

  5. Mixing Qualitative and Quantitative Research in Developmental Science: Uses and Methodological Choices

    ERIC Educational Resources Information Center

    Yoshikawa, Hirokazu; Weisner, Thomas S.; Kalil, Ariel; Way, Niobe

    2008-01-01

    Multiple methods are vital to understanding development as a dynamic, transactional process. This article focuses on the ways in which quantitative and qualitative methodologies can be combined to enrich developmental science and the study of human development, focusing on the practical questions of "when" and "how." Research situations that may…

  6. TITLE OF ABSTRACT: MECHANISMS UNDERLYING SYNERGISTIC DEVELOPMENTAL TOXICITY OF POLYCYCLIC AROMATIC HYDROCARBONS IN ZEBRAFISH (DANIO RERIO)

    EPA Science Inventory

    Understanding the molecular pathways of synergistic developmental toxicity of PAHs will lead to benefits for human as well as wildlife health. As additive models of toxicity are currently used to estimate the hazard of complex mixtures, implementation of synergistic models wh...

  7. Anatomy of the pectoral and forelimb muscles of wildtype and green fluorescent protein-transgenic axolotls and comparison with other tetrapods including humans: a basis for regenerative, evolutionary and developmental studies

    PubMed Central

    Diogo, R; Tanaka, E M

    2012-01-01

    The axolotl Ambystoma mexicanum is one of the most used model organisms in evolutionary, developmental and regenerative studies, particularly because it can reconstitute a fully functional and complete forelimb/hindlimb. Surprisingly, there is no publication that describes all the pectoral and forelimb muscles of this species or provides a comparative framework between these muscles and those of other model organisms and of modern humans. In the present paper we describe and illustrate all these muscles in A. mexicanum and provide the first report about the myology of adults of a model organism that is based on analyses and dissections of both wildtype animals and transgenic animals that express green fluorescent protein (GFP) in muscle fibers. On the one hand, the inclusion of GFP-transgenic animals allows us to show the muscles as more commonly seen, and thus easier to understand, by current developmental and regenerative biologists. On the other hand, by including wildtype and GFP-transgenic animals and by visualizing these latter animals with and without a simultaneous transmission laser light, we were able to obtain a more complete and clearer understanding of the exact limit of the fleshy and tendinous parts of the muscles and their specific connections with the skeletal elements. This in turn allowed us to settle some controversies in previous anatomical and comparative studies. As most developmental, regenerative and evolutionary biologists are interested in comparing their observations of A. mexicanum with observations in other model organisms, and ultimately in using this information to increase the understanding of human evolution and medicine, we also provide tables showing the homologies between the pectoral and forelimb muscles of axolotls, of model organisms such as mice, frogs and chicken, and of Homo sapiens. An example illustrating the outcomes of using our methodology and of our observations is that they revealed that, contrary to what is often

  8. Understanding our Genetic Inheritance: The U.S. Human Genome Project, The First Five Years FY 1991--1995

    DOE R&D Accomplishments Database

    1990-04-01

    The Human Genome Initiative is a worldwide research effort with the goal of analyzing the structure of human DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century and will by of immense benefit to the field of medicine. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that affect mankind, as well as the many multifactorial diseases in which genetic predisposition plays an important role. A centrally coordinated project focused on specific objectives is believed to be the most efficient and least expensive way of obtaining this information. The basic data produced will be collected in electronic databases that will make the information readily accessible on convenient form to all who need it. This report describes the plans for the U.S. human genome project and updates those originally prepared by the Office of Technology Assessment (OTA) and the National Research Council (NRC) in 1988. In the intervening two years, improvements in technology for almost every aspect of genomics research have taken place. As a result, more specific goals can now be set for the project.

  9. Understanding our genetic inheritance: The US Human Genome Project, The first five years FY 1991--1995

    SciTech Connect

    1990-04-01

    The Human Genome Initiative is a worldwide research effort with the goal of analyzing the structure of human DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century and will by of immense benefit to the field of medicine. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that affect mankind, as well as the many multifactorial diseases in which genetic predisposition plays an important role. A centrally coordinated project focused on specific objectives is believed to be the most efficient and least expensive way of obtaining this information. The basic data produced will be collected in electronic databases that will make the information readily accessible on convenient form to all who need it. This report describes the plans for the U.S. human genome project and updates those originally prepared by the Office of Technology Assessment (OTA) and the National Research Council (NRC) in 1988. In the intervening two years, improvements in technology for almost every aspect of genomics research have taken place. As a result, more specific goals can now be set for the project.

  10. Developmental toxicology: status of the field and contribution of the National Toxicology Program.

    PubMed Central

    Schwetz, B A; Harris, M W

    1993-01-01

    The NTP has conducted developmental toxicity studies on more than 50 chemicals, often in multiple species. Several chemicals caused developmental toxicity in the absence of any toxicity to the mother. Although hazard to humans is determined by the level of exposure to the chemical and its inherent toxicity, those agents that selectively disturb the development of the conceptus are of particular concern because other manifestations of toxicity would not warn the mother of overexposure. Whether the LOAEL (lowest-observed adverse effect level) for maternal toxicity was high or low did not correlate with the potential of chemicals to cause developmental toxicity. The form of developmental toxicity that determined the LOAEL most frequently was decreased body weight in mice and rats, but not rabbits, where the LOAEL was determined more often by an increase in resorptions. Several in vitro and short-term tests appear promising as screens to predict the outcome of developmental toxicity studies in mammals. However, the only screens that have undergone formal validation studies are those evaluated by the NTP. Improvements in our ability to predict risk to humans have been limited by our knowledge of the mechanisms by which agents cause developmental toxicity. Thus, future growth is dependent on a better understanding of the biological processes that regulate normal development, therein providing the necessary framework for understanding mechanisms of abnormal development. PMID:8354175

  11. Transcending the Limitations of the Social Sciences: Insight, Understanding, and the Humanities in Educational Administration.

    ERIC Educational Resources Information Center

    Ryan, James

    1994-01-01

    Considers the role of the humanities in the study and practice of educational administration, offering significant insights into the human condition and the philosophical and moral aspects of education. Discusses the limitations of the subject-object dualism underpinning traditional social science. Explains how Slipperjack's "Honor the Sun,"…

  12. Human-Computer Interaction (HCI) in Educational Environments: Implications of Understanding Computers as Media.

    ERIC Educational Resources Information Center

    Berg, Gary A.

    2000-01-01

    Reviews literature in the field of human-computer interaction (HCI) as it applies to educational environments. Topics include the origin of HCI; human factors; usability; computer interface design; goals, operations, methods, and selection (GOMS) models; command language versus direct manipulation; hypertext; visual perception; interface…

  13. Why Primates? The Importance of Nonhuman Primates for Understanding Human Infancy

    ERIC Educational Resources Information Center

    Weiss, Daniel J.; Santos, Laurie R.

    2006-01-01

    We introduce the thematic collection by noting some striking similarities in the cognitive abilities of human infants and nonhuman primates. What are the implications of these similarities for our comprehension of human infant cognition? After providing a brief historical and conceptual background on comparative behavioral research, we discuss how…

  14. "A Friend Who Understand Fully": Notes on Humanizing Research in a Multiethnic Youth Community

    ERIC Educational Resources Information Center

    Paris, Django

    2011-01-01

    In this article, I conceptualize ethnographic, qualitative, and social language research with marginalized and oppressed communities as "humanizing research". Humanizing research is a methodological stance, which requires that our inquiries involve dialogic consciousness-raising and the building of relationships of dignity and care for both…

  15. School-Based Human Rights Education: Young Bahrainis' Knowledge and Understanding

    ERIC Educational Resources Information Center

    Eid, Fatima H.

    2014-01-01

    The growing interest in Human Rights Education (HRE) is linked in this paper to the UN Convention on the Rights of the Child (CRC, 1989). The linkage between citizenship education and HRE is also highlighted, along with the necessary critiques of human rights pronouncements regarding the situation of HRE in Bahrain while the challenges ahead in…

  16. Understanding the Human Genome Project: Using Stations to Provide a Comprehensive Overview

    ERIC Educational Resources Information Center

    Soto, Julio G.

    2005-01-01

    A lesson was designed for lower division general education, non-major biology lecture-only course that included the historical and scientific context, some of the skills used to study the human genome, results, conclusions and ethical consideration. Students learn to examine and compare the published Human Genome maps, and employ the strategies…

  17. Oversight on the Developmentally Disabled Assistance and Bill of Rights Act. Hearing Before the Subcommittee on the Handicapped of the Committee on Human Resources, U.S. Senate, 95th Congress, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate.

    Presented is testimony given before the Subcommittee on the Handicapped of the Senate Committee on Human Resources regarding the Developmentally Disabled Assistance and Bill of Rights Act. Statements are included from representatives of such agencies and organizations as the National Association for Retarded Citizens, American Occupational Therapy…

  18. The Importance of HRA in Human Space Flight: Understanding the Risks

    NASA Technical Reports Server (NTRS)

    Hamlin, Teri

    2010-01-01

    Human performance is critical to crew safety during space missions. Humans interact with hardware and software during ground processing, normal flight, and in response to events. Human interactions with hardware and software can cause Loss of Crew and/or Vehicle (LOCV) through improper actions, or may prevent LOCV through recovery and control actions. Humans have the ability to deal with complex situations and system interactions beyond the capability of machines. Human Reliability Analysis (HRA) is a method used to qualitatively and quantitatively assess the occurrence of human failures that affect availability and reliability of complex systems. Modeling human actions with their corresponding failure probabilities in a Probabilistic Risk Assessment (PRA) provides a more complete picture of system risks and risk contributions. A high-quality HRA can provide valuable information on potential areas for improvement, including training, procedures, human interfaces design, and the need for automation. Modeling human error has always been a challenge in part because performance data is not always readily available. For spaceflight, the challenge is amplified not only because of the small number of participants and limited amount of performance data available, but also due to the lack of definition of the unique factors influencing human performance in space. These factors, called performance shaping factors in HRA terminology, are used in HRA techniques to modify basic human error probabilities in order to capture the context of an analyzed task. Many of the human error modeling techniques were developed within the context of nuclear power plants and therefore the methodologies do not address spaceflight factors such as the effects of microgravity and longer duration missions. This presentation will describe the types of human error risks which have shown up as risk drivers in the Shuttle PRA which may be applicable to commercial space flight. As with other large PRAs

  19. Developmental Perspectives on Oxytocin and Vasopressin

    PubMed Central

    Hammock, Elizabeth A D

    2015-01-01

    The related neuropeptides oxytocin and vasopressin are involved in species-typical behavior, including social recognition behavior, maternal behavior, social bonding, communication, and aggression. A wealth of evidence from animal models demonstrates significant modulation of adult social behavior by both of these neuropeptides and their receptors. Over the last decade, there has been a flood of studies in humans also implicating a role for these neuropeptides in human social behavior. Despite popular assumptions that oxytocin is a molecule of social bonding in the infant brain, less mechanistic research emphasis has been placed on the potential role of these neuropeptides in the developmental emergence of the neural substrates of behavior. This review summarizes what is known and assumed about the developmental influence of these neuropeptides and outlines the important unanswered questions and testable hypotheses. There is tremendous translational need to understand the functions of these neuropeptides in mammalian experience-dependent development of the social brain. The activity of oxytocin and vasopressin during development should inform our understanding of individual, sex, and species differences in social behavior later in life. PMID:24863032

  20. Developmentally Restricted Genetic Determinants of Human Arsenic Metabolism: Association between Urinary Methylated Arsenic and CYT19 Polymorphisms in Children

    PubMed Central

    Meza, Maria Mercedes; Yu, Lizhi; Rodriguez, Yelitza Y.; Guild, Mischa; Thompson, David; Gandolfi, A. Jay; Klimecki, Walter T.

    2005-01-01

    We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7–11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18–79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials. PMID:15929903

  1. Developmentally restricted genetic determinants of human arsenic metabolism: association between urinary methylated arsenic and CYT19 polymorphisms in children.

    PubMed

    Meza, Maria Mercedes; Yu, Lizhi; Rodriguez, Yelitza Y; Guild, Mischa; Thompson, David; Gandolfi, A Jay; Klimecki, Walter T

    2005-06-01

    We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7-11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18-79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials. PMID:15929903

  2. Beat Keeping in a Sea Lion As Coupled Oscillation: Implications for Comparative Understanding of Human Rhythm.

    PubMed

    Rouse, Andrew A; Cook, Peter F; Large, Edward W; Reichmuth, Colleen

    2016-01-01

    Human capacity for entraining movement to external rhythms-i.e., beat keeping-is ubiquitous, but its evolutionary history and neural underpinnings remain a mystery. Recent findings of entrainment to simple and complex rhythms in non-human animals pave the way for a novel comparative approach to assess the origins and mechanisms of rhythmic behavior. The most reliable non-human beat keeper to date is a California sea lion, Ronan, who was trained to match head movements to isochronous repeating stimuli and showed spontaneous generalization of this ability to novel tempos and to the complex rhythms of music. Does Ronan's performance rely on the same neural mechanisms as human rhythmic behavior? In the current study, we presented Ronan with simple rhythmic stimuli at novel tempos. On some trials, we introduced "perturbations," altering either tempo or phase in the middle of a presentation. Ronan quickly adjusted her behavior following all perturbations, recovering her consistent phase and tempo relationships to the stimulus within a few beats. Ronan's performance was consistent with predictions of mathematical models describing coupled oscillation: a model relying solely on phase coupling strongly matched her behavior, and the model was further improved with the addition of period coupling. These findings are the clearest evidence yet for parity in human and non-human beat keeping and support the view that the human ability to perceive and move in time to rhythm may be rooted in broadly conserved neural mechanisms. PMID:27375418

  3. Beat Keeping in a Sea Lion As Coupled Oscillation: Implications for Comparative Understanding of Human Rhythm

    PubMed Central

    Rouse, Andrew A.; Cook, Peter F.; Large, Edward W.; Reichmuth, Colleen

    2016-01-01

    Human capacity for entraining movement to external rhythms—i.e., beat keeping—is ubiquitous, but its evolutionary history and neural underpinnings remain a mystery. Recent findings of entrainment to simple and complex rhythms in non-human animals pave the way for a novel comparative approach to assess the origins and mechanisms of rhythmic behavior. The most reliable non-human beat keeper to date is a California sea lion, Ronan, who was trained to match head movements to isochronous repeating stimuli and showed spontaneous generalization of this ability to novel tempos and to the complex rhythms of music. Does Ronan's performance rely on the same neural mechanisms as human rhythmic behavior? In the current study, we presented Ronan with simple rhythmic stimuli at novel tempos. On some trials, we introduced “perturbations,” altering either tempo or phase in the middle of a presentation. Ronan quickly adjusted her behavior following all perturbations, recovering her consistent phase and tempo relationships to the stimulus within a few beats. Ronan's performance was consistent with predictions of mathematical models describing coupled oscillation: a model relying solely on phase coupling strongly matched her behavior, and the model was further improved with the addition of period coupling. These findings are the clearest evidence yet for parity in human and non-human beat keeping and support the view that the human ability to perceive and move in time to rhythm may be rooted in broadly conserved neural mechanisms. PMID:27375418

  4. Utilizing induced pluripotent stem cells (iPSCs) to understand the actions of estrogens in human neurons.

    PubMed

    Shum, Carole; Macedo, Sara C; Warre-Cornish, Katherine; Cocks, Graham; Price, Jack; Srivastava, Deepak P

    2015-08-01

    This article is part of a Special Issue "Estradiol and Cognition". Over recent years tremendous progress has been made towards understanding the molecular and cellular mechanism by which estrogens exert enhancing effects on cognition, and how they act as a neuroprotective or neurotrophic agent in disease. Currently, much of this work has been carried out in animal models with only a limited number of studies using native human tissue or cells. Recent advances in stem cell technology now make it possible to reprogram somatic cells from humans into induced pluripotent stem cells (iPSCs), which can subsequently be differentiated into neurons of specific lineages. Importantly, the reprogramming of cells allows for the generation of iPSCs that retain the genetic "makeup" of the donor. Therefore, it is possible to generate iPSC-derived neurons from patients diagnosed with specific diseases, that harbor the complex genetic background associated with the disorder. Here, we review the iPSC technology and how it's currently being used to model neural development and neurological diseases. Furthermore, we explore whether this cellular system could be used to understand the role of estrogens in human neurons, and present preliminary data in support of this. We further suggest that the use of iPSC technology offers a novel system to not only further understand estrogens' effects in human cells, but also to investigate the mechanism by which estrogens are beneficial in disease. Developing a greater understanding of these mechanisms in native human cells will also aid in the development of safer and more effective estrogen-based therapeutics. PMID:26143621

  5. Utilizing induced pluripotent stem cells (iPSCs) to understand the actions of estrogens in human neurons

    PubMed Central

    Shum, Carole; Macedo, Sara C.; Warre-Cornish, Katherine; Cocks, Graham; Price, Jack; Srivastava, Deepak P.

    2015-01-01

    This article is part of a Special Issue “Estradiol and Cognition”. Over recent years tremendous progress has been made towards understanding the molecular and cellular mechanism by which estrogens exert enhancing effects on cognition, and how they act as a neuroprotective or neurotrophic agent in disease. Currently, much of this work has been carried out in animal models with only a limited number of studies using native human tissue or cells. Recent advances in stem cell technology now make it possible to reprogram somatic cells from humans into induced pluripotent stem cells (iPSCs), which can subsequently be differentiated into neurons of specific lineages. Importantly, the reprogramming of cells allows for the generation of iPSCs that retain the genetic “makeup” of the donor. Therefore, it is possible to generate iPSC-derived neurons from patients diagnosed with specific diseases, that harbor the complex genetic background associated with the disorder. Here, we review the iPSC technology and how it's currently being used to model neural development and neurological diseases. Furthermore, we explore whether this cellular system could be used to understand the role of estrogens in human neurons, and present preliminary data in support of this. We further suggest that the use of iPSC technology offers a novel system to not only further understand estrogens' effects in human cells, but also to investigate the mechanism by which estrogens are beneficial in disease. Developing a greater understanding of these mechanisms in native human cells will also aid in the development of safer and more effective estrogen-based therapeutics. PMID:26143621

  6. Rethinking Developmental Science

    PubMed Central

    Aldwin, Carolyn M.

    2014-01-01

    The articles in this issue are all based on the invited addresses given by the authors at the 2013 biennial meeting of the Society for the Study of Human Development. All of the authors address the unfolding paradigm shift in developmental sciences, from reductionism to relational developmental system theories. This theoretical stance involves the recognition of Individual ↔ context transactions, with multiple co-acting partners existing in dynamic relationships across the lifespan and life course. The articles address not only theoretical issues, but also methodological advances and their applications. While acknowledging the importance of new data collection and analytical techniques that permit the testing of more complex theoretical models, the articles demonstrate that well-designed questions from this theoretical perspective can also yield novel findings which are highly relevant to current real-world problems and social policy issues. PMID:25598750

  7. Creatine kinase expression and creatine phosphate accumulation are developmentally regulated during differentiation of mouse and human monocytes

    PubMed Central

    1984-01-01

    We have studied the expression of creatine kinase (CK) and the accumulation of creatine phosphate during the differentiation of human and mouse peripheral blood monocytes. Mouse monocytes cultured for 24 h do not contain detectable levels of CK and creatine phosphate. However, resident tissue macrophages and inflammatory elicited macrophages obtained from the peritoneal cavities of mice have 70 and 300 mU per mg protein of CK activity and contain 3 and 6 mol of creatine phosphate per mol of ATP, respectively. The major isozyme of CK in these cells has been identified as the brain form. These findings suggest that the differentiation of monocytes into macrophages is associated with the expression of CK and the accumulation of creatine phosphate. We have found a similar pattern in human monocytes. Human blood monocytes, maintained in culture for 24 or 48 h, do not contain detectable levels of CK or creatine phosphate. Monocyte-derived macrophages (monocytes maintained in tissue cultures for 1 to 2 wk) have up to 100 mU per mg protein of CK activity and contain 0.5 mol of creatine phosphate per mol of ATP. Human macrophages express multiple isozymes of CK including the brain (BB) and possibly the mitochondrial forms of this enzyme. Thus, the expression of CK and the accumulation of creatine phosphate in human monocytes is induced by their in vitro cultivation. The induction of CK during in vitro cultivation occurs independently of the concentration of creatine in the medium. However, the size of the creatine phosphate pool varies with respect to extracellular creatine concentration. Creatine phosphate and CK are not detectable in freshly isolated human lymphocytes, polymorphonuclear leukocytes or erythrocytes, but are found in freshly isolated human platelets. PMID:6699543

  8. The application of ecological theory towards an understanding of the human microbiome

    PubMed Central

    Costello, Elizabeth K.; Stagaman, Keaton; Dethlefsen, Les; Bohannan, Brendan J. M.; Relman, David A.

    2014-01-01

    The human microbial ecosystem plays a diversity of roles in human health and disease. Each individual can be viewed as an island-like “patch” of habitat occupied by microbial assemblages formed by the fundamental processes of community ecology, i.e., dispersal, local diversification, environmental selection, and ecological drift. In this review, we consider how community assembly theory, and as an example, metacommunity theory, could be used to help explain the dynamics of the human microbiome, and in particular, compositional variability within and between hosts. We explore three core scenarios of human microbiome assembly: development in infants, representing assembly in previously unoccupied habitat; recovery from antibiotics, representing assembly after disturbance; and invasion by pathogens, representing assembly in the context of invasive species. Judicious application of ecological theory may lead to improved strategies for maintaining and restoring the microbiota, and the crucial health-associated ecosystem services that it provides. PMID:22674335

  9. USE OF PRIMATE FOLLICULOGENESIS MODELS IN UNDERSTANDING HUMAN REPRODUCTIVE BIOLOGY AND APPLICABILITY TO TOXICOLOGY

    EPA Science Inventory

    The nonhuman primate reproductive system provides an excellent model for studying basic physiological processes applicable to humans. This article reviews hormonal observations and experimental manipulations useful in the evaluation of ovarian events in various stages of the repr...

  10. Understanding and Responding to Youth Substance Use: The Contribution of a Health and Human Rights Framework

    PubMed Central

    Gruskin, Sofia; Plafker, Karen; Smith-Estelle, Allison

    2001-01-01

    This article examines the utility of a health and human rights framework for conceptualizing and responding to the causes and consequences of substance use among young people. It provides operational definitions of “youth” and “substances,” a review of current international and national efforts to address substance use among youths, and an introduction to human rights and the intersection between health and human rights. A methodology for modeling vulnerability in relation to harmful substance use is introduced and contemporary international and national responses are discussed. When governments uphold their obligations to respect, protect, and fulfill human rights, vulnerability to harmful substance use and its consequences can be reduced. PMID:11726374

  11. The role of metagenomics in understanding the human microbiome in health and disease

    PubMed Central

    Martín, Rebeca; Miquel, Sylvie; Langella, Philippe; Bermúdez-Humarán, Luis G

    2014-01-01

    The term microbiome refers to the genetic material of the catalog of microbial taxa associated with humans. As in all ecosystems, the microbiota reaches a dynamic equilibrium in the human body, which can be altered by environmental factors and external stimuli. Metagenomics is a relatively new field of study of microbial genomes within diverse environmental samples, which is of increasing importance in microbiology. The introduction of this ecological perception of microbiology is the key to achieving real knowledge about the influence of the microbiota in human health and disease. The aim of this review is to summarize the link between the human microbiota (focusing on the intestinal, vaginal, skin, and airway body sites) and health from this ecological point of view, highlighting the contribution of metagenomics in the advance of this field. PMID:24429972

  12. Understanding the Human Genome Project — A Fact Sheet | NIH MedlinePlus the Magazine

    MedlinePlus

    ... The Human Genome Project spurred a revolution in biotechnology innovation around the world and played a key ... the U.S. the global leader in the new biotechnology sector. In April 2003, researchers successfully completed the ...

  13. The Ticking Clock of Cayo Santiago Macaques and Its Implications for Understanding Human Circadian Rhythm Disorders

    PubMed Central

    Rogers, Jeffrey; Gonzalez-Martinez, Janis; Farrer, Lindsay A.

    2016-01-01

    The circadian clock disorders in humans remain poorly understood. However, their impact on the development and progression of major human conditions, from cancer to insomnia, metabolic or mental illness becomes increasingly apparent. Addressing human circadian disorders in animal models is, in part, complicated by inverse temporal relationship between the core clock and specific physiological or behavioral processes in diurnal and nocturnal animals. Major advantages of a macaque model for translational circadian research, as a diurnal vertebrate phylogenetically close to humans, are further emphasized by the discovery of the first familial circadian disorder in non-human primates among the rhesus monkeys originating from Cayo Santiago. The remarkable similarity of their pathological phenotypes to human Delayed Sleep Phase Disorder (DSPD), high penetrance of the disorder within one branch of the colony and the large number of animals available provide outstanding opportunities for studying the mechanisms of circadian disorders, their impact on other pathological conditions, and for the development of novel and effective treatment strategies. PMID:25940511

  14. Pathways of Understanding: the Interactions of Humanity and Global Environmental Change

    NASA Technical Reports Server (NTRS)

    Jacobson, Harold K.; Katzenberger, John; Lousma, Jack; Mooney, Harold A.; Moss, Richard H.; Kuhn, William; Luterbacher, Urs; Wiegandt, Ellen

    1992-01-01

    How humans, interacting within social systems, affect and are affected by global change is explored. Recognizing the impact human activities have on the environment and responding to the need to document the interactions among human activities, the Consortium for International Earth Science Information Network (CIESIN) commissioned a group of 12 scientists to develop a framework illustrating the key human systems that contribute to global change. This framework, called the Social Process Diagram, will help natural and social scientists, educators, resource managers and policy makers envision and analyze how human systems interact among themselves and with the natural system. The Social Process Diagram consists of the following blocks that constitute the Diagram's structural framework: (1) fund of knowledge and experience; (2) preferences and expectations; (3) factors of production and technology; (4) population and social structure; (5) economic systems; (6) political systems and institutions; and (7) global scale environmental processes. To demonstrate potential ways the Diagram can be used, this document includes 3 hypothetical scenarios of global change issues: global warming and sea level rise; the environmental impact of human population migration; and energy and the environment. These scenarios demonstrate the Diagram's usefulness for visualizing specific processes that might be studied to evaluate a particular global change issues. The scenario also shows that interesting and unanticipated questions may emerge as links are explored between categories on the Diagram.

  15. Developmental Changes in the Understanding of Generics

    ERIC Educational Resources Information Center

    Gelman, Susan A.; Bloom, Paul

    2007-01-01

    Generic sentences (such as "Birds lay eggs") are important in that they refer to kinds (e.g., birds as a group) rather than individuals (e.g., the birds in the henhouse). The present set of studies examined aspects of how generic nouns are understood by English speakers. Adults and children (4- and 5-year-olds) were presented with scenarios about…

  16. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    EPA Science Inventory

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultur...

  17. The Perception of Four Basic Emotions in Human and Nonhuman Faces by Children with Autism and Other Developmental Disabilities

    ERIC Educational Resources Information Center

    Gross, Thomas F.

    2004-01-01

    Children who experienced autism, mental retardation, and language disorders; and, children in a clinical control group were shown photographs of human female, orangutan, and canine (boxer) faces expressing happiness, sadness, anger, surprise and a neutral expression. For each species of faces, children were asked to identify the happy, sad, angry,…

  18. Directly Comparing Computer and Human Performance in Language Understanding and Visual Reasoning.

    ERIC Educational Resources Information Center

    Baker, Eva L.; And Others

    Evaluation models are being developed for assessing artificial intelligence (AI) systems in terms of similar performance by groups of people. Natural language understanding and vision systems are the areas of concentration. In simplest terms, the goal is to norm a given natural language system's performance on a sample of people. The specific…

  19. Cognitive neuroscience in forensic science: understanding and utilizing the human element

    PubMed Central

    Dror, Itiel E.

    2015-01-01

    The human element plays a critical role in forensic science. It is not limited only to issues relating to forensic decision-making, such as bias, but also relates to most aspects of forensic work (some of which even take place before a crime is ever committed or long after the verification of the forensic conclusion). In this paper, I explicate many aspects of forensic work that involve the human element and therefore show the relevance (and potential contribution) of cognitive neuroscience to forensic science. The 10 aspects covered in this paper are proactive forensic science, selection during recruitment, training, crime scene investigation, forensic decision-making, verification and conflict resolution, reporting, the role of the forensic examiner, presentation in court and judicial decisions. As the forensic community is taking on the challenges introduced by the realization that the human element is critical for forensic work, new opportunities emerge that allow for considerable improvement and enhancement of the forensic science endeavour. PMID:26101281

  20. A systems approach to understanding human rhinovirus and influenza virus infection.

    PubMed

    Kim, Taek-Kyun; Bheda-Malge, Anjali; Lin, Yakang; Sreekrishna, Koti; Adams, Rachel; Robinson, Michael K; Bascom, Charles C; Tiesman, Jay P; Isfort, Robert J; Gelinas, Richard

    2015-12-01

    Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild. In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days. We modeled host responses to these viral infections with time and documented the qualitative and quantitative differences in innate immune activation and regulation. PMID:26437235

  1. Cognitive neuroscience in forensic science: understanding and utilizing the human element.

    PubMed

    Dror, Itiel E

    2015-08-01

    The human element plays a critical role in forensic science. It is not limited only to issues relating to forensic decision-making, such as bias, but also relates to most aspects of forensic work (some of which even take place before a crime is ever committed or long after the verification of the forensic conclusion). In this paper, I explicate many aspects of forensic work that involve the human element and therefore show the relevance (and potential contribution) of cognitive neuroscience to forensic science. The 10 aspects covered in this paper are proactive forensic science, selection during recruitment, training, crime scene investigation, forensic decision-making, verification and conflict resolution, reporting, the role of the forensic examiner, presentation in court and judicial decisions. As the forensic community is taking on the challenges introduced by the realization that the human element is critical for forensic work, new opportunities emerge that allow for considerable improvement and enhancement of the forensic science endeavour. PMID:26101281

  2. Developmental dyslexia.

    PubMed

    Démonet, Jean-François; Taylor, Margot J; Chaix, Yves

    2004-05-01

    Developmental dyslexia, or specific reading disability, is a disorder in which children with normal intelligence and sensory abilities show learning deficits for reading. Substantial evidence has established its biological origin and the preponderance of phonological disorders even though important phenotypic variability and comorbidity have been recorded. Diverse theories have been proposed to account for the cognitive and neurological aspects of dyslexia. Findings of genetic studies show that different loci affect specific reading disability although a direct relation has not been established between symptoms and a given genomic locus. In both children and adults with dyslexia, results of neuroimaging studies suggest defective activity and abnormal connectivity between regions crucial for language functions--eg, the left fusiform gyrus for reading--and changes in brain activity associated with performance improvement after various remedial interventions. PMID:15121410

  3. Evolution of Humans: Understanding the Nature and Methods of Science through Cooperative Learning

    ERIC Educational Resources Information Center

    Lee, Yeung Chung

    2011-01-01

    This article describes the use of an enquiry-based approach to the study of human evolution in a practical context, integrating role-playing, jigsaw cooperative learning and scientific argumentation. The activity seeks to unravel the evolutionary relationships of five hominids and one ape from rather "messy" evidence. This approach enhanced the…

  4. Understanding and Modulating Mammalian-Microbial Communication for Improved Human Health

    PubMed Central

    Mani, Sridhar; Boelsterli, Urs A.; Redinbo, Matthew R.

    2013-01-01

    The fact that the bacteria in the human gastrointestinal (GI) tract play a symbiotic role was noted as early as 1885, well before we began to manage microbial infections using antibiotics. However, even with the first antimicrobial compounds used in humans, the sulfa drugs, microbes were recognized to be critically involved in the biotransformation of these therapeutics. Thus, the roles played by the microbiota in physiology and in the management of human health have long been appreciated. Detailed examinations of GI symbiotic bacteria that started in the early 2000s and the first phases of the Human Microbiome Project that were completed in 2012 have ushered in an exciting period of granularity with respect to the ecology, genetics, and chemistry of the mammalian-microbial axes of communication. Here we review aspects of the biochemical pathways at play between commensal GI bacteria and several mammalian systems, including both local-epithelia and nonlocal responses including inflammation, immunology, metabolism, and neurobiology. Finally, we discuss how the microbial biotransformation of therapeutic compounds, such as anticancer or nonsteroidal anti-inflammatory drugs, can be modulated to reduce toxicity and potentially improve therapeutic efficacy. PMID:24160697

  5. Toward a 21st-Century Understanding of Humans' Relation to Nature: Two Hats?

    ERIC Educational Resources Information Center

    Rennie, Scott

    2008-01-01

    From its inception, environmental education (EE) has shouldered the imposition of impartiality on its methods and practices. Considering the reality of global climate change, the author urges the adoption of the more accurate theory of humans' relation to the natural world. This theory necessitates partiality toward healthy, functioning natural…

  6. Grasping the Affordances, Understanding the Reasoning: Toward a Dialectical Theory of Human Tool Use

    ERIC Educational Resources Information Center

    Osiurak, Francois; Jarry, Christophe; Le Gall, Didier

    2010-01-01

    One of the most exciting issues in psychology is, What are the psychological mechanisms underlying human tool use? The computational approach assumes that the use of a tool (e.g., a hammer) requires the extraction of sensory information about object properties (heavy, rigid), which can then be translated into appropriate motor outputs (grasping,…

  7. Understanding hereditary diseases using the dog and human as companion model systems

    PubMed Central

    Tsai, Kate L.; Clark, Leigh Anne

    2007-01-01

    Animal models are requisite for genetic dissection of, and improved treatment regimens for, human hereditary diseases. While several animals have been used in academic and industrial research, the primary model for dissection of hereditary diseases has been the many strains of the laboratory mouse. However, given its greater (than the mouse) genetic similarity to the human, high number of naturally occurring hereditary diseases, unique population structure, and the availability of the complete genome sequence, the purebred dog has emerged as a powerful model for study of diseases. The major advantage the dog provides is that it is afflicted with approximately 450 hereditary diseases, about half of which have remarkable clinical similarities to corresponding diseases of the human. In addition, humankind has a strong desire to cure diseases of the dog so these two facts make the dog an ideal clinical and genetic model. This review highlights several of these shared hereditary diseases. Specifically, the canine models discussed herein have played important roles in identification of causative genes and/or have been utilized in novel therapeutic approaches of interest to the dog and human. PMID:17653794

  8. Assessment of the United States Military Academy's Academic Program Outcome Goal: Understand Human Behavior.

    ERIC Educational Resources Information Center

    Beach, Johnston

    The assessment model used to examine the human behavior outcome goal had three components: purpose, principles, and process. The purpose was to improve programs and respond to external agencies. Six principles provided a framework and addressed three general criteria: effectiveness, efficiency, and accuracy. The process contained four components:…

  9. Vitamin D signaling in the bovine immune system: A model for understanding human vitamin D requirements

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocr...

  10. Students' Understanding of Connections between Human Engineered and Natural Environmental Systems

    ERIC Educational Resources Information Center

    Tsurusaki, Blakely K.; Anderson, Charles W.

    2010-01-01

    This research draws on developments in educational research where "learning progressions" are emerging as a strategy for synthesizing research on science learning and applying that research to policy and practice, and advances in the natural sciences, where "interdisciplinary research on coupled human and natural systems" has become increasingly…

  11. Population Growth. Understanding Global Change: Earth Science and Human Impacts. Global Change Instruction Program.

    ERIC Educational Resources Information Center

    Jacobsen, Judith E.

    The Global Change Instruction Program was designed by college professors to fill a need for interdisciplinary materials on the emerging science of global change. This instructional module concentrates on interactions between population growth and human activities that produce global change. The materials are designed for undergraduate students…

  12. Leveraging Small Aquarium Fishes to Advance Understanding of Environmentally Influenced Human Disorders and Diseases

    EPA Science Inventory

    Small aquarium fishes provide a model organism that recapitulates the development, physiology and specific disease processes present in humans without the many limitations of rodent-based models currently in use. Fish models offer advantages in cost, rapid life-cycles, and extern...

  13. Understanding and modulating mammalian-microbial communication for improved human health.

    PubMed

    Mani, Sridhar; Boelsterli, Urs A; Redinbo, Matthew R

    2014-01-01

    The fact that the bacteria in the human gastrointestinal (GI) tract play a symbiotic role was noted as early as 1885, well before we began to manage microbial infections using antibiotics. However, even with the first antimicrobial compounds used in humans, the sulfa drugs, microbes were recognized to be critically involved in the biotransformation of these therapeutics. Thus, the roles played by the microbiota in physiology and in the management of human health have long been appreciated. Detailed examinations of GI symbiotic bacteria that started in the early 2000s and the first phases of the Human Microbiome Project that were completed in 2012 have ushered in an exciting period of granularity with respect to the ecology, genetics, and chemistry of the mammalian-microbial axes of communication. Here we review aspects of the biochemical pathways at play between commensal GI bacteria and several mammalian systems, including both local-epithelia and nonlocal responses impacting inflammation, immunology, metabolism, and neurobiology. Finally, we discuss how the microbial biotransformation of therapeutic compounds, such as anticancer or nonsteroidal anti-inflammatory drugs, can be modulated to reduce toxicity and potentially improve therapeutic efficacy. PMID:24160697

  14. Understanding Generational Diversity: Strategic Human Resource Management and Development across the Generational "Divide"

    ERIC Educational Resources Information Center

    Amayah, Angela Titi; Gedro, Julie

    2014-01-01

    There are more generations in today's workforce than ever before, which has the possibility to create challenges for Human Resource professionals. The purpose of this article is to interrogate existing stereotypes and generalities about the characteristics of different generations with respect to the workplace, and to offer suggestions for…

  15. Human-Level Natural Language Understanding: False Progress and Real Challenges

    ERIC Educational Resources Information Center

    Bignoli, Perrin G.

    2013-01-01

    The field of Natural Language Processing (NLP) focuses on the study of how utterances composed of human-level languages can be understood and generated. Typically, there are considered to be three intertwined levels of structure that interact to create meaning in language: syntax, semantics, and pragmatics. Not only is a large amount of…

  16. Understanding the Dorsal and Ventral Systems of the Human Cerebral Cortex: Beyond Dichotomies

    ERIC Educational Resources Information Center

    Borst, Gregoire; Thompson, William L.; Kosslyn, Stephen M.

    2011-01-01

    Traditionally, characterizations of the macrolevel functional organization of the human cerebral cortex have focused on the left and right cerebral hemispheres. However, the idea of left brain versus right brain functions has been shown to be an oversimplification. We argue here that a top-bottom divide, rather than a left-right divide, is a more…

  17. Understanding Protein Synthesis: A Role-Play Approach in Large Undergraduate Human Anatomy and Physiology Classes

    ERIC Educational Resources Information Center

    Sturges, Diana; Maurer, Trent W.; Cole, Oladipo

    2009-01-01

    This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section…

  18. Understanding the Role of ECM Protein Composition and Geometric Micropatterning for Engineering Human Skeletal Muscle.

    PubMed

    Duffy, Rebecca M; Sun, Yan; Feinberg, Adam W

    2016-06-01

    Skeletal muscle lost through trauma or disease has proven difficult to regenerate due to the challenge of differentiating human myoblasts into aligned, contractile tissue. To address this, we investigated microenvironmental cues that drive myoblast differentiation into aligned myotubes for potential applications in skeletal muscle repair, organ-on-chip disease models and actuators for soft robotics. We used a 2D in vitro system to systematically evaluate the role of extracellular matrix (ECM) protein composition and geometric patterning for controlling the formation of highly aligned myotubes. Specifically, we analyzed myotubes differentiated from murine C2C12 cells and human skeletal muscle derived cells (SkMDCs) on micropatterned lines of laminin compared to fibronectin, collagen type I, and collagen type IV. Results showed that laminin supported significantly greater myotube formation from both cells types, resulting in greater than twofold increase in myotube area on these surfaces compared to the other ECM proteins. Species specific differences revealed that human SkMDCs uniaxially aligned over a wide range of micropatterned line dimensions, while C2C12s required specific line widths and spacings to do the same. Future work will incorporate these results to engineer aligned human skeletal muscle tissue in 2D for in vitro applications in disease modeling, drug discovery and toxicity screening. PMID:26983843

  19. Reconciling Human Smoking Behavior and Machine Smoking Patterns: Implications for Understanding Smoking Behavior and the Impact on Laboratory Studies

    PubMed Central

    Marian, Catalin; O'Connor, Richard J.; Djordjevic, Mirjana; Rees, Vaughan W.; Hatsukami, Dorothy K.; Shields, Peter G.

    2009-01-01

    Introduction Recent Food and Drug Administration legislation enables the mandating of product performance standards for cigarette smoke and the evaluation of manufacturers’ health claims for modified tobacco products. Laboratory studies used for these evaluations, and also to understand tobacco smoke toxicology, use machines to generate smoke. The goal of this review is to critically evaluate methods to assess human smoking behavior and replicate this in the laboratory. Methods Smoking behavior and smoking machine studies were identified using PubMed and publically available databases for internal tobacco company documents. Results The smoking machine was developed to generate smoke to allow for comparing cigarette tar and nicotine yields. The intent was to infer relative human disease risk, but this concept was flawed because humans tailor their smoking to the product and chemical yields and toxicological effects change with different smoking profiles. While smoking machines also allow for mechanistic assessments of smoking-related diseases, the interpretations also are limited. However, available methods to assess how humans puff could be used to provide better laboratory assessments, but these need to be validated. Separately, the contribution of smoke mouth-holding and inhalation to dose need to be assessed, because these parts of smoking are not captured by the smoking machine. Better comparisons of cigarettes might be done by tailoring human puff profiles to the product based on human studies and comparing results across regimens. Conclusions There are major research gaps that limit the use of smoking machine studies for informing tobacco control regulation and mechanistic studies. PMID:19959678

  20. Fetal Microchimerism in Cancer Protection and Promotion: Current Understanding in Dogs and the Implications for Human Health.

    PubMed

    Bryan, Jeffrey N

    2015-05-01

    Fetal microchimerism is the co-existence of small numbers of cells from genetically distinct individuals living within a mother's body following pregnancy. During pregnancy, bi-directional exchange of cells occurs resulting in maternal microchimerism and even sibling microchimerism in offspring. The presence of fetal microchimerism has been identified with lower frequency in patients with cancers such as breast and lymphoma and with higher frequency in patients with colon cancer and autoimmune diseases. Microchimeric cells have been identified in healing and healed tissues as well as normal and tumor tissues. This has led to the hypothesis that fetal microchimerism may play a protective role in some cancers and may provoke other cancers or autoimmune disease. The long periods of risk for these diseases make it a challenge to prospectively study this phenomenon in human populations. Dogs get similar cancers as humans, share our homes and environmental exposures, and live compressed life-spans, allowing easier prospective study of disease development. This review describes the current state of understanding of fetal microchimerism in humans and dogs and highlights the similarities of the common cancers mammary carcinoma, lymphoma, and colon cancer between the two species. Study of fetal microchimerism in dogs might hold the key to characterization of the type and function of microchimeric cells and their role in health and disease. Such an understanding could then be applied to preventing and treating disease in humans. PMID:25693490

  1. Developmental validation of the Quantifiler Duo DNA Quantification kit for simultaneous quantification of total human and human male DNA and detection of PCR inhibitors in biological samples.

    PubMed

    Barbisin, Maura; Fang, Rixun; O'Shea, Cristin E; Calandro, Lisa M; Furtado, Manohar R; Shewale, Jaiprakash G

    2009-03-01

    The Quantifiler Duo DNA Quantification kit enables simultaneous quantification of human DNA and human male DNA as well as detection of inhibitors of PCR in a single real-time PCR well. Pooled human male genomic DNA is used to generate standard curves for both human (ribonuclease P RNA component H1) and human male (sex determining region Y) specific targets. A shift in the cycle threshold (C(T)) values for the internal positive control monitors the presence of PCR inhibitors in a sample. The assay is human specific and exhibits a high dynamic range from 0.023 to 50 ng/microL. In addition, the multiplex assay can detect as little as 25 pg/microL of human male DNA in the presence of a 1000-fold excess of human female DNA. The multiplex assay provides assessment of the DNA extract and guidance for the selection of the appropriate AmpFlSTR Amplification Kit to obtain interpretable short tandem repeat profiles. PMID:19175708

  2. The Extended Nutrigenomics – Understanding the Interplay between the Genomes of Food, Gut Microbes, and Human Host

    PubMed Central

    Kussmann, Martin; Van Bladeren, Peter J.

    2011-01-01

    Comprehensive investigation of nutritional health effects at the molecular level requires the understanding of the interplay between three genomes, the food, the gut microbial, and the human host genome. Food genomes are researched for discovery and exploitation of macro- and micronutrients as well as specific bioactives, with those genes coding for bioactive proteins and peptides being of central interest. The human gut microbiota encompasses a complex ecosystem in the intestine with profound impact on host metabolism. It is being studied at genomic and, more recently, also at proteomic and metabonomic level. Humans are being characterized at the level of genetic pre-disposition and inter-individual variability in terms of (i) response to nutritional interventions and direction of health trajectories; (ii) epigenetic, metabolic programming at certain life stages with health consequences later in life and even for subsequent generations; and (iii) acute genomic expression as a holistic response to diet, monitored at gene transcript, protein and metabolite level. Modern nutrition science explores health-related aspects of bioactive food components, thereby promoting health, preventing, or delaying the onset of disease, optimizing performance and assessing benefits and risks in individuals and subpopulations. Personalized nutrition means adapting food to individual needs, depending on the human host’s life stage, -style, and -situation. Traditionally, nutrigenomics and nutri(epi)genetics are seen as the key sciences to understand human variability in preferences and requirements for diet as well as responses to nutrition. This article puts the three nutrition and health-relevant genomes into perspective, namely the food, the gut microbial and the human host’s genome, and calls for an “extended nutrigenomics” approach in order to build the future tools for personalized nutrition, health maintenance, and disease prevention. We discuss examples of these genomes

  3. The effects of an interdisciplinary undergraduate human biology program on socioscientific reasoning, content learning, and understanding of inquiry

    NASA Astrophysics Data System (ADS)

    Eastwood, Jennifer L.

    Preparing students to take informed positions on complex problems through critical evaluation is a primary goal of university education. Socioscientific issues (SSI) have been established as effective contexts for students to develop this competency, as well as reasoning skills and content knowledge. This mixed-methods study investigates the effects of an interdisciplinary undergraduate human biology program focused on the development of evidence-based reasoning to form personal commitments on SSI. Specifically, the study investigates how human biology majors differ from traditional biology majors in their reasoning with SSI, their perceptions of experiences with SSI, their understanding of scientific inquiry, their levels and perceptions of science content knowledge, and their general program perceptions. These outcomes were assessed through open-ended questionnaires on SSI and scientific inquiry and a basic biology concept test administered to 95 participants representing both programs and 16 semi-structured student interviews. Although the two groups did not differ significantly in their decisions or factors influencing their decisions in SSI, human biology majors showed higher levels of socioscientific reasoning, suggesting that learning contextualized in SSI helped them understand and reason with similar issues. While biology majors reported few experiences with socioscientific reasoning, human biology majors felt well equipped to reason with SSI and more likely to consider alternative perspectives in their decision making. Human biology majors also were more likely to view social science research as a form of inquiry and less likely to view scientific inquiry as purely experimental. No difference was found between groups in basic biology content knowledge, although human biology majors felt they were exposed to less detailed biology content. This exploratory study illustrates a novel approach to interdisciplinary, SSI-based science education at the college

  4. Humans on the International Space Station-How Research, Operations, and International Collaboration are Leading to New Understanding of Human Physiology and Performance in Microgravity

    NASA Technical Reports Server (NTRS)

    Ronbinson, Julie A.; Harm, Deborah L.

    2009-01-01

    As the International Space Station (ISS) nears completion, and full international utilization is achieved, we are at a scientific crossroads. ISS is the premier location for research aimed at understanding the effects of microgravity on the human body. For applications to future human exploration, it is key for validation, quantification, and mitigation of a wide variety of spaceflight risks to health and human performance. Understanding and mitigating these risks is the focus of NASA s Human Research Program. However, NASA s approach to defining human research objectives is only one of many approaches within the ISS international partnership (including Roscosmos, the European Space Agency, the Canadian Space Agency, and the Japan Aerospace Exploration Agency). Each of these agencies selects and implements their own ISS research, with independent but related objectives for human and life sciences research. Because the science itself is also international and collaborative, investigations that are led by one ISS partner also often include cooperative scientists from around the world. The operation of the ISS generates significant additional data that is not directly linked to specific investigations. Such data comes from medical monitoring of crew members, life support and radiation monitoring, and from the systems that have been implemented to protect the health of the crew (such as exercise hardware). We provide examples of these international synergies in human research on ISS and highlight key early accomplishments that derive from these broad interfaces. Taken as a whole, the combination of diverse research objectives, operational data, international sharing of research resources on ISS, and scientific collaboration provide a robust research approach and capability that no one partner could achieve alone.

  5. A Mid-Layer Model for Human Reliability Analysis: Understanding the Cognitive Causes of Human Failure Events

    SciTech Connect

    Stacey M. L. Hendrickson; April M. Whaley; Ronald L. Boring; James Y. H. Chang; Song-Hua Shen; Ali Mosleh; Johanna H. Oxstrand; John A. Forester; Dana L. Kelly; Erasmia L. Lois

    2010-06-01

    The Office of Nuclear Regulatory Research (RES) is sponsoring work in response to a Staff Requirements Memorandum (SRM) directing an effort to establish a single human reliability analysis (HRA) method for the agency or guidance for the use of multiple methods. As part of this effort an attempt to develop a comprehensive HRA qualitative approach is being pursued. This paper presents a draft of the method’s middle layer, a part of the qualitative analysis phase that links failure mechanisms to performance shaping factors. Starting with a Crew Response Tree (CRT) that has identified human failure events, analysts identify potential failure mechanisms using the mid-layer model. The mid-layer model presented in this paper traces the identification of the failure mechanisms using the Information-Diagnosis/Decision-Action (IDA) model and cognitive models from the psychological literature. Each failure mechanism is grouped according to a phase of IDA. Under each phase of IDA, the cognitive models help identify the relevant performance shaping factors for the failure mechanism. The use of IDA and cognitive models can be traced through fault trees, which provide a detailed complement to the CRT.

  6. A mid-layer model for human reliability analysis : understanding the cognitive causes of human failure events.

    SciTech Connect

    Shen, Song-Hua; Chang, James Y. H.; Boring,Ronald L.; Whaley, April M.; Lois, Erasmia; Hendrickson, Stacey M. Langfitt; Oxstrand, Johanna H.; Forester, John Alan; Kelly, Dana L.; Mosleh, Ali

    2010-03-01

    The Office of Nuclear Regulatory Research (RES) at the US Nuclear Regulatory Commission (USNRC) is sponsoring work in response to a Staff Requirements Memorandum (SRM) directing an effort to establish a single human reliability analysis (HRA) method for the agency or guidance for the use of multiple methods. As part of this effort an attempt to develop a comprehensive HRA qualitative approach is being pursued. This paper presents a draft of the method's middle layer, a part of the qualitative analysis phase that links failure mechanisms to performance shaping factors. Starting with a Crew Response Tree (CRT) that has identified human failure events, analysts identify potential failure mechanisms using the mid-layer model. The mid-layer model presented in this paper traces the identification of the failure mechanisms using the Information-Diagnosis/Decision-Action (IDA) model and cognitive models from the psychological literature. Each failure mechanism is grouped according to a phase of IDA. Under each phase of IDA, the cognitive models help identify the relevant performance shaping factors for the failure mechanism. The use of IDA and cognitive models can be traced through fault trees, which provide a detailed complement to the CRT.

  7. Lessons from the analysis of nonhuman primates for understanding human aging and neurodegenerative diseases

    PubMed Central

    Verdier, Jean-Michel; Acquatella, Isabelle; Lautier, Corinne; Devau, Gina; Trouche, Stéphanie; Lasbleiz, Christelle; Mestre-Francés, Nadine

    2015-01-01

    Animal models are necessary tools for solving the most serious challenges facing medical research. In aging and neurodegenerative disease studies, rodents occupy a place of choice. However, the most challenging questions about longevity, the complexity and functioning of brain networks or social intelligence can almost only be investigated in nonhuman primates. Beside the fact that their brain structure is much closer to that of humans, they develop highly complex cognitive strategies and they are visually-oriented like humans. For these reasons, they deserve consideration, although their management and care are more complicated and the related costs much higher. Despite these caveats, considerable scientific advances have been possible using nonhuman primates. This review concisely summarizes their role in the study of aging and of the mechanisms involved in neurodegenerative disorders associated mainly with cognitive dysfunctions (Alzheimer's and prion diseases) or motor deficits (Parkinson's and related diseases). PMID:25788873

  8. Students' Participation in an Interdisciplinary, Socioscientific Issues Based Undergraduate Human Biology Major and Their Understanding of Scientific Inquiry

    NASA Astrophysics Data System (ADS)

    Eastwood, Jennifer L.; Sadler, Troy D.; Sherwood, Robert D.; Schlegel, Whitney M.

    2013-06-01

    The purpose of this study was to examine whether Socioscientific Issues (SSI) based learning environments affect university students' epistemological understanding of scientific inquiry differently from traditional science educational contexts. We identify and compare conceptions of scientific inquiry of students participating in an interdisciplinary, SSI-focused undergraduate human biology major (SSI) and those participating in a traditional biology major (BIO). Forty-five SSI students and 50 BIO students completed an open-ended questionnaire examining their understanding of scientific inquiry. Eight general themes including approximately 60 subthemes emerged from questionnaire responses, and the numbers of students including each subtheme in their responses were statistically compared between groups. A subset of students participated in interviews, which were used to validate and triangulate questionnaire data and probe students' understanding of scientific inquiry in relation to their majors. We found that both groups provided very similar responses, differing significantly in only five subthemes. Results indicated that both groups held generally adequate understandings of inquiry, but also a number of misconceptions. Small differences between groups supported by both questionnaires and interviews suggest that the SSI context contributed to nuanced understandings, such as a more interdisciplinary and problem-centered conception of scientific inquiry. Implications for teaching and research are discussed.

  9. Systems biological approaches to measure and understand vaccine immunity in humans

    PubMed Central

    Li, Shuzhao; Nakaya, Helder I; Kazmin, Dmitri A; Oh, Jason; Pulendran, Bali

    2013-01-01

    Recent studies have demonstrated the utility of using systems approaches to identify molecular signatures that can be used to predict vaccine immunity in humans. Such approaches are now being used extensively in vaccinology, and are beginning to yield novel insights about the molecular networks driving vaccine immunity. In this review, we present a broad review of the methodologies involved in these studies, and discuss the promise and challenges involved in this emerging field of “systems vaccinology.” PMID:23796714

  10. New dimensions in our understanding of the human health effects of environmental pollutants

    SciTech Connect

    Carpenter, D.O.

    1996-12-31

    The term {open_quotes}hazardous{close_quotes} waste is used primarily in reference to potential hazards to human health and, to a lesser decree, hazards to wildlife and the ecosystem. Many of the chemicals associated with hazardous waste sites are also widely distributed throughout the environment; therefore, the health hazards associated with hazardous waste sites are not different from those associated with general environmental contamination. Until recently, it was generally assumed that cancer was the human disease of greatest concern associated with toxic chemicals. In fact, most governmental regulations related to exposure are designed on the basis of presumed cancer risks. Since the evidence that hazardous chemicals can cause cancer is strong, it is appropriate to be concerned about cancer risk. Recent evidence, however, has triggered a reevaluation of the assumption that only cancer is of concern. New evidence suggests that noncancer endpoints may occur more frequently than cancer, may affect a greater number of individuals, and may occur at lower concentrations. Of particular concern is evidence of irreversible effects on the embryo and very young children, which influence intelligence, attention span, sexual development, and immune function. Although these effects are often subtle and difficult to quantify, the combined evidence is sufficiently compelling to necessitate a reevaluation of those outcomes of primary concern to human health. 57 refs., 2 figs., 3 tabs.

  11. Application of chemometrics in understanding the spatial distribution of human pharmaceuticals in surface water.

    PubMed

    Al-Odaini, Najat Ahmed; Zakaria, Mohamad Pauzi; Zali, Muniirah Abdul; Juahir, Hafizan; Yaziz, Mohamad Ismail; Surif, Salmijah

    2012-11-01

    The growing interest in the environmental occurrence of veterinary and human pharmaceuticals is essentially due to their possible health implications to humans and ecosystem. This study assesses the occurrence of human pharmaceuticals in a Malaysian tropical aquatic environment taking a chemometric approach using cluster analysis, discriminant analysis and principal component analysis. Water samples were collected from seven sampling stations along the heavily populated Langat River basin on the west coast of peninsular Malaysia and its main tributaries. Water samples were extracted using solid-phase extraction and analyzed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for 18 pharmaceuticals and one metabolite, which cover a range of six therapeutic classes widely consumed in Malaysia. Cluster analysis was applied to group both pharmaceutical pollutants and sampling stations. Cluster analysis successfully clustered sampling stations and pollutants into three major clusters. Discriminant analysis was applied to identify those pollutants which had a significant impact in the definition of clusters. Finally, principal component analysis using a three-component model determined the constitution and data variance explained by each of the three main principal components. PMID:22193630

  12. Restless Genomes: Humans as a Model Organism for Understanding Host-Retrotransposable Element Dynamics

    PubMed Central

    Hedges, Dale J.; Belancio, Victoria P.

    2015-01-01

    Since their initial discovery in maize, there have been various attempts to categorize the relationship between transposable elements (TEs) and their host organisms. These have ranged from TEs being selfish parasites to their role as essential, functional components of organismal biology. Research over the past several decades has, in many respects, only served to complicate the issue even further. On the one hand, investigators have amassed substantial evidence concerning the negative effects that TE-mutagenic activity can have on host genomes and organismal fitness. On the other hand, we find an increasing number of examples, across several taxa, of TEs being incorporated into functional biological roles for their host organism. Some 45% of our own genomes are comprised of TE copies. While many of these copies are dormant, having lost their ability to mobilize, several lineages continue to actively proliferate in modern human populations. With its complement of ancestral and active TEs, the human genome exhibits key aspects of the host–TE dynamic that has played out since early on in organismal evolution. In this review, we examine what insights the particularly well-characterized human system can provide regarding the nature of the host–TE interaction. PMID:21310298

  13. Understanding The Individual Impacts Of Human Interventions And Climate Change On Hydrologic Variables In India

    NASA Astrophysics Data System (ADS)

    Sharma, T.; Chhabra, S., Jr.; Karmakar, S.; Ghosh, S.

    2015-12-01

    We have quantified the historical climate change and Land Use Land Cover (LULC) change impacts on the hydrologic variables of Indian subcontinent by using Variable Infiltration Capacity (VIC) mesoscale model at 0.5° spatial resolution and daily temporal resolution. The results indicate that the climate change in India has predominating effects on the basic water balance components such as water yield, evapotranspiration and soil moisture. This analysis is with the assumption of naturalised hydrologic cycle, i.e., the impacts of human interventions like construction of controlled (primarily dams, diversions and reservoirs) and water withdrawals structures are not taken into account. The assumption is unrealistic since there are numerous anthropogenic disturbances which result in large changes on vegetation composition and distribution patterns. These activities can directly or indirectly influence the dynamics of water cycle; subsequently affecting the hydrologic processes like plant transpiration, infiltration, evaporation, runoff and sublimation. Here, we have quantified the human interventions by using the reservoir and irrigation module of VIC model which incorporates the irrigation schemes, reservoir characteristics and water withdrawals. The impact of human interventions on hydrologic variables in many grids are found more predominant than climate change and might be detrimental to water resources at regional level. This spatial pattern of impacts will facilitate water manager and planners to design and station hydrologic structures for a sustainable water resources management.

  14. Understanding the role of representations of human-leopard conflict in Mumbai through media-content analysis.

    PubMed

    Bhatia, Saloni; Athreya, Vidya; Grenyer, Richard; MacDonald, David W

    2013-06-01

    Attempts to minimize the effects of human-wildlife conflict (HWC) on conservation goals require an understanding of the mechanisms by which such conflicts are caused and sustained. This necessitates looking beyond the natural sciences to the human dimensions of wildlife management. Public dissemination of information regarding HWC occurs largely through the mass media. We conducted a content analysis of print media articles on human-leopard conflict in Mumbai, India. We sought to understand the framing of HWC and the changes in media coverage over a 10-year period (2001-2011) during which a large number of attacks on people prior to 2005 were followed by a program of trapping and relocation. After 2005, when there was a decrease in the level of conflict, the tone of English-language media reports changed. The perpetrator framing was over 5 times more likely before 2005, whereas a neutral framing was twice as likely after 2005. English-language and non-English-language print media differed significantly in their framing of HWC and in the kinds of solutions advocated. Our results also suggest the print mass media in Mumbai could be an influential conduit for content that diminishes HWC. These media outlets seem attentive to human-leopard conflict, capable of correcting erroneous perceptions and facilitating mitigation and effective management. We believe better contact and mutual understanding between conservation professionals and the mass media could be an important component of managing HWC. We further suggest that in such interactions conservation professionals need to be aware of cultural and linguistic differences in reporting within the country. PMID:23530914

  15. Characterization of a female-specific cDNA derived from a developmentally regulated mRNA in the human blood fluke Schistosoma mansoni.

    PubMed

    Bobek, L; Rekosh, D M; van Keulen, H; LoVerde, P T

    1986-08-01

    We have isolated and characterized a cDNA clone that is derived from a developmentally regulated mRNA found only in mature female schistosomes. The mRNA is approximately 950 nucleotides in length and is not detectable in immature female schistosomes isolated from single-sex infections, in male worms, or in eggs. During normal bisexual infections, the mRNA species is first detected 28 days after infection (the time of worm pairing) and increases to a high level 35 days after infection, coinciding with the start of egg production. The nucleotide sequence of the cDNA shows two large open reading frames in the coding strand. Several features of the clone, including the deduced sequence of the polypeptide encoded by one of the reading frames, suggest a relationship to the silk moth chorion (egg shell) gene family. The isolation of this clone provides us with a probe for further studies of female schistosome development and is a first step toward a detailed understanding of this process at the molecular level. PMID:3461449

  16. In vitro fertilization (IVF) in mammals: epigenetic and developmental alterations. Scientific and bioethical implications for IVF in humans.

    PubMed

    Ventura-Juncá, Patricio; Irarrázaval, Isabel; Rolle, Augusto J; Gutiérrez, Juan I; Moreno, Ricardo D; Santos, Manuel J

    2015-01-01

    The advent of in vitro fertilization (IVF) in animals and humans implies an extraordinary change in the environment where the beginning of a new organism takes place. In mammals fertilization occurs in the maternal oviduct, where there are unique conditions for guaranteeing the encounter of the gametes and the first stages of development of the embryo and thus its future. During this period a major epigenetic reprogramming takes place that is crucial for the normal fate of the embryo. This epigenetic reprogramming is very vulnerable to changes in environmental conditions such as the ones implied in IVF, including in vitro culture, nutrition, light, temperature, oxygen tension, embryo-maternal signaling, and the general absence of protection against foreign elements that could affect the stability of this process. The objective of this review is to update the impact of the various conditions inherent in the use of IVF on the epigenetic profile and outcomes of mammalian embryos, including superovulation, IVF technique, embryo culture and manipulation and absence of embryo-maternal signaling. It also covers the possible transgenerational inheritance of the epigenetic alterations associated with assisted reproductive technologies (ART), including its phenotypic consequences as is in the case of the large offspring syndrome (LOS). Finally, the important scientific and bioethical implications of the results found in animals are discussed in terms of the ART in humans. PMID:26683055

  17. Developmental Disabilities and Child Welfare.

    ERIC Educational Resources Information Center

    Rycus, Judith S.; Hughes, Ronald C.

    This monograph addresses common misconceptions about developmental disabilities, describes the conditions that child welfare workers are most likely to see, provides examples of effective interventions, and stresses the importance of early intervention to promote healthy development. Specific chapters include: (1) "Understanding Developmental…

  18. Vygotsky's Developmental and Educational Psychology

    ERIC Educational Resources Information Center

    Langford, Peter E.

    2005-01-01

    Vygotsky is widely considered one of the most significant and influential psychologists of the twentieth century. Nevertheless, true appreciation of his theories has been hindered by a lack of understanding of the background to his thought. "Vygotsky's Developmental and Educational Psychology" aims to demonstrate how we can come to a new and…

  19. Conducting Policy-Relevant Developmental Psychopathology Research

    ERIC Educational Resources Information Center

    Petersen, Anne C.

    2006-01-01

    Policy, defined broadly to include public policy as well as institutional or organizational policy, is useful for sustaining change in human development and its contexts and systems. The role for developmental psychopathology research in policy analysis and policy making is discussed. To assure that developmental psychopathology research is useful…

  20. Reproductive and Developmental Toxicity of Formaldehyde: A Systematic Review

    PubMed Central

    Duong, Anh; Steinmaus, Craig; McHale, Cliona M.; Vaughan, Charles P.; Zhang, Luoping

    2011-01-01

    Formaldehyde, the recently classified carcinogen and ubiquitous environmental contaminant, has long been suspected of causing adverse reproductive and developmental effects, but previous reviews were inconclusive, due in part, to limitations in the design of many of the human population studies. In the current review, we systematically evaluated evidence of an association between formaldehyde exposure and adverse reproductive and developmental effects, in human populations and in vivo animal studies, in the peer-reviewed literature. The mostly retrospective human studies provided evidence of an association of maternal exposure with adverse reproductive and developmental effects. Further assessment of this association by meta-analysis revealed an increased risk of spontaneous abortion (1.76, 95% CI 1.20–2.59, p=0.002) and of all adverse pregnancy outcomes combined (1.54, 95% CI 1.27–1.88, p<0.001), in formaldehyde-exposed women, although differential recall, selection bias, or confounding cannot be ruled out. Evaluation of the animal studies including all routes of exposure, doses and dosing regimens studied, suggested positive associations between formaldehyde exposure and reproductive toxicity, mostly in males. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. To clarify these associations, well-designed molecular epidemiologic studies, that include quantitative exposure assessment and diminish confounding factors, should examine both reproductive and developmental outcomes associated with exposure in males and females. Together with mechanistic and animal studies, this will allow us to better understand the systemic effect of formaldehyde exposure. PMID:21787879