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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. 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…

  3. Evolutionary psychology and evolutionary developmental psychology: understanding the evolution of human behavior and development.

    PubMed

    Hernández Blasi, Carlos; Causey, Kayla

    2010-02-01

    This is an introduction to this special issue on evolutionary psychology (EP) and evolutionary developmental psychology (EDP). We suggest here that, contrary to some common assumptions, mainstream psychology continues to be essentially non Darwinian and that EP and EDP are new approaches that can potentially help us to change this situation. We then present the organization of the special issue (composed of six papers). We conclude that evolution is certainly not the final consideration in psychology, but emphasize its importance as the basis upon which all modern behaviors and development are built.

  4. Understanding Natural Kinds: A Developmental Comparison.

    ERIC Educational Resources Information Center

    Gelman, Susan A.; Markman, Ellen M.

    A study investigated how young children understand natural kind terms by examining how 3- and 4-year-olds rely on category membership to draw inductive inferences about objects. One hundred four children (53 girls and 51 boys) from six preschools in California and Michigan participated in the study. The children were shown 10 sets of pictures of…

  5. Developmental biomechanics of the human cervical spine.

    PubMed

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

    2013-04-05

    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.

  6. Developmental and Individual Differences in Understanding of Fractions

    ERIC Educational Resources Information Center

    Siegler, Robert S.; Pyke, Aryn A.

    2013-01-01

    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 crosssectional design. Results indicated that the difference…

  7. 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)…

  8. Applied Developmental Biology: Making Human Pancreatic Beta Cells for Diabetics.

    PubMed

    Melton, Douglas A

    2016-01-01

    Understanding the genes and signaling pathways that determine the differentiation and fate of a cell is a central goal of developmental biology. Using that information to gain mastery over the fates of cells presents new approaches to cell transplantation and drug discovery for human diseases including diabetes.

  9. Children's understanding of scientific concepts: A developmental study

    NASA Astrophysics Data System (ADS)

    Bickerton, Gillian Valerie

    Combining theory-oriented inquiry and research that aims to improve instruction is a major goal of neo-Piagetian theory. Within this tradition, Case's (1992) developmental model enables educational researchers to conduct a detailed analysis of the structural and conceptual changes that occur in children's representation of knowledge in different domains at various points in their development. In so doing, it is now possible for educators to first assess children's "entering competence" in a specific subject and then set developmentally realistic instructional goals. Using Case's (1992) model as a theoretical framework, a developmental study was conducted investigating children's understanding of scientific phenomena, specifically buoyancy, at the ages of 6, 8, and 10 years. The main goal was to determine whether or not children's conceptual levels of understanding change systematically with age in a progressive manner consistent with neo-Piagetian stages of development hypothesized by Case. Participants attended one elementary school in a suburban school district near Vancouver, B.C. Sixty children were individually administered a set of five buoyancy tasks that varied in level of difficulty and involved objects of different weights, shapes and sizes. Each student was asked to predict whether an object would float or sink in different liquids and to support their prediction with an explanation. Analyses using the neo-Piagetian approach of articulating the semantic and syntactic nature of children's mental structures were conducted on the students' responses. Shape, size, weight and substance were identified as the semantic components of buoyancy which are syntactically related Using Case's dimensional metric for classifying different levels of conceptual understanding of buoyancy, the results of the study confirmed that children's understanding of buoyancy did progress through the developmental sequence as hypothesized. The structural progression from

  10. The role of developmental plasticity and epigenetics in human health.

    PubMed

    Gluckman, Peter D; Hanson, Mark A; Low, Felicia M

    2011-03-01

    Considerable epidemiological, experimental and clinical data have amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. This relationship reflects plastic responses made by the developing organism as an evolved strategy to cope with immediate or predicted circumstances, to maximize fitness in the context of the range of environments potentially faced. There is now increasing evidence, both in animals and humans, that such developmental plasticity is mediated in part by epigenetic mechanisms. However, recognition of the importance of developmental plasticity as an important factor in influencing later life health-particularly within the medical and public health communities-is low, and we argue that this indifference cannot be sustained in light of the growing understanding of developmental processes and the rapid rise in the prevalence of obesity and metabolic disease globally.

  11. Understanding child sexual behavior problems: a developmental psychopathology framework.

    PubMed

    Elkovitch, Natasha; Latzman, Robert D; Hansen, David J; Flood, Mary Fran

    2009-11-01

    Children exhibiting sexual behavior have increasingly gained the attention of child welfare and mental health systems, as well as the scientific community. While a heterogeneous group, children with sexual behavior problems consistently demonstrate a number of problems related to adjustment and overall development. In order to appropriately intervene with these children, a comprehensive understanding of etiology is imperative. The overarching goal of the present paper is to review the extant research on mechanisms associated with the development of problematic sexual behavior in childhood within a developmental psychopathology framework. What is known about normative and nonnormative sexual behavior in childhood is reviewed, highlighting definitional challenges and age-related developmental differences. Further, the relationship between child sexual abuse and child sexual behavior problems is discussed, drawing attention to factors impacting this relationship. Risk factors for child sexual behavior problems, beyond that of sexual abuse, are also reviewed utilizing a transactional-ecological framework. Finally, we conclude with a discussion of implications of a developmental psychopathology perspective on problematic child sexual behaviors to inform future research and intervention efforts. Such implications include the need for attention to normative childhood sexual behavior, developmental sensitivity, and examinations of ecological domain in concert.

  12. Building artificial humans to understand humans.

    PubMed

    Ishiguro, Hiroshi; Nishio, Shuichi

    2007-01-01

    If we could build an android as a very humanlike robot, how would we humans distinguish a real human from an android? The answer to this question is not so easy. In human-android interaction, we cannot see the internal mechanism of the android, and thus we may simply believe that it is a human. This means that a human can be defined from two perspectives: one by organic mechanism and the other by appearance. Further, the current rapid progress in artificial organs makes this distinction confusing. The approach discussed in this article is to create artificial humans with humanlike appearances. The developed artificial humans, an android and a geminoid, can be used to improve understanding of humans through psychological and cognitive tests conducted using the artificial humans. We call this new approach to understanding humans android science.

  13. 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.

  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. 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

  16. Modeling anesthetic developmental neurotoxicity using human stem cells

    PubMed Central

    Bai, Xiaowen; Twaroski, Danielle; Bosnjak, Zeljko J.

    2013-01-01

    Mounting pre-clinical evidence in rodents and non-human primates has demonstrated that prolonged exposure of developing animals to general anesthetics can induce widespread neuronal cell death followed by long-term memory and learning disabilities. In vitro experimental evidence from cultured neonatal animal neurons confirmed the in vivo findings. However, there is no direct clinical evidence of the detrimental effects of anesthetics in human fetuses, infants, or children. Development of an in vitro neurogenesis system using human stem cells has opened up avenues of research for advancing our understanding of human brain development and the issues relevant to anesthetic-induced developmental toxicity in human neuronal lineages. Recent studies from our group, as well as other groups, showed that isoflurane influences human neural stem cell proliferation and neurogenesis, while ketamine induces neuroapoptosis. Application of this high throughput in vitro stem cell neurogenesis approach is a major stride toward assuring the safety of anesthetic agents in young children. This in vitro human model allows us to (1) screen the toxic effects of various anesthetics under controlled conditions during intense neuronal growth, (2) find the trigger for the anesthetic-induced catastrophic chain of toxic events, and (3) develop prevention strategies to avoid this toxic effect. In this paper, we reviewed the current findings in anesthetic-induced neurotoxicity studies, specifically focusing on the in vitro human stem cell model. PMID:23859832

  17. Creating to understand - developmental biology meets engineering in Paris.

    PubMed

    Kicheva, Anna; Rivron, Nicolas C

    2017-03-01

    In November 2016, developmental biologists, synthetic biologists and engineers gathered in Paris for a meeting called 'Engineering the embryo'. The participants shared an interest in exploring how synthetic systems can reveal new principles of embryonic development, and how the in vitro manipulation and modeling of development using stem cells can be used to integrate ideas and expertise from physics, developmental biology and tissue engineering. As we review here, the conference pinpointed some of the challenges arising at the intersection of these fields, along with great enthusiasm for finding new approaches and collaborations.

  18. Measuring Developmental Levels of Understanding of Ability and Effort.

    ERIC Educational Resources Information Center

    Miller, Arden T.; Nicholls, John G.

    Discussed are research methods used to measure developmental changes in children's reasoning about ability. While adults generally differentiate ability, effort, luck, and task difficulty as causes for success and failure, children progressively think that effort or outcome is ability (level 1), that effort is the cause of performance outcomes…

  19. 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…

  20. 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.

  1. Webinar Presentation: Using in Vitro and in Vivo Models to Inform Understanding of Developmental Neurotoxicity

    EPA Pesticide Factsheets

    This presentation, Using in Vitro and in Vivo Models to Inform Understanding of Developmental Neurotoxicity, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Interdisciplinary Approaches to Neurodevelopment held on Sept. 9, 2015.

  2. Comparative developmental psychology: how is human cognitive development unique?

    PubMed

    Rosati, Alexandra G; Wobber, Victoria; Hughes, Kelly; Santos, Laurie R

    2014-04-29

    The fields of developmental and comparative psychology both seek to illuminate the roots of adult cognitive systems. Developmental studies target the emergence of adult cognitive systems over ontogenetic time, whereas comparative studies investigate the origins of human cognition in our evolutionary history. Despite the long tradition of research in both of these areas, little work has examined the intersection of the two: the study of cognitive development in a comparative perspective. In the current article, we review recent work using this comparative developmental approach to study non-human primate cognition. We argue that comparative data on the pace and pattern of cognitive development across species can address major theoretical questions in both psychology and biology. In particular, such integrative research will allow stronger biological inferences about the function of developmental change, and will be critical in addressing how humans come to acquire species-unique cognitive abilities.

  3. Teachers' Explanations of a Key Developmental Understanding of Multiplicative Reasoning

    ERIC Educational Resources Information Center

    Rhee, Katherine L.

    2012-01-01

    This qualitative research study explores teachers' understandings of multiplicative reasoning as a key developmental understanding (KDU). A KDU entails knowingly applying the same mathematical concepts within different contexts. A KDU supports an individual to build a connected understanding of mathematics as opposed to only understanding…

  4. 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.

  5. 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

  6. Defining the Genetic Architecture of Human Developmental Language Impairment

    PubMed Central

    Li, Ning; Bartlett, Christopher W.

    2012-01-01

    Language is a uniquely human trait, which poses limitations on animal models for discovering biological substrates and pathways. Despite this challenge, rapidly developing biotechnology in the field of genomics has made human genetics studies a viable alternative route for defining the molecular neuroscience of human language. This is accomplished by studying families that transmit both normal and disordered language across generations. The language disorder reviewed here is specific language impairment (SLI), a developmental deficiency in language acquisition despite adequate opportunity, normal intelligence, and without any apparent neurological etiology. Here, we describe disease gene discovery paradigms as applied to SLI families and review the progress this field has made. After review the evidence that genetic factors influence SLI, we discuss methods and findings from scans of the human chromosomes, including the main replicated regions on chromosomes 13, 16 and 19 and two identified genes, ATP2C2 and CMIP that appear to account for the language variation on chromosome 16. Additional work has been done on candidate genes, i.e., genes chosen a priori and not through a genome scanning studies, including several studies of CNTNAP2 and some recent work implicating BDNF as a gene × gene interaction partner of genetic variation on chromosome 13 that influences language. These recent developments may allow for better use of post-mortem human brain samples functional studies and animal models for circumscribed language subcomponents. In the future, the identification of genetic variation associated with language phenotypes will provide the molecular pathways to understanding human language. PMID:22365959

  7. Understanding of logical necessity: developmental antecedents and cognitive consequences.

    PubMed

    Morris, A K; Sloutsky, V M

    1998-06-01

    Does abstract reasoning develop naturally, and does instruction contribute to its development? In an attempt to answer these questions, this article specifically focuses on effects of prolonged instruction on the development of abstract deductive reasoning and, more specifically, on the development of understanding of logical necessity. It was hypothesized that instructional emphasis on the metalevel of deduction within a knowledge domain can amplify the development of deductive reasoning both within and across this domain. The article presents 2 studies that examine the development of understanding of logical necessity in algebraic and verbal deductive reasoning. In the first study, algebraic and verbal reasoning tasks were administered to 450 younger and older adolescents selected across different instructional settings in England and in Russia. In the second study, algebraic and verbal reasoning tasks were administered to 287 Russian younger and older adolescents selected across different instructional settings. The results support the hypothesis, indicating that prolonged instruction with an emphasis on the metalevel of algebraic deduction contributes to the development of understanding of logical necessity in both algebraic and verbal deductive reasoning. Findings also suggest that many adolescents do not develop an understanding of logical necessity naturally.

  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. 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…

  10. A Developmental Sequence of Skills in Adolescents' Intergroup Understanding

    ERIC Educational Resources Information Center

    Karcher, Michael, J.; Fischer, Kurt, W.

    2004-01-01

    This study explores the psychometric properties of a proposed sequence of socioemotional cognitive skills in the domain of intergroup understanding as assessed by interview and questionnaire data from 91 Caucasian and Hispanic adolescents. The proposed sequence of skills was measured under two support conditions to test hypotheses about a…

  11. 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.

  12. Reading comprehension and understanding idiomatic expressions: a developmental study.

    PubMed

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

    2004-12-01

    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 simple word-by-word comprehension strategy and to integrate figurative meaning into contextual information. In a preliminary phase, we used a standardized battery of tests (Cornoldi & Colpo, 1998) to assess the ability of second graders and fourth graders to comprehend written texts. Three groups were identified at each age level: good, medium, and poor comprehenders. Children were then presented with familiar idiomatic expressions which also have a literal meaning (e.g., "break the ice"). Idioms were embedded in short stories: in Experiment 1 only the idiomatic interpretation was contextually appropriate, in Experiment 2 a literal reading of the string was also plausible in the context. A multiple-choice task was used in both experiments: children were asked to choose one answer among three corresponding to: (a) the idiomatic meaning; (b) the literal meaning; and (c) an interpretation contextually appropriate but not connected with the idiomatic or literal meaning of the idiom string. The results of both experiments showed that the ability to understand a text indeed predicted children's understanding of idioms in context. To verify whether possible improvements in children's comprehension skills might produce an increase in figurative language understanding, Experiment 3 was carried out. A group of poor comprehenders who participated in Experiments 1 and 2 was tested eight months later. The results of Experiment 3 showed that children whose general comprehension skills improved their performance on an idiom comprehension test.

  13. 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

    2016-07-07

    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.

  14. 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

  15. 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.

  16. Human pluripotent stem cells: an emerging model in developmental biology.

    PubMed

    Zhu, Zengrong; Huangfu, Danwei

    2013-02-01

    Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development 'in a dish'. We also summarize some of the recently developed genetic tools that greatly facilitate the interrogation of gene function during hPSC differentiation. With the development of high-throughput screening technologies, hPSCs have the potential to revolutionize gene discovery in mammalian development.

  17. From emotion resonance to empathic understanding: a social developmental neuroscience account.

    PubMed

    Decety, Jean; Meyer, Meghan

    2008-01-01

    The psychological construct of empathy refers to an intersubjective induction process by which positive and negative emotions are shared, without losing sight of whose feelings belong to whom. Empathy can lead to personal distress or to empathic concern (sympathy). The goal of this paper is to address the underlying cognitive processes and their neural underpinnings that constitute empathy within a developmental neuroscience perspective. In addition, we focus on how these processes go awry in developmental disorders marked by impairments in social cognition, such as autism spectrum disorder, and conduct disorder. We argue that empathy involves both bottom-up and top-down information processing, underpinned by specific and interacting neural systems. We discuss data from developmental psychology as well as cognitive neuroscience in support of such a model, and highlight the impact of neural dysfunctions on social cognitive developmental behavior. Altogether, bridging developmental science and cognitive neuroscience helps approach a more complete understanding of social cognition. Synthesizing these two domains also contributes to a better characterization of developmental psychopathologies that impacts the development of effective treatment strategies.

  18. Theory of Mind "Beliefs", 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 belief 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 belief abilities were examined. EDEI-R [Perron-Borelli M. (1996). "Echelles Differentielles…

  19. 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…

  20. Developmental Counseling and Therapy: An Effective Approach to Understanding and Counseling Children.

    ERIC Educational Resources Information Center

    Myers, Jane E.; Shoffner, Marie F.; Briggs, Michele Kielty

    2002-01-01

    Reviews the cognitive development of children, with a focus on Piagetian theory as a framework for understanding Developmental Counseling and Therapy (DCT). Describes both the assessment process and intervention planning, and provides specific applications to counseling children in school settings. (Contains 35 references.) (GCP)

  1. 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…

  2. What Community College Developmental Mathematics Students Understand about Mathematics, Part 2: The Interviews

    ERIC Educational Resources Information Center

    Givvin, Karen B.; Stigler, James W.; Thompson, Belinda J.

    2011-01-01

    In a prior issue of "MathAMATYC Educator," we reported on our efforts to find out what community college developmental mathematics students understand about mathematics (Stigler, Givvin, & Thompson, 2010). Our work painted a distressing picture of students' mathematical knowledge. No matter what kind of mathematical question we…

  3. Children's Understanding of the Simultaneity of Two Emotions: A Five-Stage Developmental Acquisition Sequence.

    ERIC Educational Resources Information Center

    Harter, Susan; Buddin, Bonnie Johns

    1987-01-01

    This study documented a developmental model of children's understanding of the simultaneity of two emotions. Fourteen children at each of the nine age levels from 4 to 12 were studied. Children were questioned about (1) two emotions of same valence directed at the same target, (2) same valence/different target, (3) different valence/different…

  4. 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…

  5. 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…

  6. Developmental regulation of the human antibody repertoire.

    PubMed

    Schroeder, H W; Mortari, F; Shiokawa, S; Kirkham, P M; Elgavish, R A; Bertrand, F E

    1995-09-29

    The ability to respond to antigen develops in a programmed fashion during ontogeny. In human, "fetal" immunoglobulin gene segment utilization appears biased towards a small set of evolutionarily conserved V gene segments. Many of these gene segments are also used in antibodies with antigen specificities that do not arise until after infancy. The human fetus primarily regulates the diversity of the antibody repertoire through control of the H (heavy) chain CDR 3, which is generated by VDJ joining and forms the center of the antigen-binding site. Molecular modeling suggests that limitations in the length and composition of fetal CDR 3 intervals result in antibodies that contain a relatively "flat" antigen-binding surface that could serve to maximize the number of different interactions possible between the antibody and potential antigens. We propose that these limitations in the sequence and structure of H chain CDR 3 contribute to the low affinity and multireactivity of fetal antibody repertoires. The specific mechanisms used to generate a restricted fetal repertoire appear to differ between human and mouse. Nevertheless, included in the final products of both human and mouse fetal B cells will be antibodies that are quite homologous in composition and structure. The precise role that these antibodies play in the development of immunocompetence remains to be elucidated.

  7. PTK7 marks the first human developmental EMT in vitro.

    PubMed

    Chan, David N; Azghadi, Soheila F; Feng, Jun; Lowry, William E

    2012-01-01

    Epithelial to mesenchymal transitions (EMTs) are thought to be essential to generate diversity of tissues during early fetal development, but these events are essentially impossible to study at the molecular level in vivo in humans. The first EMT event that has been described morphologically in human development occurs just prior to generation of the primitive streak. Because human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) are thought to most closely resemble cells found in epiblast-stage embryos prior to formation of the primitive streak, we sought to determine whether this first human EMT could be modeled in vitro with pluripotent stem cells. The data presented here suggest that generating embryoid bodies from hESCs or hiPSCs drives a procession of EMT events that can be observed within 24-48 hours after EB generation. These structures possess the typical hallmarks of developmental EMTs, and portions also display evidence of primitive streak and mesendoderm. We identify PTK7 as a novel marker of this EMT population, which can also be used to purify these cells for subsequent analyses and identification of novel markers of human development. Gene expression analysis indicated an upregulation of EMT markers and ECM proteins in the PTK7+ population. We also find that cells that undergo this developmental EMT retain developmental plasticity as sorting, dissociation and re-plating reestablishes an epithelial phenotype.

  8. The EvoDevoCI: a concept inventory for gauging students' understanding of evolutionary developmental biology.

    PubMed

    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 developmental biology, or "evo-devo." To assist in efforts to improve evo-devo instruction among undergraduate biology majors, we designed a concept inventory (CI) for evolutionary developmental biology, the EvoDevoCI. The CI measures student understanding of six core evo-devo concepts using four scenarios and 11 multiple-choice items, all inspired by authentic scientific examples. Distracters were designed to represent the common conceptual difficulties students have with each evo-devo concept. The tool was validated by experts and administered at four institutions to 1191 students during preliminary (n = 652) and final (n = 539) field trials. We used student responses to evaluate the readability, difficulty, discriminability, validity, and reliability of the EvoDevoCI, which included items ranging in difficulty from 0.22-0.55 and in discriminability from 0.19-0.38. Such measures suggest the EvoDevoCI is an effective tool for assessing student understanding of evo-devo concepts and the prevalence of associated common conceptual difficulties among both novice and advanced undergraduate biology majors.

  9. 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

  10. Endocytosis of cholera toxin by human enterocytes is developmentally regulated.

    PubMed

    Lu, Lei; Khan, Sameer; Lencer, Wayne; Walker, W Allan

    2005-08-01

    Many secretory diarrheas including cholera are more prevalent and fulminant in young infants than in older children and adults. Cholera toxin (CT) elicits a cAMP-dependent chloride secretory response in intestinal epithelia, which accounts for the fundamental pathogenesis of this toxigenic diarrhea. We have previously reported that the action of this bacterial enterotoxin is excessive in immature enterocytes and under developmental regulation. In this study, we tested the hypothesis that enhanced endocytosis by immature human enterocytes may, in part, account for the excessive secretory response to CT noted in the immature intestine and that enterocyte endocytosis of CT is developmentally regulated. To test this hypothesis, we used specific inhibitors to define endocytic pathways in mature and immature cell lines. We showed that internalization of CT in adult enterocytes is less and occurs via the caveolae/raft-mediated pathway in contrast to an enhanced immature human enterocyte CT uptake that occurs via a clathrin pathway. We also present evidence that this clathrin pathway is developmentally regulated as demonstrated by its response to corticosteroids, a known maturation factor that causes a decreased CT endocytosis by this pathway.

  11. 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.

  12. 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

  13. Human ecology in understanding environmental health problems.

    PubMed

    Suzuki, T

    1977-01-01

    The role of human ecology in understanding of environmental health problems is discussed, and the importance of study on "regional" ecosystems is emphasized in consideration of recent arguments on theoretical frame work of human ecology. After brief conceptual discussion on "regional" ecosystems, the environmental health on hunter-gatherer populations, and then, the influence of agricultural development is discussed in relation to the "closedness" of regional ecosystems. Finally, by an example, e.g. islanders on small islands of southern Japan, the differentiation of economic activities by island is shown as the most important regulating factor for the accumulation of mercury in islanders.

  14. Ecological Human Brain and Young Children's "Naturalist Intelligence" from the Perspective of Developmentally and Culturally Appropriate Practice (DCAP).

    ERIC Educational Resources Information Center

    Hyun, Eunsook

    Based on the view that young children have a different intellectual culture from adults' in the way they know and understand nature, this paper explores ecological human brain development, children's intellectual culture of naturalist intelligence, and developmentally and culturally congruent curricula for young children. The paper discusses the…

  15. 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

  16. A Theoretical Approach to Understanding Population Dynamics with Seasonal Developmental Durations

    NASA Astrophysics Data System (ADS)

    Lou, Yijun; Zhao, Xiao-Qiang

    2017-04-01

    There is a growing body of biological investigations to understand impacts of seasonally changing environmental conditions on population dynamics in various research fields such as single population growth and disease transmission. On the other side, understanding the population dynamics subject to seasonally changing weather conditions plays a fundamental role in predicting the trends of population patterns and disease transmission risks under the scenarios of climate change. With the host-macroparasite interaction as a motivating example, we propose a synthesized approach for investigating the population dynamics subject to seasonal environmental variations from theoretical point of view, where the model development, basic reproduction ratio formulation and computation, and rigorous mathematical analysis are involved. The resultant model with periodic delay presents a novel term related to the rate of change of the developmental duration, bringing new challenges to dynamics analysis. By investigating a periodic semiflow on a suitably chosen phase space, the global dynamics of a threshold type is established: all solutions either go to zero when basic reproduction ratio is less than one, or stabilize at a positive periodic state when the reproduction ratio is greater than one. The synthesized approach developed here is applicable to broader contexts of investigating biological systems with seasonal developmental durations.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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…

  2. 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…

  3. Developmental expression of mucin genes in the human gastrointestinal system

    PubMed Central

    Reid, C; Harris, A

    1998-01-01

    Background and aims—Mucin glycoproteins play a key role in the normal function of the epithelium lining the gastrointestinal tract. The expression of mucin genes, MUC 3, 4, 5AC, 5B, 6, 7, and 8 in human fetal tissues was examined to establish the localisation and age of onset of expression of each mucin gene during human development. 
Methods—Mucin gene expression was assayed by mRNA in situ hybridisation. 
Results—Expression of MUC3 was detected in the small intestine and colon from 13 weeks gestation onwards and at low levels in the main pancreatic duct at 13 weeks only. MUC4 expression was seen at a low level in the colonic epithelium from 13 weeks of gestation but not elsewhere in the gastrointestinal tract. MUC5AC mRNA was detected in the colon at 17 weeks and at high levels in the stomach at 23 weeks. MUC6 transcripts were evident in the pancreatic ducts from 13 weeks of gestation and at high levels in the stomach at 23 weeks. MUC5B, MUC7, and MUC8 transcripts were not detected. 
Conclusions—Mucin genes are expressed from the early mid-trimester of gestation in the developing human fetal gastrointestinal tract. 

 Keywords: mucin; developmental expression; gastrointestinal tract PMID:9536947

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

    PubMed

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

    2015-11-01

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

  5. Computational Everyday Life Human Behavior Understanding

    NASA Astrophysics Data System (ADS)

    Motomura, Yoichi; Nishida, Yoshifumi

    Human behavior understanding in everyday life is promising but not established research field. Our project named 'open life matrix' is focused on this field. In these years, many sensor houses and robotic room projects have been studied and sensing and network technology have been established. However, still we have problems to realize everyday life support information systems and services. There are two major problems. The first one is data representation and computational modeling problem in everyday life. The second one is that we don't have a good way to realize valuable services from research outcomes. We propose a challenge to solve these problems by a scheme for accumulating common data set and probabilistic causal modeling during everyday life services.

  6. 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.

  7. 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

  8. 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…

  9. Developmental regulation of human truncated nerve growth factor receptor

    SciTech Connect

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R. )

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system.

  10. Developmental changes in purine phosphoribosyltransferases in human and rat tissues.

    PubMed Central

    Adams, A; Harkness, R A

    1976-01-01

    1. The hypoxanthine/guanine and adenine phosphoribosyltransferase activities in a wide variety of human tissues were studied during their growth and development from foetal life onward. A wide range of activities develop after birth, with especially high values in the central nervous system and testes. 2. Postnatal development of hypoxanthine/guanine phosphoribosyltransferase was also defined in the rat. Although there were increases in the central nervous system and testes, there was also a rise in activity in the liver, which was less marked in man. 3. A sensitive radiochemical assay method, using dTTP to inhibit 5'-nucleotidase activity, suitable for tissue extracts, was developed. 4. No definite evidence of the existence of tissue-specific isoenzymes of hypoxanthine/guanine or adenine phosphoribosyltransferase was found. Hypoxanthine/guanine phosphoribosyltransferase in testes, however, had a significantly different thermal-denaturation rate constant. 5. The findings are discussed in an attempt to relate activity of hypoxanthine/guanine phosphoribosyltransferase to biological function. Growth as well as some developmental changes appear to be related to increase in the activity of this enzyme. PMID:1016239

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

    PubMed Central

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

    2014-01-01

    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. PMID:25348053

  12. 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.

  13. 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

  14. Understanding the developmental pathways pulmonary fibroblasts may follow during alveolar regeneration.

    PubMed

    McGowan, Stephen

    2017-03-01

    Although pulmonary alveolar interstitial fibroblasts are less specialized than their epithelial and endothelial neighbors, they play essential roles during development and in response to lung injury. At birth, they must adapt to the sudden mechanical changes imposed by the onset of respiration and to a higher ambient oxygen concentration. In diseases such as bronchopulmonary dysplasia and interstitial fibrosis, their adaptive responses are overwhelmed leading to compromised gas-exchange function. Thus, although fibroblasts do not directly participate in gas-exchange, they are essential for creating and maintaining an optimal environment at the alveolar epithelial-endothelial interface. This review summarizes new information and concepts about the ontogeny differentiation, and function of alveolar fibroblasts. Alveolar development will be emphasized, because the development of strategies to evoke alveolar repair and regeneration hinges on thoroughly understanding the way that resident fibroblasts populate specific locations in which extracellular matrix must be produced and remodeled. Other recent reviews have described the disruption that diseases cause to the fibroblast niche and so my objective is to illustrate how the unique developmental origins and differentiation pathways could be harnessed favorably to augment certain fibroblast subpopulations and to optimize the conditions for alveolar regeneration.

  15. 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

  16. 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

  17. 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…

  18. 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.

  19. Implications of the idea of neurodiversity for understanding the origins of developmental disorders.

    PubMed

    Masataka, Nobuo

    2017-03-01

    Neurodiversity, a term initially used mostly by civil and human rights movements since the 1990s, refers to the notion that cognitive as well as emotional properties characteristic of developmental disorders such as autism spectrum disorders (ASD) are not necessarily deficits, but fall within normal behavioural variations exhibited by humans. The purpose of the present article is to examine the relevance of this notion to scientific research on ASD. On the assumption that one crucial survival advantage of intelligent activity is vigilance toward dangers in the external world, and such vigilance must work in the social domain as well as in the non-social domain, the author argues that the pattern of operation of an individual person's mind can be categorized according to the domain toward which that individual is more oriented. Individuals with ASD, overall, do not rely upon their social relationships but rather are predisposed to process perceived non-social objects in more depth, which manifests itself as hyper-sensation and hyper-attention to detail. It can be assumed that underconnectivity among cortical areas and subcortical areas underlies such mental operation neurologically. One of the main predictions based on this assumption is that all facets of psychological function are susceptible to disruption in ASD. Indeed, it has traditionally been thought that there are such general deficits in this disorder. However, contrary to the prevalent belief that people with ASD lack empathy, in fact people with ASD are capable of empathizing with the minds of others if those others are people with ASD. Thus, the neurological underconnectivity in ASD certainly leads some processing of information in the mind to work with less coordination, but has in fact contributed to providing Homo sapiens with behavioural variants. Finally, the clinical implications of the advantages of viewing ASD as a variation in neurodiversity are discussed.

  20. Implications of the idea of neurodiversity for understanding the origins of developmental disorders

    NASA Astrophysics Data System (ADS)

    Masataka, Nobuo

    2017-03-01

    Neurodiversity, a term initially used mostly by civil and human rights movements since the 1990s, refers to the notion that cognitive as well as emotional properties characteristic of developmental disorders such as autism spectrum disorders (ASD) are not necessarily deficits, but fall within normal behavioural variations exhibited by humans. The purpose of the present article is to examine the relevance of this notion to scientific research on ASD. On the assumption that one crucial survival advantage of intelligent activity is vigilance toward dangers in the external world, and such vigilance must work in the social domain as well as in the non-social domain, the author argues that the pattern of operation of an individual person's mind can be categorized according to the domain toward which that individual is more oriented. Individuals with ASD, overall, do not rely upon their social relationships but rather are predisposed to process perceived non-social objects in more depth, which manifests itself as hyper-sensation and hyper-attention to detail. It can be assumed that underconnectivity among cortical areas and subcortical areas underlies such mental operation neurologically. One of the main predictions based on this assumption is that all facets of psychological function are susceptible to disruption in ASD. Indeed, it has traditionally been thought that there are such general deficits in this disorder. However, contrary to the prevalent belief that people with ASD lack empathy, in fact people with ASD are capable of empathizing with the minds of others if those others are people with ASD. Thus, the neurological underconnectivity in ASD certainly leads some processing of information in the mind to work with less coordination, but has in fact contributed to providing Homo sapiens with behavioural variants. Finally, the clinical implications of the advantages of viewing ASD as a variation in neurodiversity are discussed.

  1. Global Environmental change: Understanding the Human Dimensions

    SciTech Connect

    Morrisette, P.M.

    1993-01-01

    This book is from the National Research Council's Committee on the Human dimensions of Global Change. The object is to examine what is known about human dimensions of global environmental change, identify the major immediate needs for knowledge, and recommend a strategy over the next 5-10 years. Case studies are used in human causes of global change. issues related to theory, methods, and data are covered, as well as institutional needs for interdicipinary approaches.

  2. Beyond ;Deficit-Based; thinking in autism research. Comment on ;Implications of the idea of neurodiversity for understanding the origins of developmental disorders; by Nobuo Masataka

    NASA Astrophysics Data System (ADS)

    Silberman, Steve

    2017-03-01

    Nobuo's paper [1] marks a pioneering attempt to reconcile the provocative concept of neurodiversity - the notion that developmental disabilities like autism, dyslexia, and ADHD are not inherently pathological, but reflect natural human variations that deserve societal accommodations equivalent to those afforded to people with physical disabilities - with the ongoing effort to investigate the neurological underpinnings of these conditions. As the framework of neurodiversity rapidly gains social acceptance and influence in education, employment, service provision, and related fields, it is important for researchers to understand this concept and consider how it may inform and shape their work in the coming years. Nobuo's paper provides a useful template for these efforts.

  3. 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.

  4. 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

  5. Ecological Approaches to Understanding Human Crowding.

    ERIC Educational Resources Information Center

    Baron, Reuben M.

    1979-01-01

    Characteristics of the ecological approach to perception are presented. The affordance concept and its relevance is emphasized. Human crowding is discussed in affordance terms. There is a comparison given between present affordance analysis and ecological analysis. (Author/SA)

  6. 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

  7. 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

  8. Learning to Understand Natural Language with Less Human Effort

    DTIC Science & Technology

    2015-05-01

    Learning to Understand Natural Language with Less Human Effort Jayant Krishnamurthy CMU-CS-15-110 May 2015 School of Computer Science Carnegie Mellon...COVERED 00-00-2015 to 00-00-2015 4. TITLE AND SUBTITLE Learning to Understand Natural Language with Less Human Effort 5a. CONTRACT NUMBER 5b...require less human annotation are necessary in order to learn to understand natural language in these more challenging settings. This thesis explores

  9. Developmental connections between cranial components and the emergence of the first permanent molar in humans

    PubMed Central

    Sardi, Marina L; Rozzi, Fernando Ramírez

    2007-01-01

    The age of emergence of the first molar (M1) is a developmental event correlated with many variables of primate life history, such as adult brain size. The evolution of human life history is characterized by the inclusion of childhood, which takes place between weaning and M1 emergence. Children still depend on adults for nutrition due to their small digestive system and their immature brains. By contrast, juveniles are not dependent because of M1 emergence, which enables shifting to adult type diet, and attainment of nearly adult brain size. In this study, developmental connections between M1 emergence and growth of cranial components were explored in two ways in order to understand the developmental basis of their evolutionary connections: (1) differences in growth trajectories of cranial components with respect to M1 emergence and (2) differences between individuals with and without fully emerged M1. Growth of anteroneural, midneural, posteroneural, otic, optic, respiratory, masticatory and alveolar cranial components was analysed in human skulls of individuals aged 0–20 years and in an adult reference skull. Volumetric indices were calculated to estimate size. Two subsamples were selected in order to focus on the transition between deciduous and permanent dentition: those with full deciduous dentition and before M1 reaches the occlusal plane; and those who present M1 in full emergence and no other cheek-tooth at the occlusal plane. The principal results were as follows. (1) Trajectories fitted using the whole sample are characterized by an inflection point that takes place before M1 emergence for neural components and around M1 emergence for facial components. (2) Associations between growth and age tend to be strong in those with full deciduous dentition, and weak in those who present M1 in full emergence. (3) Individuals who present M1 in full emergence are larger than those with full deciduous dentition. (4) Growth of components linked to the central

  10. 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

  11. 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.

  12. 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.

  13. Machine Understanding of Human Implicit Intention

    DTIC Science & Technology

    2013-05-18

    Cognitive Neurodynamics , Hokkaido, Japan, June 2011, Hokkaido, Japan (Plenary Talk) - Soo-Young Lee, Implicit Intention Recognition and Hierarchical...subject’s response with the accuracy of about 80% by SVM. 15. SUBJECT TERMS Brain Science and Engineering; Cognitive Neuroscience; Human-Computer...oscillations have been related to a variety of functions such as perception, cognition , sleep, etc. For a long time, researchers have found the sensory and

  14. A Thomistic understanding of human death.

    PubMed

    Eberl, Jason T

    2005-02-01

    I investigate Thomas Aquinas's metaphysical account of human death, which is defined in terms of a rational soul separating from its material body. The question at hand concerns what criterion best determines when this separation occurs. Aquinas argues that a body has a rational soul only insofar as it is properly organised to support the soul's vegetative, sensitive, and rational capacities. According the 'higher-brain' concept of death, when a body can no longer provide the biological foundation necessary for the operation of conscious rational thought and volition, a substantial change occurs in which the rational soul departs and the body left behind is a 'humanoid animal' or a mere 'vegetable.' I argue that the separation of soul and body does not occur until the body ceases to function as a unified, integrated organism. A rational soul is not only the seat of a human being's rational capacities; it is also the principle of the body's sensitive and vegetative capacities. Since Aquinas defines a human being as a composite of soul and body, and not with merely the exercise of rational capacities, the determination of death requires incontrovertible evidence that the body has ceased all the operations that correspond to the soul's proper capacities. The evidence of this is the body's loss of its integrative organic unity and the criterion for determining when this loss occurs is the irreversible cessation of whole-brain functioning.

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

    PubMed

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

    2013-09-01

    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.

  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. [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.

  18. 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.

  19. 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).

  20. Understanding the origins of human cancer

    DOE PAGES

    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

  1. 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…

  2. 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...

  3. Understanding Teachers' Perceptions of the Motor Difficulties of Children with Developmental Coordination Disorder (DCD)

    ERIC Educational Resources Information Center

    Rivard, Lisa M.; Missiuna, Cheryl; Hanna, Steven; Wishart, Laurie

    2007-01-01

    Background: Children with developmental coordination disorder (DCD) are often identified by classroom teachers and the identification process relies heavily on teachers' perceptions. The literature would suggest that teachers' perceptions may be influenced by a child's gender, behaviour and the type of motor problem they demonstrate. To date, the…

  4. 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…

  5. Counseling Theory: Understanding the Trend toward Eclecticism from a Developmental Perspective.

    ERIC Educational Resources Information Center

    Brabeck, Mary M.; Welfel, Elizabeth Reynolds

    1985-01-01

    Examines eclecticism in counseling from a developmental perspective. Suggests that an individual's view of eclecticism may be influenced by his/her level of intellectual development. Discusses two types of eclecticism: one recognizes alternatives and the other seeks to limit them. Includes comments and further suggestions by other authors and a…

  6. Towards a Conceptual Basis for Understanding Developmental Guidance and Counselling Model

    ERIC Educational Resources Information Center

    Aluede, Oyaziwo; Imonikhe, Justina; Afen-Akpaida, Justina

    2007-01-01

    Comprehensive developmental guidance and counselling model is a 21st century school counselling intervention emphasizing school guidance curriculum, individual student planning, responsive counselling services and system support. The aims of this paper therefore, were to articulately define comprehensive guidance and counselling within the…

  7. 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

  8. Understanding the complexity of human gait dynamics.

    PubMed

    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.

  9. 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.

  10. Contribution of Neuroimaging Studies to Understanding Development of Human Cognitive Brain Functions.

    PubMed

    Morita, Tomoyo; Asada, Minoru; Naito, Eiichi

    2016-01-01

    Humans experience significant physical and mental changes from birth to adulthood, and a variety of perceptual, cognitive and motor functions mature over the course of approximately 20 years following birth. To deeply understand such developmental processes, merely studying behavioral changes is not sufficient; simultaneous investigation of the development of the brain may lead us to a more comprehensive understanding. Recent advances in noninvasive neuroimaging technologies largely contribute to this understanding. Here, it is very important to consider the development of the brain from the perspectives of "structure" and "function" because both structure and function of the human brain mature slowly. In this review, we first discuss the process of structural brain development, i.e., how the structure of the brain, which is crucial when discussing functional brain development, changes with age. Second, we introduce some representative studies and the latest studies related to the functional development of the brain, particularly for visual, facial recognition, and social cognition functions, all of which are important for humans. Finally, we summarize how brain science can contribute to developmental study and discuss the challenges that neuroimaging should address in the future.

  11. Contribution of Neuroimaging Studies to Understanding Development of Human Cognitive Brain Functions

    PubMed Central

    Morita, Tomoyo; Asada, Minoru; Naito, Eiichi

    2016-01-01

    Humans experience significant physical and mental changes from birth to adulthood, and a variety of perceptual, cognitive and motor functions mature over the course of approximately 20 years following birth. To deeply understand such developmental processes, merely studying behavioral changes is not sufficient; simultaneous investigation of the development of the brain may lead us to a more comprehensive understanding. Recent advances in noninvasive neuroimaging technologies largely contribute to this understanding. Here, it is very important to consider the development of the brain from the perspectives of “structure” and “function” because both structure and function of the human brain mature slowly. In this review, we first discuss the process of structural brain development, i.e., how the structure of the brain, which is crucial when discussing functional brain development, changes with age. Second, we introduce some representative studies and the latest studies related to the functional development of the brain, particularly for visual, facial recognition, and social cognition functions, all of which are important for humans. Finally, we summarize how brain science can contribute to developmental study and discuss the challenges that neuroimaging should address in the future. PMID:27695409

  12. 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

  13. 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

  14. Understanding Random Effects in Group-Based Trajectory Modeling: An Application of Moffitt's Developmental Taxonomy.

    PubMed

    Saunders, Jessica M

    2010-01-01

    The group-based trajectory modeling approach is a systematic way of categorizing subjects into different groups based on their developmental trajectories using formal and objective statistical criteria. With the recent advancement in methods and statistical software, modeling possibilities are almost limitless; however, parallel advances in theory development have not kept pace. This paper examines some of the modeling options that are becoming more widespread and how they impact both empirical and theoretical findings. The key issue that is explored is the impact of adding random effects to the latent growth factors and how this alters the meaning of a group. The paper argues that technical specification should be guided by theory, and Moffitt's developmental taxonomy is used as an illustration of how modeling decisions can be matched to theory.

  15. 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…

  16. Mineralisation of developmentally hypomineralised human enamel in vitro.

    PubMed

    Crombie, F A; Cochrane, N J; Manton, D J; Palamara, J E A; Reynolds, E C

    2013-01-01

    Molar-incisor hypomineralisation (MIH) is a problematic and costly condition. Caries remineralising agents are often recommended for MIH management despite the lack of evidence that these lesions have the capacity for increasing their mineral content. Following surface layer removal ± NaOCl pre-treatment and 14-day exposure to a CPP-ACFP solution at pH 5.5, MIH lesions were analysed using transverse microradiography and polarised light microscopy. Lesions were highly variable but treatment with the remineralising solution increased mineral content (1,828 ± 461 vol% min · µm, %R = 17.7 ± 5.7) and porosity decreased demonstrating the proof of concept that the mineral content of developmentally hypomineralised enamel can be improved after eruption.

  17. Human developmental biology viewed from a microbial perspective

    PubMed Central

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

    2017-01-01

    Preface Most people think of human development only in terms of ‘human’ cells and organs. Here, we discuss another facet involving human-associated microbial communities. A microbial perspective of human development provides opportunities to refine our definitions of healthy pre- and postnatal growth and to develop new strategies for disease prevention and treatment. Considering the dramatic changes in lifestyles and disease patterns that are occurring with globalization, we issue a call for human microbial observatory programs designed to examine microbial community development in birth cohorts representing populations with diverse anthropologic characteristics, including those undergoing rapid change. PMID:27383979

  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. Evidence for developmental programming of cerebral laterality in humans.

    PubMed

    Jones, Alexander; Osmond, Clive; Godfrey, Keith M; Phillips, David I W

    2011-02-16

    Adverse fetal environments are associated with depression, reduced cognitive ability and increased stress responsiveness in later life, but underlying mechanisms are unknown. Environmental pressures on the fetus, resulting from variations in placental function and maternal nutrition, health and stress might alter neurodevelopment, promoting the development of some brain regions over others. As asymmetry of cerebral activity, with greater right hemisphere activity, has been associated with psychopathology, we hypothesized that regional specialization during fetal life might be reflected persistently in the relative activity of the cerebral hemispheres. We tested this hypothesis in 140 healthy 8-9 year-old children, using tympanic membrane temperature to assess relative blood flow to the cerebral hemispheres at rest and following psychosocial stress (Trier Social Stress Test for Children). Their birth weight and placental weight had already been measured when their mothers took part in a previous study of pregnancy outcomes. We found that children who had a smaller weight at birth had evidence of greater blood flow to the right hemisphere than to the left hemisphere (r = -.09, P = .29 at rest; r = -.18, P = .04 following stress). This finding was strengthened if the children had a relatively low birth weight for their placental weight (r = -.17, P = .05 at rest; r = -.31, P = .0005 following stress). Our findings suggest that lateralization of cerebral activity is influenced persistently by early developmental experiences, with possible consequences for long-term neurocognitive function.

  20. 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 =…

  1. 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…

  2. Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis.

    PubMed

    Williams, Amy Lavin; Watson, Rebecca E; DeSesso, John M

    2012-01-01

    Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals. To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed. An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring. Furthermore, no plausible mechanisms of action for such effects were elucidated. Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined. These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.

  3. 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"…

  4. 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...

  5. 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...

  6. Developmental Changes in Children's Understanding of the Similarity between Photographs and Their Referents

    ERIC Educational Resources Information Center

    Uttal, David H.; Gentner, Dedre; Liu, Linda L.; Lewis, Alison R.

    2008-01-01

    In a series of three experiments, we investigated the development of children's understanding of the similarities between photographs and their referents. Based on prior work on the development of analogical understanding (e.g. Gentner & Rattermann, 1991), we suggest that the appreciation of this relation involves multiple levels. Photographs…

  7. Exploring and Understanding the Biochemical Diversity of the Human Microbiota.

    PubMed

    Koppel, Nitzan; Balskus, Emily P

    2016-01-21

    Recent studies have illuminated a remarkable diversity and abundance of microbes living on and within the human body. While we are beginning to appreciate associations of certain bacteria and genes with particular host physiological states, considerable information is lacking about the relevant functional activities of the human microbiota. The human gut microbiome encodes tremendous potential for the biosynthesis and transformation of compounds that are important for both microbial and host physiology. Implementation of chemical knowledge and techniques will be required to improve our understanding of the biochemical diversity of the human microbiota. Such efforts include the characterization of novel microbial enzymes and pathways, isolation of microbial natural products, and development of tools to modulate biochemical functions of the gut microbiota. Ultimately, a molecular understanding of gut microbial activities will be critical for elucidating and manipulating these organisms' contributions to human health and disease.

  8. Oocyte Developmental Competence: Insights from Cross-Species Differential Gene Expression and Human Oocyte-Specific Functional Gene Networks.

    PubMed

    Biase, Fernando H

    2017-03-01

    Understanding oocyte developmental competence remains a key challenge for reproductive biology and systems sciences. The transcriptome of oocytes in eutherians is highly complex and is associated with the success of embryo development. Due to sample limitations from humans, animal models are used for investigation of the oocyte transcriptome. Nonetheless, little is known about the diversity of the oocyte transcriptome across eutherians. In this report, comprehensive investigation of 7 public data sets in 4 species, human, macaque, mice, and cattle, shows that 16,572 genes are expressed in oocytes. Approximately 26% of the genes were expressed in all four species. There were 1390, 489, and 187 genes specifically expressed in human, mice, and cattle oocytes, respectively. Coexpression clustering of the genes specifically expressed in human oocytes revealed functional enrichment (FDR <0.05) of Gene Ontology (GO) terms important for oocyte physiology (i.e., "cellular response to metal ion," "negative regulation of growth," "hormone activity," and "receptor activity"). Interrogation of 4 data sets revealed 26 genes whose expressions were significantly (FDR ≤0.1) associated with oocyte developmental competence and concordant fold change in 2 studies. The genes AK2, AKAP1, ECHS1, MRPL10, MRPL24, PTRH2, STX17, SUCLG1, SUOX, and TOMM34 were associated with the GO term "mitochondrion" (FDR <0.01). Collectively, the results offer new insights on gene transcript levels associated with oocyte developmental competence and the central role of mitochondrion for oocyte's health among eutherians. Caution should be exercised, however, when extending the inferences related to gene expression associated with oocyte quality across eutherians.

  9. Developmental Origins of Hypoxic Pulmonary Hypertension and Systemic Vascular Dysfunction: Evidence from Humans.

    PubMed

    Sartori, Claudio; Rimoldi, Stefano F; Duplain, Hervé; Stuber, Thomas; Garcin, Sophie; Rexhaj, Emrush; Allemann, Yves; Scherrer, Urs

    2016-01-01

    Epidemiological studies have shown an association between pathologic events occurring during fetal/perinatal life and the development of cardiovascular and metabolic disease in adulthood. These observations have led to the so-called developmental origin of adult disease hypothesis. More recently, evidence has been provided that the pulmonary circulation is also an important target for the developmental programming of adult disease in both experimental animal models and in humans. Here we will review this evidence and provide insight into mechanisms that may play a pathogenic role.

  10. Bridging epidemiology and model organisms to increase understanding of endocrine disrupting chemicals and human health effects.

    PubMed

    Woodruff, Tracey J

    2011-10-01

    Concerning temporal trends in human reproductive health has prompted concern about the role of environmentally mediated risk factors. The population is exposed to chemicals present in air, water, food and in a variety of consumer and personal care products, subsequently multiple chemicals are found human populations around the globe. Recent reviews find that endocrine disrupting chemicals (EDCs) can adversely affect reproductive and developmental health. However, there are still many knowledge gaps. This paper reviews some of the key scientific concepts relevant to integrating information from human epidemiologic and model organisms to understand the relationship between EDC exposure and adverse human health effects. Additionally, areas of new insights which influence the interpretation of the science are briefly reviewed, including: enhanced understanding of toxicity pathways; importance of timing of exposure; contribution of multiple chemical exposures; and low dose effects. Two cases are presented, thyroid disrupting chemicals and anti-androgens chemicals, which illustrate how our knowledge of the relationship between EDCs and adverse human health effects is strengthened and data gaps reduced when we integrate findings from animal and human studies.

  11. Human Development Theories: A Comparison of Classic Human Development Theorists and the Implications for a Model of Developmental Social Interaction.

    ERIC Educational Resources Information Center

    Ollhoff, Jim

    This paper explores several theories of human development, with particular attention to the development of social interaction. Part 1 compares and contrasts major developmental theories, including those of Freud, Erikson, Piaget, Kohlberg, Kegan, Fowler, and Selman. From birth to 1 year, infants are laying the foundation that will guide their…

  12. Developmental Trajectories of Peer-Reported Aggressive Behavior: The Role of Friendship Understanding, Friendship Quality, and Friends’ Aggressive Behavior

    PubMed Central

    Malti, Tina; McDonald, Kristina; Rubin, Kenneth H.; Rose-Krasnor, Linda; Booth-LaForce, Cathryn

    2015-01-01

    Objective To investigate developmental trajectories in peer-reported aggressive behavior across the transition from elementary-to-middle school, and whether aggressive behavior trajectories were associated with friendship quality, friends’ aggressive behavior, and the ways in which children think about their friendships. Method Participants included a community sample of 230 5th grade children who were assessed when they made a transition from elementary-to-middle school (6th grade). Peer nominations were used to assess the target child’s and friend’s aggressive behavior. Self- and friend reports were used to measure friendship quality; friendship understanding was assessed via a structured interview. Results General Growth Mixture Modeling (GGMM) revealed three distinct trajectories of peer-reported aggressive behavior across the school transition: low-stable, decreasing, and increasing. Adolescents’ understanding of friendship formation differentiated the decreasing from the low-stable aggressive behavior trajectories, and the understanding of friendship trust differentiated the increasing from the low-stable aggressive and decreasing aggressive behavior trajectories. Conclusions The findings indicated that a sophisticated understanding of friendship may serve as a protective factor for initially aggressive adolescents as they transition into middle school. Promoting a deepened understanding of friendship relations and their role in one’s own and others’ well-being may serve as an important prevention and intervention strategy to reduce aggressive behavior. PMID:26688775

  13. 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

  14. Human Neurospheres as Three-Dimensional Cellular Systems for Developmental Neurotoxicity Testing

    PubMed Central

    Moors, Michaela; Rockel, Thomas Dino; Abel, Josef; Cline, Jason E.; Gassmann, Kathrin; Schreiber, Timm; Schuwald, Janette; Weinmann, Nicole; Fritsche, Ellen

    2009-01-01

    Background Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the “3 Rs” (reduction, replacement, and refinement) of animal testing and the European regulation of chemicals [Registration, Evaluation, and Authorisation of Chemicals (REACH)], alternative testing strategies are needed in order to refine and reduce animal experiments and allow faster and less expensive screening. Objectives The goal of this study was to establish a three-dimensional test system for DNT screening based on human fetal brain cells. Methods We established assays suitable for detecting disturbances in basic processes of brain development by employing human neural progenitor cells (hNPCs), which grow as neurospheres. Furthermore, we assessed effects of mercury and oxidative stress on these cells. Results We found that human neurospheres imitate proliferation, differentiation, and migration in vitro. Exposure to the proapoptotic agent staurosporine further suggests that human neurospheres possess functioning apoptosis machinery. The developmental neurotoxicants methylmercury chloride and mercury chloride decreased migration distance and number of neuronal-like cells in differentiated hNPCs. Furthermore, hNPCs undergo caspase-independent apoptosis when exposed toward high amounts of oxidative stress. Conclusions Human neurospheres are likely to imitate basic processes of brain development, and these processes can be modulated by developmental neurotoxicants. Thus, this three-dimensional cell system is a promising approach for DNT testing. PMID:19654924

  15. Qualitative and quantitative comparability of human and animal developmental neurotoxicants: a workshop summary.

    PubMed

    Rees, D C; Francis, E Z; Kimmel, C A

    1990-01-01

    A Workshop on the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity was held in Williamsburg, Va. on April 11-13, 1989. Based upon data presented at the Workshop, the degree of qualitative and quantitative comparability between data obtained from humans and experimental animals is reviewed for several developmental neurotoxicants (lead, agents of abuse, alcohol, PCBs, phenytoin, methylmercury, and ionizing radiation). Qualitative comparability was considered for the following functional categories: motor development and function, cognitive function, sensory function, motivation/arousal behavior, and social behavior. Quantitative comparability was assessed by comparing administered dose as well as measures of internal dose (e.g., blood levels) for selected agents. Comparability of qualitative changes between humans and rodents was most apparent when comparisons were made on the basis of general categories of behavioral function. These data support the use of animal models in assessing risk for developmental neurotoxicants and provide guidance on the types of functional end points that can be incorporated into a developmental neurotoxicity testing battery. Evidence of quantitative comparability was most apparent when an internal measure of dose (e.g., blood level) was used.

  16. A human pluripotent stem cell platform for assessing developmental neural toxicity screening

    PubMed Central

    2013-01-01

    A lack of affordable and effective testing and screening procedures mean surprisingly little is known about the health hazards of many of the tens of thousands of chemicals in use in the world today. The recent rise in the number of children affected by neurological disorders such as autism has stirred valuable debate about the role chemicals play in our daily life, highlighting the need for improved methods of assessing chemicals for developmental neural toxicity. Current methods of testing chemicals for developmental neural toxicity include animal testing with rats or mice and in vitro testing using cultured primary cells or cell lines. Here, we review the current state of neural toxicity screening, analyze the limitations of these methods and, under the National Institutes of Health's new Microphysiological Systems initiative, describe a human pluripotent stem cell-based platform for developmental neural toxicity screens. PMID:24565336

  17. 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.

  18. Human enteric defensins. Gene structure and developmental expression.

    PubMed

    Mallow, E B; Harris, A; Salzman, N; Russell, J P; DeBerardinis, R J; Ruchelli, E; Bevins, C L

    1996-02-23

    Paneth cells, secretory epithelial cells of the small intestinal crypts, are proposed to contribute to local host defense. Both mouse and human Paneth cells express a collection of antimicrobial proteins, including members of a family of antimicrobial peptides named defensins. In this study, data from an anchored polymerase chain reaction (PCR) strategy suggest that only two defensin mRNA isoforms are expressed in the human small intestine, far fewer than the number expressed in the mouse. The two isoforms detected by this PCR approach were human defensin family members, HD-5 and HD-6. The gene encoding HD-6 was cloned and characterized. HD-6 has a genomic organization similar to HD-5, and the two genes have a striking pattern of sequence similarity localized chiefly in their proximal 5'-flanking regions. Analysis of human fetal RNA by reverse transcriptase-PCR detected enteric defensin HD-5 mRNA at 13.5 weeks of gestation in the small intestine and the colon, but by 17 weeks HD-5 was restricted to the small intestine. HD-6 mRNA was detectable at 13.5-17 weeks of gestation in the small intestine but not in the colon. This pattern of expression coincides with the previously described appearance of Paneth cells as determined by ultrastructural approaches. Northern analysis of total RNA from small intestine revealed quantifiable enteric defensin mRNA in five samples from 19 24 weeks of gestation at levels approximately 40-250-fold less than those observed in the adult, with HD-5 mRNA levels greater than those of HD-6 in all samples. In situ hybridization analysis localized expression of enteric defensin mRNA to Paneth cells at 24 weeks of gestation, as is seen in the newborn term infant and the adult. Consistent with earlier morphological studies, the ratio of Paneth cell number per crypt was reduced in samples at 24 weeks of gestation compared with the adult, and this lower cell number partially accounts for the lower defensin mRNA levels as determined by Northern

  19. 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,…

  20. 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…

  1. Developmental Sequences in Children's Understanding of Death with Implications for Counselors.

    ERIC Educational Resources Information Center

    Matter, Darryl E.; Matter, Roxana Marie

    1982-01-01

    Proposes children develop an understanding about death in an orderly sequence progressing from total unawareness in early childhood to the point of logical consideration in terms of cause and effect. Discusses implications for parents, teachers, and counselors for helping children deal with death. (RC)

  2. Non-human primates: a comparative developmental perspective on yawning.

    PubMed

    Anderson, James R

    2010-01-01

    There is a long history of yawning in Old World monkeys being viewed as a form of communication, in particular, as a kind of threat. Yawning in agonistic and tense situations is seen in adult males, in particular, and it varies with male hormonal levels and social status. Experiments are reviewed that demonstrate operant control of the rate of yawning in adult male macaques, using food rewards. This indicates a degree of flexibility in the production of yawning. However, although adult male Old World monkeys often engage in 'canine contests', there is little evidence for the contagious yawning seen in humans. Experiments are reviewed showing that chimpanzees tested under comparable conditions to human adults, namely exposed to video sequences showing yawns, may yawn contagiously to yawn stimuli. Chimpanzees also yawn to computer animations of yawns. There is controversy in the literature over whether other species, including dogs and some monkeys, may also show contagious yawning. Further research is required to address unresolved issues. A hypothesis is put forward that in modern industrial society adults' natural pattern of yawning is inhibited, and that being reminded to yawn by seeing another individual yawn (contagious yawning) can help us to catch up on missed yawns. This would explain the lack of contagious yawning reported in young children and chimpanzees in natural surroundings, as these populations do not have the same social constraints on yawning.

  3. 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…

  4. Understanding the Identities of Mixed-Race College Students through a Developmental Ecology Lens.

    ERIC Educational Resources Information Center

    Renn, Kristen A.

    2003-01-01

    Using an ecology model of human development, frames the exploration of racial identities of 38 college students with multiple racial heritages. Maps the influence of interactions within and between specific environments on students' decisions to identify in one or more of five patterns of mixed race identity found in a previous study. (Contains 43…

  5. To Encounter, to Build the World and to Become a Human Being. Advocating for a Material-Cultural Turn in Developmental Psychology.

    PubMed

    Moro, Christiane

    2016-12-01

    Why have material world of daily life and material objects in their conventional features or to say it in other words, why have the mundane world and mundane objects, in which the human beings live and children come to, encounter, experience and develop through, received so little attention from psychologists thus remaining a blind spot in mainstream developmental psychology? Certainly the object has not been totally forgotten (e.g. Piaget's constructivist paradigm) but it has been considered as theoretically determined by the categories of understanding (cf. Kant), and considered as a key to understanding the world in its physical properties by the infant. But the material world and the material objects that are used for everyday purposes (i.e. pragmatically) belonging to material culture, have been totally neglected by developmental psychologists. Reacting to the Kantian agenda of developmental psychology but also to heterodox non developmentalist thinkers such as Gibson who is a growing source of inspiration for developmental psychologists today, we challenge the taken-for-granted mundane world, arguing for the importance of material objects related to material culture in psychological development during the prelinguistic period. On the basis of recent research in early development grounded in the Vygotskian paradigm, we discuss this issue through Marxist Anthropology, Material Culture Studies and Phenomenology. As a consequence we advocate for a material-cultural turn in psychological development in order to place the issue of material world and material objects in their pragmatic and semiotic features on the agenda of developmental psychology.

  6. Children's skill in making predictions and their understanding of what predicting means: A developmental study

    NASA Astrophysics Data System (ADS)

    McNay, Margaret; Melville, Kathleen W.

    The purpose of this study was to describe the development of elementary students' skill in making predictions and of their understanding of what predicting means. The study involved observing and assessing the performance of 167 children on the Physical Manipulation Test (PMT), a test involving the manipulation of science materials and equipment. Children were interviewed about what they understand predicting to mean, how they use it at school and at home, and why they think it is important. For each of the seven topics tested, even the youngest children were able to offer predictions. Accuracy varied with the topic, increasing between Grades 1 and 4 and leveling off after that. The increase in skill involved children's growing ability to attend to patterns discerned through their own observations. Four levels in the development of predicting skill, as it relates to particular topics, are described. Children's understanding of predicting showed steady improvement through Grade 6. Children's awareness of their use of predicting at school and at home, and their ability to explain the importance of predicting, also increased through Grades 1 to 6, with a spurt at Grade 4. Children understood predicting to be an internal process in which one uses knowledge to anticipate a future event; they regarded predicting as an important way of being intellectually involved with the world.

  7. The grass leaf developmental gradient as a platform for a systems understanding of the anatomical specialization of C(4) leaves.

    PubMed

    Nelson, Timothy

    2011-05-01

    C(4) photosynthesis relies on spatial and quantitative specializations of common features of leaf anatomy, including venation pattern, bundle sheath cell and chloroplast differentiation, plasmodesmatal abundance, and secondary cell wall enhancement. It has thus far been challenging to dissect the molecular basis for these C(4)-specific alterations in spatial and quantitative patterns of regulation. The target downstream networks of genes and protein interactions that produce these fundamental anatomical features in both C(4) and C(3) species are poorly understood. The developing leaves of monocot grasses provide a base-to-tip gradient of developmental stages that can provide the platform for comprehensive molecular and anatomical data that can yield a better understanding both of the regulators and the targets that produce C(4) patterns, through a variety of gene discovery and systems analysis strategies.

  8. Purification of human NK cell developmental intermediates from lymph nodes and tonsils.

    PubMed

    Freud, Aharon G; Caligiuri, Michael A

    2010-01-01

    Accumulating data indicate that human natural killer (NK) cells undergo terminal maturation in secondary lymphoid tissues (SLTs) including lymph nodes (LNs) and tonsils. In addition, recent studies have revealed that maturing NK cells progress through at least five functionally discrete stages of development within SLTs. These discoveries provide unique possibilities for researchers to investigate the natural processes governing human NK cell development, as they exist in vivo, through analysis of NK cell maturational intermediates found in situ. Herein we describe a detailed, yet simple, four-step protocol for the viable enrichment and purification of human NK cell developmental intermediates from LNs and tonsils.

  9. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma.

    PubMed

    Tirosh, Itay; Venteicher, Andrew S; Hebert, Christine; Escalante, Leah E; Patel, Anoop P; Yizhak, Keren; Fisher, Jonathan M; Rodman, Christopher; Mount, Christopher; Filbin, Mariella G; Neftel, Cyril; Desai, Niyati; Nyman, Jackson; Izar, Benjamin; Luo, Christina C; Francis, Joshua M; Patel, Aanand A; Onozato, Maristela L; Riggi, Nicolo; Livak, Kenneth J; Gennert, Dave; Satija, Rahul; Nahed, Brian V; Curry, William T; Martuza, Robert L; Mylvaganam, Ravindra; Iafrate, A John; Frosch, Matthew P; Golub, Todd R; Rivera, Miguel N; Getz, Gad; Rozenblatt-Rosen, Orit; Cahill, Daniel P; Monje, Michelle; Bernstein, Bradley E; Louis, David N; Regev, Aviv; Suvà, Mario L

    2016-11-10

    Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.

  10. A New World Information Order for Better Human Understanding.

    ERIC Educational Resources Information Center

    Masmoudi, Mustapha

    Many studies, particularly the report of the International Commission for the Study of Communication Problems (ICSCP), have tried to define a new world information order for better human understanding. What appears to be needed is the establishment of a new, open-ended, conceptual framework leading to a freer, more efficient, more equitable,…

  11. 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…

  12. 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

  13. 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.

  14. 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.

  15. Linking social change and developmental change: shifting pathways of human development.

    PubMed

    Greenfield, Patricia M

    2009-03-01

    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 low-technology environments to urban residence, formal schooling, commerce, and high-technology environments. The former ecology is summarized by the German term Gemeinschaft ("community") and the latter by the German term Gesellschaft ("society"; Tönnies, 1887/1957). A review of empirical research demonstrates that, through adaptive processes, movement of any ecological variable in a Gesellschaft direction shifts cultural values in an individualistic direction and developmental pathways toward more independent social behavior and more abstract cognition--to give a few examples of the myriad behaviors that respond to these sociodemographic changes. In contrast, the (much less frequent) movement of any ecological variable in a Gemeinschaft direction is predicted to move cultural values and developmental pathways in the opposite direction. In conclusion, sociocultural environments are not static either in the developed or the developing world and therefore must be treated dynamically in developmental research.

  16. Modeling vision: computational science for understanding human visual perception.

    PubMed

    Mrowka, Ralf; Freytag, Alexander; Reuter, Stefanie

    2017-03-25

    Human visual perception system is complex and involves a considerable portion of the brain's cortex. Hence, the wish to understand complex neuronal function is obvious, and the idea to model this by means of artificial neuronal networks might have been born at the time when first computational machines were constructed (Alan Turing, Intelligent machinery, 1948, h t t p: //www.npl.co.uk/about/history/notable-individuals/turing/intelligent-machinery) This article is protected by copyright. All rights reserved.

  17. 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

  18. 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

  19. Embodied artificial agents for understanding human social cognition.

    PubMed

    Wykowska, Agnieszka; Chaminade, Thierry; Cheng, Gordon

    2016-05-05

    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?'

  20. 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

  1. 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

  2. Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes.

    PubMed

    Flax, J D; Aurora, S; Yang, C; Simonin, C; Wills, A M; Billinghurst, L L; Jendoubi, M; Sidman, R L; Wolfe, J H; Kim, S U; Snyder, E Y

    1998-11-01

    Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. These self-renewing clones give rise to all fundamental neural lineages in vitro. Following transplantation into germinal zones of the newborn mouse brain they participate in aspects of normal development, including migration along established migratory pathways to disseminated central nervous system regions, differentiation into multiple developmentally and regionally appropriate cell types, and nondisruptive interspersion with host progenitors and their progeny. These human NSCs can be genetically engineered and are capable of expressing foreign transgenes in vivo. Supporting their gene therapy potential, secretory products from NSCs can correct a prototypical genetic metabolic defect in neurons and glia in vitro. The human NSCs can also replace specific deficient neuronal populations. Cryopreservable human NSCs may be propagated by both epigenetic and genetic means that are comparably safe and effective. By analogy to rodent NSCs, these observations may allow the development of NSC transplantation for a range of disorders.

  3. "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…

  4. Proteome Analysis of Distinct Developmental Stages of Human Natural Killer (NK) Cells

    PubMed Central

    Scheiter, Maxi; Lau, Ulrike; van Ham, Marco; Bulitta, Björn; Gröbe, Lothar; Garritsen, Henk; Klawonn, Frank; König, Sebastian; Jänsch, Lothar

    2013-01-01

    The recent Natural Killer (NK) cell maturation model postulates that CD34+ hematopoietic stem cells (HSC) first develop into CD56bright NK cells, then into CD56dimCD57− and finally into terminally maturated CD56dimCD57+. The molecular mechanisms of human NK cell differentiation and maturation however are incompletely characterized. Here we present a proteome analysis of distinct developmental stages of human primary NK cells, isolated from healthy human blood donors. Peptide sequencing was used to comparatively analyze CD56bright NK cells versus CD56dim NK cells and CD56dimCD57− NK cells versus CD56dimCD57+ NK cells and revealed distinct protein signatures for all of these subsets. Quantitative data for about 3400 proteins were obtained and support the current differentiation model. Furthermore, 11 donor-independently, but developmental stage specifically regulated proteins so far undescribed in NK cells were revealed, which may contribute to NK cell development and may elucidate a molecular source for NK cell effector functions. Among those proteins, S100A4 (Calvasculin) and S100A6 (Calcyclin) were selected to study their dynamic subcellular localization. Upon activation of human primary NK cells, both proteins are recruited into the immune synapse (NKIS), where they colocalize with myosin IIa. PMID:23315794

  5. 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

  6. 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.

  7. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Ethylene Glycol.

    PubMed

    2004-01-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for ethylene glycol (EG) to cause adverse effects on reproduction and development in humans. EG was selected for evaluation due to recent toxicity and occupational exposure information and widespread exposure in the general public. EG is a small, hydroxy-substituted hydrocarbon used as a chemical intermediate in the production of polyester compounds. It is also found in automotive anti-freeze, industrial coolants, hydraulic fluids, and windshield deicer fluids. The results of this evaluation on EG are published in a NTP-CERHR monograph which includes: 1) the Expert Panel Report on the Reproductive and Developmental Toxicity of Ethylene Glycol, 2) the NTP Brief, 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 EG on human development and reproduction based on the conclusions of the NTP-CERHR Expert Panel Report and the public comments received on that report. These conclusions concurred with those of the expert panel. First, although EG could possibly affect human development if exposures are sufficiently high, there is negligible concern for developmental effects in humans at current proposed/estimated exposure levels. There is no direct evidence that exposure of people to EG adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure to high doses of EG can adversely affect development in mice and rats. These studies indicate doses that exceed saturation of the glycolic acid metabolism are needed to produce developmental toxicity. Proposed exposure scenarios constructed by the expert panel and current proposed/estimated exposure levels suggest that human exposures are at least 100- to 1000-fold lower than the dose expected to result in metabolic

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

    PubMed

    Shi, Lei; Zhang, Zhe; Su, Bing

    2016-02-16

    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.

  9. Pluripotent stem cell-derived organoids: using principles of developmental biology to grow human tissues in a dish.

    PubMed

    McCauley, Heather A; Wells, James M

    2017-03-15

    Pluripotent stem cell (PSC)-derived organoids are miniature, three-dimensional human tissues generated by the application of developmental biological principles to PSCs in vitro The approach to generate organoids uses a combination of directed differentiation, morphogenetic processes, and the intrinsically driven self-assembly of cells that mimics organogenesis in the developing embryo. The resulting organoids have remarkable cell type complexity, architecture and function similar to their in vivo counterparts. In the past five years, human PSC-derived organoids with components of all three germ layers have been generated, resulting in the establishment of a new human model system. Here, and in the accompanying poster, we provide an overview of how principles of developmental biology have been essential for generating human organoids in vitro, and how organoids are now being used as a primary research tool to investigate human developmental biology.

  10. Early human communication helps in understanding language evolution.

    PubMed

    Lenti Boero, Daniela

    2014-12-01

    Building a theory on extant species, as Ackermann et al. do, is a useful contribution to the field of language evolution. Here, I add another living model that might be of interest: human language ontogeny in the first year of life. A better knowledge of this phase might help in understanding two more topics among the "several building blocks of a comprehensive theory of the evolution of spoken language" indicated in their conclusion by Ackermann et al., that is, the foundation of the co-evolution of linguistic motor skills with the auditory skills underlying speech perception, and the possible phylogenetic interactions of protospeech production with referential capabilities.

  11. Understanding the contribution of synonymous mutations to human disease.

    PubMed

    Sauna, Zuben E; Kimchi-Sarfaty, Chava

    2011-08-31

    Synonymous mutations - sometimes called 'silent' mutations - are now widely acknowledged to be able to cause changes in protein expression, conformation and function. The recent increase in knowledge about the association of genetic variants with disease, particularly through genome-wide association studies, has revealed a substantial contribution of synonymous SNPs to human disease risk and other complex traits. Here we review current understanding of the extent to which synonymous mutations influence disease, the various molecular mechanisms that underlie these effects and the implications for future research and biomedical applications.

  12. 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].

  13. 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

  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.

  15. A developmental stage-specific switch from DAZL to BOLL occurs during fetal oogenesis in humans, but not mice.

    PubMed

    He, Jing; Stewart, Kayleigh; Kinnell, Hazel L; Anderson, Richard A; Childs, Andrew J

    2013-01-01

    The Deleted in Azoospermia gene family encodes three germ cell-specific RNA-binding proteins (DAZ, DAZL and BOLL) that are essential for gametogenesis in diverse species. Targeted disruption of Boll in mice causes male-specific spermiogenic defects, but females are apparently fertile. Overexpression of human BOLL promotes the derivation of germ cell-like cells from genetically female (XX), but not male (XY) human ES cells however, suggesting a functional role for BOLL in regulating female gametogenesis in humans. Whether BOLL is expressed during oogenesis in mammals also remains unclear. We have therefore investigated the expression of BOLL during fetal oogenesis in humans and mice. We demonstrate that BOLL protein is expressed in the germ cells of the human fetal ovary, at a later developmental stage than, and almost mutually-exclusive to, the expression of DAZL. Strikingly, BOLL is downregulated, and DAZL re-expressed, as primordial follicles form, revealing BOLL expression to be restricted to a narrow window during fetal oogenesis. By quantifying the extent of co-expression of DAZL and BOLL with markers of meiosis, we show that this window likely corresponds to the later stages of meiotic prophase I. Finally, we demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl. These data reveal significant similarities and differences between the expression of BOLL homologues during oogenesis in humans and mice, and raise questions as to the validity of the Boll(-/-) mouse as a model for understanding BOLL function during human oogenesis.

  16. Developmental origins of health and disease: experimental and human evidence of fetal programming for metabolic syndrome.

    PubMed

    de Gusmão Correia, M L; Volpato, A M; Águila, M B; Mandarim-de-Lacerda, C A

    2012-07-01

    The concept of developmental origins of health and disease has been defined as the process through which the environment encountered before birth, or in infancy, shapes the long-term control of tissue physiology and homeostasis. The evidence for programming derives from a large number of experimental and epidemiological observations. Several nutritional interventions during diverse phases of pregnancy and lactation in rodents are associated with fetal and neonatal programming for metabolic syndrome. In this paper, recent experimental models and human epidemiological studies providing evidence for the fetal programming associated with the development of metabolic syndrome and related diseases are revisited.

  17. Understanding human activity patterns based on space-time-semantics

    NASA Astrophysics Data System (ADS)

    Huang, Wei; Li, Songnian

    2016-11-01

    Understanding human activity patterns plays a key role in various applications in an urban environment, such as transportation planning and traffic forecasting, urban planning, public health and safety, and emergency response. Most existing studies in modeling human activity patterns mainly focus on spatiotemporal dimensions, which lacks consideration of underlying semantic context. In fact, what people do and discuss at some places, inferring what is happening at the places, cannot be simple neglected because it is the root of human mobility patterns. We believe that the geo-tagged semantic context, representing what individuals do and discuss at a place and a specific time, drives a formation of specific human activity pattern. In this paper, we aim to model human activity patterns not only based on space and time but also with consideration of associated semantics, and attempt to prove a hypothesis that similar mobility patterns may have different motivations. We develop a spatiotemporal-semantic model to quantitatively express human activity patterns based on topic models, leading to an analysis of space, time and semantics. A case study is conducted using Twitter data in Toronto based on our model. Through computing the similarities between users in terms of spatiotemporal pattern, semantic pattern and spatiotemporal-semantic pattern, we find that only a small number of users (2.72%) have very similar activity patterns, while the majority (87.14%) show different activity patterns (i.e., similar spatiotemporal patterns and different semantic patterns, similar semantic patterns and different spatiotemporal patterns, or different in both). The population of users that has very similar activity patterns is decreased by 56.41% after incorporating semantic information in the corresponding spatiotemporal patterns, which can quantitatively prove the hypothesis.

  18. Model organisms inform the search for the genes and developmental pathology underlying malformations of the human hindbrain

    PubMed Central

    Aldinger, Kimberly A.; Elsen, Gina E.; Prince, Victoria E.; Millen, Kathleen J.

    2009-01-01

    Congenital malformations the human hindbrain, including the cerebellum, are poorly understood largely because their recognition is a relatively recent advance for imaging diagnostics. Cerebellar malformations are the most obvious and best characterized hindbrain malformations due to their relative ease to view by MRI and the recent identification of several causative genes1. Malformations of the pons and medulla have also been described both in isolation and in association with cerebellar malformations2. Although little is understood regarding the specific developmental pathologies underlying hindbrain malformations in humans, much is known regarding the mechanisms and genes driving hindbrain development in vertebrate model organisms. Thus, studies in vertebrate models provide a developmental framework in which to categorize human hindbrain malformations and serve to inform our thinking regarding disrupted developmental processes and candidate genes. Here we survey the basic principles of vertebrate hindbrain development and integrate our current knowledge of human hindbrain malformations into this framework. PMID:19778712

  19. Developmental Reprogramming in Mesenchymal Stromal Cells of Human Subjects with Idiopathic Pulmonary Fibrosis

    PubMed Central

    Chanda, Diptiman; Kurundkar, Ashish; Rangarajan, Sunad; Locy, Morgan; Bernard, Karen; Sharma, Nirmal S.; Logsdon, Naomi J.; Liu, Hui; Crossman, David K.; Horowitz, Jeffrey C.; De Langhe, Stijn; Thannickal, Victor J.

    2016-01-01

    Cellular plasticity and de-differentiation are hallmarks of tissue/organ regenerative capacity in diverse species. Despite a more restricted capacity for regeneration, humans with age-related chronic diseases, such as cancer and fibrosis, show evidence of a recapitulation of developmental gene programs. We have previously identified a resident population of mesenchymal stromal cells (MSCs) in the terminal airways-alveoli by bronchoalveolar lavage (BAL) of human adult lungs. In this study, we characterized MSCs from BAL of patients with stable and progressive idiopathic pulmonary fibrosis (IPF), defined as <5% and ≥10% decline, respectively, in forced vital capacity over the preceding 6-month period. Gene expression profiles of MSCs from IPF subjects with progressive disease were enriched for genes regulating lung development. Most notably, genes regulating early tissue patterning and branching morphogenesis were differentially regulated. Network interactive modeling of a set of these genes indicated central roles for TGF-β and SHH signaling. Importantly, fibroblast growth factor-10 (FGF-10) was markedly suppressed in IPF subjects with progressive disease, and both TGF-β1 and SHH signaling were identified as critical mediators of this effect in MSCs. These findings support the concept of developmental gene re-activation in IPF, and FGF-10 deficiency as a potentially critical factor in disease progression. PMID:27869174

  20. 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

  1. 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.

  2. 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.

  3. USING ACTION UNDERSTANDING TO UNDERSTAND THE LEFT INFERIOR PARIETAL CORTEX IN THE HUMAN BRAIN

    PubMed Central

    Passingham, RE; Chung, A; Goparaju, B; Cowey, A; Vaina, LM

    2015-01-01

    In an fMRI study we tried to establish whether the areas in the human brain that are involved in the understanding of actions are homologous with the inferior parietal cortex (area PFG) in macaque monkeys. Cells have been described in area PFG that discharge differentially depending upon whether the observer sees food being brought to the mouth or a small object being put in a container. In our study the observers saw videos in which the use of different objects was demonstrated in pantomime; and after viewing the videos, the subject had to pick the object that was appropriate to the pantomime. We found a cluster of activated voxels in parietal areas PFop and PFt and this cluster was greater in the left hemisphere than in the right. We suggest a mechanism that could account for this asymmetry, relate our results to handedness and suggest that they shed light on the human syndrome of apraxia. Finally, we suggest that during the evolution of the hominids, this same pantomime mechanism could have been used to ‘name’ or request objects. PMID:25086203

  4. Somatic mutation in single human neurons tracks developmental and transcriptional history

    PubMed Central

    Evrony, Gilad D.; Mehta, Bhaven K.; Karger, Amir; Lee, Soohyun; Chittenden, Thomas W.; D’Gama, Alissa M.; Cai, Xuyu; Luquette, Lovelace J.; Lee, Eunjung; Park, Peter J.; Walsh, Christopher A.

    2015-01-01

    Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) in the human brain. We identified thousands of somatic SNVs by single-cell sequencing of 36 neurons from the cerebral cortex of three normal individuals. Unlike germline and cancer SNVs, which are often caused by errors in DNA replication, neuronal mutations appear to reflect damage during active transcription. Somatic mutations create nested lineage trees, allowing them to be dated relative to developmental landmarks and revealing a polyclonal architecture of the human cerebral cortex. Thus, somatic mutations in the brain represent a durable and ongoing record of neuronal life history, from development through postmitotic function. PMID:26430121

  5. 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…

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. Allelic diversity in human developmental neurogenetics: insights into biology and disease

    PubMed Central

    Walsh, Christopher A.; Engle, Elizabeth C.

    2010-01-01

    One of the biggest challenges in neuroscience is illuminating the architecture of developmental brain disorders, which include structural malformations of the brain and nerves, intellectual disability, epilepsy, as well as some psychiatric conditions like autism and potentially schizophrenia. Ongoing gene identification reveals a great diversity of genetic causes underlying abnormal brain development, illuminating new biochemical pathways often not suspected based on genetic studies in other organisms. Our greater understanding of genetic disease also shows the complexity of “allelic diversity”, in which distinct mutations in a given gene can cause a wide range of distinct diseases or other phenotypes. These diverse alleles not only provide a platform for discovery of critical protein-protein interactions in a genetic fashion, but also illuminate the likely genetic architecture of as yet poorly characterized neurological disorders. PMID:20955932

  13. 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...

  14. Understanding

    ERIC Educational Resources Information Center

    Buxkemper, Andra C.; Hartfiel, D. J.

    2003-01-01

    There is no common agreement on the meaning of the word "understand". However, there is agreement on what students should be able to do with material they understand. Bloom et al. discuss kinds of tasks a student should be able to do, provided that the student understands. In a similar way, Biggs and Collis provide a taxonomy intended to evaluate…

  15. 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…

  16. 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…

  17. 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…

  18. Alcohol Use in Emerging Adulthood: Can Moffitt's Developmental Theory Help Us Understand Binge Drinking among College Students?

    ERIC Educational Resources Information Center

    Reckdenwald, Amy; Ford, Jason A.; Murray, Brittany N.

    2016-01-01

    It is well-known that college students are at an increased risk for alcohol use and binge drinking compared to their same-age peers who are not in college. We use Moffitt's developmental taxonomy, specifically, her discussion of adolescence-limited offending, to contextualize this finding regarding this minor form of deviance. We also incorporate…

  19. Evolutionary developmental psychology.

    PubMed

    King, Ashley C; Bjorklund, David F

    2010-02-01

    The field of evolutionary developmental psychology can potentially broaden the horizons of mainstream evolutionary psychology by combining the principles of Darwinian evolution by natural selection with the study of human development, focusing on the epigenetic effects that occur between humans and their environment in a way that attempts to explain how evolved psychological mechanisms become expressed in the phenotypes of adults. An evolutionary developmental perspective includes an appreciation of comparative research and we, among others, argue that contrasting the cognition of humans with that of nonhuman primates can provide a framework with which to understand how human cognitive abilities and intelligence evolved. Furthermore, we argue that several aspects of childhood (e.g., play and immature cognition) serve both as deferred adaptations as well as imparting immediate benefits. Intense selection pressure was surely exerted on childhood over human evolutionary history and, as a result, neglecting to consider the early developmental period of children when studying their later adulthood produces an incomplete picture of the evolved adaptations expressed through human behavior and cognition.

  20. Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age

    PubMed Central

    Souza, C.C.R.; Dombroski, T.C.D.; Machado, H.R.; Oliveira, R.S.; Rocha, L.B.; Rodrigues, A.R.A.; Neder, L.; Chimelli, L.; Corrêa, V.M.A.; Larson, R.E.; Martins, A.R.

    2013-01-01

    Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence. PMID:23558932

  1. 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

  2. Fostering young people's support for participatory human rights through their developmental niches.

    PubMed

    Torney-Purta, Judith; Barber, Carolyn

    2011-10-01

    The last 6 decades of empirical research on civic engagement among young people living in democracies and of the recognition of international human rights have seen the achievement of many milestones. This article focuses on some connections between these 2 areas and examines the ways in which everyday settings such as neighborhoods and the schools that exist within them can foster support for human rights (especially the practice of participatory rights) among adolescents. Secondary analysis of the International Association for the Evaluation of Educational Achievement Civic Education (CIVED) Study (data collected in 1999 from nationally representative samples of 14-year-olds in 28 countries) is presented. A cluster analysis of 12 attitudinal scales in 5 countries sharing the Western European tradition (Australia, England, Finland, Sweden, and the United States) is presented. A new conceptual model is also introduced, a modification of Super and Harkness's Developmental Niche. This model frames an analysis unpacking some findings from the CIVED Study and focusing on the everyday experiences and neighborhood niches for the development of participatory human rights. The larger message is that research on social justice attitudes among young people is a valuable form of social advocacy and action.

  3. 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

  4. 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 ...

  5. 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…

  6. 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...

  7. 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...

  8. 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…

  9. 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

  10. 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

  11. NTP-CERHR monograph on the potential human reproductive and developmental effects of hydroxyurea.

    PubMed

    2008-10-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for hydroxyurea to cause adverse effects on reproduction and development in humans. Hydroxyurea is a drug used to treat cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease in children, aside from blood transfusion and, in severe cases, hematopoietic stem cell transplantation. Hydroxyurea is FDA-approved for use in adults with sickle cell anemia to reduce the frequency of painful crises and the need for blood transfusions. Hydroxyurea may be given to children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea is associated with known side effects such as cytotoxicity and myelosuppression, and hydroxyurea is genotoxic (can damage DNA). CERHR selected hydroxyurea for evaluation because of: its increasing use for treatment of sickle cell disease in children and adults, knowledge that it inhibits DNA synthesis and is cytotoxic, and published evidence of reproductive and developmental toxicity in rodents. The results of this evaluation are published in the NTP-CERHR Monograph on Hydroxyurea, which includes the NTP Brief and Expert Panel Report on the Reproductive and Developmental Toxicity of Hydroxyurea. Additional information related to the evaluation process, including public comments received on the draft NTP Brief and the final expert panel report, are available on the CERHR website (http:// cerhr.niehs.nih.gov/). See hydroxyurea under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs.nih.gov/chemicals/hydroxyurea/hydroxyurea-eval.html). The NTP reached the following conclusions on the possible effects of exposure to hydroxyurea on human reproduction or development. The possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern

  12. 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.

  13. 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.

  14. 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…

  15. 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.

  16. Understanding the recent evolution of the human genome: insights from human-chimpanzee genome comparisons.

    PubMed

    Kehrer-Sawatzki, Hildegard; Cooper, David N

    2007-02-01

    The sequencing of the chimpanzee genome and the comparison with its human counterpart have begun to reveal the spectrum of genetic changes that has accompanied human evolution. In addition to gross karyotypic rearrangements such as the fusion that formed human chromosome 2 and the human-specific pericentric inversions of chromosomes 1 and 18, there is considerable submicroscopic structural variation involving deletions, duplications, and inversions. Lineage-specific segmental duplications, detected by array comparative genomic hybridization and direct sequence comparison, have made a very significant contribution to this structural divergence, which is at least three-fold greater than that due to nucleotide substitutions. Since structural genomic changes may have given rise to irreversible functional differences between the diverging species, their detailed analysis could help to identify the biological processes that have accompanied speciation. To this end, interspecies comparisons have revealed numerous human-specific gains and losses of genes as well as changes in gene expression. The very considerable structural diversity (polymorphism) evident within both lineages has, however, hampered the analysis of the structural divergence between the human and chimpanzee genomes. The concomitant evaluation of genetic divergence and diversity at the nucleotide level has nevertheless served to identify many genes that have evolved under positive selection and may thus have been involved in the development of human lineage-specific traits. Genes that display signs of weak negative selection have also been identified and could represent candidate loci for complex genomic disorders. Here, we review recent progress in comparing the human and chimpanzee genomes and discuss how the differences detected have improved our understanding of the evolution of the human genome.

  17. 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…

  18. Annual research review: A developmental psychopathology approach to understanding callous-unemotional traits in children and adolescents with serious conduct problems.

    PubMed

    Frick, Paul J; Ray, James V; Thornton, Laura C; Kahn, Rachel E

    2014-06-01

    Recent research has suggested that the presence of significant levels of callous-unemotional (CU) traits designates a clinically important and etiologically distinct subgroup of children and adolescents with serious conduct problems. Based on this research, CU traits have been included in the most recent revision of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5; American Psychiatric Association, 2013)--as a specifier for the diagnosis of conduct disorder. In this review, we attempt to understand CU traits within a developmental psychopathological framework. Specifically, we summarize research on the normal development of the prosocial emotions of empathy and guilt (i.e., conscience) and we illustrate how the development of CU traits can be viewed as the normal development of conscience gone awry. Furthermore, we review research on the stability of CU traits across different developmental periods and highlight factors that can influence this stability. Finally, we highlight the implications of this developmental psychopathological framework for future etiological research, for assessment and diagnostic classification, and for treatment of children with serious conduct problems.

  19. Understanding culture and ethnicity: basic rudiments of an "anthropsychological" perspective for understanding human behavior.

    PubMed

    Chestnut, D E

    2000-01-01

    While there appears to be general consensus in the behavioral sciences as to the importance of culture and ethnicity in shaping behavior, the discipline of psychology, a major producer of psychotherapists, is often resistant to the study of the basic concepts; seeing it as the domain of other disciplines. Thus, psychologically trained practitioners may not have rudimentary understanding of these concept; while endorsing and even trying to incorporate ethnically and culturally sensitive practices and techniques. This paper provides a basic reformulation of culture and ethnicity and presents the novel concept of an "anthropsychological" model for understanding individual behavior while being sensitive to ethnicity and culture.

  20. 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…

  1. 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…

  2. [Towards understanding human ecology in nursing practice: a concept analysis].

    PubMed

    Huynh, Truc; Alderson, Marie

    2010-06-01

    Human ecology is an umbrella concept encompassing several social, physical, and cultural elements existing in the individual's external environment. The pragmatic utility method was used to analyze the "human ecology" concept in order to ascertain the conceptual fit with nursing epistemology and to promote its use by nurses in clinical practice. Relevant articles for the review were retrieved from the MEDLINE, CINAHL, PsycINFO, and CSA databases using the terms "human ecology," "environment," "nursing," and "ecology." Data analysis revealed that human ecology is perceived as a theoretical perspective designating a complex, multilayered, and multidimensional system, one that comprises individuals and their reciprocal interactions with their global environments and the subsequent impact of these interactions upon their health. Human ecology preconditions include the individuals, their environments, and their transactions. Attributes of this concept encompass the characteristics of an open system (e.g., interdependence, reciprocal).

  3. Pregnancy and childhood health and developmental outcomes with the use of posthumous human sperm.

    PubMed

    Robson, Stephen J; Campbell, Simone; McDonald, Janelle; Tremellen, Kelton; Carlin, Emily; Maybury, Genevieve

    2015-10-01

    Although there is now considerable experience in obtaining sperm from a cadaver, there is little or no published data regarding pregnancy, birth and long-term childhood health and development outcomes when posthumous sperm is used in in vitro fertilisation (IVF). We report the results from treatment of four women undergoing IVF treatment using posthumously acquired human sperm from their deceased partners. In all cases, testicular tissue was obtained in a mortuary setting, and the duration from death to posthumous sperm retrieval ranged from 12 to 48 h. The age of women treated ranged from 31 to 41 years. Fertilization rates ranged from 40 to 100%. Singleton pregnancies were obtained for each of the four women. One pregnancy was complicated by preterm birth at 31 weeks; the other three delivered at term. One baby was growth restricted but morphologically normal; the other children had term birthweights in the normal range. All four children were have shown normal health and developmental outcomes, with the follow-up ranging from 1 to 7 years.

  4. Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells.

    PubMed

    Tang, Xin; Zhou, Li; Wagner, Alecia M; Marchetto, Maria C N; Muotri, Alysson R; Gage, Fred H; Chen, Gong

    2013-09-01

    Neurons derived from human induced-pluripotent stem cells (hiPSCs) have been used to model a variety of neurological disorders. Different protocols have been used to differentiate hiPSCs into neurons, but their functional maturation process has varied greatly among different studies. Here, we demonstrate that laminin, a commonly used substrate for iPSC cultures, was inefficient to promote fully functional maturation of hiPSC-derived neurons. In contrast, astroglial substrate greatly accelerated neurodevelopmental processes of hiPSC-derived neurons. We have monitored the neural differentiation and maturation process for up to two months after plating hiPSC-derived neuroprogenitor cells (hNPCs) on laminin or astrocytes. We found that one week after plating hNPCs, there were 21-fold more newly differentiated neurons on astrocytes than on laminin. Two weeks after plating hNPCs, there were 12-fold more dendritic branches in neurons cultured on astrocytes than on laminin. Six weeks after plating hNPCs, the Na(+) and K(+) currents, as well as glutamate and GABA receptor currents, were 3-fold larger in neurons cultured on astrocytes than on laminin. And two months after plating hNPCs, the spontaneous synaptic events were 8-fold more in neurons cultured on astrocytes than on laminin. These results highlight a critical role of astrocytes in promoting neural differentiation and functional maturation of human neurons derived from hiPSCs. Moreover, our data presents a thorough developmental timeline of hiPSC-derived neurons in culture, providing important benchmarks for future studies on disease modeling and drug screening.

  5. Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells

    PubMed Central

    Tang, Xin; Zhou, Li; Wagner, Alecia M.; Marchetto, Maria C.N.; Muotri, Alysson R.; Gage, Fred H.; Chen, Gong

    2014-01-01

    Neurons derived from human induced-pluripotent stem cells (hiPSCs) have been used to model a variety of neurological disorders. Different protocols have been used to differentiate hiPSCs into neurons, but their functional maturation process has varied greatly among different studies. Here, we demonstrate that laminin, a commonly used substrate for iPSC cultures, was inefficient to promote fully functional maturation of hiPSC-derived neurons. In contrast, astroglial substrate greatly accelerated neurodevelopmental processes of hiPSC-derived neurons. We have monitored the neural differentiation and maturation process for up to two months after plating hiPSC-derived neuroprogenitor cells (hNPCs) on laminin or astrocytes. We found that one week after plating hNPCs, there were 21-fold more newly differentiated neurons on astrocytes than on laminin. Two weeks after plating hNPCs, there were 12-fold more dendritic branches in neurons cultured on astrocytes than on laminin. Six weeks after plating hNPCs, the Na+ and K+ currents, as well as glutamate and GABA receptor currents, were 3-fold larger in neurons cultured on astrocytes than on laminin. And two months after plating hNPCs, the spontaneous synaptic events were 8-fold more in neurons cultured on astrocytes than on laminin. These results highlight a critical role of astrocytes in promoting neural differentiation and functional maturation of human neurons derived from hiPSCs. Moreover, our data presents a thorough developmental timeline of hiPSC-derived neurons in culture, providing important benchmarks for future studies on disease modeling and drug screening. PMID:23759711

  6. 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.

  7. Understanding Human Culture as an Event in the Biota

    ERIC Educational Resources Information Center

    Hartley, Peter E.

    1974-01-01

    The role of human feelings as well as physiologicalfacts in ecological concerns is considered. New terms are proposed to facilitate thinking about the ecosystem - the entire system of relationships on which life is contingent. (LS)

  8. 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.

  9. Developmental regulation of planar cell polarity and hair-bundle morphogenesis in auditory hair cells: lessons from human and mouse genetics.

    PubMed

    Lu, Xiaowei; Sipe, Conor W

    2016-01-01

    Hearing loss is the most common and costly sensory defect in humans and genetic causes underlie a significant proportion of affected individuals. In mammals, sound is detected by hair cells (HCs) housed in the cochlea of the inner ear, whose function depends on a highly specialized mechanotransduction organelle, the hair bundle. Understanding the factors that regulate the development and functional maturation of the hair bundle is crucial for understanding the pathophysiology of human deafness. Genetic analysis of deafness genes in animal models, together with complementary forward genetic screens and conditional knock-out mutations in essential genes, have provided great insights into the molecular machinery underpinning hair-bundle development and function. In this review, we highlight recent advances in our understanding of hair-bundle morphogenesis, with an emphasis on the molecular pathways governing hair-bundle polarity and orientation. We next discuss the proteins and structural elements important for hair-cell mechanotransduction as well as hair-bundle cohesion and maintenance. In addition, developmental signals thought to regulate tonotopic features of HCs are introduced. Finally, novel approaches that complement classic genetics for studying the molecular etiology of human deafness are presented. WIREs Dev Biol 2016, 5:85-101. doi: 10.1002/wdev.202 For further resources related to this article, please visit the WIREs website.

  10. 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.

  11. Eomesodermin and T-bet mark developmentally distinct human natural killer cells

    PubMed Central

    Liu, Kang; Reiner, Steven L.

    2017-01-01

    Immaturity of the immune system of human fetuses and neonates is often invoked to explain their increased susceptibility to infection; however, the development of the fetal innate immune system in early life remains incompletely explored. We now show that the most mature NK cells found in adult (or postnatal) human circulation (CD94–CD16+) are absent during ontogeny. Human fetal NK cells were found to express the 2 signature T-box transcription factors essential for the development of all murine NK and NK-like cells, eomesodermin (Eomes) and T-bet. The single-cell pattern of Eomes and T-bet expression during ontogeny, however, revealed a stereotyped pattern of reciprocal dominance, with immature NK cells expressing higher amounts of Eomes and more mature NK cells marked by greater abundance of T-bet. We also observed a stereotyped pattern of tissue-specific NK cell maturation during human ontogeny, with fetal liver being more restrictive to NK cell maturity than fetal bone barrow, spleen, or lung. These results support the hypothesis that maturation of human NK cells has a discrete restriction until postnatal life, and provide a framework to better understand the increased susceptibility of fetuses and newborns to infection. PMID:28289707

  12. From Human Activity to Conceptual Understanding of the Chain Rule

    ERIC Educational Resources Information Center

    Jojo, Zingiswa Mybert Monica; Maharaj, Aneshkumar; Brijlall, Deonarain

    2013-01-01

    This article reports on a study which investigated first year university engineering students' construction of the definition of the concept of the chain rule in differential calculus at a University of Technology in South Africa. An APOS (Action-Process-Objects-Schema) approach was used to explore conceptual understanding displayed by students in…

  13. Borna Disease Virus Phosphoprotein Impairs the Developmental Program Controlling Neurogenesis and Reduces Human GABAergic Neurogenesis

    PubMed Central

    Scordel, Chloé; Szelechowski, Marion; Poulet, Aurélie; Richardson, Jennifer; Benchoua, Alexandra; Gonzalez-Dunia, Daniel; Eloit, Marc; Coulpier, Muriel

    2015-01-01

    It is well established that persistent viral infection may impair cellular function of specialized cells without overt damage. This concept, when applied to neurotropic viruses, may help to understand certain neurologic and neuropsychiatric diseases. Borna disease virus (BDV) is an excellent example of a persistent virus that targets the brain, impairs neural functions without cell lysis, and ultimately results in neurobehavioral disturbances. Recently, we have shown that BDV infects human neural progenitor cells (hNPCs) and impairs neurogenesis, revealing a new mechanism by which BDV may interfere with brain function. Here, we sought to identify the viral proteins and molecular pathways that are involved. Using lentiviral vectors for expression of the bdv-p and bdv-x viral genes, we demonstrate that the phosphoprotein P, but not the X protein, diminishes human neurogenesis and, more particularly, GABAergic neurogenesis. We further reveal a decrease in pro-neuronal factors known to be involved in neuronal differentiation (ApoE, Noggin, TH and Scg10/Stathmin2), demonstrating that cellular dysfunction is associated with impairment of specific components of the molecular program that controls neurogenesis. Our findings thus provide the first evidence that a viral protein impairs GABAergic human neurogenesis, a process that is dysregulated in several neuropsychiatric disorders. They improve our understanding of the mechanisms by which a persistent virus may interfere with brain development and function in the adult. PMID:25923687

  14. Understanding the Association of Human Rhinovirus with Asthma.

    PubMed

    Stone, Cosby A; Miller, E Kathryn

    2015-09-16

    Human rhinoviruses are ubiquitous seasonal pathogens. They have known associations with first onset of wheezing illnesses in children and with asthma exacerbations in patients of all ages. It is not yet certain whether human rhinoviruses play a direct role in the pathogenesis of asthma by activating deleterious inflammatory responses or if they only serve as a catalyst to accelerate the disease in genetically predisposed individuals. There have been previously demonstrated reductions in the development of the asthmatic phenotype with passive immunization against respiratory syncytial virus; however, in the case of rhinovirus, there are barriers to effective vaccine development, such as the lack of a common antigenic target due to alterations of surface markers among subtypes. It remains to be determined whether certain subtypes of human rhinovirus are more asthmagenic and therefore worthy of greater attention as vaccine candidates, but several studies have suggested that RV-C and certain RV-A strains may be more strongly linked with asthma.

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

    DOE PAGES

    Petljak, Mia; Alexandrov, Ludmil B.

    2016-05-04

    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

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

    SciTech Connect

    Petljak, Mia; Alexandrov, Ludmil B.

    2016-05-04

    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 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.

  17. 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.

  18. 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.

  19. 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…

  20. 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.

  1. 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…

  2. Understanding Human Impact: Second Graders Explore Watershed Dynamics

    ERIC Educational Resources Information Center

    Magruder, Robin; Rosenauer, Julia

    2016-01-01

    This article describes a second grade science enrichment unit with a focus on human impact, both positive and negative, on the living and nonliving components of the local watershed. Investigating the local watershed gave the unit a personal and pragmatic connection to students' lives because they depend on the local watershed for what they need…

  3. 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 ...

  4. 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)

  5. Understanding Human Coronavirus HCoV-NL63.

    PubMed

    Abdul-Rasool, Sahar; Fielding, Burtram C

    2010-05-25

    Even though coronavirus infection of humans is not normally associated with severe diseases, the identification of the coronavirus responsible for the outbreak of severe acute respiratory syndrome showed that highly pathogenic coronaviruses can enter the human population. Shortly thereafter, in Holland in 2004, another novel human coronavirus (HCoV-NL63) was isolated from a seven-month old infant suffering from respiratory symptoms. This virus has subsequently been identified in various countries, indicating a worldwide distribution. HCoV-NL63 has been shown to infect mainly children and the immunocommpromised, who presented with either mild upper respiratory symptoms (cough, fever and rhinorrhoea) or more serious lower respiratory tract involvement such as bronchiolitis and croup, which was observed mainly in younger children. In fact, HCoV-NL63 is the aetiological agent for up to 10% of all respiratory diseases. This review summarizes recent findings of human coronavirus HCoV-NL63 infections, including isolation and identification, phylogeny and taxonomy, genome structure and transcriptional regulation, transmission and pathogenesis, and detection and diagnosis.

  6. The Human Functional Genomics Project: Understanding Generation of Diversity.

    PubMed

    Pappalardo, Jenna L; Hafler, David A

    2016-11-03

    Generation of biologic diversity is a cornerstone of immunity, yet the tools to investigate the causal influence of genetic and environmental factors have been greatly limited. Studies from the Human Functional Genomics Project, presented in Cell and other Cell Press journals, integrate environmental and genetic factors with the direction and magnitude of immune responses to decipher inflammatory disease pathogenesis.

  7. Understanding and Targeting the ALT Pathway in Human Breast Cancer

    DTIC Science & Technology

    2014-09-01

    by ectopic expression of ESCO2. PLoS One 4, e6936 (2009). 35. Leung, J. W. et al. Alpha thalassemia/ mental retardation syndrome X-linked gene...identified mutations and loss of ATRX protein as being hallmarks of ALT- immortalized cell lines and tumors. Our efforts to understand the mechanism...by which loss of ATRX facilitates telomere recombination have uncovered a novel role for this protein in promoting telomere cohesion. Furthermore

  8. 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.

  9. 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

  10. Fly Models of Human Diseases: Drosophila as a Model for Understanding Human Mitochondrial Mutations and Disease.

    PubMed

    Sen, A; Cox, R T

    2017-01-01

    Mitochondrial diseases are a prevalent, heterogeneous class of diseases caused by defects in oxidative phosphorylation, whose severity depends upon particular genetic mutations. These diseases can be difficult to diagnose, and current therapeutics have limited efficacy, primarily treating only symptoms. Because mitochondria play a pivotal role in numerous cellular functions, especially ATP production, their diminished activity has dramatic physiological consequences. While this in and of itself makes treating mitochondrial disease complex, these organelles contain their own DNA, mtDNA, whose products are required for ATP production, in addition to the hundreds of nucleus-encoded proteins. Drosophila offers a tractable whole-animal model to understand the mechanisms underlying loss of mitochondrial function, the subsequent cellular and tissue damage that results, and how these organelles are inherited. Human and Drosophila mtDNAs encode the same set of products, and the homologous nucleus-encoded genes required for mitochondrial function are conserved. In addition, Drosophila contain sufficiently complex organ systems to effectively recapitulate many basic symptoms of mitochondrial diseases, yet are relatively easy and fast to genetically manipulate. There are several Drosophila models for specific mitochondrial diseases, which have been recently reviewed (Foriel, Willems, Smeitink, Schenck, & Beyrath, 2015). In this review, we highlight the conservation between human and Drosophila mtDNA, the present and future techniques for creating mtDNA mutations for further study, and how Drosophila has contributed to our current understanding of mitochondrial inheritance.

  11. 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

  12. A hierarchical framework for understanding human-human interactions in video surveillance

    NASA Astrophysics Data System (ADS)

    Park, Sangho; Aggarwal, J. K.

    2005-01-01

    Understanding human behavior in video is essential in numerous applications including smart surveillance, video annotation/retrieval, and human-computer interaction. However, recognizing human interactions is a challenging task due to ambiguity in body articulation, variations in body size and appearance, loose clothing, mutual occlusion, and shadows. In this paper we present a framework for recognizing human actions and interactions in color video, and a hierarchical graphical model that unifies multiple-level processing in video computing: pixel level, blob level, object level, and event level. A mixture of Gaussian (MOG) model is used at the pixel level to train and classify individual pixel colors. A relaxation labeling with attribute relational graph (ARG) is used at the blob level to merge the pixels into coherent blobs and to register inter-blob relations. At the object level, the poses of individual body parts are recognized using Bayesian networks (BNs). At the event level, the actions of a single person are modeled using a dynamic Bayesian network (DBN). The results of the object-level descriptions for each person are juxtaposed along a common timeline to identify an interaction between two persons. The linguistic 'verb argument structure' is used to represent human action in terms of triplets. A meaningful semantic description in terms of is obtained. Our system achieves semantic descriptions of positive, neutral, and negative interactions between two persons including hand-shaking, standing hand-in-hand, and hugging as the positive interactions, approaching, departing, and pointing as the neutral interactions, and pushing, punching, and kicking as the negative interactions.

  13. A hierarchical framework for understanding human-human interactions in video surveillance

    NASA Astrophysics Data System (ADS)

    Park, Sangho; Aggarwal, J. K.

    2004-12-01

    Understanding human behavior in video is essential in numerous applications including smart surveillance, video annotation/retrieval, and human-computer interaction. However, recognizing human interactions is a challenging task due to ambiguity in body articulation, variations in body size and appearance, loose clothing, mutual occlusion, and shadows. In this paper we present a framework for recognizing human actions and interactions in color video, and a hierarchical graphical model that unifies multiple-level processing in video computing: pixel level, blob level, object level, and event level. A mixture of Gaussian (MOG) model is used at the pixel level to train and classify individual pixel colors. A relaxation labeling with attribute relational graph (ARG) is used at the blob level to merge the pixels into coherent blobs and to register inter-blob relations. At the object level, the poses of individual body parts are recognized using Bayesian networks (BNs). At the event level, the actions of a single person are modeled using a dynamic Bayesian network (DBN). The results of the object-level descriptions for each person are juxtaposed along a common timeline to identify an interaction between two persons. The linguistic 'verb argument structure' is used to represent human action in terms of triplets. A meaningful semantic description in terms of is obtained. Our system achieves semantic descriptions of positive, neutral, and negative interactions between two persons including hand-shaking, standing hand-in-hand, and hugging as the positive interactions, approaching, departing, and pointing as the neutral interactions, and pushing, punching, and kicking as the negative interactions.

  14. 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.

  15. 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.

  16. Use of a Mouse In Vitro Fertilization Model to Understand the Developmental Origins of Health and Disease Hypothesis

    PubMed Central

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

    2014-01-01

    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

  17. Intra-individual stability and developmental change in hair cortisol among postpartum mothers and infants: Implications for understanding chronic stress.

    PubMed

    Liu, Cindy H; Snidman, Nancy; Leonard, Alexandra; Meyer, Jerrold; Tronick, Ed

    2016-05-01

    The study goal was to determine the intra-individual stability, developmental change, and maternal-reported correlates (socio-demographic, stress experiences, hair characteristics, and care) of hair cortisol in mothers and their infants. To assess cortisol deposition in hair during the periods of 6-to-9 months and 9-to-12 months of age, 3 cm segments of hair samples deemed to represent approximately 3 months of retrospective hair cortisol were sampled longitudinally at 9- and 12-months in 41 mothers and infants. Bivariate correlations and mean level comparisons of log-transformed hair cortisol levels at 9- (T1) and 12-months (T2) in mothers and infants were examined. Hair cortisol values were positively correlated from T1 to T2 for mothers (r = .41, p < .05) and infants (r = .39, p < .05). Hair cortisol values did not significantly differ from T1 to T2 in infants but decreased for mothers (F(1,34) = 9.2, p < .01). Maternal and infant hair cortisol was not associated with each other at either time point. Self-reported measures of stress, and hair characteristics and care were not associated with hair cortisol. This is the first study to obtain hair cortisol from more than one time point within the first year after birth in mothers and infants. The intra-individual stability of hair cortisol suggests that it may be a possible biomarker for detecting change in chronic stress experiences within the first year of life and in the postpartum period.

  18. Understanding actors and object-goals in the human brain.

    PubMed

    Ramsey, Richard; Hamilton, Antonia F de C

    2010-04-15

    When another person takes 10 pounds from your hand, it matters if they are a shopkeeper or a robber. That is, the meaning of a simple, goal-directed action can vary depending on the identity of the actors involved. Research examining action understanding has identified an action observation network (AON) that encodes action features such as goals and kinematics. However, it is not yet known how or where the brain links actor identity to action goal. In the present paper, we used a repetition suppression paradigm during functional magnetic resonance imaging (fMRI) to examine the neural representation of actor identity within the context of object-directed actions. Participants watched video clips of two different actors with two different object-goals. Repeated presentation of the same actor suppressed the blood oxygen level-dependent (BOLD) response in fusiform gyrus and occipitotemporal cortex. In contrast, repeated presentation of an action with the same object-goal suppressed the BOLD response throughout the AON. Our data reveal an extended brain network for understanding other people and their everyday actions that go beyond the traditional action observation network.

  19. 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…

  20. Towards an understanding of British public attitudes concerning human cloning.

    PubMed

    Shepherd, Richard; Barnett, Julie; Cooper, Helen; Coyle, Adrian; Moran-Ellis, Jo; Senior, Victoria; Walton, Chris

    2007-07-01

    The ability of scientists to apply cloning technology to humans has provoked public discussion and media coverage. The present paper reports on a series of studies examining public attitudes to human cloning in the UK, bringing together a range of quantitative and qualitative methods to address this question. These included a nationally representative survey, an experimental vignette study, focus groups and analyses of media coverage. Overall the research presents a complex picture of attitude to and constructions of human cloning. In all of the analyses, therapeutic cloning was viewed more favourably than reproductive cloning. However, while participants in the focus groups were generally negative about both forms of cloning, and this was also reflected in the media analyses, quantitative results showed more positive responses. In the quantitative research, therapeutic cloning was generally accepted when the benefits of such procedures were clear, and although reproductive cloning was less accepted there was still substantial support. Participants in the focus groups only differentiated between therapeutic and reproductive cloning after the issue of therapeutic cloning was explicitly raised; initially they saw cloning as being reproductive cloning and saw no real benefits. Attitudes were shown to be associated with underlying values associated with scientific progress rather than with age, gender or education, and although there were a few differences in the quantitative data based on religious affiliation, these tended to be small effects. Likewise in the focus groups there was little direct appeal to religion, but the main themes were 'interfering with nature' and the 'status of the embryo', with the latter being used more effectively to try to close down further discussion. In general there was a close correspondence between the media analysis and focus group responses, possibly demonstrating the importance of media as a resource, or that the media reflect

  1. Understanding Human Glycosylation Disorders: Biochemistry Leads the Charge*

    PubMed Central

    Freeze, Hudson H.

    2013-01-01

    Nearly 70 inherited human glycosylation disorders span a breathtaking clinical spectrum, impacting nearly every organ system and launching a family-driven diagnostic odyssey. Advances in genetics, especially next generation sequencing, propelled discovery of many glycosylation disorders in single and multiple pathways. Interpretation of whole exome sequencing results, insights into pathological mechanisms, and possible therapies will hinge on biochemical analysis of patient-derived materials and animal models. Biochemical diagnostic markers and readouts offer a physiological context to confirm candidate genes. Recent discoveries suggest novel perspectives for textbook biochemistry and novel research opportunities. Basic science and patients are the immediate beneficiaries of this bidirectional collaboration. PMID:23329837

  2. Understanding human resource management practices in Botswana's public health sector.

    PubMed

    Seitio-Kgokgwe, Onalenna Stannie; Gauld, Robin; Hill, Philip C; Barnett, Pauline

    2016-11-21

    Purpose The purpose of this paper is to assess the management of the public sector health workforce in Botswana. Using institutional frameworks it aims to document and analyse human resource management (HRM) practices, and make recommendations to improve employee and health system outcomes. Design/methodology/approach The paper draws from a large study that used a mixed methods approach to assess performance of Botswana's Ministry of Health (MOH). It uses data collected through document analysis and in-depth interviews of 54 key informants comprising policy makers, senior staff of the MOH and its stakeholder organizations. Findings Public health sector HRM in Botswana has experienced inadequate planning, poor deployment and underutilization of staff. Lack of comprehensive retention strategies and poor working conditions contributed to the failure to attract and retain skilled personnel. Relationships with both formal and informal environments affected HRM performance. Research limitations/implications While document review was a major source of data for this paper, the weaknesses in the human resource information system limited availability of data. Practical implications This paper presents an argument for the need for consideration of formal and informal environments in developing effective HRM strategies. Originality/value This research provides a rare system-wide approach to health HRM in a Sub-Saharan African country. It contributes to the literature and evidence needed to guide HRM policy decisions and practices.

  3. Improving animal and human health through understanding liver fluke immunology.

    PubMed

    Piedrafita, D; Spithill, T W; Smith, R E; Raadsma, H W

    2010-08-01

    Sheep, goats and cattle represent the most numerous and economically important agricultural species worldwide used as sources for milk, fibre and red meat. In addition, in the developing world, these species often represent the sole asset base for small-holder livestock farmers and cattle/buffaloes often provide the majority of draught power for crop production. Production losses caused by helminth diseases of these animals are a major factor in extending the cycle of poverty in developing countries and a major food security issue for developed economies. Fasciola spp. are one of the most important zoonotic diseases with a global economic impact in livestock production systems and a poorly defined but direct effect on human health. Improvements in human and animal health will require a concerted research effort into the development of new accurate and simple diagnostic tests and increased vaccine and drug development against Fasciola infections. Here, the use of definitive natural host breeds with contrasting resistance to Fasciola infections is discussed as a resource to contrast parasite-host interactions and identify parasite immune evasion strategies. Such studies are likely to boost the discovery of new vaccine, drug and diagnostic candidates and provide the foundation for future genetic selection of resistant animals.

  4. Can human movement analysis contribute to usability understanding?

    PubMed

    Belda-Lois, Juan-Manuel; de-Rosario, Helios; Pons, Romà; Poveda, Rakel; Morón, Ana; Porcar, Rosa; García, Ana-Cruz; Gómez, Amelia

    2010-08-01

    Nowadays human-machine interfaces are evaluated using different methodologies. These methodologies rarely consider the human movements involved in the interaction, and if so, the movements are considered in a simplistic manner. Another often neglected aspect is the relationship between the learning process and the use of the interface. Traditional approaches of cognitive modeling consider learning as just one continuous process. However there is some current evidence of concurrent processes on different time scales. This paper aims to answer, with experimental measurements, if learning actually implies a set of concurrent processes, if those processes are related to the coordinative aspects of hand movement, and how this can vary between young adult and elderly users. Two different interfaces, a washing machine and a domotic system, were analyzed with 23 and 20 people, respectively, classified as men or women and elderly (over 55) or adult (between 40 and 50). The results of the study provide support for the existence of different concurrent processes in learning, previously demonstrated for motor tasks. Moreover, the learning process is actually associated with changes in movement patterns. Finally, the results show that the progression of the learning process depends on age, although elderly people are equally capable of learning to use technological systems as young adults.

  5. 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

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

    PubMed

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

    2013-07-05

    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.

  7. Neuronal developmental gene and miRNA signatures induced by histone deacetylase inhibitors in human embryonic stem cells

    PubMed Central

    Meganathan, K; Jagtap, S; Srinivasan, S P; Wagh, V; Hescheler, J; Hengstler, J; Leist, M; Sachinidis, A

    2015-01-01

    Human embryonic stem cells (hESCs) may be applied to develop human-relevant sensitive in vitro test systems for monitoring developmental toxicants. The aim of this study was to identify potential developmental toxicity mechanisms of the histone deacetylase inhibitors (HDAC) valproic acid (VPA), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) relevant to the in vivo condition using a hESC model in combination with specific differentiation protocols and genome-wide gene expression and microRNA profiling. Analysis of the gene expression data showed that VPA repressed neural tube and dorsal forebrain (OTX2, ISL1, EMX2 and SOX10)-related transcripts. In addition, VPA upregulates axonogenesis and ventral forebrain-associated genes, such as SLIT1, SEMA3A, DLX2/4 and GAD2. HDACi-induced expression of miR-378 and knockdown of miR-378 increases the expression of OTX2 and EMX2, which supports our hypothesis that HDACi targets forebrain markers through miR-378. In conclusion, multilineage differentiation in vitro test system is very sensitive for monitoring molecular activities relevant to in vivo neuronal developmental toxicity. Moreover, miR-378 seems to repress the expression of the OTX2 and EMX2 and therefore could be a regulator of the development of neural tube and dorsal forebrain neurons. PMID:25950486

  8. Generation of Functional Human Retinal Ganglion Cells with Target Specificity from Pluripotent Stem Cells by Chemically Defined Recapitulation of Developmental Mechanism.

    PubMed

    Teotia, Pooja; Chopra, Divyan A; Dravid, Shashank Manohar; Van Hook, Matthew J; Qiu, Fang; Morrison, John; Rizzino, Angie; Ahmad, Iqbal

    2017-03-01

    Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) lead to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, that is, the embryonic stem cells and induced pluripotent stem cells. Here, we demonstrate a rapid and safe, stage-specific, chemically defined protocol that selectively generates RGCs across species, including human, by recapitulating the developmental mechanism. The de novo generated RGCs from pluripotent cells are similar to native RGCs at the molecular, biochemical, functional levels. They also express axon guidance molecules, and discriminate between specific and nonspecific targets, and are nontumorigenic. Stem Cells 2017;35:572-585.

  9. Immunoinformatics and its relevance to understanding human immune disease.

    PubMed

    Brusic, Vladimir; Petrovsky, Nikolai

    2005-05-01

    Immunology research is characterized by the production of increasingly vast amounts of data, fuelled by genomics and proteomics projects and large-scale screening of pathogen- and antigen-host interactions. The need to store, manage and analyze this rapidly growing resource of experimental, clinical and epidemiologic data has given rise to the field known as immunoinformatics. Immunoinformatics represents computational methods and resources that are used in the study of immune function. It lies at the intersection of experimental and computational sciences and encompasses domain-specific databases, computational models and strategies drawn from artificial intelligence. For example, computational or artificial intelligence models are increasingly being used to simulate and improve our understanding of immune system behavior, such as antigen processing and presentation, as well as for analysis of host and pathogen genomes. Systemic models focus on simulating the behavior of cells or whole organs and can be used for applications such as tracking the course of infection or optimization of immunization protocols. Immunomics, the large-scale screening of immune processes, which includes powerful immunoinformatic tools, offers great promise for future translation of basic immunology research advances into clinical practice. Immunoinformatics is central to the research fields of immunogenomics, immunoproteomics and computational vaccinology.

  10. An effective clean-up technique for GC/EI-HRMS determination of developmental neurotoxicants in human breast milk.

    PubMed

    Čechová, Eliška; Seifertová, Marta; Kukučka, Petr; Vojta, Šimon; Quaak, Ilona; de Cock, Marijke; van de Bor, Margot; Kočan, Anton

    2017-02-01

    The increasing number of children suffering from developmental disorders has raised questions regarding their association with the presence of environmental contaminants in mothers and children. We therefore developed a new method for the determination of 78 proven and potential developmental neurotoxicants, including polychlorinated biphenyls, legacy pesticides, pyrethroids, and old and new halogenated flame retardants in breast milk. The essential part of sample preparation was dialysis as a non-destructive clean-up step which was newly used at 10 °C and showed more efficient lipid removal (up to 96%) than the conventional methods such as gel permeation chromatography or freezing-lipid filtration and thus ensured low limits of detection (LOD) by reducing the sample volume prior to injection. Next advantages were significant solvent reduction and no risk of sample cross-contamination. Gas chromatography coupled with high resolution mass spectrometry (GC-HRMS) was subsequently used for the separation and compound quantification. The method was validated using breast milk samples fortified with the analyzed compounds. Recoveries for most of the compounds ranged from 63 to 121% with a relative standard deviation of 2-25%, and LODs ranged between 0.001 and 0.87 ng g(-1) lipid weight. The method was applied to breast milk samples from a Dutch birth cohort where 35 out of the 78 compounds were quantified in more than 60% of the samples. For novel flame retardants, the method provides unique results regarding their occurrence in human matrices in Europe. Overall, the analysis of a complex mixture of developmental neurotoxicants could be useful for the assessment of the influence of the studied compounds to child health and development. Graphical abstract Flow diagram of the method and levels of the developmental neurotoxicants in Dutch human milk samples.

  11. Human Computer Collaboration at the Edge: Enhancing Collective Situation Understanding with Controlled Natural Language

    DTIC Science & Technology

    2016-09-06

    Integrating hard and soft information sources for D2D using controlled natural language ,” in Proc 15th International Conference on Information Fusion, 2012...Human Computer Collaboration at the Edge: Enhancing Collective Situation Understanding with Controlled Natural Language Alun Preece∗, William...of humans and machines, we propose a conversational interface using Controlled Natural Language (CNL), which is both human readable and machine

  12. Can Animal Models Contribute to Understanding Tinnitus Heterogeneity in Humans?

    PubMed Central

    Eggermont, Jos J.

    2016-01-01

    The brain activity of humans with tinnitus of various etiologies is typically studied with electro- and magneto-encephalography and functional magnetic resonance imaging-based imaging techniques. Consequently, they measure population responses and mostly from the neocortex. The latter also underlies changes in neural networks that may be attributed to tinnitus. However, factors not strictly related to tinnitus such as hearing loss and hyperacusis, as well as other co-occurring disorders play a prominent role in these changes. Different types of tinnitus can often not be resolved with these brain-imaging techniques. In animal models of putative behavioral signs of tinnitus, neural activity ranging from auditory nerve to auditory cortex, is studied largely by single unit recordings, augmented by local field potentials (LFPs), and the neural correlates of tinnitus are mainly based on spontaneous neural activity, such as spontaneous firing rates and pair-wise spontaneous spike-firing correlations. Neural correlates of hyperacusis rely on measurement of stimulus-evoked activity and are measured as increased driven firing rates and LFP amplitudes. Connectivity studies would rely on correlated neural activity between pairs of neurons or LFP amplitudes, but are only recently explored. In animal models of tinnitus, only two etiologies are extensively studied; tinnitus evoked by salicylate application and by noise exposure. It appears that they have quite different neural biomarkers. The unanswered question then is: does this different etiology also result in different tinnitus? PMID:27895575

  13. 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,…

  14. 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

  15. 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...

  16. 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…

  17. 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

  18. A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles.

    PubMed

    Hoelting, Lisa; Scheinhardt, Benjamin; Bondarenko, Olesja; Schildknecht, Stefan; Kapitza, Marion; Tanavde, Vivek; Tan, Betty; Lee, Qian Yi; Mecking, Stefan; Leist, Marcel; Kadereit, Suzanne

    2013-04-01

    Nanoparticles (NPs) have been shown to accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Here, we developed a human embryonic stem cell (hESC)-derived 3-dimensional (3-D) in vitro model that allows for testing of potential developmental neurotoxicants. Early central nervous system PAX6(+) precursor cells were generated from hESCs and differentiated further within 3-D structures. The 3-D model was characterized for neural marker expression revealing robust differentiation toward neuronal precursor cells, and gene expression profiling suggested a predominantly forebrain-like development. Altered neural gene expression due to exposure to non-cytotoxic concentrations of the known developmental neurotoxicant, methylmercury, indicated that the 3-D model could detect DNT. To test for specific toxicity of NPs, chemically inert polyethylene NPs (PE-NPs) were chosen. They penetrated deep into the 3-D structures and impacted gene expression at non-cytotoxic concentrations. NOTCH pathway genes such as HES5 and NOTCH1 were reduced in expression, as well as downstream neuronal precursor genes such as NEUROD1 and ASCL1. FOXG1, a patterning marker, was also reduced. As loss of function of these genes results in severe nervous system impairments in mice, our data suggest that the 3-D hESC-derived model could be used to test for Nano-DNT.

  19. Can we understand how developmental stress enhances performance under future threat with the Yerkes-Dodson law?

    PubMed Central

    Chaby, Lauren E; Sheriff, Michael J; Hirrlinger, Amy M; Braithwaite, Victoria A

    2015-01-01

    Recently we have shown that adult rats exposed to chronic stress during adolescence increase foraging performance in high-threat conditions by 43% compared to rats reared without stress. Our findings suggest that stress during adolescence can prepare rats to better function under future threat, which supports hypotheses describing an adaptive role for the long-term consequences of early stress (e.g. the thrifty phenotype and maternal mismatch hypotheses). These hypotheses often predict that early stress will impair performance in low-threat conditions later in life. However, we did not find any difference in performance under low-threat conditions between adolescent-stressed and unstressed adult animals. To understand why stress during adolescence may affect performance in high-threat but not in low-threat conditions, we discuss our findings in the framework of the Yerkes-Dodson law, a key precept of psychology that has been used for over a century to describe how stress affects performance. PMID:26479861

  20. 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…

  1. Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons.

    PubMed

    Delli Carri, Alessia; Onorati, Marco; Lelos, Mariah J; Castiglioni, Valentina; Faedo, Andrea; Menon, Ramesh; Camnasio, Stefano; Vuono, Romina; Spaiardi, Paolo; Talpo, Francesca; Toselli, Mauro; Martino, Gianvito; Barker, Roger A; Dunnett, Stephen B; Biella, Gerardo; Cattaneo, Elena

    2013-01-15

    Medium-sized spiny neurons (MSNs) are the only neostriatum projection neurons, and their degeneration underlies some of the clinical features of Huntington's disease. Using knowledge of human developmental biology and exposure to key neurodevelopmental molecules, human pluripotent stem (hPS) cells were induced to differentiate into MSNs. In a feeder-free adherent culture, ventral telencephalic specification is induced by BMP/TGFβ inhibition and subsequent SHH/DKK1 treatment. The emerging FOXG1(+)/GSX2(+) telencephalic progenitors are then terminally differentiated, resulting in the systematic line-independent generation of FOXP1(+)/FOXP2(+)/CTIP2(+)/calbindin(+)/DARPP-32(+) MSNs. Similar to mature MSNs, these neurons carry dopamine and A2a receptors, elicit a typical firing pattern and show inhibitory postsynaptic currents, as well as dopamine neuromodulation and synaptic integration ability in vivo. When transplanted into the striatum of quinolinic acid-lesioned rats, hPS-derived neurons survive and differentiate into DARPP-32(+) neurons, leading to a restoration of apomorphine-induced rotation behavior. In summary, hPS cells can be efficiently driven to acquire a functional striatal fate using an ontogeny-recapitulating stepwise method that represents a platform for in vitro human developmental neurobiology studies and drug screening approaches.

  2. Developmental changes in the protein profiles of human cardiac and skeletal muscle.

    PubMed

    Tipler, T D; Edwards, Y H; Hopkinson, D A

    1978-05-01

    1. The use of SDS electrophoresis as a tool for the analysis of development processes in man has been evaluated. 2. The protein profiles of cardiac and skeletal muscle from foetal (10--24 weeks gestation) infant and adult specimens have been analysed and striking developmental changes were found which involved all the major proteins. 3. Before 20 weeks gestation the soluble protein profile of skeletal muscle appears to consist largely of extracellular proteins. 4. Myoglobin was found in foetal cardiac muscle from 20 weeks gestation but was not demonstrable in foetal (greater than 24 weeks) skeletal muscle. Foetal and adult myoglobin were indistinguishable. 5. A limited survey of the protein patterns of brain, liver and kidney was carried out. In general these tissues show less developmental change than skeletal or cardiac muscle.

  3. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-Isodecyl Phthalate (DIDP).

    PubMed

    2003-04-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-isodecyl phthalate (DIDP) to cause adverse effects on reproduction and development in humans. DIDP 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. DIDP is a mixture of branched, C-10 phthalate isomers used to add flexibility to a wide variety of polyvinylchloride (PVC) plastic products such as artificial leather, toys, carpet backing, and pool liners. The results of this evaluation on DIDP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-Isodecyl Phthalate, 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 DIDP on human development and reproduction. First, although DIDP could possibly affect human development if exposures are sufficiently high, there is minimal concern for developmental effects in fetuses and children at current proposed/estimated exposure levels. There is no direct evidence that exposure of people to DIDP adversely affects reproduction or development, but show that oral exposure of pregnant rats to high doses (200 and 1000 mg/kg bodyweight/day) of DIDP can adversely affect fetal development. Human exposure information for DIDP was not available, but it was assumed that the general US population would be exposed to 3-30 mug/kg body weight/day, based upon the range of estimated exposures for DEHP, a more widely used phthalate. Second, there is negligible concern for reproductive toxicity in exposed adults. Studies evaluated showed that, at

  4. 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…

  5. 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…

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

    PubMed

    Kong, Xiangyi; Yang, Shuting; 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.

  7. Perchlorate and radioiodide kinetics across life stages in the human: using PBPK models to predict dosimetry and thyroid inhibition and sensitive subpopulations based on developmental stage.

    PubMed

    Clewell, Rebecca A; Merrill, Elaine A; Gearhart, Jeffery M; Robinson, Peter J; Sterner, Teresa R; Mattie, David R; Clewell, Harvey J

    2007-03-01

    Perchlorate (ClO4(-)) is a drinking-water contaminant, known to disrupt thyroid hormone homeostasis in rats. This effect has only been seen in humans at high doses, yet the potential for long term effects from developmental endocrine disruption emphasizes the need for improved understanding of perchlorate's effect during the perinatal period. Physiologically based pharmacokinetic/dynamic (PBPK/PD) models for ClO4(-) and its effect on thyroid iodide uptake were constructed for human gestation and lactation data. Chemical specific parameters were estimated from life-stage and species-specific relationships established in previously published models for various life-stages in the rat and nonpregnant adult human. With the appropriate physiological descriptions, these kinetic models successfully simulate radioiodide data culled from the literature for gestation and lactation, as well as ClO4(-) data from populations exposed to contaminated drinking water. These models provide a framework for extrapolating from chemical exposure in laboratory animals to human response, and support a more quantitative understanding of life-stage-specific susceptibility to ClO4(-). The pregnant and lactating woman, fetus, and nursing infant were predicted to have higher blood ClO4(-) concentrations and greater thyroid iodide uptake inhibition at a given drinking-water concentration than either the nonpregnant adult or the older child. The fetus is predicted to receive the greatest dose (per kilogram body weight) due to several factors, including placental sodium-iodide symporter (NIS) activity and reduced maternal urinary clearance of ClO4(-). The predicted extent of iodide inhibition in the most sensitive population (fetus) is not significant (approximately 1%) at the U.S. Environmental Protection Agency reference dose (0.0007 mg/kg-d).

  8. 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.

  9. 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

  10. The dynamic lift of developmental process.

    PubMed

    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 human-like intelligence: the heterogeneity of the component processes, the embedding of development in a social world, and developmental processes that change the cognitive system as a function of the history of soft-assemblies of these heterogeneous processes in specific tasks. The paper uses examples from human development and from developmental robotics to show how these processes also may underlie biological intelligence and enable us to generate more advanced forms of artificial intelligence.

  11. 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

  12. 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...

  13. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-isononyl Phthalate (DINP).

    PubMed

    2003-03-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-isononyl phthalate (DINP) to cause adverse effects on reproduction and development in humans. DINP 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. DINP is a mixture of branched, C-9 phthalate isomers used to add flexibility to a wide variety of plastic products such as toys, garden hoses, flooring tiles, tarps, and pool liners. The results of this evaluation on DINP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-isononyl Phthalate, 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 DINP on human development and reproduction. First, although DINP could possibly affect human development if exposures are sufficiently high, there is minimal concern for DINP causing adverse effects to human reproduction or fetal development. There is no direct evidence that exposure of people to DINP adversely affects reproduction or development, but studies show that oral exposure of pregnant rats to high doses (500 and 1000 mg/kg bodyweight/day) of DINP can adversely affect fetal development. Effects on pup growth were noted in a 2-generation reproductive toxicity study in rats at doses of 143-285 mg/kg body weight/day. Human exposure information for DINP was not available but it was assumed that the general US population would be exposed to 3-30 mug/kg body weight/day, based upon the range of estimated exposures for DEHP, a more widely used phthalate. Second, based on

  14. 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.

  15. 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.

  16. 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…

  17. Understanding the linkages and feedbacks in human-water systems: development of an integrated systems framework

    NASA Astrophysics Data System (ADS)

    Hermans, C. M.; Vorosmarty, C. J.; Arrigo, J. S.; Parolari, A.; Thomas, B.

    2010-12-01

    Over the last four centuries human activity in the northeastern United States, has significantly altered the hydrologic cycle through direct and indirect means. Successfully observing, understanding, modeling and predicting the dynamics of present day hydrologic systems requires integrating the cumulative consequences of, not only our current actions, but our historic ones. Over time, we have uncovered evidence of significant alteration to the biogeochemistry, geomorphology, and surface and groundwater hydrology of the Northeast region’s water cycle - with significant implications to human, ecological and hydrological systems. While hydrologists traditionally have placed humans external to our hydrology models, we are moving toward a better understanding of these interactions and feedbacks between natural and human systems. This necessitates understanding the particulars of the hydrologic cycle on one hand, the particulars of the human system on the other, as well as understanding the intermediary impacts on land-use and land cover. Here we present a preliminary framework and results of a series of systems models that attempt to capture, in a simple way, the relationships between the human, natural, and hydrologic systems in the northeastern United States. The model incorporates various historic hydrologic, biogeochemical, land use, economic and social science data, and is used to explore various scenarios and hypotheses. The quantification of historical and current dynamics between human adaptations and manipulations, hydrologic change and the associated feedbacks allows us to explore how human society and water evolved together over in the northeastern United States, namely - What are the key human change agents driving water system dynamics in the northeast US and how are natural systems, engineered systems and human objectives linked?

  18. The Concept of Human Nature in Three Cultures: A Developmental Approach.

    ERIC Educational Resources Information Center

    Oerter, Rolf

    This study compares the concept of human nature in Germany, Java, and the United States. The study assumes cross-cultural similarities in the formal structure of the concept of human nature, while hypothesizing variation in content, for example, in the value systems. Four components of the concept of human nature were presented (personality…

  19. Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.

    PubMed

    Godfrey, Keith M; Haugen, Guttorm; Kiserud, Torvid; Inskip, Hazel M; Cooper, Cyrus; Harvey, Nicholas C W; Crozier, Sarah R; Robinson, Sian M; Davies, Lucy; Hanson, Mark A

    2012-01-01

    Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001) and at age 4 years (r = 0.16, P = 0.02). In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02). This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04). We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

  20. Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay

    PubMed Central

    He, Miao; Kratz, Lisa E.; Michel, Joshua J.; Vallejo, Abbe N.; Ferris, Laura; Kelley, Richard I.; Hoover, Jacqueline J.; Jukic, Drazen; Gibson, K. Michael; Wolfe, Lynne A.; Ramachandran, Dhanya; Zwick, Michael E.; Vockley, Jerry

    2011-01-01

    Defects in cholesterol synthesis result in a wide variety of symptoms, from neonatal lethality to the relatively mild dysmorphic features and developmental delay found in individuals with Smith-Lemli-Opitz syndrome. We report here the identification of mutations in sterol-C4-methyl oxidase–like gene (SC4MOL) as the cause of an autosomal recessive syndrome in a human patient with psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay. This gene encodes a sterol-C4-methyl oxidase (SMO), which catalyzes demethylation of C4-methylsterols in the cholesterol synthesis pathway. C4-Methylsterols are meiosis-activating sterols (MASs). They exist at high concentrations in the testis and ovary and play roles in meiosis activation. In this study, we found that an accumulation of MASs in the patient led to cell overproliferation in both skin and blood. SMO deficiency also substantially altered immunocyte phenotype and in vitro function. MASs serve as ligands for liver X receptors α and β (LXRα and LXRβ), which are important in regulating not only lipid transport in the epidermis, but also innate and adaptive immunity. Deficiency of SMO represents a biochemical defect in the cholesterol synthesis pathway, the clinical spectrum of which remains to be defined. PMID:21285510

  1. Infants understand the referential nature of human gaze but not robot gaze.

    PubMed

    Okumura, Yuko; Kanakogi, Yasuhiro; Kanda, Takayuki; Ishiguro, Hiroshi; Itakura, Shoji

    2013-09-01

    Infants can acquire much information by following the gaze direction of others. This type of social learning is underpinned by the ability to understand the relationship between gaze direction and a referent object (i.e., the referential nature of gaze). However, it is unknown whether human gaze is a privileged cue for information that infants use. Comparing human gaze with nonhuman (robot) gaze, we investigated whether infants' understanding of the referential nature of looking is restricted to human gaze. In the current study, we developed a novel task that measured by eye-tracking infants' anticipation of an object from observing an agent's gaze shift. Results revealed that although 10- and 12-month-olds followed the gaze direction of both a human and a robot, only 12-month-olds predicted the appearance of objects from referential gaze information when the agent was the human. Such a prediction for objects reflects an understanding of referential gaze. Our study demonstrates that by 12 months of age, infants hold referential expectations specifically from the gaze shift of humans. These specific expectations from human gaze may enable infants to acquire various information that others convey in social learning and social interaction.

  2. 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

    2015-06-17

    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.

  3. Understanding the meaning of human dignity in Korea: a content analysis

    PubMed Central

    Jo, Kae-Hwa; Doorenbos, Ardith

    2010-01-01

    This study aims to understand the meaning of human dignity among adults in Korea. The authors utilized a qualitative study design. Data were collected with non-structured questions in a sample of 74 Korean adults and were then analyzed with qualitative content analysis. There were 4 categories, 31 themes and 106 theme clusters classified. The four categories that emerged were: fullness of dignity, loss of dignity, reinforcement of dignity, and enfeeblement of dignity. The results of this study may contribute to healthcare professionals’ understanding of Korean adults’ human dignity. PMID:19430413

  4. Computational approaches towards understanding human long non-coding RNA biology.

    PubMed

    Jalali, Saakshi; Kapoor, Shruti; Sivadas, Ambily; Bhartiya, Deeksha; Scaria, Vinod

    2015-07-15

    Long non-coding RNAs (lncRNAs) form the largest class of non-protein coding genes in the human genome. While a small subset of well-characterized lncRNAs has demonstrated their significant role in diverse biological functions like chromatin modifications, post-transcriptional regulation, imprinting etc., the functional significance of a vast majority of them still remains an enigma. Increasing evidence of the implications of lncRNAs in various diseases including cancer and major developmental processes has further enhanced the need to gain mechanistic insights into the lncRNA functions. Here, we present a comprehensive review of the various computational approaches and tools available for the identification and annotation of long non-coding RNAs. We also discuss a conceptual roadmap to systematically explore the functional properties of the lncRNAs using computational approaches.

  5. Deletion of Porcn in Mice Leads to Multiple Developmental Defects and Models Human Focal Dermal Hypoplasia (Goltz Syndrome)

    PubMed Central

    Liu, Wei; Shaver, Timothy M.; Balasa, Alfred; Ljungberg, M. Cecilia; Wang, Xiaoling; Wen, Shu; Nguyen, Hoang; Van den Veyver, Ignatia B.

    2012-01-01

    Background Focal Dermal Hypoplasia (FDH) is a genetic disorder characterized by developmental defects in skin, skeleton and ectodermal appendages. FDH is caused by dominant loss-of-function mutations in X-linked PORCN. PORCN orthologues in Drosophila and mice encode endoplasmic reticulum proteins required for secretion and function of Wnt proteins. Wnt proteins play important roles in embryo development, tissue homeostasis and stem cell maintenance. Since features of FDH overlap with those seen in mouse Wnt pathway mutants, FDH likely results from defective Wnt signaling but molecular mechanisms by which inactivation of PORCN affects Wnt signaling and manifestations of FDH remain to be elucidated. Results We introduced intronic loxP sites and a neomycin gene in the mouse Porcn locus for conditional inactivation. Porcn-ex3-7flox mice have no apparent developmental defects, but chimeric mice retaining the neomycin gene (Porcn-ex3-7Neo-flox) have limb, skin, and urogenital abnormalities. Conditional Porcn inactivation by EIIa-driven or Hprt-driven Cre recombinase results in increased early embryonic lethality. Mesenchyme-specific Prx-Cre-driven inactivation of Porcn produces FDH-like limb defects, while ectodermal Krt14-Cre-driven inactivation produces thin skin, alopecia, and abnormal dentition. Furthermore, cell-based assays confirm that human PORCN mutations reduce WNT3A secretion. Conclusions These data indicate that Porcn inactivation in the mouse produces a model for human FDH and that phenotypic features result from defective WNT signaling in ectodermal- and mesenchymal-derived structures. PMID:22412863

  6. 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.

  7. The Development of the Concept of Temperature When Assessed via Three Developmental Models. Tel-Aviv University Unit on Human Development and Education. Working Paper No. 46.

    ERIC Educational Resources Information Center

    Frenkel, Pnina; Strauss, Sidney

    The purpose of this study was to determine how children at different ages understand the concept of temperature, examining particularly the logicomathematical aspects of the concept. In doing so, three developmental approaches were compared: (1) Piaget's structuralist approach; (2) Siegler's rule assessment approach; and (3) Anderson and…

  8. Snakes, evolution, behavior systems, and autism spectrum disorder. Comment on: ;Implications of the idea of neurodiversity for understanding the origins of developmental disorders; by Nobuo Masataka

    NASA Astrophysics Data System (ADS)

    Burghardt, Gordon M.

    2017-03-01

    Nobuo Masataka [1] has provided a novel and ambitious approach to understanding variations in mental and neural functioning in humans by embedding them in the concept of neurodiversity. He is particularly interested in Autism Spectrum Disorder (ASD) and views it as on a continuum falling within normal human behavioral variation. If this is true and ASD has been maintained in a population by selection, then, he argues, ASD individuals may have had survival advantages during the EEA (environment of evolutionary adaptiveness), before the advent of large and complex societies. After this point, properly interpreting and responding to social and global cues gained importance at the expense of detailed feature based processing of nonsocial features of the environment.

  9. 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.

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

    PubMed

    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.

  11. Enamel Defects of Human Primary Dentition as Virtual Memory of Early Developmental Events

    PubMed Central

    Asl Aminabadi, Naser; Ghertasi Oskouei, Sina; Pouralibaba, Firoz; Jamali, Zahra; Pakdel, Farzaneh

    2009-01-01

    Background and aims The objectives of the present study were to investigate the prevalence and the position of enamel defects of primary teeth and hence to estimate the approximate time of an insult. Materials and methods 121 children aged 3 to 5 years were included in the study. The Modified Developmental De-fects of Enamel Index was used to diagnose and classify the defects. The defects were categorized as hypoplasia, hypocalcification or a combination of them. Each tooth was investigated for occlusal/incisal, middle, cervical, incisomiddle, cervicomiddle and complete crown defects. Results 55.37% of the children were affected by enamel defects, 23.96% being categorized as hypocalcification and 22.31% as hypoplasia. The enamel defects were more abundant in maxillary primary incisors and mandibular primary canines. Minimum involvement was seen in maxillary primary second molars and mandibular primary lateral incisors. The prevalence of cervical defects in maxillary primary incisors was significantly more than the middle or incisal defects (P < 0.05). The prevalence of incisal defects in mandibular primary incisors was significantly more than the middle or cervical defects (P < 0.05). Conclusion The results revealed a considerable number of enamel defects which are multiple, symmetric and chrono-logically accordant with the estimated neonatal line in primary teeth of healthy children. PMID:23230497

  12. Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

    PubMed

    Murphy, M O; Cohn, D M; Loria, A S

    2017-03-01

    The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood.

  13. (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…

  14. 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)

  15. 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)

  16. 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…

  17. 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…

  18. The role of genomic imprinting in human developmental disorders: lessons from Prader-Willi syndrome.

    PubMed

    Hanel, M L; Wevrick, R

    2001-03-01

    Normal human development involves a delicate interplay of gene expression in specific tissues at narrow windows of time. Temporally and spatially regulated gene expression is controlled both by gene-specific factors and chromatin-specific factors. Genomic imprinting is the expression of specific genes primarily from only one allele at particular times during development, and is one mechanism implicated in the intricate control of gene expression. Two human genetic disorders, Prader-Willi syndrome (PWS, MIM 176270) and Angelman syndrome (AS, MIM 105830), result from rearrangements of chromosome 15q11-q13, an imprinted region of the human genome. Despite their rarity, disorders such as PWS and AS can give focused insight into the role of genomic imprinting and imprinted genes in human development.

  19. 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

  20. 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.

  1. 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

  2. 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

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

    PubMed

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

    2015-09-01

    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.

  4. Human teratogens and genetic phenocopies. Understanding pathogenesis through human genes mutation.

    PubMed

    Cassina, Matteo; Cagnoli, Giulia A; Zuccarello, Daniela; Di Gianantonio, Elena; Clementi, Maurizio

    2017-01-01

    Exposure to teratogenic drugs during pregnancy is associated with a wide range of embryo-fetal anomalies and sometimes results in recurrent and recognizable patterns of malformations; however, the comprehension of the mechanisms underlying the pathogenesis of drug-induced birth defects is difficult, since teratogenesis is a multifactorial process which is always the result of a complex interaction between several environmental factors and the genetic background of both the mother and the fetus. Animal models have been extensively used to assess the teratogenic potential of pharmacological agents and to study their teratogenic mechanisms; however, a still open issue concerns how the information gained through animal models can be translated to humans. Instead, significant information can be obtained by the identification and analysis of human genetic syndromes characterized by clinical features overlapping with those observed in drug-induced embryopathies. Until now, genetic phenocopies have been reported for the embryopathies/fetopathies associated with prenatal exposure to warfarin, leflunomide, mycophenolate mofetil, fluconazole, thalidomide and ACE inhibitors. In most cases, genetic phenocopies are caused by mutations in genes encoding for the main targets of teratogens or for proteins belonging to the same molecular pathways. The aim of this paper is to review the proposed teratogenic mechanisms of these drugs, by the analysis of human monogenic disorders and their molecular pathogenesis.

  5. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation.

    PubMed Central

    Adida, C.; Crotty, P. L.; McGrath, J.; Berrebi, D.; Diebold, J.; Altieri, D. C.

    1998-01-01

    Inhibitors of programmed cell death (apoptosis) may regulate tissue differentiation and aberrantly promote cell survival in neoplasia. A novel apoptosis inhibitor of the IAP gene family, designated survivin, was recently found in all of the most common human cancers but not in normal, terminally differentiated adult tissues. The expression of survivin in embryonic and fetal development was investigated. Immunohistochemistry and in situ hybridization studies demonstrated strong expression of survivin in several apoptosis-regulated fetal tissues, including the stem cell layer of stratified epithelia, endocrine pancreas, and thymic medulla, with a pattern that did not overlap with that of another apoptosis inhibitor, bcl-2. A sequence-specific antibody to survivin immunoblotted a single approximately 16.5-kd survivin band in human fetal lung, liver, heart, kidney, and gastrointestinal tract. In mouse embryo, prominent and nearly ubiquitous distribution of survivin was found at embryonic day (E)11.5, whereas at E15 to -21, survivin expression was restricted to the distal bronchiolar epithelium of the lung and neural-crest-derived cells, including dorsal root ganglion neurons, hypophysis, and the choroid plexus. These data suggest that expression of survivin in embryonic and fetal development may contribute to tissue homeostasis and differentiation independently of bcl-2. Aberrations of this developmental pathway may result in prominent re-expression of survivin in neoplasia and abnormally prolonged cell viability. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9422522

  6. Analysis of developmental processes possibly related to human dental sexual dimorphism in permanent and deciduous canines.

    PubMed

    Moss, M L; Moss-Salentijn, L

    1977-05-01

    Analysis of published odontometric data on human dental sexual dimorphism indicates that this characteristic is most clearly expressed by the canine teeth. Review of the several processes involved in coronal odontogenesis suggests that such dimorphism is related to an absolutely longer period of amelogenesis for both deciduous and permanent dentitions.

  7. 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…

  8. 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.

  9. 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.

  10. 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

  11. 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…

  12. Primate vocal communication: a useful tool for understanding human speech and language evolution?

    PubMed

    Fedurek, Pawel; Slocombe, Katie E

    2011-04-01

    Language is a uniquely human trait, and questions of how and why it evolved have been intriguing scientists for years. Nonhuman primates (primates) are our closest living relatives, and their behavior can be used to estimate the capacities of our extinct ancestors. As humans and many primate species rely on vocalizations as their primary mode of communication, the vocal behavior of primates has been an obvious target for studies investigating the evolutionary roots of human speech and language. By studying the similarities and differences between human and primate vocalizations, comparative research has the potential to clarify the evolutionary processes that shaped human speech and language. This review examines some of the seminal and recent studies that contribute to our knowledge regarding the link between primate calls and human language and speech. We focus on three main aspects of primate vocal behavior: functional reference, call combinations, and vocal learning. Studies in these areas indicate that despite important differences, primate vocal communication exhibits some key features characterizing human language. They also indicate, however, that some critical aspects of speech, such as vocal plasticity, are not shared with our primate cousins. We conclude that comparative research on primate vocal behavior is a very promising tool for deepening our understanding of the evolution of human speech and language, but much is still to be done as many aspects of monkey and ape vocalizations remain largely unexplored.

  13. 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.

  14. 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, ...

  15. 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...

  16. Aging of human muscle: understanding sarcopenia at the single muscle cell level.

    PubMed

    Frontera, Walter R; Zayas, Ana Rodriguez; Rodriguez, Natividad

    2012-02-01

    The loss of muscle mass with age, also known as sarcopenia, is a major scientific and public health problem. Muscle atrophy is associated with the loss of functional capacity and poor health outcomes in elderly men and women. A detailed understanding of this problem in humans can be enhanced by the use of experiments with single muscle fibers. It is likely that both muscle atrophy and a decrease in muscle-fiber quality contribute to muscle dysfunction among the elderly. A better understanding of sarcopenia at the single-fiber level may lead to the design of more effective rehabilitative interventions.

  17. Developmental transitions in the myosin heavy chain phenotype of human respiratory muscle.

    PubMed

    Lloyd, J S; Brozanski, B S; Daood, M; Watchko, J F

    1996-01-01

    We studied the expression of myosin heavy chain (MHC) isoforms in the costal diaphragm (DIA) and the genioglossus (GG) muscles from 16 to 42 weeks gestation in the human using Western blotting techniques. Embryonic/neonatal MHC (MHCemb/neo) was the predominant isoform expressed in the DIA and GG at 16-24 weeks gestation. Subsequently, MHCemb/neo expression declined and the expression of MHCslow and MHC2A increased. At term, the DIA MHC phenotype was a composite of MHCemb/neo (15% of the total MHC complement), MHCslow (32%), MHC2A (47%), and MHC2B (6%); whereas, the GG was largely comprised of MHC2A (74%). We conclude that human DIA and GG demonstrate temporally dependent changes in MHC expression during gestation- and muscle-specific MHC phenotypes as they approach term.

  18. 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...

  19. On the incomplete architecture of human ontogeny. Selection, optimization, and compensation as foundation of developmental theory.

    PubMed

    Baltes, P B

    1997-04-01

    Drawing on both evolutionary and ontogenetic perspectives, the basic biological-genetic and social-cultural architecture of human development is outlined. Three principles are involved. First, evolutionary selection pressure predicts a negative age correlation, and therefore, genome-based plasticity and biological potential decrease with age. Second, for growth aspects of human development to extend further into the life span, culture-based resources are required at ever-increasing levels. Third, because of age-related losses in biological plasticity, the efficiency of culture is reduced as life span development unfolds. Joint application of these principles suggests that the life span architecture becomes more and more incomplete with age. Degree of completeness can be defined as the ratio between gains and losses in functioning. Two examples illustrate the implications of the life span architecture proposed. The first is a general theory of development involving the orchestration of 3 component processes: selection, optimization, and compensation. The second considers the task of completing the life course in the sense of achieving a positive balance between gains and losses for all age levels. This goal is increasingly more difficult to attain as human development is extended into advanced old age.

  20. Insights from the Den: How Hibernating Bears May Help Us Understand and Treat Human Disease.

    PubMed

    Berg von Linde, Maria; Arevström, Lilith; Fröbert, Ole

    2015-10-01

    Hibernating brown bears (Ursus arctos) and black bears (Ursus americanus) spend half of the year in a physically inactive state inside their winter dens without food intake and defecating and no or little urination. Under similar extreme conditions, humans would suffer from loss of lean body mass, heart failure, thrombosis, azotemia, osteoporosis, and more. However, bears exit the den in the spring strong without organ injuries. Translational animal models are used in human medicine but traditional experimental animals have several shortcomings; thus, we believe that it is time to systematically explore new models. In this review paper, we describe physiological adaptations of hibernating bears and how similar adaptations in humans could theoretically alleviate medical conditions. The bear has solved most of the health challenges faced by humans, including heart and kidney disease, atherosclerosis and thrombosis, and muscle wasting and osteoporosis. Understanding and applying this library of information could lead to a number of major discoveries that could have implications for the understanding and treatment of human disease.

  1. Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome.

    PubMed

    Qiao, Ruimin; He, Yuyong; Pan, Bo; Xiao, Shijun; Zhang, Xufei; Li, Jing; Zhang, Zhiyan; Hong, Yuan; Xing, Yuyun; Ren, Jun

    2015-06-01

    Microtia is a congenital malformation of the outer ears. Although both genetic and environmental components have been implicated in microtia, the genetic causes of this innate disorder are poorly understood. Pigs have naturally occurring diseases comparable to those in humans, providing exceptional opportunity to dissect the molecular mechanism of human inherited diseases. Here we first demonstrated that a truncating mutation in HOXA1 causes a monogenic disorder of microtia in pigs. We further performed RNA sequencing (RNA-Seq) analysis on affected and healthy pig embryos (day 14.25). We identified a list of 337 differentially expressed genes (DEGs) between the normal and mutant samples, shedding light on the transcriptional network involving HOXA1. The DEGs are enriched in biological processes related to cardiovascular system and embryonic development, and neurological, renal and urological diseases. Aberrant expressions of many DEGs have been implicated in human innate deformities corresponding to microtia-associated syndromes. After applying three prioritizing algorithms, we highlighted appealing candidate genes for human microtia from the 337 DEGs. We searched for coding variants of functional significance within six candidate genes in 147 microtia-affected individuals. Of note, we identified one EVC2 non-synonymous mutation (p.Asp1174Asn) as a potential disease-implicating variant for a human microtia-associated syndrome. The findings advance our understanding of the molecular mechanisms underlying human microtia, and provide an interesting example of the characterization of human disease-predisposing variants using pig models.

  2. When Satisfaction Is Not Directly Related to the Support Services Received: Understanding Parents' Varied Experiences with Specialised Services for Children with Developmental Disabilities

    ERIC Educational Resources Information Center

    Robert, Marie; Leblanc, Line; Boyer, Thierry

    2015-01-01

    Parents of children with developmental disabilities (autism or intellectual disabilities) are more susceptible to stress and have a greater burden of adversity than other parents. Their well-being and satisfaction greatly depend on the system's response of finding them formal support and the help they need. This study proposes an interpretive…

  3. Understanding the Support Needs of People with Intellectual and Related Developmental Disabilities through Cluster Analysis and Factor Analysis of Statewide Data

    ERIC Educational Resources Information Center

    Viriyangkura, Yuwadee

    2014-01-01

    Through a secondary analysis of statewide data from Colorado, people with intellectual and related developmental disabilities (ID/DD) were classified into five clusters based on their support needs characteristics using cluster analysis techniques. Prior latent factor models of support needs in the field of ID/DD were examined to investigate the…

  4. Eight Problems for the Mirror Neuron Theory of Action Understanding in Monkeys and Humans

    PubMed Central

    Hickok, Gregory

    2009-01-01

    The discovery of mirror neurons in macaque frontal cortex has sparked a resurgence of interest in motor/embodied theories of cognition. This critical review examines the evidence in support of one of these theories, namely that the mirror neurons provide the basis of action understanding. It is argued that there is no evidence from monkey data that directly tests this theory, and evidence from humans makes a strong case against the position. PMID:19199415

  5. 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

  6. 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.

  7. Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes.

    PubMed

    Maury, Yves; Côme, Julien; Piskorowski, Rebecca A; Salah-Mohellibi, Nouzha; Chevaleyre, Vivien; Peschanski, Marc; Martinat, Cécile; Nedelec, Stéphane

    2015-01-01

    Specification of cell identity during development depends on exposure of cells to sequences of extrinsic cues delivered at precise times and concentrations. Identification of combinations of patterning molecules that control cell fate is essential for the effective use of human pluripotent stem cells (hPSCs) for basic and translational studies. Here we describe a scalable, automated approach to systematically test the combinatorial actions of small molecules for the targeted differentiation of hPSCs. Applied to the generation of neuronal subtypes, this analysis revealed an unappreciated role for canonical Wnt signaling in specifying motor neuron diversity from hPSCs and allowed us to define rapid (14 days), efficient procedures to generate spinal and cranial motor neurons as well as spinal interneurons and sensory neurons. Our systematic approach to improving hPSC-targeted differentiation should facilitate disease modeling studies and drug screening assays.

  8. 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

  9. Understanding specificity in metabolic pathways--structural biology of human nucleotide metabolism.

    PubMed

    Welin, Martin; Nordlund, Pär

    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.

  10. 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.

  11. The interferon-related developmental regulator 1 is used by human papillomavirus to suppress NFκB activation

    PubMed Central

    Tummers, Bart; Goedemans, Renske; Pelascini, Laetitia P. L.; Jordanova, Ekaterina S.; van Esch, Edith M. G.; Meyers, Craig; Melief, Cornelis J. M.; Boer, Judith M.; van der Burg, Sjoerd H.

    2015-01-01

    High-risk human papillomaviruses (hrHPVs) infect keratinocytes and successfully evade host immunity despite the fact that keratinocytes are well equipped to respond to innate and adaptive immune signals. Using non-infected and freshly established or persistent hrHPV-infected keratinocytes we show that hrHPV impairs the acetylation of NFκB/RelA K310 in keratinocytes. As a consequence, keratinocytes display a decreased pro-inflammatory cytokine production and immune cell attraction in response to stimuli of the innate or adaptive immune pathways. HPV accomplishes this by augmenting the expression of interferon-related developmental regulator 1 (IFRD1) in an EGFR-dependent manner. Restoration of NFκB/RelA acetylation by IFRD1 shRNA, cetuximab treatment or the HDAC1/3 inhibitor entinostat increases basal and induced cytokine expression. Similar observations are made in IFRD1-overexpressing HPV-induced cancer cells. Thus, our study reveals an EGFR–IFRD1-mediated viral immune evasion mechanism, which can also be exploited by cancer cells. PMID:26055519

  12. 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.

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

    PubMed

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

    2014-05-01

    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.

  14. Developmental constraints of quadrupedal coordination across crawling styles in human infants.

    PubMed

    Patrick, Susan K; Noah, J Adam; Yang, Jaynie F

    2012-06-01

    Human infants can crawl using several very different styles; this diversity appears at first glance to contradict our previous findings from hands-and-knees crawling, which suggested that there were strict limitations on coordination, imposed either mechanically or by the developing nervous system. To determine whether coordination was similarly restricted across crawling styles, we studied free crawling overground in 22 infants who used a number of different locomotor strategies. Despite the wide variety in the use of individual limbs and even the number of limbs used, the duration of the stance phase increased with duration of cycle, whereas the duration of the swing phase remained more constant. Additionally, all infants showed organized, rhythmic interlimb coordination. Alternating patterns (e.g., trotlike) predominated (86% of infants). Alternatively, yet much less frequently, all limbs used could work in synchrony (14% of infants). Pacelike patterns were never observed, even in infants that crawled with the belly remaining in contact with the ground so that stability was not a factor. To explore the robustness of the interlimb coordination, a perturbation that prolonged swing of the leg was imposed on 14 additional infants crawling on hands and knees overground or on the treadmill. The perturbation led to a resetting of the crawling pattern, but never to a change in the coordination of the limbs. The findings concur with those regarding other infant animals, together suggesting that the nervous system itself limits the coordination patterns available at a young age.

  15. 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

  16. 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

  17. 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

  18. 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…

  19. 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

  20. Understanding the nature of wealth and its effects on human fitness

    PubMed Central

    Mulder, Monique Borgerhoff; Beheim, Bret A.

    2011-01-01

    Studying fitness consequences of variable behavioural, physiological and cognitive traits in contemporary populations constitutes the specific contribution of human behavioural ecology to the study of human diversity. Yet, despite 30 years of evolutionary anthropological interest in the determinants of fitness, there exist few principled investigations of the diverse sources of wealth that might reveal selective forces during recent human history. To develop a more holistic understanding of how selection shapes human phenotypic traits, be these transmitted by genetic or cultural means, we expand the conventional focus on associations between socioeconomic status and fitness to three distinct types of wealth—embodied, material and relational. Using a model selection approach to the study of women's success in raising offspring in an African horticultural population (the Tanzanian Pimbwe), we find that the top performing models consistently include relational and material wealth, with embodied wealth as a less reliable predictor. Specifically, child mortality risk is increased with few household assets, parent nonresidency, child legitimacy, and one or more parents having been accused of witchcraft. The use of multiple models to test various hypotheses greatly facilitates systematic comparative analyses of human behavioural diversity in wealth accrual and investment across different kinds of societies. PMID:21199839

  1. Cultural influences on children's understanding of the human body and the concept of life.

    PubMed

    Panagiotaki, Georgia; Nobes, Gavin

    2014-09-01

    This study aimed to identify the age by which children begin to demonstrate a biological understanding of the human body and the idea that the purpose of body functioning is to maintain life. The study also explored the influence of education, culturally specific experiences and religion on knowledge acquisition in this domain. Children aged between 4 and 7 years from three different cultural backgrounds (White British, British Muslim, and Pakistani Muslim) were interviewed about the human body and its functioning. At least half of the 4- to 5-year-olds in each cultural group, and almost all 6- to 7-year-olds, referred to the maintenance of life when explaining organs' functions and so were classified as 'life theorizers'. Pakistani Muslim children gave fewer biological responses to questions about organs' functions and the purpose of eating and breathing, but referred to life more than their British counterparts. Irrespective of cultural group, older children understood organ location and function better than younger children. These findings support Jaakkola and Slaughter's (2002, Br. J. Dev. Psychol., 20, 325) view that children's understanding of the body as a 'life machine' emerges around the ages of 4-5 years. They also suggest that, despite many similarities in children's ideas cross-culturally, different educational input and culturally specific experiences influence aspects of their biological understanding.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Toward a better understanding of the impact of mass transit air pollutants on human health.

    PubMed

    Kim, Ki-Hyun; Kumar, Pawan; Szulejko, Jan E; Adelodun, Adedeji A; Junaid, Muhammad Faisal; Uchimiya, Minori; Chambers, Scott

    2017-05-01

    Globally, modern mass transport systems whether by road, rail, water, or air generate airborne pollutants in both developing and developed nations. Air pollution is the primary human health concern originating from modern transportation, particularly in densely-populated urban areas. This review will specifically focus on the origin and the health impacts of carbonaceous traffic-related air pollutants (TRAP), including particulate matter (PM), volatile organic compounds (VOCs), and elemental carbon (EC). We conclude that the greatest current challenge regarding urban TRAP is understanding and evaluating the human health impacts well enough to set appropriate pollution control measures. Furthermore, we provide a detailed discussion regarding the effects of TRAP on local environments and pedestrian health in low and high traffic-density environments.

  8. 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.

  9. Gene Coexpression Networks in Human Brain Developmental Transcriptomes Implicate the Association of Long Noncoding RNAs with Intellectual Disability

    PubMed Central

    Gudenas, Brian L.; Wang, Liangjiang

    2015-01-01

    The advent of next-generation sequencing for genetic diagnoses of complex developmental disorders, such as intellectual disability (ID), has facilitated the identification of hundreds of predisposing genetic variants. However, there still exists a vast gap in our knowledge of causal genetic factors for ID as evidenced by low diagnostic yield of genetic screening, in which identifiable genetic causes are not found for the majority of ID cases. Most methods of genetic screening focus on protein-coding genes; however, noncoding RNAs may outnumber protein-coding genes and play important roles in brain development. Long noncoding RNAs (lncRNAs) specifically have been shown to be enriched in the brain and have diverse roles in gene regulation at the transcriptional and posttranscriptional levels. LncRNAs are a vastly uncharacterized group of noncoding genes, which could function in brain development and harbor ID-predisposing genetic variants. We analyzed lncRNAs for coexpression with known ID genes and affected biological pathways within a weighted gene coexpression network derived from RNA-sequencing data spanning human brain development. Several ID-associated gene modules were found to be enriched for lncRNAs, known ID genes, and affected biological pathways. Utilizing a list of de novo and pathogenic copy number variants detected in ID probands, we identified lncRNAs overlapping these genetic structural variants. By integrating our results, we have made a prioritized list of potential ID-associated lncRNAs based on the developing brain gene coexpression network and genetic structural variants found in ID probands. PMID:26523118

  10. Ancient human disturbances may be skewing our understanding of Amazonian forests.

    PubMed

    McMichael, Crystal N H; Matthews-Bird, Frazer; Farfan-Rios, William; Feeley, Kenneth J

    2017-01-17

    Although the Amazon rainforest houses much of Earth's biodiversity and plays a major role in the global carbon budget, estimates of tree biodiversity originate from fewer than 1,000 forest inventory plots, and estimates of carbon dynamics are derived from fewer than 200 recensus plots. It is well documented that the pre-European inhabitants of Amazonia actively transformed and modified the forest in many regions before their population collapse around 1491 AD; however, the impacts of these ancient disturbances remain entirely unaccounted for in the many highly influential studies using Amazonian forest plots. Here we examine whether Amazonian forest inventory plot locations are spatially biased toward areas with high probability of ancient human impacts. Our analyses reveal that forest inventory plots, and especially forest recensus plots, in all regions of Amazonia are located disproportionately near archaeological evidence and in areas likely to have ancient human impacts. Furthermore, regions of the Amazon that are relatively oversampled with inventory plots also contain the highest values of predicted ancient human impacts. Given the long lifespan of Amazonian trees, many forest inventory and recensus sites may still be recovering from past disturbances, potentially skewing our interpretations of forest dynamics and our understanding of how these forests are responding to global change. Empirical data on the human history of forest inventory sites are crucial for determining how past disturbances affect modern patterns of forest composition and carbon flux in Amazonian forests.

  11. 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.

  12. Drought in a human-modified world: reframing drought definitions, understanding, and analysis approaches

    NASA Astrophysics Data System (ADS)

    Van Loon, Anne F.; Stahl, Kerstin; Di Baldassarre, Giuliano; Clark, Julian; Rangecroft, Sally; Wanders, Niko; Gleeson, Tom; Van Dijk, Albert I. J. M.; Tallaksen, Lena M.; Hannaford, Jamie; Uijlenhoet, Remko; Teuling, Adriaan J.; Hannah, David M.; Sheffield, Justin; Svoboda, Mark; Verbeiren, Boud; Wagener, Thorsten; Van Lanen, Henny A. J.

    2016-09-01

    In the current human-modified world, or Anthropocene, the state of water stores and fluxes has become dependent on human as well as natural processes. Water deficits (or droughts) are the result of a complex interaction between meteorological anomalies, land surface processes, and human inflows, outflows, and storage changes. Our current inability to adequately analyse and manage drought in many places points to gaps in our understanding and to inadequate data and tools. The Anthropocene requires a new framework for drought definitions and research. Drought definitions need to be revisited to explicitly include human processes driving and modifying soil moisture drought and hydrological drought development. We give recommendations for robust drought definitions to clarify timescales of drought and prevent confusion with related terms such as water scarcity and overexploitation. Additionally, our understanding and analysis of drought need to move from single driver to multiple drivers and from uni-directional to multi-directional. We identify research gaps and propose analysis approaches on (1) drivers, (2) modifiers, (3) impacts, (4) feedbacks, and (5) changing the baseline of drought in the Anthropocene. The most pressing research questions are related to the attribution of drought to its causes, to linking drought impacts to drought characteristics, and to societal adaptation and responses to drought. Example questions include

    • (i) What are the dominant drivers of drought in different parts of the world? (ii) How do human modifications of drought enhance or alleviate drought severity? (iii) How do impacts of drought depend on the physical characteristics of drought vs. the vulnerability of people or the environment? (iv) To what extent are physical and human drought processes coupled, and can feedback loops be identified and altered to lessen or mitigate drought? (v) How should we adapt our drought analysis to

    • 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.

    • Developmental Evaluation.

      ERIC Educational Resources Information Center

      Patton, Michael Quinn

      1994-01-01

      Developmental evaluation is proposed as a term to describe certain long-term partnering relationships with clients who are, themselves, engaged in ongoing program development. Rather than a model, developmental evaluation is a relationship founded on a shared purpose and is a way of being useful in innovative settings. (SLD)

    • Large-scale gene expression profiling data for the model moss Physcomitrella patens aid understanding of developmental progression, culture and stress conditions.

      PubMed

      Hiss, Manuel; Laule, Oliver; Meskauskiene, Rasa M; Arif, Muhammad A; Decker, Eva L; Erxleben, Anika; Frank, Wolfgang; Hanke, Sebastian T; Lang, Daniel; Martin, Anja; Neu, Christina; Reski, Ralf; Richardt, Sandra; Schallenberg-Rüdinger, Mareike; Szövényi, Peter; Tiko, Theodhor; Wiedemann, Gertrud; Wolf, Luise; Zimmermann, Philip; Rensing, Stefan A

      2014-08-01

      The moss Physcomitrella patens is an important model organism for studying plant evolution, development, physiology and biotechnology. Here we have generated microarray gene expression data covering the principal developmental stages, culture forms and some environmental/stress conditions. Example analyses of developmental stages and growth conditions as well as abiotic stress treatments demonstrate that (i) growth stage is dominant over culture conditions, (ii) liquid culture is not stressful for the plant, (iii) low pH might aid protoplastation by reduced expression of cell wall structure genes, (iv) largely the same gene pool mediates response to dehydration and rehydration, and (v) AP2/EREBP transcription factors play important roles in stress response reactions. With regard to the AP2 gene family, phylogenetic analysis and comparison with Arabidopsis thaliana shows commonalities as well as uniquely expressed family members under drought, light perturbations and protoplastation. Gene expression profiles for P. patens are available for the scientific community via the easy-to-use tool at https://www.genevestigator.com. By providing large-scale expression profiles, the usability of this model organism is further enhanced, for example by enabling selection of control genes for quantitative real-time PCR. Now, gene expression levels across a broad range of conditions can be accessed online for P. patens.

    • 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

    • Do robots have goals? How agent cues influence action understanding in non-human primates.

      PubMed

      Kupferberg, Aleksandra; Glasauer, Stefan; Burkart, Judith M

      2013-06-01

      The capacity to understand goals and intentions emerges early and universally in humans and is a basic precondition for the interpretation and prediction of others' actions, be it other humans, animals, or even robots. It is unclear, however, how this goal attribution system is acquired, in particular with regard to the role of prior experience with the actor and visual characteristics that are necessary. In four preferential looking time experiments we examined how familiarity, appearance, and movement of different agents influence the capability of marmosets to perceive the behavior of these agents as goal directed. To this end we compared the monkeys' reactions to the same goal-directed actions performed by four different agents: a human actor, a conspecific, a monkey-like small robot, and a black box. The results showed that monkeys attributed goals to the human actor, the conspecific, and the robot, but not the box. Thus, the monkeys extended their capacity for goal attribution not only to familiar agents, but also to agents not previously encountered, provided that they had some conspecific-like features. Our results suggest that in non-human primates, the system for goal attribution does not require previous experience with a specific agent or agent-category, as long as it exhibits certain visual characteristics like face, body or legs. Furthermore, the results suggest that the capacity to attribute goals emerged very early during evolution and, at least in marmoset monkeys, does not necessarily require pre-learned associations in order to fulfill its function when dealing with unfamiliar agents.

    • A comparison of potency differences among thyroid peroxidase (TPO) inhibitors to induce developmental toxicity and other thyroid gland-linked toxicities in humans and rats.

      PubMed

      Motonaga, Kozo; Ota, Mika; Odawara, Kyoko; Saito, Shoji; Welsch, Frank

      2016-10-01

      The potencies of resorcinol, 6-propylthiouracil (PTU) and methimazole (MMI) for inducing developmental toxicity and neurotoxicity were compared in pregnant rats, regarded as valid model for human thyroid toxicity. Profound differences on maternal thyroid hormone levels (THs), maternal toxicity as well as developmental and neurotoxicity sequelae occurred. Resorcinol affected none of those end points. PTU and MMI caused significant effects. Therapy with either PTU or MMI during the first trimester of human pregnancy can cause reductions of maternal THs, accompanied by disruptions of prenatal development. Clinical MMI studies show sporadic evidence of teratogenic effects, with equivocal relation to thyroid peroxidase (TPO) inhibition. In recent decades no MMI associated prenatal toxicity has been reported, an outcome possibly related to carefully managed therapy. Orally administered resorcinol was rapidly absorbed, metabolized and excreted and was undetectable in the thyroid. In contrast, PTU or MMI accumulated. Resorcinol's potency to inhibit TPO was profoundly lower than that of PTU or MMI. Quantum chemical calculations may explain low resorcinol reactivity with TPO. Thus, distinctions in the target organ and the TPO inhibitory potency between these chemicals are likely contributing to different reductions of maternal THs levels and affecting the potency to cause developmental toxicity and neurotoxicity.

    • The healing balm of nature: Understanding and supporting the naturalist intelligence in individuals diagnosed with ASD. Comment on: ;Implications of the idea of neurodiversity for understanding the origins of developmental disorders; by Nobuo Masataka

      NASA Astrophysics Data System (ADS)

      Armstrong, Thomas

      2017-03-01

      Masataka's [1] review article challenges the deficiency-oriented paradigm that most researchers and practitioners in the field of developmental disorders embrace with regard to children and adults diagnosed with autism spectrum disorders (ASD). While acknowledging the clear disadvantages possessed by those with ASD in the social domain, the paper challenges us to consider the possibility that people with this ;disorder; may also possess significant strengths and that knowledge of those strengths may help parents, teachers, therapists, and researchers design interventions that are better suited to assisting neurodiverse individuals in successfully adapting to the world.

    • 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

  1. 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.

  2. 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

  3. Expected Satiety: Application to Weight Management and Understanding Energy Selection in Humans.

    PubMed

    Forde, Ciarán G; Almiron-Roig, Eva; Brunstrom, Jeffrey M

    2015-03-01

    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.

  4. Understanding melatonin receptor pharmacology: latest insights from mouse models, and their relevance to human disease.

    PubMed

    Tosini, Gianluca; Owino, Sharon; Guillaume, Jean-Luc; Jockers, Ralf

    2014-08-01

    Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications toward type 2 diabetes development, visual functions, sleep disturbances, and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2 , which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1 /MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models.

  5. Alzheimer's Disease: Prototype of Cognitive Deterioration, Valuable Lessons to Understand Human Cognition.

    PubMed

    Noroozian, Maryam

    2016-02-01

    It is important for neurologists to become more familiar with neuropsychological evaluation for Alzheimer disease. The growth of this method in research, as an available, inexpensive, and noninvasive diagnostic approach, which can be administered even by non-specialist-trained examiners, makes this knowledge more necessary than ever. Such knowledge has a basic role in planning national programs in primary health care systems for prevention and early detection of Alzheimer disease. This is more crucial in developing countries, which have higher rates of dementia prevalence along with cardiovascular risk factors, lack of public knowledge about dementia, and limited social support. In addition compared to the neurological hard signs which are tangible and measurable, the concept of cognition seems to be more difficult for the neurologists to evaluate and for the students to understand. Dementia in general and Alzheimer's disease as the prototype of cognitive disorders specifically, play an important role to explore all domains of human cognition through its symptomatology and neuropsychological deficits.

  6. 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

  7. Understanding the role of prostaglandin E2 in regulating human platelet activity in health and disease

    PubMed Central

    Friedman, Eitan A.; Ogletree, Martin L.; Haddad, Elias V.; Boutaud, Olivier

    2015-01-01

    The platelet thrombus is the major pathologic entity in acute coronary syndromes, and antiplatelet agents are a mainstay of therapy. However, individual patient responsiveness to current antiplatelet drugs is variable, and all drugs carry a risk of bleeding. An understanding of the complex role of Prostaglandin E2 (PGE2) in regulating thrombosis offers opportunities for the development of novel individualized antiplatelet treatment. However, deciphering the platelet regulatory function of PGE2 has long been confounded by non-standardized experimental conditions, extrapolation of murine data to humans, and phenotypic differences in PGE2 response. This review synthesizes past and current knowledge about PGE2 effects on platelet biology, presents a rationale for standardization of experimental protocols, and provides insight into a molecular mechanism by which PGE2-activated pathways could be targeted for new personalized antiplatelet therapy to inhibit pathologic thrombosis without affecting hemostasis. PMID:26077962

  8. 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

  9. Developmental Immunotoxicity

    EPA Science Inventory

    Animal models suggest that the immature immune system is more susceptible to xenobiotics than the fully mature system, and sequelae of developmental immunotoxicant exposure may be persistent well into adulthood. Immune maturation may be delayed by xenobiotic exposure and recover...

  10. 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...

  11. 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,…

  12. 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…

  13. 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…

  14. Genetic aspects of birth defects: new understandings of old problems

    PubMed Central

    Prescott, Katrina R; Wilkie, Andrew O M

    2007-01-01

    Over the past two decades, combined advances in genetics, developmental biology and biochemistry have transformed the study of human birth defects. This review describes the importance of genome architecture, parent of origin effects (imprinting), molecular pathophysiology, developmental pathways, mosaicism and cancer predisposition syndromes in the understanding of birth defects. This knowledge can be applied to improve diagnostic accuracy, prognostic information, counselling and sometimes even treatment of these conditions. PMID:17585097

  15. Towards Understanding the Catalytic Mechanism of Human Paraoxonase 1: Experimental and In Silico Mutagenesis Studies.

    PubMed

    Tripathy, Rajan K; Aggarwal, Geetika; Bajaj, Priyanka; Kathuria, Deepika; Bharatam, Prasad V; Pande, Abhay H

    2017-02-04

    Human paraoxonase 1 (h-PON1) is a ~45-kDa serum enzyme that can hydrolyze a variety of substrates, including organophosphate (OP) compounds. It is a potential candidate for the development of antidote against OP poisoning in humans. However, insufficient OP-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced OP-hydrolyzing activity. The crystal structure of h-PON1 remains unsolved, and the molecular details of how the enzyme catalyses hydrolysis of different types of substrates are also not clear. Understanding the molecular details of the catalytic mechanism of h-PON1 is essential to engineer better variant(s) of enzyme. In this study, we have used a random mutagenesis approach to increase the OP-hydrolyzing activity of recombinant h-PON1. The mutants not only showed a 10-340-fold increased OP-hydrolyzing activity against different OP substrates but also exhibited differential lactonase and arylesterase activities. In order to investigate the mechanistic details of the effect of observed mutations on the hydrolytic activities of enzyme, molecular docking studies were performed with selected mutants. The results suggested that the observed mutations permit differential binding of substrate/inhibitor into the enzyme's active site. This may explain differential hydrolytic activities of the enzyme towards different substrates.

  16. 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

  17. Advancements toward a systems level understanding of the human oral microbiome

    PubMed Central

    McLean, Jeffrey S.

    2014-01-01

    Oral microbes represent one of the most well studied microbial communities owing to the fact that they are a fundamental part of human development influencing health and disease, an easily accessible human microbiome, a highly structured and remarkably resilient biofilm as well as a model of bacteria-bacteria and bacteria-host interactions. In the last 80 years since oral plaque was first characterized for its functionally stable physiological properties such as the highly repeatable rapid pH decrease upon carbohydrate addition and subsequent recovery phase, the fundamental approaches to study the oral microbiome have cycled back and forth between community level investigations and characterizing individual model isolates. Since that time, many individual species have been well characterized and the development of the early plaque community, which involves many cell–cell binding interactions, has been carefully described. With high throughput sequencing enabling the enormous diversity of the oral cavity to be realized, a number of new challenges to progress were revealed. The large number of uncultivated oral species, the high interpersonal variability of taxonomic carriage and the possibility of multiple pathways to dysbiosis pose as major hurdles to obtain a systems level understanding from the community to the gene level. It is now possible however to start connecting the insights gained from single species with community wide approaches. This review will discuss some of the recent insights into the oral microbiome at a fundamental level, existing knowledge gaps, as well as challenges that have surfaced and the approaches to address them. PMID:25120956

  18. 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.

  19. 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…

  20. 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

  1. Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

    NASA Technical Reports Server (NTRS)

    Globus, Ruth

    2016-01-01

    factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

  2. 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…

  3. 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…

  4. Constructivist developmental theory is needed in developmental neuroscience

    NASA Astrophysics Data System (ADS)

    Arsalidou, Marie; Pascual-Leone, Juan

    2016-12-01

    Neuroscience techniques provide an open window previously unavailable to the origin of thoughts and actions in children. Developmental cognitive neuroscience is booming, and knowledge from human brain mapping is finding its way into education and pediatric practice. Promises of application in developmental cognitive neuroscience rests however on better theory-guided data interpretation. Massive amounts of neuroimaging data from children are being processed, yet published studies often do not frame their work within developmental models—in detriment, we believe, to progress in this field. Here we describe some core challenges in interpreting the data from developmental cognitive neuroscience, and advocate the use of constructivist developmental theories of human cognition with a neuroscience interpretation.

  5. 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

  6. Folate metabolite profiling of different cell types and embryos suggests variation in folate one-carbon metabolism, including developmental changes in human embryonic brain.

    PubMed

    Leung, Kit-Yi; De Castro, Sandra C P; Cabreiro, Filipe; Gustavsson, Peter; Copp, Andrew J; Greene, Nicholas D E

    2013-06-01

    Folates act as co-factors for transfer of one-carbon units for nucleotide production, methylation and other biosynthetic reactions. Comprehensive profiling of multiple folates can be achieved using liquid chromatography tandem mass spectrometry, enabling determination of their relative abundance that may provide an indication of metabolic differences between cell types. For example, cell lines exposed to methotrexate showed a dose-dependent elevation of dihydrofolate, consistent with inhibition of dihydrofolate reductase. We analysed the folate profile of E. coli sub-types as well as cell lines and embryonic tissue from both human and mouse. The folate profile of bacteria differed markedly from those of all the mammalian samples, most notably in the greater abundance of formyl tetrahydrofolate. The overall profiles of mouse and human fibroblasts and mid-gestation mouse embryos were broadly similar, with specific differences. The major folate species in these cell types was 5-methyl tetrahydrofolate, in contrast to lymphoblastoid cell lines in which the predominant form was tetrahydrofolate. Analysis of embryonic human brain revealed a shift in folate profile with increasing developmental stage, with a decline in relative abundance of dihydrofolate and increase in 5-methyl tetrahydrofolate. These cell type-specific and developmental changes in folate profile may indicate differential requirements for the various outputs of folate metabolism.

  7. 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

  8. 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.

  9. Developmental programming and transgenerational transmission of obesity.

    PubMed

    Vickers, M H

    2014-01-01

    The global obesity pandemic is often causally linked to marked changes in diet and lifestyle, namely marked increases in dietary intakes of high-energy diets and concomitant reductions in physical activity levels. However, far less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from environmental perturbations during the early-life period. Human and animal studies have highlighted the link between alterations in the early-life environment and increased susceptibility to obesity and related metabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and maternal obesity, has been shown to lead to transgenerational transmission of metabolic disorders. This association has been conceptualised as the developmental programming hypothesis whereby the impact of environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the physiology of the offspring. Further, evidence to date suggests that this developmental programming is a transgenerational phenomenon, with a number of studies showing transmission of programming effects to subsequent generations, even in the absence of continued environmental stressors, thus perpetuating a cycle of obesity and metabolic disorders. The mechanisms responsible for these transgenerational effects remain poorly understood; evidence to date suggests a number of potential mechanisms underpinning the transgenerational transmission of the developmentally programmed phenotype through both the maternal and paternal lineage. Transgenerational phenotype transmission is often seen as a form of epigenetic inheritance with evidence showing both germline and somatic inheritance of epigenetic modifications leading to phenotype changes across generations. However, there is also evidence for non-genomic components as well as an interaction between the developing fetus with the in utero

  10. Developmental disorders of vision.

    PubMed

    Galaburda, Albert M; Duchaine, Bradley C

    2003-08-01

    This review of developmental disorders of vision focuses on only a few of the many disorders that disrupt visual development. Given the enormity of the human visual system in the primate brain and complexity of visual development, however, there are likely hundreds or thousands of types of disorders affecting high-level vision. The rapid progress seen in developmental dyslexia and WMS demonstrates the possibilities and difficulties inherent in researching such disorders, and the authors hope that similar progress will be made for congenital prosopagnosia and other disorders in the near future.

  11. Trauma-Informed Day Services for Individuals with Intellectual/Developmental Disabilities: Exploring Staff Understanding and Perception within an Innovative Programme

    ERIC Educational Resources Information Center

    Keesler, John M.

    2016-01-01

    Background: Trauma-informed care (TIC) is a systems-level philosophy of service delivery which integrates choice, collaboration, empowerment, safety and trust to create an organizational culture sensitive to trauma. This study explores staff understandings and perceptions within an innovative trauma-informed day program for individuals with…

  12. Apomixis: a developmental perspective.

    PubMed

    Koltunow, Anna M; Grossniklaus, Ueli

    2003-01-01

    The term apomixis encompasses a suite of processes whereby seeds form asexually in plants. In contrast to sexual reproduction, seedlings arising from apomixis retain the genotype of the maternal parent. The transfer of apomixis and its effective utilization in crop plants (where it is largely absent) has major advantages in agriculture. The hallmark components of apomixis include female gamete formation without meiosis (apomeiosis), fertilization-independent embryo development (parthenogenesis), and developmental adaptations to ensure functional endosperm formation. Understanding the molecular mechanisms underlying apomixis, a developmentally fascinating phenomenon in plants, is critical for the successful induction and utilization of apomixis in crop plants. This review draws together knowledge gained from analyzing ovule, embryo, and endosperm development in sexual and apomictic plants. It consolidates the view that apomixis and sexuality are closely interrelated developmental pathways where apomixis can be viewed as a deregulation of the sexual process in both time and space.

  13. Genetic and Developmental Basis of Cardiovascular Malformations

    PubMed Central

    Azhar, Mohamad; Ware, Stephanie M.

    2015-01-01

    Cardiovascular malformations (CVMs) are the most common birth defect, occurring in 1–5% of all live births. Genetic, epigenetic, and environmental factors all influence the development of CVMs, and an improved understanding of causation of CVMs is a prerequisite for prevention. Cardiac development is a complex, multi-step process of morphogenesis that is under genetic regulation. Multiple developmental pathways act independently or in combination to effect proper cardiac lineage specification, differentiation, and structure. Because of this complexity, there are numerous potential mechanisms by which genetic variation can impact both fetal cardiac development and latent cardiac disease. Although the genetic contribution to CVMs is well recognized, the genetic causes of human CVMs are still identified relatively infrequently. Mouse models are important tools to investigate the molecular mechanisms underpinning cardiac development as well as the complex genetics that characterize human CVMs. In this review we provide an overview of the key genetic concepts characterizing human CVMs, review their developmental basis, and provide examples to illustrate the critical developmental and genetic concepts underlying the pathogenesis of CVMs. PMID:26876120

  14. The white matter structural network underlying human tool use and tool understanding.

    PubMed

    Bi, Yanchao; Han, Zaizhu; Zhong, Suyu; Ma, Yujun; Gong, Gaolang; Huang, Ruiwang; Song, Luping; Fang, Yuxing; He, Yong; Caramazza, Alfonso

    2015-04-29

    The ability to recognize, create, and use complex tools is a milestone in human evolution. Widely distributed brain regions in parietal, frontal, and temporal cortices have been implicated in using and understanding tools, but the roles of their anatomical connections in supporting tool use and tool conceptual behaviors are unclear. Using deterministic fiber tracking in healthy participants, we first examined how 14 cortical regions that are consistently activated by tool processing are connected by white matter (WM) tracts. The relationship between the integrity of each of the 33 obtained tracts and tool processing deficits across 86 brain-damaged patients was investigated. WM tract integrity was measured with both lesion percentage (structural imaging) and mean fractional anisotropy (FA) values (diffusion imaging). Behavioral abilities were assessed by a tool use task, a range of conceptual tasks, and control tasks. We found that three left hemisphere tracts connecting frontoparietal and intrafrontal areas overlapping with left superior longitudinal fasciculus are crucial for tool use such that larger lesion and lower mean FA values on these tracts were associated with more severe tool use deficits. These tracts and five additional left hemisphere tracts connecting frontal and temporal/parietal regions, mainly overlapping with left superior longitudinal fasciculus, inferior frontooccipital fasciculus, uncinate fasciculus, and anterior thalamic radiation, are crucial for tool concept processing. Largely consistent results were also obtained using voxel-based symptom mapping analyses. Our results revealed the WM structural networks that support the use and conceptual understanding of tools, providing evidence for the anatomical skeleton of the tool knowledge network.

  15. Molecular Profiling of Human Induced Pluripotent Stem Cell-Derived Hypothalamic Neurones Provides Developmental Insights into Genetic Loci for Body Weight Regulation.

    PubMed

    Yao, L; Liu, Y; Qiu, Z; Kumar, S; Curran, J E; Blangero, J; Chen, Y; Lehman, D M

    2017-02-01

    Recent data suggest that common genetic risks for metabolic disorders such as obesity may be human-specific and exert effects via the central nervous system. To overcome the limitation of human tissue access for study, we have generated induced human pluripotent stem cell (hiPSC)-derived neuronal cultures that recapture many features of hypothalamic neurones within the arcuate nucleus. In the present study, we have comprehensively characterised this model across development, benchmarked these neurones to in vivo events, and demonstrate a link between obesity risk variants and hypothalamic development. The dynamic transcriptome across neuronal maturation was examined using microarray and RNA sequencing methods at nine time points. K-means clustering of the longitudinal data was conducted to identify co-regulation and microRNA control of biological processes. The transcriptomes were compared with those of 103 samples from 13 brain regions reported in the Genotype-Tissue Expression database (GTEx) using principal components analysis. Genes with proximity to body mass index (BMI)-associated genetic variants were mapped to the developmentally expressed genesets, and enrichment significance was assessed with Fisher's exact test. The human neuronal cultures have a transcriptional and physiological profile of neuropeptide Y/agouti-related peptide arcuate nucleus neurones. The neuronal transcriptomes were highly correlated with adult hypothalamus compared to any other brain region from the GTEx. Also, approximately 25% of the transcripts showed substantial changes in expression across neuronal development and potential co-regulation of biological processes that mirror neuronal development in vivo. These developmentally expressed genes were significantly enriched for genes in proximity to BMI-associated variants. We confirmed the utility of this in vitro human model for studying the development of key hypothalamic neurones involved in energy balance and show that genes at

  16. A network biology approach to understanding the importance of chameleon proteins in human physiology and pathology.

    PubMed

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Marashi, Sayed-Amir

    2017-02-01

    Chameleon proteins are proteins which include sequences that can adopt α-helix-β-strand (HE-chameleon) or α-helix-coil (HC-chameleon) or β-strand-coil (CE-chameleon) structures to operate their crucial biological functions. In this study, using a network-based approach, we examined the chameleon proteins to give a better knowledge on these proteins. We focused on proteins with identical chameleon sequences with more than or equal to seven residues long in different PDB entries, which adopt HE-chameleon, HC-chameleon, and CE-chameleon structures in the same protein. One hundred and ninety-one human chameleon proteins were identified via our in-house program. Then, protein-protein interaction (PPI) networks, Gene ontology (GO) enrichment, disease network, and pathway enrichment analyses were performed for our derived data set. We discovered that there are chameleon sequences which reside in protein-protein interaction regions between two proteins critical for their dual function. Analysis of the PPI networks for chameleon proteins introduced five hub proteins, namely TP53, EGFR, HSP90AA1, PPARA, and HIF1A, which were presented in four PPI clusters. The outcomes demonstrate that the chameleon regions are in critical domains of these proteins and are important in the development and treatment of human cancers. The present report is the first network-based functional study of chameleon proteins using computational approaches and might provide a new perspective for understanding the mechanisms of diseases helping us in developing new medical therapies along with discovering new proteins with chameleon properties which are highly important in cancer.

  17. New Paradigm for Understanding In-Flight Decision Making Errors: a Neurophysiological Model Leveraging Human Factors

    PubMed Central

    Souvestre, P A; Landrock, C K; Blaber, A P

    2008-01-01

    Human factors centered aviation accident analyses report that skill based errors are known to be cause of 80% of all accidents, decision making related errors 30% and perceptual errors 6%1. In-flight decision making error is a long time recognized major avenue leading to incidents and accidents. Through the past three decades, tremendous and costly efforts have been developed to attempt to clarify causation, roles and responsibility as well as to elaborate various preventative and curative countermeasures blending state of the art biomedical, technological advances and psychophysiological training strategies. In-flight related statistics have not been shown significantly changed and a significant number of issues remain not yet resolved. Fine Postural System and its corollary, Postural Deficiency Syndrome (PDS), both defined in the 1980's, are respectively neurophysiological and medical diagnostic models that reflect central neural sensory-motor and cognitive controls regulatory status. They are successfully used in complex neurotraumatology and related rehabilitation for over two decades. Analysis of clinical data taken over a ten-year period from acute and chronic post-traumatic PDS patients shows a strong correlation between symptoms commonly exhibited before, along side, or even after error, and sensory-motor or PDS related symptoms. Examples are given on how PDS related central sensory-motor control dysfunction can be correctly identified and monitored via a neurophysiological ocular-vestibular-postural monitoring system. The data presented provides strong evidence that a specific biomedical assessment methodology can lead to a better understanding of in-flight adaptive neurophysiological, cognitive and perceptual dysfunctional status that could induce in flight-errors. How relevant human factors can be identified and leveraged to maintain optimal performance will be addressed. PMID:19048097

  18. From 'human being' to 'social subject': "unfreezing" ergonomics and the implications for understanding and intervening health-disease process.

    PubMed

    Morales, Karen Lange; García-Acosta, Gabriel

    2012-01-01

    Ergonomics has been successful in increasing productivity and comfort in the work arena. It has also contributed to reducing occupational accidents. Despite this, ergonomics is frequently limited to understanding the health-disease process related to human-technology interactions, as this process is more complex than what can be understood from an ergonomic evaluation. Recognising this limit, this work ontologically and epistemologically contrasts the notions of 'human being' and 'social subject', and concludes that the study object of ergonomics, or human-technology interaction, greatly depends on social aspects that nowadays are not tackled explicitly: route (history), project, structure, agency, motivations and power. It also analyses how participatory ergonomics tacitly includes many of these aspects, including some implications that the change of notion, from 'human being' to 'social subject', brings to the understanding of the health-disease process and the reduction of associated risks during human activities.

  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 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.

  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. Parent-offspring conflict theory: an evolutionary framework for understanding conflict within human families.

    PubMed

    Schlomer, Gabriel L; Del Giudice, Marco; Ellis, Bruce J

    2011-07-01

    Decades of research demonstrate that conflict shapes and permeates a broad range of family processes. In the current article, we argue that greater insight, integration of knowledge, and empirical achievement in the study of family conflict can be realized by utilizing a powerful theory from evolutionary biology that is barely known within psychology: parent-offspring conflict theory (POCT). In the current article, we articulate POCT for psychological scientists, extend its scope by connecting it to the broader framework of life history theory, and draw out its implications for understanding conflict within human families. We specifically apply POCT to 2 instances of early mother-offspring interaction (prenatal conflict and weaning conflict); discuss the effects of genetic relatedness on behavioral conflict between parents, children, and their siblings; review the emerging literature on parent-offspring conflict over the choice of mates and spouses; and examine parent-offspring conflict from the perspective of imprinted genes. This review demonstrates the utility of POCT, not only for explaining what is known about conflict within families but also for generating novel hypotheses, suggesting new lines of research, and moving us toward the "big picture" by integrating across biological and psychological domains of knowledge.

  3. 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

  4. 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.

  5. Increasing our understanding of human cognition through the study of Fragile X Syndrome.

    PubMed

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

    2014-02-01

    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.

  6. Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis.

    PubMed

    Liu, Qun; Kriksunov, Irina A; Graeff, Richard; Munshi, Cyrus; Lee, Hon Cheung; Hao, Quan

    2006-10-27

    The enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide adenine dinucleotide (NAD(+)) has been proposed to go through an oxocarbenium ion-like transition state. Because of the instability of the ionic intermediate, there has been no structural report on such a transient reactive species. Human CD38 is an ectoenzyme that can use NAD(+) to synthesize two calcium-mobilizing molecules. By using NAD(+) and a surrogate substrate, NGD(+), we captured and determined crystal structures of the enzyme complexed with an intermediate, a substrate, and a product along the reaction pathway. Our results showed that the intermediate is stabilized by polar interactions with the catalytic residue Glu(226) rather than by a covalent linkage. The polar interactions between Glu(226) and the substrate 2',3'-OH groups are essential for initiating catalysis. Ser(193) was demonstrated to have a regulative role during catalysis and is likely to be involved in intermediate stabilization. In addition, a product inhibition effect by ADP-ribose (through the reorientation of the product) or GDP-ribose (through the formation of a covalently linked GDP-ribose dimer) was observed. These structural data provide insights into the understanding of multiple catalysis and clues for drug design.

  7. FUNCTIONAL UNDERSTANDING OF THE DIVERSE EXON-INTRON STRUCTURES OF HUMAN GPCR GENES

    PubMed Central

    HAMMOND, DOROTHY A.; OLMAN, VICTOR

    2014-01-01

    The GPCR genes have a variety of exon-intron structures even though their proteins are all structurally homologous. We have examined all human GPCR genes with at least two functional protein isoforms, totaling 199, aiming to gain an understanding of what may have contributed to the large diversity of the exon-intron structures of the GPCR genes. The 199 genes have a total of 808 known protein splicing isoforms with experimentally verified functions. Our analysis reveals that 1,301 (80.6%) adjacent exon-exon pairs out of the total of 1,613 in the 199 genes have either exactly one exon skipped or the intron in-between retained in at least one of the 808 protein splicing isoforms. This observation has a statistical significance p-value of 2.051762* e−09, assuming that the observed splicing isoforms are independent of the exon-intron structures. Our interpretation of this observation is that the exon boundaries of the GPCR genes are not randomly determined; instead they may be selected to facilitate specific alternative splicing for functional purposes. PMID:24467758

  8. 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.

  9. Molecular Mechanisms of Midfacial Developmental Defects

    PubMed Central

    Suzuki, Akiko; Sangani, Dhruvee R.; Ansari, Afreen; Iwata, Junichi

    2015-01-01

    The morphogenesis of midfacial processes requires the coordination of a variety of cellular functions of both mesenchymal and epithelial cells to develop complex structures. Any failure or delay in midfacial development as well as any abnormal fusion of the medial and lateral nasal and maxillary prominences will result in developmental defects in the midface with a varying degree of severity, including cleft, hypoplasia, and midline expansion. In spite of the advances in human genome sequencing technology, the causes of nearly 70 percent of all birth defects, which include midfacial development defects, remain unknown. Recent studies in animal models have highlighted the importance of specific signaling cascades and genetic-environmental interactions in the development of the midfacial region. This review will summarize the current understanding of the morphogenetic processes and molecular mechanisms underlying midfacial birth defects based on mouse models with midfacial developmental abnormalities. PMID:26562615

  10. Developmental Dependencies.

    ERIC Educational Resources Information Center

    Hochhauser, Mark

    Researchers have long focused upon the problems of student/adolescent drug use; however, such a limited perspective may actually provide inaccurate information as to the actual nature and extent of total drug use. It may be more appropriate to emphasize a lifespan developmental perspective regarding drug abuse behaviors, insofar as drug use must…

  11. 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.

  12. Cardiac vectors in the healthy human fetus: developmental changes assessed by magnetocardiography and realistic approximations of the volume conductor

    PubMed Central

    Tao, R; Popescu, EA; Drake, WB; Popescu, M

    2014-01-01

    This study sought to characterize the developmental changes of three measures used to describe the morphology of the fetal cardiac vector: QRS peak-amplitude, QRS duration and QRS time-amplitude integral. To achieve this objective, we rely on a recently developed methodology for fetal cardiac vector estimation, using multichannel fetal magnetocardiographic (fMCG) recordings and realistic approximations of the volume conductors obtained from free-hand ultrasound imaging. Fetal magnetocardiographic recordings and 3D ultrasound images were obtained from 23 healthy, uncomplicated pregnancies for a total of 77 recordings performed at gestational ages between 22 weeks and 37 weeks. We report the developmental changes of the cardiac vector parameters with respect to gestational age and estimated fetal weight, as well as their dependence on the estimated ventricular mass derived from cardiac dimensions measured with M-mode ultrasound. The normative values can be used along with the cardiac time intervals reported by previous fMCG studies to assist future clinical studies investigating conditions that affect fetal cardiac function. PMID:23604003

  13. Cardiac vectors in the healthy human fetus: developmental changes assessed by magnetocardiography and realistic approximations of the volume conductor.

    PubMed

    Tao, R; Popescu, E A; Drake, W B; Popescu, M

    2013-05-01

    This study sought to characterize the developmental changes of three measures used to describe the morphology of the fetal cardiac vector: QRS peak-amplitude, QRS duration and QRS time-amplitude integral. To achieve this objective, we rely on a recently developed methodology for fetal cardiac vector estimation, using multichannel fetal magnetocardiographic (fMCG) recordings and realistic approximations of the volume conductors obtained from free-hand ultrasound imaging. fMCG recordings and 3D ultrasound images were obtained from 23 healthy, uncomplicated pregnancies for a total of 77 recordings performed at gestational ages between 22 and 37 weeks. We report the developmental changes of the cardiac vector parameters with respect to gestational age and estimated fetal weight, as well as their dependence on the estimated ventricular mass derived from cardiac dimensions measured with M-mode ultrasound. The normative values can be used along with the cardiac time intervals reported by previous fMCG studies to assist future clinical studies investigating conditions that affect fetal cardiac function.

  14. Developmental Biology and Regenerative Medicine: Addressing the Vexing Problem of Persistent Muscle Atrophy in the Chronically Torn Human Rotator Cuff

    PubMed Central

    Meyer, Gretchen A.

    2016-01-01

    Persistent muscle atrophy in the chronically torn rotator cuff is a significant obstacle for treatment and recovery. Large atrophic changes are predictive of poor surgical and nonsurgical outcomes and frequently fail to resolve even following functional restoration of loading and rehabilitation. New insights into the processes of muscle atrophy and recovery gained through studies in developmental biology combined with the novel tools and strategies emerging in regenerative medicine provide new avenues to combat the vexing problem of muscle atrophy in the rotator cuff. Moving these treatment strategies forward likely will involve the combination of surgery, biologic/cellular agents, and physical interventions, as increasing experimental evidence points to the beneficial interaction between biologic therapies and physiologic stresses. Thus, the physical therapy profession is poised to play a significant role in defining the success of these combinatorial therapies. This perspective article will provide an overview of the developmental biology and regenerative medicine strategies currently under investigation to combat muscle atrophy and how they may integrate into the current and future practice of physical therapy. PMID:26847008

  15. 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

  16. RNA tumor viruses, oncogenes, human cancer and AIDS: On the frontiers of understanding

    SciTech Connect

    Furmanski, P.; Hager, J.C.; Rich, M.A.

    1985-01-01

    This book contains 31 papers divided into six sections. The section headings are: Molecular Genetics of the RNA Tumor Viruses, Endogenous Retrovirus Sequences in Human Cells, Molecular Biology of Human Cancers, HTLV/LAV, T-Cell Leukemia and AIDS, Experimental Model Systems for the Study of Human Neoplasia and Related Diseases, and Perspectives.

  17. Understanding Historical Human Migration Patterns and Interbreeding (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

    ScienceCinema

    Willerslev, Eske [University of Copenhagen

    2016-07-12

    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.

  18. 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.

  19. An eye-tracking investigation of developmental changes in infants’ exploration of upright and inverted human faces

    PubMed Central

    Oakes, Lisa M.; Ellis, Ann E.

    2011-01-01

    We used eye-tracking to examine 4.5- to 12.5-month-old infants’ (N = 92) eye-movements during 3-s presentations of upright and inverted faces. Scanning of inverted faces was statistically indistinguishable at 4.5, 6.5, 8, and 12.5 months of age; at each of these ages infants disproportionately scanned the region containing the eyes. Scanning of upright faces changed over this age range. When viewing upright faces, 4.5-month-old and 6.5-month-old infants focused disproportionately on the region containing the eyes, whereas 12.5-month-old and 8-month-old infants distributed looking more broadly, scanning more of the internal area of the faces. These results are consistent with other observed developmental differences in face processing, and provide insight into how moment-to-moment face processing changes during infancy. PMID:23525142

  20. Social status, glucocorticoids, immune function, and health: can animal studies help us understand human socioeconomic-status-related health disparities?

    PubMed

    Cavigelli, Sonia A; Chaudhry, Hashim S

    2012-08-01

    For humans in developed nations, socioeconomic status (SES)--relative income, education and occupational position in a society--is a strong predictor of morbidity and mortality rates, with increasing SES predicting longer life span (e.g. Marmot et al., 1991). Mechanisms underlying this relationship have been examined, but the relative role of each mechanism still remains unknown. By understanding the relative role of specific mechanisms that underlie dramatic health disparities between high and low social status individuals we can begin to identify effective, targeted methods to alleviate health disparities. In the current paper, we take advantage of a growing number of animal studies that have quantified biological health-related correlates (glucocorticoid production and immune function) of social status and compare these studies to the current literature on human SES and health to determine if and how animal studies can further our understanding of SES-associated human health disparities. Specifically, we compared social-status related glucocorticoid production and immune function in humans and animals. From the review, we show that our present understanding of the relationships between social status and glucocorticoid production/immune function is still growing, but that there are already identifiable parallels (and non-parallels) between humans and animals. We propose timely areas of future study focused on (1) specific aspects of social status that may influence stress-related physiology, (2) mechanisms underlying long-term influences of social status on physiology and health, and (3) intervention studies to alleviate potentially negative physiological correlates of social status.

  1. The Blue LED Nobel Prize: Historical context, current scientific understanding, human benefit

    SciTech Connect

    Tsao, Jeffrey Y.; Han, Jung; Haitz, Roland H.; Pattison, P. Morgan

    2015-06-19

    Here, the paths that connect scientific understanding with tools and technology are rarely linear. Sometimes scientific understanding leads and enables, sometimes tools and technologies lead and enable. But by feeding on each other, they create virtuous spirals of forward and backward innovation.

  2. The ticking clock of Cayo Santiago macaques and its implications for understanding human circadian rhythm disorders.

    PubMed

    Zhdanova, Irina V; Rogers, Jeffrey; González-Martínez, 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.

  3. Developmental imaging: the avian embryo hatches to the challenge.

    PubMed

    Kulesa, Paul M; McKinney, Mary C; McLennan, Rebecca

    2013-06-01

    The avian embryo provides a multifaceted model to study developmental mechanisms because of its accessibility to microsurgery, fluorescence cell labeling, in vivo imaging, and molecular manipulation. Early two-dimensional planar growth of the avian embryo mimics human development and provides unique access to complex cell migration patterns using light microscopy. Later developmental events continue to permit access to both light and other imaging modalities, making the avian embryo an excellent model for developmental imaging. For example, significant insights into cell and tissue behaviors within the primitive streak, craniofacial region, and cardiovascular and peripheral nervous systems have come from avian embryo studies. In this review, we provide an update to recent advances in embryo and tissue slice culture and imaging, fluorescence cell labeling, and gene profiling. We focus on how technical advances in the chick and quail provide a clearer understanding of how embryonic cell dynamics are beautifully choreographed in space and time to sculpt cells into functioning structures. We summarize how these technical advances help us to better understand basic developmental mechanisms that may lead to clinical research into human birth defects and tissue repair.

  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.

  5. 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.

  6. Understanding risk perceptions to enhance communication about human-wildlife interactions and the impacts of zoonotic disease.

    PubMed

    Decker, Daniel J; Evensen, Darrick T N; Siemer, William F; Leong, Kirsten M; Riley, Shawn J; Wild, Margaret A; Castle, Kevin T; Higgins, Charles L

    2010-01-01

    Inclusion of wildlife in the concept of One Health is important for two primary reasons: (1) the physical health of humans, domesticated animals, and wildlife is linked inextricably through shared diseases, and (2) humans' emotional well-being can be affected by their perceptions of animal health. Although an explicit premise of the One Health Initiative is that healthy wildlife contribute to human health, and vice versa, the initiative also suggests implicitly that wildlife may pose threats to human health through zoonotic disease transmission. As people learn more about One Health, an important question surfaces: How will they react to communications carrying the message that human health and wildlife health are linked? In the absence of adequate relevant research data, we recommend caution in the production and dissemination of One Health messages because of possible unintended or collateral effects. Understanding how and why individuals perceive risks related to wildlife diseases is essential for determining message content that promotes public support for healthy wildlife populations, on the one hand, and, on the other, for identifying messages that might inadvertently increase concern about human health effects of diseased wildlife. To that end, we review risk perception research and summarize the few empirical studies that exist on perceived risk associated with zoonoses. We conclude with some research questions that need answering to help One Health practitioners better understand how the public will interpret their messages and thus how to communicate positively and without negative collateral consequences for wildlife conservation.

  7. 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.

  8. Pluripotent stem cells reveal the developmental biology of human megakaryocytes and provide a source of platelets for clinical application.

    PubMed

    Takayama, Naoya; Eto, Koji

    2012-10-01

    Human pluripotent stem cells [PSCs; including human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)] can infinitely proliferate in vitro and are easily accessible for gene manipulation. Megakaryocytes (MKs) and platelets can be created from human ESCs and iPSCs in vitro and represent a potential source of blood cells for transfusion and a promising tool for studying the human thrombopoiesis. Moreover, disease-specific iPSCs are a powerful tool for elucidating the pathogenesis of hematological diseases and for drug screening. In that context, we and other groups have developed in vitro MK and platelet differentiation systems from human pluripotent stem cells (PSCs). Combining this co-culture system with a drug-inducible gene expression system enabled us to clarify the novel role played by c-MYC during human thrombopoiesis. In the next decade, technical advances (e.g., high-throughput genomic sequencing) will likely enable the identification of numerous gene mutations associated with abnormal thrombopoiesis. Combined with such technology, an in vitro system for differentiating human PSCs into MKs and platelets could provide a novel platform for studying human gene function associated with thrombopoiesis.

  9. 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…

  10. 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…

  11. 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…

  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. 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

  14. 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

  15. Towards an understanding of the link between environmental emissions and human body burdens of PCBs using CoZMoMAN.

    PubMed

    Breivik, Knut; Czub, Gertje; McLachlan, Michael S; Wania, Frank

    2010-01-01

    Different factors affect how organic contaminants released into the environment over time distribute and accumulate, enter various food-chains, and potentially cause toxic effects in wildlife and humans. A sound chemical risk assessment thus requires the determination of the quantitative relationship between emissions and human exposure. This study aimed to assess the extent of the quantitative and mechanistic understanding of the link between environmental emissions and human body burdens for polychlorinated biphenyls (PCBs) in the western part of the Baltic Sea drainage basin and to identify any remaining knowledge gaps. An integrated, non-steady state model calculating human body burden from environmental emissions (CoZMoMAN) was created by linking the multi-compartment environmental fate model CoZMo-POP 2 with the human food chain bioaccumulation model ACC-HUMAN. CoZMoMAN predicted concentrations of seven PCB congeners in 11 key model compartments to typically within a factor of 2 to 4 of measured values, although larger discrepancies are noted for soils and humans. We conclude that whereas the most important processes which link emissions of PCBs to human body burdens are quite well understood in this region, some critical knowledge gaps related to the time trend of historical emissions remain to be addressed.

  16. 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…

  17. IDM Supervision: An Integrated Developmental Model for Supervising Counselors and Therapists.

    ERIC Educational Resources Information Center

    Stoltenberg, Cal D.; McNeill, Brian; Delworth, Ursula

    Understanding change over time in one's ability to function as a professional is fundamental in the practice of clinical supervision. Drawing on developmental models of human behavior, a model of the development over time of therapy practice is presented. Specific domains of clinical practice and overriding structures that provide markers in…

  18. 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

  19. 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.

  20. Developmental dyscalculia.

    PubMed

    Price, Gavin R; Ansari, Daniel

    2013-01-01

    Developmental dyscalculia (DD) is a learning disorder affecting the acquisition of school level arithmetic skills present in approximately 3-6% of the population. At the behavioral level DD is characterized by poor retrieval of arithmetic facts from memory, the use of immature calculation procedures and counting strategies, and the atypical representation and processing of numerical magnitude. At the neural level emerging evidence suggests DD is associated with atypical structure and function in brain regions associated with the representation of numerical magnitude. The current state of knowledge points to a core deficit in numerical magnitude representation in DD, but further work is required to elucidate causal mechanisms underlying the disorder.

  1. 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

  2. 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

  3. 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

  4. The role of metagenomics in understanding the human microbiome in health and disease.

    PubMed

    Martín, Rebeca; Miquel, Sylvie; Langella, Philippe; Bermúdez-Humarán, Luis G

    2014-04-01

    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.

  5. 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

  6. 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

  7. Epithelial and stromal developmental patterns in a novel substitute of the human skin generated with fibrin-agarose biomaterials.

    PubMed

    Carriel, Víctor; Garzón, Ingrid; Jiménez, Jose-María; Oliveira, Ana-Celeste-Ximenes; Arias-Santiago, Salvador; Campos, Antonio; Sánchez-Quevedo, Maria-Carmen; Alaminos, Miguel

    2012-01-01

    Development of human skin substitutes by tissue engineering may offer new therapeutic alternatives to the use of autologous tissue grafts. For that reason, it is necessary to investigate and develop new biocompatible biomaterials that support the generation of a proper human skin construct. In this study, we generated a novel model of bioengineered human skin substitute using human cells obtained from skin biopsies and fibrin-agarose biomaterials and we evaluated this model both at the ex vivo and the in vivo levels. Once the dermal fibroblasts and the epithelial keratinocytes were isolated and expanded in culture, we used fibrin-agarose scaffolds for the development of a full-thickness human skin construct, which was evaluated after 1, 2, 3 and 4 weeks of development ex vivo. The skin substitutes were then grafted onto immune-deficient nude mice and analyzed at days 10, 20, 30 and 40 postimplantation using transmission electron microscopy, histochemistry and immunofluorescence. The results demonstrated that the fibrin-agarose artificial skin had adequate biocompatibility and proper biomechanical properties. A proper development of both the bioengineered dermis and epidermis was found after 30 days in vivo, although the tissues kept ex vivo and those implanted in the animal model for 10 or 20 days showed lower levels of differentiation. In summary, our model of fibrin-agarose skin equivalent was able to reproduce the structure and histological architecture of the native human skin, especially after long-term in vivo implantation, suggesting that these tissues could reproduce the native skin.

  8. 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.

  9. 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

  10. Developmental Biology: We Are All Walking Mutants.

    PubMed

    Trainor, Paul A

    2016-01-01

    What is Developmental Biology? Developmental Biology is a discipline that evolved from the collective fields of embryology, morphology, and anatomy, which firmly established that structure underpins function. In its simplest terms, Developmental Biology has come to describe how a single cell becomes a completely formed organism. However, this definition of Developmental Biology is too narrow. Developmental Biology describes the properties of individual cells; their organization into tissues, organs, and organisms; their homeostasis, regeneration, aging, and ultimately death. Developmental Biology provides a context for cellular reprogramming, stem cell biology, regeneration, tissue engineering, evolutionary development and ecology, and involves the reiterated use of the same cellular mechanisms and signaling pathways throughout the lifespan of an organism. Using neural crest cells as an example, this review explores the contribution of Developmental Biology to our understanding of development, evolution, and disease.

  11. 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…

  12. Genetically-modified human pluripotent stem cells: new hopes for the understanding and the treatment of neurological diseases?

    PubMed

    Nedelec, Stéphane; Onteniente, Brigitte; Peschanski, Marc; Martinat, Cécile

    2013-04-01

    The fundamental inaccessibility of the human neural cell types affected by neurological disorders prevents their isolation for in vitro studies of disease mechanisms or for drug screening efforts. Pluripotent stem cells represent a new interesting way to generate models of human neurological disorders, explore the physiopathological mechanisms and develop new therapeutic strategies. Disease-specific human embryonic stem cells were the first source of material to be used to study certain disease states. The recent demonstration that human somatic cells, such as fibroblasts or blood cells, can be genetically converted to induced pluripotent stem cells (hiPSCs) together with the continuous improvement of methods to differentiate these cells into disease-affected neuronal subtypes opens new perspectives to model and understand a large number of human pathologies. This review focuses on the opportunities concerning the use disease-specific human pluripotent stem cells as well as the different challenges that still need to be overcome. We also discuss the recent improvements in the genetic manipulation of human pluripotent stem cells and the consequences of these on disease modeling and drug screening for neurological diseases.

  13. 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

  14. Man Bites Mosquito: Understanding the Contribution of Human Movement to Vector-Borne Disease Dynamics

    PubMed Central

    Adams, Ben; Kapan, Durrell D.

    2009-01-01

    In metropolitan areas people travel frequently and extensively but often in highly structured commuting patterns. We investigate the role of this type of human movement in the epidemiology of vector-borne pathogens such as dengue. Analysis is based on a metapopulation model where mobile humans connect static mosquito subpopulations. We find that, due to frequency dependent biting, infection incidence in the human and mosquito populations is almost independent of the duration of contact. If the mosquito population is not uniformly distributed between patches the transmission potential of the pathogen at the metapopulation level, as summarized by the basic reproductive number, is determined by the size of the largest subpopulation and reduced by stronger connectivity. Global extinction of the pathogen is less likely when increased human movement enhances the rescue effect but, in contrast to classical theory, it is not minimized at an intermediate level of connectivity. We conclude that hubs and reservoirs of infection can be places people visit frequently but briefly and the relative importance of human and mosquito populations in maintaining the pathogen depends on the distribution of the mosquito population and the variability in human travel patterns. These results offer an insight in to the paradoxical observation of resurgent urban vector-borne disease despite increased investment in vector control and suggest that successful public health intervention may require a dual approach. Prospective studies can be used to identify areas with large mosquito populations that are also visited by a large fraction of the human population. Retrospective studies can be used to map recent movements of infected people, pinpointing the mosquito subpopulation from which they acquired the infection and others to which they may have transmitted it. PMID:19707544

  15. 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

  16. Terrain Analysis for Human-Robot Interaction (TAH-RI): Enabling Terrain Understanding to Improve Tactical Behavior

    DTIC Science & Technology

    2005-04-01

    Contractor Report 2005-04 Terrain Analysis for Human-Robot Interaction (TAH-RI): Enabling Terrain Understanding to Improve Tactical Behavior Jim...Hicinbothom, Dawn Riddle, Ken Graves CHI Systems, Inc. Robin Murphy University of South Florida This report is published to meet legal and contractual...for the Behavioral and Social Sciences Approved for public release; distribution is unlimited REPORT DOCUMENTATION PAGE 1. REPORT DATE (dd-mm-yy) 2

  17. From Mice to Men: research models of developmental programming.

    PubMed

    Rabadán-Diehl, C; Nathanielsz, P

    2013-02-01

    Developmental programming can be defined as a response to a specific challenge to the mammalian organism during a critical developmental time window that alters the trajectory of development with persistent effects on offspring phenotype and predisposition to future illness. We focus on the need for studies in relevant, well-characterized animal models in the context of recent research discoveries on the challenges, mechanisms and outcomes of developmental programming. We discuss commonalities and differences in general principles of developmental programming as they apply to several species, including humans. The consequences of these differences are discussed. Obesity, metabolic disorders and cardiovascular diseases are associated with the highest percentage of morbidity and mortality worldwide. Although many of the causes are associated with lifestyle, high-energy diets and lack of physical activity, recent evidence has linked developmental programming to the epidemic of metabolic diseases. A better understanding of comparative systems physiology of mother, fetus and neonate using information provided by rapid advances in molecular biology has the potential to improve the lifetime health of future generations by providing better women's health, diagnostic tools and preventative and therapeutic interventions in individuals exposed during their development to programming influences.

  18. 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.

  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. Cognitive neuroscience in forensic science: understanding and utilizing the human element.

    PubMed

    Dror, Itiel E

    2015-08-05

    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.

  1. [Developmental dyslexia].

    PubMed

    Galaburda, A M; Cestnick, L

    2003-02-01

    Developmental dyslexia makes up an important proportion of the known learning disorders. Until the late 1970s most research on dyslexia was carried out by educators and educational psychologists, but soon after the publication of some dyslexic cases with focal disorders of neuronal migration to the cerebral cortex, interest in the neurobiological and neurocognitive underpinnings of dyslexia grew, especially in Europe and North America. There are at least two types of developmental dyslexia--phonological and surface. Surface dyslexia refers to a disorder in which the difficulty lies in reading irregular words, whereas phonological dyslexia is characterized by difficulty with pseudowords. Phonological dyslexia is the more common of the two types. Surface dyslexia does not present a major problem in a language such as Spanish, where the number of irregular words is indeed very small. Still, in languages such as English, where irregular words are common, the phonological type of developmental dyslexia is much more common. Phonologic dyslexics have problems with phonological awareness, that is, the conscious knowledge and manipulation of speech sounds, which is the most proximate explanation for their difficulty in reading pseudowords. Many, but not all, phonologic dyslexics also have problems processing rapidly changing sounds, even if not linguistic, and some slow sounds, too. The same group tends to have visual problems, especially involving the so-called magnocellular pathway of the visual system, which, among others, has the role of analyzing movement. Accompanying these perceptual and cognitive deficits, phonologic dyslexics also show abnormal brain activation to phonological tasks, as shown in functional magnetic resonance studies (figure). In addition, dyslexic brains show focal malformations, ectopias and microgyria, of the cerebral cortex, involving mainly the left perisylvian region and the word form area in the temporo-occipital junction. There are also

  2. Developmental regulation of the adhesive and enzymatic activity of vascular adhesion protein-1 (VAP-1) in humans.

    PubMed

    Salmi, Marko; Jalkanen, Sirpa

    2006-09-01

    Vascular adhesion protein-1 (VAP-1) is a homodimeric glycoprotein that belongs to a unique subgroup of cell-surface-expressed oxidases. In adults, endothelial VAP-1 supports leukocyte rolling, firm adhesion, and transmigration in both enzyme activity-dependent and enzyme activity-independent manner. Here we studied the induction and function of VAP-1 during human ontogeny. We show that VAP-1 is already found in the smooth muscle at embryonic week 7. There are marked time-dependent switches in VAP-1 expression in the sinusoids of the liver, in the peritubular capillaries of the kidney, in the capillaries of the heart, and in the venules in the lamina propria of the gut. Fetal VAP-1 is dimerized, and it is enzymatically active. VAP-1 in fetal-type venules is able to bind cord blood lymphocytes. Also, adenovirally transfected VAP-1 on human umbilical vein endothelial cells is involved in rolling and firm adhesion of cord blood lymphocytes under conditions of physiologic shear stress. We conclude that VAP-1 is synthesized from early on in human vessels and it is functionally intact already before birth. Thus, VAP-1 may contribute critically to the oxidase activities in utero, and prove important for lymphocyte trafficking during human ontogeny.

  3. 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...

  4. 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,…

  5. 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,…

  6. 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...

  7. 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…

  8. 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…

  9. 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…

  10. 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

  11. 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…

  12. 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…

  13. 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...

  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. Can Human Pluripotent Stem Cell-Derived Cardiomyocytes Advance Understanding of Muscular Dystrophies?

    PubMed

    Kalra, Spandan; Montanaro, Federica; Denning, Chris

    2016-08-30

    Muscular dystrophies (MDs) are clinically and molecularly a highly heterogeneous group of single-gene disorders that primarily affect striated muscles. Cardiac disease is present in several MDs where it is an important contributor to morbidity and mortality. Careful monitoring of cardiac issues is necessary but current management of cardiac involvement does not effectively protect from disease progression and cardiac failure. There is a critical need to gain new knowledge on the diverse molecular underpinnings of cardiac disease in MDs in order to guide cardiac treatment development and assist in reaching a clearer consensus on cardiac disease management in the clinic. Animal models are available for the majority of MDs and have been invaluable tools in probing disease mechanisms and in pre-clinical screens. However, there are recognized genetic, physiological, and structural differences between human and animal hearts that impact disease progression, manifestation, and response to pharmacological interventions. Therefore, there is a need to develop parallel human systems to model cardiac disease in MDs. This review discusses the current status of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC) to model cardiac disease, with a focus on Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM1). We seek to provide a balanced view of opportunities and limitations offered by this system in elucidating disease mechanisms pertinent to human cardiac physiology and as a platform for treatment development or refinement.

  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. Can Human Pluripotent Stem Cell-Derived Cardiomyocytes Advance Understanding of Muscular Dystrophies?

    PubMed Central

    Kalra, Spandan; Montanaro, Federica; Denning, Chris

    2016-01-01

    Muscular dystrophies (MDs) are clinically and molecularly a highly heterogeneous group of single-gene disorders that primarily affect striated muscles. Cardiac disease is present in several MDs where it is an important contributor to morbidity and mortality. Careful monitoring of cardiac issues is necessary but current management of cardiac involvement does not effectively protect from disease progression and cardiac failure. There is a critical need to gain new knowledge on the diverse molecular underpinnings of cardiac disease in MDs in order to guide cardiac treatment development and assist in reaching a clearer consensus on cardiac disease management in the clinic. Animal models are available for the majority of MDs and have been invaluable tools in probing disease mechanisms and in pre-clinical screens. However, there are recognized genetic, physiological, and structural differences between human and animal hearts that impact disease progression, manifestation, and response to pharmacological interventions. Therefore, there is a need to develop parallel human systems to model cardiac disease in MDs. This review discusses the current status of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC) to model cardiac disease, with a focus on Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM1). We seek to provide a balanced view of opportunities and limitations offered by this system in elucidating disease mechanisms pertinent to human cardiac physiology and as a platform for treatment development or refinement. PMID:27854224

  18. 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…

  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. 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