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

    PubMed Central

    Epstein, C J

    1995-01-01

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

  3. 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…

  4. Understanding Allyhood as a Developmental Process

    ERIC Educational Resources Information Center

    Waters, Rhian

    2010-01-01

    Understanding allyhood as a developmental process will allow educators and program directors to reach a broader number of students with more powerful outcomes in line with student learning and development goals. Designing programs that promote ally development as a component of social justice education will allow programs to tailor ally…

  5. NEW FRONTIER IN UNDERSTANDING THE MECHANISMS OF DEVELOPMENTAL ABNORMALITIES

    EPA Science Inventory

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

  6. Many human accelerated regions are developmental enhancers

    PubMed Central

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

    2013-01-01

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

  7. Piaget and Normalization: Developmental Humanism

    ERIC Educational Resources Information Center

    Grunewald, Karl; And Others

    1977-01-01

    The technology of behaviorism and the social consciousness of normalization have produced monumental changes for developmentally handicapped children but lack an intrinsic developmental perspective. Piaget's cognitive-developmental theory is proposed as a framework to provide content, direction and structure for educational and habilitative…

  8. 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)…

  9. How Neuropsychology Informs Our Understanding of Developmental Disorders

    ERIC Educational Resources Information Center

    Pennington, Bruce F.

    2009-01-01

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


  10. DEVELOPMENTAL IMMUNOTOXICITY AND HUMAN DEVELOPMENT

    EPA Science Inventory

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

  11. Understanding human DNA sequence variation.

    PubMed

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

    2004-01-01

    Over the past century researchers have identified normal genetic variation and studied that variation in diverse human populations to determine the amounts and distributions of that variation. That information is being used to develop an understanding of the demographic histories of the different populations and the species as a whole, among other studies. With the advent of DNA-based markers in the last quarter century, these studies have accelerated. One of the challenges for the next century is to understand that variation. One component of that understanding will be population genetics. We present here examples of many of the ways these new data can be analyzed from a population perspective using results from our laboratory on multiple individual DNA-based polymorphisms, many clustered in haplotypes, studied in multiple populations representing all major geographic regions of the world. These data support an "out of Africa" hypothesis for human dispersal around the world and begin to refine the understanding of population structures and genetic relationships. We are also developing baseline information against which we can compare findings at different loci to aid in the identification of loci subject, now and in the past, to selection (directional or balancing). We do not yet have a comprehensive understanding of the extensive variation in the human genome, but some of that understanding is coming from population genetics. PMID:15388768

  12. BRAF gene: From human cancers to developmental syndromes.

    PubMed

    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

    2015-07-01

    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

  13. Developmental and Individual Differences in Understanding of Fractions

    PubMed Central

    Siegler, Robert S.; Pyke, Aryn A.

    2014-01-01

    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 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 two grades, whereas higher achieving children showed much greater knowledge in 8th than 6th grade, despite both groups having been in the same classrooms, using the same textbooks, and having the same teachers and classmates. Individual differences in both fraction arithmetic and mathematics achievement test scores were predicted by differences in fraction magnitude knowledge and whole number division, even after the contributions of reading achievement and executive functioning were statistically controlled. Instructional implications of the findings are discussed. PMID:23244401

  14. 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

  15. Understanding Human Mobility from Twitter.

    PubMed

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Franchini, LucĂ­a F; Pollard, Katherine S

    2015-09-15

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

  18. Evolutionary and developmental understanding of the spinal accessory nerve.

    PubMed

    Tada, Motoki N; Kuratani, Shigeru

    2015-01-01

    The vertebrate spinal accessory nerve (SAN) innervates the cucullaris muscle, the major muscle of the neck, and is recognized as a synapomorphy that defines living jawed vertebrates. Morphologically, the cucullaris muscle exists between the branchiomeric series of muscles innervated by special visceral efferent neurons and the rostral somitic muscles innervated by general somatic efferent neurons. The category to which the SAN belongs to both developmentally and evolutionarily has long been controversial. To clarify this, we assessed the innervation and cytoarchitecture of the spinal nerve plexus in the lamprey and reviewed studies of SAN in various species of vertebrates and their embryos. We then reconstructed an evolutionary sequence in which phylogenetic changes in developmental neuronal patterning led towards the gnathostome-specific SAN. We hypothesize that the SAN arose as part of a lamprey-like spinal nerve plexus that innervates the cyclostome-type infraoptic muscle, a candidate cucullaris precursor. PMID:26605049

  19. 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,…

  20. 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


  1. 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…

  2. 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 forgetting. States of mind contributing to error are thus extremely difficult to manage; they can happen to the best of people at any time. (7) People do not act in isolation. Their behaviour is shaped by circumstances. The same is true for errors and violations. The likelihood of an unsafe act being committed is heavily influenced by the nature of the task and by the local workplace conditions. These, in turn, are the product of "upstream" organisational factors. Great gains in safety can ve achieved through relatively small modifications of equipment and workplaces. (8) Automation and increasing advanced equipment do not cure human factors problems, they merely relocate them. In contrast, training people to work effectively in teams costs little, but has achieved significant enhancements of human performance in aviation. (9) Effective risk management depends critically on a confidential and preferable anonymous incident monitoring system that records the individual, task, situational, and organisational factors associated with incidents and near misses. (10) Effective risk management means the simultaneous and targeted deployment of limited remedial resources at different levels of the system: the individual or team, the task, the situation, and the organisation as a whole. PMID:10151618

  3. Understanding adverse events: human factors.

    PubMed

    Reason, J

    1995-06-01

    (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 forgetting. States of mind contributing to error are thus extremely difficult to manage; they can happen to the best of people at any time. (7) People do not act in isolation. Their behaviour is shaped by circumstances. The same is true for errors and violations. The likelihood of an unsafe act being committed is heavily influenced by the nature of the task and by the local workplace conditions. These, in turn, are the product of "upstream" organisational factors. Great gains in safety can ve achieved through relatively small modifications of equipment and workplaces. (8) Automation and increasing advanced equipment do not cure human factors problems, they merely relocate them. In contrast, training people to work effectively in teams costs little, but has achieved significant enhancements of human performance in aviation. (9) Effective risk management depends critically on a confidential and preferable anonymous incident monitoring system that records the individual, task, situational, and organisational factors associated with incidents and near misses. (10) Effective risk management means the simultaneous and targeted deployment of limited remedial resources at different levels of the system: the individual or team, the task, the situation, and the organisation as a whole. PMID:10151618

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

    PubMed

    Levy, Joshua; Finnegan, Paul

    2016-02-01

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

  5. Deafness and Human Sexuality: A Developmental Review.

    ERIC Educational Resources Information Center

    Shaul, Susan

    1981-01-01

    The literature on the psychosocial development of deaf children is reviewed as it pertains to human sexuality. It appears that many deaf children, while in need of sexual information and opportunities for affective development, are generally exposed to neither. (Author)

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

    PubMed Central

    Zhu, Zengrong; Huangfu, Danwei

    2013-01-01

    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. PMID:23362344

  7. Understanding Latino Children and Adolescents in the Mainstream: Placing Culture at the Center of Developmental Models

    ERIC Educational Resources Information Center

    Raffaelli, Marcela; Carlo, Gustavo; Carranza, Miguel A.; Gonzalez-Kruger, Gloria E.

    2005-01-01

    Demographic shifts in the U.S. population require developmental researchers to increase their attention to cultural diversity. Conceptual models that incorporate culturally relevant variables and focus on normative and positive development are needed to produce a more balanced understanding of Latino youth development. (Contains 1 table and 1…

  8. 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…

  9. 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…

  10. Understanding Developmental Coordination Disorder and Its Impact on Families: The Contribution of Single Case Studies

    ERIC Educational Resources Information Center

    Peters, Judith M.; Henderson, Sheila E.

    2008-01-01

    The aim of this study was to employ the single case study approach to address unresolved issues in our understanding of Developmental Coordination Disorder. From a large cohort of clinically referred UK primary school children, six boys and one girl were selected to participate. The experiences of each child as he/she journeyed through the process…

  11. 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…

  12. 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 asked, students…

  13. 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…

  14. The EvoDevoCI: A Concept Inventory for Gauging Students’ Understanding of Evolutionary Developmental Biology

    PubMed Central

    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. PMID:24297293

  15. 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

  16. Developmental covariation of human vault and base throughout postnatal ontogeny.

    PubMed

    Barbeito-Andrés, Jimena; Ventrice, Fernando; Anzelmo, Marisol; Pucciarelli, Héctor M; Sardi, Marina L

    2015-01-01

    In the present study, we analyzed postnatal ontogenetic integration among morphological traits of the human neurocranium. Particularly, the covariation between the vault and the base during postnatal life was assessed. Since the association between these regions may depend on the generalized change produced by allometry, we tested its effect on their covariation. On a sample of adults and subadults ranging from 0 to 31 years, 3D coordinates of neurocranial landmarks and semilandmarks were digitized and geometric morphometric technics were applied. Main aspects of shape variation were examined using Principal Components analysis. Covariation between the vault and the base was examined by Partial Least Squares analysis. According to our results, the vault and the base covary strongly during postnatal ontogeny and their relation depends largely on allometry. Two size variables were studied: centroid size, which was obtained from the recorded morphometric points, and endocranial volume, taken as an estimation of brain size. Although growing brain was found to be a developmental process that contributes to covariation among neurocranial traits, there would be other factors that exert their influence during ontogeny. These results lead to reconsider cranial morphological evolution taking into account the developmental constraints given by ontogenetic patterns of integration and reinforcing the idea that in human evolution a suite of relevant characters may be fuelled by few developmental processes. PMID:25458178

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

    PubMed

    Looman, Wendy Sue

    2006-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  19. 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


  20. 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…

  1. 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


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

    ERIC Educational Resources Information Center

    Guiffrida, Douglas A.

    2009-01-01

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

  3. Developmental changes in human cerebral functional organization for word generation.

    PubMed

    Brown, Timothy T; Lugar, Heather M; Coalson, Rebecca S; Miezin, Fran M; Petersen, Steven E; Schlaggar, Bradley L

    2005-03-01

    A fundamental issue in cognitive neuroscience is the nature of developmental changes in human cerebral functional organization for higher cognitive functions. Event-related functional magnetic resonance imaging was used to measure developmental changes in the functional neuroanatomy subserving controlled lexical association. First, brain regions showing significant differences in activity between school-age children and young adults, despite equivalent task performance, were identified. Then, activity in these regions was more fully characterized in individuals spanning the ages of 7-32 years old. Cross-sectional and regression analyses showed systematic increases and decreases in levels of activity over age, by region. Age-related increases in activity were primarily newly recruited, later-stage processing regions, such as in left frontal and left parietal cortex. Decreases, on the other hand, were all positive activations that attenuated with age and were found across a wider neuroanatomical range, including earlier processing regions such as bilateral extrastriate cortex. The hemodynamic magnitude, neuroanatomical location and maturational timecourse of these progressive and regressive changes have implications for models of the developing specialization in human cerebral functional organization. PMID:15297366

  4. Characterization of ticlopidine-induced developmental and teratogenic defects in Xenopus embryos and human endothelial cells.

    PubMed

    Park, Mi Seon; Kim, Jong-Woo; Park, Inji; Lee, Hyun-Kyung; Kim, Chowon; Jo, Changrae; Kim, Yoo-Kyung; Min, Byung-Hwa; Ryoo, Jaewoong; Lee, Dong-Seok; Bae, Jong-Sup; Kim, Sang-Hyun; Ye, Sang Kyu; Park, Mae-Ja; Lee, Hyun-Shik

    2015-10-01

    Ticlopidine is an anti-platelet drug that inhibits platelet aggregation via the functional alteration of platelet membranes. However, the mechanism underlying the adverse developmental effects of ticlopidine has not been clearly demonstrated. In this study, we evaluated the developmental toxicity and teratogenicity of ticlopidine on Xenopus laevis embryos and in human umbilical vein endothelial cells (HUVECs) using a frog embryo teratogenesis assay-Xenopus (FETAX) and blood and lymph vessel formation assays. Ticlopidine induced teratogenicity and inhibited growth, as evidenced by mortality rates and embryo lengths, respectively. Moreover, ticlopidine induced severe hemorrhages and inhibited both blood and lymph vessel formation by modulating the expression of xMsr and Prox1 in Xenopus embryos. Additionally, Nkx2.5 and Cyl104 levels were perturbed by ticlopidine exposure, and more extensive aberrations were observed in the liver and heart using whole-mount in situ hybridization. In addition, ticlopidine reduced branching in HUVECs by blocking the effect of the angiogenic vascular endothelial growth factor (VEGF). Results from this study suggest that ticlopidine is a developmental toxicant and teratogen and therefore this is a step forward in our understanding of the effects of ticlopidine during developmental processes. PMID:26327247

  5. Elementary school-age children's developmental understanding of the causes of cancer.

    PubMed

    Chin, D G; Schonfeld, D J; O'Hare, L L; Mayne, S T; Salovey, P; Showalter, D R; Cicchetti, D V

    1998-12-01

    This study examines children's conceptual understanding and factual knowledge of the causes of cancer. Using a standardized, developmentally based, semistructured interview (ASK [AIDS (acquired immunodeficiency syndrome) Survey for Kids]), 784 children (43% black, 38% white, and 18% Hispanic; 48% female) in kindergarten through sixth grade attending six public elementary/middle schools in New Haven, Connecticut, were asked open-ended questions about the causes of cancer and, for comparison, the causes of colds and AIDS. Responses were scored for level of conceptual understanding and coded for factual content and factual accuracy. The level of conceptual understanding for causality of cancer increased consistently as grade level increased. When comparisons were made among the illnesses, children's level of conceptual understanding was significantly lower for the causes of cancer than for the causes of colds (p < .0001), but not significantly different from that of AIDS. Although the single most frequent cause of cancer mentioned was cigarettes/smoking (24%), more than one in five students stated that casual contact or contagion was a cause of cancer. More children cited causal contact/contagion than cited the following factually accurate or logically contributory causes combined: poor diet, air/water pollution or overexposure to sun, alcohol, and old age. Slightly more than one half of students in kindergarten through sixth grade worried about getting cancer, and the vast majority (80%) knew that cancer could be fatal. Children have a less sophisticated conceptual understanding of cancer than of colds and a very limited factual knowledge base for cancer, and thus they have the capacity to increase both their understanding and knowledge. These results have implications for the creation of developmentally appropriate cancer prevention curricula for elementary school-age children. PMID:9866086

  6. 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 theories perspective), discrete groups could not be formed. Instead, a gradual increase in accuracy and differentiation was observed. Additional support for this perspective was found when the responses of participants who had additional exposure provided responses that were more accurate, differentiated, and sophisticated than those of participants with no additional exposure. Theoretical and educational implications of these findings are discussed.

  7. Developmental gene expression profiles of the human pathogen Schistosoma japonicum

    PubMed Central

    Gobert, Geoffrey N; Moertel, Luke; Brindley, Paul J; McManus, Donald P

    2009-01-01

    Background The schistosome blood flukes are complex trematodes and cause a chronic parasitic disease of significant public health importance worldwide, schistosomiasis. Their life cycle is characterised by distinct parasitic and free-living phases involving mammalian and snail hosts and freshwater. Microarray analysis was used to profile developmental gene expression in the Asian species, Schistosoma japonicum. Total RNAs were isolated from the three distinct environmental phases of the lifecycle – aquatic/snail (eggs, miracidia, sporocysts, cercariae), juvenile (lung schistosomula and paired but pre-egg laying adults) and adult (paired, mature males and egg-producing females, both examined separately). Advanced analyses including ANOVA, principal component analysis, and hierarchal clustering provided a global synopsis of gene expression relationships among the different developmental stages of the schistosome parasite. Results Gene expression profiles were linked to the major environmental settings through which the developmental stages of the fluke have to adapt during the course of its life cycle. Gene ontologies of the differentially expressed genes revealed a wide range of functions and processes. In addition, stage-specific, differentially expressed genes were identified that were involved in numerous biological pathways and functions including calcium signalling, sphingolipid metabolism and parasite defence. Conclusion The findings provide a comprehensive database of gene expression in an important human pathogen, including transcriptional changes in genes involved in evasion of the host immune response, nutrient acquisition, energy production, calcium signalling, sphingolipid metabolism, egg production and tegumental function during development. This resource should help facilitate the identification and prioritization of new anti-schistosome drug and vaccine targets for the control of schistosomiasis. PMID:19320991

  8. Understanding Goals: Teaching the Humanities for Understanding in Middle School.

    ERIC Educational Resources Information Center

    Hetland, Lois

    This paper focuses on the "Understanding Goals" element from the "Teaching for Understanding" framework. The study featured a one-year study program covering colonial America and integrating history, English, anthropology, geography, and the arts. The paper presents: (1) a definition of "Understanding Goals"; (2) a story of how one teacher came to…

  9. Enhancer-adoption as a mechanism of human developmental disease.

    PubMed

    Lettice, Laura A; Daniels, Sarah; Sweeney, Elizabeth; Venkataraman, Shanmugasundaram; Devenney, Paul S; Gautier, Philippe; Morrison, Harris; Fantes, Judy; Hill, Robert E; FitzPatrick, David R

    2011-12-01

    Disruption of the long-range cis-regulation of developmental gene expression is increasingly recognized as a cause of human disease. Here, we report a novel type of long-range cis-regulatory mutation, in which ectopic expression of a gene is driven by an enhancer that is not its own. We have termed this gain of regulatory information as "enhancer adoption." We mapped the breakpoints of a de novo 7q inversion in a child with features of a holoprosencephaly spectrum (HPES) disorder and severe upper limb syndactyly with lower limb synpolydactyly. The HPES plausibly results from the 7q36.3 breakpoint dislocating the sonic hedgehog (SHH) gene from enhancers that are known to drive expression in the early forebrain. However, the limb phenotype cannot be explained by loss of known SHH enhancers. The SHH transcription unit is relocated to 7q22.1, ?190 kb 3' of a highly conserved noncoding element (HCNE2) within an intron of EMID2. We show that HCNE2 functions as a limb bud enhancer in mouse embryos and drives ectopic expression of Shh in vivo recapitulating the limb phenotype in the child. This developmental genetic mechanism may explain a proportion of the novel or unexplained phenotypes associated with balanced chromosome rearrangements. PMID:21948517

  10. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    EPA Science Inventory

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

  14. Genetic approaches to understanding human obesity

    PubMed Central

    Ramachandrappa, Shwetha; Farooqi, I. Sadaf

    2011-01-01

    Obesity and its associated comorbidities represent one of the biggest public health challenges facing the world today. The heritability of body weight is high, and genetic variation plays a major role in determining the interindividual differences in susceptibility or resistance to the obesogenic environment. Here we discuss how genetic studies in humans have contributed to our understanding of the central pathways that govern energy homeostasis. We discuss how the arrival of technological advances such as next-generation sequencing will result in a major acceleration in the pace of gene discovery. The study of patients harboring these genetic variants has informed our understanding of the molecular and physiological pathways involved in energy homeostasis. We anticipate that future studies will provide the framework for the development of a more rational targeted approach to the prevention and treatment of genetically susceptible individuals. PMID:21633175

  15. 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.

  16. 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…

  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. 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. PMID:26293597

  19. Bisphenol A and congenital developmental defects in humans.

    PubMed

    Guida, Maurizio; Troisi, Jacopo; Ciccone, Carla; Granozio, Giovanni; Cosimato, Cosimo; Di Spiezio Sardo, Attilio; Ferrara, Cinzia; Guida, Marco; Nappi, Carmine; Zullo, Fulvio; Di Carlo, Costantino

    2015-04-01

    Over 50% of the causes of fetal malformations in humans are still unknown. Recent evidence suggests the relationship between environmental exposure to endocrine disruptors and fetal malformations. Our study aims to establish the role of Bisphenol A (BPA), if any, in altering human reproduction. We enrolled 151 pregnant women who were divided into two groups: case group (CS, n=101), women with established diagnosis of developmental defect, and control group (CL, n=50), pregnant women with normally developed fetus. Total, free and conjugated BPA were measured in their blood using GC-MS with isotopic dilution. The results show a correlation between environmental exposure to BPA and the genesis of fetal malformations. Conjugated BPA, which was higher in the CL, casts light on the hypothesis that a reduced ability to metabolize the chemical in the mother can concur to the occurrence of malformation. In a more detailed manner, in case of chromosomal malformations, the average value of free BPA appears to be nearly three times greater than that of the controls. Similarly, in case of central and peripheral nervous system non-chromosomal malformations, the value of free BPA is nearly two times greater than that of the controls. PMID:25796969

  20. 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

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

    PubMed

    Frappart, Sören; Raijmakers, Maartje; Frède, Valérie

    2014-04-01

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

  2. 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.

  3. 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

  4. 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.

  5. 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…

  6. 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


  7. Human Hepatic UGT2B15 Developmental Expression

    PubMed Central

    Divakaran, Karthika; McCarver, D Gail

    2014-01-01

    Human hepatic UGT2B15 developmental expression changes may alter the metabolism of important drugs and toxicants such as bisphenol A (BPA). Previously, UGT2B15 ontogeny knowledge consisted of transcript data, a dubious surrogate for protein expression. Herein, UGT2B15 protein content was determined in human hepatic microsomes (n = 236, 8 weeks gestation to 18 years). The impact of a common, functional single nucleotide polymorphism (g.253G>T), present in UGT2B15*2 and *5 alleles, was also tested. UGT2B15 expression began during late fetal life, at about 18% of mature values (medians = 48, 267 pmoles/mg of microsomal protein, respectively; p < 0.001). UGT2B15 neonatal (n = 39) and late fetal (?28 weeks, n = 10) content was similar, but lower than that of infants between 3 and 15 weeks age (n = 46; medians = 38, 48, 404 pmoles/mg microsomal protein, respectively; p < 0.001). Values for the latter group were higher compared with the remaining age group (15 weeks to 18 years; n = 82, p < 0.001). UGT2B15 expression varied 31-fold across the entire sample, and within groups, ranged from 4- to 27-fold. Among postnatal samples, age group, the presence of g.253T and male gender were each significantly associated with greater UGT2B15 expression (p < 0.001, <0.01, and <0.05, respectively; stepwise linear regression). In summary, hepatic UGT2B15 protein onset begins in late gestation; however, the greatest rate of change occurs during the first few weeks after birth. We speculate that the fetus and neonate may have lower clearance of some UGT2B15 substrates, such as BPA, compared with older individuals. PMID:24980262

  8. A human integrin-?3 mutation confers major renal developmental defects.

    PubMed

    Shukrun, Rachel; Vivante, Asaf; Pleniceanu, Oren; Vax, Einav; Anikster, Yair; Dekel, Benjamin; Lotan, Danny

    2014-01-01

    The development of the mammalian kidney is a highly complex process dependent upon the interplay of various cell types, secreted morphogens, and the extra-cellular matrix (ECM). Although integrins are the most important receptors for ECM proteins and are ubiquitously expressed during kidney development, mice lacking expression of integrin ?3 (Itga3) do not demonstrate a reduced number of nephrons, but mostly a disorganized GBM (glomerular basement membrane) leading to proteinuria. Thus, ITGA3 is considered mostly a passive GBM stabilizer and not an active player in nephrogenesis. Recently, mutations in the human ITGA3 were shown to cause congenital nephrotic syndrome, epidermolysis bullosa and interstitial lung disease, otherwise termed NEP syndrome (Nephrotic syndrome, Epidermolysis bullosa and Pulmonary disease). Herein, we performed histological and molecular analysis on the kidneys of a single patient from the initial cohort harboring an ITGA3 mutation, to illuminate the role of ITGA3 in human renal development. We show the patient to harbor a unique phenotype at birth, including severe unilateral renal hypodysplasia. Interrogation of global gene expression in the hypodysplastic kidney versus three controls (fetal, child and adult kidneys) revealed perturbed expression in several renal developmental pathways implicated in hypodysplasia, including the Wnt, BMP (bone morphogenetic protein) and TGF (transforming growth factor) pathways. Moreover, the affected kidney showed upregulation of early embryonic genes (e.g. OCT4 and PAX8) concomitant with downregulated kidney differentiation markers, implying a defect in proper renal differentiation. In conclusion, we show for the first time that ITGA3 is not merely a passive anchor for renal ECM proteins, as predicted by mouse models. Instead, our results may suggest it plays a central role in the interplay of cells, morphogens and ECM, required for proper nephrogenesis, thus adding ITGA3 to the list of CAKUT (congenital anomalies of the kidney and urinary tract)-causing genes. PMID:24621570

  9. Middle Pleistocene human facial morphology in an evolutionary and developmental context.

    PubMed

    Freidline, Sarah E; Gunz, Philipp; Harvati, Katerina; Hublin, Jean-Jacques

    2012-11-01

    Neanderthals and modern humans exhibit distinct facial architectures. The patterning of facial morphology of their predecessors, the Middle Pleistocene humans, is more mosaic showing a mix of archaic and modern morphologies. Significant changes in facial size and robusticity occurred throughout Pleistocene human evolution, resulting in temporal trends in both facial reduction and enlargement. However, the allometric patterning in facial morphology in archaic humans is not well understood. This study explores temporal trends in facial morphology in order to gain a clearer understanding of the polarity of features, and describes the allometric patterning of facial shape. The modern human sample comprises cross-sectional growth series of four morphologically distinct human populations. The fossil sample covers specimens from the Middle Pleistocene to the Upper Paleolithic. We digitized landmarks and semilandmarks on surface and computed tomography scans and analyzed the Procrustes shape coordinates. Principal component analyses were performed, and Procrustes distances were used to identify phenetic similarities between fossil hominins. In order to explore the influence of size on facial features, allometric trajectories were calculated for fossil and modern human groups, and developmental simulations were performed. We show that facial features can be used to separate Pleistocene humans into temporal clusters. The distinctly modern human pattern of facial morphology is already present around 170 ka. Species- and population-specific facial features develop before two years of age, and several of the large-scale facial differences between Neanderthals and Middle Pleistocene humans are due to scaling along a shared allometric trajectory. These features include aspects of the frontal bone, browridge morphology, nasal aperture size and facial prognathism. Infraorbital surface topography and orientation of the midface in the European Middle Pleistocene hominins is intermediate between the African Middle Pleistocene and Neanderthal condition. This could suggest that the European Middle Pleistocene hominins display incipient Neanderthal features. PMID:22981042

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

    EPA Science Inventory

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

  11. 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…

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

    PubMed

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

    2015-06-01

    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

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

    PubMed Central

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

  14. 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…

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

    ERIC Educational Resources Information Center

    Ouellette-Kuntz, HĂ©lĂšne; 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


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

    ERIC Educational Resources Information Center

    Franks, Bridget A.

    2011-01-01

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


  17. Understanding human trafficking in the United States.

    PubMed

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

    2009-01-01

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

  18. 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.

  19. 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)

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

    PubMed

    Umulis, David M; Othmer, Hans G

    2015-05-01

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

  1. 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 account. These results demonstrate that experience of sign language enhances the ability to imitate manual gestures once representations have been established, and suggest that the inherent motor patterns of lexical manual gestures are better suited for representation than those of non-signs. This set of findings prompts a developmental version of the ELU model, D-ELU. PMID:26909050

  2. 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 account. These results demonstrate that experience of sign language enhances the ability to imitate manual gestures once representations have been established, and suggest that the inherent motor patterns of lexical manual gestures are better suited for representation than those of non-signs. This set of findings prompts a developmental version of the ELU model, D-ELU. PMID:26909050

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

    PubMed

    Lerner, Richard M

    2015-06-01

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

  4. 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

  5. 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

  6. 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.; University of Wisconsin-Madison, Madison, WI 53706

    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 pregnancy. Black-Right-Pointing-Pointer Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.

  7. Understanding human-induced climate change

    NASA Astrophysics Data System (ADS)

    Trenberth, K. E.

    2012-12-01

    There are many difficulties in communicating the urgency of human-induced climate change. In this paper we focus on two. The assumption of no climate change is pervasive in scientific circles and elsewhere, unless proven otherwise, in spite of global studies to the contrary. This exceedingly conservative approach produces Type II errors: a false negative. It wrongly concludes there is no human influence, when there is. This kind of error is very common! And it is perpetrated by climate scientists. It is exacerbated by shortcomings in datasets (length, inhomogeneities) and models (inability to replicate the phenomenon of interest (hurricanes, tornadoes, thunderstorms, monsoons, blocking) owing to grid sizes and numerical constraints, and model errors.) The result is a gross understatement of the human influence on climate. The second issue is distinguishing weather versus climate. We ask "even if there is a well determined climate change, say 2°C increase in global mean temperature 50 years from now, how would the weather be different?" In fact much of the time the weather would be familiar - except perhaps occurring at different times of the year. The 2012 "June temperatures in March" in the United States is a case in point. Hence the main impacts occur when records are broken in summer, when conditions go well outside of any previously experienced, as has happened in the United States in 2011 and 2012, and Russia in 2010. The resulting widespread droughts, heat waves and wildfires have been devastating. Breaking records at other times of the year can leave a mark (warmer winters, more bugs etc) but seem more benign although not to ecosystems.

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

    PubMed

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

    2016-01-01

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

  9. 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).

  10. Understanding the origins of human cancer

    DOE PAGESBeta

    Alexandrov, L. B.

    2015-12-04

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

  11. 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.

  12. 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…

  13. 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…

  14. 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...

  15. 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


  16. Understanding Developmental Systems in Adolescence: Implications for Methodological Strategies, Data Analytic Approaches, and Training.

    ERIC Educational Resources Information Center

    Lerner, Richard M.; Lerner, Jacqueline V.; De Stefanis, Imma; Apfel, Alison

    2001-01-01

    Discusses contemporary theories of adolescence, stressing developmental systems models that integrate individual and contextual levels of analysis. Maintains that adolescence should be studied with multivariate-longitudinal designs, change-sensitive measures, and data analytic strategies capitalizing on triangulation across quantitative and…

  17. 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…

  18. 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…

  19. 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


  20. 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 · ”m, %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. PMID:23363890

  1. "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


  2. "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…

  3. 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. PMID:22202229

  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. 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"…

  6. 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...

  7. 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"


  8. 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…

  9. 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 =…

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

    EPA Science Inventory

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

  11. 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


  12. Commentary: Developmental connectomics to advance our understanding of typical and atypical brain development – Commentary on Vertes & Bullmore (2015)

    PubMed Central

    Graham, Alice M.; Fair, Damien A.

    2015-01-01

    VĂ©rtes and Bullmore's article lays a framework for applying connectomics, the study of brain function from the perspective of underlying network organization, to advance understanding of healthy and maladaptive brain development. They elucidate the power of connectomics for bridging both different levels of analysis (e.g. from synapses to brain regions) and multiple academic fields. In this commentary, we highlight important themes and remaining questions stemming from VĂ©rtes and Bullmore's work, including: (1) the application of connectomics in the context of integrating analyses across multiple spatial and temporal dimensions, (2) the extent to which connectomics might be applied in translational and clinical studies of development, (3) growth connectomics and the Developmental Origins of Health and Disease (DOHaD) hypothesis, and (4) the importance and complexity of sound methodological practices in applying connectomics to developmental and clinical science. Ongoing work in these areas will be important for fulfilling the promise of connectomics as a bridge between neuroscience, developmental science, and translational and clinical research. PMID:25714740

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

    PubMed

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

    2015-06-01

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

  14. Life history and development--a framework for understanding developmental plasticity in lower termites.

    PubMed

    Korb, Judith; Hartfelder, Klaus

    2008-08-01

    Termites (Isoptera) are the phylogenetically oldest social insects, but in scientific research they have always stood in the shadow of the social Hymenoptera. Both groups of social insects evolved complex societies independently and hence, their different ancestry provided them with different life-history preadaptations for social evolution. Termites, the 'social cockroaches', have a hemimetabolous mode of development and both sexes are diploid, while the social Hymenoptera belong to the holometabolous insects and have a haplodiploid mode of sex determination. Despite this apparent disparity it is interesting to ask whether termites and social Hymenoptera share common principles in their individual and social ontogenies and how these are related to the evolution of their respective social life histories. Such a comparison has, however, been much hampered by the developmental complexity of the termite caste system, as well as by an idiosyncratic terminology, which makes it difficult for non-termitologists to access the literature. Here, we provide a conceptual guide to termite terminology based on the highly flexible caste system of the "lower termites". We summarise what is known about ultimate causes and underlying proximate mechanisms in the evolution and maintenance of termite sociality, and we try to embed the results and their discussion into general evolutionary theory and developmental biology. Finally, we speculate about fundamental factors that might have facilitated the unique evolution of complex societies in a diploid hemimetabolous insect taxon. This review also aims at a better integration of termites into general discussions on evolutionary and developmental biology, and it shows that the ecology of termites and their astounding phenotypic plasticity have a large yet still little explored potential to provide insights into elementary evo-devo questions. PMID:18979593

  15. Understanding the complex etiologies of developmental disorders: Behavioral and molecular genetic approaches

    PubMed Central

    Willcutt, Erik G.; Pennington, Bruce F.; Duncan, Laramie; Smith, Shelley D.; Keenan, Janice M.; Wadsworth, Sally; DeFries, John C.; Olson, Richard K.

    2010-01-01

    Objective This paper has two primary goals. First, a brief tutorial on behavioral and molecular genetic methods is provided for readers without extensive training in these areas. To illustrate the application of these approaches to developmental disorders, etiologically-informative studies of reading disability (RD), math disability (MD), and attention-deficit/hyperactivity disorder (ADHD) are then reviewed. Implications of the results for these specific disorders and for developmental disabilities as a whole are discussed, and novel directions for future research are highlighted. Method Previous family and twin studies of RD, MD, and ADHD are reviewed systematically, and the extensive molecular genetic literatures on each disorder are summarized. To illustrate four novel extensions of these etiologically-informative approaches, new data are presented from the Colorado Learning Disabilities Research Center, an ongoing twin study of the etiology of RD, ADHD, MD, and related disorders. Conclusions RD, MD, and ADHD are familial and heritable, and co-occur more frequently than expected by chance. Molecular genetic studies suggest that all three disorders have complex etiologies, with multiple genetic and environmental risk factors each contributing to overall risk for each disorder. Neuropsychological analyses indicate that the three disorders are each associated with multiple neuropsychological weaknesses, and initial evidence suggests that comorbidity between the three disorders is due to common genetic risk factors that lead to slow processing speed PMID:20814254

  16. 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

  17. Human Learning: A Developmental Analysis. Students Library of Education Series.

    ERIC Educational Resources Information Center

    McFarland, H.S.N.

    There is a great variety of evidence about human learning which should be considered when forming a policy about any learning situation. The learner himself, the subject he studies, the institution, teaching methods, and studying techniques are all variables of learning; also, each variable can be viewed from several perspectives: behaviorist,…

  18. 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

  19. Intrafollicular influences on human oocyte developmental competence: perifollicular vascularity, oocyte metabolism and mitochondrial function.

    PubMed

    Van Blerkom, J

    2000-07-01

    While genetic and epigenetic factors have been associated with the developmental competence of human oocytes and embryos produced by IVF, how such factors develop or influence the oocyte remain to be explained. This paper reviews evidence which suggests that the degree of perifollicular vascular expansion associated with increased rates of blood flow are developmentally important for the generation of a normal follicle and competent oocyte. The degree of vascular development is follicle specific and differences between follicles might reflect their unique abilities to regulate angiogenic growth factor(s) production by the follicle cells in response to hypoxia. The notion that mitochondrial function in oocytes and early embryos could be influenced by intrafollicular conditions, and that differential patterns of mitochondrial segregation occur in blastomeres during early cleavage, is discussed with respect to the role of these organelles as critical determinants of developmental competence. PMID:11041523

  20. 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. PMID:26933733

  1. An enhanced role and expanded developmental origins for gamma-aminobutyric acidergic interneurons in the human cerebral cortex.

    PubMed

    Clowry, Gavin J

    2015-10-01

    Human beings have considerably expanded cognitive abilities compared with all other species and they also have a relatively larger cerebral cortex compared with their body size. But is a bigger brain the only reason for higher cognition or have other features evolved in parallel? Humans have more and different types of GABAergic interneurons, found in different places, than our model species. Studies are beginning to show differences in function. Is this expanded repertoire of functional types matched by an evolution of their developmental origins? Recent studies support the idea that generation of interneurons in the ventral telencephalon may be more complicated in primates, which have evolved a large and complex outer subventricular zone in the ganglionic eminences. In addition, proportionally more interneurons appear to be produced in the caudal ganglionic eminence, the majority of which populate the superficial layers of the cortex. Whether or not the cortical proliferative zones are a source of interneurogenesis, and to what extent and of what significance, is a contentious issue. As there is growing evidence that conditions such as autism, schizophrenia and congenital epilepsy may have developmental origins in the failure of interneuron production and migration, it is important we understand fully the similarities and differences between human development and our animal models. PMID:24839870

  2. Beyond Developmentalism? Early Childhood Teachers' Understandings of Multiage Grouping in Early Childhood Education and Care

    ERIC Educational Resources Information Center

    Edwards, Susan; Blaise, Mindy; Hammer, Marie

    2009-01-01

    Postdevelopmental perspectives in early childhood education and care increasingly reference alternative ways of understanding learning, growth and development in early learning. Drawing on these ideas, this paper examines research findings which focused on early childhood teachers' understandings of multiage grouping. The findings suggested that…

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

    PubMed

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

    2011-08-01

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

  4. Increase developmental plasticity of human keratinocytes with gene suppression

    PubMed Central

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

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Rabinowitch, Tal-Chen

    2015-12-01

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

  6. 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.

  7. British and Pakistani children's understanding of death: cultural and developmental influences.

    PubMed

    Panagiotaki, Georgia; Nobes, Gavin; Ashraf, Aisha; Aubby, Herjit

    2015-03-01

    This study explored British and Pakistani 4- to 7-year-olds' (N = 188) understanding of death. The aim was to examine possible influences on the acquisition of the subcomponents of the death concept by investigating how they are understood by children of different ages and cultural and religious backgrounds. Three groups of children were compared: White British and British Muslim living in London, and Pakistani Muslim living in rural Pakistan. In line with previous research (Slaughter, 2005, Aust. Psychol., 40(3), 179), irreversibility of death was one of the first subcomponents to be acquired, while causality was the last. The two groups of British children shared many similarities in their understanding of inevitability, applicability, irreversibility, and cessation. Pakistani Muslim children understood irreversibility earlier than did children in both British groups. In all three cultural groups, children's responses demonstrated very limited understanding of causality. Our findings support the view that aspects of a mature understanding of death develop between the ages of 4 and 7 years and that the process of understanding death as a biological event is, to a great extent, universal. They also suggest that aspects of children's reasoning are influenced by culturally specific experiences, particularly those arising from living in rural versus urban settings. PMID:25262770

  8. [Developmental capacity of human embryos after cryopreservation in the unicellular zygote stage].

    PubMed

    Tesarík, J; Hanzelka, Z; Trávník, P

    1989-12-01

    This study deals with the developmental competence of human embryos after cryopreservation at the one-cell stage using propanediol as cryoprotectant. From 11 frozen zygotes, nine underwent cleavage after thawing. The occurrence of multinuclear blastomeres was the most frequent abnormality which, however, can often be observed in fresh embryos as well. The results of an ultrastructural analysis of the developing frozen-thawed embryos, with special attention to markers of embryonic genome expression, did not show any noticeable impairment of the developmental competence of these embryos as compared with parameters previously described for unfrozen embryos. The findings are discussed with particular reference to current freezing policies in human in-vitro fertilization programmes. PMID:2630040

  9. Developmental regulation of human cortex transcription and its clinical relevance at base resolution

    PubMed Central

    Jaffe, Andrew E.; Shin, Jooheon; Collado-Torres, Leonardo; Leek, Jeffrey T.; Tao, Ran; Li, Chao; Gao, Yuan; Jia, Yankai; Maher, Brady J.; Hyde, Thomas M.

    2014-01-01

    Transcriptome analysis of human brain provides fundamental insight about development and disease, but largely relies on existing annotation. We sequenced transcriptomes of 72 prefrontal cortex samples across six life stages, and identified 50,650 differentially expression regions (DERs) associated with developmental and aging, agnostic of annotation. While many DERs annotated to non-exonic sequence (41.1%), most were similarly regulated in cytosolic mRNA extracted from independent samples. The DERs were developmentally conserved across 16 brain regions and within the developing mouse cortex, and were expressed in diverse cell and tissue types. The DERs were further enriched for active chromatin marks and clinical risk for neurodevelopmental disorders like schizophrenia. Lastly, we demonstrate quantitatively that these DERs associate with a changing neuronal phenotype related to differentiation and maturation. These data highlight conserved molecular signatures of transcriptional dynamics across brain development, some potential clinical relevance and the incomplete annotation of the human brain transcriptome. PMID:25501035

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

    PubMed

    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. PMID:19265682

  11. 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.

  12. 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…

  13. 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,


  14. 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


  15. 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…

  16. 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 the growing availability of global space-borne data to track the dynamics of floodplains as human-water systems. In particular, we can nowadays carry out global observations of floodplain topography and inundation patterns as well as human population dynamics. It is expected that these innovative observations will help understand the dynamics of floodplain systems across scales, different hydro-climatic conditions and along gradients of human impacts. Such an advanced understanding might then allow better predictions of future trajectories and therefore contribute to the reduction of flood risk.

  17. The significance of the subplate for evolution and developmental plasticity of the human brain

    PubMed Central

    Judaơ, Miloơ; Sedmak, Goran; Kostović, Ivica

    2013-01-01

    The human life-history is characterized by long development and introduction of new developmental stages, such as childhood and adolescence. The developing brain had important role in these life-history changes because it is expensive tissue which uses up to 80% of resting metabolic rate (RMR) in the newborn and continues to use almost 50% of it during the first 5 postnatal years. Our hominid ancestors managed to lift-up metabolic constraints to increase in brain size by several interrelated ecological, behavioral and social adaptations, such as dietary change, invention of cooking, creation of family-bonded reproductive units, and life-history changes. This opened new vistas for the developing brain, because it became possible to metabolically support transient patterns of brain organization as well as developmental brain plasticity for much longer period and with much greater number of neurons and connectivity combinations in comparison to apes. This included the shaping of cortical connections through the interaction with infant's social environment, which probably enhanced typically human evolution of language, cognition and self-awareness. In this review, we propose that the transient subplate zone and its postnatal remnant (interstitial neurons of the gyral white matter) probably served as the main playground for evolution of these developmental shifts, and describe various features that makes human subplate uniquely positioned to have such a role in comparison with other primates. PMID:23935575

  18. 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…

  19. 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


  20. 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


  1. [Developmental origin of human adult disease: which importance for obstetrical practice?].

    PubMed

    Picone, O; Servely, J-L; Chavatte-Palmer, P

    2007-06-01

    The Developmental Origins of Human Adult Disease are thought to be secondary to a perturbation of the embryonic or fetal development, which leads to metabolic disorders such as diabetes or hypertension at adulthood. Maternal undernutrition or overnutrition, repeated glucocorticosteroids administered to the mother, or placental dysfunction are the most frequently considered causal factors. Therefore, it is necessary that the obstetrician is aware of these phenomena, as this knowledge may contribute to the prevention of adult diseases. Little is known yet, on the pathophysiological or epigenetic mechanisms that lead to theses observations, and more studies are needed both in humans and animal models. PMID:17321694

  2. Developmental myosin heavy chains in the adult human diaphragm: coexpression patterns and effect of COPD.

    PubMed

    Nguyen, T; Shrager, J; Kaiser, L; Mei, L; Daood, M; Watchko, J; Rubinstein, N; Levine, S

    2000-04-01

    In preliminary experiments we noted developmental (i.e., embryonic and neonatal) myosin heavy chains (MHCs) in the diaphragms of patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that this finding represented new fiber formation secondary to injury associated with the mechanical stress of COPD or previously undescribed MHCs in the human diaphragm. To distinguish between these possibilities, we analyzed diaphragmatic biopsies obtained from 9 patients with severe COPD (forced expiratory volume in 1 s = 21 +/- 2% predicted, residual volume = 283 +/- 22% predicted) and 10 age-matched controls. First, using immunocytochemistry with specific monoclonal antibodies, we noted that control diaphragms had greater proportions of fibers expressing embryonic (50 +/- 2 vs. 28 +/- 3%, P < 0.0001) and neonatal (52 +/- 2 vs. 32 +/- 3%, P < 0.001) MHCs than COPD diaphragms. Second, SDS-PAGE demonstrated that these developmental MHCs represented only a very small fraction of the diaphragmatic MHC content. Third, the RT-PCR demonstrated mRNA coding for embryonic and neonatal MHCs in COPD and control diaphragms. Last, COPD and control diaphragms exhibited normal histology on light microscopy. We conclude that the presence of developmental MHC isoforms does not indicate new fiber formation in diaphragms of patients with severe COPD. Although these results represent the first systematic description of embryonic and neonatal MHCs in normal adult human diaphragms, their function remains to be elucidated. PMID:10749841

  3. Survival and developmental potential of stored human early cleavage stage embryos.

    PubMed

    Edgar, D H; Archer, J; Gook, D A; Jericho, H; Wilton, L; Bourne, H

    2004-07-01

    Human early cleavage stage embryos which survive cryopreservation and thawing fully intact demonstrate similar developmental potential to equivalent non frozen embryos when returned to the in vivo environment, whereas blastomere loss is directly related to the loss of potential for subsequent implantation in thawed embryos. This suggests that blastomere lysis during freezing and thawing does not occur preferentially in non viable blastomeres. Prefreeze growth rate rather than prefreeze blastomere number per se correlates with the developmental potential of stored embryos. When blastomere loss occurs as a consequence of cryopreservation, development of thawed early cleavage stage embryos to the blastocyst stage in vitro is impaired and the resultant blastocysts have a reduced total cell content. Blastomere loss is more prevalent in embryos which have been biopsied for preimplantation genetic diagnosis but this increased sensitivity can be circumvented by modification of the standard cryopreservation protocol. PMID:15196708

  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. Variation at Genes Influencing Facial Morphology Are Not Associated with Developmental Imprecision in Human Faces

    PubMed Central

    Windhager, Sonja; Schaschl, Helmut; Schaefer, Katrin; Mitteroecker, Philipp; Huber, Susanne; Wallner, Bernard; Fieder, Martin

    2014-01-01

    Facial asymmetries are commonly used as a proxy for human developmental imprecision resulting from inbreeding, and thus reduced genetic heterozygosity. Several environmental factors influence human facial asymmetry (e.g., health care, parasites), but the generalizability of findings on genetic stressors has been limited in humans by sample characteristics (island populations, endogamy) and indirect genetic assessment (inference from pedigrees). In a sample of 3215 adult humans from the Rotterdam Study, we therefore studied the relationship of facial asymmetry, estimated from nine mid-facial landmarks, with genetic variation at 102 single nucleotide polymorphism (SNP) loci recently associated with facial shape variation. We further tested whether the degree of individual heterozygosity is negatively correlated with facial asymmetry. An ANOVA tree regression did not identify any SNP relating to either fluctuating asymmetry or total asymmetry. In a general linear model, only age and sex—but neither heterozygosity nor any SNP previously reported to covary with facial shape—was significantly related to total or fluctuating asymmetry of the midface. Our study does not corroborate the common assumption in evolutionary and behavioral biology that morphological asymmetries reflect heterozygosity. Our results, however, may be affected by a relatively small degree of inbreeding, a relatively stable environment, and an advanced age in the Rotterdam sample. Further large-scale genetic studies, including gene expression studies, are necessary to validate the genetic and developmental origin of morphological asymmetries. PMID:24914781

  6. Variation at genes influencing facial morphology are not associated with developmental imprecision in human faces.

    PubMed

    Windhager, Sonja; Schaschl, Helmut; Schaefer, Katrin; Mitteroecker, Philipp; Huber, Susanne; Wallner, Bernard; Fieder, Martin

    2014-01-01

    Facial asymmetries are commonly used as a proxy for human developmental imprecision resulting from inbreeding, and thus reduced genetic heterozygosity. Several environmental factors influence human facial asymmetry (e.g., health care, parasites), but the generalizability of findings on genetic stressors has been limited in humans by sample characteristics (island populations, endogamy) and indirect genetic assessment (inference from pedigrees). In a sample of 3215 adult humans from the Rotterdam Study, we therefore studied the relationship of facial asymmetry, estimated from nine mid-facial landmarks, with genetic variation at 102 single nucleotide polymorphism (SNP) loci recently associated with facial shape variation. We further tested whether the degree of individual heterozygosity is negatively correlated with facial asymmetry. An ANOVA tree regression did not identify any SNP relating to either fluctuating asymmetry or total asymmetry. In a general linear model, only age and sex--but neither heterozygosity nor any SNP previously reported to covary with facial shape--was significantly related to total or fluctuating asymmetry of the midface. Our study does not corroborate the common assumption in evolutionary and behavioral biology that morphological asymmetries reflect heterozygosity. Our results, however, may be affected by a relatively small degree of inbreeding, a relatively stable environment, and an advanced age in the Rotterdam sample. Further large-scale genetic studies, including gene expression studies, are necessary to validate the genetic and developmental origin of morphological asymmetries. PMID:24914781

  7. 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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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


  9. "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…

  10. 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

  11. 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

  12. 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

  13. Invited commentary: Improving the human condition through rigorous, applied developmental research.

    PubMed

    Rhodes, Jean E

    2014-06-01

    This invited commentary describes the shifts toward a more positive characterization of young people over the past 30 years. After describing the new focus on the strengths of young people and the need to ground our understanding in developmental science, it provides an overview of the major contributions of this special issue to the field of positive youth development. Taken together, the groundbreaking work on the 4-H study demonstrates the increasing methodological and statistical sophistication of this strength-based approach. PMID:24723049

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

    PubMed

    Shi, Lei; Zhang, Zhe; Su, Bing

    2016-01-01

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

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

    PubMed Central

    Shi, Lei; Zhang, Zhe; Su, Bing

    2016-01-01

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

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

    PubMed

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

    2013-12-01

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

  17. Human-vehicle interaction by hand sign understanding

    NASA Astrophysics Data System (ADS)

    Dong, Guo; Ming, Xie; Yin, Xiaoming

    1999-07-01

    The interactive ability of intelligent electric vehicle with human has the capital importance of convincing public to accept the existence and usage of intelligent electric vehicle, it can greatly enhance the safety of intelligent electric vehicle in public service. In this paper, an interactive model based on hand gesture understanding is represented, it offers more compact and intuitive meanings than other interactive models in an outdoor environment. The Typical hand gestures are defined to guide the motion of vehicle by considering gesture differentiation and human tendency in the model, they are classified as motion-oriented and direction-oriented gestures for different interactive intentions. The color distribution of human skin is analyzed in different color spaces, it reveals that human skin colors cluster in a specific region with the irregular appearance, they have more differences in intensity than colors among the people. A color model of human skin is built for hand gesture segmentation by using the training procedure of RCE neural network, it has the ability of delineating the pattern class with arbitrary appearance in feature space. The quality of hand gesture segmentation is further improved by the procedure of hand-forearm separation. A hand tracking mechanism is proposed to locate the hand by camera pan-tilt and zooming. The gesture recognition is implemented by template matching of multiple features.

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

    NASA Astrophysics Data System (ADS)

    Krajíček, Jiƙí

    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].

  19. 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

  20. Developmental changes of aldehyde oxidase activity and protein expression in human liver cytosol.

    PubMed

    Tayama, Yoshitaka; Sugihara, Kazumi; Sanoh, Seigo; Miyake, Katsushi; Kitamura, Shigeyuki; Ohta, Shigeru

    2012-01-01

    Aldehyde oxidase (AO) plays a role in metabolizing many drugs, such as methotrexate and 6-mercaptopurine. We previously showed that AO activity in rat liver rapidly increases from birth, reaching a plateau within 4 weeks, and is regulated at the protein expression level. However, developmental changes of AO activity and protein expression in human liver have not been reported. Here, we investigated the developmental changes and variability of AO in 16 human livers (13 children ranging from 13 days to 12 years old and 3 adults, 17, 34 and 45 years old). Young children (13 days to 4 months after birth) showed little liver AO activity, evaluated in terms of the activities for oxidation of N-1-methylnicotinamide to N-1-methyl-2-pyridone-5-carboxamide and N-1-methyl-4-pyridone-3-carboxamide in liver cytosol. However, these oxidase activities were markedly increased after 4 months, reaching the adult level by about 2 years of age. The AO band density in immunoblotting analysis was well correlated with the AO activity among all subjects (p < 0.01, r(2) = 0.771). Therefore, AO activity in the liver of young children is regulated at the AO protein expression level. Thus, as in rats, the AO activity in humans rapidly increases soon after birth, and is regulated at the protein expression level. PMID:22453079

  1. Toward An Integrative "Educare" System: An Investigation of Teachers' Understanding and Uses of Developmentally Appropriate Practices for Young Children in Korea

    ERIC Educational Resources Information Center

    Kim, Juhu; Kim, Sun-Young; Maslak, Mary Ann

    2005-01-01

    The purpose of this study was to investigate how early childhood teachers in Korea understand developmentally appropriate practices (DAP) and follow DAP's instructional guidelines. In order to obtain insights for developing "educare," an integrated system for the education and care of young children in Korea, a comparison of early childhood…

  2. 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. Am J Phys Anthropol 159:S232-S274, 2016. © 2016 Wiley Periodicals, Inc. PMID:26808108

  3. 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. PMID:25514950

  4. 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 ?-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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

    Dietert, Rodney R.

    2014-01-01

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

  7. Flavonoids as Antioxidants and Developmental Regulators: Relative Significance in Plants and Humans

    PubMed Central

    Brunetti, Cecilia; Di Ferdinando, Martina; Fini, Alessio; Pollastri, Susanna; Tattini, Massimiliano

    2013-01-01

    Phenylpropanoids, particularly flavonoids have been recently suggested as playing primary antioxidant functions in the responses of plants to a wide range of abiotic stresses. Furthermore, flavonoids are effective endogenous regulators of auxin movement, thus behaving as developmental regulators. Flavonoids are capable of controlling the development of individual organs and the whole-plant; and, hence, to contribute to stress-induced morphogenic responses of plants. The significance of flavonoids as scavengers of reactive oxygen species (ROS) in humans has been recently questioned, based on the observation that the flavonoid concentration in plasma and most tissues is too low to effectively reduce ROS. Instead, flavonoids may play key roles as signaling molecules in mammals, through their ability to interact with a wide range of protein kinases, including mitogen-activated protein kinases (MAPK), that supersede key steps of cell growth and differentiation. Here we discuss about the relative significance of flavonoids as reducing agents and signaling molecules in plants and humans. We show that structural features conferring ROS-scavenger ability to flavonoids are also required to effectively control developmental processes in eukaryotic cells. PMID:23434657

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

    PubMed

    Dietert, Rodney R

    2014-01-01

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

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

    PubMed

    dos Santos, Rafael Guimarăes

    2013-01-01

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

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

    PubMed

    Lodato, Michael A; Woodworth, Mollie B; Lee, Semin; 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

    2015-10-01

    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

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

    PubMed Central

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

    2014-01-01

    Understanding of other’s actions as goal-directed is considered a fundamental ability underlying cognitive and social development in human infants. A number of studies using the habituation-dishabituation paradigm have shown that the ability to discern intentional relations, in terms of goal-directedness of an action towards an object, appears around 5 months of age. The question of whether non-human species can perceive other’s actions as goal-directed has been more controversial, however there is mounting evidence that at least some primates species do. Recently domestic dogs have been shown to be particularly sensitive to human communicative cues and more so in cooperative and intentional contexts. Furthermore, they have been shown to imitate selectively. Taken together these results suggest that dogs may perceive others' actions as goal-directed, however no study has investigated this issue directly. In the current study, adopting an infant habituation-dishabituation paradigm, we investigated whether dogs attribute intentions to an animate (a human) but not an inanimate (a black box) agent interacting with an object. Following an habituation phase in which the agent interacted always with one of two objects, two sets of 3 trials were presented: new side trials (in which the agent interacted with the same object as in the habituation trial but placed in a novel location) and new goal trials (in which the agent interacted with the other object placed in the old location). Dogs showed a similar pattern of response to that shown in infants, looking longer in the new goal than new side trials when they saw the human agent interact with the object. No such difference emerging with the inanimate agent (the black box). Results provide the first evidence that a non-primate species can perceive another individual’s actions as goal-directed. We discuss results in terms of the prevailing mentalisitic and non-mentalistic hypotheses regarding goal-attribution. PMID:25229452

  12. 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…

  13. 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


  14. 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

  15. Understanding physical activity and motivations for children with developmental coordination disorder: an investigation using the theory of planned behavior.

    PubMed

    Kwan, Matthew Y W; Cairney, John; Hay, John A; Faught, Brent E

    2013-11-01

    Developmental coordination disorder (DCD) is a neurodevelopmental condition, affecting approximately 5-6% of children. Previous research has consistently found children with DCD being less physically active compared to typically-developing (TD) children; however, the psychosocial factors associated with physical activity for children with DCD are poorly understood. The purpose of this study was to examine how theory-based physical activity cognitions impacts physical activity behaviors for children with and without DCD. Participants included a sample of boys (N=61, Mage=13.25 ±.46) with DCD (n=19) and without DCD (n=42), drawn from a larger prospective cohort study. A questionnaire with psychosocial measures was first administered, and accelerometers were used to assess their physical activity behavior over the subsequent week. Findings indicate that DCD was significantly associated with lower physical activity (F(1,58)=6.51, p<.05), and poorer physical activity cognitions (F(4,56) Wilks Lambda=2.78, p<.05). Meditational analyses found attitudes (B=.23, p<.05) and subjective norms (B=.31, p<.05) partially mediating the relationship between DCD and physical activity. Overall, this study further confirms that the activity deficit that exists among boys with DCD, and that the relationship is partially mediated through some physical activity cognitions. Interventions should target the perceived approval of influential people, and the personal evaluations of physical activity for boys with motoric difficulties. These findings further emphasizes the discrepancy in physical activity that exist between boys with DCD and TD boys, and highlight the need to better understand the psychological factors related to physical activity for children with DCD. PMID:24013157

  16. 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

  17. 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

  18. 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:25429365

  19. 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

  20. 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.

  1. 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...

  2. 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...

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

    PubMed Central

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

    2014-01-01

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

  4. Understanding Human Motion Skill with Peak Timing Synergy

    NASA Astrophysics Data System (ADS)

    Ueno, Ken; Furukawa, Koichi

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

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

    PubMed

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

    2015-02-01

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

  6. 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

  7. To Your Health: NLM update transcript - International efforts to understand the human brain

    MedlinePLUS

    ... NLM update Transcript International efforts to understand the human brain : 12/07/2015 To use the sharing features ... together to revolutionize the scientific understanding of the human brain, explains a perspective recently published in Science. The ...

  8. 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


  9. 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...

  10. 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


  11. 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…

  12. 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 ...

  13. 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...

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

    PubMed Central

    Brenhouse, Heather C.; Andersen, Susan L.

    2011-01-01

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

  15. 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…

  16. 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…

  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. 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


  19. Optical techniques to understand biofunctional adaptation in human dentine

    NASA Astrophysics Data System (ADS)

    Kishen, Anil; Asundi, Anand K.

    2004-08-01

    Human tooth structure in the oral environment is subjected to mechanical forces and thermal fluctuations. Dentine, the major component of the tooth structure, is a bio-composite, mainly composed of a highly mineralized phase and a collagenous phase. When subjected to changes in load and/or temperature, dentine will experience stresses and strains distribution within their structure. Though such effects are found to cause deleterious effects on artificial dental restorations, biological structures such as dentine seem to posses an inherent ability to adapt to functional thermo-mechanical loads. Optical techniques enable visualization and quantification of deformation, strain and stress on dental structures and provide a better understanding on their thermo-mechanical response. In this study 2-dimensional and 3-dimensional digital photoelasticity, digital moiré interferometry and Electronic Speckle Pattern Interferometry (ESPI) are all shown to be quite promising in this application. This paper will highlight these techniques and the corresponding applications. These experiments will aid in designing and development of better dental restorations and implants in clinical practice.

  20. Advancing our understanding of the human microbiome using QIIME

    PubMed Central

    Navas-Molina, José A.; Peralta-Sånchez, Juan M.; Gonzålez, Antonio; McMurdie, Paul J.; Våzquez-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

  1. 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 Right-Wing-Authoritarianism personality scale. Using this uniquely rich data set I develop a model of the nature and organization of these various attitude structures. Data analyses on explanation of public acceptance or rejection of evolution indicate that the Right-wing-authoritarianism and religious factors including beliefs in God's existence, views of the Bible, frequency of church attendance, and Evangelical Protestant affiliation are significant predictors across all measures. Scientific literacy, genetic science knowledge and familiarity, in general, are another contributor to prediction of public attitudes toward evolution. On measurement validity, consistency of measurement and responses are examined. The results from data analyses reveal the effect of question wording form and context is at play. In addition, public beliefs and knowledge about evolution are not consistent, rather contradictory, and are susceptible to framing effects. As scholars of public opinion warn, we should avoid the referendum view of polls on controversial issues (Schuman 2008; Moore 2008; Bishop 2005). Findings from this research lead to two key conclusions. First, great caution should be taken interpreting poll results on human evolution. Second, for better understanding of public opinion on this issue, a modified standard question should replace the current question.

  2. Assignment of the developmentally regulated gene NEDD1 to human chromosome 12q22 by fluorescence in situ hybridization.

    PubMed

    Takai, S; Yoshida, Y; Noda, M; Yamada, K; Kumar, S

    1995-01-01

    The developmentally regulated mouse gene Nedd 1 encodes a protein showing similarities with the beta-subunit of heterotrimeric GTP-binding proteins and has growth suppressing activity when overexpressed in various cultured cell types. We have mapped the human homolog (NEDD1) of the mouse gene to chromosome 12q22 by fluorescence in situ hybridization using R-banded human (pro)metaphase chromosomes. PMID:7814034

  3. Developmental expression and function of DKKL1/Dkkl1 in humans and mice

    PubMed Central

    2012-01-01

    Background Experiments were designed to identify the developmental expression and function of the Dickkopf-Like1 (DKKL1/Dkkl1) gene in humans and mice. Methods Mouse testes cDNA samples were collected at multiple postnatal times (days 4, 9, 18, 35, and 54, as well as at 6?months) and hybridized to Affymetrix mouse whole genome Genechips. To further characterize the homologous gene DKKL1 in human beings, the expression profiles between human adult testis and foetal testis were compared using Affymetrix human Genechips. The characteristics of DKKL1/Dkkl1 were analysed using various cellular and molecular biotechnologies. Results The expression of Dkkl1 was not detected in mouse testes on days 4 or 9, but was present on days 18, 35, and 54, as well as at 6?months, which was confirmed by RT-PCR and Western blot results. Examination of the tissue distribution of Dkkl1 demonstrated that while Dkkl1 mRNA was abundantly expressed in testes, little to no expression of Dkkl1 was observed in the epididymis or other tissues. In an in vitro fertilization assay, a Dkkl1 antibody was found to significantly reduce fertilization. Human Genechips results showed that the hybridization signal intensity of DKKL1 was 405.56-fold higher in adult testis than in foetal testis. RT-PCR analysis of multiple human tissues indicated that DKKL1 mRNA was exclusively expressed in the testis. Western blot analysis also demonstrated that DKKL1 was mainly expressed in human testis with a molecular weight of approximately 34?kDa. Additionally, immunohistochemical staining showed that the DKKL1 protein was predominantly located in spermatocytes and round spermatids in human testes. An examination of the expression levels of DKKL1 in infertile male patients revealed that while no DKKL1 appeared in the testes of patients with Sertoli cell only syndrome (SCOS) or cryptorchidism, DKKL1 was observed with variable expression in patients with spermatogenic arrest. Conclusions These results, together with previous studies, suggest that DKKL1/Dkkl1 may play an important role in testicular development and spermatogenesis and may be an important factor in male infertility. PMID:22817830

  4. 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 Brief and the final expert panel report, are available on the CERHR website (http://cerhr.niehs.nih.gov/). See bisphenol A under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs. nih.gov/chemicals/bisphenol/bisphenol.html). The NTP reached the following conclusions on the possible effects of exposure to bisphenol A on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. The NTP has some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has minimal concern for effects on the mammary gland and an earlier age for puberty for females in fetuses, infants, and children at current human exposures to bisphenol A. The NTP has negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects, or reduced birth weight and growth in their offspring. The NTP has negligible concern that exposure to bisphenol A will cause reproductive effects in non-occupationally exposed adults and minimal concern for workers exposed to higher levels in occupational settings. NTP will transmit the NTP-CERHR Monograph on Bisphenol A to federal and state agencies, interested parties, and the public and make it available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD from CERHR. PMID:19407859

  5. Developmental changes in calcium content of ultrastructurally distinct subcellular compartments of preimplantation human embryos.

    PubMed

    Sousa, M; Barros, A; Silva, J; Tesarik, J

    1997-02-01

    The ultrastructural localization of mobilizable Ca2+ in different subcellular compartments of human oocytes and preimplantation embryos was studied using the potassium-pyroantimonate technique and transmission electron microscopy; the specificity was confirmed by chelation experiments and X-ray microanalysis. In unfertilized oocytes, Ca2+ was detected in small vesicles beneath the plasma membrane as well as in other forms of smooth endoplasmic reticulum (SER) and in mitochondria but not in cortical granules. In pronuclear zygotes and blastomeres of cleaving embryos, Ca(2+)-rich vesicles were no longer present close to the plasma membrane, and the entire periphery was poor in Ca(2+)-containing organelles which, however, were abundant in the perinuclear region. The uneven Ca2+ loading of SER and mitochondria from the pronuclear stage onwards suggests that Ca2+ release from both these types of organelle contributes to the embryonic Ca2+ signals. During mitosis, less Ca2+ was detected with organelles, but the antimonate reaction product was more abundant in the cytosol. These data suggest that, in addition to different forms of SER, mitochondria also act as a source of mobilizable Ca2+ in preimplantation human embryos. The previously described developmental and cell cycle related changes in the characteristics of Ca2+ signals are associated with the redistribution and structural reorganization of these organelles. PMID:9239713

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. The Developmental Perspective in Integral Counseling

    ERIC Educational Resources Information Center

    Cook-Greuter, Susanne R.; Soulen, Jeffrey

    2007-01-01

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

  10. The Developmental Perspective in Integral Counseling

    ERIC Educational Resources Information Center

    Cook-Greuter, Susanne R.; Soulen, Jeffrey

    2007-01-01

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


  11. 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…

  12. Functional and developmental properties of human embryonic stem cells-derived cardiomyocytes.

    PubMed

    Binah, Ofer; Dolnikov, Katya; Sadan, Oshra; Shilkrut, Mark; Zeevi-Levin, Naama; Amit, Michal; Danon, Asaf; Itskovitz-Eldor, Joseph

    2007-01-01

    Cardiovascular diseases are the most frequent cause of death in the industrialized world, with the main contributor being myocardial infarction. Given the high morbidity and mortality rates associated with congestive heart failure, the shortage of donor hearts for transplantation, complications resulting from immunosuppression, and long-term failure of transplanted organs, regeneration of the diseased myocardium by cell transplantation is an attractive therapeutic modality. Because it is desired that the transplanted cells fully integrate within the diseased myocardium, contribute to its contractile performance, and respond appropriately to various physiological stimuli (eg, beta-adrenergic stimulation), our major long-term goal is to investigate the developmental changes in functional properties and hormonal responsiveness of human embryonic stem cells-derived cardiomyocytes (hESC-CM). Furthermore, because one of the key obstacles in advancing cardiac cell therapy is the low differentiation rate of hESC into cardiomyocytes, which reduces the clinical efficacy of cell transplantation, our second major goal is to develop efficient protocols for directing the cardiomyogenic differentiation of hESC in vitro. To accomplish the first goal, we investigated the functional properties of hESC-CM (<90 days old), respecting the contractile function and the underlying intracellular Ca(2+) handling. In addition, we performed Western blot analysis of the key Ca(2+)-handling proteins SERCA2, calsequestrin, phospholamban and the Na(+)/Ca(2+) exchanger. Our major findings were the following: (1) In contrast to the mature myocardium, hESC-CM exhibit negative force-frequency relationships and do not present postrest potentiation. (2) Ryanodine and thapsigargin do not affect the [Ca(2+)](i) transient and contraction, suggesting that, at this developmental stage, the contraction does not depend on sarcoplasmic reticulum Ca(2+) release. (3) In agreement with the finding that a voltage-dependent Ca(2+) current is present in hESC-CM and contributes to the mechanical function, verapamil completely blocks contraction. (4) Although hESC-CM express SERCA2 and Na(+)/Ca(2+) exchanger at levels comparable to those of the adult human myocardium, calsequestrin and phospholamban are not expressed. (4) In agreement with other reports, hESC-CM are responsive to beta-adrenergic stimulation. These findings show that the mechanical function related to intracellular Ca(2+) handling of hESC-CM differs from the adult myocardium, probably because of immature sarcoplasmic reticulum capacity. PMID:17993321

  13. 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…

  14. 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


  15. Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan.

    PubMed

    Li, Wei; Wu, Bing; Batrachenko, Anastasia; Bancroft-Wu, Vivian; Morey, Rajendra A; Shashi, Vandana; Langkammer, Christian; De Bellis, Michael D; Ropele, Stefan; Song, Allen W; Liu, Chunlei

    2014-06-01

    As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron-rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age-related changes of susceptibility were in good agreement with the findings from R2* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing. PMID:24038837

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

    PubMed

    Halperin, Jeffrey M

    2016-04-01

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

  17. 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…

  18. 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


  19. 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…

  20. UNDERSTANDING THE RELATIONSHIPS BETWEEN AIR QUALITY AND HUMAN HEALTH

    EPA Science Inventory

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

  1. 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. PMID:26265594

  2. Large-scale objective association of mouse phenotypes with human symptoms through structural variation identified in patients with developmental disorders.

    PubMed

    Boulding, Hannah; Webber, Caleb

    2012-05-01

    Copy number variants (CNVs) are thought to underlie many human developmental abnormalities. However, it is unclear how many of these CNVs exert their pathogenic effects or, in particular, how distinct CNVs at dispersed loci can give rise to the same abnormality. We hypothesize that the mouse orthologs of genes whose copy number change gives rise to the same human abnormality might also yield a similar phenotype when disrupted in mice. Thus, by bringing together a large number of disparate CNVs, we may be able to identify an unusually overrepresented phenotype among the affected genes' mouse orthologs. We obtained 1,624 de novo CNVs identified in patients with developmental abnormalities from Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources and European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations database. Forming CNV sets for each of 1,088 distinct human abnormalities, we were able to associate a total of 143 (13%) human abnormalities with mouse model phenotypes. Although many mouse phenotypes are readily comparable to their associated human abnormality, others are less so, generating novel biological hypotheses. Of the 2,086 candidate genes that contribute to these associations, 65% have not been previously associated with human disease in Online Mendelian Inheritance in Man, and their distribution suggests both extensive pleiotropy and epistasis while also proposing a small number of simple additive consequences. PMID:22396327

  3. 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.

  4. 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)

  5. Non-invasive imaging of human embryos to predict developmental competence

    PubMed Central

    Pera, Renee A. Reijo

    2015-01-01

    Although some aspects of human embryo development are conserved with those of other species, including the mouse, many aspects such as the timing of reprogramming and occurrence in the absence of transcription, duration of transcriptional silence and identity of genes with modulated expression in the oocyte to embryo transition, appear to be unique. Yet, frequently, the only data available for understanding the programs of early embryo development is that derived from model or agricultural species. We suggest that a specific understanding of basic aspects of human embryo development can affect a two-fold positive impact: 1) We can improve the health of a substantial subset of patients who seek assisted reproduction by improving diagnostics of viable embryo development in the clinic and, 2) we can use the information we gather to improve derivation and diagnosis of pluripotent stem cell lines (including reference or gold-standard human embryonic stem cell (hESC) lines and closely-related induced pluripotent stem cell (iPSC) lines) and their fates in novel basic and clinical applications. PMID:21802136

  6. Borna disease virus phosphoprotein impairs the developmental program controlling neurogenesis and reduces human GABAergic neurogenesis.

    PubMed

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

    2015-04-01

    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

  7. 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

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

    MedlinePLUS

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

  9. 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.

  10. Planning and understanding: A computational approach to human reasoning

    SciTech Connect

    Wilensky, R.

    1983-01-01

    This text brings together two areas of cognitive science: common sense problem-solving and natural language understanding. To do this, three theories are presented: a theory of plan generation, a theory of plan-based understanding, and a theory of the structure of plans that underlies both theories of processing. The theory stresses the complexity of the structure of plans rather than the problem of searching for the solution in a problem space. In addition, the theory examines commonplace situations rather than plan production, and simulation and goal detection in place of more conventional bug detection and plan modification techniques. Contents: Introduction; Tenets of a theory of plans; Planning in everyday situations; Meta-planning; Explanation-driven understanding; Goal relationships; Negative goal relationships; Reasoning about goal conflict; Reasoning about goal competition,; Positive goal relationships; Computer implementation - representation of task networks; Computer implementation - programs; Bibliography; Index.

  11. Differential Gene Expression Profiling of Functionally and Developmentally Distinct Human Prostate Epithelial Populations

    PubMed Central

    Liu, Haibo; Cadaneanu, Radu M; Lai, Kevin; Zhang, Baohui; Huo, Lihong; An, Dong Sun; Li, Xinmin; Lewis, Michael S; Garraway, Isla P

    2015-01-01

    BACKGROUND Human fetal prostate buds appear in the 10th gestational week as solid cords, which branch and form lumens in response to androgen 1. Previous in vivo analysis of prostate epithelia isolated from benign prostatectomy specimens indicated that Epcam+CD44?CD49fHi basal cells possess efficient tubule initiation capability relative to other subpopulations 2. Stromal interactions and branching morphogenesis displayed by adult tubule-initiating cells (TIC) are reminiscent of fetal prostate development. In the current study, we evaluated in vivo tubule initiation by human fetal prostate cells and determined expression profiles of fetal and adult epithelial subpopulations in an effort to identify pathways used by TIC. METHODS Immunostaining and FACS analysis based on Epcam, CD44, and CD49f expression demonstrated the majority (99.9%) of fetal prostate epithelial cells (FC) were Epcam+CD44? with variable levels of CD49f expression. Fetal populations isolated via cell sorting were implanted into immunocompromised mice. Total RNA isolation from Epcam+CD44?CD49fHi FC, adult Epcam+CD44?CD49fHi TIC, Epcam+CD44+CD49fHi basal cells (BC), and Epcam+CD44?CD49fLo luminal cells (LC) was performed, followed by microarray analysis of 19 samples using the Affymetrix Gene Chip Human U133 Plus 2.0 Array. Data was analyzed using Partek Genomics Suite Version 6.4. Genes selected showed >2-fold difference in expression and P < 5.00E-2. Results were validated with RT-PCR. RESULTS Grafts retrieved from Epcam+CD44? fetal cell implants displayed tubule formation with differentiation into basal and luminal compartments, while only stromal outgrowths were recovered from Epcam- fetal cell implants. Hierarchical clustering revealed four distinct groups determined by antigenic profile (TIC, BC, LC) and developmental stage (FC). TIC and BC displayed basal gene expression profiles, while LC expressed secretory genes. FC had a unique profile with the most similarities to adult TIC. Functional, network, and canonical pathway identification using Ingenuity Pathway Analysis Version 7.6 compiled genes with the highest differential expression (TIC relative to BC or LC). Many of these genes were found to be significantly associated with prostate tumorigenesis. CONCLUSIONS Our results demonstrate clustering gene expression profiles of FC and adult TIC. Pathways associated with TIC are known to be deregulated in cancer, suggesting a cell-of-origin role for TIC versus re-emergence of pathways common to these cells in tumorigenesis. Prostate 75: 764–776, 2015. © The Authors. The Prostate, published by Wiley Periodicals, Inc. PMID:25663004

  12. 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

  13. Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females

    PubMed Central

    Fulp, Carl; Gomez, Ernest; Nasrallah, Ilya; Minarcik, Jeremy; Sudi, Jyotsna; Christian, Susan L.; Mancini, Grazia; Labosky, Patricia; Dobyns, William; Brooks-Kayal, Amy

    2009-01-01

    Mutations in the X-linked aristaless-related homeobox gene (ARX) have been linked to structural brain anomalies as well as multiple neurocognitive deficits. The generation of Arx-deficient mice revealed several morphological anomalies, resembling those observed in patients and an interneuron migration defect but perinatal lethality precluded analyses of later phenotypes. Interestingly, many of the neurological phenotypes observed in patients with various ARX mutations can be attributed, in part, to interneuron dysfunction. To directly test this possibility, mice carrying a floxed Arx allele were generated and crossed to Dlx5/6CRE-IRES-GFP(Dlx5/6CIG) mice, conditionally deleting Arx from ganglionic eminence derived neurons including cortical interneurons. We now report that Arx−/y;Dlx5/6CIG (male) mice exhibit a variety of seizure types beginning in early-life, including seizures that behaviourally and electroencephalographically resembles infantile spasms, and show evolution through development. Thus, this represents a new genetic model of a malignant form of paediatric epilepsy, with some characteristics resembling infantile spasms, caused by mutations in a known infantile spasms gene. Unexpectedly, approximately half of the female mice carrying a single mutant Arx allele (Arx−/+;Dlx5/6CIG) also developed seizures. We also found that a subset of human female carriers have seizures and neurocognitive deficits. In summary, we have identified a previously unrecognized patient population with neurological deficits attributed to ARX mutations that are recapitulated in our mouse model. Furthermore, we show that perturbation of interneuron subpopulations is an important mechanism underling the pathogenesis of developmental epilepsy in both hemizygous males and carrier females. Given the frequency of ARX mutations in patients with infantile spasms and related disorders, our data unveil a new model for further understanding the pathogenesis of these disorders. PMID:19439424

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2014-01-01

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

  16. 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…

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

    PubMed

    Ross, Gordon J; Jones, Tim

    2015-06-01

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

  18. 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.

  19. Benchmarking Text Understanding Systems to Human Performance: An Exploration.

    ERIC Educational Resources Information Center

    Butler, Frances A.; And Others

    This study, part of a larger effort to develop a methodology for evaluating intelligent computer systems (Artificial Intelligence Systems), explores the use of benchmarking as an evaluation technique. Benchmarking means comparing the performance of intelligent computer systems with human performance on the same task. Benchmarking in evaluation has…

  20. 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)

  1. 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 ...

  2. 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


  3. 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…

  4. 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.

  5. 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.

  6. Applying artificial vision models to human scene understanding

    PubMed Central

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

    2015-01-01

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

  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. Anogenital human papillomavirus infection. Changes in understanding and management.

    PubMed Central

    Sellors, J. W.; Law, C.

    1994-01-01

    Knowledge of the natural history and clinical management of anogenital human papillomavirus (HPV) infection is changing rapidly. Consequently, it is important for family physicians to keep current. This article updates the epidemiology, detection, and treatment of HPV-related disease and discusses commonly confused conditions and answers to patients' questions. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 p96-a Figure 10 Figure 11 PMID:8312760

  9. 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.

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

    PubMed

    Tomanek, Robert J

    2016-01-01

    Although considerable advances in our understanding of mammalian and avian embryonic coronary development have occurred during the last decade, our current knowledge of this topic in humans is limited. Accordingly, the aim of this study was to determine if the development of the human coronary vasculature in humans is like that of other mammals and avians. The data document a progression of events involving mesenchymal cell-containing villi from the proepicardium, establishment of blood islands and a capillary network. The major finding of the study is direct evidence that the capillary plexus associated with spindle cells and erythroblasts invades the base of the aorta to form coronary ostia. A role for the dorsal mesocardium is also indicated by the finding that cells from this region are continuous with the aorta and pulmonary artery. The development of the tunica media of the coronary arteries follows the same base-apex progression as in other species, with the development of branches occurring late in the embryonic period. The fetal period is characterized by 1) growth and a numerical increase in the smallest arterial branches, veins, and venules, 2) innervation of arteries, and 3) inclusion of elastic fibers in the tunica media of the coronary arteries and development of the tunica adventitia. In conclusion, the data demonstrate that the development of the coronary system in humans is similar to that of other mammalian and avian species, and for the first time documents that the formation of the ostia and coronary stems in humans occurs by ingrowth of a vascular plexus and associated cells from the epicardium. Anat Rec, 299:25-41, 2016. © 2015 Wiley Periodicals, Inc. PMID:26475042

  11. Using animal models to understand cancer pain in humans.

    PubMed

    Currie, Gillian L; Sena, Emily S; Fallon, Marie T; Macleod, Malcolm R; Colvin, Lesley A

    2014-06-01

    Cancer pain is not a single entity but a complex pain state involving different pain syndromes, with inflammatory, neuropathic, compressive, and ischaemic mechanisms. Current therapeutic regimens are based largely on opioids, although opioid treatment can lead to many side effects. Studies using animal models of cancer pain are aimed at understanding cancer pain and developing novel therapies. The most frequently reported models are of bone cancer pain, predominantly modelling pain associated with tumour growth within bone marrow. Here we summarise recent findings from studies using animal models of cancer pain and discuss the methodological quality of these studies. PMID:24760492

  12. 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 public discourse accurately. However, focus group responses did not simply reflect media coverage. PMID:17449156

  13. 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

  14. Nuclear medical PET-study in the causal relationship between mastication and brain function in human evolutionary and developmental processes.

    PubMed

    Kubota, Kinziro; Momose, Toshimitsu; Abe, Atushi; Narita, Noriyuki; Ohtomo, Kuni; Minaguchi, Shunsuke; Funakoshi, Masaya; Sasaki, Yasuhito; Kojima, Yoshiki

    2003-12-01

    The principal author (Kubote 1995, 1997, 1998, 1999, 2000 a, b) has proposed that chewing food well from infancy will lead to a clear-headed and robust person, following which the same concept has been presented to the general public by the mass media. Unfortunately, however, there does not yet seem to be any direct evidence to support this claim. It is thus necessary to review mastication from the standpoint of the new concept of evidence-based medicine (EBM) and to create a new direction in medicodental research and treatment from the viewpoint of human evolution, because the causal relationship between mastication and brain function has never been clarified either in fossil science research or in the modem scientific bibliography. To confirm the human historical fossil record in regard to the causal relationship between the development of mastication and brain function in human evolutionary processes, the effect of gum chewing on brain reaction was examined in humans by means of a positron-emission tomography (PET) camera (Momose et al. 1997) after an antecubital intravenous injection of H215O. Powerful activation of the cortical cells was demonstrated in multiple cortical areas involving the marginal areas of the bilateral central sulci of the cerebral cortex (Fig. 1), and the activated areas coincided with our previous results in region of interest (ROI) analysis (Momose et al. 1887). Three-dimensionally, numerous cortical cells were shown to form nuclei on relief maps (Fig. 2). As diets and feeding habits changed in a stepwise manner from frugivorous to omnivorous via herbivorous and carnivorous over the lengthy progress of evolution, the brain concomitantly grew and the cranial capacity gradually increased in volume from 500 cm3, food from plant sources to animal sources (700 cm3), and then to both (1500 cm3), during the human evolutionary and developmental processes. Gradual increases in the cranial capacity of human fossils during the developmental stage have been demonstrated also by PET images of the human brain acquired by means of a PET camera and an antecubital intravenous injection of H215O during mastication that showed powerful activation of cortical cells in multiple areas. It could be concluded that human fossils give us concrete information on how to feed our children in the modern human life style from infancy to adulthood, so that we should bring children up by adhering to images of the principal feeding habits discovered during this research on human evolutionary and developmental processes. PMID:14704002

  15. Developmental Fate and Cellular Maturity Encoded in Human Regulatory DNA Landscapes

    PubMed Central

    Reynolds, Alex; Humbert, Richard; Miller, Brady; Paige, Sharon L.; Vernot, Benjamin; Cheng, Jeffrey B.; Thurman, Robert E.; Sandstrom, Richard; Haugen, Eric; Heimfeld, Shelly; Murry, Charles E.; Akey, Joshua M.; Stamatoyannopoulos, John A.

    2014-01-01

    SUMMARY Cellular-state information between generations of developing cells may be propagated via regulatory regions. We report consistent patterns of gain and loss of DNase I-hypersensitive sites (DHSs) as cells progress from embryonic stem cells (ESCs) to terminal fates. DHS patterns alone convey rich information about cell fate and lineage relationships distinct from information conveyed by gene expression. Developing cells share a proportion of their DHS landscapes with ESCs; that proportion decreases continuously in each cell type as differentiation progresses, providing a quantitative benchmark of developmental maturity. Developmentally stable DHSs densely encode binding sites for transcription factors involved in autoregulatory feedback circuits. In contrast to normal cells, cancer cells extensively reactivate silenced ESC DHSs and those from developmental programs external to the cell lineage from which the malignancy derives. Our results point to changes in regulatory DNA landscapes as quantitative indicators of cell-fate transitions, lineage relationships, and dysfunction. PMID:23953118

  16. 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. PMID:20580455

  17. 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

  18. 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. PMID:20626812

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

    PubMed

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

    2013-07-01

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

  20. The Prevalence of Chromosomal Deletions Relating to Developmental Delay and/or Intellectual Disability in Human Euploid Blastocysts

    PubMed Central

    He, Wenyin; Sun, Xiaofang; Liu, Lian; Li, Man; Jin, Hua; Wang, Wei-Hua

    2014-01-01

    Chromosomal anomalies in human embryos produced by in vitro fertilization are very common, which include numerical (aneuploidy) and structural (deletion, duplication or others) anomalies. Our previous study indicated that chromosomal deletion(s) is the most common structural anomaly accounting for approximately 8% of euploid blastocysts. It is still unknown if these deletions in human euploid blastocysts have clinical significance. In this study, we analyzed 15 previously diagnosed euploid blastocysts that had chromosomal deletion(s) using Agilent oligonucleotide DNA microarray platform and localized the gene location in each deletion. Then, we used OMIM gene map and phenotype database to investigate if these deletions are related with some important genes that cause genetic diseases, especially developmental delay or intellectual disability. As results, we found that the detectable chromosomal deletion size with Agilent microarray is above 2.38 Mb, while the deletions observed in human blastocysts are between 11.6 to 103 Mb. With OMIM gene map and phenotype database information, we found that deletions can result in loss of 81-464 genes. Out of these genes, 34–149 genes are related with known genetic problems. Furthermore, we found that 5 out of 15 samples lost genes in the deleted region, which were related to developmental delay and/or intellectual disability. In conclusion, our data indicates that all human euploid blastocysts with chromosomal deletion(s) are abnormal and transfer of these embryos may cause birth defects and/or developmental and intellectual disabilities. Therefore, the embryos with chromosomal deletion revealed by DNA microarray should not be transferred to the patients, or further gene map and/or phenotype seeking is necessary before making a final decision. PMID:24409323

  1. Contours of risk: spatializing human behaviors to understand disease dynamics in changing landscapes.

    PubMed

    Hausermann, Heidi; Tschakert, Petra; Smithwick, Erica A H; Ferring, David; Amankwah, Richard; Klutse, Erasmus; Hagarty, Julianne; Kromel, Lindsay

    2012-09-01

    We echo viewpoints presented in recent publications from EcoHealth and other journals arguing for the need to understand linkages between human health, disease ecology, and landscape change. We underscore the importance of incorporating spatialities of human behaviors and perceptions in such analyses to further understandings of socio-ecological interactions mediating human health. We use Buruli ulcer, an emerging necrotizing skin infection and serious health concern in central Ghana, to illustrate our argument. PMID:22805769

  2. 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

  3. Out of Sight Is Not out of Mind: Developmental Changes in Infants' Understanding of Visual Perception during the Second Year

    ERIC Educational Resources Information Center

    Poulin-Dubois, Diane; Sodian, Beate; Metz, Ulrike; Tilden, Joanne; Schoeppner, Barbara

    2007-01-01

    Three experiments investigated 14-, 18-, and 24- month-old infants' understanding of visual perception. Infants viewed films in which a protagonist was either able to view the location of a hidden object (Visual Access condition) or was blindfolded when the object location was revealed (No Visual Access condition). When requested to find the…

  4. 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


  5. 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,…

  6. 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,


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

    PubMed

    Zabala, Aiora; Pascual, Unai

    2016-01-01

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

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

    PubMed Central

    Zabala, Aiora; Pascual, Unai

    2016-01-01

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

  9. Developmental robustness.

    PubMed

    Keller, Evelyn Fox

    2002-12-01

    Developmental robustness, the capacity to stay "on track" despite the myriad vicissitudes that inevitably plague a developing organism, is, I argue, a prerequisite for natural selection and key to our understanding of the evolution of developmental processes. But how is such robustness achieved? And how can we reconcile this property with the delicate precision that seems to characterize so many developmental mechanisms, with what Michael Behe calls "irreducible complexity"? By looking at context, I argue. Developmental mechanisms must be robust with respect to the kinds of insults they are most likely to face, but with respect to less likely vicissitudes, they can be fragile. More specifically, I examine the relative absence of reaction-diffusion mechanisms in development and suggest that such mechanisms, theoretically attractive though they may be, have been judged by evolution to be ill suited for providing protection against the kinds of vicissitudes developing organisms are most likely to face, and have been supplanted by more intricate mechanisms that are protected from insult by structural design. PMID:12547680

  10. 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…

  11. 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...

  12. EVALUATIVE PROCESS FOR ASSESSING HUMAN REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF AGENTS

    EPA Science Inventory

    Agents that may affect reproductive and developmental toxicity are of great concern to the general public. espite this, both the regulatory and public health arenas have been made somewhat haphazard use of the existing data when interpreting these health effects. ppropriate infor...

  13. GENETIC ANOMALIES IN MAMMALIAN GERM CELLS AND THEIR SIGNIFICANCE FOR HUMAN REPRODUCTIVE AND DEVELOPMENTAL RISK

    EPA Science Inventory

    The induction of heritable mutations in germ cells represents a potential health concern. his paper will highlight several themes in the area of germ-cell mutagenesis and their implications in reproductive and developmental risk. dditionally, factors that influence the yield of g...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-07-01

    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

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

    PubMed Central

    1977-01-01

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

  17. Systematically labeling developmental stage-specific genes for the study of pancreatic ?-cell differentiation from human embryonic stem cells.

    PubMed

    Liu, Haisong; Yang, Huan; Zhu, Dicong; Sui, Xin; Li, Juan; Liang, Zhen; Xu, Lei; Chen, Zeyu; Yao, Anzhi; Zhang, Long; Zhang, Xi; Yi, Xing; Liu, Meng; Xu, Shiqing; Zhang, Wenjian; Lin, Hua; Xie, Lan; Lou, Jinning; Zhang, Yong; Xi, Jianzhong; Deng, Hongkui

    2014-10-01

    The applications of human pluripotent stem cell (hPSC)-derived cells in regenerative medicine has encountered a long-standing challenge: how can we efficiently obtain mature cell types from hPSCs? Attempts to address this problem are hindered by the complexity of controlling cell fate commitment and the lack of sufficient developmental knowledge for guiding hPSC differentiation. Here, we developed a systematic strategy to study hPSC differentiation by labeling sequential developmental genes to encompass the major developmental stages, using the directed differentiation of pancreatic ? cells from hPSCs as a model. We therefore generated a large panel of pancreas-specific mono- and dual-reporter cell lines. With this unique platform, we visualized the kinetics of the entire differentiation process in real time for the first time by monitoring the expression dynamics of the reporter genes, identified desired cell populations at each differentiation stage and demonstrated the ability to isolate these cell populations for further characterization. We further revealed the expression profiles of isolated NGN3-eGFP(+) cells by RNA sequencing and identified sushi domain-containing 2 (SUSD2) as a novel surface protein that enriches for pancreatic endocrine progenitors and early endocrine cells both in human embryonic stem cells (hESC)-derived pancreatic cells and in the developing human pancreas. Moreover, we captured a series of cell fate transition events in real time, identified multiple cell subpopulations and unveiled their distinct gene expression profiles, among heterogeneous progenitors for the first time using our dual reporter hESC lines. The exploration of this platform and our new findings will pave the way to obtain mature ? cells in vitro. PMID:25190258

  18. Systematically labeling developmental stage-specific genes for the study of pancreatic ?-cell differentiation from human embryonic stem cells

    PubMed Central

    Liu, Haisong; Yang, Huan; Zhu, Dicong; Sui, Xin; Li, Juan; Liang, Zhen; Xu, Lei; Chen, Zeyu; Yao, Anzhi; Zhang, Long; Zhang, Xi; Yi, Xing; Liu, Meng; Xu, Shiqing; Zhang, Wenjian; Lin, Hua; Xie, Lan; Lou, Jinning; Zhang, Yong; Xi, Jianzhong; Deng, Hongkui

    2014-01-01

    The applications of human pluripotent stem cell (hPSC)-derived cells in regenerative medicine has encountered a long-standing challenge: how can we efficiently obtain mature cell types from hPSCs? Attempts to address this problem are hindered by the complexity of controlling cell fate commitment and the lack of sufficient developmental knowledge for guiding hPSC differentiation. Here, we developed a systematic strategy to study hPSC differentiation by labeling sequential developmental genes to encompass the major developmental stages, using the directed differentiation of pancreatic ? cells from hPSCs as a model. We therefore generated a large panel of pancreas-specific mono- and dual-reporter cell lines. With this unique platform, we visualized the kinetics of the entire differentiation process in real time for the first time by monitoring the expression dynamics of the reporter genes, identified desired cell populations at each differentiation stage and demonstrated the ability to isolate these cell populations for further characterization. We further revealed the expression profiles of isolated NGN3-eGFP+ cells by RNA sequencing and identified sushi domain-containing 2 (SUSD2) as a novel surface protein that enriches for pancreatic endocrine progenitors and early endocrine cells both in human embryonic stem cells (hESC)-derived pancreatic cells and in the developing human pancreas. Moreover, we captured a series of cell fate transition events in real time, identified multiple cell subpopulations and unveiled their distinct gene expression profiles, among heterogeneous progenitors for the first time using our dual reporter hESC lines. The exploration of this platform and our new findings will pave the way to obtain mature ? cells in vitro. PMID:25190258

  19. 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

  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. 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


  2. 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/TGFÎČ 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. PMID:23250204

  3. Genetic and Developmental Basis of Cardiovascular Malformations.

    PubMed

    Azhar, Mohamad; Ware, Stephanie M

    2016-03-01

    Cardiovascular malformations (CVMs) are the most common birth defect, occurring in 1% to 5% of all live births. Genetic, epigenetic, and environmental factors all influence the development of CVMs, and an improved understanding of the causation of CVMs is a prerequisite for prevention. Cardiac development is a complex, multistep process of morphogenesis that is under genetic regulation. Although the genetic contribution to CVMs is well recognized, the genetic causes of human CVMs are still identified infrequently. This article discusses the key genetic concepts characterizing human CVMs, their developmental basis, and the critical developmental and genetic concepts underlying their pathogenesis. PMID:26876120

  4. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Butyl Phthalate (DBP).

    PubMed

    2003-04-01

    TThe National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-butyl phthalate (DBP) to cause adverse effects on reproduction and development in humans. DBP 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. Unlike many phthalates, DBP is not currently used as a plasticizer in polyvinyl chloride plastics. DBP is a component of latex adhesives and is used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes. The results of this evaluation on DBP 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-n-Butyl 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 DBP on human development and reproduction. First, although DBP could possibly affect human reproduction and development if exposures are sufficiently high, the NTP concludes that there is negligible concern for reproductive toxicity in exposed adults. Second, the NTP concludes that there is minimal concern for developmental effects when pregnant women are exposed to DBP levels estimated by the panel (2-10 mug/kg body weight/day). There is no direct evidence that exposure of people to DBP adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure to high doses of DBP (>/=100 mg/kg body weight/day) may adversely affect the prenatal and early postnatal development in rodents. Finally, based on exposure estimates in women of reproductive age, the NTP concludes that there is some concern for DBP causing adverse effects to human development, particularly development of the male reproductive system. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available electronically in PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511). PMID:15995736

  5. 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 high exposure levels, there is no evidence of adverse reproductive effects in rats. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available electronically in PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511). PMID:15995727

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

    PubMed

    Hou, Zhonggang; Zhang, Jue; Schwartz, Michael P; Stewart, Ron; Page, C David; Murphy, William L; Thomson, James A

    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. PMID:24565336

  7. 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

  8. 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

  9. 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…

  10. 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


  11. 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…

  12. Evaluation of Developmental Toxicants and Signaling Pathways in a Functional Test Based on the Migration of Human Neural Crest Cells

    PubMed Central

    Zimmer, Bastian; Lee, Gabsang; Balmer, Nina V; Meganathan, Kesavan; Sachinidis, Agapios; Studer, Lorenz

    2012-01-01

    Background: Information on the potential developmental toxicity (DT) of the majority of chemicals is scarce, and test capacities for further animal-based testing are limited. Therefore, new approaches with higher throughput are required. A screening strategy based on the use of relevant human cell types has been proposed by the U.S. Environmental Protection Agency and others. Because impaired neural crest (NC) function is one of the known causes for teratologic effects, testing of toxicant effects on NC cells is desirable for a DT test battery. Objective: We developed a robust and widely applicable human-relevant NC function assay that would allow for sensitive screening of environmental toxicants and defining toxicity pathways. Methods: We generated NC cells from human embryonic stem cells, and after establishing a migration assay of NC cells (MINC assay), we tested environmental toxicants as well as inhibitors of physiological signal transduction pathways. Results: Methylmercury (50 nM), valproic acid (> 10 ”M), and lead-acetate [Pb(CH3CO2)4] (1 ”M) affected the migration of NC cells more potently than migration of other cell types. The MINC assay correctly identified the NC toxicants triadimefon and triadimenol. Additionally, it showed different sensitivities to various organic and inorganic mercury compounds. Using the MINC assay and applying classic pharmacologic inhibitors and large-scale microarray gene expression profiling, we found several signaling pathways that are relevant for the migration of NC cells. Conclusions: The MINC assay faithfully models human NC cell migration, and it reveals impairment of this function by developmental toxicants with good sensitivity and specificity. PMID:22571897

  13. 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...

  14. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Butyl Benzyl Phthalate (BBP).

    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 butyl benzyl phthalate (BBP) to cause adverse effects on reproduction and development in humans. BBP 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. BBP is used in the production of vinyl tiles and polyvinyl chloride (PVC) to make products such as food conveyor belts, carpet tile, tarps, artificial leather, automotive trim, and traffic cones. The results of this evaluation on BBP 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 Butyl Benzyl 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 BBP on human development and reproduction. First, the NTP concludes there is negligible concern for adverse reproductive effects in exposed men. Data are insufficient to reach a conclusion on possible eproductive effects in exposed women. There is no direct evidence that exposure of people to BBP adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure of laboratory animals to high doses (>/=1000 mg/kg body weight/day) of BBP can adversely affect development, including development of the male reproductive tract. Second, the NTP concludes that there is minimal concern for developmental effects in fetuses and children. Evidence showed adverse reproductive effects in rats at doses of 100 mg/kg body weight/day, but not at 20 mg/kg/day. Exposure estimates for women of reproductive age were estimated to be 7.8 mug/kg body weight/day. Therefore, this estimated exposure is at least 2,500-to 25,000- fold lower than the toxic dose in rats. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511). PMID:15995737

  15. 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


  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. 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. PMID:22927915

  18. Developmental toxicity guideline critique

    SciTech Connect

    Johnson, E.M.

    1987-07-01

    The toxicity guidelines include the following major sections: definitions and terminology; qualitative assessment which provides a brief description of the most commonly used developmental toxicity experimental protocol; endpoint assays; functional effects; short term testing; pharmacokinetics; studies of humans; structure-activity relationships; decision-making regarding developmental toxicity; and risk assessment.

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

    PubMed

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

    2015-01-01

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

  20. 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.

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

    PubMed

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

    2015-11-01

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

  2. In Utero Exposures, Infant Growth, and DNA Methylation of Repetitive Elements and Developmentally Related Genes in Human Placenta

    PubMed Central

    Wilhelm-Benartzi, Charlotte S.; Houseman, E. Andres; Maccani, Matthew A.; Poage, Graham M.; Koestler, Devin C.; Langevin, Scott M.; Gagne, Luc A.; Banister, Carolyn E.; Padbury, James F.

    2011-01-01

    Background: Fetal programming describes the theory linking environmental conditions during embryonic and fetal development with risk of diseases later in life. Environmental insults in utero may lead to changes in epigenetic mechanisms potentially affecting fetal development. Objectives: We examined associations between in utero exposures, infant growth, and methylation of repetitive elements and gene-associated DNA in human term placenta tissue samples. Methods: Placental tissues and associated demographic and clinical data were obtained from subjects delivering at Women and Infants Hospital in Providence, Rhode Island (USA). Methylation levels of long interspersed nuclear element-1 (LINE-1) and the Alu element AluYb8 were determined in 380 placental samples from term deliveries using bisulfite pyrosequencing. Genomewide DNA methylation profiles were obtained in a subset of 184 samples using the Illumina Infinium HumanMethylation27 BeadArray. Multiple linear regression, model-based clustering methods, and gene set enrichment analysis examined the association between birth weight percentile, demographic variables, and repetitive element methylation and gene-associated CpG locus methylation. Results: LINE-1 and AluYb8 methylation levels were found to be significantly positively associated with birth weight percentile (p = 0.01 and p < 0.0001, respectively) and were found to differ significantly among infants exposed to tobacco smoke and alcohol. Increased placental AluYb8 methylation was positively associated with average methylation among CpG loci found in polycomb group target genes; developmentally related transcription factor binding sites were overrepresented for differentially methylated loci associated with both elements. Conclusions: Our results suggest that repetitive element methylation markers, most notably AluYb8 methylation, may be susceptible to epigenetic alterations resulting from the intrauterine environment and play a critical role in mediating placenta function, and may ultimately inform on the developmental basis of health and disease. PMID:22005006

  3. Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration.

    PubMed

    Pallocca, Giorgia; Grinberg, Marianna; Henry, Margit; Frickey, Tancred; Hengstler, Jan G; Waldmann, Tanja; Sachinidis, Agapios; RahnenfĂŒhrer, Jörg; Leist, Marcel

    2016-01-01

    The in vitro test battery of the European research consortium ESNATS ('novel stem cell-based test systems') has been used to screen for potential human developmental toxicants. As part of this effort, the migration of neural crest (MINC) assay has been used to evaluate chemical effects on neural crest function. It identified some drug-like compounds in addition to known environmental toxicants. The hits included the HSP90 inhibitor geldanamycin, the chemotherapeutic arsenic trioxide, the flame-retardant PBDE-99, the pesticide triadimefon and the histone deacetylase inhibitors valproic acid and trichostatin A. Transcriptome changes triggered by these substances in human neural crest cells were recorded and analysed here to answer three questions: (1) can toxicants be individually identified based on their transcript profile; (2) how can the toxicity pattern reflected by transcript changes be compacted/dimensionality-reduced for practical regulatory use; (3) how can a reduced set of biomarkers be selected for large-scale follow-up? Transcript profiling allowed clear separation of different toxicants and the identification of toxicant types in a blinded test study. We also developed a diagrammatic system to visualize and compare toxicity patterns of a group of chemicals by giving a quantitative overview of altered superordinate biological processes (e.g. activation of KEGG pathways or overrepresentation of gene ontology terms). The transcript data were mined for potential markers of toxicity, and 39 transcripts were selected to either indicate general developmental toxicity or distinguish compounds with different modes-of-action in read-across. In summary, we found inclusion of transcriptome data to largely increase the information from the MINC phenotypic test. PMID:26705709

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

    PubMed

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

    2015-06-01

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

  5. 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…

  6. 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

  7. 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.

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

    PubMed Central

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

    2011-01-01

    Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3? that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3?), and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define novel candidates for related human diseases. PMID:21423666

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

    PubMed Central

    Paulus, Markus

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. (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


  12. 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)

  13. 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…

  14. 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…

  15. 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


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

    PubMed Central

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

    2014-01-01

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

  17. Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs.

    PubMed

    Yu, Y; Zhang, C; Zhou, G; Wu, S; Qu, X; Wei, H; Xing, G; Dong, C; Zhai, Y; Wan, J; Ouyang, S; Li, L; Zhang, S; Zhou, K; Zhang, Y; Wu, C; He, F

    2001-08-01

    Fetal liver intriguingly consists of hepatic parenchymal cells and hematopoietic stem/progenitor cells. Human fetal liver aged 22 wk of gestation (HFL22w) corresponds to the turning point between immigration and emigration of the hematopoietic system. To gain further molecular insight into its developmental and functional characteristics, HFL22w was studied by generating expressed sequence tags (ESTs) and by analyzing the compiled expression profiles of liver at different developmental stages. A total of 13,077 ESTs were sequenced from a 3'-directed cDNA library of HFL22w, and classified as follows: 5819 (44.5%) matched to known genes; 5460 (41.8%) exhibited no significant homology to known genes; and the remaining 1798 (13.7%) were genomic sequences of unknown function, mitochondrial genomic sequences, or repetitive sequences. Integration of ESTs of known human genes generated a profile including 1660 genes that could be divided into 15 gene categories according to their functions. Genes related to general housekeeping, ESTs associated with hematopoiesis, and liver-specific genes were highly expressed. Genes for signal transduction and those associated with diseases, abnormalities, or transcription regulation were also noticeably active. By comparing the expression profiles, we identified six gene groups that were associated with different developmental stages of human fetal liver, tumorigenesis, different physiological functions of Itoh cells against the other types of hepatic cells, and fetal hematopoiesis. The gene expression profile therefore reflected the unique functional characteristics of HFL22w remarkably. Meanwhile, 110 full-length cDNAs of novel genes were cloned and sequenced. These novel genes might contribute to our understanding of the unique functional characteristics of the human fetal liver at 22 wk. PMID:11483580

  18. Understanding challenges in the front lines of home health care: a human-systems approach.

    PubMed

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

    2014-11-01

    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

  19. Developmental Silencing of Human ?-Globin Gene Expression Is Mediated by the Transcriptional Repressor RREB1*

    PubMed Central

    Chen, Ruei-Lin; Chou, Yu-Chi; Lan, Yii-Jenq; Huang, Ting-Shuo; Shen, C.-K. James

    2010-01-01

    The mammalian embryonic ?-globin genes, including that of humans, are expressed at the early embryonic stage and then switched off during erythroid development. This autonomous silencing of the ?-globin gene transcription is probably regulated by the cooperative work of various protein-DNA and protein-protein complexes formed at the ?-globin promoter and its upstream enhancer (HS-40). We present data here indicating that a protein-binding motif, ZF2, contributes to the repression of the HS-40-regulated human ?-promoter activity in erythroid cell lines and in transgenic mice. Combined site-directed mutagenesis and EMSA suggest that repression of the human ?-globin promoter is mediated through binding of the zinc finger factor RREB1 to ZF2. This model is further supported by the observation that human ?-globin gene transcription is elevated in the human erythroid K562 cell line or the primary erythroid culture upon RNA interference (RNAi)2 knockdown of RREB1 expression. These data together suggest that RREB1 is a putative repressor for the silencing of the mammalian ?-globin genes during erythroid development. Because ?-globin is a powerful inhibitor of HbS polymerization, our experiments have provided a foundation for therapeutic up-regulation of ?-globin gene expression in patients with severe hemoglobinopathies. PMID:20133935

  20. Understanding the interactions between bacteria in the human gut through metabolic modeling

    PubMed Central

    Shoaie, Saeed; Karlsson, Fredrik; Mardinoglu, Adil; Nookaew, Intawat; Bordel, Sergio; Nielsen, Jens

    2013-01-01

    The human gut microbiome plays an influential role in maintaining human health, and it is a potential target for prevention and treatment of disease. Genome-scale metabolic models (GEMs) can provide an increased understanding of the mechanisms behind the effects of diet, the genotype-phenotype relationship and microbial robustness. Here we reconstructed GEMs for three key species, (Bacteroides thetaiotamicron, Eubacterium rectale and Methanobrevibacter smithii) as relevant representatives of three main phyla in the human gut (Bacteroidetes, Firmicutes and Euryarchaeota). We simulated the interactions between these three bacteria in different combinations of gut ecosystems and compared the predictions with the experimental results obtained from colonization of germ free mice. Furthermore, we used our GEMs for analyzing the contribution of each species to the overall metabolism of the gut microbiota based on transcriptome data and demonstrated that these models can be used as a scaffold for understanding bacterial interactions in the gut. PMID:23982459

  1. 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...

  2. 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

  3. 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…

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

    PubMed

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

    2015-01-01

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

  5. 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…

  6. 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


  7. 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.

  8. 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

  9. 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.

  10. Developmental origins of adult diseases

    PubMed Central

    Mathew, Vivek; Ayyar, S. Vageesh

    2012-01-01

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

  11. Developmental dyslexia.

    PubMed

    Peterson, Robin L; Pennington, Bruce F

    2015-01-01

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

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

    PubMed Central

    Ye, Kaixiong; Gu, Zhenglong

    2011-01-01

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

  13. 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...

  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. Allowing for Psychosis to be Approachable and Understandable as a Human Experience: A Role for the Humanities in Psychotherapy Supervision.

    PubMed

    Leonhardt, Bethany L; Hamm, Jay A; Fogley, Rebecca L; Buck, Kelly D; Roe, David; Lysaker, Paul H

    2015-01-01

    Psychiatry and related mental health fields, in particular psychotherapy, have a long history of close ties with the humanities. That bond has weakened, however, over the last few decades as medicalized views of mental health and treatment have emerged. In this paper, we explore the potential of the reintroduction of the humanities, specifically novels and related literary genre, into the supervision of student clinicians working with clients who have psychosis. We believe that incorporation of novels and related literary genre into supervision can lead to unique and deepened understanding of the experience of psychosis, and can create an opportunity for a working therapeutic alliance. The potential mechanisms that create these unique opportunities to understand psychopathology are explored, and considerations for the implications for treatment, training, and future research are presented. PMID:26241798

  16. Hypoxia Alters the Expression of Dipeptidyl Peptidase 4 and Induces Developmental Remodeling of Human Preadipocytes

    PubMed Central

    Chowdhury, Helena H.; Velebit, Jelena; Radić, Nataơa; Frančič, Vito; Kreft, Marko; Zorec, Robert

    2016-01-01

    Dipeptidyl peptidase 4 (DPP4), a transmembrane protein, has been identified in human adipose tissue and is considered to be associated with obesity-related type 2 diabetes. Since adipose tissue is relatively hypoxic in obese participants, we investigated the expression of DPP4 in human preadipocytes (hPA) and adipocytes in hypoxia, during differentiation and upon insulin stimulation. The results show that DPP4 is abundantly expressed in hPA but very sparsely in adipocytes. During differentiation in vitro, the expression of DPP4 in hPA is reduced on the addition of differentiation medium, indicating that this protein can be hPA marker. Long term hypoxia altered the expression of DPP4 in hPA. In in vitro hypoxic conditions the protease activity of shed DPP4 is reduced; however, in the presence of insulin, the increase in DPP4 expression is potentiated by hypoxia. PMID:26881257

  17. Developmental validation of the Quantifiler(ź) HP and Trio Kits for human DNA quantification in forensic samples.

    PubMed

    Holt, Allison; Wootton, Sharon Chao; Mulero, Julio J; Brzoska, Pius M; Langit, Emanuel; Green, Robert L

    2016-03-01

    The quantification of human genomic DNA is a necessary first step in the DNA casework sample analysis workflow. DNA quantification determines optimal sample input amounts for subsequent STR (short tandem repeat) genotyping procedures, as well as being a useful screening tool to identify samples most likely to provide probative genotypic evidence. To better mesh with the capabilities of newest-generation STR analysis assays, the Quantifiler(ź) HP and Quantifiler(ź) Trio DNA Quantification Kits were designed for greater detection sensitivity and more robust performance with samples that contain PCR inhibitors or degraded DNA. The new DNA quantification kits use multiplex TaqMan(ź) assay-based fluorescent probe technology to simultaneously quantify up to three human genomic targets, allowing samples to be assessed for total human DNA, male contributor (i.e., Y-chromosome) DNA, as well as a determination of DNA degradation state. The Quantifiler HP and Trio Kits use multiple-copy loci to allow for significantly improved sensitivity compared to earlier-generation kits that employ single-copy target loci. The kits' improved performance provides better predictive ability for results with downstream, newest-generation STR assays, and their shortened time-to-result allows more efficient integration into the forensic casework analysis workflow. PMID:26774100

  18. Species differences in developmental toxicity of epoxiconazole and its relevance to humans.

    PubMed

    Schneider, Steffen; Hofmann, Thomas; Stinchcombe, Stefan; Moreno, Maria Cecilia Rey; Fegert, Ivana; Strauss, Volker; Gröters, Sibylle; Fabian, Eric; Thiaener, Jutta; Fussell, Karma C; van Ravenzwaay, Bennard

    2013-06-01

    Epoxiconazole, a triazole-based fungicide, was tested in toxicokinetic, prenatal and pre-postnatal toxicity studies in guinea pigs, following oral (gavage) administration at several dose levels (high dose: 90 mg/kg body weight per day). Maternal toxicity was evidenced by slightly increased abortion rates and by histopathological changes in adrenal glands, suggesting maternal stress. No compound-related increase in the incidence of malformations or variations was observed in the prenatal study. In the pre-postnatal study, epoxiconazole did not adversely affect gestation length, parturition, or postnatal growth and development. Administration of epoxiconazole did not alter circulating estradiol levels. Histopathological examination of the placentas did not reveal compound-related effects. The results in guinea pigs are strikingly different to those observed in pregnant rats, in which maternal estrogen depletion, pathological alteration of placentas, increased gestation length, late fetal death, and dystocia were observed after administration of epoxiconazole. In the studies reported here, analysis of maternal plasma concentrations and metabolism after administration of radiolabeled epoxiconazole demonstrated that the different results in rats and guinea pigs were not due to different exposures of the animals. A comprehensive comparison of hormonal regulation of pregnancy and birth in murid rodents and primates indicates that the effects on pregnancy and parturition observed in rats are not applicable to humans. In contrast, the pregnant guinea pig shares many similarities to pregnant humans regarding hormonal regulation and is therefore considered to be a suitable species for extrapolation of related effects to humans. PMID:23630118

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

    PubMed Central

    Kim, Jinseop S.; Kaiser, Marcus

    2014-01-01

    The connectome, or the entire connectivity of a neural system represented by a network, ranges across various scales from synaptic connections between individual neurons to fibre tract connections between brain regions. Although the modularity they commonly show has been extensively studied, it is unclear whether the connection specificity of such networks can already be fully explained by the modularity alone. To answer this question, we study two networks, the neuronal network of Caenorhabditis elegans and the fibre tract network of human brains obtained through diffusion spectrum imaging. We compare them to their respective benchmark networks with varying modularities, which are generated by link swapping to have desired modularity values. We find several network properties that are specific to the neural networks and cannot be fully explained by the modularity alone. First, the clustering coefficient and the characteristic path length of both C. elegans and human connectomes are higher than those of the benchmark networks with similar modularity. High clustering coefficient indicates efficient local information distribution, and high characteristic path length suggests reduced global integration. Second, the total wiring length is smaller than for the alternative configurations with similar modularity. This is due to lower dispersion of connections, which means each neuron in the C. elegans connectome or each region of interest in the human connectome reaches fewer ganglia or cortical areas, respectively. Third, both neural networks show lower algorithmic entropy compared with the alternative arrangements. This implies that fewer genes are needed to encode for the organization of neural systems. While the first two findings show that the neural topologies are efficient in information processing, this suggests that they are also efficient from a developmental point of view. Together, these results show that neural systems are organized in such a way as to yield efficient features beyond those given by their modularity alone. PMID:25180307

  20. 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. PMID:22239884

  1. 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. PMID:26083277

  2. Molecular mechanisms of midfacial developmental defects.

    PubMed

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

    2016-03-01

    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. Despite the advances in human genome sequencing technology, the causes of nearly 70% 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. Developmental Dynamics 245:276-293, 2016. © 2015 Wiley Periodicals, Inc. PMID:26562615

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

    PubMed Central

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

    2015-01-01

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

  4. Genetic approaches to understanding human adaptation to altitude in the Andes.

    PubMed

    Rupert, J L; Hochachka, P W

    2001-09-01

    Despite the initial discomfort often experienced by visitors to high altitude, humans have occupied the Andean altiplano for more than 10000 years, and millions of people, indigenous and otherwise, currently live on these plains, high in the mountains of South America, at altitudes exceeding 3000 m. While, to some extent, acclimatization can accommodate the one-third decrease in oxygen availability, having been born and raised at altitude appears to confer a substantial advantage in high-altitude performance compared with having been born and raised at sea level. A number of characteristics have been postulated to contribute to a high-altitude Andean phenotype; however, the relative contributions of developmental adaptation (within the individual) and genetic adaptation (within the population of which the individual is part) to the acquisition of this phenotype have yet to be resolved. A complex trait is influenced by multiple genetic and environmental factors and, in humans, it is inherently very difficult to determine what proportion of the trait is dictated by an individual's genetic heritage and what proportion develops in response to the environment in which the person is born and raised. Looking for changes in putative adaptations in vertically migrant populations, determining the heritability of putative adaptive traits and genetic association analyses have all been used to evaluate the relative contributions of nurture and nature to the Andean phenotype. As the evidence for a genetic contribution to high-altitude adaptation in humans has been the subject of several recent reviews, this article instead focuses on the methodology that has been employed to isolate the effects of 'nature' from those of 'nurture' on the acquisition of the high-altitude phenotype in Andean natives (Quechua and Aymara). The principles and assumptions underlying the various approaches, as well as some of the inherent strengths and weaknesses of each, are briefly discussed. PMID:11581329

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

    PubMed Central

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

    2015-01-01

    ABSTRACT 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. PMID:26035869

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. The interferon-related developmental regulator 1 is used by human papillomavirus to suppress NF?B 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 NF?B/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 NF?B/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

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

    PubMed

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

    2016-04-01

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

  11. An investigation of the general, reproductive and postnatal developmental toxicity of Betapol, a human milk fat equivalent.

    PubMed

    Spurgeon, M J; Palmer, A K; Hepburn, P A

    2003-10-01

    Betapol consists of triglyceride fatty acids commonly found in vegetable and animal fats. A similarity to human milk fat indicated a potential use in infant formulae as well as for food use in general. To test the potential for substantial equivalence with a related food grade oil, palm oil, Betapol was fed to rats at 15% content in the diet using an augmented two-generation study, in order to obtain information on general (6 months), reproductive and postnatal developmental toxicity in a single study rather than separate studies. For comparison there were two control groups, namely a comparative control fed a diet containing 15% of food grade oil and a negative, or laboratory standard control fed a commercial rodent breeding diet (LAD), containing 2.3-4.7% fat. It was reasoned that if Betapol fed groups showed differences from the comparative control in the direction of the negative control these would reflect differences in the nutritional value of the high fat diets. Presence of a toxicant might be indicated by differences from the comparative control group opposite to the negative control group. The group fed 15% Betapol showed occasional, statistically significant differences from the comparative control group but the direction of difference was towards the negative control group and did not indicate the presence of an unexpected toxicant. PMID:12909269

  12. 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

  13. Evidence for developmental dopaminergic alterations in the human immunodeficiency virus-1 transgenic rat.

    PubMed

    Webb, Katy M; Aksenov, Michael Y; Mactutus, Charles F; Booze, Rosemarie M

    2010-03-01

    Neurologic impairments associated with human immunodeficiency virus (HIV) infection in pediatric patients may affect quality of life, and can develop despite antiretroviral therapy (ART). Behavioral changes observed in clinical studies of HIV-infected children suggest alterations in dopaminergic neurotransmission. Findings from our model of choice, the HIV-1 transgenic rat, reveal a significant increase in phosphorylated tyrosine hydroxylase protein expression and a decrease in dopamine transporter mRNA, without changes in tyrosine hydroxylase (TH) or dopamine transporter (DAT) protein or in more general markers of protein and gene expression levels in the HIV-1 transgenic rat midbrain. Thus these findings suggest selective vulnerability of the dopamine system in developing brains to HIV-1 infection. PMID:20337512

  14. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  17. 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

  18. 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…

  19. Our Globe Vs. Our Brain: Modeling and Understanding the Climate Vs. Human Cognition.

    NASA Astrophysics Data System (ADS)

    Lewandowsky, S.

    2014-12-01

    Climate models have made a notable contribution to increasing our understanding of the climate system, and in particular its response to forcings from greenhouse gases. In parallel, models of the human cognitive system have also made a notable contribution to our understanding of how people think and reason, and in particular the limitations of human cognition. In light of the challenges that climate change poses to politics and society at large, the intersection of human cognition and the climate system deserves to be examined more closely. For example, recent analyses (Lewandowsky et al., 2014, Climatic Change) have shown that the magnitude of uncertainty about future temperature increases is associated with the magnitude of future risk: That is, the greater the uncertainty, the greater the expected damage costs and risk of mitigation failure. Greater uncertainty should therefore lead to greater, not lesser, concern about climate change. However, there is evidence that uncertainty sometimes has the opposite effect on people, for example by inviting "wishful thinking." I review some of the mismatches between the actual behavior of the climate system and people's responses to climate change. I also identify some ways in which people and the climate behave similarly: For example, the climate system is known to include "amplifying loops" and "tipping points", and I argue that human societies may similarly amplify small disturbances from climate change into larger ones.

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

    SciTech Connect

    Welin, Martin; Nordlund, Paer; Division of Biophysics, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm

    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.

  1. 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


  2. 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…

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  5. Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation.

    PubMed

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

    2013-09-24

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

  6. Developmentally stable chromatin structure in the human. beta. -globin gene cluster

    SciTech Connect

    Forrester, W.C.; Thompson, C.; Elder, J.T.; Groudine, M.

    1986-03-01

    The DNase I-hypersensitive sites in the human embryonic ..beta..-globin gene region have been mapped in erythroid-enriched fractions of disaggregated fetal livers, in adult nucleated red blood cells, and in fetal brain tissue. The analysis of a region extending 11 kilobases (kb) 5' of the epsilion-globin gene reveals many minor nuclease-hypersensitive sites and one major site located 6.1 kb upstream of the epsilon-globin gene. All of these hypersensitive sites are erythroid-specific, and the major site is stable throughout erythroid development. As assayed by nuclear runoff transcription, little or no epsilon-globin gene expression is detectable in fetal or adult erythroid cells. Thus, the presence of the major hypersensitive site 5' of the epsilon-globin gene in both fetal and adult erythroid cells demonstrates that this site is not specifically correlated with transcription of the gene or with a particular stage of development. Rather, this site may reflect an early event in erythroid differentiation. In addition, DNase I has been used to probe the overall sensitivity of epsilon-globin chromatin in fetal erythroid cells. The findings indicate that the epsilon-globin gene as well as the other genes in the ..beta..-globin cluster reside within the chomatin domain that is more DNase I-sensitive than bulk chromatin.

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

    PubMed Central

    Patrick, Susan K.; Noah, J. Adam

    2012-01-01

    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. PMID:22402655

  8. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

  11. 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

  12. 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

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

    PubMed

    Mabbott, Neil A

    2015-10-01

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

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

    PubMed Central

    2015-01-01

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

  15. 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. PMID:24628109

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

    EPA Science Inventory

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

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

    PubMed

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

    2016-04-19

    Decades of research on human fertility has presented a clear picture ofhowfertility varies, including its dramatic decline over the last two centuries in most parts of the world.Whyfertility varies, both between and within populations, is not nearly so well understood. Fertility is a complex phenomenon, partly physiologically and partly behaviourally determined, thus an interdisciplinary approach is required to understand it. Evolutionary demographers have focused on human fertility since the 1980s. The first wave of evolutionary demographic research made major theoretical and empirical advances, investigating variation in fertility primarily in terms of fitness maximization. Research focused particularly on variation within high-fertility populations and small-scale subsistence societies and also yielded a number of hypotheses for why fitness maximization seems to break down as fertility declines during the demographic transition. A second wave of evolutionary demography research on fertility is now underway, paying much more attention to the cultural and psychological mechanisms underpinning fertility. It is also engaging with the complex, multi-causal nature of fertility variation, and with understanding fertility in complex modern and transitioning societies. Here, we summarize the history of evolutionary demographic work on human fertility, describe the current state of the field, and suggest future directions. PMID:27022071

  18. Understanding structural-functional relationships in the human brain: a large-scale network perspective.

    PubMed

    Wang, Zhijiang; Dai, Zhengjia; Gong, Gaolang; Zhou, Changsong; He, Yong

    2015-06-01

    Relating the brain's structural connectivity (SC) to its functional connectivity (FC) is a fundamental goal in neuroscience because it is capable of aiding our understanding of how the relatively fixed SC architecture underlies human cognition and diverse behaviors. With the aid of current noninvasive imaging technologies (e.g., structural MRI, diffusion MRI, and functional MRI) and graph theory methods, researchers have modeled the human brain as a complex network of interacting neuronal elements and characterized the underlying structural and functional connectivity patterns that support diverse cognitive functions. Specifically, research has demonstrated a tight SC-FC coupling, not only in interregional connectivity strength but also in network topologic organizations, such as community, rich-club, and motifs. Moreover, this SC-FC coupling exhibits significant changes in normal development and neuropsychiatric disorders, such as schizophrenia and epilepsy. This review summarizes recent progress regarding the SC-FC relationship of the human brain and emphasizes the important role of large-scale brain networks in the understanding of structural-functional associations. Future research directions related to this topic are also proposed. PMID:24962094

  19. 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.

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

    PubMed

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

    2015-06-01

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

  1. 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

  2. Interpreting sex differences in enamel hypoplasia in human and non-human primates: Developmental, environmental, and cultural considerations.

    PubMed

    Guatelli-Steinberg, D; Lukacs, J R

    1999-01-01

    The purpose of this review is to provide a synoptic, critical evaluation of the evidence of, and potential etiological factors contributing to, sex differences in the expression of enamel hypoplasia (EH). Specifically, this review considers theoretical expectations and empirical evidence bearing on two central issues. The first of these is the impact of a theorized inherent male vulnerability to physiological stress on sex differences in EH. The second issue is the potential contribution to sex differences in EH of intrinsic differences in male and female enamel composition and development. To address this first issue, EH frequencies by sex are examined in samples subject to a high degree of physiological stress. Based on the concept of inherent male vulnerability (or female buffering), males in stressful environments would be expected to exhibit higher EH frequencies than females. This expectation is evaluated in light of cultural practices of sex-biased investment that mediate the relationship between environmental stress and EH expression. Defects forming prenatally afford an opportunity to study this relationship without the confounding effects of sex-biased postnatal investment. Data bearing on this issue derive from previously conducted studies of EH in permanent and deciduous teeth in both modern and archaeological samples as well as from new data on Indian schoolchildren. To address the second issue, fundamental male-female enamel differences are evaluated for their potential impact on EH expression. A large sex difference in the duration of canine crown formation in non-human primates suggests that male canines may have greater opportunity to record stress events than those of females. This expectation is examined in great apes, whose canines often record multiple episodes of stress and are sexually dimorphic in crown formation times. With respect to the first issue, in most studies, sex differences in EH prevalence are statistically nonsignificant. However, when sex differences are significant, there is a slight trend for them to be greater in males than in females, suggesting a weak influence of greater male vulnerability. Cultural practices of sex-biased investment in children appear to have greater impact on EH expression than does male vulnerability/female buffering. With respect to the second issue, sex differences in the composition and development of enamel were reviewed and determined to have limited or unknown impact on EH expression. Of these factors, only the duration of crown formation was expected to affect EH expression by sex within the great apes. The data support an association between higher defect counts in the canines of great ape males relative to those of females that may be the result of longer crown formation times in the canines of great ape males. This review concludes with an assessment of the nature of the evidence currently available to examine these issues and suggests future avenues for research focused on elucidating them. PMID:10601984

  3. 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

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

    PubMed

    Lega, Bradley C

    2006-03-01

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

  5. Understanding the influence of watershed storage caused by human interferences on ET variance

    NASA Astrophysics Data System (ADS)

    Zeng, R.; Cai, X.

    2014-12-01

    Understanding the temporal variance of evapotranspiration (ET) at the watershed scale remains a challenging task, because it is affected by complex climate conditions, soil properties, vegetation, groundwater and human activities. In a changing environment with extensive and intensive human interferences, understanding ET variance and its factors is important for sustainable water resources management. This study presents an analysis of the effect of storage change caused by human activities on ET variance Irrigation usually filters ET variance through the use of surface and groundwater; however, over-amount irrigation may cause the depletion of watershed storage, which changes the coincidence of water availability and energy supply for ET. This study develops a framework by incorporating the water balance and the Budyko Hypothesis. It decomposes the ET variance to the variances of precipitation, potential ET, catchment storage change, and their covariances. The contributions of ET variance from the various components are scaled by some weighting functions, expressed as long-term climate conditions and catchment properties. ET variance is assessed by records from 32 major river basins across the world. It is found that ET variance is dominated by precipitation variance under hot-dry condition and by evaporative demand variance under cool-wet condition; while the coincidence of water and energy supply controls ET variance under moderate climate condition. Watershed storage change plays an increasing important role in determining ET variance with relatively shorter time scale. By incorporating storage change caused by human interferences, this framework corrects the over-estimation of ET variance in hot-dry climate and under-estimation of ET variance in cool-wet climate. Furthermore, classification of dominant factors on ET variance shows similar patterns as geographic zonation.

  6. METROPOLITAN ATLANTA DEVELOPMENTAL DISABILITIES PROGRAM (MADDSP)

    EPA Science Inventory

    To address the problem of developmental disabilities among children, CDC, the former Division of Birth Defects and Developmental Disabilities, which was funded by the Agency for Toxic Substances and Disease Registry (ATSDR), and the Georgia Department of Human Resources, initiate...

  7. Symmetry States of the physical space: an expanded reference frame for understanding human consciousness.

    PubMed

    Manek, Nisha J

    2012-01-01

    A remarkable phenomenon is taking place around the globe, one that I have been fortunate enough to witness and in which to participate. The relics of the historical Buddha, also known as Siddhartha or Shakyamuni Buddha, still survive today over 2500 years since his enlightenment, and, for the first time in history, are traveling throughout the world. In common Buddhist practice, relics are highly venerated and treasured remains of realized Masters. It is very rare for relics to travel from city to city and be available for viewing by the general public. The Buddha relic tour is demonstrating that a direct experience of the spiritual state is not mysterious, nor is it for a select few. The spiritual state, here defined as a universal theme of unconditional love, is a component of human evolutionary unfoldment, a process through which thousands of human beings have passed, and through which thousands more will pass. We are "waking up" as a species. Consequently, more information is required about this transformation of human consciousness. The Buddha relics offer us a priceless means by which we can obtain a richer perspective about the nature of human consciousness, spiritual realities such as love, and ultimately understanding ourselves. PMID:22106870

  8. Improving the Understanding of Pathogenesis of Human Papillomavirus 16 via Mapping Protein-Protein Interaction Network

    PubMed Central

    Dong, Yongcheng; Kuang, Qifan; Dai, Xu; Li, Rong; Wu, Yiming; Leng, Weijia; Li, Yizhou; Li, Menglong

    2015-01-01

    The human papillomavirus 16 (HPV16) has high risk to lead various cancers and afflictions, especially, the cervical cancer. Therefore, investigating the pathogenesis of HPV16 is very important for public health. Protein-protein interaction (PPI) network between HPV16 and human was used as a measure to improve our understanding of its pathogenesis. By adopting sequence and topological features, a support vector machine (SVM) model was built to predict new interactions between HPV16 and human proteins. All interactions were comprehensively investigated and analyzed. The analysis indicated that HPV16 enlarged its scope of influence by interacting with human proteins as much as possible. These interactions alter a broad array of cell cycle progression. Furthermore, not only was HPV16 highly prone to interact with hub proteins and bottleneck proteins, but also it could effectively affect a breadth of signaling pathways. In addition, we found that the HPV16 evolved into high carcinogenicity on the condition that its own reproduction had been ensured. Meanwhile, this work will contribute to providing potential new targets for antiviral therapeutics and help experimental research in the future. PMID:25961044

  9. Developmental programming and epigenetics.

    PubMed

    Gabory, Anne; Attig, Linda; Junien, Claudine

    2011-12-01

    The ways in which epigenetic modifications fix the effects of early environmental events, ensuring sustained responses to transient stimuli that result in modified gene expression patterns and phenotypes later in life, are a topic of considerable interest. This article focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics, positions, and functions of epigenetic marks. Most epigenetic studies have addressed the long-term effects of environmental stressors on a small number of epigenetic marks, at the global or individual gene level, in humans and in animal models. In parallel, increasing numbers of studies based on high-throughput technologies are revealing additional complexity in epigenetic processes by highlighting the importance of crosstalk between different epigenetic marks in humans and mice. A number of studies focusing on metabolic programming and the developmental origin of health and disease have identified links between early nutrition, epigenetic processes, and long-term illness. The existence of a self-propagating epigenetic cycle has been shown. Moreover, recent studies have shown an obvious sexual dimorphism both for programming trajectories and in response to the same environmental insult. Despite recent progress, however, we are still far from understanding how, when, and where environmental stressors disturb key epigenetic mechanisms. Thus, the need to identify original key marks and monitor the changes they undergo throughout development, during an individual's lifetime, or over several generations remains a challenging issue. PMID:22049164

  10. Developmental Disabilities and Child Welfare.

    ERIC Educational Resources Information Center

    Rycus, Judith S.; Hughes, Ronald C.

    This monograph addresses common misconceptions about developmental disabilities, describes the conditions that child welfare workers are most likely to see, provides examples of effective interventions, and stresses the importance of early intervention to promote healthy development. Specific chapters include: (1) "Understanding Developmental…

  11. 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 will provide an introduction to the problem and a personal perspective to move forward to set up improved operational models to assist societal planning to mitigate the global water crisis.

  12. Understanding and predicting binding between human leukocyte antigens (HLAs) and peptides by network analysis

    PubMed Central

    2015-01-01

    Background As the major histocompatibility complex (MHC), human leukocyte antigens (HLAs) are one of the most polymorphic genes in humans. Patients carrying certain HLA alleles may develop adverse drug reactions (ADRs) after taking specific drugs. Peptides play an important role in HLA related ADRs as they are the necessary co-binders of HLAs with drugs. Many experimental data have been generated for understanding HLA-peptide binding. However, efficiently utilizing the data for understanding and accurately predicting HLA-peptide binding is challenging. Therefore, we developed a network analysis based method to understand and predict HLA-peptide binding. Methods Qualitative Class I HLA-peptide binding data were harvested and prepared from four major databases. An HLA-peptide binding network was constructed from this dataset and modules were identified by the fast greedy modularity optimization algorithm. To examine the significance of signals in the yielded models, the modularity was compared with the modularity values generated from 1,000 random networks. The peptides and HLAs in the modules were characterized by similarity analysis. The neighbor-edges based and unbiased leverage algorithm (Nebula) was developed for predicting HLA-peptide binding. Leave-one-out (LOO) validations and two-fold cross-validations were conducted to evaluate the performance of Nebula using the constructed HLA-peptide binding network. Results Nine modules were identified from analyzing the HLA-peptide binding network with a highest modularity compared to all the random networks. Peptide length and functional side chains of amino acids at certain positions of the peptides were different among the modules. HLA sequences were module dependent to some extent. Nebula archived an overall prediction accuracy of 0.816 in the LOO validations and average accuracy of 0.795 in the two-fold cross-validations and outperformed the method reported in the literature. Conclusions Network analysis is a useful approach for analyzing large and sparse datasets such as the HLA-peptide binding dataset. The modules identified from the network analysis clustered peptides and HLAs with similar sequences and properties of amino acids. Nebula performed well in the predictions of HLA-peptide binding. We demonstrated that network analysis coupled with Nebula is an efficient approach to understand and predict HLA-peptide binding interactions and thus, could further our understanding of ADRs. PMID:26424483

  13. 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

  14. Four decades of teaching developmental biology in Germany.

    PubMed

    Grunz, Horst

    2003-01-01

    I have taught developmental biology in Essen for 30 years. Since my department is named Zoophysiologie (Zoophysiology), besides Developmental Biology, I also have to teach General Animal Physiology. This explains why the time for teaching developmental biology is restricted to a lecture course, a laboratory course and several seminar courses. However, I also try to demonstrate in the lecture courses on General Physiology the close relationship between developmental biology, physiology, morphology, anatomy, teratology, carcinogenesis, evolution and ecology (importance of environmental factors on embryogenesis). Students are informed that developmental biology is a core discipline of biology. In the last decade, knowledge about molecular mechanisms in different organisms has exponentially increased. The students are trained to understand the close relationship between conserved gene structure, gene function and signaling pathways, in addition to or as an extension of, classical concepts. Public reports about the human genome project and stem cell research (especially therapeutic and reproductive cloning) have shown that developmental biology, both in traditional view and at the molecular level, is essential for the understanding of these complex topics and for serious and non-emotional debate. PMID:12705670

  15. Developmental Career Counseling.

    ERIC Educational Resources Information Center

    O'Brien, Michael T.

    This paper outlines a developmental self psychology for use by career counselors with career clients. It offers a definition of a psychological self, draws from the work of Mead, Vygotsky, and Kohut to develop an understanding of the processes involved in the development and internalization of a psychological self, and connects the work of career…

  16. 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

  17. Advanced simulation technology used to reduce accident rates through a better understanding of human behaviors and human perception

    NASA Astrophysics Data System (ADS)

    Manser, Michael P.; Hancock, Peter A.

    1996-06-01

    Human beings and technology have attained a mutually dependent and symbiotic relationship. It is easy to recognize how each depends on the other for survival. It is also easy to see how technology advances due to human activities. However, the role technology plays in advancing humankind is seldom examined. This presentation examines two research areas where the role of advanced visual simulation systems play an integral and essential role in understanding human perception and behavior. The ultimate goal of this research is the betterment of humankind through reduced accident and death rates in transportation environments. The first research area examined involved the estimation of time-to-contact. A high-fidelity wrap-around simulator (RAS) was used to examine people's ability to estimate time-to- contact. The ability of people to estimate the amount of time before an oncoming vehicle will collide with them is a necessary skill for avoiding collisions. A vehicle approached participants at one of three velocities, and while en route to the participant, the vehicle disappeared. The participants' task was to respond when they felt the accuracy of time-to-contact estimates and the practical applications of the result. The second area of research investigates the effects of various visual stimuli on underground transportation tunnel walls for the perception of vehicle speed. A RAS is paramount in creating visual patterns in peripheral vision. Flat-screen or front-screen simulators do not have this ability. Results are discussed in terms of speed perception and the application of these results to real world environments.

  18. 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…

  19. 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,…

  20. 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...

  1. 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...

  2. 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


  3. 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,


  4. Application of high-throughput sequencing in understanding human oral microbiome related with health and disease

    PubMed Central

    Chen, Hui; Jiang, Wen

    2014-01-01

    The oral microbiome is one of most diversity habitat in the human body and they are closely related with oral health and disease. As the technique developing, high-throughput sequencing has become a popular approach applied for oral microbial analysis. Oral bacterial profiles have been studied to explore the relationship between microbial diversity and oral diseases such as caries and periodontal disease. This review describes the application of high-throughput sequencing for characterization of oral microbiota and analyzing the changes of the microbiome in the states of health or disease. Deep understanding the knowledge of microbiota will pave the way for more effective prevent dentistry and contribute to the development of personalized dental medicine. PMID:25352835

  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. Developmental regulation of AMPA receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury: Part II. Human cerebral white matter and cortex

    PubMed Central

    Talos, Delia M.; Follett, Pamela L.; Folkerth, Rebecca D.; Fishman, Rachel E.; Trachtenberg, Felicia L.; Volpe, Joseph J.; Jensen, Frances E.

    2010-01-01

    This report is the second of a two-part evaluation of developmental differences in α–amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit expression in cell populations within white matter and cortex. In Part I, we report that in rat, developmental expression of Ca2+ permeable (GluR2-lacking) AMPARs correlated at the regional and cellular level with increased susceptibility to hypoxia/ischemia (H/I), suggesting an age-specific role of these receptors in the pathogenesis of brain injury. Part II examines the regional and cellular progression of AMPAR subunits in human white matter and cortex from midgestation through early childhood. Similar to the rodent, there is a direct correlation between selective vulnerability to H/I and expression of GluR2-lacking AMPARs in human brain. In midgestational cases aged 20-24 postconceptional weeks (PCW) and in premature infants (25-37 PCW), we found that radial glia, premyelinating oligodendrocytes and subplate neurons transiently expressed GluR2-lacking AMPARs. Notably, prematurity represents a developmental window of selective vulnerability for white matter injury, such as periventricular leukomalacia (PVL). During term (38-42 PCW) and post-term neonatal (43-46 PCW) periods, age windows characterized by increased susceptibility to cortical injury and seizures, GluR2 expression was low in the neocortex, specifically on cortical pyramidal and non-pyramidal neurons. This study indicates that Ca2+ permeable AMPAR blockade may represent an age-specific therapeutic strategy for potential use in humans. Furthermore, these data help validate specific rodent maturational stages as appropriate models for evaluation of H/I pathophysiology. PMID:16680761

  7. DEVELOPMENTAL LEVEL AND VOCATIONAL INTERESTS (SVIB).

    ERIC Educational Resources Information Center

    SAGE, ELLIS H.

    DEVELOPMENTAL TASKS OF IMPLEMENTING A VOCATIONAL ROLE IN LATE ADOLESCENCE WERE UNRELATED TO A DEVELOPMENTAL SCALE (DS) FOR COLLEGE FRESHMENT (N=107 MALES). THE DEVELOPMENTAL TASKS CORRELATED SIGNIFICANTLY WITH SOME JACKSON PERSONALITY RESEARCH FORM NEEDS (PRF)--(1) INTEREST PATTERNING CORRELATED WITH UNDERSTANDING (.31) AND AFFILIATION (-.22),…

  8. Developmental Trends.

    ERIC Educational Resources Information Center

    Howe, Frederick C.

    1993-01-01

    Explores developmental patterns in children from kindergarten through grade six. Highlights physical development, including height, activity level, motor skills, and health; mental development, including abstract thought, academic focus, learning difficulties, subject preferences, and creativity; psychosocial development, including interpersonal


  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. Developmental Trends.

    ERIC Educational Resources Information Center

    Howe, Frederick C.

    1993-01-01

    Explores developmental patterns in children from kindergarten through grade six. Highlights physical development, including height, activity level, motor skills, and health; mental development, including abstract thought, academic focus, learning difficulties, subject preferences, and creativity; psychosocial development, including interpersonal…

  11. 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 rigorous prediction of future conflicts, a critical requirement for effective conflict management in the context of increasing human-wildlife interactions. PMID:25757801

  12. 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…

  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. 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…

  15. Volunteer human subjects' understandings of their participation in a biomedical research experiment.

    PubMed

    Morris, Norma; Bàlmer, Brian

    2006-02-01

    The paper focuses on how volunteer human subjects in research understand their own participation in experimentation. We ask how they view their own role, the experimental setting, and how they articulate their understanding of the researcher-subject relationship. The empirical basis of the study is participant-observation and qualitative semi-structures interviews with volunteers in an experimental setting far removed from the more commonly studied randomised control trial (RCT), namely, the early stage testing of a prototype instrument for breast imaging. Analysis of this empirical data leads us to conclude that research subjects do not conform solely to one or other of the models of the researcher-subject relationship suggested in the literature. Rather, the interaction needs to be considered as a social situation which volunteer subjects actively negotiate in real time. They move through multiple roles and identities as part of the navigation through unfamiliar social territory, in order to establish a relationship in which they can feel socially comfortable and appropriately valued. PMID:16085345

  16. 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

  17. Toward Human-Carnivore Coexistence: Understanding Tolerance for Tigers in Bangladesh.

    PubMed

    Inskip, Chloe; Carter, Neil; Riley, Shawn; Roberts, Thomas; MacMillan, Douglas

    2016-01-01

    Fostering local community tolerance for endangered carnivores, such as tigers (Panthera tigris), is a core component of many conservation strategies. Identification of antecedents of tolerance will facilitate the development of effective tolerance-building conservation action and secure local community support for, and involvement in, conservation initiatives. We use a stated preference approach for measuring tolerance, based on the 'Wildlife Stakeholder Acceptance Capacity' concept, to explore villagers' tolerance levels for tigers in the Bangladesh Sundarbans, an area where, at the time of the research, human-tiger conflict was severe. We apply structural equation modeling to test an a priori defined theoretical model of tolerance and identify the experiential and psychological basis of tolerance in this community. Our results indicate that beliefs about tigers and about the perceived current tiger population trend are predictors of tolerance for tigers. Positive beliefs about tigers and a belief that the tiger population is not currently increasing are both associated with greater stated tolerance for the species. Contrary to commonly-held notions, negative experiences with tigers do not directly affect tolerance levels; instead, their effect is mediated by villagers' beliefs about tigers and risk perceptions concerning human-tiger conflict incidents. These findings highlight a need to explore and understand the socio-psychological factors that encourage tolerance towards endangered species. Our research also demonstrates the applicability of this approach to tolerance research to a wide range of socio-economic and cultural contexts and reveals its capacity to enhance carnivore conservation efforts worldwide. PMID:26760035

  18. Human Cytochrome P450 1A1 Structure and Utility in Understanding Drug and Xenobiotic Metabolism*

    PubMed Central

    Walsh, Agnes A.; Szklarz, Grazyna D.; Scott, Emily E.

    2013-01-01

    Cytochrome P450 (CYP) 1A1 is an extrahepatic monooxygenase involved in the metabolism of endogenous substrates and drugs, as well as the activation of certain toxins and environmental pollutants. CYP1A1 is particularly well known for its ability to biotransform polycyclic aromatic hydrocarbons, such as benzo[a]pyrene in tobacco smoke, into carcinogens. CYP1A1 possesses functional similarities and differences with human CYP1A2 and CYP1B1 enzymes, but the structural basis for this has been unclear. We determined a 2.6 Å structure of human CYP1A1 with the inhibitor α-naphthoflavone. α-Naphthoflavone binds within an enclosed active site, with the planar benzochromen-4-one core packed flat against the I helix that composes one wall of the active site, and the 2-phenyl substituent oriented toward the catalytic heme iron. Comparisons with previously determined structures of the related cytochrome P450 1A2 and 1B1 enzymes reveal distinct features among the active sites that may underlie the functional variability of these enzymes. Finally, docking studies probed the ability of CYP1A structures to assist in understanding their known in vitro interactions with several typical substrates and inhibitors. PMID:23508959

  19. 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

  20. The dolphin's (Tursiops truncatus) understanding of human gazing and pointing: knowing what and where.

    PubMed

    Pack, Adam A; Herman, Louis M

    2007-02-01

    The authors tested whether the understanding by dolphins (Tursiops truncatus) of human pointing and head-gazing cues extends to knowing the identity of an indicated object as well as its location. In Experiment 1, the dolphins Phoenix and Akeakamai processed the identity of a cued object (of 2 that were present), as shown by their success in selecting a matching object from among 2 alternatives remotely located. Phoenix was errorless on first trials in this task. In Experiment 2, Phoenix reliably responded to a cued object in alternate ways, either by matching it or by acting directly on it, with each type of response signaled by a distinct gestural command given after the indicative cue. She never confused matching and acting. In Experiment 3, Akeakamai was able to process the geometry of pointing cues (but not head-gazing cues), as revealed by her errorless responses to either a proximal or distal object simultaneously present, when each object was indicated only by the angle at which the informant pointed. The overall results establish that these dolphins could identify, through indicative cues alone, what a human is attending to as well as where. PMID:17324073

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

    PubMed

    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

  2. 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

  3. 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…

  4. 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


  5. 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…

  6. 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 novel target genes, termed forerunner (FR) genes, involved in early phases of cancer development. PMID:18458673

  7. 'What's up, (R)DoC?'--can identifying core dimensions of early functioning help us understand, and then reduce, developmental risk for mental disorders?

    PubMed

    Sonuga-Barke, Edmund J S

    2014-08-01

    In the U.S. the National Institute of Mental Health (NIMH), the main funder of mental health research in the world, has recently changed its funding model to promote a radically new perspective for mental health science. This bold, and for some controversial, initiative, termed the Research Diagnostic Criteria (or RDoC for short), intends to shift the focus of research, and eventually clinical practice, away from existing diagnostic categories, as recently updated in the DSM-5, towards 'new ways of classifying psychopathology based on dimensions of observable behavior and neurobiological measures.' This reorientation from discrete categorical disorder manifestations to underlying cross-cutting dimensions of individual functioning has generated considerable debate across the community of mental health researchers and clinicians (with strong views voiced both pro and con). Given its pivotal role in defining the research agenda globally, there is little doubt that this US science funding initiative will also have ramifications for researchers and clinicians worldwide. In this Editorial we focus specifically on the translational potential of the dimensional RDoC approach, properly extended to developmental models of early risk, in terms of its value as a potential driver of early intervention/prevention models; in the current issue of the JCPP this is exemplified by a number of papers thata address the mapping of underlying dimensions of core functioning to disorder risk, providing evidence for their potential predictive power as early markers of later disorder processes. PMID:25039570

  8. Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors.

    PubMed

    Eberhardt, Esther; Havlicek, Steven; Schmidt, Diana; Link, Andrea S; Neacsu, Cristian; Kohl, Zacharias; Hampl, Martin; Kist, Andreas M; Klinger, Alexandra; Nau, Carla; Schüttler, Jürgen; Alzheimer, Christian; Winkler, Jürgen; Namer, Barbara; Winner, Beate; Lampert, Angelika

    2015-09-01

    Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain. PMID:26321143

  9. Pattern of Functional TTX-Resistant Sodium Channels Reveals a Developmental Stage of Human iPSC- and ESC-Derived Nociceptors

    PubMed Central

    Eberhardt, Esther; Havlicek, Steven; Schmidt, Diana; Link, Andrea S.; Neacsu, Cristian; Kohl, Zacharias; Hampl, Martin; Kist, Andreas M.; Klinger, Alexandra; Nau, Carla; Schüttler, Jürgen; Alzheimer, Christian; Winkler, Jürgen; Namer, Barbara; Winner, Beate; Lampert, Angelika

    2015-01-01

    Summary Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain. PMID:26321143

  10. Understanding human – bat interactions in NSW, Australia: improving risk communication for prevention of Australian bat lyssavirus

    PubMed Central

    2014-01-01

    Background Australian bat lyssavirus (ABLV) infects a number of flying fox and insectivorous bats species in Australia. Human infection with ABLV is inevitably fatal unless prior vaccination and/or post-exposure treatment (PET) is given. Despite ongoing public health messaging about the risks associated with bat contact, surveillance data have revealed a four-fold increase in the number of people receiving PET for bat exposure in NSW between 2007 and 2011. Our study aimed to better understand these human – bat interactions in order to identify additional risk communication messages that could lower the risk of potential ABLV exposure. All people aged 18 years or over whom received PET for non-occupation related potential ABLV exposure in the Hunter New England Local Health District of Australia between July 2011 and July 2013 were considered eligible for the study. Eligible participants were invited to a telephone interview to explore the circumstances of their bat contact. Interviews were then transcribed and thematically analysed by two independent investigators. Results Of 21 eligible participants that were able to be contacted, 16 consented and participated in a telephone interview. Participants reported bats as being widespread in their environment but reported a general lack of awareness about ABLV, particularly the risk of disease from bat scratches. Participants who attempted to ‘rescue’ bats did so because of a deep concern for the bat’s welfare. Participants reported a change in risk perception after the exposure event and provided suggestions for public health messages that could be used to raise awareness about ABLV. Conclusions Reframing the current risk messages to account for the genuine concern of people for bat welfare may enhance the communication. The potential risk to the person and possible harm to the bat from an attempted ‘rescue’ should be promoted, along with contact details for animal rescue groups. The potential risk of ABLV from bat scratches merits greater emphasis. PMID:24984790

  11. Understanding the mercury reduction issue: the impact of mercury on the environment and human health.

    PubMed

    Kao, Richard T; Dault, Scott; Pichay, Teresa

    2004-07-01

    Mercury has been used in both medicine and dentistry for centuries. Recent media attention regarding the increased levels of mercury in dietary fish, high levels of mercury in air emissions, and conjecture that certain diseases may be caused by mercury exposure has increased public awareness of the potential adverse health effects of high doses of mercury. Dentistry has been criticized for its continued use of mercury in dental amalgam for both public health and environmental reasons. To address these concerns, dental professionals should understand the impact of the various levels and types of mercury on the environment and human health. Mercury is unique in its ability to form amalgams with other metals. Dental amalgam--consisting of silver, copper, tin, and mercury--has been used as a safe, stable, and cost-effective restorative material for more than 150 years. As a result of this use, the dental profession has been confronted by the public on two separate health issues concerning the mercury content in amalgam. The first issue is whether the mercury amalgamated with the various metals to create dental restorations poses a health issue for patients. The second is whether the scraps associated with amalgam placement and the removal of amalgam restorations poses environmental hazards which may eventually have an impact on human health. Despite the lack of scientific evidence for such hazards, there is growing pressure for the dental profession to address these health issues. In this article, the toxicology of mercury will be reviewed and the impact of amalgam on health and the environment will be examined. PMID:15468538

  12. 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

  13. New paradigm for understanding in-flight decision making errors: a neurophysiological model leveraging human factors.

    PubMed

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

    2008-08-01

    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

  14. Müllerianosis: four developmental (embryonic) mullerian diseases.

    PubMed

    Batt, Ronald E; Yeh, John

    2013-09-01

    The theory of müllerianosis predicts that embryonic müllerian tissue, misplaced during organogenesis, results in the formation of 4 benign müllerian diseases-developmental adenomyosis, endometriosis, endosalpingiosis, and endocervicosis-(developmental müllerian diseases) that will be identified in human female fetuses, infants, children, adolescents, and adults. Direct evidence is presented to support the existence of developmental adenomyosis, developmental endometriosis, and developmental endocervicosis in human female fetuses along with strong circumstantial evidence supporting the existence of all 4 developmental müllerian diseases in human female infants, children, adolescents, and adults. This evidence throws light upon the pathogenesis of rare müllerian lesions whose pathogenesis remains inexplicable by classical and modern theories. Furthermore, this research has scientific and clinical relevance: scientific relevance because it opens up a new field of comparative research-the 4 developmental müllerian diseases complement the 4 acquired müllerian diseases; clinical relevance because it identifies rare müllerian diseases curable by complete surgical excision. PMID:23314961

  15. Pitfalls in developmental diagnosis.

    PubMed

    Blasco, P A

    1991-12-01

    The more common and more glaring pitfalls in developmental diagnosis encountered during infancy and early childhood have been outlined. Much of the ability to avoid these traps depends on a comfortable understanding of the four spheres of early child development and a sound familiarity with the principles of developmental assessment, especially the separation of intellectual and motor entities. Motor milestones are excellent indicators of motor competence but correlate poorly with intellectual capacity. Language and problem-solving milestones in infancy provide the best insights into a child's intellectual potential, and their evolution is independent of motor competence. They may be obscured by motor disability and as a result may be more difficult to demonstrate, but that is a separate issue. In that instance there is nothing subtle about the fact that one is already dealing with a disabled infant. Psychosocial abilities (affective milestones) are critical in understanding the whole child and in making a meaningful statement about behavior, but they lend little additional information to the assessment of intellectual and motor competence. For physicians the "curb-side consult" is a highly efficient tool that has great practical application to developmental concerns and especially to the avoidance of the pitfalls described. Every practitioner should have a resource in developmental and behavioral pediatrics with whom he or she can communicate in an informal fashion. This is especially valuable in situations in which the urgency or even the need for referral (a time-consuming, expensive, and often anxiety-provoking process) is not clear. PMID:1719470

  16. 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

    In semi-arid regions of Africa, rivers are of vital importance to humans for the many direct ecosystem services they provide and, in some cases, for their potential to irrigate and power larger-scale development. More than in most regions of the world, Africans still rely individually on rivers for domestic water, nutrition, and other materials contributing to their daily welfare. This has led to a uniquely African adaptation of the environmental flow concept to incorporate the basic water needs of people as well as ecosystems. The combined flow is referred to as the 'Reserve'. East Africa has seen comparatively little development of its water resources to-date, but ambitious initiatives are underway to increase water use in new large-scale irrigation schemes and hydropower projects. Consequently, a number of comprehensive environmental flow assessments and ecohydrological research activities have recently been carried out in the region. This presentation briefly reviews the initiatives underway across the region but focuses mainly on combined research and flow-setting efforts in the transboundary Mara River Basin of Kenya and Tanzania, home to more than 800,000 people and the region's most popular conservation areas, Masai-Mara National Reserve and Serengeti National Park. Since 2006 a team of scientists, in cooperation with water authorities and the World Wide Fund for Nature (WWF), has investigated the hydrology, hydraulics, biology, and human uses of the Mara River in order to make initial environmental flow (reserve) recommendations. The flow regime of the still largely unregulated Mara River, based on analyses or 20+ years of data from three gauging stations, is highly variable and perennial flow in the middle reaches is dependent on inflows from two tributaries draining the heavily deforested Mau Escarpment, one of Kenya's five water towers. Downstream flows are also seasonally influenced by inflows from ephemeral tributaries that drain degraded grazing 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.

  17. 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. PMID:21604906

  18. 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.

  19. From competencies to human interests: ways of knowing and understanding in medical education.

    PubMed

    Kumagai, Arno K

    2014-07-01

    When considering the teaching and learning of topics of social relevance in medicine, such as professionalism, medical ethics, the doctor-patient relationship, and issues of diversity and social justice, one is tempted to ask, are the ways of knowing in these fields different from that in the biomedical and clinical sciences? Furthermore, given that the competency approach is dominant in medical education, one might also ask, is the competency model truly appropriate for all of the types of knowledge necessary to become a good physician? These questions are not merely academic, for they are at the core of how these subjects are taught, learned, and assessed.The goal of this article is threefold: first, to explore the nature of knowing and the educational goals in different areas of medicine and, in particular, those areas that have social relevance; second, to critically review the concept of competencies when applied to education in these areas; and third, to explore alternative strategies for teaching, learning, and assessment. This discussion reflects a view that the goal of education in areas of social relevance in medicine should be the enhancement of an understanding of-a deep and abiding connection with-the social responsibilities of the physician. Moving beyond competencies, this approach aspires toward the development of practical wisdom (phronesis) which, when embodied in the physician, links the knowledge and skills of the biomedical and clinical sciences with a moral orientation and call to action that addresses human interests in the practice of medicine. PMID:24662200

  20. Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment

    PubMed Central

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

    2012-01-01

    Benzene causes acute myeloid leukemia and probably other hematological malignancies. As benzene also causes hematotoxicity even in workers exposed to levels below the US permissible occupational exposure limit of 1 part per million, further assessment of the health risks associated with its exposure, particularly at low levels, is needed. Here, we describe the probable mechanism by which benzene induces leukemia involving the targeting of critical genes and pathways through the induction of genetic, chromosomal or epigenetic abnormalities and genomic instability, in a hematopoietic stem cell (HSC); stromal cell dysregulation; apoptosis of HSCs and stromal cells and altered proliferation and differentiation of HSCs. These effects modulated by benzene-induced oxidative stress, aryl hydrocarbon receptor dysregulation and reduced immunosurveillance, lead to the generation of leukemic stem cells and subsequent clonal evolution to leukemia. A mode of action (MOA) approach to the risk assessment of benzene was recently proposed. This approach is limited, however, by the challenges of defining a simple stochastic MOA of benzene-induced leukemogenesis and of identifying relevant and quantifiable parameters associated with potential key events. An alternative risk assessment approach is the application of toxicogenomics and systems biology in human populations, animals and in vitro models of the HSC stem cell niche, exposed to a range of levels of benzene. These approaches will inform our understanding of the mechanisms of benzene toxicity and identify additional biomarkers of exposure, early effect and susceptibility useful for risk assessment. PMID:22166497

  1. Economic and nutritional analyses offer substantial synergies for understanding human nutrition.

    PubMed

    Alderman, Harold; Behrman, Jere R; Hoddinott, John

    2007-03-01

    There is growing recognition that interventions designed to improve human nutritional status have, in addition to their intrinsic value, instrumental value in terms of economic outcomes. In many cases, productivity gains alone provide sufficient economic returns to justify investments using benefit and cost criteria. The often-held belief that nutrition programs are welfare interventions that divert resources that could be better used in other ways to raise national incomes is incorrect. Many investments in nutrition are in fact very good economic investments. This recognition has developed out of work that integrates insights from nutrition and economics. Further exploration of this interface is the focus of this article, which seeks: 1) to outline recent contributions that integrate research results from both economics and nutrition, particularly in the context of poor countries; and 2) to describe some areas in which enhanced collaboration is likely to have substantial payoffs in terms of both improved knowledge and more informed policy choices. Collaborative cross-disciplinary research on the topics described here is likely to have substantial payoffs, not only in terms of our understanding of nutritional and economic issues, but also in the improved design of programs and policies that seek to benefit nutritional-related outcomes. PMID:17311936

  2. Understanding goal-directed human actions and physical causality: the role of mother-infant interaction.

    PubMed

    Hohenberger, Annette; Elsabbagh, Mayada; Serres, Josette; de Schoenen, Scania; Karmiloff-Smith, Annette; Aschersleben, Gisa

    2012-12-01

    This study addresses the relation between early cognitive development and mother-infant interaction. Infants at the age of 6 and 10 months recruited from labs in three European countries--Germany, Great Britain, and France--were tested on two cognitive tasks: understanding of goal-directed human action and physical causality. Mother-infant interaction was assessed with the CARE-Index. In the goal-directed action task, the overall sample of the 6-month olds did not yet reliably discriminate between an object-change and a path-change trial while a subsample of infants of modestly controlling mothers did. All infants at 10 months of age showed discrimination. In the physical causality task, the overall sample of the 6-month olds did not yet reliably discriminate between an expected and an unexpected launching event. At 10 months of age, the overall sample showed discrimination, due to the major subsample of infants of highly sensitive mothers. Our findings support the view that exogenous factors influence cognitive development within a particular time window, in highly specific ways, depending on the age of the subjects, the cognitive domain, and the quality of mother-infant interaction. PMID:23063850

  3. Ad cerebrum per scientia: Ira Hirsh, psychoacoustics, and new approaches to understanding the human brain

    NASA Astrophysics Data System (ADS)

    Lauter, Judith

    2002-05-01

    As Research Director of CID, Ira emphasized the importance of combining information from biology with rigorous studies of behavior, such as psychophysics, to better understand how the brain and body accomplish the goals of everyday life. In line with this philosophy, my doctoral dissertation sought to explain brain functional asymmetries (studied with dichotic listening) in terms of the physical dimensions of a library of test sounds designed to represent a speech-music continuum. Results highlighted individual differences plus similarities in terms of patterns of relative ear advantages, suggesting an organizational basis for brain asymmetries depending on physical dimensions of stimulus and gesture with analogs in auditory, visual, somatosensory, and motor systems. My subsequent work has employed a number of noninvasive methods (OAEs, EPs, qEEG, PET, MRI) to explore the neurobiological bases of individual differences in general and functional asymmetries in particular. This research has led to (1) the AXS test battery for assessing the neurobiology of human sensory-motor function; (2) the handshaking model of brain function, describing dynamic relations along all three body/brain axes; (3) the four-domain EPIC model of functional asymmetries; and (4) the trimodal brain, a new model of individual differences based on psychoimmunoneuroendocrinology.

  4. 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. PMID:26613996

  5. Use of Both Cumulus Cells’ Transcriptomic Markers and Zona Pellucida Birefringence to Select Developmentally Competent Oocytes in Human Assisted Reproductive Technologies

    PubMed Central

    2015-01-01

    Background Selection of the best oocyte for subsequent steps of fertilization and embryo transfer was shown to be the crucial step in human infertility treatment procedure. Oocyte selection using morphological criteria mainly Zona pellucida (ZP) has been the gold standard method in assisted reproductive technologies (ART) clinics, but this selection approach has limitations in terms of accuracy, objectivity and constancy. Recent studies using OMICs-based approaches have allowed the identification of key molecular markers that quantitatively and non-invasively predict the oocyte quality for higher pregnancy rates and efficient infertility treatment. These biomarkers are a valuable reinforcement of the morphological selection criteria widely used in in vitro fertilization (IVF) clinics. In this context, this study was designed to investigate the relationship between transcriptomic predictors of oocyte quality found by our group and the conventional morphological parameters of oocyte quality mainly the ZP birefringence. Results Microarray data revealed that 48 and 27 differentially expressed candidate genes in cumulus cells (CCs) were respectively overexpressed and underexpressed in the ZGP (Zona Good Pregnant) versus ZBNP (Zona Bad Non Pregnant) groups. More than 70% of previously reported transcriptomic biomarkers of oocyte developmental competence were confirmed in this study. The analysis of possible association between ZP birefringence versus molecular markers approach showed an absence of correlation between them using the current set of markers. Conclusions This study suggested a new integrative approach that matches morphological and molecular approaches used to select developmentally competent oocytes able to lead to successful pregnancy and the delivery of healthy baby. For each ZP birefringence score, oocytes displayed a particular CCs' gene expression pattern. However, no correlations were found between the 7 gene biomarkers of oocyte developmental potential and the ZP birefringence score. Further studies using larger lists of candidate markers are required to identify suitable genes that are highly correlated with the morphological criteria, and therefore able to reinforce the accuracy of oocyte selection and the effectiveness of infertility treatment. PMID:25923296

  6. [Developmental dysphasia].

    PubMed

    Turki, Ilhem; Miladi, Najoua

    2005-05-01

    Developmental dysphasia is a specific, primary and lasting oral language disorder (expressive or comprehensive) is the absence of any sensorineural damage oral organ dystunction or psychiatric and psychologic disorders. Pathogensis is still unknown. Diagnosis is based on exprssive and comprehensive language investigation. Therapy should be early and multidisciplinary. PMID:16044895

  7. DEVELOPMENTAL DYSLEXIA.

    ERIC Educational Resources Information Center

    CRITCHLEY, MACDONALD

    DYSLEXIA IS DEFINED AS A FORM OF VERBAL AMNESIA IN WHICH THE PATIENT HAS LOST THE MEMORY OF THE CONVENTIONAL MEANING OF GRAPHIC SYMBOLS. DEVELOPMENTAL DYSLEXIA HAS LONG BEEN THE SUBJECT OF PROFESSIONAL DISPUTES IN MEDICINE, EDUCATION, AND PSYCHOLOGY. THE BOOK TRACES THE GROWTH OF KNOWLEDGE ABOUT DYSLEXIA AND DESCRIBES CONFLICTING IDEAS AS TO…

  8. Developmental delay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrition support is essential for the care of the child with developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the child’s nutrition status, feeding ability, and medical condition may be determined. Nutrition assessments may be performed at leas...

  9. Developmental dyscalculia.

    PubMed

    Shalev, Ruth S

    2004-10-01

    Developmental dyscalculia is a specific learning disability affecting the normal acquisition of arithmetic skills. Genetic, neurobiologic, and epidemiologic evidence indicates that dyscalculia, like other learning disabilities, is a brain-based disorder. However, poor teaching and environmental deprivation have also been implicated in its etiology. Because the neural network of both hemispheres comprises the substrate of normal arithmetic skills, dyscalculia can result from dysfunction of either hemisphere, although the left parietotemporal area is of particular significance. The prevalence of developmental dyscalculia is 5 to 6% in the school-aged population and is as common in girls as in boys. Dyscalculia can occur as a consequence of prematurity and low birthweight and is frequently encountered in a variety of neurologic disorders, such as attention-deficit hyperactivity disorder (ADHD), developmental language disorder, epilepsy, and fragile X syndrome. Developmental dyscalculia has proven to be a persisting learning disability, at least for the short term, in about half of affected preteen pupils. Educational interventions for dyscalculia range from rote learning of arithmetic facts to developing strategies for solving arithmetic exercises. The long-term prognosis of dyscalculia and the role of remediation in its outcome are yet to be determined. PMID:15559892

  10. Aberrant expression of maternal Plk1 and Dctn3 results in the developmental failure of human in-vivo- and in-vitro-matured oocytes.

    PubMed

    Fan, Yong; Zhao, Hong-Cui; Liu, Jianqiao; Tan, Tao; Ding, Ting; Li, Rong; Zhao, Yue; Yan, Jie; Sun, Xiaofang; Yu, Yang; Qiao, Jie

    2015-01-01

    Fertilisation is the first step in embryonic development, and dynamic changes of key genes may potentially improve assisted reproduction techniques efficiency during this process. Here, we analysed genes that were differentially expressed between oocytes and zygotes and focused on cytokinesis-related genes. Plk1 and Dctn3 were identified as showing dramatic changes in expression during fertilisation and were suggested to play a key role in inducing aneuploidy in zygotes and 8-cell embryos. Moreover, we found that maternal Plk1 and Dctn3 were expressed at lower levels in in vitro matured oocytes, which may have contributed to the high ratio of resulting embryos with abnormal Plk1 and Dctn3 expression levels, thereby reducing the developmental competence of the resulting embryos. Furthermore, the overexpression of Dctn3 can silence Plk1 expression, which suggests a potential regulation mechanism. In conclusion, our present study showed that aberrant expression of Plk1 and Dctn3 increases embryo aneuploidy and developmental failure, particularly in in vitro matured oocytes. Our results facilitate a better understanding of the effects of oocyte maternal gene expression on embryonic development and can be used to improve the outcome of assisted reproduction techniques. PMID:25645239

  11. Aberrant expression of maternal Plk1 and Dctn3 results in the developmental failure of human in-vivo- and in-vitro-matured oocytes

    PubMed Central

    Fan, Yong; Zhao, Hong-Cui; Liu, Jianqiao; Tan, Tao; Ding, Ting; Li, Rong; Zhao, Yue; Yan, Jie; Sun, Xiaofang; Yu, Yang; Qiao, Jie

    2015-01-01

    Fertilisation is the first step in embryonic development, and dynamic changes of key genes may potentially improve assisted reproduction techniques efficiency during this process. Here, we analysed genes that were differentially expressed between oocytes and zygotes and focused on cytokinesis-related genes. Plk1 and Dctn3 were identified as showing dramatic changes in expression during fertilisation and were suggested to play a key role in inducing aneuploidy in zygotes and 8-cell embryos. Moreover, we found that maternal Plk1 and Dctn3 were expressed at lower levels in in vitro matured oocytes, which may have contributed to the high ratio of resulting embryos with abnormal Plk1 and Dctn3 expression levels, thereby reducing the developmental competence of the resulting embryos. Furthermore, the overexpression of Dctn3 can silence Plk1 expression, which suggests a potential regulation mechanism. In conclusion, our present study showed that aberrant expression of Plk1 and Dctn3 increases embryo aneuploidy and developmental failure, particularly in in vitro matured oocytes. Our results facilitate a better understanding of the effects of oocyte maternal gene expression on embryonic development and can be used to improve the outcome of assisted reproduction techniques. PMID:25645239

  12. Understanding the links between humans, climate change, water and carbon and in a Corn Belt Watershed

    NASA Astrophysics Data System (ADS)

    Secchi, S.; Perez Lapena, B.; Teshager, A. D.; Bhattarai, M. D.; Schoof, J. T.

    2014-12-01

    Accounting for the value of ecosystem services is difficult for several reasons: we need to understand and model the behavior of humans, and how they respond to changes in policies, we need to quantify the changes in material fluxes or ecological responses resulting from their behavior, and finally we need to monetize the value of those material fluxes. Since coupled human-natural systems are highly idiosyncratic, integrated modeling can be challenging because it is not easy to transfer results from one system to another. Moreover, modeling changes in multiple ecosystem services often requires the simultaneous coordination of several biophysical models. In a non-static world, climate change models are also often necessary to identify future challenges and opportunities for better policy-making. We will discuss results from an integrated modeling perspective for the Raccoon River watershed in central Iowa. The watershed is in the heart of the Corn Belt, and it is under very intensive agricultural production which results in nitrate levels so high that a Total Maximum Daily Load has been put in place. The Des Moines Water Works that provides water to Iowa's capital either from the Raccoon or the Des Moines River has had to build several layers of treatment to ensure the water is safe to drink. We will present results from the integration of an agent-based model with a surface water quality model (the Soil and Water Assessment Tool) and an edge of field environmental model (the Environmental Policy Integrated Climate). The integration can simultaneously provide changes in water quality indicators - particularly nitrates, which can be monetized using the avoided cost method - and carbon sequestration - for which monetary values are readily available in the literature. This integrated system is linked to regional climate change models to help assess changes in agricultural productivity and farmers' behavior in the future. We will discuss the importance of quantifying and monetizing as many services as possible in the context of conservation and agricultural policies that compensate farmers for more environmentally friendly agricultural practices such as the use of no till or the planting of perennial grasses. Monetizing ecosystem services allows for the direct comparison of the costs and benefits of these policies.

  13. Reflections on Multiculturalism in Developmental Education.

    ERIC Educational Resources Information Center

    Bruch, Patrick L.; Higbee, Jeanne L.

    2002-01-01

    Reports on an effort to better understand the impasse and create conditions for constructive local discussions and reforms relating to multiculturalism. Reports how a group of developmental education professionals in a large, interdisciplinary developmental education unit understand multiculturalism. Explores the potentials and challenges involved…

  14. Developmental changes in KCNQ2 and KCNQ3 expression in human brain: possible contribution to the age-dependent etiology of benign familial neonatal convulsions.

    PubMed

    Kanaumi, Takeshi; Takashima, Sachio; Iwasaki, Hiroshi; Itoh, Masayuki; Mitsudome, Akihisa; Hirose, Shinichi

    2008-05-01

    Several mutations of KCNQ2 and KCNQ3 are considered to be associated with benign familial neonatal convulsions (BFNC). BFNC is characterized by seizures starting within several days of life and spontaneous remission within weeks to months. KCNQ channel is a heteromeric voltage-dependent potassium channel consisting of KCNQ2 and KCNQ3 subunits. To clarify the age-dependent etiology of BFNC, we examined the developmental changes in KCNQ2 and KCNQ3 expression in human hippocampus, temporal lobe, cerebellum and medulla oblongata obtained from 23 subjects who died at 22 gestation weeks to adulthood. Formalin-fixed and paraffin-embedded specimens were used for immunohistochemistry. Unique developmental changes in KCNQ2 and KCNQ3 were found in each region. A high expression of KCNQ2 was identified in the hippocampus, temporal cortex, cerebellar cortex and medulla oblongata in fetal life, but such expression decreased after birth. The expression of KCNQ3 increased in late fetal life to infancy. Simultaneous and high expressions of KCNQ2 and KCNQ3 were observed in each region from late fetal life to early infancy, coinciding with the time when BFNC occurs. Such coexpression may contribute to the pathogenesis of BFNC. PMID:18166285

  15. Combining metagenomics, metatranscriptomics and viromics to explore novel microbial interactions: towards a systems-level understanding of human microbiome.

    PubMed

    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. 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; SoberĂłn, Xavier; Del Pozo-Yauner, Luis; Ochoa-Leyva, AdriĂĄn

    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

  17. Developmental psychopathology: concepts and challenges.

    PubMed

    Rutter, M; Sroufe, L A

    2000-01-01

    The defining features of developmental psychopathology concepts include attention to the understanding of causal processes, appreciation of the role of developmental mechanisms, and consideration of continuities and discontinuities between normality and psychopathology. Accomplishments with respect to these issues are reviewed in relation to attachment disorders, antisocial behavior, autism, depressive disorder, schizophrenia, and intellectual development. Major research challenges remain in relation to measurement issues, comorbidity, gender differences, cognitive processing, nature-nurture interplay, heterotypic continuity, continuities between normal variations and disorders, developmental programming, and therapeutic mechanisms in effective treatments. PMID:11014739

  18. Developmental Risk I: Depression and the Developing Brain

    PubMed Central

    Weir, John M.; Zakama, Arthurine; Rao, Uma

    2012-01-01

    SYNOPSIS This article discusses recent findings on the neurobiology of pediatric depression as well as the interplay between genetic and environmental factors in determining the risk for the disorder. Utilizing data from both animal and human studies, the authors focus on the evolving understanding of the developmental neurobiology of emotional regulation, cognitive function and social behavior as it applies to the risk and clinical course of depression. Treatment implications and directions for future research are also discussed. PMID:22537725

  19. miRNA expression profiling in a human stem cell-based model as a tool for developmental neurotoxicity testing.

    PubMed

    Pallocca, Giorgia; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Pamies, David; Laurenza, Incoronata; Bal-Price, Anna

    2013-08-01

    The main aim of this study was to evaluate whether microRNA (miRNA) profiling could be a useful tool for in vitro developmental neurotoxicity (DNT) testing. Therefore, to identify the possible DNT biomarkers among miRNAs, we have studied the changes in miRNA expressions in a mixed neuronal/glial culture derived from carcinoma pluripotent stem cells (NT2 cell line) after exposure to methyl mercury chloride (MeHgCl) during the process of neuronal differentiation (2-36 days in vitro (DIV1)). The neuronal differentiation triggered by exposure to retinoic acid (RA) was characterized in the control culture by mRNA expression analysis of neuronal specific markers such as MAP2, NF-200, Tubulin ?III, MAPT-tau, synaptophysin as well as excitatory (NMDA, AMPA) and inhibitory (GABA) receptors. The results obtained from the miRNA expression analysis have identified the presence of a miRNA signature which is specific for neural differentiation in the control culture and another for the response to MeHgCl-induced toxicity. In differentiated neuronal control cultures, we observed the downregulation of the stemness phenotype-linked miR-302 cluster and the overexpression of several miRNAs specific for neuronal differentiation (e.g. let-7, miR-125b and miR-132). In the cultures exposed to MeHgCl (400 nM), we observed an overexpression of a signature composed of five miRNAs (miR-302b, miR-367, miR-372, miR-196b and miR-141) that are known to be involved in the regulation of developmental processes and cellular stress response mechanisms. Using gene ontology term and pathway enrichment analysis of the validated targets of the miRNAs deregulated by the toxic treatment, the possible effect of MeHgCl exposure on signalling pathways involved in axon guidance and learning and memory processes was revealed. The obtained data suggest that miRNA profiling could provide simplified functional evaluation of the toxicity pathways involved in developmental neurotoxicity in comparison with the transcriptomics studies. PMID:23903816

  20. Human Pluripotent Stem Cell-Derived Radial Glia Recapitulate Developmental Events and Provide Real-Time Access to Cortical Neurons and Astrocytes

    PubMed Central

    Peng, Chian-Yu; Pan, Liuliu; Kessler, John A.

    2015-01-01

    Studies of human cerebral cortex development are limited by difficulties in accessing and manipulating human neural tissue at specific development stages. We have derived human radial glia (hRG), which are responsible for most cerebral cortex neurogenesis, from human pluripotent stem cells. These hRG display the hallmark morphological, cellular, and molecular features of radial glia in vitro. They can be passaged and generate layer-specific subtypes of cortical neurons in a temporal and passage-dependent fashion. In later passages, they adopt a distinct progenitor phenotype that gives rise to cortical astrocytes and GABAergic interneurons. These hRG are also capable of following developmental cues to engraft, differentiate, migrate, and integrate into the embryonic mouse cortex when injected into E14 lateral ventricles. Moreover, hRG-derived cells can be cryopreserved at specific stages and retain their stage-specific phenotypes and competence when revived. Our study demonstrates that cultured hRG maintain a cell-intrinsic clock that regulates the progressive generation of stage-specific neuronal and glial subtypes. It also describes an easily accessible cell source for studying hRG lineage specification and progression and an on-demand supply of specific cortical neuron subtypes and astrocytes. PMID:25834120

  1. 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

  2. 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.

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

    ScienceCinema

    Willerslev, Eske [University of Copenhagen

    2013-01-15

    Eske Willerslev from the University of Copenhagen on "Understanding Historical Human Migration Patterns and Interbreeding Using the Ancient Genomes of a Palaeo-Eskimo and an Aboriginal Australian" at the 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, California.

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

    SciTech Connect

    Willerslev, Eske

    2012-03-21

    Eske Willerslev from the University of Copenhagen on "Understanding Historical Human Migration Patterns and Interbreeding Using the Ancient Genomes of a Palaeo-Eskimo and an Aboriginal Australian" at the 7th Annual Genomics of Energy & Environment Meeting on March 21, 2012 in Walnut Creek, California.

  5. Evo-Devo insights from pathological networks: exploring craniosynostosis as a developmental mechanism for modularity and complexity in the human skull.

    PubMed

    Esteve-Altava, Borja; Rasskin-Gutman, Diego

    2015-07-20

    Bone fusion has occurred repeatedly during skull evolution in all tetrapod lineages, leading to a reduction in the number of bones and an increase in their morphological complexity. The ontogeny of the human skull includes also bone fusions as part of its normal developmental process. However, several disruptions might cause premature closure of cranial sutures (craniosynostosis), reducing the number of bones and producing new skull growth patterns that causes shape changes. Here, we compare skull network models of a normal newborn with different craniosynostosis conditions, the normal adult stage, and phylogenetically reconstructed forms of a primitive tetrapod, a synapsid, and a placental mammal. Changes in morphological complexity of newborn-to-synostosed skulls are two to three times less than in newborn-to-adult; and even smaller when we compare them to the increases among the reconstructed ancestors in the evolutionary transitions. In addition, normal, synostosed, and adult human skulls show the same connectivity modules: facial and cranial. Differences arise in the internal structure of these modules. In the adult skull the facial module has an internal hierarchical organization, whereas the cranial module has a regular network organization. However, all newborn forms, normal and synostosed, do not reach such kind of internal organization. We conclude that the subtle changes in skull complexity at the developmental scale can change the modular substructure of the newborn skull to more integrated modules in the adult skull, but is not enough to generate radical changes as it occurs at a macroevolutionary scale. The timing of closure of craniofacial sutures, together with the conserved patterns of morphological modularity, highlights a potential relation between the premature fusion of bones and the evolution of the shape of the skull in hominids. PMID:25324462

  6. 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…

  7. 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


  8. TITLE OF ABSTRACT: MECHANISMS UNDERLYING SYNERGISTIC DEVELOPMENTAL TOXICITY OF POLYCYCLIC AROMATIC HYDROCARBONS IN ZEBRAFISH (DANIO RERIO)

    EPA Science Inventory

    Understanding the molecular pathways of synergistic developmental toxicity of PAHs will lead to benefits for human as well as wildlife health. As additive models of toxicity are currently used to estimate the hazard of complex mixtures, implementation of synergistic models wh...

  9. 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 stated in the literature, A. mexicanum has a muscle coracoradialis that has both a well developed proximal fleshy belly and a distal long and thin tendon, supporting the idea that this muscle very likely corresponds to at least part of the amniote biceps brachii. Our observations also: (i) confirmed that the flexores digitorum minimi, interphalangeus digiti 3, pronator quadratus and palmaris profundus 1 are present as distinct muscles in A. mexicanum, supporting the idea that the latter muscle does not correspond to the pronator accessorius of reptiles; (ii) confirmed that the so-called extensor antebrachii radialis is present as a distinct muscle in this species and, importantly, indicated that this muscle corresponds to the supinator of other tetrapods; (iii) showed that, contrary to some other urodeles, including some other Ambystoma species, there is no distinct muscle epitrochleoanconeus in A. mexicanum and; (iv) showed that the ulnar and radial bundles of the abductor et extensor digiti 1 correspond to the abductor pollicis longus and extensor pollicis longus of other tetrapods, respectively. PMID:22957800

  10. A novel 2q37 microdeletion containing human neural progenitors genes including STK25 results in severe developmental delay, epilepsy, and microcephaly.

    PubMed

    Imitola, Jaime; Khurana, Divya S; Teplyuk, Nadiya M; Zucker, Mark; Jethva, Reena; Legido, Agustin; Krichevsky, Ana M; Frangieh, Michael; Walsh, Christopher A; Carvalho, Karen S

    2015-11-01

    2q37 microdeletion syndrome is a rare syndrome characterized by neurodevelopmental delay, bone, cardiovascular, and neurological alterations. This syndrome is typically associated with loss of genetic material of approximately 100 genes in the 2q37 band. However, the genes associated with neurodevelopmental phenotype in this syndrome are still unknown. We identified a deleted region of 496?kb by whole genome array CGH in a patient who fulfilled criteria for 2q37 microdeletion syndrome with developmental delay, microcephaly, hypoplasia of the corpus callosum, hand wringing, toe walking, and seizures. The deleted segment contains genes that are highly expressed in the developing human cortical plate and the subventricular zone (SVZ) in vivo and human neural progenitors in vitro, including SEPT2, THAP4, ATG4B, PPP1R7, and STK25. Network analysis revealed that STK25 was the most interacting gene associated with neural development in this deletion. Our report narrows the likely causative genomic region for microcephaly and neurodevelopmental delay in 2q37 microdeletion syndrome to a small genomic region enriched with neural progenitor genes that may represent an important locus for the development of the human cortex and corpus callosum. PMID:26238961

  11. 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.

  12. 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.

  13. In vitro analysis of the homing properties of human lymphocytes: developmental regulation of functional receptors for high endothelial venules.

    PubMed

    Jalkanen, S T; Butcher, E C

    1985-09-01

    Circulating lymphocytes leave the blood by binding to specialized high endothelial cells lining postcapillary venules in lymphoid organs or sites of chronic inflammations, migrating through the vessel wall into the surrounding tissue. The capacity of lymphocytes to recognize and bind to high endothelial venules (HEVs) is thus central to the overall process of lymphocyte traffic and recirculation. We show that viable human lymphocytes bind selectively to HEVs in frozen sections of normal human lymph nodes, thus defining a simple in vitro model for the study of human lymphocyte homing properties. Optimal conditions for the quantitative analysis of lymphocyte-HEV interaction are described. Furthermore, by using this assay, we demonstrate that the ability of human lymphocyte populations to bind to HEVs parallels their presumed migratory status in vivo. Thus, thymocytes and bone marrow cells, which are sessile in vivo, bind poorly to HEVs in comparison with mature circulating lymphocytes in peripheral blood or in peripheral lymphoid tissues. These results indicate that HEV-binding ability is a regulated property of mature lymphocytes and, as demonstrated previously in animal models, probably plays a fundamental role in controlling lymphocyte traffic in humans. The in vitro model of lymphocyte-HEV interaction thus provides a unique means to assay the migratory properties of normal and neoplastic human lymphocyte subsets, to analyze the role of lymphocyte traffic mechanisms in normal and pathologic inflammatory reactions, and to define some of the molecular mechanisms responsible for the control of lymphocyte migration and positioning in humans. PMID:4027380

  14. 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


  15. 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…

  16. Understanding the Human Genome Project: Using Stations to Provide a Comprehensive Overview

    ERIC Educational Resources Information Center

    Soto, Julio G.

    2005-01-01

    A lesson was designed for lower division general education, non-major biology lecture-only course that included the historical and scientific context, some of the skills used to study the human genome, results, conclusions and ethical consideration. Students learn to examine and compare the published Human Genome maps, and employ the strategies…

  17. 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


  18. 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

  19. Developmental perspectives on oxytocin and vasopressin.

    PubMed

    Hammock, Elizabeth A D

    2015-01-01

    The related neuropeptides oxytocin and vasopressin are involved in species-typical behavior, including social recognition behavior, maternal behavior, social bonding, communication, and aggression. A wealth of evidence from animal models demonstrates significant modulation of adult social behavior by both of these neuropeptides and their receptors. Over the last decade, there has been a flood of studies in humans also implicating a role for these neuropeptides in human social behavior. Despite popular assumptions that oxytocin is a molecule of social bonding in the infant brain, less mechanistic research emphasis has been placed on the potential role of these neuropeptides in the developmental emergence of the neural substrates of behavior. This review summarizes what is known and assumed about the developmental influence of these neuropeptides and outlines the important unanswered questions and testable hypotheses. There is tremendous translational need to understand the functions of these neuropeptides in mammalian experience-dependent development of the social brain. The activity of oxytocin and vasopressin during development should inform our understanding of individual, sex, and species differences in social behavior later in life. PMID:24863032

  20. 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 of complex machines, human error in the Shuttle PRA proved to be an important contributor (12 percent) to LOCV. An existing HRA technique was adapted for use in the Shuttle PRA, but additional guidance and improvements are needed to make the HRA task in space-related PRAs easier and more accurate. Therefore, this presentation will also outline plans for expanding current HRA methodology to more explicitly cover spaceflight performance shaping factors.

  1. Utilizing induced pluripotent stem cells (iPSCs) to understand the actions of estrogens in human neurons.

    PubMed

    Shum, Carole; Macedo, Sara C; Warre-Cornish, Katherine; Cocks, Graham; Price, Jack; Srivastava, Deepak P

    2015-08-01

    This article is part of a Special Issue "Estradiol and Cognition". Over recent years tremendous progress has been made towards understanding the molecular and cellular mechanism by which estrogens exert enhancing effects on cognition, and how they act as a neuroprotective or neurotrophic agent in disease. Currently, much of this work has been carried out in animal models with only a limited number of studies using native human tissue or cells. Recent advances in stem cell technology now make it possible to reprogram somatic cells from humans into induced pluripotent stem cells (iPSCs), which can subsequently be differentiated into neurons of specific lineages. Importantly, the reprogramming of cells allows for the generation of iPSCs that retain the genetic "makeup" of the donor. Therefore, it is possible to generate iPSC-derived neurons from patients diagnosed with specific diseases, that harbor the complex genetic background associated with the disorder. Here, we review the iPSC technology and how it's currently being used to model neural development and neurological diseases. Furthermore, we explore whether this cellular system could be used to understand the role of estrogens in human neurons, and present preliminary data in support of this. We further suggest that the use of iPSC technology offers a novel system to not only further understand estrogens' effects in human cells, but also to investigate the mechanism by which estrogens are beneficial in disease. Developing a greater understanding of these mechanisms in native human cells will also aid in the development of safer and more effective estrogen-based therapeutics. PMID:26143621

  2. 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

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

    PubMed Central

    Rabadán-Diehl, C.; Nathanielsz, P.

    2012-01-01

    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. PMID:23525085

  4. Human Cytomegalovirus Intrahost Evolution – A New Avenue for Understanding and Controlling Herpesvirus Infections

    PubMed Central

    Renzette, Nicholas; Gibson, Laura; Jensen, Jeffrey D.; Kowalik, Timothy F.

    2014-01-01

    Human cytomegalovirus (HCMV) is exquisitely adapted to the human host, and much research has focused on its evolution over long timescales spanning millennia. Here, we review recent data exploring the evolution of the virus on much shorter timescales, on the order of days or months. We describe the intrahost genetic diversity of the virus isolated from humans, and how this diversity contributes to HCMV spatiotemporal evolution. We propose mechanisms to explain the high levels of intrahost diversity and discuss how this new information may shed light on HCMV infection and pathogenesis. PMID:25154343

  5. Interbeing and Mindfulness: A Bridge to Understanding Jean Watson's Theory of Human Caring.

    ERIC Educational Resources Information Center

    Sitzman, Kathleen L.

    2002-01-01

    Explains and compares Thich Naht Hanh's concept of interbeing and mindfulness and Jean Watson's theory of human caring. Describes the application of mindful practices to holistic nursing and nursing education. (Contains 12 references.) (SK)

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

    PubMed Central

    MartĂ­n, Rebeca; Miquel, Sylvie; Langella, Philippe; BermĂșdez-HumarĂĄn, 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

  7. USE OF PRIMATE FOLLICULOGENESIS MODELS IN UNDERSTANDING HUMAN REPRODUCTIVE BIOLOGY AND APPLICABILITY TO TOXICOLOGY

    EPA Science Inventory

    The nonhuman primate reproductive system provides an excellent model for studying basic physiological processes applicable to humans. This article reviews hormonal observations and experimental manipulations useful in the evaluation of ovarian events in various stages of the repr...

  8. Non-Immortalized Human Tenocyte Cultures as a Vehicle for Understanding Cellular Aspects to Tendinopathy.

    PubMed Central

    Yao, L.; Bestwick, C.S.; Bestwick, L.A.; Aspden, R.M; Maffulli, N.

    2011-01-01

    Summary The biochemical mechanisms underlying tendinopathy are obscure. We briefly describe preliminary observations of human tenocyte behaviour in culture as a vehicle for determining the role of reactive oxygen in tendon pathology. PMID:23905032

  9. 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

  10. 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.

  11. 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. Am. J. Primatol. 78:117-126, 2016. © 2016 The Authors. American Journal of Primatology published by Wiley Periodicals, Inc. PMID:25940511

  12. 77 FR 43335 - Administration on Intellectual and Developmental Disabilities; Agency Information Collection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-24

    ... HUMAN SERVICES Administration for Community Living Administration on Intellectual and Developmental... Reporting Form for State Councils on Developmental Disabilities AGENCY: Administration for Community Living... Developmental Disabilities, Administration on Community Living, Washington, DC 20447 or by fax at (202)...

  13. 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

  14. 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,


  15. 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 ToxCastℱ chemical screening and prioritization research project. Metabolites from hES cultur...

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

    EPA Science Inventory

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultur...

  17. Directly Comparing Computer and Human Performance in Language Understanding and Visual Reasoning.

    ERIC Educational Resources Information Center

    Baker, Eva L.; And Others

    Evaluation models are being developed for assessing artificial intelligence (AI) systems in terms of similar performance by groups of people. Natural language understanding and vision systems are the areas of concentration. In simplest terms, the goal is to norm a given natural language system's performance on a sample of people. The specific…

  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. PMID:26437235

  19. Developmental parallels in understanding minds and bodies.

    PubMed

    Leslie, Alan M

    2005-10-01

    A recent article by Onishi and Baillargeon presents evidence that 15-month-old infants attribute false beliefs (FBs) to other people. If correct, it lends dramatic new support to the idea that mental state concepts ("theory of mind") emerge from a specialized neurocognitive mechanism that matures during the second year of life. But it also raises new puzzles concerning the FB task--puzzles that have intriguing parallels in results from infants' reasoning about solid bodies. PMID:16125434

  20. 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…