Sample records for debate vii neurobiology

  1. Recombinant factor VIIa treatment for asymptomatic factor VII deficient patients going through major surgery.

    PubMed

    Livnat, Tami; Shenkman, Boris; Spectre, Galia; Tamarin, Ilia; Dardik, Rima; Israeli, Amnon; Rivkind, Avraham; Shabtai, Moshe; Marinowitz, Uri; Salomon, Ophira

    2012-07-01

    Factor VII deficiency is the most common among the rare autosomal recessive coagulation disorders worldwide. In factor VII deficient patients, the severity and clinical manifestations cannot be reliably determined by factor VII levels. Severe bleeding tends to occur in individuals with factor VII activity levels of 2% or less of normal. Patients with 2-10% factor VII vary between asymptomatic to severe life threatening haemorrhages behaviour. Recombinant factor VIIa (rFVIIa) is the most common replacement therapy for congenital factor VII deficiency. However, unlike haemophilia patients for whom treatment protocols are straight forward, in asymptomatic factor VII deficiency patients it is still debatable. In this study, we demonstrate that a single and very low dose of recombinant factor VIIa enabled asymptomatic patients with factor VII deficiency to go through major surgery safely. This suggestion was also supported by thrombin generation, as well as by thromboelastometry.

  2. [The brain-mind debate. Problems in the philosophy of science with regard to psychiatry].

    PubMed

    Tretter, F

    2007-05-01

    The present interdisciplinary brain-mind debate with regard to neurobiology shows deficits in the criticism of methods and in the precision of language and argumentation. Simplifying localisations of psychic functions, insufficient explanations and over-interpretations in the sense of physical determinism are the consequence. This can be demonstrated in deficits of neurobiological theories of volitional action. Therefore, the current concept of man is less perturbed than is proposed by neurobiologists. For psychiatry besides the neurobiological approach also a separate way of building models seems to be useful if present theoretical psychology and systems science would be regarded. In particular, the systems science of natural systems offers new opportunities to bridge gaps between disciplines involved in the brain-mind debate.

  3. Factor VII assay

    MedlinePlus

    Stable factor; Proconvertin; Autoprothrombin I ... be caused by an abnormally low level of factor VII. ... Decreased factor VII activity may be related to: Deficiency of factor VII Disorder in which the proteins that control ...

  4. [Neurobiological determinism: questionable inferences on human freedom of choice and forensic criminal responsibility].

    PubMed

    Urbaniok, F; Hardegger, J; Rossegger, A; Endrass, J

    2006-08-01

    Several authors argue that criminal behavior is generally caused by neurobiological deficits. Based on this neurobiological perspective of assumed causality, the concept of free will is questioned, and the theory of neurobiological determinism of all human behavior is put forward, thus maintaining that human beings are not responsible for their actions, and consequently the principle of guilt should be given up in criminal law. In this context the controversial debate on determinism and indeterminism, which has been held for centuries, has flared up anew, especially within the science of criminal law. When critically examining the current state of research, it becomes apparent that the results do not support the existence of a universally valid neurobiological causality of criminal behavior, nor a theory of an absolute neurobiological determinism. Neither is complete determination of all phenomena in the universe--as maintained--the logical conclusion of the principle of causality, nor is it empirically confirmed. Analyzed methodically, it cannot be falsified, and thus, as a theory which cannot be empirically tested, it represents a dogma against which plausible objections can be made. The criticism of the concept of free will, and even more so of human accountability and criminal responsibility, is not put forward in a valid way. The principle of relative determinism--the evaluation of the degree of determinism of personality factors potentially reducing criminal responsibility, which includes concrete observations and analysis of behavior--thus remains a central and cogent approach to the assessment of criminal responsibility. To sum up, the theories proposed by some authors on the complete neurobiological determinism of human behavior, and the subsequent impossibility of individual responsibility and guilt, reveal both methodical misconception and a lack of empirical foundation.

  5. Neurobiological Correlates in Internet Gaming Disorder: A Systematic Literature Review

    PubMed Central

    Kuss, Daria J.; Pontes, Halley M.; Griffiths, Mark D.

    2018-01-01

    Internet Gaming Disorder (IGD) is a potential mental disorder currently included in the third section of the latest (fifth) edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) as a condition that requires additional research to be included in the main manual. Although research efforts in the area have increased, there is a continuing debate about the respective criteria to use as well as the status of the condition as mental health concern. Rather than using diagnostic criteria which are based on subjective symptom experience, the National Institute of Mental Health advocates the use of Research Domain Criteria (RDoC) which may support classifying mental disorders based on dimensions of observable behavior and neurobiological measures because mental disorders are viewed as biological disorders that involve brain circuits that implicate specific domains of cognition, emotion, and behavior. Consequently, IGD should be classified on its underlying neurobiology, as well as its subjective symptom experience. Therefore, the aim of this paper is to review the neurobiological correlates involved in IGD based on the current literature base. Altogether, 853 studies on the neurobiological correlates were identified on ProQuest (in the following scholarly databases: ProQuest Psychology Journals, PsycARTICLES, PsycINFO, Applied Social Sciences Index and Abstracts, and ERIC) and on MEDLINE, with the application of the exclusion criteria resulting in reviewing a total of 27 studies, using fMRI, rsfMRI, VBM, PET, and EEG methods. The results indicate there are significant neurobiological differences between healthy controls and individuals with IGD. The included studies suggest that compared to healthy controls, gaming addicts have poorer response-inhibition and emotion regulation, impaired prefrontal cortex (PFC) functioning and cognitive control, poorer working memory and decision-making capabilities, decreased visual and auditory functioning, and a

  6. Neurobiological Correlates in Internet Gaming Disorder: A Systematic Literature Review.

    PubMed

    Kuss, Daria J; Pontes, Halley M; Griffiths, Mark D

    2018-01-01

    Internet Gaming Disorder (IGD) is a potential mental disorder currently included in the third section of the latest (fifth) edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) as a condition that requires additional research to be included in the main manual. Although research efforts in the area have increased, there is a continuing debate about the respective criteria to use as well as the status of the condition as mental health concern. Rather than using diagnostic criteria which are based on subjective symptom experience, the National Institute of Mental Health advocates the use of Research Domain Criteria (RDoC) which may support classifying mental disorders based on dimensions of observable behavior and neurobiological measures because mental disorders are viewed as biological disorders that involve brain circuits that implicate specific domains of cognition, emotion, and behavior. Consequently, IGD should be classified on its underlying neurobiology, as well as its subjective symptom experience. Therefore, the aim of this paper is to review the neurobiological correlates involved in IGD based on the current literature base. Altogether, 853 studies on the neurobiological correlates were identified on ProQuest (in the following scholarly databases: ProQuest Psychology Journals, PsycARTICLES, PsycINFO, Applied Social Sciences Index and Abstracts, and ERIC) and on MEDLINE, with the application of the exclusion criteria resulting in reviewing a total of 27 studies, using fMRI, rsfMRI, VBM, PET, and EEG methods. The results indicate there are significant neurobiological differences between healthy controls and individuals with IGD. The included studies suggest that compared to healthy controls, gaming addicts have poorer response-inhibition and emotion regulation, impaired prefrontal cortex (PFC) functioning and cognitive control, poorer working memory and decision-making capabilities, decreased visual and auditory functioning, and a

  7. Cannabis and psychosis: Neurobiology

    PubMed Central

    Shrivastava, Amresh; Johnston, Megan; Terpstra, Kristen; Bureau, Yves

    2014-01-01

    Cannabis is a known risk factor for schizophrenia, although the exact neurobiological process through which the effects on psychosis occur is not well-understood. In this review, we attempt to develop and discuss a possible pathway for the development of psychosis. We examine the neurobiological changes due to cannabis to see if these changes are similar to those seen in schizophrenic patients the findings show similarities; however, these mere similarities cannot establish a ‘cause-effect’ relationship as a number of people with similar changes do not develop schizophrenia. Therefore, the ‘transition-to-psychosis’ due to cannabis, despite being a strong risk factor, remains uncertain based upon neurobiological changes. It appears that other multiple factors might be involved in these processes which are beyond neurobiological factors. Major advances have been made in understanding the underpinning of marijuana dependence, and the role of the cannabinoid system, which is a major area for targeting medications to treat marijuana withdrawal and dependence, as well as other addictions is of now, it is clear that some of the similarities in the neurobiology of cannabis and schizophrenia may indicate a mechanism for the development of psychosis, but its trajectories are undetermined. PMID:24574553

  8. Quantum neurophysics: From non-living matter to quantum neurobiology and psychopathology.

    PubMed

    Tarlacı, Sultan; Pregnolato, Massimo

    2016-05-01

    The concepts of quantum brain, quantum mind and quantum consciousness have been increasingly gaining currency in recent years, both in scientific papers and in the popular press. In fact, the concept of the quantum brain is a general framework. Included in it are basically four main sub-headings. These are often incorrectly used interchangeably. The first of these and the one which started the quantum mind/consciousness debate was the place of consciousness in the problem of measurement in quantum mechanics. Debate on the problem of quantum measurement and about the place of the conscious observer has lasted almost a century. One solution to this problem is that the participation of a conscious observer in the experiment will radically change our understanding of the universe and our relationship with the outside world. The second topic is that of quantum biology. This topic has become a popular field of research, especially in the last decade. It concerns whether or not the rules of quantum physics operate in biological structures. It has been shown in the latest research on photosynthesis, the sense of smell and magnetic direction finding in animals that the laws of quantum physics may operate in warm-wet-noisy biological structures. The third sub-heading is quantum neurobiology. This topic has not yet gained wide acceptance and is still in its early stages. Its primary purpose is directed to understand whether the laws of quantum physics are effective in the biology of the nervous system or not. A further step in brain neurobiology, toward the understanding of consciousness formation, is the research of quantum laws effects upon neural network functions. The fourth and final topic is quantum psychopathology. This topic takes its basis and its support from quantum neurobiology. It comes from the idea that if quantum physics is involved in the normal working of the brain, diseased conditions of the brain such as depression, anxiety, dementia, schizophrenia and

  9. Genetics Home Reference: factor VII deficiency

    MedlinePlus

    ... Facebook Twitter Home Health Conditions Factor VII deficiency Factor VII deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Factor VII deficiency is a rare bleeding disorder that varies ...

  10. Neurobiology of anxious depression: a review.

    PubMed

    Ionescu, Dawn F; Niciu, Mark J; Mathews, Daniel C; Richards, Erica M; Zarate, Carlos A

    2013-04-01

    Anxious depression is a common, distinct clinical subtype of major depressive disorder (MDD). This review summarizes current neurobiological knowledge regarding anxious depression. Peer-reviewed articles, published January 1970 through September 2012, were identified via PUBMED, EMBASE, and Cochrane Library, using the following key words: anxious depression electroencephalography (EEG), anxious depression functional magnetic resonance imaging (fMRI), anxious depression genetics, anxious depression neurobiology, and anxious melancholia neurobiology. Despite a general dearth of neurobiological research, the results suggest that anxious depression-when defined either syndromally or dimensionally-has distinct neurobiological findings that separate it from nonanxious depression. Structural neuroimaging, EEG, genetics, and neuropsychiatric studies revealed differences in subjects with anxious depression compared to other groups. Endocrine differences between individuals with anxious depression and those with nonanxious depression have also been noted, as evidenced by abnormal responses elicited by exogenous stimulation of the system. Despite these findings, heterogeneity in the definition of anxious depression complicates the results. Because exploring the neurobiology of this depressive subtype is important for improving diagnosis, prognosis, and treatment, enrichment strategies to decrease heterogeneity within the field should be employed for future research. © 2013 Wiley Periodicals, Inc.

  11. Neurobiological consequences of childhood trauma.

    PubMed

    Nemeroff, Charles B

    2004-01-01

    There is considerable evidence to suggest that adverse early-life experiences have a profound effect on the developing brain. Neurobiological changes that occur in response to untoward early-life stress can lead to lifelong psychiatric sequelae. Children who are exposed to sexual or physical abuse or the death of a parent are at higher risk for development of depressive and anxiety disorders later in life. Preclinical and clinical studies have shown that repeated early-life stress leads to alterations in central neurobiological systems, particularly in the corticotropin-releasing factor system, leading to increased responsiveness to stress. Clearly, exposure to early-life stressors leads to neurobiological changes that increase the risk of psychopathology in both children and adults. Identification of the neurobiological substrates that are affected by adverse experiences in early life should lead to the development of more effective treatments for these disorders. The preclinical and clinical studies evaluating the consequences of early-life stress are reviewed.

  12. Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

    PubMed

    Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

    2013-08-01

    Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Intelsat VII program and the future

    NASA Astrophysics Data System (ADS)

    Madon, P. J.; Sachdev, D. K.

    The evolution of the Intelsat VII spacecraft is discussed. The role of competitive procurement process in this evolution is addressed, and the overall system-level features of the spacecraft are reviewed. The time frame for the five Intelsat VII missions is summarized, and follow-up projects to Intelsat VII are discussed.

  14. Newly diagnosed congenital factor VII deficiency and utilization of recombinant activated factor VII (NovoSeven(®)).

    PubMed

    Bartosh, Nicole S; Tomlin, Tara; Cable, Christian; Halka, Kathleen

    2013-01-01

    This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa). Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding. A 19-year-old African-American male presented to the emergency room after an altercation that resulted in significant trauma. He sustained bilateral mandibular angle fractures and orbital floor fractures, requiring urgent surgical correction. On initial evaluation, he was noted to have a prolonged prothrombin time of 40.1 seconds, with an International Normalized Ratio of 4.0, a normal activated partial thromboplastin time of 29.9 seconds, and a platelet count of 241. After receiving vitamin K and fresh frozen plasma, he was taken to the operating room for a temporary rigid maxillomandibular fixation. A 1:1 mixing study with normal plasma corrected the prothrombin time (decreasing from 40.7 to 14.7 seconds) and a factor VII assay revealed 5% of the normal factor VII level. The patient was diagnosed with congenital factor VII deficiency. Due to his coagulopathy and the extensive surgical correction needed, rFVIIa was administered and surgery was accomplished without hemorrhagic sequelae. This case report and review describes a rare congenital disease, the history of rFVIIa use, and its mechanism. rFVIIA use in our patient provided a treatment option that allowed the necessary surgical correction, but further prospective studies on dose optimization would ensure adequate dosing with minimal risk of severe side effects.

  15. Neurobiological correlates of cognitions in fear and anxiety: a cognitive-neurobiological information-processing model.

    PubMed

    Hofmann, Stefan G; Ellard, Kristen K; Siegle, Greg J

    2012-01-01

    We review likely neurobiological substrates of cognitions related to fear and anxiety. Cognitive processes are linked to abnormal early activity reflecting hypervigilance in subcortical networks involving the amygdala, hippocampus, and insular cortex, and later recruitment of cortical regulatory resources, including activation of the anterior cingulate cortex and prefrontal cortex to implement avoidant response strategies. Based on this evidence, we present a cognitive-neurobiological information-processing model of fear and anxiety, linking distinct brain structures to specific stages of information processing of perceived threat.

  16. Towards a neurobiological model of offending.

    PubMed

    Mitchell, Ian J; Beech, Anthony R

    2011-07-01

    In this paper we consider how disturbances in the neurobiological/neurochemical processes at a young age lead to problematic attachment styles in later life, and which can potentiate probability of offending behavior. In particular, we will contrast attachment and offending patterns of the more generalist type of offender (i.e., those who have a varied criminal career, committing both violent and non-violent offenses, in extremis the psychopathic type of offender), with the more specialist sexual offender (prototypically, the fixated pedophile), in the light of a preliminary neurobiological model. Here, we will argue that these two extremes of offenders show, or are predicted to show, differential patterns of neurochemical/neurobiological functioning. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Implementation is crucial but must be neurobiologically grounded. Comment on “Toward a computational framework for cognitive biology: Unifying approaches from cognitive neuroscience and comparative cognition” by W. Tecumseh Fitch

    NASA Astrophysics Data System (ADS)

    Bornkessel-Schlesewsky, Ina; Schlesewsky, Matthias; Small, Steven L.

    2014-09-01

    From the perspective of language, Fitch's [1] claim that theories of cognitive computation should not be separated from those of implementation surely deserves applauding. Recent developments in the Cognitive Neuroscience of Language, leading to the new field of the Neurobiology of Language [2-4], emphasise precisely this point: rather than attempting to simply map cognitive theories of language onto the brain, we should aspire to understand how the brain implements language. This perspective resonates with many of the points raised by Fitch in his review, such as the discussion of unhelpful dichotomies (e.g., Nature versus Nurture). Cognitive dichotomies and debates have repeatedly turned out to be of limited usefulness when it comes to understanding language in the brain. The famous modularity-versus-interactivity and dual route-versus-connectionist debates are cases in point: in spite of hundreds of experiments using neuroimaging (or other techniques), or the construction of myriad computer models, little progress has been made in their resolution. This suggests that dichotomies proposed at a purely cognitive (or computational) level without consideration of biological grounding appear to be "asking the wrong questions" about the neurobiology of language. In accordance with these developments, several recent proposals explicitly consider neurobiological constraints while seeking to explain language processing at a cognitive level (e.g. [5-7]).

  18. 40 CFR Appendix Vii to Part 600 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 31 2013-07-01 2013-07-01 false [Reserved] VII Appendix VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND GREENHOUSE GAS EXHAUST EMISSIONS OF MOTOR VEHICLES Appendix VII to Part 600 [Reserved] ...

  19. 40 CFR Appendix Vii to Part 600 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 31 2012-07-01 2012-07-01 false [Reserved] VII Appendix VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND GREENHOUSE GAS EXHAUST EMISSIONS OF MOTOR VEHICLES Appendix VII to Part 600 [Reserved] ...

  20. 40 CFR Appendix Vii to Part 600 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 30 2014-07-01 2014-07-01 false [Reserved] VII Appendix VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND GREENHOUSE GAS EXHAUST EMISSIONS OF MOTOR VEHICLES Appendix VII to Part 600 [Reserved] ...

  1. Newly diagnosed congenital factor VII deficiency and utilization of recombinant activated factor VII (NovoSeven®)

    PubMed Central

    Bartosh, Nicole S; Tomlin, Tara; Cable, Christian; Halka, Kathleen

    2013-01-01

    This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa). Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding. Case report A 19-year-old African-American male presented to the emergency room after an altercation that resulted in significant trauma. He sustained bilateral mandibular angle fractures and orbital floor fractures, requiring urgent surgical correction. On initial evaluation, he was noted to have a prolonged prothrombin time of 40.1 seconds, with an International Normalized Ratio of 4.0, a normal activated partial thromboplastin time of 29.9 seconds, and a platelet count of 241. After receiving vitamin K and fresh frozen plasma, he was taken to the operating room for a temporary rigid maxillomandibular fixation. A 1:1 mixing study with normal plasma corrected the prothrombin time (decreasing from 40.7 to 14.7 seconds) and a factor VII assay revealed 5% of the normal factor VII level. The patient was diagnosed with congenital factor VII deficiency. Due to his coagulopathy and the extensive surgical correction needed, rFVIIa was administered and surgery was accomplished without hemorrhagic sequelae. Conclusion This case report and review describes a rare congenital disease, the history of rFVIIa use, and its mechanism. rFVIIA use in our patient provided a treatment option that allowed the necessary surgical correction, but further prospective studies on dose optimization would ensure adequate dosing with minimal risk of

  2. Role of hepsin in factor VII activation in zebrafish.

    PubMed

    Khandekar, Gauri; Jagadeeswaran, Pudur

    2014-01-01

    Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor VIIa. However, the mechanism of initial generation of factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor VIIa and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor VIIa concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor VIIa levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor VIIa plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish. © 2013.

  3. Nature and autonomy: an organizational view of social and neurobiological aspects of self-regulation in behavior and development.

    PubMed

    Ryan, R M; Kuhl, J; Deci, E L

    1997-01-01

    The concepts of self-regulation and autonomy are examined within an organizational framework. We begin by retracing the historical origins of the organizational viewpoint in early debates within the field of biology between vitalists and reductionists, from which the construct of self-regulation emerged. We then consider human autonomy as an evolved behavioral, developmental, and experiential phenomenon that operates at both neurobiological and psychological levels and requires very specific supports within higher order social organizations. We contrast autonomy or true self-regulation with controlling regulation (a nonautonomous form of intentional behavior) in phenomenological and functional terms, and we relate the forms of regulation to the developmental processes of intrinsic motivation and internalization. Subsequently, we describe how self-regulation versus control may be characterized by distinct neurobiological underpinnings, and we speculate about some of the adaptive advantages that may underlie the evolution of autonomy. Throughout, we argue that disturbances of autonomy, which have both biological and psychological etiologies, are central to many forms of psychopathology and social alienation.

  4. The neurobiology of psychopathy: a neurodevelopmental perspective.

    PubMed

    Gao, Yu; Glenn, Andrea L; Schug, Robert A; Yang, Yaling; Raine, Adrian

    2009-12-01

    We provide an overview of the neurobiological underpinnings of psychopathy. Cognitive and affective-emotional processing deficits are associated with abnormal brain structure and function, particularly the amygdala and orbitofrontal cortex. There is limited evidence of lower cortisol levels being associated with psychopathic personality. Initial developmental research is beginning to suggest that these neurobiological processes may have their origins early in life. Findings suggest that psychopathic personality may, in part, have a neurodevelopmental basis. Future longitudinal studies delineating neurobiological correlates of the analogues of interpersonal-affective and antisocial features of psychopathy in children are needed to further substantiate a neurodevelopmental hypothesis of psychopathy.

  5. Pathogenesis of lumbar spine disease in mucopolysaccharidosis VII

    PubMed Central

    Smith, Lachlan J; Baldo, Guilherme; Wu, Susan; Liu, Yuli; Whyte, Michael P; Giugliani, Roberto; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

    2012-01-01

    Mucopolysaccharidosis type VII (MPS VII) is characterized by deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan and dermatan sulfate glycosaminoglycans (GAGs), and multisystemic disease. MPS VII patients can develop kypho-scoliotic deformity and spinal cord compression due to disease of intervertebral discs, vertebral bodies, and associated tissues. We have previously demonstrated in MPS VII dogs that intervertebral discs degenerate, vertebral bodies have irregular surfaces, and vertebral body epiphyses have reduced calcification, but the pathophysiological mechanisms underlying these changes are unclear. We hypothesized that some of these manifestations could be due to upregulation of destructive proteases, possibly via the binding of GAGs to Toll-like receptor 4 (TLR4), as has been proposed for other tissues in MPS models. In this study, the annulus fibrosus of the intervertebral disc of 6 month-old MPS VII dogs had cathepsin B and K activities that were 117- and 2-fold normal, respectively, which were associated with elevations in mRNA levels for cathepsins as well as TLR4. The epiphyses of MPS VII dogs had a marked elevation in mRNA for the cartilage-associated gene collagen II, consistent with a developmental delay in the conversion of the cartilage to bone in this region. A spine from a human patient with MPS VII exhibited similar increased cartilage in the vertebral bodies adjacent to the end plates, disorganization of the intervertebral discs, and irregular vertebral end plate morphology. These data suggest that the pathogenesis of destructive changes in the spine in MPS VII may involve upregulation of cathepsins. Inhibition of destructive proteases, such as cathepsins, might reduce spine disease in patients with MPS VII or related disorders. PMID:22513347

  6. Neurobiology of Addictions: Implications for Clinical Practice.

    ERIC Educational Resources Information Center

    Spence, Richard T., Ed.; DiNitto, Diana M., Ed.; Straussner, Shulamith Lala Ashenberg, Ed.

    This book offers helping professionals an introduction to the neurobiological aspects of substance abuse. It presents the basic information on the subject, including the various neurobiological theories of addiction, and places them in a psychosocial context. In addition to connecting the theoretical information with practical applications, the…

  7. Use of recombinant factor VII for tooth extractions in a patient with severe congenital factor VII deficiency: a case report.

    PubMed

    Weinstock, Robert J; Onyejiuwa, Andrew; Shnayder, Garry; Clarkson, Earl I

    2015-04-01

    Patients with factor VII deficiency have an increased risk of prolonged perioperative hemorrhage. In this article, the authors present a case of severe factor VII deficiency in a patient who required tooth extraction. A 44-year-old woman with severe congenital factor VII deficiency sought care for a symptomatic, carious, and nonrestorable maxillary right second molar that required extraction. The authors obtained hematologic consultation, and the patient underwent the extraction under general anesthesia in the inpatient setting. Perioperative management included performing relevant laboratory studies, preoperative recombinant factor VII infusion, and postoperative intravenous aminocaproic acid administration. No hemorrhagic complications occurred throughout the perioperative course. The degree of factor VII deficiency correlates poorly with bleeding risk. Perioperative management is variable, requiring preoperative consultation with a hematologist. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

  8. Synergistic effect of factor VII gene polymorphisms causing mild factor VII deficiency in a case of severe factor X deficiency.

    PubMed

    Deshpande, Rutuja; Ghosh, Kanjaksha; Shetty, Shrimati

    2017-01-01

    Congenital combined deficiency of coagulation factors VII and X are mainly attributed to large deletions involving both the genes in chromosome 13 or occasionally due to the coincidental occurrence of independently occurring mutations. We report the molecular basis of congenital combined deficiency of factors VII and X in a 6-year-old female child. Direct DNA sequencing of both factor VII (F7) and factor X (F10) genes showed a novel homozygous missense mutation p.Cys90Tyr (c.307G>A) in exon 4 of F10. No mutations were detected in F7; however, the patient was homozygous for three polymorphic alleles known to be associated with reduced factor VII levels. The present case illustrates the synergistic effect of multiple polymorphisms resulting in phenotypic factor VII deficiency in the absence of a pathogenic mutation.

  9. Obesity and addiction: neurobiological overlaps.

    PubMed

    Volkow, N D; Wang, G-J; Tomasi, D; Baler, R D

    2013-01-01

    Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

  10. 19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

  11. 19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

  12. 19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 3 2011-04-01 2011-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

  13. 19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 3 2013-04-01 2013-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

  14. 19 CFR Annex Vii to Part 351 - Antidumping Investigations Timeline

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 3 2012-04-01 2012-04-01 false Antidumping Investigations Timeline VII Annex VII to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VII Annex VII to Part 351—Antidumping Investigations Timeline ER19MY97.001 ...

  15. First living-related liver transplant to cure factor VII deficiency.

    PubMed

    Mohan, Neelam; Karkra, Sakshi; Jolly, Anu S; Vohra, Vijay; Mohanka, Ravi; Rastogi, Amit; Soin, A S

    2015-09-01

    Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first-ever youngest baby reported worldwide. A six-month-old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life-threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre-, intra- and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. The Debate Debate

    ERIC Educational Resources Information Center

    Tumposky, Nancy Rennau

    2004-01-01

    Debate has been a well-known pedagogical technique since there have been written records about teaching and learning. Originally employed for learning philosophy and theology, debate was later used in the fields of history, law, literature, and the physical sciences. This author asserts, however, that, although the benefits of debate are…

  17. The New Neurobiology of Autism

    PubMed Central

    Minshew, Nancy J.; Williams, Diane L.

    2008-01-01

    This review covers a fraction of the new research developments in autism but establishes the basic elements of the new neurobiologic understanding of autism. Autism is a polygenetic developmental neurobiologic disorder with multiorgan system involvement, though it predominantly involves central nervous system dysfunction. The evidence supports autism as a disorder of the association cortex, both its neurons and their projections. In particular, it is a disorder of connectivity, which appears, from current evidence, to primarily involve intrahemispheric connectivity. The focus of connectivity studies thus far has been on white matter, but alterations in functional magnetic resonance imaging activation suggest that intracortical connectivity is also likely to be disturbed. Furthermore, the disorder has a broad impact on cognitive and neurologic functioning. Deficits in high-functioning individuals occur in processing that places high demands on integration of information and coordination of multiple neural systems. Intact or enhanced abilities share a dependence on low information-processing demands and local neural connections. This multidomain model with shared characteristics predicts an underlying pathophysiologic mechanism that impacts the brain broadly, according to a common neurobiologic principle. The multiorgan system involvement and diversity of central nervous system findings suggest an epigenetic mechanism. PMID:17620483

  18. [Neurotheology: neurobiological models of religious experience].

    PubMed

    Passie, T; Warncke, J; Peschel, T; Ott, U

    2013-03-01

    Religions are evolutionary selected social and cultural phenomena. They represent today belief and normative systems on which the main parts of our culture are based. For a long time religions have been seen as mainly originating from a spectrum of religious experiences. These include a broad spectrum of experiences and are astonishingly widespread in the population. The most consistent and transculturally uniform religious experiences are the mystical experiences. Only these (and the prayer experience) have factually been researched in detail neurobiologically. This article presents a review of empirical results and hypothetical approaches to explain mystical religious experiences neurobiologically. Some of the explanatory hypotheses possess logical evidence, some are even supported by neurobiological studies, but all of them have their pitfalls and are at best partially consistent. One important insight from the evidence reviewed here is that there may be a whole array of different neurophysiological conditions which may result in the same core religious mystical experiences.

  19. A product Pearson-type VII density distribution

    NASA Astrophysics Data System (ADS)

    Nadarajah, Saralees; Kotz, Samuel

    2008-01-01

    The Pearson-type VII distributions (containing the Student's t distributions) are becoming increasing prominent and are being considered as competitors to the normal distribution. Motivated by real examples in decision sciences, Bayesian statistics, probability theory and Physics, a new Pearson-type VII distribution is introduced by taking the product of two Pearson-type VII pdfs. Various structural properties of this distribution are derived, including its cdf, moments, mean deviation about the mean, mean deviation about the median, entropy, asymptotic distribution of the extreme order statistics, maximum likelihood estimates and the Fisher information matrix. Finally, an application to a Bayesian testing problem is illustrated.

  20. Recombinant activated factor VII in cardiac surgery: single-center experience.

    PubMed

    Singh, Sarvesh Pal; Chauhan, Sandeep; Choudhury, Minati; Malik, Vishwas; Choudhary, Shiv Kumar

    2014-02-01

    The widespread off-label use of recombinant activated factor VII for the control of refractory postoperative hemorrhage continues despite a warning from the Food and Drug Administration. Although effective in reducing the need for transfusion of blood and blood products, safety concerns still prevail. To compare the dosing and efficacy of recombinant activated factor VII between pediatric and adult patients, and in the operating room and intensive care unit. The records of 69 patients (33 children and 36 adults) who underwent cardiovascular surgery and received recombinant activated factor VII were reviewed retrospectively. The dose of recombinant activated factor VII, mediastinal drainage, use of blood and blood products, incidence of thrombosis, and 28-day mortality were studied. the efficacy of recombinant activated factor VII was comparable in adults and children, despite the lower dose in adults. Prophylactic use of recombinant activated factor VII decreased the incidence of mediastinal exploration and the duration of intensive care unit stay. A 4.3% incidence of thrombotic complications was observed in this study. The efficacious dose of recombinant activated factor VII is much less in adults compared to children. Prophylactic use of recombinant activated factor VII decreases the dose required, the incidence of mediastinal exploration, and intensive care unit stay, with no survival benefit.

  1. LEA Title VII Program Evaluations. Panel Presentations.

    ERIC Educational Resources Information Center

    Balu, Raj

    These panel presentations focus on LEA Title VII Program Evaluations. Raj Balu, an administrator of bilingual programs in Chicago presents information regarding the bilingual education program in the Chicago public schools, as well as information on Title VII programs and what kind of evaluation is being done. Jesus Salazar, who is currently…

  2. Clinical course of sly syndrome (mucopolysaccharidosis type VII)

    PubMed Central

    Montaño, Adriana M; Lock-Hock, Ngu; Steiner, Robert D; Graham, Brett H; Szlago, Marina; Greenstein, Robert; Pineda, Mercedes; Gonzalez-Meneses, Antonio; Çoker, Mahmut; Bartholomew, Dennis; Sands, Mark S; Wang, Raymond; Giugliani, Roberto; Macaya, Alfons; Pastores, Gregory; Ketko, Anastasia K; Ezgü, Fatih; Tanaka, Akemi; Arash, Laila; Beck, Michael; Falk, Rena E; Bhattacharya, Kaustuv; Franco, José; White, Klane K; Mitchell, Grant A; Cimbalistiene, Loreta; Holtz, Max; Sly, William S

    2016-01-01

    Background Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of β-glucuronidase (GUS). Patients’ phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data. Methods We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease. Results We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS. Conclusions MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity

  3. Neurobiology of dysregulated motivational systems in drug addiction

    PubMed Central

    Edwards, Scott; Koob, George F

    2010-01-01

    The progression from recreational drug use to drug addiction impacts multiple neurobiological processes and can be conceptualized as a transition from positive to negative reinforcement mechanisms driving both drug-taking and drug-seeking behaviors. Neurobiological mechanisms for negative reinforcement, defined as drug taking that alleviates a negative emotional state, involve changes in the brain reward system and recruitment of brain stress (or antireward) systems within forebrain structures, including the extended amygdala. These systems are hypothesized to be dysregulated by excessive drug intake and to contribute to allostatic changes in reinforcement mechanisms associated with addiction. Points of intersection between positive and negative motivational circuitry may further drive the compulsivity of drug addiction but also provide a rich neurobiological substrate for therapeutic intervention. PMID:20563312

  4. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography

    PubMed Central

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Background: Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. Methods: PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Results: Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). Results of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). Conclusion: It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII. PMID:26034723

  5. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography.

    PubMed

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). RESULTS of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII.

  6. Neurobiology Research Findings: How the Brain Works during Reading

    ERIC Educational Resources Information Center

    Kweldju, Siusana

    2015-01-01

    In the past, neurobiology for reading was identical with neuropathology. Today, however, the advancement of modern neuroimaging techniques has contributed to the understanding of the reading processes of normal individuals. Neurobiology findings today have uncovered and illuminated the fundamental neural mechanism of reading. The findings have…

  7. Pathogenesis of mitral valve disease in mucopolysaccharidosis VII dogs.

    PubMed

    Bigg, Paul W; Baldo, Guilherme; Sleeper, Meg M; O'Donnell, Patricia A; Bai, Hanqing; Rokkam, Venkata R P; Liu, Yuli; Wu, Susan; Giugliani, Roberto; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

    2013-11-01

    Mucopolysaccharidosis VII (MPS VII) is due to the deficient activity of β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiovascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed. Electron microscopy demonstrated that collagen fibrils were of normal diameter, but failed to align into large parallel arrays. mRNA analysis demonstrated a modest reduction in the expression of genes that encode collagen or collagen-associated proteins such as the proteoglycan decorin which helps collagen fibrils assemble, and a marked increase for genes that encode proteases such as cathepsins. Indeed, enzyme activity for cathepsin B (CtsB) was 19-fold normal. MPS VII dogs that received neonatal intravenous injection of a gamma retroviral vector had an improved signal for structurally-intact collagen, and reduced CtsB activity relative to that seen in untreated MPS VII dogs. We conclude that MR in untreated MPS VII dogs was likely due to abnormalities in MV collagen structure. This could be due to upregulation of enzymes that degrade collagen or collagen-associated proteins, to the accumulation of GAGs that compete with proteoglycans such as decorin for binding to collagen, or to other causes. Further delineation of the etiology of abnormal collagen structure may lead to treatments that improve biomechanical properties of the MV and other tissues. © 2013.

  8. Pathogenesis of Mitral Valve Disease in Mucopolysaccharidosis VII Dogs

    PubMed Central

    Bigg, Paul W.; Baldo, Guilherme; Sleeper, Meg M.; O'Donnell, Patricia A.; Bai, Hanqing; Rokkam, Venkata R.P.; Liu, Yuli; Wu, Susan; Giugliani, Roberto; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

    2013-01-01

    Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiavascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed. Electron microscopy demonstrated that collagen fibrils were of normal diameter, but failed to align into large parallel arrays. mRNA analysis demonstrated a modest reduction in the expression of genes that encode collagen or collagen-associated proteins such as the proteoglycan decorin which helps collagen fibrils assemble, and a marked increase for genes that encode proteases such as cathepsins. Indeed, enzyme activity for cathepsin B (CtsB) was 19-fold normal. MPS VII dogs that received neonatal intravenous injection of a gamma retroviral vector had an improved signal for structurally-intact collagen, and reduced CtsB activity relative to that seen in untreated MPS VII dogs. We conclude that MR in untreated MPS VII dogs was likely due to abnormalities in MV collagen structure. This could be due to upregulation of enzymes that degrade collagen or collagen-associated proteins, to the accumulation of GAGs that compete with proteoglycans such as decorin for binding to collagen, or to other causes. Further delineation of the etiology of abnormal collagen structure may lead to treatments that improve biomechanical properties of the MV and other tissues. PMID:23856419

  9. The Neurobiology of Intervention and Prevention in Early Adversity.

    PubMed

    Fisher, Philip A; Beauchamp, Kate G; Roos, Leslie E; Noll, Laura K; Flannery, Jessica; Delker, Brianna C

    2016-01-01

    Early adverse experiences are well understood to affect development and well-being, placing individuals at risk for negative physical and mental health outcomes. A growing literature documents the effects of adversity on developing neurobiological systems. Fewer studies have examined stress neurobiology to understand how to mitigate the effects of early adversity. This review summarizes the research on three neurobiological systems relevant to interventions for populations experiencing high levels of early adversity: the hypothalamic-adrenal-pituitary axis, the prefrontal cortex regions involved in executive functioning, and the system involved in threat detection and response, particularly the amygdala. Also discussed is the emerging field of epigenetics and related interventions to mitigate early adversity. Further emphasized is the need for intervention research to integrate knowledge about the neurobiological effects of prenatal stressors (e.g., drug use, alcohol exposure) and early adversity. The review concludes with a discussion of the implications of this research topic for clinical psychology practice and public policy.

  10. Is prophylaxis required for delivery in women with factor VII deficiency?

    PubMed Central

    Baumann Kreuziger, Lisa M.; Morton, Colleen T.; Reding, Mark T.

    2013-01-01

    Introduction Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant hemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is unclear whether prophylaxis is necessary prior to delivery. Aim To define management, hemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Methods Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using “factor VII deficiency” and “pregnancy” or “surgery.” Overall 34 articles, 4 abstracts, and 3 institutional cases were reviewed. Results Literature from 1953–2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Hemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 cesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing cesarean section compared to vaginal delivery. Post-partum hemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. Conclusion We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum hemorrhage was seen in deliveries with and without prophylaxis. Therefore we recommend that rfVIIa be available in the case of hemorrhage or surgical intervention, but not as mandatory prophylaxis. PMID:23607277

  11. Is prophylaxis required for delivery in women with factor VII deficiency?

    PubMed

    Baumann Kreuziger, L M; Morton, Colleen T; Reding, Mark T

    2013-11-01

    Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant haemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is not clear whether prophylaxis is necessary prior to delivery. The aim of this study was to define management, haemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using "factor VII deficiency" and "pregnancy" or "surgery." Overall 34 articles, four abstracts, and three institutional cases were reviewed. Literature from 1953 to 2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Haemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 caesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing caesarean section compared to vaginal delivery. Post-partum haemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum haemorrhage was seen in deliveries with and without prophylaxis. Therefore, we recommend that rfVIIa be available in the case of haemorrhage or surgical intervention, but not as mandatory prophylaxis. © 2013 John Wiley & Sons Ltd.

  12. [The neurobiology of antisocial behaviour].

    PubMed

    Loomans, M M; Tulen, J H M; van Marle, H J C

    2010-01-01

    Neuro-imaging is being used increasingly to provide explanations for antisocial behaviour. To make a neurobiological contribution to the diagnosis of many types of antisocial behaviour. The literature was searched using PubMed and combinations of the keywords 'psychopathy', 'antisocial', 'neurobiology' and 'neuro-anatomy' for the period 1990-2009. Impairments in the prefrontal cortex, amygdala, hippocampus, superior temporal gyrus, corpus callosum and anterior cingulate cortex provide a possible explanation for a large number of the symptoms associated with antisocial behaviour. The concept of psychopathy is connected mainly with impairments in a prefrontal-temporal-limbic system. CONCLUSION Combinations of deficiencies in the associated brain areas and malfunctioning of the communication between the various brain structures seem to play a more important role than deficiencies in the separate brain structures.

  13. Age-related changes in factor VII proteolysis in vivo.

    PubMed

    Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

    1996-08-01

    Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

  14. 32 CFR 2003.7 - Support Staff (Article VII).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false Support Staff (Article VII). 2003.7 Section 2003... (ISCAP) BYLAWS, RULES, AND APPEAL PROCEDURES Bylaws § 2003.7 Support Staff (Article VII). The staff of..., provides program and administrative support for the Panel. The Executive Secretary supervises the staff in...

  15. 32 CFR 2003.7 - Support Staff (Article VII).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Support Staff (Article VII). 2003.7 Section 2003... (ISCAP) BYLAWS, RULES, AND APPEAL PROCEDURES Bylaws § 2003.7 Support Staff (Article VII). The staff of..., provides program and administrative support for the Panel. The Executive Secretary supervises the staff in...

  16. Acquired factor VII deficiency associated with acute myeloid leukemia.

    PubMed

    Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

    2015-04-01

    Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

  17. Gene therapy ameliorates cardiovascular disease in dogs with mucopolysaccharidosis VII.

    PubMed

    Sleeper, M M; Fornasari, B; Ellinwood, N M; Weil, M A; Melniczek, J; O'Malley, T M; Sammarco, C D; Xu, L; Ponder, K P; Haskins, M E

    2004-08-17

    Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease caused by deficient beta-glucuronidase (GUSB) activity resulting in defective catabolism of glycosaminoglycans (GAGs). Cardiac disease is a major cause of death in MPS VII because of accumulation of GAGs in cardiovascular cells. Manifestations include cardiomyopathy, mitral and aortic valve thickening, and aortic root dilation and may cause death in the early months of life or may be compatible with a fairly normal lifespan. We previously reported that neonatal administration of a retroviral vector (RV) resulted in transduction of hepatocytes, which secreted GUSB into the blood and could be taken up by cells throughout the body. The goal of this study was to evaluate the effect on cardiac disease. Six MPS VII dogs were treated intravenously with an RV-expressing canine GUSB. Echocardiographic parameters, cardiovascular lesions, and biochemical parameters of these dogs were compared with those of normal and untreated MPS VII dogs. RV-treated dogs were markedly improved compared with untreated MPS VII dogs. Most RV-treated MPS VII dogs had mild or moderate mitral regurgitation at 4 to 5 months after birth, which improved or disappeared when evaluated at 9 to 11 and at 24 months. Similarly, mitral valve thickening present early in some animals disappeared over time, whereas aortic dilation and aortic valve thickening were absent at all times. Both myocardium and aorta had significant levels of GUSB and reduction in GAGs.

  18. [Coagulation factor VII levels in uremic patients and theirs influence factors].

    PubMed

    Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

    2004-12-01

    This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P < 0.05]. (2) After hemodialysis the FVIIa, FVII:C and FVIIAg levels in uremic patients significantly enhanced to 5.56 +/- 1.45 microg/L, (200.8 +/- 68.7)% and (124.1 +/- 19.3)% respectively (P < 0.05). (3) The abnormal increase of coagulation factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

  19. Blood glucose may condition factor VII levels in diabetic and normal subjects.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Torella, R

    1988-12-01

    Increased factor VII levels have been reported in Type 1 (insulin-dependent) diabetic subjects. A direct correlation between fasting plasma glucose and factor VII level was found to exist in both diabetic and normal subjects. Induced-hyperglycaemia was able to increase factor VII levels in both diabetic patients and normal control subjects while, when euglycaemia was achieved in diabetic patients, factor VII values returned to normal range. This study shows that the level of factor VII may be directly conditioned by circulating blood glucose and, therefore, stresses the role of hyperglycaemia in conditioning coagulation abnormalities in diabetes mellitus.

  20. Applying neurobiology to the treatment of adults with anorexia nervosa.

    PubMed

    Hill, Laura; Peck, Stephanie Knatz; Wierenga, Christina E; Kaye, Walter H

    2016-01-01

    Anorexia nervosa is a severe, biologically based brain disorder with significant medical complications. It is critical that new, effective treatments are developed to interrupt the persistent course of the illness due to the medical and psychological sequelae. Several psychosocial, behavioral and pharmacologic interventions have been investigated in adult anorexia nervosa; however, evidence shows that their impact is weak and treatment effects are generally small. This paper describes a new neurobiological anorexia nervosa model that shifts focus from solely external influences, such as social and family, to include internal influences that integrate genetic and neurobiological contributions, across the age span. The model serves as a theoretical structure for a new, five-day treatment, outlined in this paper, targeting anorexia nervosa temperament, which integrates neurobiological dimensions into evidence-based treatment interventions. The treatment is in two phases. Phase I is a five day, 40 hour treatment for anorexia nervosa adults. Phase II is the follow-up and is currently being developed. Preliminary qualitative acceptability data on 37 adults with anorexia nervosa and 60 supports (e.g., spouses, parents, aunts, friends, partners, children of anorexia nervosa adults) are promising from Phase I. Clients with anorexia nervosa and their supports report that learning neurobiological facts improved their understanding of the illness and helped equip them with better tools to manage anorexia nervosa traits and symptoms. In addition, nutritional knowledge changed significantly. This is the first neurobiologically based, five-day treatment for adults with anorexia nervosa and their supports. It is a new model that outlines underlying genetic and neurobiological contributions to anorexia nervosa that serves as a foundation to treat both traits and symptoms. Preliminary qualitative findings are promising, with both clients and supports reporting that the

  1. Research Review: The Neurobiology and Genetics of Maltreatment and Adversity

    ERIC Educational Resources Information Center

    McCrory, Eamon; De Brito, Stephane A.; Viding, Essi

    2010-01-01

    The neurobiological mechanisms by which childhood maltreatment heightens vulnerability to psychopathology remain poorly understood. It is likely that a complex interaction between environmental experiences (including poor caregiving) and an individual's genetic make-up influence neurobiological development across infancy and childhood, which in…

  2. PTSD: from neurobiology to pharmacological treatments

    PubMed Central

    Kelmendi, Benjamin; Adams, Thomas G.; Yarnell, Stephanie; Southwick, Steven; Abdallah, Chadi G.; Krystal, John H.

    2016-01-01

    Posttraumatic stress disorder (PTSD) is a chronic debilitating psychiatric disorder characterized by symptoms of re-experience, avoidance, and hyperarousal that can arise immediately or many years after exposure to a traumatic event and injury. Although extensive research has been done over the past 30 years, the etiology of PTSD remains largely unknown. Several neurobiological systems have been implicated in the pathophysiology and vulnerability for developing PTSD; however, first-line pharmacotherapies are limited. Less than 30% achieve full remission, and even then, approved pharmacological treatments often take weeks for therapeutic effect. This article aims to review the pathophysiology of PTSD within multiple neurobiological systems and how these mechanisms are used as pharmacologic targets of treatment, as well as their potential for future targets of intervention. Highlights of the article We reviewed the neurobiological abnormalities in PTSD as they relate to well-established, preliminary, and future targets for pharmacological interventions. Abnormalities across different neurotransmitter systems have been implicated in the pathophysiology of PTSD but none of these systems function uniformly among all patients with PTSD First-line pharmacotherapy for PTSD provides a suboptimal response rates. Future pharmacological targets for PTSD include the cannabinoid and oxytocin systems, as well glutamatergic modulating agents. Drug development for PTSD should specifically address various dimensions of PTSD symptomatology. PMID:27837583

  3. Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

    PubMed

    Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

    2017-03-28

    Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

  4. Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy

    PubMed Central

    Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

    2017-01-01

    Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition—even in homozygous subjects—to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency. PMID:28350321

  5. Rhenium(VII) Catalysis of Prins Cyclization Reactions

    PubMed Central

    Tadpetch, Kwanruthai; Rychnovsky, Scott D.

    2009-01-01

    The rhenium(VII) complex O3ReOSiPh3 are particularly effective catalyst for Prins cyclizations using aromatic and α,β-unsaturated aldehydes. The reaction conditions are mild and the highly substituted 4-hydroxy tetrahydropyran products are formed stereoselectively. Rhenium(VII) complexes appear to spontaneously form esters with alcohols and to directly activate electron rich alcohols for solvolysis. Re2O7 and perrhenic acid were equally effective in catalyzing these cyclizations. PMID:18816133

  6. Life-threatening bleeding in a case of autoantibody-induced factor VII deficiency.

    PubMed

    Okajima, K; Ishii, M

    1999-02-01

    A male patient presented with life-threatening bleeding induced by autoantibody-induced factor VII (F.VII) deficiency. This patient had macroscopic hematuria, skin ecchymosis, gastrointestinal bleeding, and a neck hematoma that was causing disturbed respiration. He developed acute renal failure and acute hepatic failure, probably due to obstruction of the ureters and the biliary tract, respectively. Although activated partial thromboplastin time was normal, prothrombin time (PT) was remarkably prolonged at 71.8 seconds compared to 14.0 seconds in a normal control. Both the immunoreactive level of F.VII antigen and the F.VII activity of the patient's plasma samples were < 1.0% of normal. Although an equal part of normal plasma was added to the patient's plasma, PT was not corrected. The patient's plasma inhibited F.VII activity. These findings suggested the presence of a plasma inhibitor for F.VII. After administration of large doses of methylprednisolone, PT was gradually shortened and plasma levels of F.VII increased over time. Bleeding, acute renal failure, and acute hepatic failure improved markedly following the steroid treatment. These observations suggest that life-threatening bleeding can be induced by autoantibody-induced F.VII deficiency and that immunosuppressive therapy using large doses of steroid can be successful in inhibiting the production of the autoantibody.

  7. The neurobiology of syntax: beyond string sets.

    PubMed

    Petersson, Karl Magnus; Hagoort, Peter

    2012-07-19

    The human capacity to acquire language is an outstanding scientific challenge to understand. Somehow our language capacities arise from the way the human brain processes, develops and learns in interaction with its environment. To set the stage, we begin with a summary of what is known about the neural organization of language and what our artificial grammar learning (AGL) studies have revealed. We then review the Chomsky hierarchy in the context of the theory of computation and formal learning theory. Finally, we outline a neurobiological model of language acquisition and processing based on an adaptive, recurrent, spiking network architecture. This architecture implements an asynchronous, event-driven, parallel system for recursive processing. We conclude that the brain represents grammars (or more precisely, the parser/generator) in its connectivity, and its ability for syntax is based on neurobiological infrastructure for structured sequence processing. The acquisition of this ability is accounted for in an adaptive dynamical systems framework. Artificial language learning (ALL) paradigms might be used to study the acquisition process within such a framework, as well as the processing properties of the underlying neurobiological infrastructure. However, it is necessary to combine and constrain the interpretation of ALL results by theoretical models and empirical studies on natural language processing. Given that the faculty of language is captured by classical computational models to a significant extent, and that these can be embedded in dynamic network architectures, there is hope that significant progress can be made in understanding the neurobiology of the language faculty.

  8. The neurobiology of syntax: beyond string sets

    PubMed Central

    Petersson, Karl Magnus; Hagoort, Peter

    2012-01-01

    The human capacity to acquire language is an outstanding scientific challenge to understand. Somehow our language capacities arise from the way the human brain processes, develops and learns in interaction with its environment. To set the stage, we begin with a summary of what is known about the neural organization of language and what our artificial grammar learning (AGL) studies have revealed. We then review the Chomsky hierarchy in the context of the theory of computation and formal learning theory. Finally, we outline a neurobiological model of language acquisition and processing based on an adaptive, recurrent, spiking network architecture. This architecture implements an asynchronous, event-driven, parallel system for recursive processing. We conclude that the brain represents grammars (or more precisely, the parser/generator) in its connectivity, and its ability for syntax is based on neurobiological infrastructure for structured sequence processing. The acquisition of this ability is accounted for in an adaptive dynamical systems framework. Artificial language learning (ALL) paradigms might be used to study the acquisition process within such a framework, as well as the processing properties of the underlying neurobiological infrastructure. However, it is necessary to combine and constrain the interpretation of ALL results by theoretical models and empirical studies on natural language processing. Given that the faculty of language is captured by classical computational models to a significant extent, and that these can be embedded in dynamic network architectures, there is hope that significant progress can be made in understanding the neurobiology of the language faculty. PMID:22688633

  9. Neurobiological Correlates in Forensic Assessment: A Systematic Review

    PubMed Central

    van der Gronde, Toon; Kempes, Maaike; van El, Carla; Rinne, Thomas; Pieters, Toine

    2014-01-01

    Background With the increased knowledge of biological risk factors, interest in including this information in forensic assessments is growing. Currently, forensic assessments are predominantly focused on psychosocial factors. A better understanding of the neurobiology of violent criminal behaviour and biological risk factors could improve forensic assessments. Objective To provide an overview of the current evidence about biological risk factors that predispose people to antisocial and violent behaviour, and determine its usefulness in forensic assessment. Methods A systematic literature search was conducted using articles from PsycINFO, Embase and Pubmed published between 2000 and 2013. Results This review shows that much research on the relationship between genetic predisposition and neurobiological alterations with aggression is performed on psychiatric patients or normal populations. However, the number of studies comparing offenders is limited. There is still a great need to understand how genetic and neurobiological alterations and/or deficits are related to violent behaviour, specifically criminality. Most studies focus on only one of the genetic or neurobiological fields related to antisocial and/or violent behaviour. To reliably correlate the findings of these fields, a standardization of methodology is urgently needed. Conclusion Findings from the current review suggest that violent aggression, like all forms of human behaviour, both develops under specific genetic and environmental conditions, and requires interplay between these conditions. Violence should be considered as the end product of a chain of life events, during which risks accumulate and potentially reinforce each other, displaying or triggering a specific situation. This systematic review did not find evidence of predispositions or neurobiological alterations that solely explain antisocial or violent behaviour. With better designed studies, more correlation between diverse fields, and more

  10. Neurobiological correlates in forensic assessment: a systematic review.

    PubMed

    van der Gronde, Toon; Kempes, Maaike; van El, Carla; Rinne, Thomas; Pieters, Toine

    2014-01-01

    With the increased knowledge of biological risk factors, interest in including this information in forensic assessments is growing. Currently, forensic assessments are predominantly focused on psychosocial factors. A better understanding of the neurobiology of violent criminal behaviour and biological risk factors could improve forensic assessments. To provide an overview of the current evidence about biological risk factors that predispose people to antisocial and violent behaviour, and determine its usefulness in forensic assessment. A systematic literature search was conducted using articles from PsycINFO, Embase and Pubmed published between 2000 and 2013. This review shows that much research on the relationship between genetic predisposition and neurobiological alterations with aggression is performed on psychiatric patients or normal populations. However, the number of studies comparing offenders is limited. There is still a great need to understand how genetic and neurobiological alterations and/or deficits are related to violent behaviour, specifically criminality. Most studies focus on only one of the genetic or neurobiological fields related to antisocial and/or violent behaviour. To reliably correlate the findings of these fields, a standardization of methodology is urgently needed. Findings from the current review suggest that violent aggression, like all forms of human behaviour, both develops under specific genetic and environmental conditions, and requires interplay between these conditions. Violence should be considered as the end product of a chain of life events, during which risks accumulate and potentially reinforce each other, displaying or triggering a specific situation. This systematic review did not find evidence of predispositions or neurobiological alterations that solely explain antisocial or violent behaviour. With better designed studies, more correlation between diverse fields, and more standardisation, it might be possible to

  11. [Conversion disorder : functional neuroimaging and neurobiological mechanisms].

    PubMed

    Lejeune, J; Piette, C; Salmon, E; Scantamburlo, G

    2017-04-01

    Conversion disorder is a psychiatric disorder often encountered in neurology services. This condition without organic lesions was and still is sometimes referred as an imaginary illness or feigning. However, the absence of organic lesions does not exclude the possibility of cerebral dysfunction. The etiologic mechanisms underlying this disorder remain uncertain even today.The advent of cognitive and functional imaging opens up a field of exploration for psychiatry in understanding the neurobiological mechanisms underlying mental disorders and especially the conversion disorder. This article reports several neuroimaging studies of conversion disorder and attempts to generate hypotheses about neurobiological mechanisms.

  12. Neurobiology of rhythmic motor entrainment.

    PubMed

    Molinari, Marco; Leggio, Maria G; De Martin, Martina; Cerasa, Antonio; Thaut, Michael

    2003-11-01

    Timing is extremely important for movement, and understanding the neurobiological basis of rhythm perception and reproduction can be helpful in addressing motor recovery after brain lesions. In this quest, the science of music might provide interesting hints for better understanding the brain timing mechanism. The report focuses on the neurobiological substrate of sensorimotor transformation of time data, highlighting the power of auditory rhythmic stimuli in guiding motor acts. The cerebellar role of timing is addressed in subjects with cerebellar damage; subsequently, cerebellar timing processing is highlighted through an fMRI study of professional musicians. The two approaches converge to demonstrate that different levels of time processing exist, one conscious and one not, and to support the idea that timing is a distributed function. The hypothesis that unconscious motor responses to auditory rhythmic stimuli can be relevant in guiding motor recovery and modulating music perception is advanced and discussed.

  13. 40 CFR Appendixes I-Vii to Part 85 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 18 2011-07-01 2011-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

  14. 40 CFR Appendixes I-Vii to Part 85 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

  15. 40 CFR Appendixes I-Vii to Part 85 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 19 2012-07-01 2012-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

  16. 40 CFR Appendixes I-Vii to Part 85 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 19 2013-07-01 2013-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

  17. 40 CFR Appendixes I-Vii to Part 85 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 19 2014-07-01 2014-07-01 false [Reserved] I Appendixes I-VII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Appendixes I-VII to Part 85 [Reserved] ...

  18. SUPPORT FOR BEIR VII

    EPA Science Inventory

    The office is supporting the continued funding of National Academy of Sciences Study to update our understanding of the effects of low-level radiation. In particular, this study, entitled the Biological Effects of Ionizing Radiation VII, will draw upon the most recent data avail...

  19. 40 CFR Appendixes Vi-Vii to Part 600 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false [Reserved] VI Appendixes VI-VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Appendixes VI-VII to Part 600 [Reserved] ...

  20. 40 CFR Appendixes Vi-Vii to Part 600 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 30 2011-07-01 2011-07-01 false [Reserved] VI Appendixes VI-VII to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Appendixes VI-VII to Part 600 [Reserved] ...

  1. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    PubMed

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  2. Anatomic Variability of the Upper Mediastinal Lymph Node Level VII.

    PubMed

    Hartl, Dana M; Breuskin, Ingrid; Mirghani, Haïtham; Berdelou, Amandine; Déandréis, Désirée; Pottier, Edwige; Borget, Isabelle; Schlumberger, Martin; Leboulleux, Sophie

    2016-08-01

    Lymph node level VII, between the sternal notch and the innominate artery, is a frequent site of lymph node metastases in thyroid cancer. The objective of this study was to determine the cranial-caudal dimensions of level VII in patients undergoing central neck dissection for thyroid cancer and its accessibility through a neck incision only. Consecutive patients undergoing central neck dissection for thyroid cancer, with no previous neck dissection, mediastinal or thoracic surgery. The innominate artery was identified and the distance between the sternal notch and the upper border of the artery was measured to the nearest .5 mm. The sizes of level VII were compared with respect to age, sex, height, body mass index, type of neck dissection (therapeutic or prophylactic), and the incidence of previous thyroidectomy. One-hundred-one consecutive patients (65 women, 36 men, mean age 44 years (range 15-87) underwent prophylactic (n = 55) or therapeutic (n = 46) bilateral central compartment neck dissection. Level VII was accessible via the horizontal neck incision in all cases. Sizes of level VII ranged from 6 cm above the sternal notch to 35 mm below the sternal notch, with a mean distance of 3.5 mm below the sternal notch. The innominate artery was at the level of the sternal notch in 29 patients, and cranial to the sternal notch in 20 cases. No statistical relationship with age, sex, therapeutic/prophylactic neck dissection, previous surgery, body mass index or height was found. The maximal distance below the sternal notch was 35 mm. Level VII did not exist in 49 % of patients, and was less than 25 mm caudal to the sternal notch in 95 % of cases. Distinguishing level VII from level VI in thyroid cancer surgery may not be pertinent, due to the ease of access via a classic horizontal neck incision and the small sizes of level VII in the majority of patients.

  3. Neurobiological findings related to Internet use disorders.

    PubMed

    Park, Byeongsu; Han, Doug Hyun; Roh, Sungwon

    2017-07-01

    In the last 10 years, numerous neurobiological studies have been conducted on Internet addiction or Internet use disorder. Various neurobiological research methods - such as magnetic resonance imaging; nuclear imaging modalities, including positron emission tomography and single photon emission computed tomography; molecular genetics; and neurophysiologic methods - have made it possible to discover structural or functional impairments in the brains of individuals with Internet use disorder. Specifically, Internet use disorder is associated with structural or functional impairment in the orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex. These regions are associated with the processing of reward, motivation, memory, and cognitive control. Early neurobiological research results in this area indicated that Internet use disorder shares many similarities with substance use disorders, including, to a certain extent, a shared pathophysiology. However, recent studies suggest that differences in biological and psychological markers exist between Internet use disorder and substance use disorders. Further research is required for a better understanding of the pathophysiology of Internet use disorder. © 2016 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

  4. Interrelation between factor VII, prekallikrein, and hyperfibrinolysis in advanced cirrhosis.

    PubMed Central

    Violi, F; Alessandri, C; Ferro, D; Saliola, M; Cordova, C; Musca, A; Balsano, F

    1989-01-01

    Factor VII and prekallikrein activities were studied in 37 patients with liver cirrhosis who were in a decompensated state. Sixteen of them died 30-70 days after admission; 21 survived and were discharged after 30-80 days. Seven who died and six survivors had signs of hyperfibrinolysis: factor VII activity differentiated the two groups independently of the presence of hyperfibrinolysis. The presence of hyperfibrinolysis significantly reduced prekallikrein activity, which did not differentiate clearly survivors from non-survivors. Long term follow up of survivors showed a good correlation between factor VII and prekallikrein activities with long term survival. Hyperfibrinolysis seemed to influence the clinical course of patients: 87% of patients with hyperfibrinolysis who died had fatal haemorrhagic episodes. Low factor VII activity may be a precursor of terminal liver insufficiency. PMID:2613916

  5. The neurobiology of individuality

    NASA Astrophysics Data System (ADS)

    de Bivort, Benjamin

    2015-03-01

    Individuals often display conspicuously different patterns of behavior, even when they are very closely related genetically. These differences give rise to our sense of individuality, but what is their molecular and neurobiological basis? Individuals that are nominally genetically identical differ at various molecular and neurobiological levels: cell-to-cell variation in somatic genomes, cell-to-cell variation in expression patterns, individual-to-individual variation in neuronal morphology and physiology, and individual-to-individual variation in patterns of brain activity. It is unknown which of these levels is fundamentally causal of behavioral differences. To investigate this problem, we use the fruit fly Drosophila melanogaster, whose genetic toolkit allows the manipulation of each of these mechanistic levels, and whose rapid lifecycle and small size allows for high-throughput automation of behavioral assays. This latter point is crucial; identifying inter-individual behavioral differences requires high sample sizes both within and across individual animals. Automated behavioral characterization is at the heart of our research strategy. In every behavior examined, individual flies have individual behavioral preferences, and we have begun to identify both neural genes and circuits that control the degree of behavioral variability between individuals.

  6. Neurobiology of wisdom: a literature overview.

    PubMed

    Meeks, Thomas W; Jeste, Dilip V

    2009-04-01

    Wisdom is a unique psychological trait noted since antiquity, long discussed in humanities disciplines, recently operationalized by psychology and sociology researchers, but largely unexamined in psychiatry or biology. To discuss recent neurobiological studies related to subcomponents of wisdom identified from several published definitions/descriptions of wisdom by clinical investigators in the field, ie, prosocial attitudes/behaviors, social decision making/pragmatic knowledge of life, emotional homeostasis, reflection/self-understanding, value relativism/tolerance, and acknowledgment of and dealing effectively with uncertainty. Literature focusing primarily on neuroimaging/brain localization and secondarily on neurotransmitters, including their genetic determinants. Studies involving functional neuroimaging or neurotransmitter functioning, examining human (rather than animal) subjects, and identified via a PubMed search using keywords from any of the 6 proposed subcomponents of wisdom were included. Studies were reviewed by both of us, and data considered to be potentially relevant to the neurobiology of wisdom were extracted. Functional neuroimaging permits exploration of neural correlates of complex psychological attributes such as those proposed to comprise wisdom. The prefrontal cortex figures prominently in several wisdom subcomponents (eg, emotional regulation, decision making, value relativism), primarily via top-down regulation of limbic and striatal regions. The lateral prefrontal cortex facilitates calculated, reason-based decision making, whereas the medial prefrontal cortex is implicated in emotional valence and prosocial attitudes/behaviors. Reward neurocircuitry (ventral striatum, nucleus accumbens) also appears important for promoting prosocial attitudes/behaviors. Monoaminergic activity (especially dopaminergic and serotonergic), influenced by several genetic polymorphisms, is critical to certain subcomponents of wisdom such as emotional

  7. The neurobiology of the stress-resistant brain

    PubMed Central

    FLESHNER, MONIKA; MAIER, STEVEN F.; LYONS, DAVID M.; RASKIND, MURRAY A.

    2012-01-01

    The 2010 Neurobiology of Stress Workshop brought together scientists from all over the world to share and discuss their results from studies examining the consequences of acute, repeated, and chronic stressor exposure on health and disease. Session IV entitled “The neurobiology of the stress-resistant brain” explored how we can intervene to promote stress resistance and stress resilience. Four scientists, who explore this topic from unique and convergent perspectives, presented their experimental results derived from studies in rat (Fleshner and Maier), non-human primates (Lyons), and human (Raskind). Summaries of each presentation, supporting publications, and overall take-home messages from the session are presented. PMID:21790482

  8. Learning from history: the legacy of Title VII in academic family medicine.

    PubMed

    Newton, Warren; Arndt, Jane E

    2008-11-01

    The current renaissance of interest in primary care could benefit from reviewing the history of federal investment in academic family medicine. The authors review 30 years of experience with the Title VII, Section 747 Training in Primary Care Medicine and Dentistry (Title VII) grant program, addressing three questions: (1) What Title VII grant programs were available to family medicine, and what were their goals? (2) How did Title VII change the discipline? and (3) What impact did Title VII family medicine programs have outside the discipline?Title VII grant programs evolved from broad support for the new discipline of family medicine to a sharper focus on specific national workforce objectives such as improving care for underserved and vulnerable populations and increasing diversity in the health professions. Grant programs were instrumental in establishing family medicine in nearly all medical schools and in supporting the educational underpinnings of the field. Title VII grants helped enhance the social capital of the discipline. Outside family medicine, Title VII fostered the development of innovative ambulatory education, institutional initiatives focusing on underserved and vulnerable populations, and primary care research capacity. Adverse effects include relative inattention to clinical and research missions in family medicine academic units and, institutionally, the development of medical education initiatives without core institutional support, which has put innovation and extension of education to communities at risk as grant funding has decreased. Reinvestment in academic family medicine can yield substantial benefits for family medicine and help reorient academic health centers. This article is part of a theme issue of Academic Medicine on the Title VII health professions training programs.

  9. Factor VII deficiency: a single-center experience.

    PubMed

    Salcioglu, Zafer; Akcay, Arzu; Sen, Hulya Sayilan; Aydogan, Gonul; Akici, Ferhan; Tugcu, Deniz; Ayaz, Nuray Aktay; Baslar, Zafer

    2012-11-01

    Congenital factor VII deficiency is the most common form of rare coagulation factor deficiencies. This article presents a retrospective evaluation of 73 factor VII deficiency cases that had been followed at our center. The study consisted of 48 males and 25 females (2 months-19 years). Thirty-one (42.5%) of them were asymptomatic. Out of symptomatic patients, 17 had severe clinical symptoms, whereas 8 presented with moderate and 17 with mild symptoms. The symptoms listed in order of frequency were as follows: epistaxis, petechia or ecchymose, easy bruising, and oral cavity bleeding. The genotype was determined in 8 patients. Recombinant activated factor VII (rFVIIa) was used to treat 49 bleeding episodes in 8 patients after 2002. In 2 patients with repeated central nervous system bleeding prophylaxis with rFVIIa was administered. No allergic and thrombotic events were observed during both treatment and prophylaxis courses. Antibody occurrence was not detected in the patients during treatment.

  10. Neurobiological and neurocognitive effects of chronic cigarette smoking and alcoholism.

    PubMed

    Durazzo, Timothy C; Meyerhoff, Dieter J

    2007-05-01

    Chronic cigarette smoking is associated with adverse effects on cardiac, pulmonary, and vascular function as well as the increased risk for various forms of cancer. However, little is known about the effects of chronic smoking on human brain function. Although smoking rates have decreased in the developed world, they remain high in individuals with alcohol use disorders (AUD) and other neuropsychiatric conditions. Despite the high prevalence of chronic smoking in AUD, few studies have addressed the potential neurobiological or neurocognitive consequences of chronic smoking in alcohol use disorders. Here, we review the the neurobiological and neurocognitive findings in both AUD and chronic cigarette smoking, followed by a review of the effects of comorbid cigarette smoking on neurobiology and neurocognition in AUD. Recent research suggests that comorbid chronic cigarette smoking modulates magnetic resonance-detectable brain injury and neurocognition in alcohol use disorders and adversely affects neurobiological and neurocognitive recovery in abstinent alcoholics.. Consideration of the potential separate and interactive effects of chronic smoking and alcohol use disorders may have significant implications for pharmacological and behavioral treatment interventions.

  11. It's no debate, debates are great.

    PubMed

    Dy-Boarman, Eliza A; Nisly, Sarah A; Costello, Tracy J

    A debate can be a pedagogical method used to instill essential functions in pharmacy students. This non-traditional teaching method may help to further develop a number of skills that are highlighted in the current Accreditation Council for Pharmacy Education Standards 2016 and Center for the Advancement of Pharmacy Education Educational Outcomes 2013. Debates have also been used as an educational tool in other health disciplines. Current pharmacy literature does illustrate the use of debates in various areas within the pharmacy curriculum in both required and elective courses; however, the current body of literature would suggest that debates are an underutilized teaching tool in pharmacy experiential education. With all potential benefits of debates as a teaching tool, pharmacy experiential preceptors should further explore their use in the experiential setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients

    PubMed Central

    Woodley, David T.; Cogan, Jon; Hou, Yingping; Lyu, Chao; Marinkovich, M. Peter; Keene, Douglas

    2017-01-01

    BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease caused by mutations in the gene encoding type VII collagen, the major component of anchoring fibrils (AF). We previously demonstrated that gentamicin produced functional type VII collagen in RDEB cells harboring nonsense mutations. Herein, we determined whether topical or intradermal gentamicin administration induces type VII collagen and AFs in RDEB patients. METHODS. A double-blind, placebo-controlled pilot trial assessed safety and efficacy of topical and intradermal gentamicin in 5 RDEB patients with nonsense mutations. The topical arm tested 0.1% gentamicin ointment or placebo application 3 times daily at 2 open erosion sites for 2 weeks. The intradermal arm tested daily intradermal injection of gentamicin solution (8 mg) or placebo into 2 intact skin sites for 2 days in 4 of 5 patients. Primary outcomes were induction of type VII collagen and AFs at the test sites and safety assessment. A secondary outcome assessed wound closure of topically treated erosions. RESULTS. Both topical and intradermal gentamicin administration induced type VII collagen and AFs at the dermal-epidermal junction of treatment sites. Newly created type VII collagen varied from 20% to 165% of that expressed in normal human skin and persisted for 3 months. Topical gentamicin corrected dermal-epidermal separation, improved wound closure, and reduced blister formation. There were no untoward side effects from gentamicin treatments. Type VII collagen induction did not generate anti–type VII collagen autoantibodies in patients’ blood or skin. CONCLUSION. Topical and intradermal gentamicin suppresses nonsense mutations and induces type VII collagen and AFs in RDEB patients. Gentamicin therapy may provide a readily available treatment for RDEB patients with nonsense mutations. TRIAL REGISTRATION. ClinicalTrials.gov NCT02698735. FUNDING. Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa

  13. Structural incorporation of MgCl2 into ice VII at room temperature

    NASA Astrophysics Data System (ADS)

    Watanabe, Mao; Komatsu, Kazuki; Noritake, Fumiya; Kagi, Hiroyuki

    2017-05-01

    Raman spectra and X-ray diffraction patterns were obtained from 1:100 and 1:200 \\text{MgCl}2:\\text{H}2\\text{O} solutions (in molar ratio) at pressures up to 6 GPa using diamond anvil cells (DACs) and compared with those of pure water. The O-H stretching band from ice VII crystallized from the 1:200 solution was approximately 10 cm-1 higher than that of pure ice VII. The phase boundaries between ice VII and VIII crystallized from the MgCl2 solutions at 4 GPa were 2 K lower than those of pure ice VII and VIII. These observations indicate that ice VII incorporates MgCl2 into its structure. The unit cell volumes of ice VII crystallized from pure water and the two solutions coincided with each other within the experimental error, and salt incorporation was not detectable from the cell volume. Possible configurations of ion substitution and excess volume of ice VIII were simulated on the basis of density functional theory (DFT) calculations.

  14. The neurobiological basis of temperament: towards a better understanding of psychopathology.

    PubMed

    Whittle, Sarah; Allen, Nicholas B; Lubman, Dan I; Yücel, Murat

    2006-01-01

    The ability to characterise psychopathologies on the basis of their underlying neurobiology is critical in improving our understanding of disorder etiology and making more effective diagnostic and treatment decisions. Given the well-documented relationship between temperament (i.e. core personality traits) and psychopathology, research investigating the neurobiological substrates that underlie temperament is potentially key to our understanding of the biological basis of mental disorder. We present evidence that specific areas of the prefrontal cortex (including the dorsolateral prefrontal, anterior cingulate, and orbitofrontal cortices) and limbic structures (including the amygdala, hippocampus and nucleus accumbens) are key regions associated with three fundamental dimensions of temperament: Negative Affect, Positive Affect, and Constraint. Proposed relationships are based on two types of research: (a) research into the neurobiological correlates of affective and cognitive processes underlying these dimensions; and (b) research into the neurobiology of various psychopathologies, which have been correlated with these dimensions. A model is proposed detailing how these structures might comprise neural networks whose functioning underlies the three temperaments. Recommendations are made for future research into the neurobiology of temperament, including the need to focus on neural networks rather than individual structures, and the importance of prospective, longitudinal, multi-modal imaging studies in at-risk youth.

  15. Neurocontrol and neurobiology - New developments and connections

    NASA Technical Reports Server (NTRS)

    Werbos, Paul J.; Pellionisz, Andras J.

    1992-01-01

    At McDonnell-Douglas, controllers which combine adaptive critic networks with the use of backpropagation in real time have solved difficult control problems crucial to the feasibility of building the National Aerospace Plane (NASP) able to reach earth orbit. As details emerged, parallels to neurobiology have grown stronger and have begun to lead to empirical possibilities of importance to neuroscience. This has led to thoughts of institutional collaboration facilitating what could become a Newtonian revolution in neuroscience, with cognitive implications as well. The authors elaborate on each of these points. The topics discussed are recent progress in neurocontrol; progress in optimization and reinforcement learning; implications for neurobiology and science policy; and a new view of the brain.

  16. Cocaine Addiction: Neurobiology and Related Current Research in Pharmacotherapy.

    PubMed

    Panikkar, Gopakumar P.

    1999-09-01

    In this article, recent research studies in the field of cocaine addiction are reviewed, with an eye toward emergent options for treatment innovation. Particular attention is paid to the neurobiology and specific neurotransmitter and receptor mechanisms involved in cocaine abuse, dependence, and other unique phenomena of addiction such as sensitization, craving, compulsive drug use, and withdrawal. The vicissitudes in the dopamine theory of brain reward mechanisms, dopaminergic effects of cocaine, and emerging roles of GABA, serotonin, glutamate, and nitric oxide in cocaine addiction and its sequelae are discussed. Neuroanatomic findings elicited with imaging studies using PET and functional MRI are summarized. These findings support the role of specific brain regions within the dopaminergic system such as the ventral tegmentum and nucleus accumbens in the induction of the cocaine "high" and craving, respectively. Research approaches to the problem of developing effective pharmacotherapeutic options to render cocaine ineffective and modalities under study, such as dopamine uptake inhibitors and immunotherapy, are also discussed in the context of a variety of practical problems faced by these experimental therapies. Pharmacotherapeutic strategies and new directions in this research, such as the adaptive changes of the opioid system in cocaine addiction, are reviewed. Potential areas for further study are brought forth for further debate and possible clinical evaluation.

  17. Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.

    PubMed

    Giuntoli, Beatrice; Shukla, Vinay; Maggiorelli, Federica; Giorgi, Federico M; Lombardi, Lara; Perata, Pierdomenico; Licausi, Francesco

    2017-10-01

    The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions. The contribution of the ERF-VIIs in regulating this set of genes in response to chemically induced or submergence-stimulated mitochondria malfunctioning was found to depend on the plant developmental stage. A similar age-dependent mechanism also restrained ERF-VII activity upon the core-hypoxic genes, independently of the N-end rule pathway, which is accounted for the control of the anaerobic response. To conclude, this study shed new light on a dual role of ERF-VII proteins under submergence: as positive regulators of the hypoxic response and as repressors of oxidative-stress related genes, depending on the developmental stage at which plants are challenged by stress conditions. © 2017 John Wiley & Sons Ltd.

  18. Blister-inducing antibodies target multiple epitopes on collagen VII in mice

    PubMed Central

    Csorba, Kinga; Chiriac, Mircea Teodor; Florea, Florina; Ghinia, Miruna Georgiana; Licarete, Emilia; Rados, Andreea; Sas, Alexandra; Vuta, Vlad; Sitaru, Cassian

    2014-01-01

    Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease of mucous membranes and the skin caused by autoantibodies against collagen VII. In silico and wet laboratory epitope mapping studies revealed numerous distinct epitopes recognized by EBA patients' autoantibodies within the non-collagenous (NC)1 and NC2 domains of collagen VII. However, the distribution of pathogenic epitopes on collagen VII has not yet been described. In this study, we therefore performed an in vivo functional epitope mapping of pathogenic autoantibodies in experimental EBA. Animals (n = 10/group) immunized against fragments of the NC1 and NC2 domains of collagen VII or injected with antibodies generated against the same fragments developed to different extent experimental EBA. Our results demonstrate that antibodies targeting multiple, distinct epitopes distributed over the entire NC1, but not NC2 domain of collagen VII induce blistering skin disease in vivo. Our present findings have crucial implications for the development of antigen-specific B- and T cell-targeted therapies in EBA. PMID:25091020

  19. Neurobiology of Childhood-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Biswas, Parthasarathy

    2008-01-01

    In the last decade there has been an exponential increase in studies on neurobiological measures in childhood-onset schizophrenia (COS). There seems to be a consensus that structural changes in COS are more marked than in adolescence-onset (AdOS) or adult-onset schizophrenia (AOS). Atrophy of total brain volume is progressive throughout the course…

  20. Pathogenesis of aortic dilatation in mucopolysaccharidosis VII mice may involve complement activation

    PubMed Central

    Baldo, Guilherme; Wu, Susan; Howe, Ruth A.; Ramamoothy, Meera; Knutsen, Russell H.; Fang, Jiali; Mecham, Robert P.; Liu, Yuli; Wu, Xiaobo; Atkinson, John P.; Ponder, Katherine P.

    2012-01-01

    Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme β-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation, which is associated with upregulation of the elastases cathepsin S (CtsS) and matrix metalloproteinase 12 (MMP12). To test the role of these enzymes, MPS VII mice were crossed with mice deficient in CtsS or MMP12, and the effect upon aortic dilatation was determined. CtsS deficiency did not protect against aortic dilatation in MPS VII mice, but also failed to prevent an upregulation of cathepsin enzyme activity. Further analysis with substrates and inhibitors specific for particular cathepsins suggests that this enzyme activity was due to CtsB, which could contribute to elastin fragmentation. Similarly, MMP12 deficiency and deficiency of both MMP12 and CtsS could not prevent aortic dilatation in MPS VII mice. Microarray and reverse-transcriptase real-time PCR were performed to look for upregulation of other elastases. This demonstrated that mRNA for complement component D was elevated in MPS VII mice, while immunostaining demonstrated high levels of complement component C3 on surfaces within the aortic media. Finally, we demonstrate that neonatal intravenous injection of a retroviral vector encoding β-glucuronidase reduced aortic dilatation. We conclude that neither CtsS nor MMP12 are necessary for elastin fragmentation in MPS VII mouse aorta, and propose that CtsB and/or complement component D may be involved. Complement may be activated by the GAGs that accumulate, and may play a role in signal transduction pathways that upregulate elastases. PMID:21944884

  1. Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

    PubMed Central

    Ruusuvuori, Eva; Huebner, Antje K; Kirilkin, Ilya; Yukin, Alexey Y; Blaesse, Peter; Helmy, Mohamed; Jung Kang, Hyo; El Muayed, Malek; Christopher Hennings, J; Voipio, Juha; Šestan, Nenad; Hübner, Christian A; Kaila, Kai

    2013-01-01

    Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CA VII (Car7) knockout (KO) mouse as well as a CA II (Car2) KO and a CA II/VII double KO, we show that mature hippocampal pyramidal neurons are endowed with two cytosolic isoforms. CA VII is predominantly expressed by neurons starting around postnatal day 10 (P10). The ubiquitous isoform II is expressed in neurons at P20. Both isoforms enhance bicarbonate-driven GABAergic excitation during intense GABAA-receptor activation. P13–14 CA VII KO mice show behavioural manifestations atypical of experimental febrile seizures (eFS) and a complete absence of electrographic seizures. A low dose of diazepam promotes eFS in P13–P14 rat pups, whereas seizures are blocked at higher concentrations that suppress breathing. Thus, the respiratory alkalosis-dependent eFS are exacerbated by GABAergic excitation. We found that CA VII mRNA is expressed in the human cerebral cortex before the age when febrile seizures (FS) occur in children. Our data indicate that CA VII is a key molecule in age-dependent neuronal pH regulation with consequent effects on generation of FS. PMID:23881097

  2. Compression Freezing Kinetics of Water to Ice VII

    DOE PAGES

    Gleason, A. E.; Bolme, C. A.; Galtier, E.; ...

    2017-07-11

    Time-resolved x-ray diffraction (XRD) of compressed liquid water shows transformation to ice VII in 6 nsec, revealing crystallization rather than amorphous solidification during compression freezing. Application of classical nucleation theory indicates heterogeneous nucleation and one-dimensional (e.g., needlelike) growth. In conclusion, these first XRD data demonstrate rapid growth kinetics of ice VII with implications for fundamental physics of diffusion-mediated crystallization and thermodynamic modeling of collision or impact events on ice-rich planetary bodies.

  3. Compression Freezing Kinetics of Water to Ice VII

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gleason, A. E.; Bolme, C. A.; Galtier, E.

    Time-resolved x-ray diffraction (XRD) of compressed liquid water shows transformation to ice VII in 6 nsec, revealing crystallization rather than amorphous solidification during compression freezing. Application of classical nucleation theory indicates heterogeneous nucleation and one-dimensional (e.g., needlelike) growth. In conclusion, these first XRD data demonstrate rapid growth kinetics of ice VII with implications for fundamental physics of diffusion-mediated crystallization and thermodynamic modeling of collision or impact events on ice-rich planetary bodies.

  4. The Neurobiology of Learning and Memory.

    ERIC Educational Resources Information Center

    Thompson, Rihard F.

    1986-01-01

    Describes recent research findings in the area of neurobiology and its relationship to learning and memory. The article provides definitions of associative and nonassociative learning, identifies essential memory trace circuits of the mammalian brain, and discusses some neural mechanisms of learning. (TW)

  5. The Neurobiology of Swallowing and Dysphagia

    ERIC Educational Resources Information Center

    Miller, Arthur J.

    2008-01-01

    The neurobiological study of swallowing and its dysfunction, defined as dysphagia, has evolved over two centuries beginning with electrical stimulation applied directly to the central nervous system, and then followed by systematic investigations that have used lesioning, transmagnetic stimulation, magnetoencephalography, and functional magnetic…

  6. The neurobiology of the human memory.

    PubMed

    Fietta, Pierluigi; Fietta, Pieranna

    2011-01-01

    Memory can be defined as the ability to acquire, process, store, and retrieve information. Memory is indispensable for learning, adaptation, and survival of every living organism. In humans, the remembering process has acquired great flexibility and complexity, reaching close links with other mental functions, such as thinking and emotions. Changes in synaptic connectivity and interactions among multiple neural networks provide the neurobiological substrates for memory encoding, retention, and consolidation. Memory may be categorized as short-term and long-term memory (according to the storage temporal duration), as implicit and explicit memory (with respect to the consciousness of remembering), as declarative (knowing that [fact]) and procedural (knowing how [skill]) memory, or as sensory (echoic, iconic and haptil), semantic, and episodic memory (according to the various remembering domains). Significant advances have been obtained in understanding memory neurobiology, but much remains to be learned in its cognitive, psychological, and phenomenological aspects.

  7. Recent Neurobiological Insights into the Concept of Insight in Psychosis

    PubMed Central

    Mythri, Starlin Vijay; Sanjay, Y

    2016-01-01

    The concept of insight in psychosis has been an interesting area in clinical psychiatry for well over a century with a surge in research interest over the past 25 years. Moreover, the past 5 years have been particularly fruitful in deciphering its neurobiological underpinnings. This article presents the development of the concept of insight in psychosis and reviews the current neurobiological research findings in this area. PMID:27335512

  8. Plasmodium falciparum ookinete expression of plasmepsin VII and plasmepsin X.

    PubMed

    Li, Fengwu; Bounkeua, Viengngeun; Pettersen, Kenneth; Vinetz, Joseph M

    2016-02-24

    Plasmodium invasion of the mosquito midgut is a population bottleneck in the parasite lifecycle. Interference with molecular mechanisms by which the ookinete invades the mosquito midgut is one potential approach to developing malaria transmission-blocking strategies. Plasmodium aspartic proteases are one such class of potential targets: plasmepsin IV (known to be present in the asexual stage food vacuole) was previously shown to be involved in Plasmodium gallinaceum infection of the mosquito midgut, and plasmepsins VII and plasmepsin X (not known to be present in the asexual stage food vacuole) are upregulated in Plasmodium falciparum mosquito stages. These (and other) parasite-derived enzymes that play essential roles during ookinete midgut invasion are prime candidates for transmission-blocking vaccines. Reverse transcriptase PCR (RT-PCR) was used to determine timing of P. falciparum plasmepsin VII (PfPM VII) and plasmepsin X (PfPM X) mRNA transcripts in parasite mosquito midgut stages. Protein expression was confirmed by western immunoblot and immunofluorescence assays (IFA) using anti-peptide monoclonal antibodies (mAbs) against immunogenic regions of PfPM VII and PfPM X. These antibodies were also used in standard membrane feeding assays (SMFA) to determine whether inhibition of these proteases would affect parasite transmission to mosquitoes. The Mann-Whitney U test was used to analyse mosquito transmission assay results. RT-PCR, western immunoblot and immunofluorescence assay confirmed expression of PfPM VII and PfPM X in mosquito stages. Whereas PfPM VII was expressed in zygotes and ookinetes, PfPM X was expressed in gametes, zygotes, and ookinetes. Antibodies against PfPM VII and PfPM X decreased P. falciparum invasion of the mosquito midgut when used at high concentrations, indicating that these proteases play a role in Plasmodium mosquito midgut invasion. Failure to generate genetic knockouts of these genes limited determination of the precise role of

  9. Type VII Collagen Expression in the Human Vitreoretinal Interface, Corpora Amylacea and Inner Retinal Layers

    PubMed Central

    Wullink, Bart; Pas, Hendri H.; Van der Worp, Roelofje J.; Kuijer, Roel; Los, Leonoor I.

    2015-01-01

    Type VII collagen, as a major component of anchoring fibrils found at basement membrane zones, is crucial in anchoring epithelial tissue layers to their underlying stroma. Recently, type VII collagen was discovered in the inner human retina by means of immunohistochemistry, while proteomic investigations demonstrated type VII collagen at the vitreoretinal interface of chicken. Because of its potential anchoring function at the vitreoretinal interface, we further assessed the presence of type VII collagen at this site. We evaluated the vitreoretinal interface of human donor eyes by means of immunohistochemistry, confocal microscopy, immunoelectron microscopy, and Western blotting. Firstly, type VII collagen was detected alongside vitreous fibers6 at the vitreoretinal interface. Because of its known anchoring function, it is likely that type VII collagen is involved in vitreoretinal attachment. Secondly, type VII collagen was found within cytoplasmic vesicles of inner retinal cells. These cells resided most frequently in the ganglion cell layer and inner plexiform layer. Thirdly, type VII collagen was found in astrocytic cytoplasmic inclusions, known as corpora amylacea. The intraretinal presence of type VII collagen was confirmed by Western blotting of homogenized retinal preparations. These data add to the understanding of vitreoretinal attachment, which is important for a better comprehension of common vitreoretinal attachment pathologies. PMID:26709927

  10. 1977 National Debate Tournament Final Debate

    ERIC Educational Resources Information Center

    Rives, Stanley G., ed.; Boaz, John K., ed.

    1977-01-01

    Presents a transcript of the final debate of the Thirty-First National Debate Tournament sponsored by the American Forensic Association in 1977. Focuses on the necessity and desirability of requiring airbags to promote automobile safety. (MH)

  11. The Neurobiology of Alcohol Consumption and Alcoholism: An Integrative History1

    PubMed Central

    Tabakoff, Boris; Hoffman, Paula L.

    2013-01-01

    Studies of the neurobiological predisposition to consume alcohol (ethanol) and to transition to uncontrolled drinking behavior (alcoholism), as well as studies of the effects of alcohol on brain function, started a logarithmic growth phase after the repeal of the 18th Amendment to the United States Constitution. Although the early studies were primitive by current technological standards, they clearly demonstrated the effects of alcohol on brain structure and function, and by the end of the 20th century left little doubt that alcoholism is a “disease” of the brain. This review traces the history of developments in the understanding of ethanol’s effects on the most prominent inhibitory and excitatory systems of brain (GABA and glutamate neurotransmission). This neurobiological information is integrated with knowledge of ethanol’s actions on other neurotransmitter systems to produce an anatomical and functional map of ethanol’s properties. Our intent is limited in scope, but is meant to provide context and integration of the actions of ethanol on the major neurobiologic systems which produce reinforcement for alcohol consumption and changes in brain chemistry that lead to addiction. The developmental history of neurobehavioral theories of the transition from alcohol drinking to alcohol addiction is presented and juxtaposed to the neurobiological findings. Depending on one’s point of view, we may, at this point in history, know more, or less, than we think we know about the neurobiology of alcoholism. PMID:24141171

  12. The Trigeminal (V) and Facial (VII) Cranial Nerves

    PubMed Central

    Sanders, Richard D.

    2010-01-01

    There are close functional and anatomical relationships between cranial nerves V and VII in both their sensory and motor divisions. Sensation on the face is innervated by the trigeminal nerves (V) as are the muscles of mastication, but the muscles of facial expression are innervated mainly by the facial nerve (VII) as is the sensation of taste. This article briefly reviews the anatomy of these cranial nerves, disorders of these nerves that are of particular importance to psychiatry, and some considerations for differential diagnosis. PMID:20386632

  13. Successful and unsuccessful psychopaths: a neurobiological model.

    PubMed

    Gao, Yu; Raine, Adrian

    2010-01-01

    Despite increasing interest in psychopathy research, surprisingly little is known about the etiology of non-incarcerated, successful psychopaths. This review provides an analysis of current knowledge on the similarities and differences between successful and unsuccessful psychopaths derived from five population sources: community samples, individuals from employment agencies, college students, industrial psychopaths, and serial killers. An initial neurobiological model of successful and unsuccessful psychopathy is outlined. It is hypothesized that successful psychopaths have intact or enhanced neurobiological functioning that underlies their normal or even superior cognitive functioning, which in turn helps them to achieve their goals using more covert and nonviolent methods. In contrast, in unsuccessful, caught psychopaths, brain structural and functional impairments together with autonomic nervous system dysfunction are hypothesized to underlie cognitive and emotional deficits and more overt violent offending.

  14. Debating Historical Propositions: Toward a Unique Genre of NEDA Debate.

    ERIC Educational Resources Information Center

    Scott, David K.

    The best way to develop a unique identity for the National Education Debate Association (NEDA) is to debate propositions distinct from National Debate Tournament (NDT) and the Cross Examination Debate Association (CEDA). A neglected area of debate includes propositions temporally framed in the past. Yet, the present propositional categories of…

  15. (99)Tc(VII) Retardation, Reduction, and Redox Rate Scaling in Naturally Reduced Sediments.

    PubMed

    Liu, Yuanyuan; Liu, Chongxuan; Kukkadapu, Ravi K; McKinley, James P; Zachara, John; Plymale, Andrew E; Miller, Micah D; Varga, Tamas; Resch, Charles T

    2015-11-17

    An experimental and modeling study was conducted to investigate pertechnetate (Tc(VII)O4(-)) retardation, reduction, and rate scaling in three sediments from Ringold formation at U.S. Department of Energy's Hanford site, where (99)Tc is a major contaminant in groundwater. Tc(VII) was reduced in all the sediments in both batch reactors and diffusion columns, with a faster rate in a sediment containing a higher concentration of HCl-extractable Fe(II). Tc(VII) migration in the diffusion columns was reductively retarded with retardation degrees correlated with Tc(VII) reduction rates. The reduction rates were faster in the diffusion columns than those in the batch reactors, apparently influenced by the spatial distribution of redox-reactive minerals along transport paths that supplied Tc(VII). X-ray computed tomography and autoradiography were performed to identify the spatial locations of Tc(VII) reduction and transport paths in the sediments, and results generally confirmed the newly found behavior of reaction rate changes from batch to column. The results from this study implied that Tc(VII) migration can be reductively retarded at Hanford site with a retardation degree dependent on reactive Fe(II) content and its distribution in sediments. This study also demonstrated that an effective reaction rate may be faster in transport systems than that in well-mixed reactors.

  16. Prophylactic treatment of hereditary severe factor VII deficiency in pregnancy.

    PubMed

    Pfrepper, Christian; Siegemund, Annelie; Hildebrandt, Sven; Kronberg, Juliane; Scholz, Ute; Niederwieser, Dietger

    2017-09-01

    : Severe hereditary factor VII deficiency is a rare bleeding disorder and may be associated with a severe bleeding phenotype. We describe a pregnancy in a 33-year-old woman with compound heterozygous factor VII deficiency and a history of severe menorrhagia and mucocutaneous bleedings. After discontinuation of contraceptives, menstruation was covered with recombinant activated factor VII (rFVIIa), and during pregnancy, rFVIIa had to be administered in first trimester in doses ranging from 15 to 90 μg/kg per day because of recurrent retroplacental hematomas and vaginal bleedings. Thrombin generation was measured in first trimester at different doses of rFVIIa and showed an increase in lag time when doses of less than 30 μg/kg/day were administered, whereas time to thrombin peak and peak thrombin were not influenced. A low-dose rFVIIa prophylactic treatment of 15 μg/kg every other day in the late second and in the third trimester was sufficient to allow a successful childbirth in this patient with severe factor VII deficiency.

  17. 76 FR 31892 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-02

    ... Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION: Notice...'' or ``Commission'') proposes to extend its existing recordkeeping requirements under title VII of the Civil Rights Act of 1964 (Title VII) and the Americans with Disabilities Act (ADA) to entities covered...

  18. Molecular neurobiology in neurology and psychiatry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kandel, E.R.

    1987-01-01

    This book contains 14 selections. Some of the titles are: An Introduction to Ion Channels; Molecular Neurobiology of the Myelinated Nerve Fiber: Ion-Channel Distributions and Their Implications for Demyelinating Diseases; A Molecular Genetic Approach to Huntington's Disease; and Molecular Features of Cell Adhesion Molecules Involved in Neural Development.

  19. Effect of neonatal gene therapy on lumbar spine disease in mucopolysaccharidosis VII dogs

    PubMed Central

    Smith, Lachlan J; Martin, John T; O'Donnell, Patricia; Wang, Ping; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

    2012-01-01

    Mucopolysaccharidosis VII (MPS VII) is due to deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan, and dermatan sulfate glycosaminoglycans in various tissues including those of the spine. Associated spine disease can be due to abnormalities in the vertebrae, the intervertebral discs, or other spine tissues. The goal of this study was to determine if neonatal gene therapy could prevent lumbar spine disease in MPS VII dogs. MPS VII dogs were injected intravenously with a retroviral vector (RV) expressing canine GUSB at 2 to 3 days after birth, which resulted in transduction of hepatocytes that secreted GUSB into blood. Expression was stable for up to 11 years, and mean survival was increased from 0.4 years in untreated dogs to 6.1 years in treated dogs. Despite a profound positive clinical effect, 6-month-old RV-treated MPS VII dogs still had hypoplastic ventral epiphyses with reduced calcification in the lumbar spine, which resulted in a reduced stiffness and increased range of motion that was not improved relative to untreated MPS VII dogs. At six to 11 years of age, ventral vertebrae remained hypoplastic in RV-treated MPS VII dogs, and there was desiccation of the nucleus pulposus in some discs. Histochemical staining demonstrated that discs did not have detectable GUSB activity despite high serum GUSB activity, which is likely due to poor diffusion into this relatively avascular structure. Thus, neonatal gene therapy cannot prevent lumbar spine disease in MPS VII dogs, which predicts that enzyme replacement therapy (ERT) will similarly be relatively ineffective even if started at birth. PMID:22510705

  20. Effect of neonatal gene therapy on lumbar spine disease in mucopolysaccharidosis VII dogs.

    PubMed

    Smith, Lachlan J; Martin, John T; O'Donnell, Patricia; Wang, Ping; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

    2012-09-01

    Mucopolysaccharidosis VII (MPS VII) is due to deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan, and dermatan sulfate glycosaminoglycans in various tissues including those of the spine. Associated spine disease can be due to abnormalities in the vertebrae, the intervertebral disks, or other spine tissues. The goal of this study was to determine if neonatal gene therapy could prevent lumbar spine disease in MPS VII dogs. MPS VII dogs were injected intravenously with a retroviral vector (RV) expressing canine GUSB at 2 to 3 days after birth, which resulted in transduction of hepatocytes that secreted GUSB into blood. Expression was stable for up to 11 years, and mean survival was increased from 0.4 years in untreated dogs to 6.1 years in treated dogs. Despite a profound positive clinical effect, 6-month-old RV-treated MPS VII dogs still had hypoplastic ventral epiphyses with reduced calcification in the lumbar spine, which resulted in a reduced stiffness and increased range of motion that were not improved relative to untreated MPS VII dogs. At six to 11 years of age, ventral vertebrae remained hypoplastic in RV-treated MPS VII dogs, and there was desiccation of the nucleus pulposus in some disks. Histochemical staining demonstrated that disks did not have detectable GUSB activity despite high serum GUSB activity, which is likely due to poor diffusion into this relatively avascular structure. Thus, neonatal gene therapy cannot prevent lumbar spine disease in MPS VII dogs, which predicts that enzyme replacement therapy (ERT) will similarly be relatively ineffective even if started at birth. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. 77 FR 5396 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-03

    ... Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION: Final... rule, extends its existing recordkeeping requirements under title VII of the Civil Rights Act of 1964 (Title VII) and the Americans with Disabilities Act (ADA) to entities covered by title II of the Genetic...

  2. Controlling legs for locomotion-insights from robotics and neurobiology.

    PubMed

    Buschmann, Thomas; Ewald, Alexander; von Twickel, Arndt; Büschges, Ansgar

    2015-06-29

    Walking is the most common terrestrial form of locomotion in animals. Its great versatility and flexibility has led to many attempts at building walking machines with similar capabilities. The control of walking is an active research area both in neurobiology and robotics, with a large and growing body of work. This paper gives an overview of the current knowledge on the control of legged locomotion in animals and machines and attempts to give walking control researchers from biology and robotics an overview of the current knowledge in both fields. We try to summarize the knowledge on the neurobiological basis of walking control in animals, emphasizing common principles seen in different species. In a section on walking robots, we review common approaches to walking controller design with a slight emphasis on biped walking control. We show where parallels between robotic and neurobiological walking controllers exist and how robotics and biology may benefit from each other. Finally, we discuss where research in the two fields diverges and suggest ways to bridge these gaps.

  3. Integrating ecology, psychology and neurobiology within a food-hoarding paradigm

    PubMed Central

    Pravosudov, Vladimir V.; Smulders, Tom V.

    2010-01-01

    Many animals regularly hoard food for future use, which appears to be an important adaptation to a seasonally and/or unpredictably changing environment. This food-hoarding paradigm is an excellent example of a natural system that has broadly influenced both theoretical and empirical work in the field of biology. The food-hoarding paradigm has played a major role in the conceptual framework of numerous fields from ecology (e.g. plant–animal interactions) and evolution (e.g. the coevolution of caching, spatial memory and the hippocampus) to psychology (e.g. memory and cognition) and neurobiology (e.g. neurogenesis and the neurobiology of learning and memory). Many food-hoarding animals retrieve caches by using spatial memory. This memory-based behavioural system has the inherent advantage of being tractable for study in both the field and laboratory and has been shaped by natural selection, which produces variation with strong fitness consequences in a variety of taxa. Thus, food hoarding is an excellent model for a highly integrative approach to understanding numerous questions across a variety of disciplines. Recently, there has been a surge of interest in the complexity of animal cognition such as future planning and episodic-like-memory as well as in the relationship between memory, the environment and the brain. In addition, new breakthroughs in neurobiology have enhanced our ability to address the mechanisms underlying these behaviours. Consequently, the field is necessarily becoming more integrative by assessing behavioural questions in the context of natural ecological systems and by addressing mechanisms through neurobiology and psychology, but, importantly, within an evolutionary and ecological framework. In this issue, we aim to bring together a series of papers providing a modern synthesis of ecology, psychology, physiology and neurobiology and identifying new directions and developments in the use of food-hoarding animals as a model system. PMID

  4. Neurobiology of Dyslexia

    PubMed Central

    Norton, Elizabeth S.; Beach, Sara D.; Gabrieli, John D. E.

    2014-01-01

    Dyslexia is one of the most common learning disabilities, yet its brain basis and core causes are not yet fully understood. Neuroimaging methods, including structural and functional magnetic resonance imaging, diffusion tensor imaging, and electrophysiology, have significantly contributed to knowledge about the neurobiology of dyslexia. Recent studies have discovered brain differences prior to formal instruction that likely encourage or discourage learning to read effectively, distinguished between brain differences that likely reflect the etiology of dyslexia versus brain differences that are the consequences of variation in reading experience, and identified distinct neural networks associated with specific psychological factors that are associated with dyslexia. PMID:25290881

  5. Alcohol-related aggression-social and neurobiological factors.

    PubMed

    Beck, Anne; Heinz, Andreas

    2013-10-01

    Alcohol-related aggression and violence are a widespread cause of personal suffering with high socioeconomic costs. In 2011, nearly one in three violent acts in Germany was committed under the influence of alcohol (31.8%). The link between alcohol consumption and aggression is promoted by various interacting factors. In this review, based on a selective search for pertinent literature in PubMed, we analyze and summarize information from original articles, reviews, and book chapters about alcohol and aggression and discuss the neurobiological basis of aggressive behavior. Aggression is promoted both by the cognitive deficits arising in connection with acute or chronic alcohol use and by prior experience of violence in particular situations where alcohol was drunk. Only a minority of persons who drink alcohol become aggressive. On the other hand, alcohol abuse and dependence together constitute the second most commonly diagnosed cause of suicide (15-43%). Current research indicates that the individual tendency toward alcohol-induced aggression depends not just on neurobiological factors, but also on personal expectations of the effects of alcohol, on prior experience of violent conflicts, and on the environmental conditions of early childhood, especially social exclusion and discrimination. Gene-environment interactions affecting the serotonergic and other neurotransmitter systems play an important role. Potential (but not yet adequately validated) therapeutic approaches involve reinforcing cognitive processes or pharmacologically modulating serotonergic neurotransmission (and other target processes). Alcohol-related aggression has manifold social and neurobiological causes. Specific treatments must be tested in controlled trials.

  6. The Life Span Model of Suicide and Its Neurobiological Foundation

    PubMed Central

    Ludwig, Birgit; Roy, Bhaskar; Wang, Qingzhong; Birur, Badari; Dwivedi, Yogesh

    2017-01-01

    The very incomprehensibility of the suicidal act has been occupying the minds of researchers and health professionals for a long time. Several theories of suicide have been proposed since the beginning of the past century, and a myriad of neurobiological studies have been conducted over the past two decades in order to elucidate its pathophysiology. Both neurobiology and psychological theories tend to work in parallel lines that need behavioral and empirical data respectively, to confirm their hypotheses. In this review, we are proposing a “Life Span Model of Suicide” with an attempt to integrate the “Stress-Diathesis Model” and the “Interpersonal Model of Suicide” into a neurobiological narrative and support it by providing a thorough compilation of related genetic, epigenetic, and gene expression findings. This proposed model comprises three layers, forming the capability of suicide: genetic factors as the predisposing Diathesis on one side and Stress, characterized by epigenetic marks on the other side, and in between gene expression and gene function which are thought to be influenced by Diathesis and Stress components. The empirical evidence of this model is yet to be confirmed and further research, specifically epigenetic studies in particular, are needed to support the presence of a life-long, evolving capability of suicide and identify its neurobiological correlates. PMID:28261051

  7. [Neurobiología y psicoanálisis].

    PubMed

    Rosler, J Roberto

    2002-01-01

    There would be a conceptual bridge between Psychoanalysis and the Neurosciences that would allow the translation of psychoanalytic concepts into neural mechanisms and vice-versa. Different Freudian postulates, such as that different types of anxiety would emerge from various cerebral interactions, the motivational regulatory functions of the impulse, the conscious emotion as the perception of something basically unconscious, the mechanism of repression in the traumatic memory, the existence of a system associated with the unconscious affective processes and regulated by the principle of pleasure - displeasure, the emotional representation as a basis of the more primitive cerebral structures, and the Oedipo complex, among others, are finding their biological ratification in different laboratory studies. This conceptual bridge would not only be a "Psychoanalysis-Neurobiological mechanisms" translator, but would also, through the integrated conceptualization of the psychoanalytical neurobiological aspects of emotion, generate relevant therapeutic models.

  8. Neurobiological constraints on behavioral models of motivation.

    PubMed

    Nader, K; Bechara, A; van der Kooy, D

    1997-01-01

    The application of neurobiological tools to behavioral questions has produced a number of working models of the mechanisms mediating the rewarding and aversive properties of stimuli. The authors review and compare three models that differ in the nature and number of the processes identified. The dopamine hypothesis, a single system model, posits that the neurotransmitter dopamine plays a fundamental role in mediating the rewarding properties of all classes of stimuli. In contrast, both nondeprived/deprived and saliency attribution models claim that separate systems make independent contributions to reward. The former identifies the psychological boundary defined by the two systems as being between states of nondeprivation (e.g. food sated) and deprivation (e.g. hunger). The latter identifies a boundary between liking and wanting systems. Neurobiological dissociations provide tests of and explanatory power for behavioral theories of goal-directed behavior.

  9. 76 FR 79065 - Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ... DEPARTMENT OF LABOR Equal Employment Opportunity Commission 29 CFR Part 1602 Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA CFR Correction In Title 29 of the Code of Federal... title VII or section 107 of the ADA'' and add in their place the words ``section 709(c) of title VII...

  10. Serendipitous Discovery of Factor VII Deficiency and the Ensuing Dilemma.

    PubMed

    Umakanthan, Jayadev M; Dhakal, Prajwal; Gundabolu, Krishna; Koepsell, Scott A; Baljevic, Muhamed

    2018-03-01

    Congenital factor VII deficiency is a challenging disorder to manage, as it is associated with varied genotypes that do not clinically correlate with a bleeding phenotype. Individuals with severe factor VII deficiency (FVII: c <1%) might be asymptomatic, while patients with moderate deficiency (FVII: c level >5%) may experience severe hemorrhages. In modern medicine, due to extensive routine pre-operative laboratory testing, clinically asymptomatic patients without any bleeding history might be incidentally discovered, raising clinical dilemmas. Careful consideration of bleeding versus thrombosis risk has to be made in such cases, especially in the elderly. Clinical history of no prior bleeding complications may be a reassuring factor. Minimal required replacement dosing of recombinant activated factor VII can be given peri-operatively in such situations, with close monitoring.

  11. Altered lumbar spine structure, biochemistry and biomechanical properties in a canine model of mucopolysaccharidosis type VII

    PubMed Central

    Smith, Lachlan J; Martin, John T; Szczesny, Spencer E; Ponder, Katherine P; Haskins, Mark E; Elliott, Dawn M

    2010-01-01

    Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disorder characterized by a deficiency in β-glucuronidase activity, leading to systemic accumulation of poorly degraded glycosaminoglycans (GAG). Along with other morbidities, MPS VII is associated with paediatric spinal deformity. The objective of this study was to examine potential associations between abnormal lumbar spine matrix structure and composition in MPS VII, and spine segment and tissue-level mechanical properties, using a naturally occurring canine model with a similar clinical phenotype to the human form of the disorder. Segments from juvenile MPS VII and unaffected dogs were allocated to: radiography, gross morphology, histology, biochemistry, and mechanical testing. MPS VII spines had radiolucent lesions in the vertebral body epiphyses. Histologically, this corresponded to a GAG-rich cartilaginous region in place of bone, and elevated GAG staining was seen in the annulus fibrosus. Biochemically, MPS VII samples had elevated GAG in the outer annulus fibrosus and epiphyses, low calcium in the epiphyses, and high water content in all regions except the nucleus pulposus. MPS VII spine segments had higher range of motion and lower stiffness than controls. Endplate indentation stiffness and failure loads were significantly lower in MPS VII samples, while annulus fibrosus tensile mechanical properties were normal. Vertebral body lesions in MPS VII spines suggest a failure to convert cartilage to bone during development. Low stiffness in these regions likely contributes to mechanical weakness in motion segments and is a potential factor in the progression of spinal deformity. PMID:19918911

  12. Coagulation factor VII is regulated by androgen receptor in breast cancer.

    PubMed

    Naderi, Ali

    2015-02-01

    Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Context Processing and the Neurobiology of Post-Traumatic Stress Disorder

    PubMed Central

    Liberzon, Israel; Abelson, James L.

    2016-01-01

    Summary Progress in clinical and affective neuroscience is redefining psychiatric illness as symptomatic expression of cellular/molecular dysfunctions in specific brain circuits. Post-traumatic stress disorder (PTSD) has been an exemplar of this progress, with improved understanding of neurobiological systems subserving fear learning, salience detection, and emotion regulation explaining much of its phenomenology and neurobiology. However, many features remain unexplained and a parsimonious model that more fully accounts for symptoms and the core neurobiology remains elusive. Contextual processing is a key modulatory function of hippocampal-prefrontal-thalamic circuitry, allowing organisms to disambiguate cues and derive situation-specific meaning from the world. We propose that dysregulation within this context-processing circuit is at the core of PTSD pathophysiology, accounting for much of its phenomenology and most of its biological findings. Understanding core mechanisms like this, and their underlying neural circuits, will sharpen diagnostic precision and understanding of risk factors, enhancing our ability to develop preventive and “personalized” interventions. PMID:27710783

  14. Quantum and Multidimensional Explanations in a Neurobiological Context of Mind.

    PubMed

    Korf, Jakob

    2015-08-01

    This article examines the possible relevance of physical-mathematical multidimensional or quantum concepts aiming at understanding the (human) mind in a neurobiological context. Some typical features of the quantum and multidimensional concepts are briefly introduced, including entanglement, superposition, holonomic, and quantum field theories. Next, we consider neurobiological principles, such as the brain and its emerging (physical) mind, evolutionary and ontological origins, entropy, syntropy/neg-entropy, causation, and brain energy metabolism. In many biological processes, including biochemical conversions, protein folding, and sensory perception, the ubiquitous involvement of quantum mechanisms is well recognized. Quantum and multidimensional approaches might be expected to help describe and model both brain and mental processes, but an understanding of their direct involvement in mental activity, that is, without mediation by molecular processes, remains elusive. More work has to be done to bridge the gap between current neurobiological and physical-mathematical concepts with their associated quantum-mind theories. © The Author(s) 2014.

  15. Photosynthetic pigments of oceanic Chlorophyta belonging to prasinophytes clade VII.

    PubMed

    Lopes Dos Santos, Adriana; Gourvil, Priscillia; Rodríguez, Francisco; Garrido, José Luis; Vaulot, Daniel

    2016-02-01

    The ecological importance and diversity of pico/nanoplanktonic algae remains poorly studied in marine waters, in part because many are tiny and without distinctive morphological features. Amongst green algae, Mamiellophyceae such as Micromonas or Bathycoccus are dominant in coastal waters while prasinophytes clade VII, yet not formerly described, appear to be major players in open oceanic waters. The pigment composition of 14 strains representative of different subclades of clade VII was analyzed using a method that improves the separation of loroxanthin and neoxanthin. All the prasinophytes clade VII analyzed here showed a pigment composition similar to that previously reported for RCC287 corresponding to pigment group prasino-2A. However, we detected in addition astaxanthin for which it is the first report in prasinophytes. Among the strains analyzed, the pigment signature is qualitatively similar within subclades A and B. By contrast, RCC3402 from subclade C (Picocystis) lacks loroxanthin, astaxanthin, and antheraxanthin but contains alloxanthin, diatoxanthin, and monadoxanthin that are usually found in diatoms or cryptophytes. For subclades A and B, loroxanthin was lowest at highest light irradiance suggesting a light-harvesting role of this pigment in clade VII as in Tetraselmis. © 2015 Phycological Society of America.

  16. Title VII Evaluation, 1987-88.

    ERIC Educational Resources Information Center

    Baenen, Nancy R.; Yonan, Barbara

    Title VII federal funds have been used in the Austin (Texas) Independent School District (AISD) since 1985-86 to enhance the regular secondary bilingual and English-as-a-second-language programs for Hispanic limited English proficient (LEP) students. The four secondary campuses involved were those with the highest concentrations of Hispanic LEP…

  17. Onset of ice VII phase during ps laser pulse propagation through liquid water

    NASA Astrophysics Data System (ADS)

    Kumar, V. Rakesh; Kiran, P. Prem

    2017-01-01

    Water dominantly present in liquid state on earth gets transformed to crystalline polymorphs under different dynamic loading conditions. Out of different crystalline phases discovered till date, ice VII is observed to be stable over wide pressure (2-63 GPa) and temperature (>273 K) ranges. The formation of ice VII crystalline structure has been vastly reported during high pressure static compression using diamond anvil cell and propagation of high energy (>50 mJ/pulse) nanosecond laser pulse induced dynamic high pressures through liquid water. We present the onset of ice VII phase at low threshold of 2 mJ/pulse during 30 ps (532 nm, 10 Hz) laser pulse induced shock propagating through liquid water. Role of input pulse energy on the evolution of Stoke's and anti-Stoke's Raman shift of the dominant A1g mode of ice VII, filamentation, free-electrons, plasma shielding is presented. The H-bond network rearrangement, electron ion energy transfer time coinciding with the excitation pulse duration supported by the filamentation and plasma shielding of the ps laser pulses reduced the threshold of ice VII structure formation. Filamentation and the plasma shielding have shown the localized creation and sustenance of ice VII structure in liquid water over 3 mm length and 50 μm area of cross-section.

  18. Neurobiology of Wisdom?: A Literature Overview

    PubMed Central

    Meeks, Thomas W.; Jeste, Dilip V.

    2013-01-01

    Context Wisdom is a unique psychological trait noted since antiquity, long discussed in humanities disciplines, recently operationalized by psychology and sociology researchers, but largely unexamined in psychiatry or biology. Objective We discuss recent neurobiological studies related to subcomponents of wisdom identified from several published definitions/descriptions of wisdom by clinical investigators in the field – i.e., prosocial attitudes/behaviors, social decision-making/pragmatic knowledge of life, emotional homeostasis, reflection/self-understanding, value relativism/tolerance, and acknowledgement of and dealing effectively with uncertainty. Design Literature overview focusing primarily on neuroimaging/brain localization and secondarily on neurotransmitters, including their genetic determinants. Results Functional neuroimaging permits exploration of neural correlates of complex psychological attributes such as those proposed to comprise wisdom. The prefrontal cortex figures prominently in several wisdom subcomponents (e.g., emotional regulation, decision-making, value relativism), primarily via top-down regulation of limbic and striatal regions. The lateral prefrontal cortex facilitates calculated, reason-based decision-making, whereas the medial prefrontal cortex is implicated in emotional valence and prosocial attitudes/behaviors. Reward neurocircuitry (ventral striatum, nucleus accumbens) also appears important for promoting prosocial attitudes/behaviors. Monoaminergic activity (especially dopaminergic and serotonergic), influenced by several genetic polymorphisms, is critical to certain subcomponents of wisdom such as emotional regulation (including impulse control), decision-making, and prosocial behaviors. Conclusions We have proposed a speculative model of the neurobiology of wisdom involving fronto-striatal and fronto-limbic circuits and monoaminergic pathways. Wisdom may involve optimal balance between functions of phylogenetically more

  19. The Neurobiology of Trust and Schooling

    ERIC Educational Resources Information Center

    Sankey, Derek

    2018-01-01

    Are there neurobiological reasons why we are willing to trust other people and why "trust" and moral values such as "care" play a quite pivotal role in our social lives and the judgements we make, including our social interactions and judgements made in the context of schooling? In pursuing this question, this paper largely…

  20. Adenovirus Core Protein VII Downregulates the DNA Damage Response on the Host Genome

    PubMed Central

    Avgousti, Daphne C.; Della Fera, Ashley N.; Otter, Clayton J.; Herrmann, Christin; Pancholi, Neha J.

    2017-01-01

    ABSTRACT Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier to successful infection. The adenovirus genome is packaged with protein VII, a virally encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by the cellular DNA damage machinery. We showed that protein VII localizes to host chromatin during infection, leading us to hypothesize that protein VII may affect DNA damage responses on the cellular genome. Here we show that protein VII at cellular chromatin results in a significant decrease in accumulation of phosphorylated H2AX (γH2AX) following irradiation, indicating that protein VII inhibits DDR signaling. The oncoprotein SET was recently suggested to modulate the DDR by affecting access of repair proteins to chromatin. Since protein VII binds SET, we investigated a role for SET in DDR inhibition by protein VII. We show that knockdown of SET partially rescues the protein VII-induced decrease in γH2AX accumulation on the host genome, suggesting that SET is required for inhibition. Finally, we show that knockdown of SET also allows ATM to localize to incoming viral genomes bound by protein VII during infection with a mutant lacking early region E4. Together, our data suggest that the protein VII-SET interaction contributes to DDR evasion by adenovirus. Our results provide an additional example of a strategy used by adenovirus to abrogate the host DDR and show how viruses can modify cellular processes through manipulation of host chromatin. IMPORTANCE The DNA damage response (DDR) is a cellular network that is crucial for maintaining genome integrity. DNA viruses replicating in the nucleus challenge the resident genome and must overcome cellular responses, including the DDR. Adenoviruses are prevalent human pathogens that

  1. Let's Put "Debate" into "Presidential Debates."

    ERIC Educational Resources Information Center

    Benoit, William L.

    Presidential debates come in all shapes and sizes. The presence and length of opening statements and closing remarks, the opportunity and length of rebuttal, the nature of the questioner, and other factors have created a bewildering variety of formats. However, most scholars agree that these confrontations are not "really" debates but merely…

  2. The neurobiological link between compassion and love

    PubMed Central

    Esch, Tobias; Stefano, George B.

    2011-01-01

    Summary Love and compassion exert pleasant feelings and rewarding effects. Besides their emotional role and capacity to govern behavior, appetitive motivation, and a general ‘positive state’, even ‘spiritual’ at times, the behaviors shown in love and compassion clearly rely on neurobiological mechanisms and underlying molecular principles. These processes and pathways involve the brain’s limbic motivation and reward circuits, that is, a finely tuned and profound autoregulation. This capacity to self-regulate emotions, approach behaviors and even pair bonding, as well as social contact in general, i.e., love, attachment and compassion, can be highly effective in stress reduction, survival and overall health. Yet, molecular biology is the basis of interpersonal neurobiology, however, there is no answer to the question of what comes first or is more important: It is a cybernetic capacity and complex circuit of autoregulation that is clearly ‘amazing’. PMID:21358615

  3. Neurobiological Basis of Insight in Schizophrenia: A Systematic Review.

    PubMed

    Xavier, Rose Mary; Vorderstrasse, Allison

    2016-01-01

    Insight in schizophrenia is defined as awareness into illness, symptoms, and need for treatment and has long been associated with cognition, other psychopathological symptoms, and several adverse clinical and functional outcomes. However, the biological basis of insight is not clearly understood. The aim of this systematic review was to critically evaluate and summarize advances in the study of the biological basis of insight in schizophrenia and to identify gaps in this knowledge. A literature search of PubMed, CINAHL, PsycINFO, and EMBASE databases was conducted using search terms to identify articles relevant to the biology of insight in schizophrenia published in the last 6 years. Articles that focused on etiology of insight in schizophrenia and those that examined the neurobiology of insight in schizophrenia or psychoses were chosen for analysis. Articles on insight in conditions other than schizophrenia or psychoses and which did not investigate the neurobiological underpinnings of insight were excluded from the review. Twenty-six articles met the inclusion criteria for this review. Of the 26 articles, 3 focused on cellular abnormalities and 23 were neuroimaging studies. Preliminary data identify the prefrontal cortex, cingulate cortex, and regions of the temporal and parietal lobe (precuneus, inferior parietal lobule) and hippocampus as the neural correlates of insight. A growing body of literature attests to the neurobiological basis of insight in schizophrenia. Current evidence supports the neurobiological basis of insight in schizophrenia and identifies specific neural correlates for insight types and its dimensions. Further studies that examine the precise biological mechanisms of insight are needed to apply this knowledge to effective clinical intervention development.

  4. Is there a shared neurobiology between aggression and Internet addiction disorder?

    PubMed Central

    Hahn, Changtae; Kim, Dai-Jin

    2014-01-01

    Purpose: Evidences indicate that Internet addiction disorder (IAD) has a higher risk of developing aggression and violent behavior. A few correlation studies between IAD and aggression have implicated a common biological mechanism. However, neurobiological approaches to IAD and aggression have not yet been studied. Methods: A literature search for studies for Internet addiction disorder or aggression was performed in the PubMed database and we selected articles about neurobiology of IAD or aggression. Results: This review includes (a) common neural substrates such as the prefrontal cortex and the limbic system between aggression and IAD; (b) common neuromodulators such as dopamine, norepinephrine, serotonin, opiate and nicotine between aggression and IAD. Conclusions: Through reviewing the relevant literature, we suggested the possibility of common neurobiology between the two psychiatric phenomena and direction of research on aggression in IAD. PMID:25215210

  5. Neurobiological correlates of illness progression in the recurrent affective disorders.

    PubMed

    Post, Robert M; Fleming, Jaclyn; Kapczinski, Flavio

    2012-05-01

    Some clinical aspects of affective illness progression, such as episode-, stress-, and substance-induced sensitization, have been well documented in the literature, but others have received less attention. These include cognitive deficits, treatment-refractoriness, and neurobiological correlates of illness progression, which are the primary focus of this paper. We review the evidence that cognitive dysfunction, treatment resistance, medical comorbidities, and neurobiological abnormalities increase as a function of the number of prior episodes or duration of illness in the recurrent unipolar and bipolar disorders. Substantial evidence supports the view that cognitive dysfunction and vulnerability to a diagnosis of dementia in old age increases as a function of number of prior mood episodes as does non-response to many therapeutic interventions as well as naturalistic treatment. Neurobiological abnormalities that correlate with the number of mood episodes or duration of illness include: anatomical, functional, and biochemical deficits in the prefrontal cortex and hippocampus, as well as amygdala hyperactivity and cortisol hyper-secretion. Some neurotrophic factors and inflammatory markers may also change with greater illness burden. Causality cannot be inferred from these correlative relationships. Nonetheless, given the potentially grave consequences of episode recurrence and progression for morbidity and treatment non-responsiveness, it is clinically wise to assume episodes are causing some of the progressive cognitive and neurobiological abnormalities. As such, earlier and more sustained long-term prophylaxis to attempt to reduce these adverse outcomes is indicated. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. 40 CFR Appendix Vii to Part 86 - Standard Bench Cycle (SBC)

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... VII Appendix VII to Part 86—Standard Bench Cycle (SBC) 1. The standard bench aging durability procedures [Ref. § 86.1823-08(d)] consist of aging a catalyst-oxygen-sensor system on an aging bench which follows the standard bench cycle (SBC) described in this appendix. 2. The SBC requires use of an aging...

  7. 40 CFR Appendix Vii to Part 86 - Standard Bench Cycle (SBC)

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... VII Appendix VII to Part 86—Standard Bench Cycle (SBC) 1. The standard bench aging durability procedures [Ref. § 86.1823-08(d)] consist of aging a catalyst-oxygen-sensor system on an aging bench which follows the standard bench cycle (SBC) described in this appendix. 2. The SBC requires use of an aging...

  8. Neurobiological Formulations: Integrating Clinical and Biological Psychiatry

    ERIC Educational Resources Information Center

    Posner, Jonathan; Stewart, Jonathan; Rieder, Ronald

    2007-01-01

    Objective: The authors describe a pilot program allowing psychiatric residents to participate in neurobiological evaluations of patients with Axis I disorders. The program aimed to familiarize residents with available tools for assessing cognitive and neuroanatomical abnormalities in psychiatric patients and to foster greater interest among…

  9. Factor VII deficiency: a novel missense variant and genotype-phenotype correlation in patients from Southern Italy.

    PubMed

    Tiscia, Giovanni; Favuzzi, Giovanni; Chinni, Elena; Colaizzo, Donatella; Fischetti, Lucia; Intrieri, Mariano; Margaglione, Maurizio; Grandone, Elvira

    2017-01-01

    This study aimed at attempting to correlate genotype and phenotype in factor VII deficiency. Here, we present molecular and clinical findings of 10 patients with factor VII deficiency. From 2013 to 2016, 10 subjects were referred to our center because of a prolonged prothrombin time identified during routine or presurgery examinations or after a laboratory assessment of a bleeding episode. Mutation characterization was performed using the bioinformatics applications PROMO, SIFT, and Polyphen-2. Structural changes in the factor VII protein were analyzed using the SPDB viewer tool. Of the 10 variants we identified, 1 was responsible for a novel missense change (c.1199G>C, p.Cys400Ser); in 2 cases we identified the c.-54G>A and c.509G>A (p.Arg170His) polymorphic variants in the 5'-upstream region of the factor VII gene and exon 6, respectively. To our knowledge, neither of these polymorphic variants has been described previously in factor VII-deficient patients. In silico predictions showed differences in binding sites for transcription factors caused by the c.-54G>A variant and a probable damaging effect of the p.Cys400Ser missense change on factor VII active conformation, leading to breaking of the Cys400-Cys428 disulfide bridge. Our findings further suggest that, independently of factor VII levels and of variants potentially affecting factor VII levels, environmental factors, e.g., trauma, could heavily influence the clinical phenotype of factor VII-deficient patients.

  10. Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

    PubMed

    Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

    2009-12-15

    Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

  11. How Electroconvulsive Therapy Works?: Understanding the Neurobiological Mechanisms

    PubMed Central

    Singh, Amit; Kar, Sujita Kumar

    2017-01-01

    Electroconvulsive therapy (ECT) is a time tested treatment modality for the management of various psychiatric disorders. There have been a lot of modifications in the techniques of delivering ECT over decades. Despite lots of criticisms encountered, ECT has still been used commonly in clinical practice due to its safety and efficacy. Research evidences found multiple neuro-biological mechanisms for the therapeutic effect of ECT. ECT brings about various neuro-physiological as well as neuro-chemical changes in the macro- and micro-environment of the brain. Diverse changes involving expression of genes, functional connectivity, neurochemicals, permeability of blood-brain-barrier, alteration in immune system has been suggested to be responsible for the therapeutic effects of ECT. This article reviews different neurobiological mechanisms responsible for the therapeutic efficacy of ECT. PMID:28783929

  12. Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs

    PubMed Central

    Peck, Sun H.; O'Donnell, Philip J.M.; Kang, Jennifer L.; Malhotra, Neil R.; Dodge, George R.; Pacifici, Maurizio; Shore, Eileen M.; Haskins, Mark E.; Smith, Lachlan J.

    2015-01-01

    Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein

  13. Neurobiological correlates of social functioning in autism.

    PubMed

    Neuhaus, Emily; Beauchaine, Theodore P; Bernier, Raphael

    2010-08-01

    Although autism is defined by deficits in three areas of functioning (social, communicative, and behavioral), impairments in social interest and restricted behavioral repertoires are central to the disorder. As a result, a detailed understanding of the neurobiological systems subserving social behavior may have implications for prevention, early identification, and intervention for affected families. In this paper, we review a number of potential neurobiological mechanisms--across several levels of analysis--that subserve normative social functioning. These include neural networks, neurotransmitters, and hormone systems. After describing the typical functioning of each system, we review available empirical findings specific to autism. Among the most promising potential mechanisms of social behavioral deficits in autism are those involving neural networks including the amygdala, the mesocorticolimbic dopamine system, and the oxytocin system. Particularly compelling are explanatory models that integrate mechanisms across biological systems, such as those linking dopamine and oxytocin with brain regions critical to reward processing. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. 29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The employee coverage of the prohibitions against discrimination based on sex contained in title VII is...

  15. Neurobiological correlates of internet gaming disorder: Similarities to pathological gambling.

    PubMed

    Fauth-Bühler, M; Mann, K

    2017-01-01

    The number of massively multiplayer online games (MMOs) is on the rise worldwide along with the fascination that they inspire. Problems occur when the use of MMOs becomes excessive at the expense of other life domains. Although not yet formally included as disorder in common diagnostic systems, internet gaming disorder (IGD) is considered a "condition for further study" in section III of the DSM-5. The current review aims to provide an overview of cognitive and neurobiological data currently available on IGD, with a particular focus on impulsivity, compulsivity, and sensitivity to reward and punishment. Additionally, we also compare these findings on IGD with data from studies on pathological gambling (PG)-so far the only condition officially classified as a behavioral addiction in the DSM-5. Multiple similarities have been observed in the neurobiology of IGD and PG, as measured by alterations in brain function and behavior. Both patients with IGD and those with PG exhibited decreased loss sensitivity; enhanced reactivity to gaming and gambling cues, respectively; enhanced impulsive choice behavior; aberrant reward-based learning; and no changes in cognitive flexibility. In conclusion, the evidence base on the neurobiology of gaming and gambling disorders is beginning to illuminate the similarities between the two. However, as only a few studies have addressed the neurobiological basis of IGD, and some of these studies suffer from significant limitations, more research is required before IGD's inclusion as a second behavioral addiction in the next versions of the ICD and DSM can be justified. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. New isochromophilones VII and VIII produced by Penicillium sp. FO-4164.

    PubMed

    Yang, D J; Tomoda, H; Tabata, N; Masuma, R; Omura, S

    1996-03-01

    New isochromophilones VII and VIII were isolated from the culture broth of Penicillium sp. FO-4164. The structures were elucidated as 6H-2-benzopyran-6,8(7H)-dione, 5-chloro-3-(3',5'-dimethyl-1',3'-heptadienyl)-1,7,8a-trihydro-7, 8a-dihydroxy-7-methyl-7-acetate for isochromophilone VII and 6H-2-benzopyran-6-one,5-chloro-3-(3',5'-dimethyl-1', 3'-heptadienyl)-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-8-acetate for isochromophilone VIII. Isochromophilones VII and VIII inhibited diacylglycerol acyltransferase activity with IC50 values of 20.0 and 127 microM and acyl-CoA: cholesterol acyltransferase activity with IC50 values of 24.5 and 47.0 microM, respectively.

  17. Insomnia: psychological and neurobiological aspects and non-pharmacological treatments.

    PubMed

    Molen, Yara Fleury; Carvalho, Luciane Bizari Coin; Prado, Lucila Bizari Fernandes do; Prado, Gilmar Fernandes do

    2014-01-01

    Insomnia involves difficulty in falling asleep, maintaining sleep or having refreshing sleep. This review gathers the existing informations seeking to explain insomnia, including those that focus on psychological aspects and those considered neurobiological. Insomnia has been defined in psychological (cognitive components, such as worries and rumination, and behavioral aspects, such as classic conditioning) and physiological terms (increased metabolic rate, with increased muscle tone, heart rate and temperature). From the neurobiological point of view, there are two perspectives: one which proposes that insomnia occurs in association with a failure to inhibit wakefulness and another that considers hyperarousal as having an important role in the physiology of sleep. The non-pharmacological interventions developed to face different aspects of insomnia are presented.

  18. Neurobiologic basis of craving for carbohydrates.

    PubMed

    Ventura, Tamara; Santander, Jaime; Torres, Rafael; Contreras, Ana María

    2014-03-01

    There is a relationship between emotional disorders, obesity, and craving for carbohydrates. This relationship complicates the success of treatments aimed at combatting obesity, which is considered to be the epidemic of the twenty-first century. We conducted a review of the neurobiologic basis for carbohydrate craving, with the hope that this understanding will enable the design of more efficient therapeutic strategies. We conducted a non-systematic literature search in PubMed using MeSH. Research on the basis of carbohydrate craving is varied, but may be grouped into five main areas: the serotonergic system, palatability and hedonic response, the motivational system, stress response systems, and gene-environment interaction. The models that integrate motivational systems with palatability and hedonic response studies are the ones that we believe can best explain both craving for carbohydrates and related addictive phenomena. Research has contributed to a greater understanding of the neurobiologic basis of carbohydrate craving. The latter, in turn, contributes to an understanding of the implications, challenges, and possible therapies that might be put in place to cope with this phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Onset of ice VII phase during ps laser pulse propagation through liquid water

    NASA Astrophysics Data System (ADS)

    Paturi, Prem Kiran; Vaddapally, Rakesh Kumar; Acrhem Team

    2015-06-01

    Water dominantly present in liquid state on earth gets transformed to crystalline polymorphs under different dynamic loading conditions. Out of 15 different crystalline phases discovered till date, ice VII is observed to be stable over wide pressure (2-63 GPa) and temperature (>273 K) ranges. We present the onset of ice VII phase at low threshold of 2 mJ/pulse during 30 ps (532 nm, 10 Hz) laser pulse induced shock propagating through liquid water. Role of input pulse energy on the evolution of Stoke's and anti-Stoke's Raman shift of the dominant A1g mode of ice VII, filamentation, free-electrons, plasma shielding is presented. The H-bond network rearrangement, electron ion energy transfer time coinciding with the excitation pulse duration supported by the filamentation and plasma shielding of the ps laser pulses reduced the threshold of ice VII structure formation. Filamentation and the plasma shielding have shown the localized creation and sustenance of ice VII structure in liquid water over 3 mm length and 50 μm area of cross-section. The work is supported by Defence Research and Developement Organization, India through Grants-in-Aid Program.

  20. The preparation and structure of salty ice VII under pressure

    NASA Astrophysics Data System (ADS)

    Klotz, Stefan; Bove, Livia E.; Strässle, Thierry; Hansen, Thomas C.; Saitta, Antonino M.

    2009-05-01

    It is widely accepted that ice, no matter what phase, is unable to incorporate large amounts of salt into its structure. This conclusion is based on the observation that on freezing of salt water, ice expels the salt almost entirely as brine. Here, we show that this behaviour is not an intrinsic physico-chemical property of ice phases. We demonstrate by neutron diffraction that substantial amounts of dissolved LiCl can be built homogeneously into the ice VII structure if it is produced by recrystallization of its glassy (amorphous) state under pressure. Such `alloyed' ice VII has significantly different structural properties compared with pure ice VII, such as an 8% larger unit cell volume, 5 times larger displacement factors, an absence of a transition to an ordered ice VIII structure and plasticity. Our study suggests that there could be a whole new class of `salty' high-pressure ice forms.

  1. The preparation and structure of salty ice VII under pressure.

    PubMed

    Klotz, Stefan; Bove, Livia E; Strässle, Thierry; Hansen, Thomas C; Saitta, Antonino M

    2009-05-01

    It is widely accepted that ice, no matter what phase, is unable to incorporate large amounts of salt into its structure. This conclusion is based on the observation that on freezing of salt water, ice expels the salt almost entirely as brine. Here, we show that this behaviour is not an intrinsic physico-chemical property of ice phases. We demonstrate by neutron diffraction that substantial amounts of dissolved LiCl can be built homogeneously into the ice VII structure if it is produced by recrystallization of its glassy (amorphous) state under pressure. Such 'alloyed' ice VII has significantly different structural properties compared with pure ice VII, such as an 8% larger unit cell volume, 5 times larger displacement factors, an absence of a transition to an ordered ice VIII structure and plasticity. Our study suggests that there could be a whole new class of 'salty' high-pressure ice forms.

  2. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{supmore » mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.« less

  3. A debate about the merits of debate in nurse education.

    PubMed

    Hartin, Peter; Birks, Melanie; Bodak, Marie; Woods, Cindy; Hitchins, Marnie

    2017-09-01

    In this 'Issues for Debate' paper, the issue is debate. Today's nurses must be able to advocate, lead, and grow 'big ideas', as well as knowing their way around a patient's body and mind. This paper reports, partly, on a research study into the use of debate to develop clinical reasoning and thinking skills in nursing students. The study was conducted with first and third-year nursing students enrolled at an Australian regional university. Students were asked to comment on the effectiveness of debate as an educational strategy. We combine the results of this research study with literature and discussion into the educational uses of debate to put the argument that using debate in nursing education can be an effective way to foster the type of creative, intelligent, thoughtful and forward-thinking nurses needed in the modern healthcare system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Effects of Recombinant Activated Factor VII in Traumatic Nonsurgical Intracranial Hemorrhage

    DTIC Science & Technology

    2006-09-01

    with inhibitors to factors VIII and IX, and it is ap- proved in Europe for the treatment of patients with acquired hemophilia, congenital FVII deficiency...GARY P. WRATTEN SURGICAL SYMPOSIUM Effects of Recombinant Activated Factor VII in Traumatic Nonsurgical Intracranial Hemorrhage Christopher E. White...OBJECTIVE: To determine whether treatment with recombi- nant activated factor VII (rFVIIa) will prevent progression of bleeding in nonsurgical

  5. Gene disruption reveals a dispensable role for plasmepsin VII in the Plasmodium berghei life cycle.

    PubMed

    Mastan, Babu S; Kumari, Anchala; Gupta, Dinesh; Mishra, Satish; Kumar, Kota Arun

    2014-06-01

    Plasmepsins (PM), aspartic proteases of Plasmodium, comprises a family of ten proteins that perform critical functions in Plasmodium life cycle. Except VII and VIII, functions of the remaining plasmepsin members have been well characterized. Here, we have generated a mutant parasite lacking PM VII in Plasmodium berghei using reverse genetics approach. Systematic comparison of growth kinetics and infection in both mosquito and vertebrate host revealed that PM VII depleted mutants exhibited no defects in development and progressed normally throughout the parasite life cycle. These studies suggest a dispensable role for PM VII in Plasmodium berghei life cycle. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Title VII funding and physician practice in rural or low-income areas.

    PubMed

    Krist, Alex H; Johnson, Robert E; Callahan, David; Woolf, Steven H; Marsland, David

    2005-01-01

    Whether Title VII funding enhances physician supply in underserved areas has not clearly been established. To determine the relation between Title VII funding in medical school, residency, or both, and the number of family physicians practicing in rural or low-income communities. A retrospective cross sectional analysis was carried out using the 2000 American Academy of Family Physicians physician database, Title VII funding records, and 1990 U.S. Census data. Included were 9,107 family physicians practicing in 9 nationally representative states in the year 2000. Physicians exposed to Title VII funding through medical school and residency were more likely to have their current practice in low-income communities (11.9% vs 9.9%, P< or =.02) and rural areas (24.5% vs 21.8%, P< or =.02). Physicians were more likely to practice in rural communities if they attended medical schools (24.2% vs 21.4%; P =.009) and residencies (24.0% vs 20.3%; P =.011) after the school or program had at least 5 years of Title VII funding vs before. Similar increases were not observed for practice in low-income communities. In a multivariate analysis, exposure to funding and attending an institution with more years of funding independently increased the odds of practicing in rural or low-income communities. Title VII funding is associated with an increase in the family physician workforce in rural and low-income communities. This effect is temporally related to initiation of funding and independently associated with effect in a multivariate analysis, suggesting a potential causal relationship. Whereas the absolute 2% increase in family physicians in these underserved communities may seem modest, it can represent a substantial increase in access to health care for community members.

  7. Managing Information Technology: Facing the Issues. Track VII: Applications and Technology Issues.

    ERIC Educational Resources Information Center

    CAUSE, Boulder, CO.

    Eight papers making up Track VII of the 1989 conference of the Professional Association for the Management of Information Technology in Higher Education (known as CAUSE, an acronym of the association's former name) are presented in this document. The focus of Track VII is on applications and technology issues, and the papers include: "The…

  8. Debating Real-World Issues.

    ERIC Educational Resources Information Center

    Koenig, Maureen

    2001-01-01

    Presents three different scientific issues to students and uses debate as a way of gaining information. Involves information collection on the topic, team preparation, and debate between teams. Includes debate format and presentation guidelines, suggestions for debate questions, information on areas to explore when preparing to debate the question…

  9. The neurobiology of psychopathy.

    PubMed

    Glenn, Andrea L; Raine, Adrian

    2008-09-01

    Numerous studies have tackled the complex challenge of understanding the neural substrates of psychopathy, revealing that brain abnormalities exist on several levels and in several structures. As we discover more about complex neural networks, it becomes increasingly difficult to clarify how these systems interact with each other to produce the distinct pattern of behavioral and personality characteristics observed in psychopathy. The authors review the recent research on the neurobiology of psychopathy, beginning with molecular neuroscience work and progressing to the level of brain structures and their connectivity. Potential factors that may affect the development of brain impairments, as well as how some systems may be targeted for potential treatment, are discussed.

  10. Musical hallucinosis: case reports and possible neurobiological models.

    PubMed

    Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

    2008-04-01

    The perception of music without a stimulus, or musical hallucination, is reported in both organic and psychiatric disorders. It is most frequently described in the elderly with associated hearing loss and accompanied by some degree of insight. In this setting it is often referred to as 'musical hallucinosis'. The aim of the authors was to present examples of this syndrome and review the current understanding of its neurobiological basis. We describe three cases of persons experiencing musical hallucinosis in the context of hearing deficits with varying degrees of associated central nervous system abnormalities. Putative neurobiological mechanisms, in particular those involving de-afferentation of a complex auditory recognition system by complete or partial deafness, are discussed in the light of current information from the literature. Musical hallucinosis can be experienced in those patients with hearing impairment and is phenomenologically distinct for hallucinations described in psychiatric disorders.

  11. Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER).

    PubMed

    Napolitano, Mariasanta; Giansily-Blaizot, Muriel; Dolce, Alberto; Schved, Jean F; Auerswald, Guenter; Ingerslev, Jørgen; Bjerre, Jens; Altisent, Carmen; Charoenkwan, Pimlak; Michaels, Lisa; Chuansumrit, Ampaiwan; Di Minno, Giovanni; Caliskan, Umran; Mariani, Guglielmo

    2013-04-01

    Because of the very short half-life of factor VII, prophylaxis in factor VII deficiency is considered a difficult endeavor. The clinical efficacy and safety of prophylactic regimens, and indications for their use, were evaluated in factor VII-deficient patients in the Seven Treatment Evaluation Registry. Prophylaxis data (38 courses) were analyzed from 34 patients with severe factor VII deficiency (<1-45 years of age, 21 female). Severest phenotypes (central nervous system, gastrointestinal, joint bleeding episodes) were highly prevalent. Twenty-one patients received recombinant activated factor VII (24 courses), four received plasma-derived factor VII, and ten received fresh frozen plasma. Prophylactic schedules clustered into "frequent" courses (three times weekly, n=23) and "infrequent" courses (≤ 2 times weekly, n=15). Excluding courses for menorrhagia, "frequent" and "infrequent" courses produced 18/23 (78%) and 5/12 (41%) "excellent" outcomes, respectively; relative risk, 1.88; 95% confidence interval, 0.93-3.79; P=0.079. Long term prophylaxis lasted from 1 to >10 years. No thrombosis or new inhibitors occurred. In conclusion, a subset of patients with factor VII deficiency needed prophylaxis because of severe bleeding. Recombinant activated factor VII schedules based on "frequent" administrations (three times weekly) and a 90 μg/kg total weekly dose were effective. These data provide a rationale for long-term, safe prophylaxis in factor VII deficiency.

  12. A review of the neurobiological basis of dyslexia in the adult population.

    PubMed

    Soriano-Ferrer, M; Piedra Martínez, E

    Adult dyslexia affects about 4% of the population. However, studies on the neurobiological basis of dyslexia in adulthood are scarce compared to paediatric studies. This review investigates the neurobiological basis of dyslexia in adulthood. Using PsycINFO, a database of psychology abstracts, we identified 11 studies on genetics, 9 neurostructural studies, 13 neurofunctional studies and 24 neurophysiological studies. Results from the review show that dyslexia is highly heritable and displays polygenic transmission. Likewise, adult neuroimaging studies found structural, functional, and physiological changes in the parieto-occipital and occipito-temporal regions, and in the inferior frontal gyrus, in adults with dyslexia. According to different studies, aetiology in cases of adult dyslexia is complex. We stress the need for neurobiological studies of dyslexia in languages with transparent spelling systems. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

    PubMed

    Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

    2017-06-01

    During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation

  14. Adolescent Neurobiological Susceptibility to Social Context

    PubMed Central

    Schriber, Roberta A.; Guyer, Amanda E.

    2016-01-01

    Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment they encounter (e.g., high vs. low parental warmth). Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped in part by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. As such, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes. PMID:26773514

  15. Body Dysmorphic Disorder: Neurobiological Features and an Updated Model

    PubMed Central

    Li, Wei; Arienzo, Donatello; Feusner, Jamie D.

    2013-01-01

    Body Dysmorphic Disorder (BDD) affects approximately 2% of the population and involves misperceived defects of appearance along with obsessive preoccupation and compulsive behaviors. There is evidence of neurobiological abnormalities associated with symptoms in BDD, although research to date is still limited. This review covers the latest neuropsychological, genetic, neurochemical, psychophysical, and neuroimaging studies and synthesizes these findings into an updated (yet still preliminary) neurobiological model of the pathophysiology of BDD. We propose a model in which visual perceptual abnormalities, along with frontostriatal and limbic system dysfunction, may combine to contribute to the symptoms of impaired insight and obsessive thoughts and compulsive behaviors expressed in BDD. Further research is necessary to gain a greater understanding of the etiological formation of BDD symptoms and their evolution over time. PMID:25419211

  16. Major depressive disorder: new clinical, neurobiological, and treatment perspectives

    PubMed Central

    Kupfer, David J; Frank, Ellen; Phillips, Mary L

    2012-01-01

    In this Seminar we discuss developments from the past 5 years in the diagnosis, neurobiology, and treatment of major depressive disorder. For diagnosis, psychiatric and medical comorbidity have been emphasised as important factors in improving the appropriate assessment and management of depression. Advances in neurobiology have also increased, and we aim to indicate genetic, molecular, and neuroimaging studies that are relevant for assessment and treatment selection of this disorder. Further studies of depression-specific psychotherapies, the continued application of antidepressants, the development of new treatment compounds, and the status of new somatic treatments are also discussed. We address two treatment-related issues: suicide risk with selective serotonin reuptake inhibitors, and the safety of antidepressants in pregnancy. Although clear advances have been made, no fully satisfactory treatments for major depression are available. PMID:22189047

  17. The Neurobiology of Moral Behavior: Review and Neuropsychiatric Implications

    PubMed Central

    Mendez, Mario F.

    2011-01-01

    Morality may be innate to the human brain. This review examines the neurobiological evidence from research involving functional magnetic resonance imaging of normal subjects, developmental sociopathy, acquired sociopathy from brain lesions, and frontotemporal dementia. These studies indicate a “neuromoral” network for responding to moral dilemmas centered in the ventromedial prefrontal cortex and its connections, particularly on the right. The neurobiological evidence indicates the existence of automatic “prosocial” mechanisms for identification with others that are part of the moral brain. Patients with disorders involving this moral network have attenuated emotional reactions to the possibility of harming others and may perform sociopathic acts. The existence of this neuromoral system has major clinical implications for the management of patients with dysmoral behavior from brain disorders and for forensic neuropsychiatry. PMID:20173686

  18. 76 FR 52656 - Lock+Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On August 4, 2011, Lock+Hydro Friends Fund VII, filed an... Friends Fund VII, 5090 Richmond Avenue 390, Houston, TX 77056; phone (877) 556- 6566 x709. FERC Contact...

  19. Attachment, Neurobiology, and Mentalizing along the Psychosis Continuum.

    PubMed

    Debbané, Martin; Salaminios, George; Luyten, Patrick; Badoud, Deborah; Armando, Marco; Solida Tozzi, Alessandra; Fonagy, Peter; Brent, Benjamin K

    2016-01-01

    In this review article, we outline the evidence linking attachment adversity to psychosis, from the premorbid stages of the disorder to its clinical forms. To better understand the neurobiological mechanisms through which insecure attachment may contribute to psychosis, we identify at least five neurobiological pathways linking attachment to risk for developing psychosis. Besides its well documented influence on the hypothalamic-pituary-adrenal (HPA) axis, insecure attachment may also contribute to neurodevelopmental risk through the dopaminergic and oxytonergic systems, as well as bear influence on neuroinflammation and oxidative stress responses. We further consider the neuroscientific and behavioral studies that underpin mentalization as a suite of processes potentially moderating the risk to transition to psychotic disorders. In particular, mentalization may help the individual compensate for endophenotypical impairments in the integration of sensory and metacognitive information. We propose a model where embodied mentalization would lie at the core of a protective, resilience response mitigating the adverse and potentially pathological influence of the neurodevelopmental cascade of risk for psychosis.

  20. Attachment, Neurobiology, and Mentalizing along the Psychosis Continuum

    PubMed Central

    Debbané, Martin; Salaminios, George; Luyten, Patrick; Badoud, Deborah; Armando, Marco; Solida Tozzi, Alessandra; Fonagy, Peter; Brent, Benjamin K.

    2016-01-01

    In this review article, we outline the evidence linking attachment adversity to psychosis, from the premorbid stages of the disorder to its clinical forms. To better understand the neurobiological mechanisms through which insecure attachment may contribute to psychosis, we identify at least five neurobiological pathways linking attachment to risk for developing psychosis. Besides its well documented influence on the hypothalamic-pituary-adrenal (HPA) axis, insecure attachment may also contribute to neurodevelopmental risk through the dopaminergic and oxytonergic systems, as well as bear influence on neuroinflammation and oxidative stress responses. We further consider the neuroscientific and behavioral studies that underpin mentalization as a suite of processes potentially moderating the risk to transition to psychotic disorders. In particular, mentalization may help the individual compensate for endophenotypical impairments in the integration of sensory and metacognitive information. We propose a model where embodied mentalization would lie at the core of a protective, resilience response mitigating the adverse and potentially pathological influence of the neurodevelopmental cascade of risk for psychosis. PMID:27597820

  1. The neuropathology and neurobiology of traumatic brain injury.

    PubMed

    Blennow, Kaj; Hardy, John; Zetterberg, Henrik

    2012-12-06

    The acute and long-term consequences of traumatic brain injury (TBI) have received increased attention in recent years. In this Review, we discuss the neuropathology and neural mechanisms associated with TBI, drawing on findings from sports-induced TBI in athletes, in whom acute TBI damages axons and elicits both regenerative and degenerative tissue responses in the brain and in whom repeated concussions may initiate a long-term neurodegenerative process called dementia pugilistica or chronic traumatic encephalopathy (CTE). We also consider how the neuropathology and neurobiology of CTE in many ways resembles other neurodegenerative illnesses such as Alzheimer's disease, particularly with respect to mismetabolism and aggregation of tau, β-amyloid, and TDP-43. Finally, we explore how translational research in animal models of acceleration/deceleration types of injury relevant for concussion together with clinical studies employing imaging and biochemical markers may further elucidate the neurobiology of TBI and CTE. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Neurobiology in public and private discourse: the case of adults with ADHD.

    PubMed

    Bröer, Christian; Heerings, Marjolijn

    2013-01-01

    How do people describe their health? How do their descriptions relate to public definitions? This article focuses on adult attention deficit hyperactivity disorder (ADHD). We look at Dutch adults who adopt the ADHD label and ask: which discourses structure their descriptions of ADHD? How do these relate to the dominant public discourse on ADHD? Do people use, for example, neurobiological explanations of ADHD? The research makes use of Q-methodology, which combines a discursive relational approach with factor analysis. We examine five different personal discourses that partly differ from the public discourse. People borrow neurobiological, psychological, sociological and even holistic arguments from public discourse to come up with a distinct set of discourses. Neurobiology resonates among adults with ADHD but does not dominate their thinking. Contrary to our expectation, this supports reflexivity instead of discipline theory. © 2012 The Authors. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

  3. Underuse of Title VII Funding for Indian Education in Arizona, Nevada, and Utah

    ERIC Educational Resources Information Center

    West Comprehensive Center at WestEd, 2015

    2015-01-01

    Title VII provides funding for the education of American Indian/Alaska Native students based on a formula grant available to school districts, charter schools, and local education agencies (LEAs). This report explores why some eligible schools and districts do not apply for federal Title VII, potentially resulting in American Indian/Alaska Native…

  4. Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology

    PubMed Central

    Leach, Jennie B.; Achyuta, Anil Kumar H.; Murthy, Shashi K.

    2009-01-01

    Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke. However, a major impediment in the advancement of this technology is the challenge of maintaining device performance during chronic implantation (months to years) due to complex intrinsic host responses such as gliosis or glial scarring. The objective of this review is to bring together research communities in neurobiology, tissue engineering, and neuroprosthetics to address the major obstacles encountered in the translation of neuroprosthetics technology into long-term clinical use. This article draws connections between specific challenges faced by current neuroprosthetics technology and recent advances in the areas of nerve tissue engineering and neurobiology. Within the context of the device–nervous system interface and central nervous system implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell biology. Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration toward novel technologies to address the complexities associated with long-term neuroprosthetic device performance. PMID:20161810

  5. Leveraging Information Technology. Track VII: Outstanding Applications.

    ERIC Educational Resources Information Center

    CAUSE, Boulder, CO.

    Eight papers from the 1987 CAUSE conference's Track VII, Outstanding Applications, are presented. They include: "Image Databases in the University" (Reid Kaplan and Gordon Mathieson); "Using Information Technology for Travel Management at the University of Michigan" (Robert E. Russell and John C. Hufziger); "On-Line Access…

  6. Autism Spectrum Disorders: Neurobiology and Current Assessment Practices

    ERIC Educational Resources Information Center

    Allen, Ryan A.; Robins, Diana L.; Decker, Scott L.

    2008-01-01

    This study reviews recent research related to the neurobiology of Autism Spectrum Disorders (ASDs) an provides an empirical analysis of current assessment practices. Data were collected through a survey of 117 school psychologists. The Childhood Autism Rating Scale (CARS), Gilliam Autism Rating Scale (GARS), and Gilliam Asperger's Disorder Scale…

  7. The Effect of Neonatal Gene Therapy on Skeletal Manifestations in Mucopolysaccharidosis VII Dogs after a Decade

    PubMed Central

    Xing, Elizabeth M.; Knox, Van W.; O'Donnell, Patricia A.; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

    2013-01-01

    Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. PMID:23628461

  8. PREFACE: VII Mexican School on Gravitation and Mathematical Physics

    NASA Astrophysics Data System (ADS)

    Alcubierre Moya, Miguel; García Compeán, Héctor Hugo; Ureña López, Luis Arturo

    2007-07-01

    The present collection of papers was presented during the VII Mexican School on Gravitation and Mathematical Physics, which was held in Playa del Carmen, Quintana Roo, México, from 26 November to 2 December 2006. The Mexican School on Gravitation and Mathematical Physics, sponsored by the Mexican Physical Society, started in 1994 with the purpose of discussing and exchanging current ideas in gravitational physics. Each school has been devoted to a particular subject, and on previous occasions these subjects have covered topics such as supergravity, branes, black holes, the early Universe, observational cosmology, and quantum gravity. At the dawn of the XXI Century, General Relativity has finally become a standard tool in our understanding of numerous astrophysical phenomena. At the same time, the new generation of large interferometric gravitational wave detectors that are just beginning operation holds the promise of finally allowing the detection of gravitational waves and opening a new window on the Universe. However, because of the complexity of the Einstein field equations, the modelling of realistic astrophysical systems and gravitational wave sources can only be done using numerical simulations. Because of this, we have dedicated our VII School to the topic of relativistic astrophysics and numerical relativity. As in all our previous Schools, international leaders in the field were invited to give courses and plenary lectures. The school was complemented with more specialized talks presented in parallel sessions, some of which are included in these proceedings. All the contributions in this volume have been refereed, and they represent a sample of the courses, invited talks and contributed talks presented during our VII School. Our deep gratitude goes to all those who contributed to these proceedings, and to making our VII Mexican School a great success. Miguel Alcubierre Moya, Héctor Hugo García Compeán and Luis Arturo Ureña López Editors

  9. [Psychotherapy of Depression as Neurobiological Process - Evidence from Neuroimaging].

    PubMed

    Rubart, Antonie; Hohagen, Fritz; Zurowski, Bartosz

    2018-06-01

    Research on neurobiological effects of psychotherapy in depression facilitates the improvement of treatment strategies. The cortico-limbic dysregulation model serves as a framework for numerous studies on neurobiological changes in depression. In this model, depression is described as hypoactivation of dorsal cortical brain regions in conjunction with hyperactivation of ventral paralimbic regions. This assumption has been supported by various studies of structural and functional brain abnormalities in depression. However, also regions not included in the original cortico-limbic dysregulation model, such as the dorsomedial prefrontal cortex, seem to play an important role in depression. Functional connectivity studies of depression have revealed an enhanced connectivity within the so-called default mode network which is involved in self-referential thinking. Studies also point to a normalization of limbic and cortical brain activity, especially in the anterior cingulate cortex, during psychotherapy. Some neurobiological markers like the activity of the anterior cingulate cortex, striatum and insula as well as hippocampal volume have been proposed to predict treatment response on a group-level. The activity of the anterior insula appears to be a candidate bio-marker for differential indication for psychotherapy or pharmacotherapy. The cortico-limbic dysregulation model and following research have inspired new forms of treatment for depression like deep brain stimulation of the subgenual anterior cingulate cortex, repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex, neurofeedback and attention training. © Georg Thieme Verlag KG Stuttgart · New York.

  10. 29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8 Section 1604.8 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The...

  11. 29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 4 2012-07-01 2012-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8 Section 1604.8 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The...

  12. 29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 4 2013-07-01 2013-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8 Section 1604.8 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The...

  13. 29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 4 2011-07-01 2011-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8 Section 1604.8 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The...

  14. Weather applications and products enabled through vehicle infrastructure integration (VII) : feasibility and concept development study

    DOT National Transportation Integrated Search

    2007-01-01

    Vehicle Infrastructure Integration (VII) involves the two-way wireless transmission of data from vehicle-to-vehicle and vehicle-to-infrastructure utilizing Dedicated Short Range Communications (DSRC). VII will enable the development of weather-relate...

  15. The Fokker "Trimotor F VII" commercial transport monoplane

    NASA Technical Reports Server (NTRS)

    1928-01-01

    Directly developed from the single engined type F VII ten passenger monoplanes, The Fokker Trimotor closely follows the commercial aircraft that preceded it. It has three Wright Whirlwind air-cooled engines, rated at 200 HP each.

  16. Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus.

    PubMed

    Watson, G L; Sayles, J N; Chen, C; Elliger, S S; Elliger, C A; Raju, N R; Kurtzman, G J; Podsakoff, G M

    1998-12-01

    Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by a genetic deficiency of beta-glucuronidase (GUS). We used a recombinant adeno-associated virus vector (AAV-GUS) to deliver GUS cDNA to MPS VII mice. The route of vector administration had a dramatic effect on the extent and distribution of GUS activity. Intramuscular injection of AAV-GUS resulted in high, localized production of GUS, while intravenous administration produced low GUS activity in several tissues. This latter treatment of MPS VII mice reduced glycosaminoglycan levels in the liver to normal and reduced storage granules dramatically. We show that a single administration of AAV-GUS can provide sustained expression of GUS in a variety of cell types and is sufficient to reverse the disease phenotype at least in the liver.

  17. Matching the Neurobiology of Learning to Teaching Principles

    ERIC Educational Resources Information Center

    Moffett, Nelle; Fleisher, Steven C.

    2013-01-01

    The authors describe principles of good teaching drawn from meta-analyses of research on teaching effectiveness. Recent developments in neurobiology are presented and aligned to provide biological support for these principles. To make it easier for college faculty to try out sample instructional strategies, the authors map principles of good…

  18. The ice VII-ice X phase transition with implications for planetary interiors

    NASA Astrophysics Data System (ADS)

    Aarestad, B.; Frank, M. R.; Scott, H.; Bricker, M.; Prakapenka, V.

    2008-12-01

    A significant amount of research on the high pressure polymorphs of H2O have detailed the lattice structure and density of these phases, namely ice VI, ice VII, and ice X. These high pressure ices are noteworthy as they may comprise a considerable part of the interior of large icy planets and satellites. However, there is a dearth of data on how the incorporation of an impurity, charged or non-charged, affects the ice VII-ice X transition. This study examined the ice VII-ice X transition that occurs at approximately 62 GPa with a pure system and two select impure systems. Solutions of pure H2O, 1.6 mole percent NaCl in H2O, and 1.60 mole percent CH3OH in H2O were compressed in a diamond anvil cell (DAC). The experiments were performed at the GSECARS 13-BM-D beam line at the Advanced Photon Source at Argonne National Laboratory. Powder diffraction data of the ice samples were collected using monochromatic X-ray radiation, 0.2755 Å, and a MAR 345 online imaging system at intervals of approximately 2 GPa up to ~71.5, ~74.5, and ~68 GPa, respectively. Analyses of the data provided volume-pressure relations (at 298 K) which were used to detail the ice VII-ice X phase transition. The pressure of the phase transition, based upon an interpretation of the X-ray diffraction data, was found to vary as a function of the impurity type. Thus, the depth of the ice VII-ice X phase transition within an ice-rich planetary body can be influenced by trace-level impurities.

  19. Can understanding the neurobiology of body dysmorphic disorder (BDD) inform treatment?

    PubMed

    Rossell, Susan L; Harrison, Ben J; Castle, David

    2015-08-01

    We aim to provide a clinically focused review of the neurobiological literature in body dysmorphic disorder (BDD), with a focus on structural and functional neuroimaging. There has been a recent influx of studies examining the underlying neurobiology of BDD using structural and functional neuroimaging methods. Despite obvious symptom similarities with obsessive-compulsive disorder (OCD), no study to date has directly compared the two groups using neuroimaging techniques. Studies have established that there are limbic and visual cortex abnormalities in BDD, in contrast to fronto-striatal differences in OCD. Such data suggests affect or visual training maybe useful in BDD. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  20. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

    PubMed Central

    Kim, Mi Eun; Jung, Inae; Na, Ju Yong; Kim, Woo Jung; Kim, Young-Ok; Park, Yong-Duk; Lee, Jun Sik

    2017-01-01

    The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1β, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics. PMID:29104209

  1. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo.

    PubMed

    Kim, Mi Eun; Jung, Inae; Lee, Jong Suk; Na, Ju Yong; Kim, Woo Jung; Kim, Young-Ok; Park, Yong-Duk; Lee, Jun Sik

    2017-11-01

    The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos , cox-2 , il-1β , tnf-α , and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

  2. The effect of neonatal gene therapy on skeletal manifestations in mucopolysaccharidosis VII dogs after a decade.

    PubMed

    Xing, Elizabeth M; Knox, Van W; O'Donnell, Patricia A; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

    2013-06-01

    Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Radiographic evaluation of bones and joints in mucopolysaccharidosis I and VII dogs after neonatal gene therapy.

    PubMed

    Herati, Ramin Sedaghat; Knox, Van W; O'Donnell, Patricia; D'Angelo, Marina; Haskins, Mark E; Ponder, Katherine P

    2008-11-01

    Mucopolysaccharidosis I (MPS I) and MPS VII are due to deficient activity of the glycosaminoglycan-degrading lysosomal enzymes alpha-L-iduronidase and beta-glucuronidase, respectively, and result in abnormal bones and joints. Here, the severity of skeletal disease in MPS I and MPS VII dogs and the effects of neonatal gene therapy were evaluated. For untreated MPS VII dogs, the lengths of the second cervical vertebrae (C2) and the femur were only 56% and 84% of normal, respectively, and bone dysplasia and articular erosions, and joint subluxation were severe. Previously, we reported that neonatal intravenous injection of a retroviral vector (RV) with the appropriate gene resulted in expression in liver and blood cells, and high serum enzyme activity. In this study, we demonstrate that C2 and femurs of RV-treated MPS VII dogs were longer at 82% and 101% of normal, respectively, and there were partial improvements of qualitative abnormalities. For untreated MPS I dogs, the lengths of C2 and femurs (91% and 96% of normal, respectively) were not significantly different from normal dogs. Qualitative changes in MPS I bones and joints were generally modest and were partially improved with RV treatment, although cervical spine disease was severe and was difficult to correct with gene therapy in both models. The greater severity of skeletal disease in MPS VII than in MPS I dogs may reflect accumulation of chondroitin sulfate in cartilage in MPS VII, or could relate to the specific mutations. Neonatal RV-mediated gene therapy ameliorates, but does not prevent, skeletal disease in MPS I and MPS VII dogs.

  4. Neurobiological Underpinnings of Math and Reading Learning Disabilities

    ERIC Educational Resources Information Center

    Ashkenazi, Sarit; Black, Jessica M.; Abrams, Daniel A.; Hoeft, Fumiko; Menon, Vinod

    2013-01-01

    The primary goal of this review is to highlight current research and theories describing the neurobiological basis of math (MD), reading (RD), and comorbid math and reading disability (MD+RD). We first describe the unique brain and cognitive processes involved in acquisition of math and reading skills, emphasizing similarities and differences in…

  5. Factors Influencing Title VII Bilingual Program Institutionalization.

    ERIC Educational Resources Information Center

    Lewis, Gerald R.; And Others

    1985-01-01

    This study of the primary restraining and driving forces that influence Title VII bilingual education programs found the external environment, the local community, to be the main factor influencing institutionalization and self-renewal. The internal environment--the local school, and the local school's organization or central office, school board,…

  6. 76 FR 57013 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-15

    ... EQUAL EMPLOYMENT OPPORTUNITY COMMISSION 29 CFR Part 1602 RIN 3046-AA89 Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION... under title VII, the ADA, and GINA. (76 FR 31892, June 2, 2011). No requests to present oral testimony...

  7. 1990 Clean Air Act Amendment Summary: Title VII

    EPA Pesticide Factsheets

    This page provides an overview of the 1990 amendments to Title VII of the Clean Air Act, which were enacted to curb acid rain, urban air pollution and toxic air emissions. The edits to this title deal with enforcement provisions.

  8. Neurobiological effects of repeated radiofrequency exposures in male senescent rats.

    PubMed

    Bouji, Marc; Lecomte, Anthony; Gamez, Christelle; Blazy, Kelly; Villégier, Anne-Sophie

    2016-11-01

    The increasing use of mobile phones by aging people raises issues about the effects of radiofrequency electromagnetic fields (RF-EMF) on the aging central nervous system. Here, we tested if mobile phone RF-EMF exposures could exacerbate senescence-typical neurobiological deficits. Thus, aged (22-24 months) and young (4-6 months) adult male rats were subjected to head RF-EMF exposures (900 MHz, specific absorption rate (SAR) of 6 W/kg, 45 min/day for 1 month in restraint rockets). To assess senescence-typical neurobiological deficits, spatial memory, emotional memory, anxiety-related behavior, locomotor activity, interleukins (IL)-1β and 6, glial fibrillary acidic protein and corticosterone were measured. Aged rats presented deficits in spatial learning, exploration, anxiety-related behaviors, and increased hippocampal ILs and cortical IL-1β. Results showed that senescence-typical neurobiological deficits were not modified by RF-EMF exposures. RF-EMF-exposed rats (young and aged adults pooled) had decreased anxiety-related behaviors in the elevated plus maze. This study which is the first to assess RF-EMF exposures during late aging did not support the hypothesis of a specific cerebral vulnerability to RF-EMF during senescence. More investigations using longer RF-EMF exposures should be performed to conclude regarding the inoffensiveness of RF-EMF exposures.

  9. Ice-VII inclusions in diamonds: Evidence for aqueous fluid in Earth’s deep mantle

    NASA Astrophysics Data System (ADS)

    Tschauner, O.; Huang, S.; Greenberg, E.; Prakapenka, V. B.; Ma, C.; Rossman, G. R.; Shen, A. H.; Zhang, D.; Newville, M.; Lanzirotti, A.; Tait, K.

    2018-03-01

    Water-rich regions in Earth’s deeper mantle are suspected to play a key role in the global water budget and the mobility of heat-generating elements. We show that ice-VII occurs as inclusions in natural diamond and serves as an indicator for such water-rich regions. Ice-VII, the residue of aqueous fluid present during growth of diamond, crystallizes upon ascent of the host diamonds but remains at pressures as high as 24 gigapascals; it is now recognized as a mineral by the International Mineralogical Association. In particular, ice-VII in diamonds points toward fluid-rich locations in the upper transition zone and around the 660-kilometer boundary.

  10. Lack of bleeding in patients with severe factor VII deficiency.

    PubMed

    Barnett, J Mark; Demel, Kurt C; Mega, Anthony E; Butera, James N; Sweeney, Joseph D

    2005-02-01

    Factor VII deficiency, although rare, is now recognized as the most common autosomal recessive inherited factor deficiency. It is usually considered to be associated with bleeding only in the severely affected subject and heterozygotes (>10%) are not considered at risk. The general recommendation for surgery is to achieve a FVII level in excess of 15% (0.15 1U/mL). We present three cases of severe factor VII deficiency, each of whom appeared hemostatically competent based on clinical history. Subject 1 is a 33 year-old African-American female with a baseline FVII of <1%, who had a fractured tibia requiring open reduction with internal fixation without any FVII replacement and subsequently underwent successful laparoscopic knee surgery with a factor VII level measured at 6%. Subject 2 is a 58 year-old African-American female with a factor VII level of 9% who underwent an elective left total hip replacement without any factor replacement and had no excessive bleeding, but who sustained a pulmonary embolism postoperatively. Subject 3 is a 19-year-old African-American male with a baseline FVII of 1% with a history of active participation in football without noticeable injury and who underwent an emergent appendectomy without bleeding. These three cases represent individuals with the severe form of FVII deficiency who did not exhibit excessive bleeding when challenged with surgical procedures. The clinical history would appear the most valuable tool in predicting the likelihood of bleeding in these patients, and we suggest that the presumption that all patients with severe FVII deficiency should receive replacement therapy before surgical procedures may not be valid in all cases. Copyright 2005 Wiley-Liss, Inc.

  11. 20 CFR Appendix Vii to Subpart C... - “Old-Law” Contribution and Benefit Base

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Appendix VII to Subpart C of Part 404 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Computing Primary Insurance Amounts Pt. 404, Subpt. C, App. VII... Security Act without the enactment of the 1977 amendments. Year Amount 1979 $18,900 1980 20,400 1981 22,200...

  12. Contribution of tertiary amino groups to Re(VII) biosorption on modified corn stalk: competitiveness and regularity.

    PubMed

    Lou, Zhenning; Zhao, Ziyi; Li, Yexia; Shan, Weijun; Xiong, Ying; Fang, Dawei; Yue, Shuang; Zang, Shuliang

    2013-04-01

    The effects of basic strength and steric hindrance of gels modified by dimethylamine, diethylamine, di-n-octylamine and di-2-ethylhexylamine, respectively, on rhenium (Re(VII)) adsorption capacity and selectivity were discussed. By comparing with the adsorption of other coexisting metals, such as Mo(VI), Cu(II), Pb(II), Fe(III), Zn(II), Mn(VII) and Ni(II), the gel modified by di-n-octylamine (DNOA-OCS) showed a high affinity for Re(VII) at higher hydrochloric acid concentration (C(H)(+)≥1.0 mol L(-1)), and the maximum adsorption capacity was 98.69 mg g(-1). This article not only described the adsorption behavior but also suggested isotherms, kinetics and thermodynamics of Re(VII) onto the DNOA-OCS gel in an aqueous medium using several models. Further study on adsorption of rhenium in a fixed-bed column packed with the DNOA-OCS gel under continuous and recirculating modes could confirm that the corn stalk gel modified by di-n-octylamine could be used as the adsorbent of Re(VII) from Mo-containing wastewater. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Towards An Integrative Theory Of Consciousness: Part 1 (Neurobiological And Cognitive Models)

    PubMed Central

    De Sousa, Avinash

    2013-01-01

    The study of consciousness is poised today at interesting crossroads. There has been a surge of research into various neurobiological underpinnings of consciousness in the past decade. The present article looks at the theories regarding this complex phenomenon, especially the ones that neurobiology, cognitive neuroscience and cognitive psychology have to offer. We will first discuss the origin and etymology of word consciousness and its usage. Neurobiological correlates of consciousness are discussed with structures like the ascending reticular activating system, the amygdala, the cerebellum, the thalamus, the frontoparietal circuits, the prefrontal cortex and the precuneus. The cellular and microlevel theories of consciousness and cerebral activity at the neuronal level contributing to consciousness are highlighted, along with the various theories posited in this area. The role of neuronal assemblies and circuits along with firing patterns and their ramifications for the understanding of consciousness are discussed. A section on the role of anaesthesia and its links to consciousness is presented, along with details of split-brain studies in consciousness and altered states of awareness, including the vegetative states. The article finally discusses the progress cognitive psychology has made in identifying and theorising various perspectives of consciousness, perceptual awareness and conscious processing. Both recent and past researches are highlighted. The importance and salient features of each theory are discussed along with the pitfalls, if present. A need for integration of various theories to understand consciousness from a holistic perspective is stressed, to enable one to reach a theory that explains the ultimate neurobiology of consciousness. PMID:23678241

  14. Neurobiology of Schizophrenia: Search for the Elusive Correlation with Symptoms

    PubMed Central

    Mathalon, Daniel H.; Ford, Judith M.

    2012-01-01

    In the last half-century, human neuroscience methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of the clinical symptoms that the diagnosis is based on have been largely unsuccessful. In this paper, we provide an overview of the conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures. These obstacles include small samples, questionable reliability and validity of measurements, medication confounds, failure to distinguish state and trait effects, correlation–causation ambiguity, and the absence of compelling animal models of specific symptoms to test mechanistic hypotheses derived from brain-symptom correlations. We conclude with recommendations to promote progress in establishing brain-symptom relationships. PMID:22654745

  15. Radiographic Evaluation of Bones and Joints in Mucopolysaccharidosis I and VII Dogs After Neonatal Gene Therapy

    PubMed Central

    Herati, Ramin Sedaghat; Knox, Van W.; O’Donnell, Patricia; D’Angelo, Marina; Haskins, Mark E.; Ponder, Katherine P.

    2009-01-01

    Mucopolysaccharidosis I (MPS I) and MPS VII are due to deficient activity of the glycosaminoglycan-degrading lysosomal enzymes α-L-iduronidase and β-glucuronidase, respectively, and result in abnormal bones and joints. Here, the severity of skeletal disease in MPS I and MPS VII dogs and the effects of neonatal gene therapy were evaluated. For untreated MPS VII dogs, the lengths of the second cervical vertebrae (C2) and the femur were only 56% and 84% of normal, respectively, and bone dysplasia and articular erosions, and joint subluxation were severe. Previously, we reported that neonatal intravenous injection of a retroviral vector (RV) with the appropriate gene resulted in expression in liver and blood cells, and high serum enzyme activity. In this study, we demonstrate that C2 and femurs of RV-treated MPS VII dogs were longer at 82% and 101% of normal, respectively, and there were partial improvements of qualitative abnormalities. For untreated MPS I dogs, the lengths of C2 and femurs (91% and 96% of normal, respectively) were not significantly different from normal dogs. Qualitative changes in MPS I bones and joints were generally modest and were partially improved with RV treatment, although cervical spine disease was severe and was difficult to correct with gene therapy in both models. The greater severity of skeletal disease in MPS VII than in MPS I dogs may reflect accumulation of chondroitin sulfate in cartilage in MPS VII, or could relate to the specific mutations. Neonatal RV-mediated gene therapy ameliorates, but does not prevent, skeletal disease in MPS I and MPS VII dogs. PMID:18707908

  16. Anti-Type VII Collagen Antibodies Are Identified in a Subpopulation of Bullous Pemphigoid Patients With Relapse

    PubMed Central

    Giusti, Delphine; Gatouillat, Grégory; Le Jan, Sébastien; Plée, Julie; Bernard, Philippe; Antonicelli, Frank; Pham, Bach-Nga

    2018-01-01

    Bullous pemphigoid (BP) is an autoimmune bullous skin disease characterized by anti-BP180 and anti-BP230 autoantibodies (AAbs). Mucous membrane involvement is an uncommon clinical feature of BP which may evoke epidermolysis bullosa acquisita, another skin autoimmune disease characterized by anti-type VII collagen AAbs. We therefore evaluated the presence of anti-type VII collagen AAbs in the serum of BP patients with and without mucosal lesions at time of diagnosis and under therapy. Anti-BP180, anti-BP230, and anti-type VII collagen AAbs were measured by ELISA in the serum of unselected patients fulfilling clinical and histo/immunopathological BP criteria at baseline (n = 71) and at time of relapse (n = 24). At baseline, anti-type VII collagen AAbs were detected in 2 out of 24 patients with BP presenting with mucosal involvement, but not in patients without mucosal lesions (n = 47). At the time of relapse, 10 out of 24 BP patients either displayed a significant induction or increase of concentrations of anti-type VII collagen AAbs (P < 0.01), independently of mucosal involvement. Those 10 relapsing BP patients were also characterized by a sustained high concentration of anti-BP180 AAb, whereas the serum anti-BP230 AAb concentrations did not vary in BP patients with relapse according to the presence of anti-type VII collagen AAbs. Thus, our study showed that anti-type VII collagen along with anti-BP180 AAbs detection stratified BP patients at time of relapse, illustrating a still dysregulated immune response that could reflect a potential epitope spreading mechanism in those BP patients. PMID:29619029

  17. A presomite human embryo of Horizon VII.

    PubMed Central

    Rewell, R E; Harrison, R G

    1976-01-01

    A presomite embryo of Horizon VII aged approximately 18 days is described and illustrated. It is compared with some other embryos of a similar age, and a considerable variation of histological characteristics within the same Horizon is noted. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:1254532

  18. Employment Discrimination: Alternative Remedies to Title VII

    ERIC Educational Resources Information Center

    Whittier, Ann M.; Whittier, Gary L.

    1975-01-01

    This article is intended to familiarize Missouri lawyers with the advantages, limitations, and important procedural aspects of four remedies that can supplement or offer alternatives to Title VII litigation in appropriate situations: The Equal Pay Act; section 1983 of the Civil Rights Act of 1871, Executive Order No. 11,246, and the Missouri Fair…

  19. The neurobiology of climate change

    NASA Astrophysics Data System (ADS)

    O'Donnell, Sean

    2018-02-01

    Directional climate change (global warming) is causing rapid alterations in animals' environments. Because the nervous system is at the forefront of animals' interactions with the environment, the neurobiological implications of climate change are central to understanding how individuals, and ultimately populations, will respond to global warming. Evidence is accumulating for individual level, mechanistic effects of climate change on nervous system development and performance. Climate change can also alter sensory stimuli, changing the effectiveness of sensory and cognitive systems for achieving biological fitness. At the population level, natural selection forces stemming from directional climate change may drive rapid evolutionary change in nervous system structure and function.

  20. The neurobiology of climate change.

    PubMed

    O'Donnell, Sean

    2018-01-06

    Directional climate change (global warming) is causing rapid alterations in animals' environments. Because the nervous system is at the forefront of animals' interactions with the environment, the neurobiological implications of climate change are central to understanding how individuals, and ultimately populations, will respond to global warming. Evidence is accumulating for individual level, mechanistic effects of climate change on nervous system development and performance. Climate change can also alter sensory stimuli, changing the effectiveness of sensory and cognitive systems for achieving biological fitness. At the population level, natural selection forces stemming from directional climate change may drive rapid evolutionary change in nervous system structure and function.

  1. Addiction Science: Uncovering Neurobiological Complexity

    PubMed Central

    Volkow, N. D.; Baler, R. D.

    2013-01-01

    Until very recently addiction-research was limited by existing tools and strategies that were inadequate for studying the inherent complexity at each of the different phenomenological levels. However, powerful new tools (e.g., optogenetics and designer drug receptors) and high throughput protocols are starting to give researchers the potential to systematically interrogate “all” genes, epigenetic marks, and neuronal circuits. These advances, combined with imaging technologies (both for preclinical and clinical studies) and a paradigm shift towards open access have spurred an unlimited growth of datasets transforming the way we investigate the neurobiology of substance use disorders (SUD) and the factors that modulate risk and resilience. PMID:23688927

  2. Ice-VII inclusions in diamonds: Evidence for aqueous fluid in Earth's deep mantle.

    PubMed

    Tschauner, O; Huang, S; Greenberg, E; Prakapenka, V B; Ma, C; Rossman, G R; Shen, A H; Zhang, D; Newville, M; Lanzirotti, A; Tait, K

    2018-03-09

    Water-rich regions in Earth's deeper mantle are suspected to play a key role in the global water budget and the mobility of heat-generating elements. We show that ice-VII occurs as inclusions in natural diamond and serves as an indicator for such water-rich regions. Ice-VII, the residue of aqueous fluid present during growth of diamond, crystallizes upon ascent of the host diamonds but remains at pressures as high as 24 gigapascals; it is now recognized as a mineral by the International Mineralogical Association. In particular, ice-VII in diamonds points toward fluid-rich locations in the upper transition zone and around the 660-kilometer boundary. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  3. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    PubMed

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

  4. Active site mutant transgene confers tolerance to human β-glucuronidase without affecting the phenotype of MPS VII mice

    PubMed Central

    Sly, William S.; Vogler, Carole; Grubb, Jeffrey H.; Zhou, Mi; Jiang, Jinxing; Zhou, Xiao Yan; Tomatsu, Shunji; Bi, Yanhua; Snella, Elizabeth M.

    2001-01-01

    Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is an autosomal recessive lysosomal storage disorder due to an inherited deficiency of β-glucuronidase. A naturally occurring mouse model for this disease was discovered at The Jackson Laboratory and shown to be due to homozygosity for a 1-bp deletion in exon 10 of the gus gene. The murine model MPS VII (gusmps/mps) has been very well characterized and used extensively to evaluate experimental strategies for lysosomal storage diseases, including bone marrow transplantation, enzyme replacement therapy, and gene therapy. To enhance the value of this model for enzyme and gene therapy, we produced a transgenic mouse expressing the human β-glucuronidase cDNA with an amino acid substitution at the active site nucleophile (E540A) and bred it onto the MPS VII (gusmps/mps) background. We demonstrate here that the mutant mice bearing the active site mutant human transgene retain the clinical, morphological, biochemical, and histopathological characteristics of the original MPS VII (gusmps/mps) mouse. However, they are now tolerant to immune challenge with human β-glucuronidase. This “tolerant MPS VII mouse model” should be useful for preclinical trials evaluating the effectiveness of enzyme and/or gene therapy with the human gene products likely to be administered to human patients with MPS VII. PMID:11226217

  5. Subjective Criteria in Employment Decisions Under Title VII

    ERIC Educational Resources Information Center

    Stacy, Donald R.

    1976-01-01

    Since higher echelon jobs have been drawn into litigation under Title VII, subjective criteria have been employed. The legal ramifications of assessing noncognitive traits such as leadership, aggressiveness, and attitude are discussed. Available from: the University of Georgia School of Law, Athens, Georgia 30602. (LBH)

  6. Artificial dirt: microfluidic substrates for nematode neurobiology and behavior.

    PubMed

    Lockery, S R; Lawton, K J; Doll, J C; Faumont, S; Coulthard, S M; Thiele, T R; Chronis, N; McCormick, K E; Goodman, M B; Pruitt, B L

    2008-06-01

    With a nervous system of only 302 neurons, the free-living nematode Caenorhabditis elegans is a powerful experimental organism for neurobiology. However, the laboratory substrate commonly used in C. elegans research, a planar agarose surface, fails to reflect the complexity of this organism's natural environment, complicates stimulus delivery, and is incompatible with high-resolution optophysiology experiments. Here we present a new class of microfluidic devices for C. elegans neurobiology and behavior: agarose-free, micron-scale chambers and channels that allow the animals to crawl as they would on agarose. One such device mimics a moist soil matrix and facilitates rapid delivery of fluid-borne stimuli. A second device consists of sinusoidal channels that can be used to regulate the waveform and trajectory of crawling worms. Both devices are thin and transparent, rendering them compatible with high-resolution microscope objectives for neuronal imaging and optical recording. Together, the new devices are likely to accelerate studies of the neuronal basis of behavior in C. elegans.

  7. 20 CFR Appendix Vii to Subpart C... - “Old-Law” Contribution and Benefit Base

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false âOld-Lawâ Contribution and Benefit Base VII... Appendix VII to Subpart C of Part 404—“Old-Law” Contribution and Benefit Base Explanation: We use these... appendix IV). This is the contribution and benefit base that would have been effective under the Social...

  8. Release of the ENDF/B-VII.1 Evaluated Nuclear Data File

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brown, David

    2012-06-30

    The Cross Section Evaluation Working Group (CSEWG) released the ENDF/B-VII.1 library on December 22, 2011. The ENDF/B-VII.1 library is CSEWG's latest recommended evaluated nuclear data file for use in nuclear science and technology applications, and incorporates advances made in the five years since the release of ENDF/B-VII.0, including: many new evaluation in the neutron sublibrary (423 in all and over 190 of these contain covariances), new fission product yields and a greatly improved decay data sublibrary. This summary barely touches on the five years worth of advances present in the ENDF/B-VII.1 library. We expect that these changes will lead tomore » improved integral performance in reactors and other applications. Furthermore, the expansion of covariance data in this release will allow for better uncertainty quantification, reducing design margins and costs. The ENDF library is an ongoing and evolving effort. Currently, the ENDF data community embarking on several parallel efforts to improve library management: (1) The adoption of a continuous integration system to provide evaluators 'instant' feedback on the quality of their evaluations and to provide data users with working 'beta' quality libraries in between major releases. (2) The transition to new hierarchical data format - the Generalized Nuclear Data (GND) format. We expect GND to enable new kinds of evaluated data which cannot be accommodated in the legacy ENDF format. (3) The development of data assimilation and uncertainty propagation techniques to enable the consistent use of integral experimental data in the evaluation process.« less

  9. Neglected but Exciting Concepts in Developmental and Neurobiological Psychology

    ERIC Educational Resources Information Center

    Jordan, Evan M.; Thomas, David G.

    2017-01-01

    This review provides an evaluative overview of five concepts specific to developmental and neurobiological psychology that are found to be largely overlooked in current textbooks. A sample of 19 introductory psychology texts was surveyed to develop a list, including glial cell signaling, grandmother cells, memory reconsolidation, brain plasticity,…

  10. 48 CFR 952.227-14 - Rights in data-general. (DOE coverage-alternates VI and VII)

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    .... (DOE coverage-alternates VI and VII) 952.227-14 Section 952.227-14 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.227-14 Rights in data-general. (DOE coverage—alternates VI and VII) Alternate VI...

  11. 48 CFR 952.227-14 - Rights in data-general. (DOE coverage-alternates VI and VII)

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    .... (DOE coverage-alternates VI and VII) 952.227-14 Section 952.227-14 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.227-14 Rights in data-general. (DOE coverage—alternates VI and VII) Alternate VI...

  12. 48 CFR 952.227-14 - Rights in data-general. (DOE coverage-alternates VI and VII)

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    .... (DOE coverage-alternates VI and VII) 952.227-14 Section 952.227-14 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 952.227-14 Rights in data-general. (DOE coverage—alternates VI and VII) Alternate VI...

  13. To what extent do neurobiological sleep-waking processes support psychoanalysis?

    PubMed

    Gottesmann, Claude

    2010-01-01

    Sigmund Freud's thesis was that there is a censorship during waking that prevents memory of events, drives, wishes, and feelings from entering the consciousness because they would induce anxiety due to their emotional or ethical unacceptability. During dreaming, because the efficiency of censorship is decreased, latent thought contents can, after dream-work involving condensation and displacement, enter the dreamer's consciousness under the figurative form of manifest content. The quasi-closed dogma of psychoanalytic theory as related to unconscious processes is beginning to find neurobiological confirmation during waking. Indeed, there are active processes that suppress (repress) unwanted memories from entering consciousness. In contrast, it is more difficult to find neurobiological evidence supporting an organized dream-work that would induce meaningful symbolic content, since dream mentation most often only shows psychotic-like activities. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Neurobiologically realistic determinants of self-organized criticality in networks of spiking neurons.

    PubMed

    Rubinov, Mikail; Sporns, Olaf; Thivierge, Jean-Philippe; Breakspear, Michael

    2011-06-01

    Self-organized criticality refers to the spontaneous emergence of self-similar dynamics in complex systems poised between order and randomness. The presence of self-organized critical dynamics in the brain is theoretically appealing and is supported by recent neurophysiological studies. Despite this, the neurobiological determinants of these dynamics have not been previously sought. Here, we systematically examined the influence of such determinants in hierarchically modular networks of leaky integrate-and-fire neurons with spike-timing-dependent synaptic plasticity and axonal conduction delays. We characterized emergent dynamics in our networks by distributions of active neuronal ensemble modules (neuronal avalanches) and rigorously assessed these distributions for power-law scaling. We found that spike-timing-dependent synaptic plasticity enabled a rapid phase transition from random subcritical dynamics to ordered supercritical dynamics. Importantly, modular connectivity and low wiring cost broadened this transition, and enabled a regime indicative of self-organized criticality. The regime only occurred when modular connectivity, low wiring cost and synaptic plasticity were simultaneously present, and the regime was most evident when between-module connection density scaled as a power-law. The regime was robust to variations in other neurobiologically relevant parameters and favored systems with low external drive and strong internal interactions. Increases in system size and connectivity facilitated internal interactions, permitting reductions in external drive and facilitating convergence of postsynaptic-response magnitude and synaptic-plasticity learning rate parameter values towards neurobiologically realistic levels. We hence infer a novel association between self-organized critical neuronal dynamics and several neurobiologically realistic features of structural connectivity. The central role of these features in our model may reflect their importance for

  15. Elevation of glycosaminoglycans in the amniotic fluid of a fetus with mucopolysaccharidosis VII

    PubMed Central

    Kubaski, Francyne; Brusius-Facchin, Ana Carolina; Mason, Robert W.; Patel, Pravin; Burin, Maira G.; Michelin-Tirelli, Kristiane; Kessler, Rejane Gus; Bender, Fernanda; Leistner-Segal, Sandra; Moreno, Carolina A.; Cavalcanti, Denise P.; Giugliani, Roberto; Tomatsu, Shunji

    2017-01-01

    Objective The aim of this study was to quantify GAGs in amniotic fluid (AF) from an MPS VII fetus compared with age-matched fetuses obtained from normal pregnancies. Method Disaccharides were measured by liquid chromatography tandem mass spectrometry (LC/MS/MS), compared to age-matched controls. Enzyme assay was performed in AF supernatant or cultured amniocytes. GUSB was analyzed by next generation sequencing using Ion Torrent Personal Genome Machine with a customized panel. Results No activity of β-glucuronidase was detected in fetal cells. The pregnancy was spontaneously terminated in the third trimester. Genetic studies identified a homozygous mutation of p.N379D (c.1135A>G) in the GUSB gene. LC/MS/MS showed that chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate levels were markedly increased in the MPS VII AF, compared to those in age-matched control AF (DS, HS, and C6S more than 10 × than age-matched controls; C4S and KS more than 3 times higher). Conclusion This is the first report of specific GAG analysis in AF from an MPS VII fetus, indicating that GAG elevation in AF occurs by 21 weeks of gestation and could be an additional tool for prenatal diagnosis of MPS VII and potentially other MPS types. PMID:28207930

  16. CASMO5 JENDL-4.0 and ENDF/B-VII.1beta4 libraries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rhodes, J.; Gheorghiu, N.; Ferrer, R.

    2012-07-01

    This paper details the generation of neutron data libraries for the CASMO5 lattice physics code based on the recently released JENDL-4.0 and ENDF/B-VII.1beta4 nuclear data evaluations. This data represents state-of-the-art nuclear data for late-2011. The key features of the new evaluations are briefly described along with the procedure for processing of this data into CASMO5, 586-energy group neutron data libraries. Finally some CASMO5 results for standard UO{sub 2} and MOX critical experiments for the two new libraries and the current ENDF/B-VII.0 CASMO5 library are presented including the B and W 1810 series, DIMPLE S06A, S06B, TCA reflector criticals with ironmore » plates and the PNL-30-35 MOX criticals. The results show that CASMO5 with the new libraries is performing well for these criticals with a very slight edge in results to the JENDL-4.0 nuclear data evaluation over the ENDF/B-VII.1beta4 evaluation. Work is currently underway to generate a CASMO5 library based on the final ENDF/B-VII.R1 evaluation released Dec. 22, 2011. (authors)« less

  17. Unmasking feigned sanity: a neurobiological model of emotion processing in primary psychopathy.

    PubMed

    van Honk, Jack; Schutter, Dennis J L G

    2006-05-01

    The neurobiological basis of primary psychopathy, an emotional disorder characterised by a lack of fear and empathy, on the one hand, and extremely violent, antisocial tendencies, on the other, is relatively unknown. Nevertheless, theoretical models that emphasise the role of fearlessness, imbalanced motivation, defective somatic markers, and dysfunctional violence inhibition mechanisms have complementary proposals regarding motivations and brain mechanisms involved. Presently, incorporating the heuristic value of these models and further theorising on the basis of recent data from neuropsychology, neuroendocrinology, neuroimaging, and repetitive transcranial magnetic stimulation (rTMS), an attempt is made to construct a neurobiological framework of emotion processing in primary psychopathy with clinical applicability. According to this framework, defective emotional processing in primary psychopathy results from bottom-up hormone-mediated imbalances at: (1) the subcortical level; (2) in subcortico-cortical "cross-talk"; that end up in an instrumental stance at the cortical level (3). An endocrine dual-system approach for the fine-tuned restoration of these hormone-mediated imbalances is proposed as a possible clinical application. This application may be capable of laying a neurobiological foundation for more successful sociotherapeutic interventions in primary psychopathy.

  18. Type VII collagen is enriched in the enamel organic matrix associated with the dentin-enamel junction of mature human teeth.

    PubMed

    McGuire, Jacob D; Walker, Mary P; Mousa, Ahmad; Wang, Yong; Gorski, Jeff P

    2014-06-01

    The inner enamel region of erupted teeth is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the residual enamel organic matrix. Since enamel-forming ameloblasts are known to express type VII collagen and type VII collagen null mice display abnormal amelogenesis, the aim of this study was to determine whether type VII collagen is a component of the enamel organic matrix at the dentin-enamel junction (DEJ) of mature human teeth. Immunofluorescent confocal microscopy of demineralized tooth sections localized type VII collagen to the organic matrix surrounding individual enamel rods near the DEJ. Morphologically, immunoreactive type VII collagen helical-bundles resembled the gnarled-pattern of enamel rods detected by Coomassie Blue staining. Western blotting of whole crown or enamel matrix extracts also identified characteristic Mr=280 and 230 kDa type VII dimeric forms, which resolved into 75 and 25 kDa bands upon reduction. As expected, the collagenous domain of type VII collagen was resistant to pepsin digestion, but was susceptible to purified bacterial collagenase. These results demonstrate the inner enamel organic matrix in mature teeth contains macromolecular type VII collagen. Based on its physical association with the DEJ and its well-appreciated capacity to complex with other collagens, we hypothesize that enamel embedded type VII collagen fibrils may contribute not only to the structural resilience of enamel, but may also play a role in bonding enamel to dentin. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Type VII Collagen is Enriched in the Enamel Organic Matrix Associated with the Dentin-Enamel Junction of Mature Human Teeth

    PubMed Central

    McGuire, Jacob D.; Walker, Mary P.; Mousa, Ahmad; Wang, Yong; Gorski, Jeff P.

    2014-01-01

    The inner enamel region of erupted teeth is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the residual enamel organic matrix. Since enamel-forming ameloblasts are known to express type VII collagen and type VII collagen null mice display abnormal amelogenesis, the aim of this study was to determine whether type VII collagen is a component of the enamel organic matrix at the dentin-enamel junction (DEJ) of mature human teeth. Immunofluorescent confocal microscopy of demineralized tooth sections localized type VII collagen to the organic matrix surrounding individual enamel rods near the DEJ. Morphologically, immunoreactive type VII collagen helical-bundles resembled the gnarled-pattern of enamel rods detected by Coomassie Blue staining. Western blotting of whole crown or enamel matrix extracts also identified characteristic Mr=280 and 230 kDa type VII dimeric forms, which resolved into 75 and 25 kDa bands upon reduction. As expected, the collagenous domain of type VII collagen was resistant to pepsin digestion, but was susceptible to purified bacterial collagenase. These results demonstrate the inner enamel organic matrix in mature teeth contains macromolecular type VII collagen. Based on its physical association with the DEJ and its well-appreciated capacity to complex with other collagens, we hypothesize that enamel embedded type VII collagen fibrils may contribute not only to the structural resilience of enamel, but may also play a role in bonding enamel to dentin. PMID:24594343

  20. Demonstration of resonant photopumping of Mo VII by Mo XII for a VUV laser near 600 {Angstrom}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ilcisin, K.J.; Aumayr, F.; Schwob, J.L.

    1993-09-01

    We present data of experiments on the resonant photopumping of Mo VII by Mo XII as a method of generating a coherent VUV source near 600 {angstrom}. The experiment is based on a scheme proposed by Feldman and Reader in which the 4p{sup 6} -- 4p{sup 5}6s transition in Mo VII in resonantly photopumped by the 5s {sup 2}S{sub 1/2} -- 4p {sup 2}P{sub 1/2} transition in Mo XII. Results of the laser produced plasma experiments show the successful enhancement of the population of the Mo VII 4p{sup 5}6s upper lasing level when pumped by an adjacent Mo VII plasma.more » No enhancement was seen in a control experiment where the Mo VII plasma was pumped by a Zr X plasma. Improvements of the intensity of the Mo XII pump source, achieved using an additional pump laser, lead to the generation of a population inversion for the VUV transition.« less

  1. Emission line spectra of S VII ? S XIV in the 20 ? 75 ? wavelength region

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lepson, J K; Beiersdorfer, P; Behar, E

    As part of a larger project to complete a comprehensive catalogue of astrophysically relevant emission lines in support of new-generation X-ray observatories using the Lawrence Livermore electron beam ion traps EBIT-I and EBIT-II, the authors present observations of sulfur lines in the soft X-ray and extreme ultraviolet regions. The database includes wavelength measurements with standard errors, relative intensities, and line assignments for 127 transitions of S VII through S XIV between 20 and 75 {angstrom}. The experimental data are complemented with a full set of calculations using the Hebrew University Lawrence Livermore Atomic Code (HULLAC). A comparison of the laboratorymore » data with Chandra measurements of Procyon allows them to identify S VII-S XI lines.« less

  2. Debates in English Teaching. The Debates in Subject Teaching Series

    ERIC Educational Resources Information Center

    Davison, Jon, Ed.; Daly, Caroline, Ed.; Moss, John, Ed.

    2012-01-01

    "Debates in English Teaching" explores the major issues all English teachers encounter in their daily professional lives. It engages with established and contemporary debates, promotes and supports critical reflection and aims to stimulate both novice and experienced teachers to reach informed judgements and argue their point of view with deeper…

  3. Debates in Religious Education. The Debates in Subject Teaching Series

    ERIC Educational Resources Information Center

    Barnes, L. Philip, Ed.

    2011-01-01

    What are the key debates in Religious Education teaching today? "Debates in Religious Education" explores the major issues all RE teachers encounter in their daily professional lives. It encourages critical reflection and aims to stimulate both novice and experienced teachers to think more deeply about their practice, and link research…

  4. Prophylactic Level VII Nodal Dissection as a Prognostic Factor in Papillary Thyroid Carcinoma: a Pilot Study of 27 Patients.

    PubMed

    Fayek, Ihab Samy

    2015-01-01

    Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinoma has been highlighted. A total of 27 patients with papillary thyroid carcinoma with N0 neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision. Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separate and independent prognostic factors for DFS at 24 months. 21 females and 6 males with a mean age of 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7), bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) and level VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-up from 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at 24 months was 87.8% and was significantly affected in relation to bilaterality (p-value<0.001), extrathyroidal extension (p-value<0.001), level VI positive ((p-value<0.001) and level VII positive ((p-value<0.001) LNs. No recurrences were detected during the follow-up period in the absence of level VI and level VII nodal involvement. Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillary thyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessity and safety of this approach.

  5. Neurobiology of emotions: an update.

    PubMed

    Esperidião-Antonio, Vanderson; Majeski-Colombo, Marilia; Toledo-Monteverde, Diana; Moraes-Martins, Glaciele; Fernandes, Juliana José; Bauchiglioni de Assis, Marjorie; Montenegro, Stefânia; Siqueira-Batista, Rodrigo

    2017-06-01

    The 'nature' of emotions is one of the archaic themes of Western thought, thematized in different cultural manifestations - such as art, science, philosophy, myths and religion -, since Ancient times. In the last decades, the advances in neurosciences have permitted the construction of hypotheses that explain emotions, especially through the studies involving the limbic system. To present an updated discussion about the neurobiology of processes relating to emotions - focusing (1) on the main neural structures that relate to emotions, (2) the paths and circuits of greater relevance, (3) the implicated neurotransmitters, (4) the connections that possess neurovegetative control and (5) the discussion about the main emotions - is the objective of this present article.

  6. Similarities and Differences in Neurobiology.

    PubMed

    Chen, Manli; Sun, Yan; Lu, Lin; Shi, Jie

    2017-01-01

    Substance addiction is a chronic, relapsing brain disease characterized by compulsive drug seeking and use despite harmful consequences. Non-substance addiction is defined recently that people may compulsively engage in an activity despite any negative consequences to their lives. Despite differences with respect to their addictive object, substance addiction and non-substance addiction may share similarities with respect to biological, epidemiological, clinical, genetic and other features. Here we review the similarities and differences in neurobiology between these two addictions with a focus on dopamine, serotonin, opioid, glutamate and norepinephrine systems. Studies suggest the involvement of all these systems in both substance addiction and non-substance addiction while differences may exist with respect to their contributions.

  7. The adenovirus major core protein VII is dispensable for virion assembly but is essential for lytic infection

    PubMed Central

    Suomalainen, Maarit; Zheng, Yueting; Boucke, Karin

    2017-01-01

    The Adenovirus (Ad) genome within the capsid is tightly associated with a virus-encoded, histone-like core protein—protein VII. Two other Ad core proteins, V and X/μ, also are located within the virion and are loosely associated with viral DNA. Core protein VII remains associated with the Ad genome during the early phase of infection. It is not known if naked Ad DNA is packaged into the capsid, as with dsDNA bacteriophage and herpesviruses, followed by the encapsidation of viral core proteins, or if a unique packaging mechanism exists with Ad where a DNA-protein complex is simultaneously packaged into the virion. The latter model would require an entirely new molecular mechanism for packaging compared to known viral packaging motors. We characterized a virus with a conditional knockout of core protein VII. Remarkably, virus particles were assembled efficiently in the absence of protein VII. No changes in protein composition were evident with VII−virus particles, including the abundance of core protein V, but changes in the proteolytic processing of some capsid proteins were evident. Virus particles that lack protein VII enter the cell, but incoming virions did not escape efficiently from endosomes. This greatly diminished all subsequent aspects of the infectious cycle. These results reveal that the Ad major core protein VII is not required to condense viral DNA within the capsid, but rather plays an unexpected role during virus maturation and the early stages of infection. These results establish a new paradigm pertaining to the Ad assembly mechanism and reveal a new and important role of protein VII in early stages of infection. PMID:28628648

  8. Neurobiological signatures associated with alcohol and drug use in the human adolescent brain

    PubMed Central

    Silveri, Marisa M.; Dager, Alecia D.; Cohen-Gilbert, Julia E.; Sneider, Jennifer T.

    2017-01-01

    Magnetic resonance (MR) techniques provide opportunities to non-invasively characterize neurobiological milestones of adolescent brain development. Juxtaposed to the critical finalization of brain development is initiation of alcohol and substance use, and increased frequency and quantity of use, patterns that can lead to abuse and addiction. This review provides a comprehensive overview of existing MR studies of adolescent alcohol and drug users. The most common alteration reported across substance used and MR modalities is in the frontal lobe (63% of published studies). This is not surprising, given that this is the last region to reach neurobiological adulthood. Comparatively, evidence is less consistent regarding alterations in regions that mature earlier (e.g., amygdala, hippocampus), however newer techniques now permit investigations beyond regional approaches that are uncovering network-level vulnerabilities. Regardless of whether neurobiological signatures exist prior to the initiation of use, this body of work provides important direction for ongoing prospective investigations of adolescent brain development, and the significant impact of alcohol and substance use on the brain during the second decade of life. PMID:27377691

  9. Neurobiological signatures associated with alcohol and drug use in the human adolescent brain.

    PubMed

    Silveri, Marisa M; Dager, Alecia D; Cohen-Gilbert, Julia E; Sneider, Jennifer T

    2016-11-01

    Magnetic resonance (MR) techniques provide opportunities to non-invasively characterize neurobiological milestones of adolescent brain development. Juxtaposed to the critical finalization of brain development is initiation of alcohol and substance use, and increased frequency and quantity of use, patterns that can lead to abuse and addiction. This review provides a comprehensive overview of existing MR studies of adolescent alcohol and drug users. The most common alterations reported across substance used and MR modalities are in the frontal lobe (63% of published studies). This is not surprising, given that this is the last region to reach neurobiological adulthood. Comparatively, evidence is less consistent regarding alterations in regions that mature earlier (e.g., amygdala, hippocampus), however newer techniques now permit investigations beyond regional approaches that are uncovering network-level vulnerabilities. Regardless of whether neurobiological signatures exist prior to the initiation of use, this body of work provides important direction for ongoing prospective investigations of adolescent brain development, and the significant impact of alcohol and substance use on the brain during the second decade of life. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Effective treatment of chemoresistant breast cancer in vitro and in vivo by a factor VII-targeted photodynamic therapy.

    PubMed

    Duanmu, J; Cheng, J; Xu, J; Booth, C J; Hu, Z

    2011-04-26

    The purpose of this study was to test a novel, dual tumour vascular endothelial cell (VEC)- and tumour cell-targeting factor VII-targeted Sn(IV) chlorin e6 photodynamic therapy (fVII-tPDT) by targeting a receptor tissue factor (TF) as an alternative treatment for chemoresistant breast cancer using a multidrug resistant (MDR) breast cancer line MCF-7/MDR. The TF expression by the MCF-7/MDR breast cancer cells and tumour VECs in MCF-7/MDR tumours from mice was determined separately by flow cytometry and immunohistochemistry using anti-human or anti-murine TF antibodies. The efficacy of fVII-tPDT was tested in vitro and in vivo and was compared with non-targeted PDT for treatment of chemoresistant breast cancer. The in vitro efficacy was determined by a non-clonogenic assay using crystal violet staining for monolayers, and apoptosis and necrosis were assayed to elucidate the underlying mechanisms. The in vivo efficacy of fVII-tPDT was determined in a nude mouse model of subcutaneous MCF-7/MDR tumour xenograft by measuring tumour volume. To our knowledge, this is the first presentation showing that TF was expressed on tumour VECs in chemoresistant breast tumours from mice. The in vitro efficacy of fVII-tPDT was 12-fold stronger than that of ntPDT for MCF-7/MDR cancer cells, and the mechanism of action involved induction of apoptosis and necrosis. Moreover, fVII-tPDT was effective and safe for the treatment of chemoresistant breast tumours in the nude mouse model. We conclude that fVII-tPDT is effective and safe for the treatment of chemoresistant breast cancer, presumably by simultaneously targeting both the tumour neovasculature and chemoresistant cancer cells. Thus, this dual-targeting fVII-tPDT could also have therapeutic potential for the treatment of other chemoresistant cancers.

  11. Debates in Citizenship Education. The Debates in Subject Teaching Series

    ERIC Educational Resources Information Center

    Arthur, James, Ed.; Cremin, Hilary, Ed.

    2011-01-01

    What are the key issues in Citizenship Education today? "Debates in Citizenship Education" encourages student and practising teachers to engage with and reflect on some of the key topics, concepts and debates that they will have to address throughout their career. It places the specialist field of Citizenship Education in a wider context…

  12. Antimicrobial peptide scolopendrasin VII, derived from the centipede Scolopendra subspinipes mutilans, stimulates macrophage chemotaxis via formyl peptide receptor 1

    PubMed Central

    Park, Yoo Jung; Lee, Ha Young; Jung, Young Su; Park, Joon Seong; Hwang, Jae Sam; Bae, Yoe-Sik

    2015-01-01

    In this study, we report that one of the antimicrobial peptides scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates actin polymerization and the subsequent chemotactic migration of macrophages through the activation of ERK and protein kinase B (Akt) activity. The scolopendrasin VII-induced chemotactic migration of macrophages is inhibited by the formyl peptide receptor 1 (FPR1) antagonist cyclosporine H. We also found that scolopendrasin VII stimulate the chemotactic migration of FPR1-transfected RBL-2H3 cells, but not that of vector-transfected cells; moreover, scolopendrasin VII directly binds to FPR1. Our findings therefore suggest that the antimicrobial peptide scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates macrophages, resulting in chemotactic migration via FPR1 signaling, and the peptide can be useful in the study of FPR1-related biological responses. [BMB Reports 2015; 48(8): 479-484] PMID:26129676

  13. "Et in Amygdala Ego"?: UG, (S)LA, and Neurobiology.

    ERIC Educational Resources Information Center

    Eubank, Lynn; Gregg, Kevin R.

    1995-01-01

    John Schumann and colleagues have argued for a neurobiological perspective on language acquisition that denies a role for a specifically linguistic mental module of the sort proposed by, for example, N. Chomsky (1986). This report challenges this perspective by offering evidence that such a mental module must be involved in the acquisition of…

  14. Sex Influences on the Neurobiology of Learning and Memory

    ERIC Educational Resources Information Center

    Andreano, Joseph M.; Cahill, Larry

    2009-01-01

    In essentially every domain of neuroscience, the generally implicit assumption that few, if any, meaningful differences exist between male and female brain function is being challenged. Here we address how this development is influencing studies of the neurobiology of learning and memory. While it has been commonly held that males show an…

  15. Contactins in the neurobiology of autism.

    PubMed

    Zuko, Amila; Kleijer, Kristel T E; Oguro-Ando, Asami; Kas, Martien J H; van Daalen, Emma; van der Zwaag, Bert; Burbach, J Peter H

    2013-11-05

    Autism is a disease of brain plasticity. Inspiring work of Willem Hendrik Gispen on neuronal plasticity has stimulated us to investigate gene defects in autism and the consequences for brain development. The central process in the pathogenesis of autism is local dendritic mRNA translation which is dependent on axodendritic communication. Hence, most autism-related gene products (i) are part of the protein synthesis machinery itself, (ii) are components of the mTOR signal transduction pathway, or (iii) shape synaptic activity and plasticity. Accordingly, prototype drugs have been recognized that interfere with these pathways. The contactin (CNTN) family of Ig cell adhesion molecules (IgCAMs) harbours at least three members that have genetically been implicated in autism: CNTN4, CNTN5, and CNTN6. In this chapter we review the genetic and neurobiological data underpinning their role in normal and abnormal development of brain systems, and the consequences for behavior. Although data on each of these CNTNs are far from complete, we tentatively conclude that these three contactins play roles in brain development in a critical phase of establishing brain systems and their plasticity. They modulate neuronal activities, such as neurite outgrowth, synaptogenesis, survival, guidance of projections and terminal branching of axons in forming neural circuits. Current research on these CNTNs concentrate on the neurobiological mechanism of their developmental functions. A future task will be to establish if proposed pharmacological strategies to counteract ASD-related symptomes can also be applied to reversal of phenotypes caused by genetic defects in these CNTN genes. © 2013 Elsevier B.V. All rights reserved.

  16. Vitalism and the Darwin Debate

    ERIC Educational Resources Information Center

    Henderson, James

    2012-01-01

    There are currently both scientific and public debates surrounding Darwinism. In the scientific debate, the details of evolution are in dispute, but not the central thesis of Darwin's theory; in the public debate, Darwinism itself is questioned. I concentrate on the public debate because of its direct impact on education in the United States. Some…

  17. ADRPM-VII applied to the long-range acoustic detection problem

    NASA Technical Reports Server (NTRS)

    Shalis, Edward; Koenig, Gerald

    1990-01-01

    An acoustic detection range prediction model (ADRPM-VII) has been written for IBM PC/AT machines running on the MS-DOS operating system. The software allows the user to predict detection distances of ground combat vehicles and their associated targets when they are involved in quasi-military settings. The program can also calculate individual attenuation losses due to spherical spreading, atmospheric absorption, ground reflection and atmospheric refraction due to temperature and wind gradients while varying parameters effecting the source-receiver problem. The purpose here is to examine the strengths and limitations of ADRPM-VII by modeling the losses due to atmospheric refraction and ground absorption, commonly known as excess attenuation, when applied to the long range detection problem for distances greater than 3 kilometers.

  18. Evaluation of off-label recombinant activated factor VII for multiple indications in children.

    PubMed

    Reiter, Pamela D; Valuck, Robert J; Taylor, Ruston S

    2007-07-01

    Despite a paucity of safety and efficacy data, the use of recombinant activated factor VII in children for off-label indications has now surpassed its use in hemophilia. A retrospective chart review was conducted of 46 subjects (age, 6.7 +/- 6 years; weight, 26 +/- 20 kg) who received recombinant activated factor VII for nonhemophiliac indications between January 1, 2004, and September 1, 2005. Indications for use included prevention (n = 6) or treatment (n = 40) of bleeding due to general surgery, hepatic failure, gastrointestinal bleeding, severe traumatic brain injury, bone marrow transplant, cardiac, acetaminophen overdose, and multiorgan system failure. Decreases in prothrombin time, partial thromboplastin time, and international normalized ratio were observed. No inappropriate thrombotic events were noted. Administration of recombinant activated factor VII was associated with a reduction in coagulation markers without obvious adverse thrombotic events at cost of $4189 per dose. These findings should be confirmed in a prospective trial.

  19. The neurobiological impact of postpartum maternal depression: prevention and intervention approaches

    PubMed Central

    Scaramella, Laura; Zeanah, Charles H.

    2016-01-01

    The lasting negative impact of postpartum depression (PPD) on offspring is well established. PDD appears to impact neurobiological pathways linked to socio-emotional regulation, cognitive and executive function, and physiologic stress response systems, systems also associated with toxic stress and negative health trajectories across the life course. Perinatal depression is expected to have significant consequences for offspring given the shared biological processes during pregnancy and the subsequent primacy of the early maternal-child relationship in shaping the child’s neurobiological development. A substantial body of literature has examined prevention and intervention efforts during the prenatal period, including the challenges associated with the medication use during pregnancy. 1,2 Recognizing the expansive nature of the existing literature, this review take a novel focus, specifically examining the current state of research defining the effect of universal, selected and indicated interventions for PDD on infant neurodevelopment. This focus was selected because of the unique nature of this time-period for the interaction of maternal psychopathology and infant development, acknowledging that both prenatal and parental depression at later developmental times points can influence child outcomes. We begin by providing a general overview of PPD and the rapid neurodevelopmental changes occurring during the first years of life. Building upon this foundation, we then discuss the specific evidence linking postpartum depression to neurobiological consequences in the offspring. We focus on the development of neural pathways with established associations those aspects of maternal caregiving most impacted by depression, including feeding and nutrition, sleep, health monitoring, play and language, and maternal sensitivity and engagement. Lastly, we discuss specific evidence related to the efficacy of current PPD efforts on infant neurobiological outcomes, highlighting

  20. Neurobiology of autism gene products: towards pathogenesis and drug targets.

    PubMed

    Kleijer, Kristel T E; Schmeisser, Michael J; Krueger, Dilja D; Boeckers, Tobias M; Scheiffele, Peter; Bourgeron, Thomas; Brose, Nils; Burbach, J Peter H

    2014-03-01

    The genetic heterogeneity of autism spectrum disorders (ASDs) is enormous, and the neurobiology of proteins encoded by genes associated with ASD is very diverse. Revealing the mechanisms on which different neurobiological pathways in ASD pathogenesis converge may lead to the identification of drug targets. The main objective is firstly to outline the main molecular networks and neuronal mechanisms in which ASD gene products participate and secondly to answer the question how these converge. Finally, we aim to pinpoint drug targets within these mechanisms. Literature review of the neurobiological properties of ASD gene products with a special focus on the developmental consequences of genetic defects and the possibility to reverse these by genetic or pharmacological interventions. The regulation of activity-dependent protein synthesis appears central in the pathogenesis of ASD. Through sequential consequences for axodendritic function, neuronal disabilities arise expressed as behavioral abnormalities and autistic symptoms in ASD patients. Several known ASD gene products have their effect on this central process by affecting protein synthesis intrinsically, e.g., through enhancing the mammalian target of rapamycin (mTOR) signal transduction pathway or through impairing synaptic function in general. These are interrelated processes and can be targeted by compounds from various directions: inhibition of protein synthesis through Lovastatin, mTOR inhibition using rapamycin, or mGluR-related modulation of synaptic activity. ASD gene products may all feed into a central process of translational control that is important for adequate glutamatergic regulation of dendritic properties. This process can be modulated by available compounds but may also be targeted by yet unexplored routes.

  1. Neurobiological Basis of Individual Variation in Stimulus-Reward Learning.

    PubMed

    Flagel, Shelly B; Robinson, Terry E

    2017-02-01

    Cues in the environment can guide behavior in adaptive ways, leading one towards valuable resources such as food, water, or a potential mate. However, cues in the environment may also serve as powerful motivators that lead to maladaptive patterns of behavior, such as addiction. Importantly, and central to this article, there is considerable individual variation in the extent to which reward cues gain motivational control over behavior. Here we describe an animal model that captures this individual variation, allowing us to better understand the psychological and neurobiological processes that contribute to cue-evoked behaviors. When a discrete cue is paired with a food reward in a Pavlovian manner it acquires greater control over motivated behavior in some rats ("sign-trackers, STs) than in others ("goal-trackers", GTs). We review studies that have exploited this animal model to parse the neurobiological mechanisms involved in learning associations between stimuli vs. those involved in attributing incentive salience to those same stimuli. The latter seems to be dependent on dopamine and subcortical circuits, whereas the former may engage more cortical "top-down" mechanisms.

  2. Early Adverse Experiences and the Neurobiology of Facial Emotion Processing

    ERIC Educational Resources Information Center

    Moulson, Margaret C.; Fox, Nathan A.; Zeanah, Charles H.; Nelson, Charles A.

    2009-01-01

    To examine the neurobiological consequences of early institutionalization, the authors recorded event-related potentials (ERPs) from 3 groups of Romanian children--currently institutionalized, previously institutionalized but randomly assigned to foster care, and family-reared children--in response to pictures of happy, angry, fearful, and sad…

  3. Title VII Sexual Harassment Guidelines and Educational Employment [and] What Can Students Do About Sex Discrimination?

    ERIC Educational Resources Information Center

    Howard, Susan; And Others

    Guidelines concerning sexual harassment of employees at educational institutions under Title VII of the Civil Rights Act of 1964 are considered. November 1980 final interpretive guidelines issued by the Equal Employment Opportunity Commission state that Title VII prohibits sexual harassment of employees, that employers are responsible for the…

  4. A systematic review of the neurobiological underpinnings of borderline personality disorder (BPD) in childhood and adolescence.

    PubMed

    Winsper, Catherine; Marwaha, Steven; Lereya, Suzet Tanya; Thompson, Andrew; Eyden, Julie; Singh, Swaran P

    2016-12-01

    Contemporary theories for the aetiology of borderline personality disorder (BPD) take a lifespan approach asserting that inborn biological predisposition is potentiated across development by environmental risk factors. In this review, we present and critically evaluate evidence on the neurobiology of BPD in childhood and adolescence, compare this evidence to the adult literature, and contextualise within a neurodevelopmental framework. A systematic review was conducted to identify studies examining the neurobiological (i.e. genetic, structural neuroimaging, neurophysiological, and neuropsychological) correlates of BPD symptoms in children and adolescents aged 19 years or under. We identified, quality assessed, and narratively summarised 34 studies published between 1980 and June 2016. Similar to findings in adult populations, twin studies indicated moderate to high levels of heritability of BPD, and there was some evidence for gene-environment interactions. Also consistent with adult reports is that some adolescents with BPD demonstrated structural (grey and white matter) alterations in frontolimbic regions and neuropsychological abnormalities (i.e. reduced executive function and disturbances in social cognition). These findings suggest that neurobiological abnormalities observed in adult BPD may not solely be the consequence of chronic morbidity or prolonged medication use. They also provide tentative support for neurodevelopmental theories of BPD by demonstrating that neurobiological markers may be observed from childhood onwards and interact with environmental factors to increase risk of BPD in young populations. Prospective studies with a range of repeated measures are now required to elucidate the temporal unfurling of neurobiological features and further delineate the complex pathways to BPD.

  5. A rare combination: congenital factor VII deficiency with Chiari malformation.

    PubMed

    Bay, Ali; Aktekin, Elif; Erkutlu, Ibrahim

    2015-12-01

    Congenital factor (VII) deficiency is a rare bleeding disorder. We present a patient with congenital FVII deficiency and congenital hydrocephalus who underwent a ventriculoperitoneal shunt operation and needed no prophylaxis after the procedure.

  6. Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging

    PubMed Central

    O’Donovan, Aoife; Slavich, George M; Epel, Elissa S.; Neylan, Thomas C

    2015-01-01

    Anxiety disorders increase risk for the early development of several diseases of aging. Elevated inflammation, a common risk factor across diseases of aging, may play a key role in the relationship between anxiety and physical disease. However, the neurobiological mechanisms linking anxiety with elevated inflammation remain unclear. In this review, we present a neurobiological model of the mechanisms by which anxiety promotes inflammation. Specifically we propose that exaggerated neurobiological sensitivity to threat in anxious individuals may lead to sustained threat perception, which is accompanied by prolonged activation of threat-related neural circuitry and threat-responsive biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory response. Over time, this pattern of responding can promote chronic inflammation through structural and functional brain changes, altered sensitivity of immune cell receptors, dysregulation of the HPA axis and ANS, and accelerated cellular aging. Chronic inflammation, in turn, increases risk for diseases of aging. Exaggerated neurobiological sensitivity to threat may thus be a treatment target for reducing disease risk in anxious individuals. PMID:23127296

  7. Neurobiology of Inflammation-Associated Anorexia

    PubMed Central

    Gautron, Laurent; Layé, Sophie

    2009-01-01

    Compelling data demonstrate that inflammation-associated anorexia directly results from the action of pro-inflammatory factors, primarily cytokines and prostaglandins E2, on the nervous system. For instance, the aforementioned pro-inflammatory factors can stimulate the activity of peripheral sensory neurons, and induce their own de novo synthesis and release into the brain parenchyma and cerebrospinal fluid. Ultimately, it results in the mobilization of a specific neural circuit that shuts down appetite. The present article describes the different cell groups and neurotransmitters involved in inflammation-associated anorexia and examines how they interact with neural systems regulating feeding such as the melanocortin system. A better understanding of the neurobiological mechanisms underlying inflammation-associated anorexia will help to develop appetite stimulants for cancer and AIDS patients. PMID:20582290

  8. The Evidence for a Neurobiological Model of Childhood Antisocial Behavior

    ERIC Educational Resources Information Center

    van Goozen, Stephanie H. M.; Fairchild, Graeme; Snoek, Heddeke; Harold, Gordon T.

    2007-01-01

    Children with persistent antisocial and aggressive behavior are diagnosed as having disruptive behavior disorder. The authors review evidence that antisocial children, and especially those who persist with this behavior as they grow older, have a range of neurobiological characteristics. It is argued that serotonergic functioning and…

  9. Investigating the air oxidation of V(II) ions in a vanadium redox flow battery

    NASA Astrophysics Data System (ADS)

    Ngamsai, Kittima; Arpornwichanop, Amornchai

    2015-11-01

    The air oxidation of vanadium (V(II)) ions in a negative electrolyte reservoir is a major side reaction in a vanadium redox flow battery (VRB), which leads to electrolyte imbalance and self-discharge of the system during long-term operation. In this study, an 80% charged negative electrolyte solution is employed to investigate the mechanism and influential factors of the reaction in a negative-electrolyte reservoir. The results show that the air oxidation of V(II) ions occurs at the air-electrolyte solution interface area and leads to a concentration gradient of vanadium ions in the electrolyte solution and to the diffusion of V(II) and V(III) ions. The effect of the ratio of the electrolyte volume to the air-electrolyte solution interface area and the concentrations of vanadium and sulfuric acid in an electrolyte solution is investigated. A higher ratio of electrolyte volume to the air-electrolyte solution interface area results in a slower oxidation reaction rate. The high concentrations of vanadium and sulfuric acid solution also retard the air oxidation of V(II) ions. This information can be utilized to design an appropriate electrolyte reservoir for the VRB system and to prepare suitable ingredients for the electrolyte solution.

  10. An interpersonal neurobiological-informed treatment model for childhood traumatic grief.

    PubMed

    Crenshaw, David A

    This article expands an earlier model of the tasks of grieving (1990, [1995], [2001]) by building on science based findings derived from research in attachment theory, neuroscience, interpersonal neurobiology, and childhood traumatic grief (CTG). The proposed treatment model is a prescriptive approach that spells out specific tasks to be undertaken by children suffering traumatic grief under the direction of a therapist who is trained in trauma-informed therapy approaches and draws heavily on the empirically derived childhood traumatic grief treatment model developed by Cohen and Mannarino (2004; Cohen, Mannarino, & Deblinger, 2006). This model expands on their work by proposing specific tasks that are informed by attachment theory research and the interpersonal neurobiological research (Schore, 2003a, 2003b; Siegel, 1999). Particular emphasis is placed on developing a coherent and meaningful narrative since this has been found as a crucial factor in recovery from trauma in attachment research (Siegel, 1999; Siegel & Hartzell, 2003).

  11. Turning Back the Title VII Clock: The Resegregation of the American Work Force through Validity Generalization.

    ERIC Educational Resources Information Center

    Goldstein, Barry L.; Patterson, Patrick O.

    1988-01-01

    Refers to Title VII of the Civil Rights Act of 1964 and the Supreme Court's disparate impact interpretation of Title VII in Griggs versus Duke Power Company. Contends that attacks on the Griggs decision are legally unsound and that claims made by advocates of validity generalization are scientifically unsupported. (Author/NB)

  12. Survey of Land-Grant Colleges and Universities. Bulletin, 1930, No. 9. Volume II. [Part VII - Index

    ERIC Educational Resources Information Center

    Office of Education, United States Department of the Interior, 1930

    1930-01-01

    The attached document covers the concluding sections of the second volume of the Survey of Land-Grant Colleges and Universities: Part VII through the index. Part VII, Extension services, is divided into the following sections: (1) Introduction; (2) Position and objectives of Smith-Lever cooperative extension; (3) Administrative organization of…

  13. Title VII funding is associated with more family physicians and more physicians serving the underserved.

    PubMed

    Meyers, D; Fryer, G E; Krol, D; Phillips, R L; Green, L A; Dovey, S M

    2002-08-15

    Title VII funding of departments of family medicine at U.S. medical schools is significantly associated with expansion of the primary care physician workforce and increased accessibility to physicians for the residents of rural and underserved areas. Title VII has been successful in achieving its stated goals and has had an important role in addressing U.S. physician workforce policy issues.

  14. Composition, apparatus, and process, for sorption of gaseous compounds of group II-VII elements

    DOEpatents

    Tom, Glenn M.; McManus, James V.; Luxon, Bruce A.

    1991-08-06

    Scavenger compositions are disclosed, which have utility for effecting the sorptive removal of hazardous gases containing Group II-VII elements of the Periodic Table, such as are widely encountered in the manufacture of semiconducting materials and semiconductor devices. Gas sorption processes including the contacting of Group II-VII gaseous compounds with such scavenger compositions are likewise disclosed, together with critical space velocity contacting conditions pertaining thereto. Further described are gas contacting apparatus, including mesh structures which may be deployed in gas contacting vessels containing such scavenger compositions, to prevent solids from being introduced to or discharged from the contacting vessel in the gas stream undergoing treatment. A reticulate heat transfer structure also is disclosed, for dampening localized exothermic reaction fronts when gas mixtures comprising Group II-VII constituents are contacted with the scavenger compositions in bulk sorption contacting vessels according to the invention.

  15. 77 FR 14516 - Lock+ Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-12

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 14339-000] Lock+ Hydro Friends Fund VII; Notice of Preliminary Permit Application Accepted for Filing and Soliciting Comments, Motions To Intervene, and Competing Applications On December 22, 2011, Lock+ Hydro Friends Fund VII filed...

  16. Debating Race, Race-ing Debate: An Extended Ethnographic Case Study of Black Intellectual Insurgency in U.S. Intercollegiate Debate

    ERIC Educational Resources Information Center

    Peterson, David Kent

    2014-01-01

    The following study is an extended ethnographic case study of a "black intellectual insurgency" within the predominantly white space of the U.S. intercollegiate policy debate activity. A growing number of black students are entering the debate activity and insisting that "whiteness" be confronted and interrogated and that…

  17. Experimental medicine in drug addiction: towards behavioral, cognitive and neurobiological biomarkers.

    PubMed

    Duka, Theodora; Crombag, Hans S; Stephens, David N

    2011-09-01

    Several theoretical frameworks have been developed to understand putative processes and mechanisms involved in addiction. Whilst these 'theories of addiction' disagree about importance and/or nature of a number of key psychological processes (e.g. the necessity of craving and/or the involvement of drug-value representations), a number of commonalities exist. For instance, it is widely accepted that Pavlovian associations between cues and environmental contexts and the drug effects acquired over the course of addiction play a critical role, especially in relapse vulnerability in detoxified addicts. Additionally, all theories of addiction (explicitly or implicitly) propose that chronic drug exposure produces persistent neuroplastic changes in neurobiological circuitries underlying critical emotional, cognitive and motivational processes, although disagreement exists as to the precise nature of these neurobiological changes and/or their psychological consequences. The present review, rather than limiting itself to any particular theoretical stance, considers various candidate psychological, neurobiological and/or behavioral processes in addiction and outlines conceptual and procedural approaches for the experimental medicine laboratory. The review discusses (1) extinction, renewal and (re)consolidation of learned associations between cues and drugs, (2) the drug reward value, (3) motivational states contributing to drug seeking and (4) reflective (top-down) and sensory (bottom-up) driven decision-making. In evaluating these psychological and/or behavioral processes and their relationship to addiction we make reference to putative underlying brain structures identified by basic animal studies and/or imaging studies with humans.

  18. Human Adenovirus Infection Causes Cellular E3 Ubiquitin Ligase MKRN1 Degradation Involving the Viral Core Protein pVII.

    PubMed

    Inturi, Raviteja; Mun, Kwangchol; Singethan, Katrin; Schreiner, Sabrina; Punga, Tanel

    2018-02-01

    Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein, VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII-interacting protein in HAdV-C5-infected cells. Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the late phase of HAdV-C5 infection in various human cell lines. MKRN1 protein degradation occurred independently of the HAdV E1B55K and E4orf6 proteins. We provide experimental evidence that the precursor pVII protein binding enhances MKRN1 self-ubiquitination, whereas the processed mature VII protein is deficient in this function. Based on these data, we propose that the pVII protein binding promotes MKRN1 self-ubiquitination, followed by proteasomal degradation of the MKRN1 protein, in HAdV-C5-infected cells. In addition, we show that measles virus and vesicular stomatitis virus infections reduce the MKRN1 protein accumulation in the recipient cells. Taken together, our results expand the functional repertoire of the HAdV-C5 precursor pVII protein in lytic virus infection and highlight MKRN1 as a potential common target during different virus infections. IMPORTANCE Human adenoviruses (HAdVs) are common pathogens causing a wide range of diseases. To achieve pathogenicity, HAdVs have to counteract a variety of host cell antiviral defense systems, which would otherwise hamper virus replication. In this study, we show that the HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. This mutual interaction between the pVII and

  19. 25 CFR 36.22 - Standard VII-Elementary instructional program.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Standard VII-Elementary instructional program. 36.22 Section 36.22 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY SITUATIONS Minimum...

  20. 25 CFR 36.22 - Standard VII-Elementary instructional program.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Standard VII-Elementary instructional program. 36.22 Section 36.22 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY SITUATIONS Minimum...

  1. 25 CFR 36.22 - Standard VII-Elementary instructional program.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Standard VII-Elementary instructional program. 36.22 Section 36.22 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY SITUATIONS Minimum...

  2. Synthesis and characterization of (18)F-labeled active site inhibited factor VII (ASIS).

    PubMed

    Erlandsson, Maria; Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Jesper B; Petersen, Lars C; Madsen, Jacob; Kjaer, Andreas

    2015-05-15

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an (18)F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[(18)F]fluorobenzoate, and the [(18)F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [(18)F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [(18)F]ASIS and ASIS could be detected. Furthermore, [(18)F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [(18)F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [(18)F]ASIS are in progress. Copyright © 2015 John Wiley & Sons, Ltd.

  3. a New ENDF/B-VII.0 Based Multigroup Cross-Section Library for Reactor Dosimetry

    NASA Astrophysics Data System (ADS)

    Alpan, F. A.; Anderson, S. L.

    2009-08-01

    The latest of the ENDF/B libraries, ENDF/B-VII.0 was released in December 2006. In this paper, the ENDF/B-VII.O evaluations were used in generating a new coupled neutron/gamma multigroup library having the same group structure of VITAMIN-B6, i.e., the 199-neutron, 42-gamma group library. The new library was generated utilizing NJOY99.259 for pre-processing and the AMPX modules for post-processing of cross sections. An ENDF/B-VI.3 based VITAMIN-B6-like library was also generated. The fine-group libraries and the ENDF/B-VI.3 based 47-neutron, 20-gamma group BUGLE-96 library were used with the discrete ordinates code DORT to obtain a three-dimensional synthesized flux distribution from r, r-θ, and r-z models for a standard Westinghouse 3-loop design reactor. Reaction rates were calculated for ex-vessel neutron dosimetry containing 63Cu(n,α)60Co, 46Ti(n,p)46Sc, 54Fe(n,P)54Mn, 58Ni(n,P)58Co, 238U(n,f)137Cs, 237Np(n,f)137Cs, and 59Co(n,γ)60Co (bare and cadmium covered) reactions. Results were compared to measurements. In comparing the 199-neutron, 42-gamma group ENDF/B-VI.3 and ENDF/B-VII.O libraries, it was observed that the ENDF/B-VI.3 based library results were in better agreement with measurements. There is a maximum difference of 7% (for the 63Cu(n,α)60Co reaction rate calculation) between ENDF/B-VI.3 and ENDF/B-VII.O. Differences between ENDF/B-VI.3 and ENDF/B-VII.O libraries are due to 16O, 1H, 90Zr, 91Zr, 92Zr, 238U, and 239Pu evaluations. Both ENDF/B-VI.3 and ENDF/B-VII.O library calculated reaction rates are within 20% of measurement and meet the criterion specified in the U. S. Nuclear Regulatory Commission Regulatory Guide 1.190, "Calculational and Dosimetry Methods for Determining Pressure Vessel Neutron Fluence."

  4. Adenovirus core protein VII contains distinct sequences that mediate targeting to the nucleus and nucleolus, and colocalization with human chromosomes.

    PubMed

    Lee, Tim W R; Blair, G Eric; Matthews, David A

    2003-12-01

    During adenovirus infection, following capsid dissociation, core protein VII enters the host cell nucleus complexed with adenovirus DNA. In order to determine whether protein VII may have an active role in this nuclear import, regions of the preVII gene were amplified by PCR, and further oligonucleotide mutants were designed with site-directed mutation of codons for the basic amino acids arginine and lysine. Fragments were cloned into a mammalian expression plasmid to express the peptides as N-terminal fusions to enhanced green fluorescent protein. Results demonstrate that preVII protein contains both nuclear and nucleolar targeting sequences. Such signals may be important in the delivery of adenovirus DNA to the host cell nucleus during adenovirus infection. Furthermore, the data suggest that protein VII may bind to human chromosomes by means of two distinct domains, one sharing homology with the N-terminal regulatory tail of histone H3.

  5. Evolutionary neurobiology and aesthetics.

    PubMed

    Smith, Christopher Upham

    2005-01-01

    If aesthetics is a human universal, it should have a neurobiological basis. Although use of all the senses is, as Aristotle noted, pleasurable, the distance senses are primarily involved in aesthetics. The aesthetic response emerges from the central processing of sensory input. This occurs very rapidly, beneath the level of consciousness, and only the feeling of pleasure emerges into the conscious mind. This is exemplified by landscape appreciation, where it is suggested that a computation built into the nervous system during Paleolithic hunter-gathering is at work. Another inbuilt computation leading to an aesthetic response is the part-whole relationship. This, it is argued, may be traced to the predator-prey "arms races" of evolutionary history. Mate selection also may be responsible for part of our response to landscape and visual art. Aesthetics lies at the core of human mentality, and its study is consequently of importance not only to philosophers and art critics but also to neurobiologists.

  6. 76 FR 24471 - Qualified Hydro 26, LLC; Lock+ Hydro Friends Fund VII; Western Minnesota Municipal Power Agency...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-02

    ...; 14113-000] Qualified Hydro 26, LLC; Lock+ Hydro Friends Fund VII; Western Minnesota Municipal Power... Hydro), Lock+ Hydro Friends Fund VII (Hydro Friends) and Western Minnesota Municipal Power Agency (WMMPA... 02114; (978) 283-2822. Hydro Friends' proposed Lock and Dam 11 Hydropower Project No. 14112 would...

  7. Recordkeeping and reporting under Title VII and the ADA--EEOC. Final rule.

    PubMed

    1991-07-26

    This final rule is based on two separate Notices of Proposed Rulemaking (NPRM) published on February 13, 1989 (54 FR 6551), and March 5, 1991 (56 FR 9185). This final rule amends 29 CFR part 1602, EEOC's regulations on Recordkeeping and Reporting under title VII of the Civil Rights Act of 1964 (title VII), to add recordkeeping requirements under the Americans with Disabilities Act of 1990 (ADA). It increases the records retention period required in part 1602 for title VII and the ADA from 6 months to one year. The Commission also is adding a new subpart R to part 1602, 29 CFR 1602.56, that will clarify that the Commission has the authority to investigate persons to determine whether they comply with the reporting or recordkeeping requirements of part 1602. In addition, the Commission is making several minor changes to sections 1602.7 and 1602.10. The Commission also is deleting section 1602.14(b) of its title VII recordkeeping regulations, which provides that the section 1602 recordkeeping requirements do not apply to temporary or seasonal positions. Information regarding such employees now must be reported on Standard Form 100 on September 30 of each year, in the same fashion as information regarding permanent employees is reported. Similarly, the Commission is deleting sections 1627.3(b) and 1627.4(a)(2) of the Age Discrimination in Employment Act recordkeeping regulations, which provide for a 90-day retention period for temporary positions, and is clarifying the mandatory nature of such recordkeeping. The Commission is not issuing a final rule on proposed section 1602.57 at this time.

  8. Neurobiological factors as predictors of cognitive-behavioral therapy outcome in individuals with antisocial behavior: a review of the literature.

    PubMed

    Cornet, Liza J M; de Kogel, Catharina H; Nijman, Henk L I; Raine, Adrian; van der Laan, Peter H

    2014-11-01

    This review focuses on the predictive value of neurobiological factors in relation to cognitive-behavioral therapy outcome among individuals with antisocial behavior. Ten relevant studies were found. Although the literature on this topic is scarce and diverse, it appears that specific neurobiological characteristics, such as physiological arousal levels, can predict treatment outcome. The predictive value of neurobiological factors is important as it could give more insight into the causes of variability in treatment outcome among individuals with antisocial behavior. Furthermore, results can contribute to improvement in current treatment selection procedures and to the development of alternative treatment options. © The Author(s) 2013.

  9. Implications for neurobiological research of cognitive models of psychosis: a theoretical paper.

    PubMed

    Garety, Philippa A; Bebbington, Paul; Fowler, David; Freeman, Daniel; Kuipers, Elizabeth

    2007-10-01

    Cognitive models of the positive symptoms of psychosis specify the cognitive, social and emotional processes hypothesized to contribute to their occurrence and persistence, and propose that vulnerable individuals make characteristic appraisals that result in specific positive symptoms. We describe cognitive models of positive psychotic symptoms and use this as the basis of discussing recent relevant empirical investigations and reviews that integrate cognitive approaches into neurobiological frameworks. Evidence increasingly supports a number of the hypotheses proposed by cognitive models. These are that: psychosis is on a continuum; specific cognitive processes are risk factors for the transition from subclinical experiences to clinical disorder; social adversity and trauma are associated with psychosis and with negative emotional processes; and these emotional processes contribute to the occurrence and persistence of psychotic symptoms. There is also evidence that reasoning biases contribute to the occurrence of delusions. The benefits of incorporating cognitive processes into neurobiological research include more sophisticated, bidirectional and interactive causal models, the amplification of phenotypes in neurobiological investigations by including emotional processes, and the adoption of more specific clinical phenotypes. For example, there is potential value in studying gene x environment x cognition/emotion interactions. Cognitive models and their derived phenotypes constitute the missing link in the chain between genetic or acquired biological vulnerability, the social environment and the expression of individual positive symptoms.

  10. Neurobiology of food addiction and adolescent obesity prevention in low- and middle-income countries.

    PubMed

    Lee, Albert; Gibbs, Susannah E

    2013-02-01

    Adolescent obesity has become an increasingly urgent issue in low- and middle-income countries. Recent relevant advances include the application of the neurobiology of addiction to food addiction and obesity. The biochemistry of the etiology of obesity indicates the need for multilevel interventions that go beyond simple behavioral approaches. Additional research on the neurobiology of food addiction and adolescent obesity in low- and middle-income countries, as well as program evaluations that examine the biochemical effects of complex interventions, is urgently needed. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  11. Quantitative analysis of the synthesis and secretion of type VII collagen in cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked immunoassay.

    PubMed

    Amano, Satoshi; Ogura, Yuki; Akutsu, Nobuko; Nishiyama, Toshio

    2007-02-01

    Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor-beta1 (TGF-beta1). The synthesis of type VII collagen was elevated by TGF-beta1, platelet-derived growth factor, tumor necrosis factor-alpha, and interleukin-1beta, but not by TGF-alpha. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level.

  12. Neurobiologic Correlates of Attention and Memory Deficits Following Critical Illness in Early Life.

    PubMed

    Schiller, Raisa M; IJsselstijn, Hanneke; Madderom, Marlous J; Rietman, André B; Smits, Marion; van Heijst, Arno F J; Tibboel, Dick; White, Tonya; Muetzel, Ryan L

    2017-10-01

    Survivors of critical illness in early life are at risk of long-term-memory and attention impairments. However, their neurobiologic substrates remain largely unknown. A prospective follow-up study. Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands. Thirty-eight school-age (8-12 yr) survivors of neonatal extracorporeal membrane oxygenation and/or congenital diaphragmatic hernia with an intelligence quotient greater than or equal to 80 and a below average score (z score ≤ -1.5) on one or more memory tests. None. Intelligence, attention, memory, executive functioning, and visuospatial processing were assessed and compared with reference data. White matter microstructure and hippocampal volume were assessed using diffusion tensor imaging and structural MRI, respectively. Global fractional anisotropy was positively associated with selective attention (β = 0.53; p = 0.030) and sustained attention (β = 0.48; p = 0.018). Mean diffusivity in the left parahippocampal region of the cingulum was negatively associated with visuospatial memory, both immediate (β = -0.48; p = 0.030) and delayed recall (β = -0.47; p = 0.030). Mean diffusivity in the parahippocampal region of the cingulum was negatively associated with verbal memory delayed recall (left: β = -0.52, p = 0.021; right: β = -0.52, p = 0.021). Hippocampal volume was positively associated with verbal memory delayed recall (left: β = 0.44, p = 0.037; right: β = 0.67, p = 0.012). Extracorporeal membrane oxygenation treatment or extracorporeal membrane oxygenation type did not influence the structure-function relationships. Our findings indicate specific neurobiologic correlates of attention and memory deficits in school-age survivors of neonatal extracorporeal membrane oxygenation and congenital diaphragmatic hernia. A better understanding of the neurobiology following critical illness, both in early and in adult life, may lead to earlier identification of patients at risk for impaired

  13. What Artificial Grammar Learning Reveals about the Neurobiology of Syntax

    ERIC Educational Resources Information Center

    Petersson, Karl-Magnus; Folia, Vasiliki; Hagoort, Peter

    2012-01-01

    In this paper we examine the neurobiological correlates of syntax, the processing of structured sequences, by comparing FMRI results on artificial and natural language syntax. We discuss these and similar findings in the context of formal language and computability theory. We used a simple right-linear unification grammar in an implicit artificial…

  14. [BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF): NEUROBIOLOGY AND MARKER VALUE IN NEUROPSYCHIATRY].

    PubMed

    Levada, O A; Cherednichenko, N V

    2015-01-01

    In this review current publications about neurobiology and marker value of brain derived neurotrophic factor (BDNF) in neuropsychiatry are analyzed. It is shown that BDNF is an important member of the family of neurotrophins which widely represented in various structures of the CNS. In prenatal period BDNF is involved in all stages of neuronal networks formation, and in the postnatal period its main role is maintaining the normal brain architectonics, involvement in the processes of neurogenesis and realization of neuroprotective functions. BDNF plays an important role in learning and memory organization, food and motor behavior. BDNF brain expression decreases with age, as well as in degenerative and vascular dementias, affective, anxiety, and behavioral disorders. The reducing of BDNF serum, level reflects the decreasing of its cerebral expression and could be used as a neurobiological marker of these pathological processes but the rising of its concentration could indicate the therapy effectiveness.

  15. Neurobiologically based interventions for autism spectrum disorders-rationale and new directions.

    PubMed

    Poustka, Luise; Brandeis, Daniel; Hohmann, Sarah; Holtmann, Martin; Bölte, Sven; Banaschewski, Tobias

    2014-01-01

    Autism spectrum disorders (ASD) are heterogeneous, neurodevelopmental disorders with early onset, characterized by a triad of impairments in reciprocal interaction and communication as well as repetitive and restricted interests and activities. Though underlying causes still remain largely unknown, there is now evidence for abnormal growth trajectories in the early brain development in ASD during vulnerable periods and subsequent impairment of neuronal organization and differentiation of neuronal networks. A growing number of studies over the last 10 years support the efficacy of behaviorally based interventions in ASD for the improvement of social communication and behavioral functioning. In contrast, research on neurobiologically based therapies for ASD is still at its beginnings. In this article, we will provide a selective overview of novel interventions and trainings based on neurobiological principles. Directions and options for future research on treatment aiming at restoration of normal plasticity in disrupted brain circuits in ASD are discussed.

  16. Expanding the versatility of phage display I: efficient display of peptide-tags on protein VII of the filamentous phage.

    PubMed

    Løset, Geir Åge; Bogen, Bjarne; Sandlie, Inger

    2011-02-24

    Phage display is a platform for selection of specific binding molecules and this is a clear-cut motivation for increasing its performance. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII), or the minor coat protein III (pIII). Display on other coat proteins such as pVII allows for display of heterologous peptide sequences on the virions in addition to those displayed on pIII and pVIII. In addition, pVII display is an alternative to pIII or pVIII display. Here we demonstrate how standard pIII or pVIII display phagemids are complemented with a helper phage which supports production of virions that are tagged with octa FLAG, HIS(6) or AviTag on pVII. The periplasmic signal sequence required for pIII and pVIII display, and which has been added to pVII in earlier studies, is omitted altogether. Tagging on pVII is an important and very useful add-on feature to standard pIII and pVII display. Any phagemid bearing a protein of interest on either pIII or pVIII can be tagged with any of the tags depending simply on choice of helper phage. We show in this paper how such tags may be utilized for immobilization and separation as well as purification and detection of monoclonal and polyclonal phage populations.

  17. Administration of recombinant activated factor VII in the intensive care unit after complex cardiovascular surgery: clinical and economic outcomes.

    PubMed

    Uber, Walter E; Toole, John M; Stroud, Martha R; Haney, Jason S; Lazarchick, John; Crawford, Fred A; Ikonomidis, John S

    2011-06-01

    Refractory bleeding after complex cardiovascular surgery often leads to increased length of stay, cost, morbidity, and mortality. Recombinant activated factor VII administered in the intensive care unit can reduce bleeding, transfusion, and surgical re-exploration. We retrospectively compared factor VII administration in the intensive care unit with reoperation for refractory bleeding after complex cardiovascular surgery. From 1501 patients who underwent cardiovascular procedures between December 2003 and September 2007, 415 high-risk patients were identified. From this cohort, 24 patients were divided into 2 groups based on whether they either received factor VII in the intensive care unit (n = 12) or underwent reoperation (n = 12) for refractory bleeding. Preoperative and postoperative data were collected to compare efficacy, safety, and economic outcomes. In-hospital survival for both groups was 100%. Factor VII was comparable with reoperation in achieving hemostasis, with both groups demonstrating decreases in chest tube output and need for blood products. Freedom from reoperation was achieved in 75% of patients receiving factor VII, whereas reoperation was effective in achieving hemostasis alone in 83.3% of patients. Prothrombin time, international normalized ratio, and median operating room time were significantly less (P < .05) in patients who received factor VII. Both groups had no statistically significant differences in other efficacy, safety, or economic outcomes. Factor VII administration in the intensive care unit appears comparable with reoperation for refractory bleeding after complex cardiovascular surgical procedures and might represent an alternative to reoperation in selected patients. Future prospective, randomized controlled trials might further define its role. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  18. Evaluation of AAV-mediated Gene Therapy for Central Nervous System Disease in Canine Mucopolysaccharidosis VII

    PubMed Central

    Gurda, Brittney L; De Guilhem De Lataillade, Adrien; Bell, Peter; Zhu, Yanqing; Yu, Hongwei; Wang, Ping; Bagel, Jessica; Vite, Charles H; Sikora, Tracey; Hinderer, Christian; Calcedo, Roberto; Yox, Alexander D; Steet, Richard A; Ruane, Therese; O'Donnell, Patricia; Gao, Guangping; Wilson, James M; Casal, Margret; Ponder, Katherine P; Haskins, Mark E

    2016-01-01

    Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease arising from mutations in β-d-glucuronidase (GUSB), which results in glycosaminoglycan (GAG) accumulation and a variety of clinical manifestations including neurological disease. Herein, MPS VII dogs were injected intravenously (i.v.) and/or intrathecally (i.t.) via the cisterna magna with AAV9 or AAVrh10 vectors carrying the canine GUSB cDNA. Although i.v. injection alone at 3 days of age resulted in normal cerebrospinal fluid (CSF) GUSB activity, brain tissue homogenates had only ~1 to 6% normal GUSB activity and continued to have elevated GAG storage. In contrast, i.t. injection at 3 weeks of age resulted in CSF GUSB activity 44-fold normal while brain tissue homogenates had >100% normal GUSB activity and reduced GAGs compared with untreated dogs. Markers for secondary storage and inflammation were eliminated in i.t.-treated dogs and reduced in i.v.-treated dogs compared with untreated dogs. Given that i.t.-treated dogs expressed higher levels of GUSB in the CNS tissues compared to those treated i.v., we conclude that i.t. injection of AAV9 or AAVrh10 vectors is more effective than i.v. injection alone in the large animal model of MPS VII. PMID:26447927

  19. Evaluation of AAV-mediated Gene Therapy for Central Nervous System Disease in Canine Mucopolysaccharidosis VII.

    PubMed

    Gurda, Brittney L; De Guilhem De Lataillade, Adrien; Bell, Peter; Zhu, Yanqing; Yu, Hongwei; Wang, Ping; Bagel, Jessica; Vite, Charles H; Sikora, Tracey; Hinderer, Christian; Calcedo, Roberto; Yox, Alexander D; Steet, Richard A; Ruane, Therese; O'Donnell, Patricia; Gao, Guangping; Wilson, James M; Casal, Margret; Ponder, Katherine P; Haskins, Mark E

    2016-02-01

    Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease arising from mutations in β-d-glucuronidase (GUSB), which results in glycosaminoglycan (GAG) accumulation and a variety of clinical manifestations including neurological disease. Herein, MPS VII dogs were injected intravenously (i.v.) and/or intrathecally (i.t.) via the cisterna magna with AAV9 or AAVrh10 vectors carrying the canine GUSB cDNA. Although i.v. injection alone at 3 days of age resulted in normal cerebrospinal fluid (CSF) GUSB activity, brain tissue homogenates had only ~1 to 6% normal GUSB activity and continued to have elevated GAG storage. In contrast, i.t. injection at 3 weeks of age resulted in CSF GUSB activity 44-fold normal while brain tissue homogenates had >100% normal GUSB activity and reduced GAGs compared with untreated dogs. Markers for secondary storage and inflammation were eliminated in i.t.-treated dogs and reduced in i.v.-treated dogs compared with untreated dogs. Given that i.t.-treated dogs expressed higher levels of GUSB in the CNS tissues compared to those treated i.v., we conclude that i.t. injection of AAV9 or AAVrh10 vectors is more effective than i.v. injection alone in the large animal model of MPS VII.

  20. The Clinical Neuroscience Course: Viewing Mental Health from Neurobiological Perspectives

    PubMed Central

    Lambert, Kelly G.

    2005-01-01

    Although the field of neuroscience is booming, a challenge for researchers in mental health disciplines is the integration of basic research findings into applied clinical approaches leading to effective therapies. Recently the National Institute of Mental Health called for translational research grants to encourage collaboration between neuroscientists and mental health professionals. In order for this “clinical neuroscience” to emerge and thrive, an important first step is the provision of appropriate course offerings so that future neuroscience researchers and mental health practitioners will have a common neurobiological base from which to make informed decisions about the most efficacious treatments for mental illnesses. Accordingly, an integrative course, Clinical Neuroscience, was developed to address these issues. After reviewing the historical origins of this emerging discipline, students are exposed to fundamental overviews of neuroanatomy, neurochemistry, and neural development before approaching the neurobiological components of several disorders (e.g., schizophrenia, depression, Tourette’s syndrome, drug abuse, obsessive compulsive disorder). Finally, the maintenance of mental health is emphasized as topics such as psychoneuroimmunology, coping with stress, and eating regulation are discussed. Important themes emphasized in this course include (1) the consideration of only empirically based evidence, (2) the view that mental illness represents a disruption of neurobiological homeostasis, (3) the acknowledgement that, because the brain is a plastic organ, the clinical relevance of environmental and behavioral influences is difficult to overestimate, and (4) the recognition of the value of ecologically relevant animal models in the investigation of various aspects of mental illness. Because of the importance of stress maintenance in mental health, exercises have been developed to increase students’ awareness of their own coping strategies

  1. The Central Role of Recognition in Auditory Perception: A Neurobiological Model

    ERIC Educational Resources Information Center

    McLachlan, Neil; Wilson, Sarah

    2010-01-01

    The model presents neurobiologically plausible accounts of sound recognition (including absolute pitch), neural plasticity involved in pitch, loudness and location information integration, and streaming and auditory recall. It is proposed that a cortical mechanism for sound identification modulates the spectrotemporal response fields of inferior…

  2. Analysis of time series for postal shipments in Regional VII East Java Indonesia

    NASA Astrophysics Data System (ADS)

    Kusrini, DE; Ulama, B. S. S.; Aridinanti, L.

    2018-03-01

    The change of number delivery goods through PT. Pos Regional VII East Java Indonesia indicates that the trend of increasing and decreasing the delivery of documents and non-documents in PT. Pos Regional VII East Java Indonesia is strongly influenced by conditions outside of PT. Pos Regional VII East Java Indonesia so that the prediction the number of document and non-documents requires a model that can accommodate it. Based on the time series plot monthly data fluctuations occur from 2013-2016 then the model is done using ARIMA or seasonal ARIMA and selected the best model based on the smallest AIC value. The results of data analysis about the number of shipments on each product sent through the Sub-Regional Postal Office VII East Java indicates that there are 5 post offices of 26 post offices entering the territory. The largest number of shipments is available on the PPB (Paket Pos Biasa is regular package shipment/non-document ) and SKH (Surat Kilat Khusus is Special Express Mail/document) products. The time series model generated is largely a Random walk model meaning that the number of shipment in the future is influenced by random effects that are difficult to predict. Some are AR and MA models, except for Express shipment products with Malang post office destination which has seasonal ARIMA model on lag 6 and 12. This means that the number of items in the following month is affected by the number of items in the previous 6 months.

  3. The Neurobiology of Bipolar Disorder: An Integrated Approach

    PubMed Central

    2016-01-01

    Bipolar disorder is a heterogeneous condition with myriad clinical manifestations and many comorbidities leading to severe disabilities in the biopsychosocial realm. The objective of this review article was to underline recent advances in knowledge regarding the neurobiology of bipolar disorder. A further aim was to draw attention to new therapeutic targets in the treatment of bipolar disorder. To accomplish these goals, an electronic search was undertaken of the PubMed database in August 2015 of literature published during the last 10 years on the pathophysiology of bipolar disorder. A wide-ranging evaluation of the existing work was done with search terms such as "mood disorders and biology," "bipolar disorder and HPA axis," "bipolar disorder and cytokines," "mood disorders and circadian rhythm," "bipolar disorder and oxidative stress," etc. This endeavor showed that bipolar disorder is a diverse condition sharing neurobiological mechanisms with major depressive disorder and psychotic spectrum disorders. There is convincing evidence of crosstalk between different biological systems that act in a deleterious manner causing expression of the disease in genetically predisposed individuals. Inflammatory mediators act in concert with oxidative stress to dysregulate hormonal, metabolic, and circadian homeostasis in precipitating and perpetuating the illness. Stress, whether biologically or psychologically mediated, is responsible for the initiation and progression of the diathesis. Bipolar spectrum disorders have a strong genetic component; severe life stresses acting through various paths cause the illness phenotype. PMID:26865997

  4. Neurobiological Adaptations to Violence across Development

    PubMed Central

    Mead, Hilary K.; Beauchaine, Theodore P.; Shannon, Katherine E.

    2009-01-01

    Adaptation to violent environments across development involves a multitude of cascading effects spanning many levels of analysis from genes to behavior. In this review, we (a) examine the potentiating effects of violence on genetic vulnerabilities and the functioning of neurotransmitter systems in producing both internalizing and externalizing psychopathology, (b) consider the impact of violence on the developing human stress and startle responses, and (c) brain development including the hippocampus and prefrontal cortex. This review integrates literature on the developmental effects of violence on rodents, non-human primates, and humans. Many neurobiological changes that are adaptive for survival in violent contexts become maladaptive in other environments, conferring life-long risk for psychopathology. PMID:20102643

  5. The neurobiology of the emotional adolescent: From the inside out

    PubMed Central

    Guyer, Amanda E.; Silk, Jennifer S.; Nelson, Eric E.

    2016-01-01

    Adolescents are commonly portrayed as highly emotional, with their behaviors often hijacked by their emotions. Research on the neural substrates of adolescent affective behavior is beginning to paint a more nuanced picture of how neurodevelopmental changes in brain function influence affective behavior, and how these influences are modulated by external factors in the environment. Recent neurodevelopmental models suggest that the brain is designed to promote emotion regulation, learning, and affiliation across development, and that affective behavior reciprocally interacts with age-specific social demands and different social contexts. In this review, we discuss current findings on neurobiological mechanisms of adolescents’ affective behavior and highlight individual differences in and social-contextual influences on adolescents’ emotionality. Neurobiological mechanisms of affective processes related to anxiety and depression are also discussed as examples. As the field progresses, it will be critical to test new hypotheses generated from the foundational empirical and conceptual work and to focus on identifying more precisely how and when neural networks change in ways that promote or thwart adaptive affective behavior during adolescence. PMID:27506384

  6. Neurobiology of cognitive remediation therapy for schizophrenia: a systematic review.

    PubMed

    Thorsen, Anders Lillevik; Johansson, Kyrre; Løberg, Else-Marie

    2014-01-01

    Cognitive impairment is an important aspect of schizophrenia, where cognitive remediation therapy (CRT) is a promising treatment for improving cognitive functioning. While neurobiological dysfunction in schizophrenia has been the target of much research, the neural substrate of cognitive remediation and recovery has not been thoroughly examined. The aim of the present article is to systematically review the evidence for neural changes after CRT for schizophrenia. The reviewed studies indicate that CRT affects several brain regions and circuits, including prefrontal, parietal, and limbic areas, both in terms of activity and structure. Changes in prefrontal areas are the most reported finding, fitting to previous evidence of dysfunction in this region. Two limitations of the current research are the few studies and the lack of knowledge on the mechanisms underlying neural and cognitive changes after treatment. Despite these limitations, the current evidence suggests that CRT is associated with both neurobiological and cognitive improvement. The evidence from these findings may shed light on both the neural substrate of cognitive impairment in schizophrenia, and how better treatment can be developed and applied.

  7. The Acid Rain Debate.

    ERIC Educational Resources Information Center

    Oates-Bockenstedt, Catherine

    1997-01-01

    Details an activity designed to motivate students by incorporating science-related issues into a classroom debate. Includes "The Acid Rain Bill" and "Position Guides" for student roles as committee members, consumers, governors, industry owners, tourism professionals, senators, and debate directors. (DKM)

  8. Schizophrenia and bipolar disorder: The road from similarities and clinical heterogeneity to neurobiological types.

    PubMed

    Dacquino, Claudia; De Rossi, Pietro; Spalletta, Gianfranco

    2015-09-20

    Although diagnosis is a central issue in medical care, in psychiatry its value is still controversial. The function of diagnosis is to indicate treatments and to help clinicians take better care of patients. The fundamental role of diagnosis is to predict outcome and prognosis. To date serious concern persists regarding the clinical utility and predictive validity of the diagnosis system in psychiatry, which is at the most syndromal. Schizophrenia and bipolar disorder, which nosologists consider two distinct disorders, are the most discussed psychiatric illnesses. Recent findings in different fields of psychiatric research, such as neuroimaging, neuropathology, neuroimmunology, neuropsychology and genetics, have led to other conceptualizations. Individuals with schizophrenia or bipolar disorder vary greatly with regard to symptoms, illness course, treatment response, cognitive and functional impairment and biological correlates. In fact, it is possible to find heterogeneous correlates even within the same syndrome, i.e., from one stage of the disorder to another. Thus, it is possible to identify different subsyndromes, which share some clinical and neurobiological characteristics. The main goal of modern psychiatry is to ovethrow these barriers and to obtain a better understanding of the biological profiles underlying heterogeneous clinical features and thus reduce the variance and lead to a homogeneous definition. The translational research model, which connects the basic neuroscience research field with clinical experience in psychiatry, aims to investigate different neurobiological features of syndromes and of the shared neurobiological features between two syndromes. In fact, this approach should help us to better understand the neurobiological pathways underlying clinical entities, and even to distinguish different, more homogeneous, diagnostic subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Vaccination against smoking: an annotated agenda for debate. A review of scientific journals, 2001-13.

    PubMed

    Wolters, Anna; de Wert, Guido; van Schayck, Onno C P; Horstman, Klasien

    2014-08-01

    The ongoing development of novel nicotine vaccines makes it urgent to identify the normative questions around this innovative health technology against smoking. A qualitative thematic analysis of peer-reviewed papers on nicotine vaccination published between 2001 and 2013. In the scientific discourse, nicotine vaccination is presented in a neurobiological frame as a potent concept for (long-term) smoking cessation. Nicotine vaccination is also considered a hypothetical strategy to prevent nicotine addiction in minors. Ethical assessments are conducted for the use of nicotine vaccination in public health and clinical medicine. Whereas vaccination for primary prevention is usually associated with public health, the hypothetical case of nicotine prevention in minors is also assessed for individualized protection. Therapeutic and preventive applications are given uneven attention: the classic goal of vaccination (primary prevention in minors) receives methodical consideration and invokes lively debate. The unprecedented use of vaccination, namely smoking cessation, is left largely unattended in the ethical analyses. While health innovations such as nicotine vaccination need broad reflection to guide decisions on their further development and possible future implementations, only a small part of the ethical and social issues of this innovative technology has been discussed. For a debate to come into existence, a 'neurobio-psycho-socio-cultural' frame of smoking and quitting appears fruitful. Important topics for reflection are the human activities and social processes in a vaccine-supported quit attempt, next to respect for individuals, possible harms and questions of (global) justice and research ethics. © 2014 Society for the Study of Addiction.

  10. Expanding the versatility of phage display II: improved affinity selection of folded domains on protein VII and IX of the filamentous phage.

    PubMed

    Løset, Geir Åge; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger

    2011-02-24

    Phage display is a leading technology for selection of binders with affinity for specific target molecules. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII) or the minor coat protein III (pIII). Whereas pVIII display suffers from drawbacks such as heterogeneity in display levels and polypeptide fusion size limitations, toxicity and infection interference effects have been described for pIII display. Thus, display on other coat proteins such as pVII or pIX might be more attractive. Neither pVII nor pIX display have gained widespread use or been characterized in detail like pIII and pVIII display. Here we present a side-by-side comparison of display on pIII with display on pVII and pIX. Polypeptides of interest (POIs) are fused to pVII or pIX. The N-terminal periplasmic signal sequence, which is required for phage integration of pIII and pVIII and that has been added to pVII and pIX in earlier studies, is omitted altogether. Although the POI display level on pIII is higher than on pVII and pIX, affinity selection with pVII and pIX display libraries is shown to be particularly efficient. Display through pVII and/or pIX represent platforms with characteristics that differ from those of the pIII platform. We have explored this to increase the performance and expand the use of phage display. In the paper, we describe effective affinity selection of folded domains displayed on pVII or pIX. This makes both platforms more attractive alternatives to conventional pIII and pVIII display than they were before.

  11. Expanding the Versatility of Phage Display II: Improved Affinity Selection of Folded Domains on Protein VII and IX of the Filamentous Phage

    PubMed Central

    Løset, Geir Åge; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger

    2011-01-01

    Background Phage display is a leading technology for selection of binders with affinity for specific target molecules. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII) or the minor coat protein III (pIII). Whereas pVIII display suffers from drawbacks such as heterogeneity in display levels and polypeptide fusion size limitations, toxicity and infection interference effects have been described for pIII display. Thus, display on other coat proteins such as pVII or pIX might be more attractive. Neither pVII nor pIX display have gained widespread use or been characterized in detail like pIII and pVIII display. Methodology/Principal Findings Here we present a side-by-side comparison of display on pIII with display on pVII and pIX. Polypeptides of interest (POIs) are fused to pVII or pIX. The N-terminal periplasmic signal sequence, which is required for phage integration of pIII and pVIII and that has been added to pVII and pIX in earlier studies, is omitted altogether. Although the POI display level on pIII is higher than on pVII and pIX, affinity selection with pVII and pIX display libraries is shown to be particularly efficient. Conclusions/Significance Display through pVII and/or pIX represent platforms with characteristics that differ from those of the pIII platform. We have explored this to increase the performance and expand the use of phage display. In the paper, we describe effective affinity selection of folded domains displayed on pVII or pIX. This makes both platforms more attractive alternatives to conventional pIII and pVIII display than they were before. PMID:21390283

  12. [Neurobiological basis of depressive disorders].

    PubMed

    Stoppel, C; Bielau, H; Bogerts, B; Northoff, G

    2006-12-01

    Depressive disorders belong to the most frequent diseases worldwide showing a lifetime prevalence of up to 20%. Moreover they are one of the leading causes for the amount of years lived with disability. Increasing knowledge about the pathological mechanisms underlying depressive syndromes is obtained by using modern neurobiological research-techniques. Thereby some older theories that have been the basis of emotion-research for decades--like the monoamine hypothesis--have been strengthened. In addition new aspects of the pathological processes underlying depressive disturbances have been unraveled. In this review established models and recent findings will be discussed, to bridge various research-fields, ranging from genetics, epigenetics and morphological changes to the functional consequences of depression. Finally therapeutic implications that could be derived from these results will be presented, showing up putative possibilities for diagnosis and treatment of depressive syndromes.

  13. The neurobiology, diagnosis, and treatment of narcolepsy.

    PubMed

    Scammell, Thomas E

    2003-02-01

    Narcolepsy is a common cause of chronic sleepiness distinguished by intrusions into wakefulness of physiological aspects of rapid eye movement sleep such as cataplexy and hallucinations. Recent advances provide compelling evidence that narcolepsy may be a neurodegenerative or autoimmune disorder resulting in a loss of hypothalamic neurons containing the neuropeptide orexin (also known as hypocretin). Because orexin promotes wakefulness and inhibits rapid eye movement sleep, its absence may permit inappropriate transitions between wakefulness and sleep. These discoveries have considerably improved our understanding of the neurobiology of sleep and should foster the development of rational treatments for a variety of sleep disorders.

  14. Molecular analysis of patients with {Beta}-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vervoort, R.; Liebaers, I.; Lissens, W.

    1996-03-01

    Although not all mucopolysaccharidosis type VII (MPS VII) neonates present with hydrops fetalis or with related symptoms, hydrops fetalis is a common form of presentation of this mucopolysaccharidosis. We used reverse-transcription-PCR-SSCP and direct sequencing to screen for mutations in the human {beta}-glucuronidase cDNA of 17 MPS VII patients with severe presentation of the disease. Mutations resulting in an unstable mRNA were detected in genomic DNA with direct sequencing of the PCR-amplified {beta}-glucuronidase exons. We found extensive genetic heterogeneity in MPS VII alleles: in addition to 6 of 12 previously reported mutations (L176F, R216W, R357X, R382C, W507X, and W627C), we detectedmore » 14 undescribed mutations in the {beta}-glucuronidase coding region that produce MPS VII alleles (G136R, E150K, S312X, Y320S, Y320C, H351Y, R382H, R374C, R435P, R477W, G572D, Y508C, K606N, and 1900{Delta}GA). The mutations in hydropic fetuses were widely scattered in the {beta}-glucuronidase gene. Analysis of three polymorphic sites of the mutant alleles (1766T/C, 1972C/T, and a new 1091+27C/G polymorphism) allowed exclusion of identity by descent for some recurrent mutations. Three of four mutations introducing a premature translation stop codon were found to affect mRNA abundance and/or structure. Expression studies provided evidence for the causal relationship between each of the mutations found in MPS VII alleles and the enzyme deficiency, in that all mutations identified exhibited markedly reduced enzyme activity expressed in COS7 cells following transfection with the mutant cDNA. 52 refs., 4 figs., 5 tabs.« less

  15. Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII.

    PubMed Central

    Vervoort, R.; Islam, M. R.; Sly, W. S.; Zabot, M. T.; Kleijer, W. J.; Chabas, A.; Fensom, A.; Young, E. P.; Liebaers, I.; Lissens, W.

    1996-01-01

    Although not all mucopolysaccharidosis type VII (MPS VII) neonates present with hydrops fetalis or with related symptoms, hydrops fetalis is a common form of presentation of this mucopolysaccharidosis. We used reverse-transcription-PCR-SSCP and direct sequencing to screen for mutations in the human beta-glucuronidase cDNA of 17 MPS VII patients with severe presentation of the disease. Mutations resulting in an unstable mRNA were detected in genomic DNA with direct sequencing of the PCR-amplified beta-glucuronidase exons. We found extensive genetic heterogeneity in MPS VII alleles: in addition to 6 or 12 previously reported mutations (L176F, R216W, R357X, R382C, W507X, and W627C), we detected 14 undescribed mutations in the beta-glucuronidase coding region that produce MPS VII alleles (G136R, E150K, S312X, Y320S, Y320C, H351Y, R382H, R374C, R435P, R477W, G572D, Y508C, K606N and 1900 delta GA). The mutations in hydropic fetuses were widely scattered in the beta-glucuronidase gene. Analysis of three polymorphic sites of the mutant alleles (1766T/C, 1972C/T and a new 1091+27C/G polymorphism) allowed exclusion of identity by descent for some recurrent mutations. Three of four mutations introducing a premature translation stop codon were found to affect mRNA abundance and/or structure. Expression studies provided evidence for the causal relationship between each of the mutations found in MPS VII alleles and the enzyme deficiency, in that all mutations identified exhibited markedly reduced enzyme activity expressed in COS7 cells following transfection with the mutant cDNA. Images Figure 2 Figure 3A Figure 3BC Figure 4 PMID:8644704

  16. Stability of prothrombin and factor VII in freeze-dried plasma

    PubMed Central

    Brozović, M.; Gurd, L. J.; Robertson, I.; Bangham, D. R.

    1971-01-01

    The stability of prothrombin and factor VII was studied using accelerated degradation tests in three preparations of freeze-dried pooled normal plasmas. In a previous report (Brozović, Gurd, Robertson, and Bangham, 1971) factor X was shown to be relatively unstable in these preparations of freeze-dried plasma: it was calculated that up to 8% of the original factor X activity would be lost after 10 years at −20°C, up to 54% at 4°C, and up to 90% at room temperature. The losses of factor VII activity were estimated to be negligible at −20°C, between 2 and 18% at 4°C, and between 20 and 70% of the original activity at 20°C, after 10 years of storage. Prothrombin was found to be less stable than factor VII: the expected loss in 10 years at −20°C may be up to 4%, at 4°C up to 30%, and at 20°C up to 83% of the initial activity. These findings indicate that in freeze-dried plasma prothrombin as well as factor X may be insufficiently stable for plasma to serve as long-term reference material for the standardization of the one-stage prothrombin time. Moreover, the loss of prothrombin and factor X in freeze-dried plasma stored at 4°C may be so high that when it is required to preserve these factors it may be necessary to store freeze-dried plasma at lower temperatures. PMID:5130534

  17. Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

    PubMed

    Sobti, R C; Maithil, Nishi; Thakur, Hitender; Sharma, Yashpaul; Talwar, K K

    2010-08-01

    The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P < 0.001, and OR 0.18, 95% CI 0.09-0.36, P < 0.001. Our study showed D allele of ACE to be associated with marginal risk of CHD, AA genotype of FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

  18. Evaluation Design 1977-1978 ESEA Title VII Bilingual Program.

    ERIC Educational Resources Information Center

    Matuszek, Paula; And Others

    A design for the evaluation of ESEA Title VII bilingual programs in the Austin Independent School District is presented. The following topics are included: (1) Evaluation Design Review Form; (2) decision questions including the actual questions addressed on three levels: the Office of Education-Level, the system-level and the project-level; (3) a…

  19. VVER-440 and VVER-1000 reactor dosimetry benchmark - BUGLE-96 versus ALPAN VII.0

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duo, J. I.

    2011-07-01

    Document available in abstract form only, full text of document follows: Analytical results of the vodo-vodyanoi energetichesky reactor-(VVER-) 440 and VVER-1000 reactor dosimetry benchmarks developed from engineering mockups at the Nuclear Research Inst. Rez LR-0 reactor are discussed. These benchmarks provide accurate determination of radiation field parameters in the vicinity and over the thickness of the reactor pressure vessel. Measurements are compared to calculated results with two sets of tools: TORT discrete ordinates code and BUGLE-96 cross-section library versus the newly Westinghouse-developed RAPTOR-M3G and ALPAN VII.0. The parallel code RAPTOR-M3G enables detailed neutron distributions in energy and space in reducedmore » computational time. ALPAN VII.0 cross-section library is based on ENDF/B-VII.0 and is designed for reactor dosimetry applications. It uses a unique broad group structure to enhance resolution in thermal-neutron-energy range compared to other analogous libraries. The comparison of fast neutron (E > 0.5 MeV) results shows good agreement (within 10%) between BUGLE-96 and ALPAN VII.O libraries. Furthermore, the results compare well with analogous results of participants of the REDOS program (2005). Finally, the analytical results for fast neutrons agree within 15% with the measurements, for most locations in all three mockups. In general, however, the analytical results underestimate the attenuation through the reactor pressure vessel thickness compared to the measurements. (authors)« less

  20. Case report: a 70-year-old man with undiagnosed factor VII deficiency presented with acute ischemic stroke.

    PubMed

    Ip, Hing-Lung; Chan, Anne Yin-Yan; Ng, Kit-Chung; Soo, Yannie Oi-Yan; Wong, Lawrence Ka-Sing

    2013-11-01

    Factor VII deficiency is an uncommon coagulation disorder that patient usually presents with bleeding diathesis, but thrombotic event has been reported. We report a case of unusual clinical presentation in a patient with undiagnosed factor VII deficiency who presented with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. The neuropsychology and neurobiology of late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: A critical review.

    PubMed

    Van Assche, Lies; Morrens, Manuel; Luyten, Patrick; Van de Ven, Luc; Vandenbulcke, Mathieu

    2017-12-01

    The current review discusses neuropsychological profiles and the longitudinal course of cognitive dysfunction in Late Onset Schizophrenia (LOS) and Very-late-onset schizophrenia-like psychosis (VLOSLP), and attempts to clarify its neurobiological underpinnings. A systematic literature search resulted in 29 publications describing original research on the neuropsychology of LOS/VLOSLP and 46 studies focussing on neurobiology. Although mildly progressive cognitive impairment is usually present, only a subgroup of LOS/VLOSLP develops dementia during a 10-year follow-up succeeding the onset of psychosis. This coincides with the absence of neuropathological evidence for neurodegeneration in many cases. Cognitive deterioration is characterized by deficits in (working) memory, language, psychomotor speed and executive functioning. Underlying neurobiological changes encompass white matter pathology, increased ventricle-to-brain ratio (VBR) with coinciding atrophy and hypo-metabolism of frontal, temporal and subcortical areas. Multiple changes in neurobiology and cognition contributing to LOS/VLOSLP may reflect stress-related accelerated brain aging rather than neurodegenerative pathology. Their involvement in the onset of illness, however, might be inversely proportional to pre-existing (psychosocial and/or genetic) vulnerability to psychosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The Contribution of Prenatal Stress to the Pathogenesis of Autism as a Neurobiological Developmental Disorder: A Dizygotic Twin Study

    ERIC Educational Resources Information Center

    Claassen, M.; Naude, H.; Pretorius, E.; Bosman, M. C.

    2008-01-01

    This paper reports on the contribution of prenatal stress to the pathogenesis of autism as a neurobiological developmental disorder in a dizygotic study. The aim was to explore whether the neurobiological impact of stress prior to week 28 of gestation might be related to the pathogenesis of autism. The following data-generating strategies were…

  3. Gravitational Neurobiology of Fish

    NASA Astrophysics Data System (ADS)

    Rahmann, H.; Anken, R. H.

    In vertebrates (including man), altered gravitational environments such as weightlessness can induce malfunctions of the inner ears, based on irregular movements of the semicircular cristae or on dislocations of the inner ear otoliths from the corresponding sensory epithelia. This will lead to illusionary tilts, since the vestibular inputs are not confirmed by the other sensory organs, which results in an intersensory conflict. Vertebrates in orbit therefore face severe orientation problems. In humans, the intersensory conflict may additionally lead to a malaise, commonly referred to as space motion sickness (SMS), a kinetosis. During the first days at weightlessness, the orientation problems (and SMS) disappear, since the brain develops a new compensatory interpretation of the available sensory data. The present review reports on the neurobiological responses - particularly of fish - observed at altered gravitational states, concerning behaviour and neuroplastic reactivities. Recent investigations employing microgravity (spaceflight, parabolic aircraft flights, clinostat) and hyper-gravity (laboratory centrifuges as ground based research tools) yielded clues and insights into the understanding of the respective basic phenomena

  4. 77 FR 64400 - Order of Succession for HUD Region VII

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-19

    ... Urban Development, designates the Order of Succession for the Kansas City Regional Office and its Field... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [FR-5550-D-10] Order of Succession for HUD Region VII..., Assistant General Counsel, Administrative Law Division, U.S. Department of Housing and Urban Development...

  5. Evaluation of the International Barrier Corporation's Mark VII median barrier.

    DOT National Transportation Integrated Search

    1992-01-01

    The International Barrier Corporation's (IBC) Mark VII median barrier consists of a steel frame (10 ft long, 42 in high, and 44 in wide at its widest point) filled with sand and covered with a top plate. The barrier has the ability to absorb some of ...

  6. [Is it still the "royal way"? The dream as a junction of neurobiology and psychoanalysis].

    PubMed

    Simon, Mária

    2011-01-01

    Some decades ago the dream seemed to be randomly generated by brain stem mechanisms in the cortical and subcortical neuronal networks. However, most recent empirical data, studies on brain lesions and functional neuroimaging results have refuted this theory. Several data support that motivation pathways, memory systems, especially implicit, emotional memory play an important role in dream formation. This essay reviews how the results of neurobiology and cognitive psychology can be fitted into the theoretical frameworks and clinical practice of the psychoanalysis. The main aim is to demonstrate that results of neurobiology and empirical observations of psychoanalysis are complementary rather than contradictory.

  7. Neurobiological Basis of Language Learning Difficulties.

    PubMed

    Krishnan, Saloni; Watkins, Kate E; Bishop, Dorothy V M

    2016-09-01

    In this paper we highlight why there is a need to examine subcortical learning systems in children with language impairment and dyslexia, rather than focusing solely on cortical areas relevant for language. First, behavioural studies find that children with these neurodevelopmental disorders perform less well than peers on procedural learning tasks that depend on corticostriatal learning circuits. Second, fMRI studies in neurotypical adults implicate corticostriatal and hippocampal systems in language learning. Finally, structural and functional abnormalities are seen in the striatum in children with language disorders. Studying corticostriatal networks in developmental language disorders could offer us insights into their neurobiological basis and elucidate possible modes of compensation for intervention. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Nonredundant functions of Arabidopsis LecRK-V.2 and LecRK-VII.1 in controlling stomatal immunity and jasmonate-mediated stomatal closure.

    PubMed

    Yekondi, Shweta; Liang, Fu-Chun; Okuma, Eiji; Radziejwoski, Amandine; Mai, Hsien-Wei; Swain, Swadhin; Singh, Prashant; Gauthier, Mathieu; Chien, Hsiao-Chiao; Murata, Yoshiyuki; Zimmerli, Laurent

    2018-04-01

    Stomatal immunity restricts bacterial entry to leaves through the recognition of microbe-associated molecular patterns (MAMPs) by pattern-recognition receptors (PRRs) and downstream abscisic acid and salicylic acid signaling. Through a reverse genetics approach, we characterized the function of the L-type lectin receptor kinase-V.2 (LecRK-V.2) and -VII.1 (LecRK-VII.1). Analyses of interactions with the PRR FLAGELLIN SENSING2 (FLS2) were performed by co-immunoprecipitation and bimolecular fluorescence complementation and whole-cell patch-clamp analyses were used to evaluate guard cell Ca 2+ -permeable cation channels. The Arabidopsis thaliana LecRK-V.2 and LecRK-VII.1 and notably their kinase activities were required for full activation of stomatal immunity. Knockout lecrk-V.2 and lecrk-VII.1 mutants were hyper-susceptible to Pseudomonas syringae infection and showed defective stomatal closure in response to bacteria or to the MAMPs flagellin and EF-Tu. By contrast, Arabidopsis over-expressing LecRK-V.2 or LecRK-VII.1 demonstrated a potentiated stomatal immunity. LecRK-V.2 and LecRK-VII.1 are shown to be part of the FLS2 PRR complex. In addition, LecRK-V.2 and LecRK-VII.1 were critical for methyl jasmonate (MeJA)-mediated stomatal closure, notably for MeJA-induced activation of guard cell Ca 2+ -permeable cation channels. This study highlights the role of LecRK-V.2 and LecRK-VII.1 in stomatal immunity at the FLS2 PRR complex and in MeJA-mediated stomatal closure. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  9. The Effect of Neonatal Gene Therapy with a Gamma Retroviral Vector on Cardiac Valve Disease in Mucopolysaccharidosis VII Dogs after a Decade

    PubMed Central

    Bigg, Paul W.; Sleeper, Meg M.; O’Donnell, Patricia A.; Liu, Yuli; Wu, Susan; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

    2013-01-01

    Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the lysosomal enzyme β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs). This study determined the long-term effect of neonatal intravenous injection of a gamma retroviral vector (RV) on cardiac valve disease in MPS VII dogs. Transduced hepatocytes secreted GUSB into blood for up to 11 years at levels similar to or greater than those achieved with enzyme replacement therapy (ERT). Valve regurgitation and thickening were scored from 0 (normal) to +4 (severely abnormal). At 1 year, untreated MPS VII dogs had mitral regurgitation, mitral valve thickening, aortic regurgitation, and aortic valve thickening scores of 2.3±0.7, 2.3±0.6, 1.8±0.5, and 1.6±0.7, respectively, which were higher than the values of 0.6±0.1, 0.1±0.4, 0.3±0.8, and 0.1±0.4, respectively, in treated MPS VII dogs. Treated MPS VII dogs maintained low aortic regurgitation and aortic valve thickening scores for their lifetime. Although mitral regurgitation and mitral valve thickening scores increased to 2.0 at ≥8 years of age in the treated MPS VII dogs, older normal dogs from the colony had similar scores, making it difficult to assess mitral valve disease. Older treated dogs had calcification within the mitral and aortic valve annulus, while GUSB staining demonstrated enzyme activity within the mitral valve. We conclude that neonatal RV-mediated gene therapy reduced cardiac valve disease in MPS VII dogs for up to 11 years, and propose that neonatal initiation of ERT should have a similar effect. PMID:23860311

  10. The Neurobiology of Affect in Language. A Supplement to "Language Learning."

    ERIC Educational Resources Information Center

    Schumann, John H.

    1997-01-01

    This document presents a theory of how the psychology and neurobiology of stimulus appraisal influence variability in second language acquisition, and extends the notion of affect developed for second language acquisition to primary language acquisition and to cognition in general. The first chapter lays out a psychological framework that develops…

  11. Experimental evidence for competitive growth advantage of genotype VII over VI: implications for foot-and-mouth disease virus serotype A genotype turnover in nature.

    PubMed

    Mohapatra, J K; Subramaniam, S; Singh, N K; Sanyal, A; Pattnaik, B

    2012-04-01

    In India, systematic genotype replacement has been observed for serotype A foot-and-mouth disease virus. After a decade of co-circulation of genotypes VI and VII, genotype VII emerged as the single dominant genotype since 2001. To derive possible explanations for such epochal evolution dynamics, in vitro intergenotype growth competition experiments involving both co- and superinfection regimes were conducted. Coinfection of BHK-21 cells demonstrated abrupt loss in the genotype VI viral load with commensurate increase in the load of genotype VII as measured by the genotype differentiating ELISA, RT-PCR and real-time RT-PCR. The superinfection dynamics was shaped by temporal spacing of infection, where the invading genotype VII took more number of passages than coinfection to eventually overtake the resident genotype VI. It was speculated that such superior replicative fitness of genotype VII could have been a possible factor for the ultimate dominance of genotype VII in nature. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Improving Bilingual Program Management. A Handbook for Title VII Directors.

    ERIC Educational Resources Information Center

    DeGeorge, George P., Ed.

    Filled with practical advice and workable techniques and strategies to help bilingual program directors deal with the problems they face, this handbook brings together ideas and suggestions from Title VII program directors, state coordinators, and superintendents with experience in bilingual programs. The handbook, written in question and answer…

  13. The Great Mini-Debate

    ERIC Educational Resources Information Center

    Benucci, Heather

    2017-01-01

    Debates remain popular in English language courses, and this activity gives students a low-stress opportunity to develop their speaking debating skills. This lesson plan is appropriate for upper intermediate or advanced students. Goals of the activity are to present an oral argument using evidence and use functional language related to agreeing,…

  14. Towards a computational(ist) neurobiology of language: Correlational, integrated, and explanatory neurolinguistics*

    PubMed Central

    Poeppel, David

    2014-01-01

    We outline what an integrated approach to language research that connects experimental, theoretical, and neurobiological domains of inquiry would look like, and ask to what extent unification is possible across domains. At the center of the program is the idea that computational/representational (CR) theories of language must be used to investigate its neurobiological (NB) foundations. We consider different ways in which CR and NB might be connected. These are (1) A Correlational way, in which NB computation is correlated with the CR theory; (2) An Integrated way, in which NB data provide crucial evidence for choosing among CR theories; and (3) an Explanatory way, in which properties of NB explain why a CR theory is the way it is. We examine various questions concerning the prospects for Explanatory connections in particular, including to what extent it makes sense to say that NB could be specialized for particular computations. PMID:25914888

  15. Towards a computational(ist) neurobiology of language: Correlational, integrated, and explanatory neurolinguistics.

    PubMed

    Embick, David; Poeppel, David

    2015-05-01

    We outline what an integrated approach to language research that connects experimental, theoretical, and neurobiological domains of inquiry would look like, and ask to what extent unification is possible across domains. At the center of the program is the idea that computational/representational (CR) theories of language must be used to investigate its neurobiological (NB) foundations. We consider different ways in which CR and NB might be connected. These are (1) A Correlational way, in which NB computation is correlated with the CR theory; (2) An Integrated way, in which NB data provide crucial evidence for choosing among CR theories; and (3) an Explanatory way, in which properties of NB explain why a CR theory is the way it is. We examine various questions concerning the prospects for Explanatory connections in particular, including to what extent it makes sense to say that NB could be specialized for particular computations.

  16. Genetics and neurobiology of aggression in Drosophila

    PubMed Central

    Zwarts, Liesbeth; Versteven, Marijke; Callaerts, Patrick

    2012-01-01

    Aggressive behavior is widely present throughout the animal kingdom and is crucial to ensure survival and reproduction. Aggressive actions serve to acquire territory, food, or mates and in defense against predators or rivals; while in some species these behaviors are involved in establishing a social hierarchy. Aggression is a complex behavior, influenced by a broad range of genetic and environmental factors. Recent studies in Drosophila provide insight into the genetic basis and control of aggression. The state of the art on aggression in Drosophila and the many opportunities provided by this model organism to unravel the genetic and neurobiological basis of aggression are reviewed. PMID:22513455

  17. Neuroeconomics: The neurobiology of value-based decision-making

    PubMed Central

    Rangel, Antonio; Camerer, Colin; Montague, P. Read

    2015-01-01

    Neuroeconomics studies the neurobiological and computational basis of value-based decision-making. Its goal is to provide a biologically-based account of human behavior that can be applied in both the natural and the social sciences. In this review we propose a framework for thinking about decision-making that allows us to bring together recent findings in the field, highlight some of the most important outstanding problems, define a common lexicon that bridges the different disciplines that inform neuroeconomics, and point the way to future applications. PMID:18545266

  18. [Neurobiology of autism: Study of a sample of autistic children].

    PubMed

    Germanò, E; Gagliano, A; Magazù, A; Calarese, T; Calabrò, M E; Bonsignore, M; Tortorella, G; Calamoneri, F

    2006-04-01

    Recent studies on the neuroanatomic, neurofunctional and/or neurochemical features of the autistic disorder (AD) gave many evidences suggesting the hypothesis that different organic factors may lead to a disruption of the cerebral development finally expressing with an autistic pattern. The aim of this study was to study a sample of subjects with AD with a wide protocol, including neurophysiological and radiological investigations as well as laboratory investigations in order to investigate the neurobiologic basis of the syndrome. The patients group included 80 subjects diagnosed as having AD. All were examined with a protocol of investigations including: brain MRI; wakefulness and sleep EEG; VEP, ABR; karyotype and search of the fragile X; serum and urinary levels of serotonin, catecolamines, omovanillic acid, aminoacids, ammonium, lactic acid, creatine kinase, piruvic acid, calcium, uric acid, total proteins, antibodies against neurotrophic agents. Eighty-eight percent of subjects had at least one pathologic neurobiological parameter. This study highlights the different noxae involved in the etiopathogenesis of AD and the percentage that every biological factor has in the development of the autistic phenotype. Furthermore, it confirms that AD corresponds to an atypical behavioural phenotype expression of a cerebral dysfunction with heterogeneous etiology.

  19. Free energy models for ice VII and liquid water derived from pressure, entropy, and heat capacity relations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Myint, Philip C.; Benedict, Lorin X.; Belof, Jonathan L.

    Here, we present equations of state relevant to conditions encountered in ramp and multiple-shock compression experiments of water. These experiments compress water from ambient conditions to pressures as high as about 14 GPa and temperatures of up to several hundreds of Kelvin. Water may freeze into ice VII during this process. Although there are several studies on the thermodynamic properties of ice VII, an accurate and analytic free energy model from which all other properties may be derived in a thermodynamically consistent manner has not been previously determined. We have developed such a free energy model for ice VII thatmore » is calibrated with pressure-volume-temperature measurements and melt curve data. Furthermore, we show that liquid water in the pressure and temperature range of interest is well-represented by a simple Mie-Grüneisen equation of state. Our liquid water and ice VII equations of state are validated by comparing to sound speed and Hugoniot data. Although they are targeted towards ramp and multiple-shock compression experiments, we demonstrate that our equations of state also behave reasonably well at pressures and temperatures that lie somewhat beyond those found in the experiments.« less

  20. Free energy models for ice VII and liquid water derived from pressure, entropy, and heat capacity relations

    DOE PAGES

    Myint, Philip C.; Benedict, Lorin X.; Belof, Jonathan L.

    2017-08-28

    Here, we present equations of state relevant to conditions encountered in ramp and multiple-shock compression experiments of water. These experiments compress water from ambient conditions to pressures as high as about 14 GPa and temperatures of up to several hundreds of Kelvin. Water may freeze into ice VII during this process. Although there are several studies on the thermodynamic properties of ice VII, an accurate and analytic free energy model from which all other properties may be derived in a thermodynamically consistent manner has not been previously determined. We have developed such a free energy model for ice VII thatmore » is calibrated with pressure-volume-temperature measurements and melt curve data. Furthermore, we show that liquid water in the pressure and temperature range of interest is well-represented by a simple Mie-Grüneisen equation of state. Our liquid water and ice VII equations of state are validated by comparing to sound speed and Hugoniot data. Although they are targeted towards ramp and multiple-shock compression experiments, we demonstrate that our equations of state also behave reasonably well at pressures and temperatures that lie somewhat beyond those found in the experiments.« less

  1. Championship Debates and Speeches 1986. Vol. 1.

    ERIC Educational Resources Information Center

    Boaz, John K., Ed.; Brey, James R., Ed.

    Including speech transcripts and judges' critiques, this book presents the results of the 1986 (1) National Debate Tournament Final Debate, sponsored by the American Forensic Association, including the affirmative and negative presentations; (2) National CEDA Tournament Final Debate, sponsored by the Cross-Examination Debate Association, including…

  2. Statistics and Title VII Proof: Prima Facie Case and Rebuttal.

    ERIC Educational Resources Information Center

    Whitten, David

    1978-01-01

    The method and means by which statistics can raise a prima facie case of Title VII violation are analyzed. A standard is identified that can be applied to determine whether a statistical disparity is sufficient to shift the burden to the employer to rebut a prima facie case of discrimination. (LBH)

  3. The effect of neonatal gene therapy with a gamma retroviral vector on cardiac valve disease in mucopolysaccharidosis VII dogs after a decade.

    PubMed

    Bigg, Paul W; Sleeper, Meg M; O'Donnell, Patricia A; Liu, Yuli; Wu, Susan; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

    2013-11-01

    Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the lysosomal enzyme β-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs). This study determined the long-term effect of neonatal intravenous injection of a gamma retroviral vector (RV) on cardiac valve disease in MPS VII dogs. Transduced hepatocytes secreted GUSB into the blood for up to 11 years at levels similar to or greater than those achieved with enzyme replacement therapy (ERT). Valve regurgitation and thickening were scored from 0 (normal) to +4 (severely abnormal). At 1 year, untreated MPS VII dogs had mitral regurgitation, mitral valve thickening, aortic regurgitation, and aortic valve thickening scores of 2.3 ± 0.7, 2.3 ± 0.6, 1.8 ± 0.5, and 1.6 ± 0.7, respectively, which were higher than the values of 0.6 ± 0.1, 0.1 ± 0.4, 0.3 ± 0.8, and 0.1 ± 0.4, respectively, in treated MPS VII dogs. Treated MPS VII dogs maintained low aortic regurgitation and aortic valve thickening scores in their lifetime. Although mitral regurgitation and mitral valve thickening scores increased to 2.0 at ≥ 8 years of age in the treated MPS VII dogs, older normal dogs from the colony had similar scores, making it difficult to assess mitral valve disease. Older treated dogs had calcification within the mitral and the aortic valve annulus, while GUSB staining demonstrated enzyme activity within the mitral valve. We conclude that neonatal RV-mediated gene therapy reduced cardiac valve disease in MPS VII dogs for up to 11 years, and propose that neonatal initiation of ERT should have a similar effect. © 2013.

  4. The neurobiology of reward and cognitive control systems and their role in incentivizing health behavior.

    PubMed

    Garavan, Hugh; Weierstall, Karen

    2012-11-01

    This article reviews the neurobiology of cognitive control and reward processes and addresses their role in the treatment of addiction. We propose that the neurobiological mechanisms involved in treatment may differ from those involved in the etiology of addiction and consequently are worthy of increased investigation. We review the literature on reward and control processes and evidence of differences in these systems in drug addicted individuals. We also review the relatively small literature on neurobiological predictors of abstinence. We conclude that prefrontal control systems may be central to a successful recovery from addiction. The frontal lobes have been shown to regulate striatal reward-related processes, to be among the regions that predict treatment outcome, and to show elevated functioning in those who have succeeded in maintaining abstinence. The evidence of the involvement of the frontal lobes in recovery is consistent with the hypothesis that recovery is a distinct process that is more than the undoing of those processes involved in becoming addicted and a return to the pre-addiction state of the individual. The extent to which these frontal systems are engaged by treatment interventions may contribute to their efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Preparing to use vehicle infrastructure integration (VII) in transportation operations : phase II.

    DOT National Transportation Integrated Search

    2009-01-01

    Vehicle infrastructure integration (VII) is an emerging approach intended to create an enabling communication capability to support vehicle-to-vehicle and vehicle-to-infrastructure communications for safety and mobility applications. The Virginia Dep...

  6. Affective Learning and the Classroom Debate

    ERIC Educational Resources Information Center

    Jagger, Suzy

    2013-01-01

    A commonly used teaching method to promote student engagement is the classroom debate. This study evaluates how affective characteristics, as defined in Bloom's taxonomy, were stimulated during debates that took place on a professional ethics module for first year computing undergraduates. The debates led to lively interactive group discussions…

  7. The neurobiology of pleasure, reward processes, addiction and their health implications.

    PubMed

    Esch, Tobias; Stefano, George B

    2004-08-01

    Modern science begins to understand pleasure as a potential component of salutogenesis. Thereby, pleasure is described as a state or feeling of happiness and satisfaction resulting from an experience that one enjoys. We examine the neurobiological factors underlying reward processes and pleasure phenomena. Further, health implications related to pleasurable activities are analyzed. With regard to possible negative effects of pleasure, we focus on addiction and motivational toxicity. Pleasure can serve cognition, productivity and health, but simultaneously promotes addiction and other negative behaviors, i.e., motivational toxicity. It is a complex neurobiological phenomenon, relying on reward circuitry or limbic activity. These processes involve dopaminergic signaling. Moreover, endorphin and endogenous morphinergic mechanisms may play a role. Natural rewarding activities are necessary for survival and appetitive motivation, usually governing beneficial biological behaviors like eating, sex and reproduction. Social contacts can further facilitate the positive effects exerted by pleasurable experiences. However, artificial stimulants can be detrimental, since flexibility and normal control of behavior are deteriorated. Additionally, addictive drugs are capable of directly acting on reward pathways. Thus, the concrete outcome of pleasant experiences may be a question of dose. Moderate pleasurable experiences are able to enhance biological flexibility and health. Hence, pleasure can be a resistance resource or may serve salutogenesis. Natural rewards are mediated by sensory organ stimulation, thereby exhibiting a potential association with complementary medical approaches. Trust and belief can be part of a self-healing potential connected with rewarding stimuli. Further, the placebo response physiologically resembles pleasure phenomena, since both involve brain's reward circuitry stimulation and subjective feelings of well-being. Pleasurable activities can stimulate

  8. Bringing basic research on early experience and stress neurobiology to bear on preventive interventions for neglected and maltreated children.

    PubMed

    Gunnar, Megan R; Fisher, Philip A

    2006-01-01

    A major focus in developmental psychopathology is on understanding developmental mechanisms and, armed with this information, intervening to improve children's outcomes. Translational research attempts to bridge the distance between understanding and intervention. In the collaborations that have formed the core of our research network on early experience, stress, and prevention science, we have focused on translating basic research on early experiences and stress neurobiology into preventive interventions for neglected and abused children. Our experiences in attempting to move from bench to bedside have led us to recognize the many challenges that face translational researchers. This review provides a brief synopsis of the animal model literature on early experience and stress neurobiology from which we glean several key bridging issues. We then review what is currently known about the impact of childhood neglect and abuse on stress neurobiology in human adults and children. Next, we describe how this work has informed the evaluation of our preventive interventions with maltreated children. Finally, we discuss several considerations that should facilitate a more complete integration of basic research on early experience and stress neurobiology into preventive intervention strategies.

  9. Pharmacodynamics of recombinant activated factor VII and plasma-derived factor VII in a cohort of severe FVII deficient patients.

    PubMed

    van Geffen, Mark; Mathijssen, Natascha C J; Holme, Pål A; Laros-van Gorkom, Britta A P; van Kraaij, Marian G J; Masereeuw, Roselinde; Peyvandi, Flora; van Heerde, Waander L

    2013-07-01

    Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) are used to prevent bleedings in severe FVII deficient patients, despite their short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously measures thrombin and plasmin generation. Ten severe FVII deficient patients were treated with 20 μg/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin generation lag-time (TG-LT) was identified as an effect-response parameter. Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the TG-LT effect at ~2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII activity to obtain TG-LT comparable to the upper limit of normal range in healthy controls (4 min) was given by the effective concentration (ECnormal), showing sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between FVII activity and other thrombin or plasmin generation parameters as measured by NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain hemostasis in patients with severe FVII deficiency during prophylaxis. These data may suggest a potential value for measurement of TG-LT in the monitoring of FVII(a) therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Intimate Debate Technique: Medicinal Use of Marijuana

    ERIC Educational Resources Information Center

    Herreid, Clyde Freeman; DeRei, Kristie

    2007-01-01

    Classroom debates used to be familiar exercises to students schooled in past generations. In this article, the authors describe the technique called "intimate debate". To cooperative learning specialists, the technique is known as "structured debate" or "constructive debate". It is a powerful method for dealing with case topics that involve…

  11. Title VII and the Male/Female Earnings Gap: An Economic Analysis.

    ERIC Educational Resources Information Center

    Beller, Andrea

    1978-01-01

    After controlling statistically for the effects of other factors that affect earnings, it was found that enforcement of sex discrimination charges under Title VII increased the relative demand for women and thus decreased the male/female earnings differential between 1967 and 1974. (Author)

  12. 11 CFR 100.92 - Candidate debates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 11 Federal Elections 1 2011-01-01 2011-01-01 false Candidate debates. 100.92 Section 100.92 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Contributions § 100.92 Candidate debates. Funds provided to defray costs incurred in staging candidate debates...

  13. 11 CFR 100.154 - Candidate debates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.154 Section 100.154 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Expenditures § 100.154 Candidate debates. Funds used to defray costs incurred in staging candidate debates in...

  14. 11 CFR 110.13 - Candidate debates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 110.13 Section 110.13... PROHIBITIONS § 110.13 Candidate debates. (a) Staging organizations. (1) Nonprofit organizations described in 26... political parties may stage candidate debates in accordance with this section and 11 CFR 114.4(f). (2...

  15. 11 CFR 110.13 - Candidate debates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 11 Federal Elections 1 2011-01-01 2011-01-01 false Candidate debates. 110.13 Section 110.13... PROHIBITIONS § 110.13 Candidate debates. (a) Staging organizations. (1) Nonprofit organizations described in 26... political parties may stage candidate debates in accordance with this section and 11 CFR 114.4(f). (2...

  16. 11 CFR 100.92 - Candidate debates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.92 Section 100.92 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Contributions § 100.92 Candidate debates. Funds provided to defray costs incurred in staging candidate debates...

  17. 11 CFR 100.154 - Candidate debates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 11 Federal Elections 1 2011-01-01 2011-01-01 false Candidate debates. 100.154 Section 100.154 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Expenditures § 100.154 Candidate debates. Funds used to defray costs incurred in staging candidate debates in...

  18. Inhalation Toxicology. VII. Times To Incapacitation and Death for Rats Exposed Continuously to Atmospheric Acrolein Vapor

    DTIC Science & Technology

    1986-05-01

    DOT FMAM-6/5INHALATION TOXICOLOGY : Office of Aviation Medicine VII. Times to Incapacitation and Washington, D.C. 20591 D ahfrR t x oe Continuously to...Accession No. 3. Recipient’s Catalog No. pOT/FAA/AM-86/5 ,4%__ _____ 4. T,tle and Subtoie S. Report Doate INHALATION TOXICOLOGY : VII. TIMES TO...Statement " Combustion toxicology ; smoke; irritant This document is available to the public gas; time-to-incapacitation; time-to- through the National

  19. Book review: The Wilderness Debate Rages On: Continuing the Great New Wilderness Debate

    Treesearch

    Peter Landres

    2009-01-01

    The Wilderness Debate Rages On is a collection of mostly previously published papers about the meaning, value, and role of wilderness and continues the discussion that was propelled by the editors' previous book The Great New Wilderness Debate (also a collection of papers) published in 1998. The editors state that this sequel to their previous book is mandated...

  20. Progressing neurobiological strategies against proteostasis failure: Challenges in neurodegeneration.

    PubMed

    Amanullah, Ayeman; Upadhyay, Arun; Joshi, Vibhuti; Mishra, Ribhav; Jana, Nihar Ranjan; Mishra, Amit

    2017-12-01

    Proteins are ordered useful cellular entities, required for normal health and organism's survival. The proteome is the absolute set of cellular expressed proteins, which regulates a wide range of physiological functions linked with all domains of life. In aging cells or under unfavorable cellular conditions, misfolding of proteins generates common pathological events linked with neurodegenerative diseases and aging. Current advances of proteome studies systematically generates some progress in our knowledge that how misfolding of proteins or their accumulation can contribute to the impairment or depletion of proteome functions. Still, the underlying causes of this unrecoverable loss are not clear that how such unsolved transitions give rise to multifactorial challengeable degenerative pathological conditions in neurodegeneration. In this review, we specifically focus and systematically summarize various molecular mechanisms of proteostasis maintenance, as well as discuss progressing neurobiological strategies, promising natural and pharmacological candidates, which can be useful to counteract the problem of proteopathies. Our article emphasizes an urgent need that now it is important for us to recognize the fundamentals of proteostasis to design a new molecular framework and fruitful strategies to uncover how the proteome defects are associated with aging and neurodegenerative diseases. A enhance understanding of progress link with proteome and neurobiological challenges may provide new basic concepts in the near future, based on pharmacological agents, linked with impaired proteostasis and neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The TFOS International Workshop on Contact Lens Discomfort: Report of the Subcommittee on Neurobiology

    PubMed Central

    Stapleton, Fiona; Marfurt, Carl; Golebiowski, Blanka; Rosenblatt, Mark; Bereiter, David; Begley, Carolyn; Dartt, Darlene; Gallar, Juana; Belmonte, Carlos; Hamrah, Pedram; Willcox, Mark

    2013-01-01

    This report characterizes the neurobiology of the ocular surface and highlights relevant mechanisms that may underpin contact lens–related discomfort. While there is limited evidence for the mechanisms involved in contact lens–related discomfort, neurobiological mechanisms in dry eye disease, the inflammatory pathway, the effect of hyperosmolarity on ocular surface nociceptors, and subsequent sensory processing of ocular pain and discomfort have been at least partly elucidated and are presented herein to provide insight in this new arena. The stimulus to the ocular surface from a contact lens is likely to be complex and multifactorial, including components of osmolarity, solution effects, desiccation, thermal effects, inflammation, friction, and mechanical stimulation. Sensory input will arise from stimulation of the lid margin, palpebral and bulbar conjunctiva, and the cornea. PMID:24058137

  2. Behavioral and neurobiological correlates of childhood apraxia of speech in Italian children.

    PubMed

    Chilosi, Anna Maria; Lorenzini, Irene; Fiori, Simona; Graziosi, Valentina; Rossi, Giuseppe; Pasquariello, Rosa; Cipriani, Paola; Cioni, Giovanni

    2015-11-01

    Childhood apraxia of speech (CAS) is a neurogenic Speech Sound Disorder whose etiology and neurobiological correlates are still unclear. In the present study, 32 Italian children with idiopathic CAS underwent a comprehensive speech and language, genetic and neuroradiological investigation aimed to gather information on the possible behavioral and neurobiological markers of the disorder. The results revealed four main aggregations of behavioral symptoms that indicate a multi-deficit disorder involving both motor-speech and language competence. Six children presented with chromosomal alterations. The familial aggregation rate for speech and language difficulties and the male to female ratio were both very high in the whole sample, supporting the hypothesis that genetic factors make substantial contribution to the risk of CAS. As expected in accordance with the diagnosis of idiopathic CAS, conventional MRI did not reveal macrostructural pathogenic neuroanatomical abnormalities, suggesting that CAS may be due to brain microstructural alterations. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Speech and Debate as Civic Education

    ERIC Educational Resources Information Center

    Hogan, J. Michael; Kurr, Jeffrey A.; Johnson, Jeremy D.; Bergmaier, Michael J.

    2016-01-01

    In light of the U.S. Senate's designation of March 15, 2016 as "National Speech and Debate Education Day" (S. Res. 398, 2016), it only seems fitting that "Communication Education" devote a special section to the role of speech and debate in civic education. Speech and debate have been at the heart of the communication…

  4. Corrective GUSB transfer to the canine mucopolysaccharidosis VII cornea using a helper-dependent canine adenovirus vector

    PubMed Central

    Serratrice, Nicolas; Cubizolle, Aurelie; Ibanes, Sandy; Mestre-Francés, Nadine; Bayo-Puxan, Neus; Creyssels, Sophie; Gennetier, Aurelie; Bernex, Florence; Verdier, Jean-Michel; Haskins, Mark E.; Couderc, Guilhem; Malecaze, Francois; Kalatzis, Vasiliki; Kremer, Eric J.

    2015-01-01

    Corneal transparency is maintained, in part, by specialized fibroblasts called keratocytes, which reside in the fibrous lamellae of the stroma. Corneal clouding, a condition that impairs visual acuity, is associated with numerous diseases, including mucopolysaccharidosis (MPS) type VII. MPS VII is due to deficiency in β-glucuronidase (β-glu) enzymatic activity, which leads to accumulation of glycosaminoglycans (GAGs), and secondary accumulation of gangliosides. Here, we tested the efficacy of canine adenovirus type 2 (CAV-2) vectors to transduce keratocyte in vivo in mice and nonhuman primates, and ex vivo in dog and human corneal explants. Following efficacy studies, we asked if we could treat corneal clouding by the injection a helper-dependent (HD) CAV-2 vector (HD-RIGIE) harboring the human cDNA coding for β-glu (GUSB) in the canine MPS VII cornea. β-Glu activity, GAG content, and lysosome morphology and physiopathology were analyzed. We found that HD-RIGIE injections efficiently transduced coxsackievirus adenovirus receptor-expressing keratocytes in the four species and, compared to mock-injected controls, improved the pathology in the canine MPS VII cornea. The key criterion to corrective therapy was the steady controlled release of β-glu and its diffusion throughout the collagen-dense stroma. These data support the continued evaluation of HD CAV-2 vectors to treat diseases affecting corneal keratocytes. PMID:24607662

  5. 29 CFR 1620.27 - Relationship to the Equal Pay Act of title VII of the Civil Rights Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Relationship to the Equal Pay Act of title VII of the Civil... OPPORTUNITY COMMISSION THE EQUAL PAY ACT § 1620.27 Relationship to the Equal Pay Act of title VII of the Civil... equal pay under the Equal Pay Act has no relationship to whether the employee is in the lower paying job...

  6. 29 CFR 1605.2 - Reasonable accommodation without undue hardship as required by section 701(j) of title VII of the...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION... address other obligations under title VII not to discriminate on grounds of religion, nor other provisions... to discrimination prohibited by title VII on the bases of race, color, sex, and national origin also...

  7. 29 CFR 1605.2 - Reasonable accommodation without undue hardship as required by section 701(j) of title VII of the...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION... address other obligations under title VII not to discriminate on grounds of religion, nor other provisions... to discrimination prohibited by title VII on the bases of race, color, sex, and national origin also...

  8. 29 CFR 1605.2 - Reasonable accommodation without undue hardship as required by section 701(j) of title VII of the...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION... address other obligations under title VII not to discriminate on grounds of religion, nor other provisions... to discrimination prohibited by title VII on the bases of race, color, sex, and national origin also...

  9. 29 CFR 1605.2 - Reasonable accommodation without undue hardship as required by section 701(j) of title VII of the...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION... address other obligations under title VII not to discriminate on grounds of religion, nor other provisions... to discrimination prohibited by title VII on the bases of race, color, sex, and national origin also...

  10. The Power of In-Class Debates

    ERIC Educational Resources Information Center

    Kennedy, Ruth R.

    2009-01-01

    The students in three sections of a class rated their knowledge and identified their view before and after each of five in-class debates. The degree of self-reported knowledge was significantly different after four of the five debates. Between 31% and 58% of participants changed their views after participating in or observing each debate. Some…

  11. Quantitative proteomics identify an association between extracellular matrix degradation and immunopathology of genotype VII Newcastle disease virus in the spleen in chickens.

    PubMed

    Hu, Zenglei; Gu, Han; Hu, Jiao; Hu, Shunlin; Wang, Xiaoquan; Liu, Xiaowen; Jiao, Xinan; Liu, Xiufan

    2018-06-15

    Pathogenesis of genotype VII Newcastle disease virus (NDV) is characterized with remarkable immunopathology in the spleen in chickens. However, the mechanism for this unique pathological phenotype is not fully understood. Previous transcriptomics data showed that genotype VII NDV JS5/05 caused a greater downregulation of extracellular matrix (ECM) genes than genotype IV virus Herts/33 in the spleen. In this study, the role of ECM in pathology of genotype VII NDV was investigated using quantitative proteomics. Pathology studies showed that JS5/05 caused severe immunopathology characterized with remarkable necrosis in the spleen, whereas Herts/33 only induced mild pathological changes. The ECM was firstly enriched from the spleens and ECM proteins of different categories were identified by LC-MS/MS. Quantitative proteomic analysis showed that JS5/05 caused a significant disruption of ECM integrity and molecular composition compared to Herts/33. Particularly, JS5/05 induced a more remarkable collagen breakdown in the spleen compared to Herts/33. Moreover, matrix metalloproteinase (MMP)-13 and -14 were significantly upregulated by JS5/05 infection. KEGG pathway analysis suggested that differential regulation of ECM proteins by JS5/05 and Herts/33 may impact pathology through different pathways. Therefore, our results suggested that MMP upregulation and consequent ECM degradation contribute to immunopathology of genotype VII NDV in the spleen. Pathogenesis of genotype VII NDV is characterized with severe immunopathology in the spleen in chickens. Elucidating the mechanism of this pathology phenotype is critical to understand pathogenesis of genotype VII NDV. Here, we present the proteomic data of an important non-cellular compartment, the extracellular matrix (ECM), in the spleen from chickens infected with genotype VII and IV NDVs. Our results suggest that significant upregulation of matrix metalloproteinases by genotype VII NDV and consequent disruption of ECM

  12. Chronic Stress in Adolescents and Its Neurobiological and Psychopathological Consequences: An RDoC Perspective.

    PubMed

    Sheth, Chandni; McGlade, Erin; Yurgelun-Todd, Deborah

    2017-01-01

    The Research Domain Criteria (RDoC) initiative provides a strategy for classifying psychopathology based on behavioral dimensions and neurobiological measures. Neurodevelopment is an orthogonal dimension in the current RDoC framework; however, it has not yet been fully incorporated into the RDoC approach. A combination of both a neurodevelopmental and RDoC approach offers a multidimensional perspective for understanding the emergence of psychopathology during development. Environmental influence (e.g., stress) has a profound impact on the risk for development of psychiatric illnesses. It has been shown that chronic stress interacts with the developing brain, producing significant changes in neural circuits that eventually increase the susceptibility for development of psychiatric disorders. This review highlights effects of chronic stress on the adolescent brain, as adolescence is a period characterized by a combination of significant brain alterations, high levels of stress, and emergence of psychopathology. The literature synthesized in this review suggests that chronic stress-induced changes in neurobiology and behavioral constructs underlie the shared vulnerability across a number of disorders in adolescence. The review particularly focuses on depression and substance use disorders; however, a similar argument can also be made for other psychopathologies, including anxiety disorders. The summarized findings underscore the need for a framework to integrate neurobiological findings from disparate psychiatric disorders and to target transdiagnostic mechanisms across disorders.

  13. Diagnosis, treatment, and neurobiology of autism in children.

    PubMed

    Lainhart, J E; Piven, J

    1995-08-01

    Autism is a developmental neuropsychiatric disorder defined by the presence of social and communicative deficits, restricted and repetitive behaviors and interests, and a characteristic course. Research suggests that hereditary factors play a principal role in the etiology of most cases. A phenotype broader than autism, including milder social and language-based cognitive deficits, appears to be inherited. Although the pathogenesis is unknown, neurobiologic mechanisms clearly underlie the disorder. Neuropathologic studies have demonstrated abnormalities in limbic structures, the cerebellum, and the cortex. New advances in behavioral therapies and pharmacologic treatment are important components of successful multidisciplinary treatment of this disorder.

  14. Bovine adenovirus 3 core protein precursor pVII localizes to mitochondria, and modulates ATP synthesis, mitochondrial Ca2+ and mitochondrial membrane potential.

    PubMed

    Anand, Sanjeev K; Gaba, Amit; Singh, Jaswant; Tikoo, Suresh K

    2014-02-01

    Viruses modulate the functions of mitochondria by translocating viral proteins to the mitochondria. Subcellular fractionation and sensitivity to proteinase K/Triton X-100 treatment of mitochondrial fractions of bovine adenovirus (BAdV)-3-infected/transfected cells suggested that core protein pVII localizes to the mitochondria and contains a functional mitochondrial localization signal. Moreover, mitochondrial localization of BAdV-3 pVII appears to help in the retention of mitochondrial Ca(2+), inducing a significant increase in the levels of ATP and maintaining the mitochondrial membrane potential (MMP) in transfected cells. In contrast, mitochondrial localization of BAdV-3 pVII has no significant effect on the levels of cytoplasmic Ca(2+) and reactive oxygen species production in the transfected cells. Consistent with these results, expression of pVII in transfected cells treated with staurosporine decreased significantly the activation of caspase-3. Our results suggested that BAdV-3 pVII localizes to mitochondria, and interferes with apoptosis by inhibiting loss of the MMP and by increasing mitochondrial Ca(2+) and ATP production.

  15. Scientific and conceptual flaws of coercive treatment models in addiction.

    PubMed

    Uusitalo, Susanne; van der Eijk, Yvette

    2016-01-01

    In conceptual debates on addiction, neurobiological research has been used to support the idea that addicted drug users lack control over their addiction-related actions. In some interpretations, this has led to coercive treatment models, in which, the purpose is to 'restore' control. However, neurobiological studies that go beyond what is typically presented in conceptual debates paint a different story. In particular, they indicate that though addiction has neurobiological manifestations that make the addictive behaviour difficult to control, it is possible for individuals to reverse these manifestations through their own efforts. Thus, addicted individuals should not be considered incapable of making choices voluntarily, simply on the basis that addiction has neurobiological manifestations, and coercive treatment models of addiction should be reconsidered in this respect. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Exploring the compassion deficit debate.

    PubMed

    Stenhouse, Rosie; Ion, Robin; Roxburgh, Michelle; Devitt, Patric Ffrench; Smith, Stephen D M

    2016-04-01

    Several recent high profile failures in the UK health care system have promoted strong debate on compassion and care in nursing. A number of papers articulating a range of positions within this debate have been published in this journal over the past two and a half years. These articulate a diverse range of theoretical perspectives and have been drawn together here in an attempt to bring some coherence to the debate and provide an overview of the key arguments and positions taken by those involved. In doing this we invite the reader to consider their own position in relation to the issues raised and to consider the impact of this for their own practice. Finally the paper offers some sense of how individual practitioners might use their understanding of the debates to ensure delivery of good nursing care. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Large proteoglycan complexes and disturbed collagen architecture in the corneal extracellular matrix of mucopolysaccharidosis type VII (Sly syndrome).

    PubMed

    Young, Robert D; Liskova, Petra; Pinali, Christian; Palka, Barbara P; Palos, Michalis; Jirsova, Katerina; Hrdlickova, Enkela; Tesarova, Marketa; Elleder, Milan; Zeman, Jiri; Meek, Keith M; Knupp, Carlo; Quantock, Andrew J

    2011-08-24

    Deficiencies in enzymes involved in proteoglycan (PG) turnover underlie a number of rare mucopolysaccharidoses (MPS), investigations of which can considerably aid understanding of the roles of PGs in corneal matrix biology. Here, the authors analyze novel pathologic changes in MPS VII (Sly syndrome) to determine the nature of PG-collagen associations in stromal ultrastructure. Transmission electron microscopy and electron tomography were used to investigate PG-collagen architectures and interactions in a cornea obtained at keratoplasty from a 22-year-old man with MPS VII, which was caused by a compound heterozygous mutation in the GUSB gene. Transmission electron microscopy showed atypical morphology of the epithelial basement membrane and Bowman's layer in MPS VII. Keratocytes were packed with cytoplasmic vacuoles containing abnormal glycosaminoglycan (GAG) material, and collagen fibrils were thinner than in normal cornea and varied considerably throughout anterior (14-32 nm), mid (13-42 nm), and posterior (17-39 nm) regions of the MPS VII stroma. PGs viewed in three dimensions were striking in appearance in that they were significantly larger than PGs in normal cornea and formed highly extended linkages with multiple collagen fibrils. Cellular changes in the MPS VII cornea resemble those in other MPS. However, the wide range of collagen fibril diameters throughout the stroma and the extensive matrix presence of supranormal-sized PG structures appear to be unique features of this disorder. The findings suggest that the accumulation of stromal chondroitin-, dermatan-, and heparan-sulfate glycosaminoglycans in the absence of β-glucuronidase-mediated degradation can modulate collagen fibrillogenesis.

  18. The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

    PubMed

    Quek, S C; Low, P S; Saha, N; Heng, C K

    2006-11-01

    Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

  19. The neurobiology of social attachment: A comparative approach to behavioral, neuroanatomical, and neurochemical studies*

    PubMed Central

    Young, Kimberly A.; Liu, Yan; Wang, Zuoxin

    2008-01-01

    The formation and maintenance of social bonds in adulthood is an essential component of human health. However studies investigating the underlying neurobiology of such behaviors have been scarce. Microtine rodents offer a unique comparative animal model to explore the neural processes responsible for pair bonding and its associated behaviors. Studies using monogamous prairie voles and other related species have recently offered insight into the neuroanatomical, neurobiological, and neurochemical underpinnings of social attachment. In this review, we will discuss the utility of the microtine rodents in comparative studies by exploring their natural history and social behavior in the laboratory. We will then summarize the data implicating vasopressin, oxytocin, and dopamine in the regulation of pair bonding. Finally, we will discuss the ways in which these neurochemical systems may interact to mediate this complex behavior. PMID:18417423

  20. The Economics of Enforcement of Title VII of the Civil Rights Act of 1964. Discussion Papers No. 313-75.

    ERIC Educational Resources Information Center

    Beller, Andrea H.

    The purpose of this paper is to estimate the effects of enforcement of Title VII to determine whether and to what extent it has helped to achieve the elimination of employment discrimination. The model developed in this paper is considered to depart from those of previous Title VII studies in two ways. First, it incorporates the effects of the…

  1. A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study.

    PubMed

    Hoffmann, Till; Assmann, Alexander; Dierksen, Angelika; Roussel, Elisabeth; Ullrich, Sebastian; Lichtenberg, Artur; Albert, Alexander; Sixt, Stephan

    2018-04-18

    Although off-label use of recombinant activated factor VII against refractory bleeding is incorporated in current guideline recommendations, safety concerns persist predominantly with respect to thromboembolic complications. We analyzed the safety and efficacy of recombinant activated factor VII at a very low dose in cardiosurgical patients with refractory bleeding. This prospective study includes 1180 cardiosurgical patients at risk of bleeding. Goal-directed substitution was based on real-time laboratory testing and clinical scoring of the bleeding intensity. All patients who fulfilled the criteria for enhanced risk of bleeding (n = 281) were consequently included in the present analysis. Patients in whom refractory bleeding developed despite substitution with specific hemostatic compounds (n = 167) received a single shot of very low-dose recombinant activated factor VII (≤20 μg/kg). Mortality and risk of thromboembolic complications, and freedom from stroke and acute myocardial infarction in particular, were analyzed (vs patients without recombinant activated factor VII) by multivariable logistic and Cox regression analyses, as well as Kaplan-Meier estimates. There was no increase in rates of mortality (30-day mortality 4.2% vs 7.0% with P = .418; follow-up survival 85.6% at 13.0 [interquartile range, 8.4-15.7] months vs 80.7% at 10.2 [interquartile range, 7.2-16.1] months with P = .151), thromboembolic complications (6.6% vs 9.6% with P = .637), renal insufficiency, need for percutaneous coronary intervention, duration of ventilation, duration of hospital stay, or rehospitalization in patients receiving very low-dose recombinant activated factor VII compared with patients not receiving recombinant activated factor VII. Complete hemostasis without any need for further hemostatic treatment was achieved after very low-dose recombinant activated factor VII administration in the majority of patients (up to 88.6% vs 0% with P < .001). The key results

  2. The Debate.

    ERIC Educational Resources Information Center

    Current Issues in Language and Society, 1997

    1997-01-01

    The transcript of a debate within a group of specialists in translation is presented. The discussion addresses: translator "visibility" in translations and reader reception; the relationship of functionalism in translation, comparative linguistics, and intercultural communication; the client's power; literary translation; the…

  3. ENDF/B-VII.1 Neutron Cross Section Data Testing with Critical Assembly Benchmarks and Reactor Experiments

    NASA Astrophysics Data System (ADS)

    Kahler, A. C.; MacFarlane, R. E.; Mosteller, R. D.; Kiedrowski, B. C.; Frankle, S. C.; Chadwick, M. B.; McKnight, R. D.; Lell, R. M.; Palmiotti, G.; Hiruta, H.; Herman, M.; Arcilla, R.; Mughabghab, S. F.; Sublet, J. C.; Trkov, A.; Trumbull, T. H.; Dunn, M.

    2011-12-01

    The ENDF/B-VII.1 library is the latest revision to the United States' Evaluated Nuclear Data File (ENDF). The ENDF library is currently in its seventh generation, with ENDF/B-VII.0 being released in 2006. This revision expands upon that library, including the addition of new evaluated files (was 393 neutron files previously, now 423 including replacement of elemental vanadium and zinc evaluations with isotopic evaluations) and extension or updating of many existing neutron data files. Complete details are provided in the companion paper [M. B. Chadwick et al., "ENDF/B-VII.1 Nuclear Data for Science and Technology: Cross Sections, Covariances, Fission Product Yields and Decay Data," Nuclear Data Sheets, 112, 2887 (2011)]. This paper focuses on how accurately application libraries may be expected to perform in criticality calculations with these data. Continuous energy cross section libraries, suitable for use with the MCNP Monte Carlo transport code, have been generated and applied to a suite of nearly one thousand critical benchmark assemblies defined in the International Criticality Safety Benchmark Evaluation Project's International Handbook of Evaluated Criticality Safety Benchmark Experiments. This suite covers uranium and plutonium fuel systems in a variety of forms such as metallic, oxide or solution, and under a variety of spectral conditions, including unmoderated (i.e., bare), metal reflected and water or other light element reflected. Assembly eigenvalues that were accurately predicted with ENDF/B-VII.0 cross sections such as unmoderated and uranium reflected 235U and 239Pu assemblies, HEU solution systems and LEU oxide lattice systems that mimic commercial PWR configurations continue to be accurately calculated with ENDF/B-VII.1 cross sections, and deficiencies in predicted eigenvalues for assemblies containing selected materials, including titanium, manganese, cadmium and tungsten are greatly reduced. Improvements are also confirmed for selected

  4. 8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

  5. 8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

  6. 8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

  7. 8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

  8. 8 CFR 233.6 - Aliens entering Guam or the Commonwealth of the Northern Mariana Islands pursuant to Title VII of...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, âConsolidated Natural Resources Act of 2008.â 233.6 Section 233.6 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY... of the Northern Mariana Islands pursuant to Title VII of Public Law 110-229, “Consolidated Natural...

  9. A Novel GUSB Mutation in Brazilian Terriers with Severe Skeletal Abnormalities Defines the Disease as Mucopolysaccharidosis VII

    PubMed Central

    Hytönen, Marjo K.; Arumilli, Meharji; Lappalainen, Anu K.; Kallio, Heli; Snellman, Marjatta; Sainio, Kirsi; Lohi, Hannes

    2012-01-01

    Hundreds of different human skeletal disorders have been characterized at molecular level and a growing number of resembling dysplasias with orthologous genetic defects are being reported in dogs. This study describes a novel genetic defect in the Brazilian Terrier breed causing a congenital skeletal dysplasia. Affected puppies presented severe skeletal deformities observable within the first month of life. Clinical characterization using radiographic and histological methods identified delayed ossification and spondyloepiphyseal dysplasia. Pedigree analysis suggested an autosomal recessive disorder, and we performed a genome-wide association study to map the disease locus using Illumina’s 22K SNP chip arrays in seven cases and eleven controls. A single association was observed near the centromeric end of chromosome 6 with a genome-wide significance after permutation (pgenome  = 0.033). The affected dogs shared a 13-Mb homozygous region including over 200 genes. A targeted next-generation sequencing of the entire locus revealed a fully segregating missense mutation (c.866C>T) causing a pathogenic p.P289L change in a conserved functional domain of β-glucuronidase (GUSB). The mutation was confirmed in a population of 202 Brazilian terriers (p = 7,71×10−29). GUSB defects cause mucopolysaccharidosis VII (MPS VII) in several species and define the skeletal syndrome in Brazilian Terriers. Our results provide new information about the correlation of the GUSB genotype to phenotype and establish a novel canine model for MPS VII. Currently, MPS VII lacks an efficient treatment and this model could be utilized for the development and validation of therapeutic methods for better treatment of MPS VII patients. Finally, since almost one third of the Brazilian terrier population carries the mutation, breeders will benefit from a genetic test to eradicate the detrimental disease from the breed. PMID:22815736

  10. Delayed presentation of traumatic facial nerve (CN VII) paralysis.

    PubMed

    Napoli, Anthony M; Panagos, Peter

    2005-11-01

    Facial nerve paralysis (Cranial Nerve VII, CN VII) can be a disfiguring disorder with profound impact upon the patient. The etiology of facial nerve paralysis may be congenital, iatrogenic, or result from neoplasm, infection, trauma, or toxic exposure. In the emergency department, the most common cause of unilateral facial paralysis is Bell's palsy, also known as idiopathic facial paralysis (IFP). We report a case of delayed presentation of unilateral facial nerve paralysis 3 days after sustaining a traumatic head injury. Re-evaluation and imaging of this patient revealed a full facial paralysis and temporal bone fracture extending into the facial canal. Because cranial nerve injuries occur in approximately 5-10% of head-injured patients, a good history and physical examination is important to differentiate IFP from another etiology. Newer generation high-resolution computed tomography (CT) scans are commonly demonstrating these fractures. An understanding of this complication, appropriate patient follow-up, and early involvement of the Otolaryngologist is important in management of these patients. The mechanism as well as the timing of facial nerve paralysis will determine the proper evaluation, consultation, and management for the patient. Patients with total or immediate paralysis as well as those with poorly prognostic audiogram results are good candidates for surgical repair.

  11. In vitro effects of recombinant activated factor VII on thrombin generation and coagulation following inhibition of platelet procoagulant activity by prasugrel.

    PubMed

    Mazzeffi, Michael; Szlam, Fania; Jakubowski, Joseph A; Tanaka, Kenichi A; Sugidachi, Atsuhiro; Levy, Jerrold H

    2013-07-01

    Prasugrel is a thienopyridyl P2Y12 antagonist with potent antiplatelet effects. At present, little is known about its effects on thrombin generation or what strategies may emergently reverse its anticoagulant effects. In the current study we evaluated whether recombinant activated factor VII may reverse prasugrel induced effects and increase thrombin generation in an in vitro model. The effect of prasugrel active metabolite, PAM (R-138727), was evaluated on platelet aggregation, thrombin generation, and rotational thromboelastometry parameters using blood from 20 healthy volunteers. Additionally, we evaluated the effects of adenosine diphosphate (ADP) and recombinant activated factor VII on restoring these parameters towards baseline values. PAM reduced maximum platelet aggregation and led to platelet disaggregation. It also decreased peak thrombin, increased lag time, and increased time to peak thrombin. Treatment with recombinant activated factor VII restored all three parameters of thrombin generation towards baseline. ADP decreased lag time and time to peak thrombin, but had no effect on peak thrombin. When recombinant activated factor VII and ADP were combined they had a greater effect on thrombin parameters than either drug alone. PAM also increased thromboelastometric clotting time and clot formation time, but had no effect on maximum clot firmness. Treatment with either recombinant activated factor VII or ADP restored these values towards baseline. Recombinant activated factor VII restores thrombin generation in the presence of PAM. In patients taking prasugrel with life-threatening refractory bleeding it has the potential to be a useful therapeutic approach. Additional clinical studies are needed to validate our findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Economic, neurobiological, and behavioral perspectives on building America’s future workforce

    PubMed Central

    Knudsen, Eric I.; Heckman, James J.; Cameron, Judy L.; Shonkoff, Jack P.

    2006-01-01

    A growing proportion of the U.S. workforce will have been raised in disadvantaged environments that are associated with relatively high proportions of individuals with diminished cognitive and social skills. A cross-disciplinary examination of research in economics, developmental psychology, and neurobiology reveals a striking convergence on a set of common principles that account for the potent effects of early environment on the capacity for human skill development. Central to these principles are the findings that early experiences have a uniquely powerful influence on the development of cognitive and social skills and on brain architecture and neurochemistry, that both skill development and brain maturation are hierarchical processes in which higher level functions depend on, and build on, lower level functions, and that the capacity for change in the foundations of human skill development and neural circuitry is highest earlier in life and decreases over time. These findings lead to the conclusion that the most efficient strategy for strengthening the future workforce, both economically and neurobiologically, and improving its quality of life is to invest in the environments of disadvantaged children during the early childhood years. PMID:16801553

  13. [Social psychiatry and neurobiology : A long overdue convergence exemplified by schizophrenia].

    PubMed

    Kawohl, W; Wyss, C; Roser, P; Brüne, M; Rössler, W; Juckel, G

    2017-05-01

    The proliferation of biological psychiatry has greatly increased over the last two decades. With the possibility to carry out brain research using modern technical methods, it seemed that social influencing factors would lose importance in the development of mental diseases; however, in actual fact this does not seem to be justified. It is necessary to overcome this separation, in that social factors are incorporated into a conceptual framework in the development of mental diseases, which simultaneously also takes the results of current neurobiological research into consideration. The aims of this review article are to summarize the current state of sociopsychiatric research and to emphasize the perspectives of the biological principles and their validity with respect to the social dimensions of psychiatry, as exemplified by schizophrenic disorders. The article presents the options for a biosocial approach in social psychiatry and gives an overview of the currently available literature. There is an abundance of neurobiological research approaches, which are closely associated with sociopsychiatric topics, such as social cognition. Social psychiatry and biological psychiatry should no longer be considered as diametrically opposed subdisciplines. On the contrary, the options which could emerge from a synthesis must be used in research and clinical practice.

  14. Linking brains and brawn: exercise and the evolution of human neurobiology.

    PubMed

    Raichlen, David A; Polk, John D

    2013-01-07

    The hunting and gathering lifestyle adopted by human ancestors around 2 Ma required a large increase in aerobic activity. High levels of physical activity altered the shape of the human body, enabling access to new food resources (e.g. animal protein) in a changing environment. Recent experimental work provides strong evidence that both acute bouts of exercise and long-term exercise training increase the size of brain components and improve cognitive performance in humans and other taxa. However, to date, researchers have not explored the possibility that the increases in aerobic capacity and physical activity that occurred during human evolution directly influenced the human brain. Here, we hypothesize that proximate mechanisms linking physical activity and neurobiology in living species may help to explain changes in brain size and cognitive function during human evolution. We review evidence that selection acting on endurance increased baseline neurotrophin and growth factor signalling (compounds responsible for both brain growth and for metabolic regulation during exercise) in some mammals, which in turn led to increased overall brain growth and development. This hypothesis suggests that a significant portion of human neurobiology evolved due to selection acting on features unrelated to cognitive performance.

  15. Neurobiological mechanisms of acupuncture for some common illnesses: a clinician's perspective.

    PubMed

    Cheng, Kwokming James

    2014-06-01

    This paper presents some previously proposed neurobiological mechanisms on how acupuncture may work in some clinical applications from a clinician's perspective. For the treatment of musculoskeletal conditions, the proposed mechanisms included microinjury, increased local blood flow, facilitated healing, and analgesia. Acupuncture may trigger a somatic autonomic reflex, thereby affecting the gastric and cardiovascular functions. Acupuncture may also change the levels of neurotransmitters such as serotonin and dopamine, thereby affecting the emotional state and craving. This mechanism may form the basis for the treatment of smoking cessation. By affecting other pain-modulating neurotransmitters such as met-enkephalin and substance P along the nociceptive pathway, acupuncture may relieve headache. Acupuncture may affect the hypothalamus pituitary axis and reduce the release of the luteinizing hormone in the treatment of polycystic ovary syndrome. In addition, two other approaches to the acupuncture mechanism, the fascia connective tissue network and the primo vascular system, are briefly reviewed. Finally, the idea of true versus sham acupuncture points, which are commonly used in clinical trials, is examined because the difference between true and sham points does not exist in the neurobiological model. Copyright © 2013. Published by Elsevier B.V.

  16. Neurobiological Phenotypes Associated with a Family History of Alcoholism

    PubMed Central

    Cservenka, Anita

    2015-01-01

    Background Individuals with a family history of alcoholism are at much greater risk for developing an alcohol use disorder (AUD) than youth or adults without such history. A large body of research suggests that there are premorbid differences in brain structure and function in family history positive (FHP) individuals relative to their family history negative (FHN) peers. Methods This review summarizes the existing literature on neurobiological phenotypes present in FHP youth and adults by describing findings across neurophysiological and neuroimaging studies. Results Neuroimaging studies have shown FHP individuals differ from their FHN peers in amygdalar, hippocampal, basal ganglia, and cerebellar volume. Both increased and decreased white matter integrity has been reported in FHP individuals compared with FHN controls. Functional magnetic resonance imaging studies have found altered inhibitory control and working memory-related brain response in FHP youth and adults, suggesting neural markers of executive functioning may be related to increased vulnerability for developing AUDs in this population. Additionally, brain activity differences in regions involved in bottom-up reward and emotional processing, such as the nucleus accumbens and amygdala, have been shown in FHP individuals relative to their FHN peers. Conclusions It is critical to understand premorbid neural characteristics that could be associated with cognitive, reward-related, or emotional risk factors that increase risk for AUDs in FHP individuals. This information may lead to the development of neurobiologically informed prevention and intervention studies focused on reducing the incidence of AUDs in high-risk youth and adults. PMID:26559000

  17. The Artilect Debate

    NASA Astrophysics Data System (ADS)

    de Garis, Hugo; Halioris, Sam

    Twenty-first-century technologies will allow the creation of massively intelligent machines, many trillions of times as smart, fast, and durable as humans. Issues concerning industrial, consumer, and military applications of mobile autonomous robots, cyborgs, and computer-based AI systems could divisively split humanity into ideological camps regarding whether "artilects" (artificial intellects) should be built or not. The artilect debate, unlike any before it, could dominate the 21st-century political landscape, and has the potential to cause conflict on a global scale. Research is needed to inform policy and individual decisions; and healthy debate should be initiated now to prepare institutions and individuals alike for the impact of AI.

  18. Student Pressure Subject of Debate

    ERIC Educational Resources Information Center

    Gewertz, Catherine

    2006-01-01

    This article discusses student pressure as a subject of debate. The latest debate about schoolwork is being fueled by three recent books: "The Homework Myth" by Alfie Kohn, "The Case Against Homework" by Sara Bennett and Nancy Kalish, and "The Overachievers", by Alexandra Robbins, which depicts overextended high…

  19. Title VII and Preferential Treatment: Response to EEOC Affirmative Action Guidelines.

    ERIC Educational Resources Information Center

    Schaffrau, Andrew J.

    1979-01-01

    Argues that Title VII prohibits preferential treatment of any group unless ordered by a court pursuant to a judicial finding of unlawful discrimination and unless the preferential treatment is limited to providing relief to judicially identified victims of that discrimination. Available from Georgetown Law Journal, 600 New Jersey Avenue,…

  20. Debate preparation/participation: an active, effective learning tool.

    PubMed

    Koklanaris, Nikki; MacKenzie, Andrew P; Fino, M Elizabeth; Arslan, Alan A; Seubert, David E

    2008-01-01

    Passive educational techniques (such as lectures) are thought to be less productive than active learning. We examined whether preparing for and participating in a debate would be an effective, active way to learn about a controversial topic. We compared quiz performance in residents who attended a lecture to residents who prepared for/participated in a debate. Twelve residents each participated in one lecture session and one debate session. Learning was evaluated via a quiz. Quizzes were given twice: before the debate/lecture and 1 week after the debate/lecture. Quiz scores were compared using repeated measures analysis of variance, with a p value of < .05 considered significant. A survey evaluating the usefulness of debating was given to all participants. There was a statistically significant difference in the pretest mean quiz score between the debate and lecture groups: 78.3% and 52.5%, respectively (p = .02). Similarly, on posttest quizzes, the average debater scored 85.8%, versus 61.7% for the lecture group (p = .003). Although no one in the debate group scored lower on a follow-up quiz, 3 residents in the lecture group did worse on follow-up. When learning about a controversial topic, residents who prepared for/participated in a debate achieved higher quiz scores and were better at retaining information than those who attended a lecture. When faced with teaching a controversial topic, organizing a debate may be more effective than giving a lecture.

  1. Toward a Neurobiology of Delusions

    PubMed Central

    Corlett, P.R.; Taylor, J.R.; Wang, X.-J.; Fletcher, P.C.; Krystal, J.H.

    2013-01-01

    Delusions are the false and often incorrigible beliefs that can cause severe suffering in mental illness. We cannot yet explain them in terms of underlying neurobiological abnormalities. However, by drawing on recent advances in the biological, computational and psychological processes of reinforcement learning, memory, and perception it may be feasible to account for delusions in terms of cognition and brain function. The account focuses on a particular parameter, prediction error – the mismatch between expectation and experience – that provides a computational mechanism common to cortical hierarchies, frontostriatal circuits and the amygdala as well as parietal cortices. We suggest that delusions result from aberrations in how brain circuits specify hierarchical predictions, and how they compute and respond to prediction errors. Defects in these fundamental brain mechanisms can vitiate perception, memory, bodily agency and social learning such that individuals with delusions experience an internal and external world that healthy individuals would find difficult to comprehend. The present model attempts to provide a framework through which we can build a mechanistic and translational understanding of these puzzling symptoms. PMID:20558235

  2. The DSM5/RDoC debate on the future of mental health research: implication for studies on human stress and presentation of the signature bank.

    PubMed

    Lupien, S J; Sasseville, M; François, N; Giguère, C E; Boissonneault, J; Plusquellec, P; Godbout, R; Xiong, L; Potvin, S; Kouassi, E; Lesage, A

    2017-01-01

    In 2008, the National Institute of Mental Health (NIMH) announced that in the next few decades, it will be essential to study the various biological, psychological and social "signatures" of mental disorders. Along with this new "signature" approach to mental health disorders, modifications of DSM were introduced. One major modification consisted of incorporating a dimensional approach to mental disorders, which involved analyzing, using a transnosological approach, various factors that are commonly observed across different types of mental disorders. Although this new methodology led to interesting discussions of the DSM5 working groups, it has not been incorporated in the last version of the DSM5. Consequently, the NIMH launched the "Research Domain Criteria" (RDoC) framework in order to provide new ways of classifying mental illnesses based on dimensions of observable behavioral and neurobiological measures. The NIMH emphasizes that it is important to consider the benefits of dimensional measures from the perspective of psychopathology and environmental influences, and it is also important to build these dimensions on neurobiological data. The goal of this paper is to present the perspectives of DSM5 and RDoC to the science of mental health disorders and the impact of this debate on the future of human stress research. The second goal is to present the "Signature Bank" developed by the Institut Universitaire en Santé Mentale de Montréal (IUSMM) that has been developed in line with a dimensional and transnosological approach to mental illness.

  3. Heptavalent Actinide Tetroxides NpO 4 – and PuO 4 –: Oxidation of Pu(V) to Pu(VII) by Adding an Electron to PuO 4

    DOE PAGES

    Gibson, John K.; de Jong, Wibe A.; Dau, Phuong D.; ...

    2017-11-14

    The highest known actinide oxidation states are Np(VII) and Pu(VII), both of which have been identified in solution and solid compounds. Recently a molecular Np(VII) complex, NpO 3(NO 3) 2-, was prepared and characterized in the gas phase. In accord with the lower stability of heptavalent Pu, no Pu(VII) molecular species has been identified. Reported here are the gas-phase syntheses and characterizations of NpO 4 - and PuO 4 -. Reactivity studies and density functional theory computations indicate the heptavalent metal oxidation state in both. This is the first instance of Pu(VII) in the absence of stabilizing effects due tomore » condensed phase solvation or crystal fields. Here, the results indicate that addition of an electron to neutral PuO 4, which has a computed electron affinity of 2.56 eV, counterintuitively results in oxidation of Pu(V) to Pu(VII), concomitant with superoxide reduction.« less

  4. Heptavalent Actinide Tetroxides NpO 4 – and PuO 4 –: Oxidation of Pu(V) to Pu(VII) by Adding an Electron to PuO 4

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gibson, John K.; de Jong, Wibe A.; Dau, Phuong D.

    The highest known actinide oxidation states are Np(VII) and Pu(VII), both of which have been identified in solution and solid compounds. Recently a molecular Np(VII) complex, NpO 3(NO 3) 2-, was prepared and characterized in the gas phase. In accord with the lower stability of heptavalent Pu, no Pu(VII) molecular species has been identified. Reported here are the gas-phase syntheses and characterizations of NpO 4 - and PuO 4 -. Reactivity studies and density functional theory computations indicate the heptavalent metal oxidation state in both. This is the first instance of Pu(VII) in the absence of stabilizing effects due tomore » condensed phase solvation or crystal fields. Here, the results indicate that addition of an electron to neutral PuO 4, which has a computed electron affinity of 2.56 eV, counterintuitively results in oxidation of Pu(V) to Pu(VII), concomitant with superoxide reduction.« less

  5. Marijuana Neurobiology and Treatment

    PubMed Central

    Elkashef, Ahmed; Vocci, Frank; Huestis, Marilyn; Haney, Margaret; Budney, Alan; Gruber, Amanda; el-Guebaly, Nady

    2008-01-01

    Marijuana is the number one illicit drug of abuse worldwide and a major public health problem, especially in the younger population. The objective of this article is to update and review the state of the science and treatments available for marijuana dependence based on a pre-meeting workshop that was presented at ISAM 2006. At the workshop, several papers were presented addressing the neurobiology and pharmacology of marijuana and treatment approaches, both psychotherapy and medications, for marijuana withdrawal. Medicolegal and ethical issues concerning marijuana medical use were also discussed. Concise summaries of these presentations are incorporated in this article, which is meant to be an updated review of the state of the science. Major advances have been made in understanding the underpinning of marijuana dependence and the role of the CNS cannabinoid system, which is a major area for targeting medications to treat marijuana withdrawal and dependence, as well as other addictions. Behavioral therapies are efficacious for facilitating abstinence from marijuana. Nefazadone, Marinol, and buspirone are showing early positive signals for efficacy in ameliorating marijuana withdrawal symptoms. Effective psychotherapeutic approaches are available and promising medications studies need to be confirmed in outpatient trials. The next few years looking promising for translational research efforts to make treatment widely accessible to patients with marijuana dependence. PMID:19042204

  6. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study.

    PubMed

    Criado-García, Juan; Fuentes, Francisco; Cruz-Teno, Cristina; García-Rios, Antonio; Jiménez-Morales, Anabel; Delgado-Lista, Javier; Mata, Pedro; Alonso, Rodrigo; López-Miranda, José; Pérez-Jiménez, Francisco

    2011-04-09

    Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97). Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

  7. Vehicle infrastructure integration (VII) based road-condition warning system for highway collision prevention.

    DOT National Transportation Integrated Search

    2009-05-01

    As a major ITS initiative, the Vehicle Infrastructure Integration (VII) program is to revolutionize : transportation by creating an enabling communication infrastructure that will open up a wide range of : safety applications. The road-condition warn...

  8. Trait and neurobiological correlates of individual differences in dream recall and dream content.

    PubMed

    Blagrove, Mark; Pace-Schott, Edward F

    2010-01-01

    Individuals differ greatly in their dream recall frequency, in their incidence of recalling types of dreams, such as nightmares, and in the content of their dreams. This chapter reviews work on the waking life correlates of these differences between people in their experience of dreaming and reviews some of the neurobiological correlates of these individual differences. The chapter concludes that despite there being trait-like aspects of general dream recall and of dream content, very few psychometrically assessed correlates for dream recall frequency and dream content have been found. More successful has been the investigation of correlates of frequency of particular types of dreams, such as nightmares and lucid dreams, and also of how waking-life experience is associated with dream content. There is also potential in establishing neurobiological correlates of individual differences in dream recall and dream content, and recent work on this is reviewed. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse.

    PubMed

    Tomie, Arthur; Grimes, Kathryn L; Pohorecky, Larissa A

    2008-06-01

    Drug abuse researchers have noted striking similarities between behaviors elicited by Pavlovian sign-tracking procedures and prominent symptoms of drug abuse. In Pavlovian sign-tracking procedures, repeated paired presentations of a small object (conditioned stimulus, CS) with a reward (unconditioned stimulus, US) elicits a conditioned response (CR) that typically consists of approaching the CS, contacting the CS, and expressing consummatory responses at the CS. Sign-tracking CR performance is poorly controlled and exhibits spontaneous recovery and long-term retention, effects that resemble relapse. Sign-tracking resembles psychomotor activation, a syndrome of behavioral responses evoked by addictive drugs, and the effects of sign-tracking on corticosterone levels and activation of dopamine pathways resemble the neurobiological effects of abused drugs. Finally, the neurobiological profile of individuals susceptible to sign-tracking resembles the pathophysiological profile of vulnerability to drug abuse, and vulnerability to sign-tracking predicts vulnerability to impulsive responding and alcohol self-administration. Implications of sign-tracking for models of drug addiction are considered.

  10. Behavioral Characteristics and Neurobiological Substrates Shared by Pavlovian Sign-Tracking and Drug Abuse

    PubMed Central

    Tomie, Arthur; Grimes, Kathryn L.; Pohorecky, Larissa A.

    2008-01-01

    Drug abuse researchers have noted striking similarities between behaviors elicited by Pavlovian sign-tracking procedures and prominent symptoms of drug abuse. In Pavlovian sign-tracking procedures, repeated paired presentations of a small object (conditioned stimulus, CS) with a reward (unconditioned stimulus, US) elicits a conditioned response (CR) that typically consists of approaching the CS, contacting the CS, and expressing consummatory responses at the CS. Sign-tracking CR performance is poorly controlled and exhibits spontaneous recovery and long-term retention, effects that resemble relapse. Sign-tracking resembles psychomotor activation, a syndrome of behavioral responses evoked by addictive drugs, and the effects of sign-tracking on corticosterone levels and activation of dopamine pathways resemble the neurobiological effects of abused drugs. Finally, the neurobiological profile of individuals susceptible to sign-tracking resembles the pathophysiological profile of vulnerability to drug abuse, and vulnerability to sign-tracking predicts vulnerability to impulsive responding and alcohol self-administration. Implications of sign-tracking for models of drug addiction are considered. PMID:18234349

  11. Sleep Neurobiology from a Clinical Perspective

    PubMed Central

    España, Rodrigo A.; Scammell, Thomas E.

    2011-01-01

    Many neurochemical systems interact to generate wakefulness and sleep. Wakefulness is promoted by neurons in the pons, midbrain, and posterior hypothalamus that produce acetylcholine, norepinephrine, dopamine, serotonin, histamine, and orexin/hypocretin. Most of these ascending arousal systems diffusely activate the cortex and other forebrain targets. NREM sleep is mainly driven by neurons in the preoptic area that inhibit the ascending arousal systems, while REM sleep is regulated primarily by neurons in the pons, with additional influence arising in the hypothalamus. Mutual inhibition between these wake- and sleep-regulating regions likely helps generate full wakefulness and sleep with rapid transitions between states. This up-to-date review of these systems should allow clinicians and researchers to better understand the effects of drugs, lesions, and neurologic disease on sleep and wakefulness. Citation: España RA; Scammell TE. Sleep neurobiology from a clinical perspective. SLEEP 2011;34(7):845-858. PMID:21731134

  12. Neurobiology of fear and specific phobias.

    PubMed

    Garcia, René

    2017-09-01

    Fear, which can be expressed innately or after conditioning, is triggered when a danger or a stimulus predicting immediate danger is perceived. Its role is to prepare the body to face this danger. However, dysfunction in fear processing can lead to psychiatric disorders in which fear outweighs the danger or possibility of harm. Although recognized as highly debilitating, pathological fear remains insufficiently treated, indicating the importance of research on fear processing. The neurobiological basis of normal and pathological fear reactions is reviewed in this article. Innate and learned fear mechanisms, particularly those involving the amygdala, are considered. These fear mechanisms are also distinguished in specific phobias, which can indeed be nonexperiential (implicating innate, learning-independent mechanisms) or experiential (implicating learning-dependent mechanisms). Poor habituation and poor extinction are presented as dysfunctional mechanisms contributing to persistence of nonexperiential and experiential phobias, respectively. © 2017 Garcia; Published by Cold Spring Harbor Laboratory Press.

  13. Reaching Out: Extending the Argument about Debate Outreach.

    ERIC Educational Resources Information Center

    Grassmick, David; Clinton, Pamela A.

    A. C. Snider has suggested that CEDA (Cross Examination Debate Association) should create an outreach program to connect CEDA debate programs with the high school policy debate community. Most debate educators would laud programs that promise to train more students in argumentation, but a pilot program shows that an outreach program does not…

  14. Curriculum Debate and Policy Change

    ERIC Educational Resources Information Center

    Elgstrom, Ole; Hellstenius, Mats

    2011-01-01

    This article investigates the underlying themes and principles that inform curriculum debate and how they are articulated in current school policy discussions. This topic is approached with the help of a case study covering the debate on which subjects should be mandatory for students at the upper secondary school curriculum in Sweden. The focus…

  15. The Two Cultures Debate Today.

    ERIC Educational Resources Information Center

    Smith, Ralph A.

    1978-01-01

    Discusses the "two cultures debate," initiated in 1959, which emphasized the moral obligation of rich countries to help poor ones, and the need to reform education in order to provide people with a common culture that included scientific literacy. Article examines reactions to the theory in 1959, directions the debate took, and status of the…

  16. Cholesterol: the debate should be terminated.

    PubMed

    Nathan, David G

    2017-07-01

    Here, I offer personal perspectives on cholesterol homeostasis that reflect my belief that certain aspects of the debate have been overstated.-Nathan, D. G. Cholesterol: the debate should be terminated. © FASEB.

  17. Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With Adverse Outcomes

    DTIC Science & Technology

    2010-07-01

    using the FVII coagulant activity (FVII:C) assay, a one- stage assay using thromboplastin tissue factor , which quantifies FVII clotting activity in...and the resultant production of dysfunctional factors II, VII, and X. This study focused on PT specifically because this measure examines the TF...ORIGINAL ARTICLE Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With

  18. Literacy as Social Action in City Debate

    ERIC Educational Resources Information Center

    Cridland-Hughes, Susan

    2012-01-01

    This study examines critical literacy and the intersections of oral, aural, written, and performative literate practices in City Debate, an afterschool program dedicated to providing debate instruction to students in a major Southeastern city. Previous research into definitions and beliefs about literacy in an urban debate program over its twenty…

  19. An interoceptive model of bulimia nervosa: A neurobiological systematic review.

    PubMed

    Klabunde, Megan; Collado, Danielle; Bohon, Cara

    2017-11-01

    The objective of our study was to examine the neurobiological support for an interoceptive sensory processing model of bulimia nervosa (BN). To do so, we conducted a systematic review of interoceptive sensory processing in BN, using the PRISMA guidelines. We searched PsychInfo, Pubmed, and Web of Knowledge databases to identify biological and behavioral studies that examine interoceptive detection in BN. After screening 390 articles for inclusion and conducting a quality assessment of articles that met inclusion criteria, we reviewed 41 articles. We found that global interoceptive sensory processing deficits may be present in BN. Specifically there is evidence of abnormal brain function, structure and connectivity in the interoceptive neural network, in addition to gastric and pain processing disturbances. These results suggest that there may be a neurobiological basis for global interoceptive sensory processing deficits in BN that remain after recovery. Data from taste and heart beat detection studies were inconclusive; some studies suggest interoceptive disturbances in these sensory domains. Discrepancies in findings appear to be due to methodological differences. In conclusion, interoceptive sensory processing deficits may directly contribute to and explain a variety of symptoms present in those with BN. Further examination of interoceptive sensory processing deficits could inform the development of treatments for those with BN. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Consciousness operationalized, a debate realigned.

    PubMed

    Carruthers, Peter; Veillet, Bénédicte

    2017-10-01

    This paper revisits the debate about cognitive phenomenology. It elaborates, defends, and improves on our earlier proposal for resolving that debate, according to which the test for irreducible phenomenology is the presence of explanatory gaps. After showing how proposals like ours have been misunderstood or misused by others, we deploy our operationalization to argue that the correct way to align the debate over cognitive phenomenology is not between sensory and (alleged) cognitive phenomenology, but rather between non-conceptual and (alleged) conceptual or propositional phenomenology. In doing so we defend three varieties of non-sensory (amodal) 1 non-conceptual phenomenology: valence, a sense of approximate number, and a sense of elapsed time. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Bridging Philosophy of Technology and Neurobiological Research: Interpreting Images from the "Slam Freezer"

    ERIC Educational Resources Information Center

    Rosenberger, Robert

    2005-01-01

    The swiftly growing field of neurobiological research utilizes highly advanced technologies (e.g., magnetic resonance imaging, electron microscopy) to mediate between investigators and the brains they investigate. Here, the author analyzes a device called the "slam freezer" that quick-freezes neurons to be studied under the microscope. Employing…

  2. The Chinese Bilingual Pilot Program, ESEA Title VII, 1974: Program Guide.

    ERIC Educational Resources Information Center

    San Francisco Unified School District, CA.

    The 1965 Elementary Secondary Education Act Title VII Chinese Bilingual Pilot Program is a bilingual/bicultural program the purpose of which is to provide for the special educational needs of children who have limited English-speaking ability, who come from environments where the dominant language is one other than English, and who come from…

  3. OATYC Journal, Vol. VII, Nos 1-2, Fall 1981-Spring 1982.

    ERIC Educational Resources Information Center

    Fullen, James, Ed.

    1982-01-01

    "OATYC Journal," which is published by the Ohio Association of Two-Year Colleges, is designed as a forum for the exchange of concepts, methods, and findings relevant to the two-year college classroom. Along with commentaries and letters of reaction from the readership, the two issues of volume VII include the following articles: (1)…

  4. The Japanese Domestic Labor Debate.

    ERIC Educational Resources Information Center

    Ueno, Chizuko

    The changing role of Japanese women can be seen in the stages of a domestic labor debate which occurred at three different times in the past 30 years. The first debate began with Ayako Ishigaki's (1955) insistence that women should have a job outside the home. Wartime production helped break down traditional divisions of labor by encouraging women…

  5. Clash! The World of Debate

    ERIC Educational Resources Information Center

    Azzam, Amy M.

    2008-01-01

    Debating has been around for a long time, with some pretty spectacular results. Look at Socrates, who was put to death in 399 BCE for corrupting the youth of Athens; his accusers could not forgive him for incessantly questioning their beliefs and making "the worse appear the better cause." More recently, debating has morphed into a sport for the…

  6. Contingency Training Alters Neurobiological Components of Emotional Resilience in Male and Female Rats.

    PubMed

    Kent, M; Scott, S; Lambert, S; Kirk, E; Terhune-Cotter, B; Thompson, B; Neal, S; Dozier, B; Bardi, M; Lambert, K

    2018-06-19

    Prior research with a rat model of behavioral therapy [i.e., effort-based reward (EBR) contingency training] suggests that strengthened associations between physical effort and desired outcomes enhance neurobiological indices of resilience. In the current study, male and female Long-Evans rats were exposed to either six weeks of EBR training or noncontingent training prior to 10 days of exposure to chronic unpredictable stress (CUS). Subsequently, all animals were exposed to a problem-solving task and then trained in a spatial learning/foraging task, the Dry Land Maze (DLM). Following habituation training and test trials, rats were assessed in a probe trial that generated a prediction error (cognitive uncertainty). Results indicated that, during CUS exposure, contingency-training enhanced dehydroepiandrosterone/corticosterone ratios (consistent with healthier stress responses), especially in male rats. Additionally, contingency training increased exploratory behaviors in the probe trial as well as differentially influenced on-task problem-solving performance in males and females. Following the probe trial, brains were exposed to histological analyses to determine the effects of sex and contingency training on various neurobiological markers. Contingency training decreased BDNF-immunoreactivity (ir) in the hippocampus CA1 and lateral habenula, implicating differential neuroplasticity responses in the training groups. Further, coordinated fos-ir activation in areas associated with emotional resilience (i.e., motivation-regulation) was observed in contingent-trained animals. In sum, the current findings confirm that behavioral training is associated with neurobiological markers of emotional resilience; however, further assessments are necessary to more accurately determine the therapeutic potential for the EBR contingency training model. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Technological Imperatives: Using Computers in Academic Debate.

    ERIC Educational Resources Information Center

    Ticku, Ravinder; Phelps, Greg

    Intended for forensic educators and debate teams, this document details how one university debate team, at the University of Iowa, makes use of computer resources on campus to facilitate storage and retrieval of information useful to debaters. The introduction notes the problem of storing and retrieving the amount of information required by debate…

  8. Biological sex affects the neurobiology of autism.

    PubMed

    Lai, Meng-Chuan; Lombardo, Michael V; Suckling, John; Ruigrok, Amber N V; Chakrabarti, Bhismadev; Ecker, Christine; Deoni, Sean C L; Craig, Michael C; Murphy, Declan G M; Bullmore, Edward T; Baron-Cohen, Simon

    2013-09-01

    In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This study seeks to answer two questions about how autism is modulated by biological sex at the level of the brain: (i) is the neuroanatomy of autism different in males and females? and (ii) does the neuroanatomy of autism fit predictions from the 'extreme male brain' theory of autism, in males and/or in females? Neuroanatomical features derived from voxel-based morphometry were compared in a sample of equal-sized high-functioning male and female adults with and without autism (n = 120, n = 30/group). The first question was investigated using a 2 × 2 factorial design, and by spatial overlap analyses of the neuroanatomy of autism in males and females. The second question was tested through spatial overlap analyses of specific patterns predicted by the extreme male brain theory. We found that the neuroanatomy of autism differed between adult males and females, evidenced by minimal spatial overlap (not different from that occurred under random condition) in both grey and white matter, and substantially large white matter regions showing significant sex × diagnosis interactions in the 2 × 2 factorial design. These suggest that autism manifests differently by biological sex. Furthermore, atypical brain areas in females with autism substantially and non-randomly (P < 0.001) overlapped with areas that were sexually dimorphic in neurotypical controls, in both grey and white matter, suggesting neural 'masculinization'. This was not seen in males with autism. How differences in neuroanatomy

  9. Online debates to enhance critical thinking in pharmacotherapy.

    PubMed

    Charrois, Theresa L; Appleton, Michelle

    2013-10-14

    To assess the impact of teaching strategies on the complexity and structure of students' arguments and type of informal reasoning used in arguments. Students were given an introduction to argumentation followed by 2 formal debates, with feedback provided in between. Four debate groups were randomly selected for evaluation. In debate 1, all groups posted 1 argument, and all 4 arguments were rationalistic and ranked as high-level arguments. In debate 2, members of the 4 groups posted a total of 33 arguments, which were evaluated and received an overall median ranking lower than that for debate 1. All debates were categorized as rationalistic. Students were able to formulate rationalistic arguments to therapeutic controversies; however, their level of argumentation decreased over the course of the study. Changes planned for the future include conducting the debates in the context of patient scenarios to increase practical applicability.

  10. Online Debates to Enhance Critical Thinking in Pharmacotherapy

    PubMed Central

    Appleton, Michelle

    2013-01-01

    Objectives. To assess the impact of teaching strategies on the complexity and structure of students’ arguments and type of informal reasoning used in arguments. Design. Students were given an introduction to argumentation followed by 2 formal debates, with feedback provided in between. Assessment. Four debate groups were randomly selected for evaluation. In debate 1, all groups posted 1 argument, and all 4 arguments were rationalistic and ranked as high-level arguments. In debate 2, members of the 4 groups posted a total of 33 arguments, which were evaluated and received an overall median ranking lower than that for debate 1. All debates were categorized as rationalistic. Conclusion. Students were able to formulate rationalistic arguments to therapeutic controversies; however, their level of argumentation decreased over the course of the study. Changes planned for the future include conducting the debates in the context of patient scenarios to increase practical applicability. PMID:24159211

  11. Neurobiological Bases of Cue- and Nicotine-induced Reinstatement of Nicotine Seeking: Implications for the Development of Smoking Cessation Medications.

    PubMed

    Stoker, Astrid K; Markou, Athina

    2015-01-01

    A better understanding of the neurobiological factors that contribute to relapse to smoking is needed for the development of efficacious smoking cessation medications. Reinstatement procedures allow the preclinical assessment of several factors that contribute to relapse in humans, including re-exposure to nicotine via tobacco smoking and the presentation of stimuli that were previously associated with nicotine administration (i.e., conditioned stimuli). This review provides an integrated discussion of the results of animal studies that used reinstatement procedures to assess the efficacy of pharmacologically targeting various neurotransmitter systems in attenuating the cue- and nicotine-induced reinstatement of nicotine seeking. The results of these animal studies have increased our understanding of the neurobiological processes that mediate the conditioned effects of stimuli that trigger reinstatement to nicotine seeking. Thus, these findings provide important insights into the neurobiological substrates that modulate relapse to tobacco smoking in humans and the ongoing search for novel efficacious smoking cessation medications.

  12. Enhanced Functional Recombinant Factor VII Production by HEK 293 Cells Stably Transfected with VKORC1 where the Gamma-Carboxylase Inhibitor Calumenin is Stably Suppressed by shRNA Transfection

    PubMed Central

    Wajih, Nadeem; Owen, John; Wallin, Reidar

    2008-01-01

    Introduction Recombinant members of the vitamin K-dependent protein family (factors IX and VII and protein C) have become important pharmaceuticals in treatment of bleeding disorders and sepsis. However, because the in vivo γ-carboxylation system in stable cell lines used for transfection has a limited capacity of post translational γ carboxylation, the recovery of fully γ-carboxylated and functional proteins is low. Materials and Methods In this work we have engineered recombinant factor VII producing HEK 293 cells to stably overexpress VKORC1, the reduced vitamin K γ-carboxylase cofactor and in addition stably silenced the γ-carboxylase inhibitory protein calumenin. Results and Conclusions Stable cell lines transfected with only a factor VII cDNA had a 9% production of functional recombinant factor VII. On the other hand, these recombinant factor VII producing cells when engineered to overexpress VKORC1 and having calumenin stably suppressed more than 80% by shRNA expression, produced 68% functional factor VII. The technology presented should be applicable to all vertebrae members of the vitamin K-dependent protein family and should lower the production cost of the clinically used factors VII, IX and protein C. PMID:18177690

  13. Enhanced functional recombinant factor VII production by HEK 293 cells stably transfected with VKORC1 where the gamma-carboxylase inhibitor calumenin is stably suppressed by shRNA transfection.

    PubMed

    Wajih, Nadeem; Owen, John; Wallin, Reidar

    2008-01-01

    Recombinant members of the vitamin K-dependent protein family (factors IX and VII and protein C) have become important pharmaceuticals in treatment of bleeding disorders and sepsis. However, because the in vivo gamma-carboxylation system in stable cell lines used for transfection has a limited capacity of post translational gamma-carboxylation, the recovery of fully gamma-carboxylated and functional proteins is low. In this work we have engineered recombinant factor VII producing HEK 293 cells to stably overexpress VKORC1, the reduced vitamin K gamma-carboxylase cofactor and in addition stably silenced the gamma-carboxylase inhibitory protein calumenin. Stable cell lines transfected with only a factor VII cDNA had a 9% production of functional recombinant factor VII. On the other hand, these recombinant factor VII producing cells when engineered to overexpress VKORC1 and having calumenin stably suppressed more than 80% by shRNA expression, produced 68% functional factor VII. The technology presented should be applicable to all vertebrae members of the vitamin K-dependent protein family and should lower the production cost of the clinically used factors VII, IX and protein C.

  14. Fe(II)- and Sulfide-Facilitated Reduction of 99Tc(VII)O4- in Microbially Reduced Hyporheic Zone Sediments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Ji-Hoon; Zachara, John M.; Fredrickson, Jim K.

    Redox-reactive, biogeochemical phases generated by reductive microbial activity in hyporheic zone sediments from a dynamic groundwater-river interaction zone were evaluated for their ability to reduce soluble pertechnetate [99Tc(VII)O4-] to less soluble Tc(IV). The sediments were bioreduced by indigenous microorganisms that were stimulated by organic substrate addition in synthetic groundwater with or without sulfate. In most treatments, 20 µmol L-1 initial aqueous Tc(VII) was reduced to near or below detection (3.82×10-9 mol L-1) over periods of days to months in suspensions of variable solids concentrations. Native sediments containing significant lithogenic Fe(II) in various phases were, in contrast, unreactive with Tc(VII). Themore » reduction rates in the bioreduced sediments increased with increases in sediment mass, in proportion to weak acid-extractable Fe(II) and sediment-associated sulfide (AVS). The rate of Tc(VII) reduction was first order with respect to both aqueous Tc(VII) concentration and sediment mass, but correlations between specific reductant concentrations and reaction rate were not found. X-ray microprobe measurements revealed a strong correlation between Tc hot spots and Fe-containing mineral particles in the sediment. However, only a portion of Fe-containing particles were Tc-hosts. The Tc-hot spots displayed a chemical signature (by EDXRF) similar to pyroxene. The application of autoradiography and electron microprobe allowed further isolation of Tc-containing particles that were invariably found to be ca 100 µm aggregates of primary mineral material embedded within a fine-grained phyllosilicate matrix. EXAFS spectroscopy revealed that the Tc(IV) within these were a combination of a Tc(IV)O2-like phase and Tc(IV)-Fe surface clusters, with a significant fraction of a TcSx-like phase in sediments incubated with SO42-. AVS was implicated as a more selective reductant at low solids concentration even though its concentration was below

  15. Fe(II)- and sulfide-facilitated reduction of 99Tc(VII)O4- in microbially reduced hyporheic zone sediments

    NASA Astrophysics Data System (ADS)

    Lee, Ji-Hoon; Zachara, John M.; Fredrickson, James K.; Heald, Steve M.; McKinley, James P.; Plymale, Andrew E.; Resch, Charles T.; Moore, Dean A.

    2014-07-01

    Redox-reactive, biogeochemical phases generated by reductive microbial activity in hyporheic zone sediments from a dynamic groundwater-river interaction zone were evaluated for their ability to reduce soluble pertechnetate [99Tc(VII)O4-] to less soluble Tc(IV). The sediments were bioreduced by indigenous microorganisms that were stimulated by organic substrate addition in synthetic groundwater with or without sulfate. In most treatments, 20 μmol L-1 initial aqueous Tc(VII) was reduced to near or below detection (3.82 × 10-9 mol L-1) over periods of days to months in suspensions of variable solids concentrations. Native sediments containing significant lithogenic Fe(II) in various phases were, in contrast, unreactive with Tc(VII). The reduction rates in the bioreduced sediments increased with increases in sediment mass, in proportion to weak acid-extractable Fe(II) and sediment-associated sulfide (AVS). The rate of Tc(VII) reduction was first order with respect to both aqueous Tc(VII) concentration and sediment mass, but correlations between specific reductant concentrations and reaction rate were not found. X-ray microprobe measurements revealed a strong correlation between Tc hot spots and Fe-containing mineral particles in the sediment. However, only a portion of Fe-containing particles were Tc-hosts. The Tc-hot spots displayed a chemical signature (by EDXRF) similar to pyroxene. The application of autoradiography and electron microprobe allowed further isolation of Tc-containing particles that were invariably found to be ca 100 μm aggregates of primary mineral material embedded within a fine-grained phyllosilicate matrix. EXAFS spectroscopy revealed that the Tc(IV) within these were a combination of a Tc(IV)O2-like phase and Tc(IV)-Fe surface clusters, with a significant fraction of a TcSx-like phase in sediments incubated with SO42-. AVS was implicated as a more selective reductant at low solids concentration even though its concentration was below that

  16. Neuroscience of Exercise: Association Among Neurobiological Mechanisms and Mental Health.

    PubMed

    Machado, Sergio; Paes, Flávia; Ferreira Rocha, Nuno Barbosa; Yuan, Ti-Fei; Mura, Gioia; Arias-Carrión, Oscar; Nardi, Antonio Egidio

    2015-01-01

    Neuroscience is an emergent research field that comprises many multidisciplinary investigations, searches for explanations about the relationship between the body and the brain. Here, we will give a little summary of this field showing the main current findings. We discuss the lack of consistent data about the relationship among exercise for neurodegenerative diseases and psychiatric disorders, sports performance and rehabilitation, and therefore, the difficult to describe cause-effect associations or to describe in detail the neurobiological mechanisms underlying these associations.

  17. Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

    PubMed

    Miyata, Naoko; Isaka, Mitsuhiro; Kojima, Hideaki; Maniwa, Tomohiro; Takahashi, Shoji; Takamiya, Osamu; Ohde, Yasuhisa

    2016-03-01

    Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

  18. The "Ad Circulorum" Fallacy and Comparative Advantage Debating or: Why Don't Debate Cases Make Sense to Outside Listeners?

    ERIC Educational Resources Information Center

    Richardson, Larry S.

    Circular reasoning is often employed in comparative advantage debate cases when only a plan and advantages are articulated without adequate reference to the resolution which inspired the proposal. The advancing of such subtopical analyses as debate cases is deleterious to the long-range interests of educational debate because the practice…

  19. Employment discrimination implications of genetic screening in the workplace under Title VII and the Rehabilitation Act.

    PubMed

    Canter, E F

    1984-01-01

    The emergence of genetic screening techniques will permit employers to exclude hypersusceptible individuals from potentially hazardous workplace environments. The denial of employment opportunities to these individuals, however, may constitute discrimination. This Note analyzes genetic screening cases with respect to currently available remedies contained in Title VII of the Civil Rights Act of 1964 and the Rehabilitation Act of 1973. The Note concludes that Title VII claims may succeed but only in limited circumstances and that Rehabilitation Act claims will encounter numerous obstacles to relief. Additionally, the Note discusses some of the implications of the use of genetic screening in the workplace.

  20. [Neurobiological foundations underlying normal and disturbed sexuality].

    PubMed

    Krüger, T H C; Kneer, J

    2017-05-01

    Sexual functions are regulated by hormonal and neurochemical factors as well as neuronal networks. An understanding of these basic principles is necessary for the diagnostics, counselling and treatment of sexual problems. Description of essential mechanisms of sexual function on a neurochemical and neuronal level. Literature search, selection and discussion of relevant studies. Analogous to the dual control model there are primary inhibitory (e. g. serotonin) and excitatory neurotransmitter systems (e.g. sex steroids and dopamine). Moreover, neuronal structures have been identified that are responsible for processing sexual stimuli. These networks are altered in subjects with sexual disorders or by pharmacological treatment, e. g. antiandrogens and selective serotonin reuptake inhibitors (SSRI) CONCLUSION: Knowledge of the neurobiology of sexuality forms the foundations for the treatment of sexual dysfunctions in psychiatry and other disciplines.

  1. Beyond Broca's and Wernicke's Areas: A New Perspective on the Neurobiology of Language.

    ERIC Educational Resources Information Center

    Lem, Lawrence

    1992-01-01

    Proposes a neurobiological model in which a greater number of brain structures than previously indicated are involved in language functions, with particular reference to second language learning. The study examines three areas of the brain rarely associated with language: the anterior cingulate gyrus, the prefrontal cortex, and the basal temporal…

  2. Testing of ENDF71x: A new ACE-formatted neutron data library based on ENDF/B-VII.1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gardiner, S. J.; Conlin, J. L.; Kiedrowski, B. C.

    The ENDF71x library [1] is the most thoroughly tested set of ACE-format data tables ever released by the Nuclear Data Team at Los Alamos National Laboratory (LANL). It is based on ENDF/B-VII. 1, the most recently released set of evaluated nuclear data files produced by the US Cross Section Evaluation Working Group (CSEWG). A variety of techniques were used to test and verify the ENDF7 1x library before its public release. These include the use of automated checking codes written by members of the Nuclear Data Team, visual inspections of key neutron data, MCNP6 calculations designed to test data formore » every included combination of isotope and temperature as comprehensively as possible, and direct comparisons between ENDF71x and previous ACE library releases. Visual inspection of some of the most important neutron data revealed energy balance problems and unphysical discontinuities in the cross sections for some nuclides. Doppler broadening of the total cross sections with increasing temperature was found to be qualitatively correct. Test calculations performed using MCNP prompted two modifications to the MCNP6 source code and also exposed bad secondary neutron yields for {sup 231,233}Pa that are present in both ENDF/B-VII.1 and ENDF/B-VII.0. A comparison of ENDF71x with its predecessor ACE library, ENDF70, showed that dramatic changes have been made in the neutron cross section data for a number of isotopes between ENDF/B-VII.0 and ENDF/B-VII.1. Based on the results of these verification tests and the validation tests performed by Kahler, et al. [2], the ENDF71x library is recommended for use in all Monte Carlo applications. (authors)« less

  3. Neurobiology of culturally common maternal responses to infant cry

    PubMed Central

    Bornstein, Marc H.; Rigo, Paola; Esposito, Gianluca; Swain, James E.; Suwalsky, Joan T. D.; Su, Xueyun; Du, Xiaoxia; Zhang, Kaihua; Cote, Linda R.; De Pisapia, Nicola; Venuti, Paola

    2017-01-01

    This report coordinates assessments of five types of behavioral responses in new mothers to their own infants’ cries with neurobiological responses in new mothers to their own infants’ cries and in experienced mothers and inexperienced nonmothers to infant cries and other emotional and control sounds. We found that 684 new primipara mothers in 11 countries (Argentina, Belgium, Brazil, Cameroon, France, Kenya, Israel, Italy, Japan, South Korea, and the United States) preferentially responded to their infants’ vocalizing distress by picking up and holding and by talking to their infants, as opposed to displaying affection, distracting, or nurturing. Complementary functional magnetic resonance imaging (fMRI) analyses of brain responses to their own infants’ cries in 43 new primipara US mothers revealed enhanced activity in concordant brain territories linked to the intention to move and to speak, to process auditory stimulation, and to caregive [supplementary motor area (SMA), inferior frontal regions, superior temporal regions, midbrain, and striatum]. Further, fMRI brain responses to infant cries in 50 Chinese and Italian mothers replicated, extended, and, through parcellation, refined the results. Brains of inexperienced nonmothers activated differently. Culturally common responses to own infant cry coupled with corresponding fMRI findings to own infant and to generic infant cries identified specific, common, and automatic caregiving reactions in mothers to infant vocal expressions of distress and point to their putative neurobiological bases. Candidate behaviors embedded in the nervous systems of human caregivers lie at the intersection of evolutionary biology and developmental cultural psychology. PMID:29078366

  4. Neurobiological phenotypes associated with a family history of alcoholism.

    PubMed

    Cservenka, Anita

    2016-01-01

    Individuals with a family history of alcoholism are at much greater risk for developing an alcohol use disorder (AUD) than youth or adults without such history. A large body of research suggests that there are premorbid differences in brain structure and function in family history positive (FHP) individuals relative to their family history negative (FHN) peers. This review summarizes the existing literature on neurobiological phenotypes present in FHP youth and adults by describing findings across neurophysiological and neuroimaging studies. Neuroimaging studies have shown FHP individuals differ from their FHN peers in amygdalar, hippocampal, basal ganglia, and cerebellar volume. Both increased and decreased white matter integrity has been reported in FHP individuals compared with FHN controls. Functional magnetic resonance imaging studies have found altered inhibitory control and working memory-related brain response in FHP youth and adults, suggesting neural markers of executive functioning may be related to increased vulnerability for developing AUDs in this population. Additionally, brain activity differences in regions involved in bottom-up reward and emotional processing, such as the nucleus accumbens and amygdala, have been shown in FHP individuals relative to their FHN peers. It is critical to understand premorbid neural characteristics that could be associated with cognitive, reward-related, or emotional risk factors that increase risk for AUDs in FHP individuals. This information may lead to the development of neurobiologically informed prevention and intervention studies focused on reducing the incidence of AUDs in high-risk youth and adults. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. 40 CFR Appendix Vii to Part 86 - Standard Bench Cycle (SBC)

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... VII to Part 86—Standard Bench Cycle (SBC) 1. The standard bench aging durability procedures [Ref. § 86.1823-08(d)] consist of aging a catalyst-oxygen-sensor system on an aging bench which follows the standard bench cycle (SBC) described in this appendix. 2. The SBC requires use of an aging bench with an...

  6. Dreams: the convergence of neurobiologic and psychoanalytic perspectives.

    PubMed

    Been, H

    1997-01-01

    Fromm's Aristotelian statement that "Dreaming is a meaningful expression of any kind of mental activity under the condition of sleep" (Fromm, 1951, p. 25) is similar to a modern neurobiological conclusion about the dreaming process. The current data from the neurosciences lead to the definition of dreams as a neuropsychological event during sleep whose manifest contents are affect laden, visual, auditory, and kinesthetic. Their functions are adaptive and problem solving in themselves. They are part of the brain's connectionist information-processing system which channel, compare, and integrate current affect-laden memories with memories of past successful strategies. Thus, the neurobiological perspective of dreams provides an underlying neuroanatomical and information-processing matrix for the dream process that further supports the current psychoanalytic view concerning their assimilative and accommodative functions. In conclusion, I would like to return to the termination phase of Mr. M's therapy. This patient planned to leave therapy approximately 22 months after the occurrence of Dream 2, as this dream had predicted. He was to be married and move to another city. Although I felt somewhat anxious about his leaving, despite his significant progress, we agreed to a termination date. Just prior to the second-to-last session Mr. M had the following dream: It took place in a large gothic building in a zoo. It is dark and depressing and filled with cages of rhesus monkeys. I go around with a nurse to inoculate the monkeys. I am scared of the virus. My future wife appears. She is immune to the virus. She is brave and she rescues me. The patient seemed pleased in relating his dream, and it offered resolution and closure for both of us despite a paucity of discussion. Two years later I received a letter from him in which he stated that he was well and had no additional "monkey dreams."

  7. The Participation and Success of Women in CEDA Debate.

    ERIC Educational Resources Information Center

    Medcalf, Lawrence D.

    A study was conducted to investigate the success of women contestants in Cross Examination Debate Association (CEDA) debate. The study sought to determine whether (1) CEDA is a more attractive debate activity for women, (2) men are more successful in CEDA debate than women, (3) the gender mix of debate teams favors all-male teams over all-female…

  8. Retarded ejaculation in men: an overview of psychological and neurobiological insights.

    PubMed

    Waldinger, Marcel D; Schweitzer, Dave H

    2005-06-01

    Disorders of orgasm and ejaculation are erroneously mixed up in the DSM-IV classification system. Male Orgasmic Disorder to denote "delayed ejaculation" is inadequate as orgasm and ejaculation represent clinical expressions of different neurobiological phenomena. Unfortunately, the DSM-IV criteria for delayed ejaculation were accepted regardless of any research with appropriate methodology and design. The psychological approach and associated psychotherapy to solve this problem is rather disappointing. The neurobiological approach, which started with animal studies, has demonstrated various neurotransmitters with the potency to inhibit ejaculation. Indeed, several experimental drugs have been tested in rats, showing the successful acceleration of ejaculation. We propose that human research should start with the development of an operational definition of delayed ejaculation. To achieve this goal, we propose unselected epidemiological stopwatch studies which also provide information on the prevalence and incidence of delayed ejaculation in men. Currently, no effective and safe drugs are available to accelerate ejaculation time in men. The best way to treat lifelong delayed ejaculation is, thus far, to inform the patients about biological and psychological inhibiting factors which they need to avoid, and to remain critical about unrealistic expectations from psychotherapy. Psychotherapy may be useful in subgroups, particularly in the absence of effective and safe drugs.

  9. Application of medical gases in the field of neurobiology

    PubMed Central

    2011-01-01

    Medical gases are pharmaceutical molecules which offer solutions to a wide array of medical needs. This can range from use in burn and stroke victims to hypoxia therapy in children. More specifically however, gases such as oxygen, helium, xenon, and hydrogen have recently come under increased exploration for their potential theraputic use with various brain disease states including hypoxia-ischemia, cerebral hemorrhages, and traumatic brain injuries. As a result, this article will review the various advances in medical gas research and discuss the potential therapeutic applications and mechanisms with regards to the field of neurobiology. PMID:22146102

  10. Internet and Video Game Addictions: Diagnosis, Epidemiology, and Neurobiology.

    PubMed

    Sussman, Clifford J; Harper, James M; Stahl, Jessica L; Weigle, Paul

    2018-04-01

    In the past 2 decades, there has been substantial increase in availability and use of digital technologies, including the Internet, computer games, smart phones, and social media. Behavioral addiction to use of technologies spawned a body of related research. The recent inclusion of Internet gaming disorder as a condition for further study in the DSM-V invigorated a new wave of researchers, thereby expanding our understanding of these conditions. This article reviews current research, theory, and practice regarding the diagnosis, epidemiology, and neurobiology of Internet and video game addictions. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia.

    PubMed

    Bossong, Matthijs G; Niesink, Raymond J M

    2010-11-01

    Cannabis use during adolescence increases the risk of developing psychotic disorders later in life. However, the neurobiological processes underlying this relationship are unknown. This review reports the results of a literature search comprising various neurobiological disciplines, ultimately converging into a model that might explain the neurobiology of cannabis-induced schizophrenia. The article briefly reviews current insights into brain development during adolescence. In particular, the role of the excitatory neurotransmitter glutamate in experience-dependent maturation of specific cortical circuitries is examined. The review also covers recent hypotheses regarding disturbances in strengthening and pruning of synaptic connections in the prefrontal cortex, and the link with latent psychotic disorders. In the present model, cannabis-induced schizophrenia is considered to be a distortion of normal late postnatal brain maturation. Distortion of glutamatergic transmission during critical periods may disturb prefrontal neurocircuitry in specific brain areas. Our model postulates that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis, transiently disturbs physiological control of the endogenous cannabinoid system over glutamate and GABA release. As a result, THC may adversely affect adolescent experience-dependent maturation of neural circuitries within prefrontal cortical areas. Depending on dose, exact time window and duration of exposure, this may ultimately lead to the development of psychosis or schizophrenia. The proposed model provides testable hypotheses which can be addressed in future studies, including animal experiments, reanalysis of existing epidemiological data, and prospective epidemiological studies in which the role of the dose-time-effect relationship should be central. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Impact of Title VII Training Programs on Community Health Center Staffing and National Health Service Corps Participation

    PubMed Central

    Rittenhouse, Diane R.; Fryer, George E.; Phillips, Robert L.; Miyoshi, Thomas; Nielsen, Christine; Goodman, David C.; Grumbach, Kevin

    2008-01-01

    PURPOSE Community health centers (CHCs) are a critical component of the health care safety net. President Bush’s recent effort to expand CHC capacity coincides with difficulty recruiting primary care physicians and substantial cuts in federal grant programs designed to prepare and motivate physicians to practice in underserved settings. This article examines the association between physicians’ attendance in training programs funded by Health Resources and Services Administration (HRSA) Title VII Section 747 Primary Care Training Grants and 2 outcome variables: work in a CHC and participation in the National Health Service Corps Loan Repayment Program (NHSC LRP). METHODS We linked the 2004 American Medical Association Physician Master-file to HRSA Title VII grants files, Medicare claims data, and data from the NHSC. We then conducted retrospective analyses to compare the proportions of physicians working in CHCs among physicians who either had or had not attended Title VII–funded medical schools or residency programs and to determine the association between having attended Title VII–funded residency programs and subsequent NHSC LRP participation. RESULTS Three percent (5,934) of physicians who had attended Title VII–funded medical schools worked in CHCs in 2001–2003, compared with 1.9% of physicians who attended medical schools without Title VII funding (P<.001). We found a similar association between Title VII funding during residency and subsequent work in CHCs. These associations remained significant (P<.001) in logistic regression models controlling for NHSC participation, public vs private medical school, residency completion date, and physician sex. A strong association was also found between attending Title VII–funded residency programs and participation in the NHSC LRP, controlling for year completed training, physician sex, and private vs public medical school. CONCLUSIONS Continued federal support of Title VII training grant programs is

  13. Ethology, Interpersonal Neurobiology, and Play: Insights into the Evolutionary Origin of the Arts

    ERIC Educational Resources Information Center

    Dissanayake, Ellen

    2017-01-01

    The author considers the biological basis of the arts in human evolution, which she holds to be grounded in ethology and interpersonal neurobiology. In the arts, she argues, ordinary reality becomes extraordinary by attention-getting, emotionally salient devices that also appear in ritualized animal behaviors, many kinds of play, and the playful…

  14. The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course.

    PubMed

    Schaefer, Jennifer E

    2016-01-01

    The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented.

  15. Debating science policy in the physics classroom.

    NASA Astrophysics Data System (ADS)

    Mayer, Shannon

    2010-03-01

    It is critically important that national and international science policy be scientifically grounded. To this end, the next generation of scientists and engineers will need to be technically competent, effective communicators of science, and engaged advisors in the debate and formulation of science policy. We describe three science policy debates developed for the physics classroom aimed at encouraging students to draw connections between their developing technical expertise and important science policy issues. The first debate considers the proposal for a 450-megawatt wind farm on public lands in Nantucket Sound and fits naturally into the curriculum related to alternative forms of energy production. The second debate considers national fuel-economy standards for sport-utility vehicles and can be incorporated into the curriculum related to heat engines. The third debate, suitable for the curriculum in optics, considers solid state lighting and implications of recent United States legislation that places stringent new energy-efficiency and reliability requirements on conventional lighting. The technical foundation for each of these debates fits naturally into the undergraduate physics curriculum and the material is suitable for a wide range of physics courses, including general science courses for non-majors.

  16. The Effect of Recombinant Activated Factor VII on Mortality in Combat-Related Casualties With Severe Trauma and Massive Transfusion

    DTIC Science & Technology

    2008-02-01

    The Effect of Recombinant Activated Factor VII on Mortality in Combat-Related Casualties With Severe Trauma and Massive Transfusion Philip C...REPORT TYPE 3. DATES COVERED 00-00-2007 to 00-00-2007 4. TITLE AND SUBTITLE The Effect of Recombinant Activated Factor VII on Mortality in Combat...Boffard study,17 the effect of rFVIIa on 24-hour blood product ad- ministration was only determined for patients who lived for at least 24 hours

  17. Investigation of inconsistent ENDF/B-VII.1 independent and cumulative fission product yields with proposed revisions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pigni, Marco T; Francis, Matthew W; Gauld, Ian C

    A recent implementation of ENDF/B-VII. independent fission product yields and nuclear decay data identified inconsistencies in the data caused by the use of updated nuclear scheme in the decay sub-library that is not reflected in legacy fission product yield data. Recent changes in the decay data sub-library, particularly the delayed neutron branching fractions, result in calculated fission product concentrations that are incompatible with the cumulative fission yields in the library, and also with experimental measurements. A comprehensive set of independent fission product yields was generated for thermal and fission spectrum neutron induced fission for 235,238U and 239,241Pu in order tomore » provide a preliminary assessment of the updated fission product yield data consistency. These updated independent fission product yields were utilized in the ORIGEN code to evaluate the calculated fission product inventories with experimentally measured inventories, with particular attention given to the noble gases. An important outcome of this work is the development of fission product yield covariance data necessary for fission product uncertainty quantification. The evaluation methodology combines a sequential Bayesian method to guarantee consistency between independent and cumulative yields along with the physical constraints on the independent yields. This work was motivated to improve the performance of the ENDF/B-VII.1 library in the case of stable and long-lived cumulative yields due to the inconsistency of ENDF/B-VII.1 fission p;roduct yield and decay data sub-libraries. The revised fission product yields and the new covariance data are proposed as a revision to the fission yield data currently in ENDF/B-VII.1.« less

  18. Management of factor VII-deficient patients undergoing joint surgeries--preliminary results of locally developed treatment regimen.

    PubMed

    Windyga, J; Zbikowski, P; Ambroziak, P; Baran, B; Kotela, I; Stefanska-Windyga, E

    2013-01-01

    Inherited factor VII (FVII) deficiency is a rare coagulation disorder with variable haemorrhagic manifestations. In severely affected cases spontaneous haemarthroses leading to advanced arthropathy have been observed. Such cases may require surgery. Therapeutic options for bleeding prevention in FVII deficient patients undergoing surgery comprise various FVII preparations but the use of recombinant activated factor VII (rFVIIa) seems to be the treatment of choice. To present the outcome of orthopaedic surgery under haemostatic coverage of rFVIIa administered according to the locally established treatment regimen in five adult patients with FVII baseline plasma levels below 10 IU dL(-1). Two patients required total hip replacement (THR); three had various arthroscopic procedures. Recombinant activated factor VII was administered every 8 h on day of surgery (D0) followed by every 12-24 h for the subsequent 9-14 days, depending on the type of surgery. Factor VII plasma coagulation activity (FVII:C) was determined daily with no predefined therapeutic target levels. Doses of rFVIIa on D0 ranged from 18 to 37 μg kg(-1) b.w. and on the subsequent days--from 13 to 30 μg kg(-1) b.w. Total rFVIIa dose per procedure ranged from 16 to 37.5 mg, and the total number of doses per procedure was 16-31. None of our patients developed excessive bleeding including those in whom FVII:C trough levels returned nearly to the baseline level on the first post-op day. Preliminary results demonstrate that rFVIIa administered according to our treatment regimen is an effective and safe haemostatic agent for hypoproconvertinaemia patients undergoing orthopaedic surgery. © 2012 Blackwell Publishing Ltd.

  19. The Back Pay Remedy in Title VII Class Actions: Problems of Procedure

    ERIC Educational Resources Information Center

    Edwards, Charles A.

    1974-01-01

    The class action for back pay has developed as a significant factor in employment discrimination litigation under Title VII of the Civil Rights Act of 1964. Problems of demonstrating each class member's entitlement are examined and a bifurcated trial procedure is proposed as a method for handling such cases. (JT)

  20. Titi Monkeys as a Novel Non-Human Primate Model for the Neurobiology of Pair Bonding


    PubMed Central

    Bales, Karen L.; Arias del Razo, Rocío; Conklin, Quinn A.; Hartman, Sarah; Mayer, Heather S.; Rogers, Forrest D.; Simmons, Trenton C.; Smith, Leigh K.; Williams, Alexia; Williams, Donald R.; Witczak, Lynea R.; Wright, Emily C.

    2017-01-01

    It is now widely recognized that social bonds are critical to human health and well-being. One of the most important social bonds is the attachment relationship between two adults, known as the pair bond. The pair bond involves many characteristics that are inextricably linked to quality of health, including providing a secure psychological base and acting as a social buffer against stress. The majority of our knowledge about the neurobiology of pair bonding comes from studies of a socially monogamous rodent, the prairie vole (Microtus ochrogaster), and from human imaging studies, which inherently lack control. Here, we first review what is known of the neurobiology of pair bonding from humans and prairie voles. We then present a summary of the studies we have conducted in titi monkeys (Callicebus cupreus)—a species of socially monogamous New World primates. Finally, we construct a neural model based on the location of neuropeptide receptors in the titi monkey brain, as well as the location of neural changes in our imaging studies, with some basic assumptions based on the prairie vole model. In this model, we emphasize the role of visual mating stimuli as well as contributions of the dopaminergic reward system and a strong role for the lateral septum. This model represents an important step in understanding the neurobiology of social bonds in non-human primates, which will in turn facilitate a better understanding of these mechanisms in humans. PMID:28955178

  1. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

    PubMed Central

    2011-01-01

    Background Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. Results This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97). Conclusions Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels. PMID:21477332

  2. Neurobiology of Aggression and Violence

    PubMed Central

    Siever, Larry J.

    2014-01-01

    Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of “top-down” control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of “top-down” control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/ gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance “top-down” control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic. PMID:18346997

  3. Behavioral inhibition: a neurobiological perspective.

    PubMed

    Morgan, Barak E

    2006-08-01

    Behavioral inhibition (BI) during early childhood has been associated with subsequent development of anxiety disorders. However, understanding of the neuroanatomical substrates of BI in humans generally has not kept pace with that of anxiety disorders. Recent interpretations and implementations of Gray's and Kagan's concepts of BI are examined from the perspective of current neurobiological models. Particular attention is given to evidence pointing to conceptual and operational limitations of self-report scales purported to measure trait BI in adults, and especially to inconsistent correlations between such behavioral inhibition system (BIS) scores and amygdala and autonomic responses to fear- or startle-inducing stimuli. Evidence showing a dissociation of both BI and trait anxiety from the amygdala is considered. Possible reasons for the poor association between BIS and trait anxiety self-report scale scores and predicted physiological outputs of the BIS are identified. Reasons to distinguish between the neural bases of BI as against trait anxiety also are discussed. The need to critically examine the role of the amygdala in BI and trait anxiety, as well as to consider other brain areas that appear to be involved in subserving these emotional traits, is emphasized.

  4. SLY1 and Syntaxin 18 specify a distinct pathway for procollagen VII export from the endoplasmic reticulum

    PubMed Central

    Nogueira, Cristina; Erlmann, Patrik; Villeneuve, Julien; Santos, António JM; Martínez-Alonso, Emma; Martínez-Menárguez, José Ángel; Malhotra, Vivek

    2014-01-01

    TANGO1 binds and exports Procollagen VII from the endoplasmic reticulum (ER). In this study, we report a connection between the cytoplasmic domain of TANGO1 and SLY1, a protein that is required for membrane fusion. Knockdown of SLY1 by siRNA arrested Procollagen VII in the ER without affecting the recruitment of COPII components, general protein secretion, and retrograde transport of the KDEL-containing protein BIP, and ERGIC53. SLY1 is known to interact with the ER-specific SNARE proteins Syntaxin 17 and 18, however only Syntaxin 18 was required for Procollagen VII export. Neither SLY1 nor Syntaxin 18 was required for the export of the equally bulky Procollagen I from the ER. Altogether, these findings reveal the sorting of bulky collagen family members by TANGO1 at the ER and highlight the existence of different export pathways for secretory cargoes one of which is mediated by the specific SNARE complex containing SLY1 and Syntaxin 18. DOI: http://dx.doi.org/10.7554/eLife.02784.001 PMID:24842878

  5. A STUDY OF THE CONCURRENT VALIDITY OF THE MINNESOTA TESTS OF CREATIVE THINKING, ABBR. FORM VII, FOR EIGHTH GRADE INDUSTRIAL ARTS STUDENTS.

    ERIC Educational Resources Information Center

    DUENK, LESTER G.

    THE PRIMARY OBJECTIVE OF THIS STUDY WAS TO ESTABLISH THE CONCURRENT VALIDITY OF THE MINNESOTA TESTS OF CREATIVE THINKING, ABBREVIATED FORM VII, (MTCT VII) BY DETERMINING THE RELATIONSHIP BETWEEN ITS SCORES AND CREATIVE ABILITY AS MEASURED BY ACCUMULATED TEACHER RATINGS OF INDUSTRIAL ARTS PROJECTS AND INVESTIGATOR-DEVELOPED TESTS OF CREATIVITY. THE…

  6. Student-Designed Service-Learning Projects in an Undergraduate Neurobiology Course.

    PubMed

    Northcutt, Katharine V

    2016-03-01

    One of the challenges in teaching a service-learning course is obtaining student buy-in from all students in the course. To circumvent this problem, I have let students in my undergraduate Neurobiology course design their own service-learning projects at the beginning of the semester. Although this can be chaotic because it requires last-minute planning, I have made it successful through facilitating student communication in the classroom, requiring thorough project proposals, meeting with students regularly, and monitoring group progress through written reflection papers. Most of my students have strong opinions about the types of projects that they want to carry out, and many students have used connections that they have already made with local organizations. Almost all projects that students have designed to this point involve teaching basic concepts of neurobiology to children of various ages while simultaneously sparking their interest in science. Through taking ownership of the project and designing it such that it works well with their strengths, interests, and weekly schedule, students have become more engaged in service learning and view it as a valuable experience. Despite some class time being shifted away from more traditional assignments, students have performed equally well in the course, and they are more eager to talk with others about course concepts. Furthermore, the feedback that I have received from community partners has been excellent, and some students have maintained their work with the organizations.

  7. Debating Paul

    ERIC Educational Resources Information Center

    Torbett, David

    2007-01-01

    This classroom note describes the lessons I learned from the use of formal debates during the two semesters I taught "Paul and Early Christianity" to undergraduates at a liberal arts college in Ohio. The purpose of the course was primarily to give students the exegetical skills to understand Paul in his own context. The secondary purpose…

  8. The default mode network and recurrent depression: a neurobiological model of cognitive risk factors.

    PubMed

    Marchetti, Igor; Koster, Ernst H W; Sonuga-Barke, Edmund J; De Raedt, Rudi

    2012-09-01

    A neurobiological account of cognitive vulnerability for recurrent depression is presented based on recent developments of resting state neural networks. We propose that alterations in the interplay between task positive (TP) and task negative (TN) elements of the Default Mode Network (DMN) act as a neurobiological risk factor for recurrent depression mediated by cognitive mechanisms. In the framework, depression is characterized by an imbalance between TN-TP components leading to an overpowering of TP by TN activity. The TN-TP imbalance is associated with a dysfunctional internally-focused cognitive style as well as a failure to attenuate TN activity in the transition from rest to task. Thus we propose the TN-TP imbalance as overarching neural mechanism involved in crucial cognitive risk factors for recurrent depression, namely rumination, impaired attentional control, and cognitive reactivity. During remission the TN-TP imbalance persists predisposing to vulnerability of recurrent depression. Empirical data to support this model is reviewed. Finally, we specify how this framework can guide future research efforts.

  9. The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas

    PubMed Central

    Friston, K. J.

    2010-01-01

    This article explores the notion that Freudian constructs may have neurobiological substrates. Specifically, we propose that Freud’s descriptions of the primary and secondary processes are consistent with self-organized activity in hierarchical cortical systems and that his descriptions of the ego are consistent with the functions of the default-mode and its reciprocal exchanges with subordinate brain systems. This neurobiological account rests on a view of the brain as a hierarchical inference or Helmholtz machine. In this view, large-scale intrinsic networks occupy supraordinate levels of hierarchical brain systems that try to optimize their representation of the sensorium. This optimization has been formulated as minimizing a free-energy; a process that is formally similar to the treatment of energy in Freudian formulations. We substantiate this synthesis by showing that Freud’s descriptions of the primary process are consistent with the phenomenology and neurophysiology of rapid eye movement sleep, the early and acute psychotic state, the aura of temporal lobe epilepsy and hallucinogenic drug states. PMID:20194141

  10. The State of College Debate According to a Survey of Its Coaches: Data to Ground the Discussion of Debate and Civic Engagement

    ERIC Educational Resources Information Center

    Hlavacik, Mark; Lain, Brian; Ivanovic, Matea; Ontiveros-Kersch, Brian

    2016-01-01

    In 2015, prominent figures from the debate community gathered at Penn State for a Conference on Speech and Debate as Civic Education. Convened in response to a perceived decline in debate's contributions to civic education, the conference also aimed to start a conversation about the future of debate education. Although a great deal can be learned…

  11. Management of Surgical Third Lower Molar Extraction and Postoperative Progress in Patients With Factor VII Deficiency: A Clinical Protocol and Focus on This Rare Pathologic Entity.

    PubMed

    Passarelli, Pier Carmine; Pasquantonio, Guido; D'Addona, Antonio

    2017-10-01

    The purpose of the present study was to analyze the management of surgical third molar extraction and postoperative progress in patients with a diagnosis of factor VII deficiency. Close collaboration between the oral-maxillofacial surgeon and hematologist will allow the team to categorize the risk and operate safely, thereby minimizing the incidence and severity of intraoperative and postoperative complications. The present retrospective study included 7 patients with factor VII deficiency who had undergone third lower molar surgery. Their factor VII deficiency ranged from 10.5 to 21.0%. Recombinant activated factor VII (rFVIIa) (coagulation factor VIIa [recombinant]; NovoSeven RT; Novo Nordisk, Bagsvaerd, Denmark) was transfused intravenously in a single dose of 25 μg/kg body weight, 30 minutes before surgical extractions. After the surgery, betamethasone, an analgesic, and an ice pack were administered. Pretreatment with recombinant activated factor VII resulted in excellent hemostasis. No hemorrhagic complications and no postoperative major bleeding were observed. The extraction of the third lower molar appears to be a safe procedure for patients with factor VII deficiency when appropriate prophylaxis with rFVIIa is used. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  12. The Past and Future of Presidential Primary Debates.

    ERIC Educational Resources Information Center

    Ritter, Kurt; Hellweg, Susan A.

    Studies focusing on televised presidential primary debates include four prespectives. From a historical perspective, televised presidential primary debates have increased slowly from 1956 through 1980. With the 1975 Federal Communications Commission ruling that independently sponsored campaign debates were news events exempt from "equal…

  13. Not all reading disabilities are dyslexia: distinct neurobiology of specific comprehension deficits.

    PubMed

    Cutting, Laurie E; Clements-Stephens, Amy; Pugh, Kenneth R; Burns, Scott; Cao, Aize; Pekar, James J; Davis, Nicole; Rimrodt, Sheryl L

    2013-01-01

    Although an extensive literature exists on the neurobiological correlates of dyslexia (DYS), to date, no studies have examined the neurobiological profile of those who exhibit poor reading comprehension despite intact word-level abilities (specific reading comprehension deficits [S-RCD]). Here we investigated the word-level abilities of S-RCD as compared to typically developing readers (TD) and those with DYS by examining the blood oxygenation-level dependent response to words varying on frequency. Understanding whether S-RCD process words in the same manner as TD, or show alternate pathways to achieve normal word-reading abilities, may provide insights into the origin of this disorder. Results showed that as compared to TD, DYS showed abnormal covariance during word processing with right-hemisphere homologs of the left-hemisphere reading network in conjunction with left occipitotemporal underactivation. In contrast, S-RCD showed an intact neurobiological response to word stimuli in occipitotemporal regions (associated with fast and efficient word processing); however, inferior frontal gyrus (IFG) abnormalities were observed. Specifically, TD showed a higher-percent signal change within right IFG for low-versus-high frequency words as compared to both S-RCD and DYS. Using psychophysiological interaction analyses, a coupling-by-reading group interaction was found in right IFG for DYS, as indicated by a widespread greater covariance between right IFG and right occipitotemporal cortex/visual word-form areas, as well as bilateral medial frontal gyrus, as compared to TD. For S-RCD, the context-dependent functional interaction anomaly was most prominently seen in left IFG, which covaried to a greater extent with hippocampal, parahippocampal, and prefrontal areas than for TD for low- as compared to high-frequency words. Given the greater lexical access demands of low frequency as compared to high-frequency words, these results may suggest specific weaknesses in accessing

  14. Not All Reading Disabilities Are Dyslexia: Distinct Neurobiology of Specific Comprehension Deficits

    PubMed Central

    Clements-Stephens, Amy; Pugh, Kenneth R.; Burns, Scott; Cao, Aize; Pekar, James J.; Davis, Nicole; Rimrodt, Sheryl L.

    2013-01-01

    Abstract Although an extensive literature exists on the neurobiological correlates of dyslexia (DYS), to date, no studies have examined the neurobiological profile of those who exhibit poor reading comprehension despite intact word-level abilities (specific reading comprehension deficits [S-RCD]). Here we investigated the word-level abilities of S-RCD as compared to typically developing readers (TD) and those with DYS by examining the blood oxygenation-level dependent response to words varying on frequency. Understanding whether S-RCD process words in the same manner as TD, or show alternate pathways to achieve normal word-reading abilities, may provide insights into the origin of this disorder. Results showed that as compared to TD, DYS showed abnormal covariance during word processing with right-hemisphere homologs of the left-hemisphere reading network in conjunction with left occipitotemporal underactivation. In contrast, S-RCD showed an intact neurobiological response to word stimuli in occipitotemporal regions (associated with fast and efficient word processing); however, inferior frontal gyrus (IFG) abnormalities were observed. Specifically, TD showed a higher-percent signal change within right IFG for low-versus-high frequency words as compared to both S-RCD and DYS. Using psychophysiological interaction analyses, a coupling-by-reading group interaction was found in right IFG for DYS, as indicated by a widespread greater covariance between right IFG and right occipitotemporal cortex/visual word-form areas, as well as bilateral medial frontal gyrus, as compared to TD. For S-RCD, the context-dependent functional interaction anomaly was most prominently seen in left IFG, which covaried to a greater extent with hippocampal, parahippocampal, and prefrontal areas than for TD for low- as compared to high-frequency words. Given the greater lexical access demands of low frequency as compared to high-frequency words, these results may suggest specific weaknesses in

  15. The next phase of Title VII funding for training primary care physicians for America's health care needs.

    PubMed

    Phillips, Robert L; Turner, Barbara J

    2012-01-01

    Health care reform will add millions of Americans to the ranks of the insured; however, their access to health care is threatened by a deep decline in the production of primary care physicians. Poorer access to primary care risks poorer health outcomes and higher costs. Meeting this increased demand requires a major investment in primary care training. Title VII, Section 747 of the Public Health Service Act previously supported the growth of the health care workforce but has been severely cut over the past 2 decades. New and expanded Title VII initiatives are required to increase the production of primary care physicians; establish high-functioning academic, community-based training practices; increase the supply of well-trained primary care faculty; foster innovation and rigorous evaluation of these programs; and ultimately to improve the responsiveness of teaching hospitals to community needs. To accomplish these goals, Congress should act on the Council on Graduate Medical Education's recommendation to increase funding for Title VII, Section 747 roughly 14-fold to $560 million annually. This amount represents a small investment in light of the billions that Medicare currently spends to support graduate medical education, and both should be held to account for meeting physician workforce needs. Expansion of Title VII, Section 747 with the goal of improving access to primary care would be an important part of a needed, broader effort to counter the decline of primary care. Failure to launch such a national primary care workforce revitalization program will put the health and economic viability of our nation at risk.

  16. The Self-Organizing Psyche: Nonlinear and Neurobiological Contributions to Psychoanalysis

    NASA Astrophysics Data System (ADS)

    Stein, A. H.

    Sigmund Freud attempted to align nineteenth century biology (and the dynamically conservative, continuous, Newtonian mechanics that underlie it) with discontinuous conscious experience. His tactics both set the future course for psychoanalytic development and introduced seemingly intractable complications into its metapsychology. In large part, these arose from what we now recognize were biological errors and dynamical oversimplifications amid his physical assumptions. Their correction, brought about by integrating nonlinear dynamics and neuro-biological research findings with W. Bion's reading of metapsychology, fundamentally supports a psychoanalysis based upon D. W. Winnicott's ideas surrounding play within transitional space.

  17. Neurobiological and Memory Models of Risky Decision Making in Adolescents versus Young Adults

    ERIC Educational Resources Information Center

    Reyna, Valerie F.; Estrada, Steven M.; DeMarinis, Jessica A.; Myers, Regina M.; Stanisz, Janine M.; Mills, Britain A.

    2011-01-01

    Predictions of fuzzy-trace theory and neurobiological approaches are examined regarding risk taking in a classic decision-making task--the framing task--as well as in the context of real-life risk taking. We report the 1st study of framing effects in adolescents versus adults, varying risk and reward, and relate choices to individual differences,…

  18. Speech perception at the interface of neurobiology and linguistics.

    PubMed

    Poeppel, David; Idsardi, William J; van Wassenhove, Virginie

    2008-03-12

    Speech perception consists of a set of computations that take continuously varying acoustic waveforms as input and generate discrete representations that make contact with the lexical representations stored in long-term memory as output. Because the perceptual objects that are recognized by the speech perception enter into subsequent linguistic computation, the format that is used for lexical representation and processing fundamentally constrains the speech perceptual processes. Consequently, theories of speech perception must, at some level, be tightly linked to theories of lexical representation. Minimally, speech perception must yield representations that smoothly and rapidly interface with stored lexical items. Adopting the perspective of Marr, we argue and provide neurobiological and psychophysical evidence for the following research programme. First, at the implementational level, speech perception is a multi-time resolution process, with perceptual analyses occurring concurrently on at least two time scales (approx. 20-80 ms, approx. 150-300 ms), commensurate with (sub)segmental and syllabic analyses, respectively. Second, at the algorithmic level, we suggest that perception proceeds on the basis of internal forward models, or uses an 'analysis-by-synthesis' approach. Third, at the computational level (in the sense of Marr), the theory of lexical representation that we adopt is principally informed by phonological research and assumes that words are represented in the mental lexicon in terms of sequences of discrete segments composed of distinctive features. One important goal of the research programme is to develop linking hypotheses between putative neurobiological primitives (e.g. temporal primitives) and those primitives derived from linguistic inquiry, to arrive ultimately at a biologically sensible and theoretically satisfying model of representation and computation in speech.

  19. Detection of O VII Lambda 1522 in IUE Spectra of Planetary Nebula Nuclei and Other Hot Stars

    NASA Technical Reports Server (NTRS)

    Feibelman, Walter A.

    1999-01-01

    We present the first detection of O VII lambda 1522 emission or absorption from archival IUE spectra in 14 planetary nebula nuclei and three PG 1159-type stars. The n = 5 approaching 6 transition of O VII was determined by Kruk & Werner and observed by them in the spectrum of the very hot PG 1159-type star H1504+65 from data obtained with the Hopkins Ultraviolet Telescope (HUT). Emission-line fluxes or absorption equivalent widths as well as radial velocities for the program stars are presented. The precise rest wavelength for the 5 approaching 6 transition requires further investigation.

  20. ANTIGENIC STRUCTURE OF THE ACTINOMYCETALES VII.

    PubMed Central

    Kwapinski, J. B.

    1964-01-01

    Kwapinski, J. B. (The University of New England, Armidale, Australia). Antigenic structure of the Actinomycetales. VII. Chemical and serological similarities of cell walls from 100 Actinomycetales strains. J. Bacteriol. 88:1211–1219. 1964.—Cell walls prepared mechanically from 100 strains of Actinomycetales were studied by chromatographic and serological methods. The cell walls of Actinomyces were found to be serologically related to those of the corynebacteria and to some strains of mycobacteria and nocardiae. The cell walls of nocardiae appeared to be more closely related to those of the mycobacteria, Streptomyces, Micromonospora, and Waksmania. The cell walls of Micromonospora and Waksmania showed certain serological similarities to those of Thermoactinomyces and nocardiae. Micropolyspora was antigenically different from other species of the Actinomycetales. Three serological groups of mycobacteria and four groups of nocardiae were distinguished. PMID:14234773

  1. Thinking About the Greenfield-Griffiths Debate.

    ERIC Educational Resources Information Center

    Kendell, Richard; Byrne, David R.

    1977-01-01

    The continuing debate between Daniel Griffiths and T. Barr Greenfield over the respective merits of the "theory-based movement" or "positivist" view of educational administration and the "phenomenological" view that organizational theories should properly consist of "multifaceted images of organizations" has become more a political debate than an…

  2. New Insights on Neurobiological Mechanisms underlying Alcohol Addiction

    PubMed Central

    Cui, Changhai; Noronha, Antonio; Morikawa, Hitoshi; Alvarez, Veronica A.; Stuber, Garret D.; Szumlinski, Karen K.; Kash, Thomas L.; Roberto, Marisa; Wilcox, Mark V.

    2012-01-01

    Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence. PMID:23159531

  3. Debating Values: Key Issues in Formatting an Argumentative Case.

    ERIC Educational Resources Information Center

    Scott, David K.

    This paper analyzes the components of an "ideal" debate using a non-policy proposition. It is argued that debates using non-policy propositions are currently plagued by a variety of problems. Value propositions on the college level are dissimilar to the value propositions used in high school Lincoln-Douglas debate. Many debaters are…

  4. Optimizing Cr(VI) and Tc(VII) remediation through nano-scale biomineral engineering

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cutting, R. S.; Coker, V. S.; Telling, N. D.

    2009-09-09

    To optimize the production of biomagnetite for the bioremediation of metal oxyanion contaminated waters, the reduction of aqueous Cr(VI) to Cr(III) by two biogenic magnetites and a synthetic magnetite was evaluated under batch and continuous flow conditions. Results indicate that nano-scale biogenic magnetite produced by incubating synthetic schwertmannite powder in cell suspensions of Geobacter sulfurreducens is more efficient at reducing Cr(VI) than either biogenic nano-magnetite produced from a suspension of ferrihydrite 'gel' or synthetic nano-scale Fe{sub 3}O{sub 4} powder. Although X-ray Photoelectron Spectroscopy (XPS) measurements obtained from post-exposure magnetite samples reveal that both Cr(III) and Cr(VI) are associated with nanoparticlemore » surfaces, X-ray Magnetic Circular Dichroism (XMCD) studies indicate that some Cr(III) has replaced octahedrally coordinated Fe in the lattice of the magnetite. Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) measurements of total aqueous Cr in the associated solution phase indicated that, although the majority of Cr(III) was incorporated within or adsorbed to the magnetite samples, a proportion ({approx}10-15 %) was released back into solution. Studies of Tc(VII) uptake by magnetites produced via the different synthesis routes also revealed significant differences between them as regards effectiveness for remediation. In addition, column studies using a {gamma}-camera to obtain real time images of a {sup 99m}Tc(VII) radiotracer were performed to visualize directly the relative performances of the magnetite sorbents against ultra-trace concentrations of metal oxyanion contaminants. Again, the magnetite produced from schwertmannite proved capable of retaining more ({approx}20%) {sup 99m}Tc(VII) than the magnetite produced from ferrihydrite, confirming that biomagnetite production for efficient environmental remediation can be fine-tuned through careful selection of the initial Fe(III) mineral

  5. A Taxonomy of CEDA Debate Critics.

    ERIC Educational Resources Information Center

    Dudczak, Craig A.; Day, Donald L.

    To develop a taxonomy of Cross Examination Debate Association (CEDA) critics, a study associated professed judging philosophy and responses to survey questions with ballot behavior and elaborated judging profiles. Subjects were debate critics who judged rounds at CEDA tournaments in the Northeast during the Spring 1989 season. In all, 13 critics…

  6. School Boundary Debate Divides Minnesota Suburb

    ERIC Educational Resources Information Center

    Samuels, Christina A.

    2011-01-01

    The author discusses how an assignment plan intended to keep schools socioeconomically balanced spurs a bitter debate in suburban Eden Prairie. The boundary debate in the 9,700-student Eden Prairie, Minnesota, district has been bruising. Eden Prairie adopted new school attendance boundaries this year based on socioeconomic balance, ensuring for…

  7. The Neurobiology of Self-knowledge in Depressed and Self-injurious Youth

    PubMed Central

    Quevedo, Karina; Martin, Jodi; Scott, Hannah; Smyda, Garry; Pfeifer, Jennifer H.

    2016-01-01

    There is limited information regarding the neurobiology underlying non-suicidal self-injury (NSSI) in clinically-referred youth. However, the salience of disturbed interpersonal relationships and disrupted self-processing associated with NSSI suggests the neural basis of social processes as a key area for additional study. Adolescent participants (N=123; M=14.75 years, SD=1.64) were divided into three groups: NSSI plus depression diagnosis (NSSI), depression only (DEP), healthy controls (HC). In the scanner, participants completed an Interpersonal Self-Processing task by taking direct (own) and indirect (mothers’, best friends’, or classmates’) perspectives regarding self-characteristics. Across all perspectives, NSSI showed higher BOLD activation in limbic areas, and anterior and posterior cortical midline structures versus DEP and HC, while HC showed greater activity in rostrolateral, frontal pole and occipital cortex than NSSI and DEP youth. Moreover, NSSI youth showed heightened responses in amygdala, hippocampus, parahippocampus, and fusiform when taking their mothers’ perspective, which were negatively correlated with self-reports of the mother’s support of adolescents’ emotional distress in the NSSI group. NSSI youth also yielded greater precuneus and posterior cingulate cortex activity during indirect self-processing from their classmates’ perspective. Findings suggest a role for disruptions in self- and emotion-processing, and conflicted social relationships in the neurobiology of NSSI among depressed adolescents. PMID:27442923

  8. Stereotypy II: A Review of Neurobiological Interpretations and Suggestions for an Integration with Behavioral Methods

    ERIC Educational Resources Information Center

    Rapp, John T.; Vollmer; Timothy R.

    2005-01-01

    Stereotypy is a relatively common behavioral disorder displayed by individuals with developmental disabilities, including autism. In this paper, we review selected studies on neurobiological interpretations of stereotypy and pharmacological interventions for stereotypy. Specifically, we review studies that evaluated the effects of serotonin uptake…

  9. Rhinology Future Debates, an EUFOREA Report.

    PubMed

    Fokkens, W J; Bachert, C; Bernal-Sprekelsen, M; Bousquet, J; Djandji, M; Dorenbaum, A; Hakimi-Mehr, D; Hendry, S; Hopkins, C; Leunig, A; Mannent, L; Mucha, D; Onerci, M; Pugin, B; Toppila-Salmi, S; Rowe, P; Seys, S F; Stimson, S; Strzembosz, A; Hellings, P W

    2017-12-01

    The first Rhinology Future Debates was held in Brussels in December 2016, organized by EUFOREA (European Forum for Research and Education in Allergy and Airways diseases). The purpose of these debates is to bring novel developments in the field of Rhinology to the attention of the medical, paramedical and patient community, in a highly credible and balanced context. For the first time in Rhinology, a peer to peer scientific exchange with key experts in the field of rhinology and key medical colleagues from leading industries let to a brainstorming and discussion event on a number of hot issues in Rhinology. Novel developments are presented by key experts from industry and/or key thought leaders in Rhinology, and then followed by a lively debate on the potential positioning of new developments in care pathways, the strengths and weaknesses of the novel development(s), and comparisons with existing and/or competing products, devices, and/or molecules. As all debates are recorded and distributed on-line with limited editing (www.rhinology-future.com), EUFOREA aims at maximizing the education of the target groups on novel developments, allowing a critical appraisal of the future and a more rapid implementation of promising novel tools, techniques and/or molecules in clinical practise in Europe. The next Rhinology Future debate will be held in Brussels in December 2017.

  10. Neurobiological Processes of Risk and Resilience in Adolescence: Implications for Policy and Prevention Science

    ERIC Educational Resources Information Center

    Busso, Daniel S.

    2014-01-01

    This article focuses on the concepts of risk and resilience and their potential to inform clinical interventions, school-based prevention programs, and social policies. Research suggests that childhood adversity can trigger a cascade of psychological and neurobiological events that can lead to mental disorders in later life. Yet little is known…

  11. VizieR Online Data Catalog: Effective collision strengths of Si VII (Sossah+, 2014)

    NASA Astrophysics Data System (ADS)

    Sossah, A. M.; Tayal, S. S.

    2017-08-01

    The purpose of present work is to calculate more accurate data for Si VII by using highly accurate target descriptions and by including a sufficient number of target states in the close-coupling expansion. We also included fine-structure effects in the close-coupling expansions to account for the relativistic effects. We used the B-spline Breit-Pauli R-matrix (BSR) codes (Zatsarinny 2006CoPhC.174..273Z) in our scattering calculations. The present method utilizes the term-dependent non-orthogonal orbital sets for the description of the target wave functions and scattering functions. The collisional and radiative parameters have been calculated for all forbidden and allowed transitions between the lowest 92 LSJ levels of 2s22p4, 2s2p5, 2p6, 2s22p33s, 2s22p33p, 2s22p33d, and 2s2p43s configurations of Si VII. (3 data files).

  12. Is Dance a Sport?: A Twenty-First-Century Debate

    ERIC Educational Resources Information Center

    Guarino, Lindsay

    2015-01-01

    This article discusses a new debate which has emerged for dancers. For many years dancers debated dance as art versus entertainment. This age-old debate still exists without a consensus, yet there is suddenly a new generation of dancers with a fresh debate. Legions of young performers are fervently proclaiming that their dance is actually a sport.…

  13. Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII

    PubMed Central

    Rowan, Daniel J.; Tomatsu, Shunji; Grubb, Jeffrey H.; Montaño, Adriana M.; Sly, William S.

    2012-01-01

    Summary Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases caused by mutations in lysosomal enzymes involved in degradation of glycosaminoglycans (GAGs). Patients with MPS grow poorly and become physically disabled due to systemic bone disease. While many of the major skeletal effects in mouse models for MPS have been described, no detailed analysis that compares GAGs levels and characteristics of bone by micro-CT has been done. The aims of this study were to assess severity of bone dysplasia among four MPS mouse models (MPS I, IIIA, IVA and VII), to determine the relationship between severity of bone dysplasia and serum keratan sulfate (KS) and heparan sulfate (HS) levels in those models, and to explore the mechanism of KS elevation in MPS I, IIIA, and VII mouse models. Clinically, MPS VII mice had the most severe bone pathology; however, MPS I and IVA mice also showed skeletal pathology. MPS I and VII mice showed severe bone dysplasia, higher bone mineral density, narrowed spinal canal, and shorter sclerotic bones by micro-CT and radiographs. Serum KS and HS levels were elevated in MPS I, IIIA, and VII mice. Severity of skeletal disease displayed by micro-CT, radiographs and histopathology correlated with the level of KS elevation. We showed that elevated HS levels in MPS mouse models could inhibit N-acetylgalactosamine-6-sulfate sulfatase enzyme. These studies suggest that KS could be released from chondrocytes affected by accumulation of other GAGs and that KS could be useful as a biomarker for severity of bone dysplasia in MPS disorders. PMID:22971960

  14. Debating Our Way toward Stronger Thinking

    ERIC Educational Resources Information Center

    Field, Kathryn

    2017-01-01

    Teachers often find it challenging to incorporate higher order thinking skills in ways that both inspire student interest and allow for meaningful differentiation. Structured debate is an activity that can facilitate all of these goals. This article explains, in detail, how debates can be structured to promote a variety of critical thinking skills…

  15. Using Debates to Teach Information Ethics

    ERIC Educational Resources Information Center

    Peace, A. Graham

    2011-01-01

    This experience report details the use of debates in a course on Information Ethics. Formal debates have been used in academia for centuries and create an environment in which students must think critically, communicate well and, above all, synthesize and evaluate the relevant classroom material. They also provide a break from the standard…

  16. A Stock Approach to Value Debate.

    ERIC Educational Resources Information Center

    Colbert, Kent R.

    Existing theories of value debating (resolutions dealing with values rather than policy) may be more effectively applied and developed when viewed as stock issues paradigms for debating values in competitive situations. Issues are vital to an advocate's cause because they are essential to the meaning of a proposition and can also provide an…

  17. The United States: A Persistent Debate

    ERIC Educational Resources Information Center

    van Scotter, Richard; Hartoonian, H. Michael; White, William E.; Davis, James E.

    2007-01-01

    American democratic society is sustained through debate among its citizens. Four sets of value tensions--(1) law versus ethics, (2) private wealth versus common wealth, (3) freedom versus equality, and (4) unity versus diversity--are central in allowing citizens to address matters of public interest through debate. These value pairs are the…

  18. The 1980 Presidential Debates. Special Issue.

    ERIC Educational Resources Information Center

    Ritter, Kurt W., Ed.

    1981-01-01

    Prepared by educators and researchers involved in argumentation and debate, the articles in this special journal issue are based upon the assumptions that presidential debates are important, are likely to continue, and are of unique interest to students, scholars, and practitioners of argument. The first two articles in the issue provide overviews…

  19. Leagues Revive Debate in City Schools

    ERIC Educational Resources Information Center

    Keller, Bess

    2008-01-01

    This article describes how the National Association for Urban Debate Leagues is reviving debate competitions among high school students in city schools. Starting in Atlanta in 1985 and boosted by seed money from the billionaire George Soros' Open Society Institute, urban educators and their supporters in 2002 formed the National Association for…

  20. Biological sex affects the neurobiology of autism

    PubMed Central

    Lombardo, Michael V.; Suckling, John; Ruigrok, Amber N. V.; Chakrabarti, Bhismadev; Ecker, Christine; Deoni, Sean C. L.; Craig, Michael C.; Murphy, Declan G. M.; Bullmore, Edward T.; Baron-Cohen, Simon

    2013-01-01

    In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This study seeks to answer two questions about how autism is modulated by biological sex at the level of the brain: (i) is the neuroanatomy of autism different in males and females? and (ii) does the neuroanatomy of autism fit predictions from the ‘extreme male brain’ theory of autism, in males and/or in females? Neuroanatomical features derived from voxel-based morphometry were compared in a sample of equal-sized high-functioning male and female adults with and without autism (n = 120, n = 30/group). The first question was investigated using a 2 × 2 factorial design, and by spatial overlap analyses of the neuroanatomy of autism in males and females. The second question was tested through spatial overlap analyses of specific patterns predicted by the extreme male brain theory. We found that the neuroanatomy of autism differed between adult males and females, evidenced by minimal spatial overlap (not different from that occurred under random condition) in both grey and white matter, and substantially large white matter regions showing significant sex × diagnosis interactions in the 2 × 2 factorial design. These suggest that autism manifests differently by biological sex. Furthermore, atypical brain areas in females with autism substantially and non-randomly (P < 0.001) overlapped with areas that were sexually dimorphic in neurotypical controls, in both grey and white matter, suggesting neural ‘masculinization’. This was not seen in males with autism. How differences in