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Sample records for final common pathway

  1. Anatomical study of the final common pathway for vocalization in the cat

    NASA Technical Reports Server (NTRS)

    Holstege, Gert

    1989-01-01

    Results are presented of an anatomical study of the neuronal pathways in the cat, via which the periaqueductal gray (PAG) produces excitation of motoneurons involved in vocalization. It is shown that a specific cell group in the lateral part of the caudal PAG and in the tegmentum just lateral to it projects bilaterally to the nucleus retroambiguus (NRA) in the caudal medulla oblongata. Neurons in the NRA in turn project, via a contralateral pathway through the ventral funiculus of the spinal cord, to the motoneuronal cell groups innervating intercostal and abdominal muscles. In the brainstem, the NRA neurons project to the motoneuronal cell groups innervating mouth-opening and perioral muscles as well as to motoneurons innervating the pharynx, soft palate, and tongue. These results indicate that the projections from PAG via NRA to vocalization motoneurons form the final common pathway in vocalization.

  2. The Dopamine Hypothesis of Schizophrenia: Version III—The Final Common Pathway

    PubMed Central

    Howes, Oliver D.; Kapur, Shitij

    2009-01-01

    The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia—version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point. PMID:19325164

  3. Memory Similarities Between Essential Tremor and Parkinson’s Disease: A Final Common Pathway?

    PubMed Central

    Lafo, Jacob A.; Jones, Jacob D.; Okun, Michael S.; Bauer, Russell M.; Price, Catherine C.; Bowers, Dawn

    2015-01-01

    Objective A growing body of literature supports the view that essential tremor (ET) involves alteration of cerebellar-thalamo-cortical networks which can result in working memory and executive deficits. In this study we tested the hypothesis that individuals with ET would exhibit worse performance on memory tasks requiring more intrinsic organization and structuring (i.e., word lists) relative to those with fewer ‘executive’ demands (i.e., stories), similar to that previously observed in individuals with Parkinson’s disease (PD). Method Participants included a convenience sample of 68 ET patients and 68 idiopathic PD patients, retrospectively matched based on age, education, and sex. All patients underwent routine neuropsychological evaluation assessing recent memory, auditory attention/working memory, language, and executive function. Memory measures included the Hopkins Verbal Learning Test-R and WMS-III Logical Memory. Results Both ET and PD patients performed significantly worse on word list than story memory recall tasks. The magnitude of the difference between these two memory tasks was similar for ET and PD patients. In both patient groups, performance on measures of executive function and auditory attention/working memory was not distinctly correlated with word list vs. story recall. Conclusions These findings suggest that frontal-executive dysfunction in both ET and PD may negatively influence performance on memory tests that are not inherently organized. Although the pathophysiology of these two ‘movement disorders’ are quite distinct, both have downstream effects on thalamo-frontal circuitry which may provide a common pathway for a similar memory phenotype. Findings are discussed in terms of neuroimaging evidence, conceptual models, and best practice. PMID:26689342

  4. A Final Common Pathway for Depression? Progress Toward a General Conceptual Framework

    PubMed Central

    Stone, Eric A.; Lin, Yan; Quartermain, David

    2008-01-01

    Functional neuroimaging studies of depressed patients have converged with functional brain mapping studies of depressed animals in showing that depression is accompanied by a hypoactivity of brain regions involved in positively motivated behavior together with a hyperactivity in regions involved in stress responses. Both sets of changes are reversed by diverse antidepressant treatments. It has been proposed that this neural pattern underlies the symptoms common to most forms of the depression, which are the loss of positively motivated behavior and increased stress. The paper discusses how this framework can organize diverse findings ranging from effects of monoamine neurotransmitters, cytokines, corticosteroids and neurotrophins on depression. The hypothesis leads to new insights concerning the relationship between the prolonged inactivity of the positive motivational network during a depressive episode and the loss of neurotrophic support, the potential antidepressant action of corticosteroid treatment, and to the key question of whether antidepressants act by inhibiting the activity of the stress network or by enhancing the activity of the positive motivational system. PMID:18023876

  5. Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia?

    PubMed

    Laviolette, Steven R

    2007-07-01

    The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit. PMID:17519393

  6. N-methyl-D-aspartate (NMDA) receptor dysfunction or dysregulation: the final common pathway on the road to schizophrenia?

    PubMed Central

    Kantrowitz, Joshua T.; Javitt, Daniel C.

    2010-01-01

    Schizophrenia is a severe mental disorder associated with a characteristic constellation of symptoms and neurocognitive deficits. At present, etiological mechanisms remain relatively unknown, although multiple points of convergence have been identified over recent years. One of the primary convergence points is dysfunction of N-methyl-D-aspartate (NMDAR)-type glutamate receptors. Antagonists of NMDAR produce a clinical syndrome that closely resembles, and uniquely incorporates negative and cognitive symptoms of schizophrenia, along with the specific pattern of neurocognitive dysfunction seen in schizophrenia. Genetic polymorphisms involving NMDAR subunits, particularly the GRIN2B subunit have been described. In addition, polymorphisms have been described in modulatory systems involving the NMDAR, including the enzymes serine racemase and D-amino acid oxidase/G72 that regulate brain D-serine synthesis. Reductions in plasma and brain glycine, D-serine and glutathione levels have been described as well, providing potential mechanisms underlying NMDAR dysfunction. Unique characteristics of the NMDAR are described that may explain the characteristic pattern of symptoms and neurocognitive deficits observed in schizophrenia. Finally, the NMDAR complex represents a convergence point for potential new treatment approaches in schizophrenia aimed at correcting underlying abnormalities in synthesis and regulation of allosteric modulators, as well as more general potentiation of pre- and post-synaptic glutamatergic and NMDAR function. PMID:20417696

  7. A common pathway toward women's health.

    PubMed

    Chibber, K S; Kaplan, R L; Padian, N S; Anderson, S J; Ling, P M; Acharya, N; Van Dyke, C; Krishnan, S

    2008-01-01

    This paper calls for an alternate approach to studying the aetiology of women's health conditions. Instead of the long-established disease-specific, compartmentalized approach, it recommends focusing on risk exposures that allows for the identification of multiple disease conditions that stem from the same risk factors. Identifying common risk factors and the related pathways to adverse health outcomes can lead to the development of interventions that would favourably affect more than one disease condition. The utility of such an approach is illustrated by a review of literature from across the globe on the association between gender inequity-related exposures and women's health (namely, three health conditions: sexually transmitted infections [STIs], including Human Immunodeficiency Virus [HIV], blindness, and depression; as well as two risk behaviours: eating disorders and tobacco use). The review demonstrates how women's health cannot be viewed independently from the larger social, economic, and political context in which women are situated. Promoting women's health necessitates more comprehensive approaches, such as gender-sensitization of other family members, and the development of more creative and flexible mechanisms of healthcare delivery, that acknowledge the gender inequity-related constraints that women face in their daily lives. PMID:19288357

  8. Emerging Common Molecular Pathways for Primary Dystonia

    PubMed Central

    LeDoux, Mark S; Dauer, William T; Warner, Thomas T

    2013-01-01

    Background The dystonias are a group of hyperkinetic movement disorders whose principal cause is neuron dysfunction at one or more interconnected nodes of the motor system. The study of genes and proteins which cause familial dystonia provides critical information about the cellular pathways involved in this dysfunction which disrupts the motor pathways at systems level. In recent years study of the increasing number of DYT genes has implicated a number of cell functions which appear to be involved in the pathogenesis of dystonia. Methods Review of literature published in English language publications available on Pubmed relating to the genetics and cellular pathology of dystonia Results and Conclusions Numerous potential pathogenetic mechanisms have been identified. We describe those which fall into three emerging thematic groups: cell cycle and transcriptional regulation in the nucleus, endoplasmic reticulum and nuclear envelope function, and control of synaptic function. PMID:23893453

  9. Common Errors in Calculating Final Grades

    ERIC Educational Resources Information Center

    Francis, Richard W.

    2006-01-01

    The author has discovered that errors in grades often occur when scores are combined for final marks. These errors are not related to the grading individual assignments. Rather, they occur when teachers at all grade levels bring individual test and assignment scores together for the students' final grades. Unfortunately, professors of mathematics…

  10. Common developmental pathways link tooth shape to regeneration

    PubMed Central

    Fraser, Gareth J.; Bloomquist, Ryan F.; Streelman, J. Todd

    2013-01-01

    In many non-mammalian vertebrates, adult dentitions result from cyclical rounds of tooth regeneration wherein simple unicuspid teeth are replaced by more complex forms. Therefore and by contrast to mammalian models, the numerical majority of vertebrate teeth develop shape during the process of replacement. Here, we exploit the dental diversity of Lake Malawi cichlid fishes to ask how vertebrates generally replace their dentition and in turn how this process acts to influence resulting tooth morphologies. First, we used immunohistochemistry to chart organogenesis of continually replacing cichlid teeth and discovered an epithelial down-growth that initiates the replacement cycle via a labial proliferation bias. Next, we identified sets of co-expressed genes from common pathways active during de novo, lifelong tooth replacement and tooth morphogenesis. Of note, we found two distinct epithelial cell populations, expressing markers of dental competence and cell potency, which may be responsible for tooth regeneration. Related gene sets were simultaneously active in putative signaling centers associated with the differentiation of replacement teeth with complex shapes. Finally, we manipulated targeted pathways (BMP, FGF, Hh, Notch, Wnt/β-catenin) in vivo with small molecules and demonstrated dose-dependent effects on both tooth replacement and tooth shape. Our data suggest that the processes of tooth regeneration and tooth shape morphogenesis are integrated via a common set of molecular signals. This linkage has subsequently been lost or decoupled in mammalian dentitions where complex tooth shapes develop in first generation dentitions that lack the capacity for lifelong replacement. Our dissection of the molecular mechanics of vertebrate tooth replacement coupled to complex shape pinpoints aspects of odontogenesis that might be re-evolved in the lab to solve problems in regenerative dentistry. PMID:23422830

  11. Common ground: stem cell approaches find shared pathways underlying ALS.

    PubMed

    Matus, Soledad; Medinas, Danilo B; Hetz, Claudio

    2014-06-01

    The development of curative therapies for genetically complex diseases such as ALS has been delayed by the lack of relevant disease models. Recent advances using induced-pluripotent-stem-cell-derived motoneurons from patients harboring distinct ALS mutations have recapitulated essential disease features and have identified some common pathways driving disease pathogenesis. PMID:24905158

  12. Pathway Analysis Incorporating Protein-Protein Interaction Networks Identified Candidate Pathways for the Seven Common Diseases

    PubMed Central

    Lin, Peng-Lin; Yu, Ya-Wen

    2016-01-01

    Pathway analysis has become popular as a secondary analysis strategy for genome-wide association studies (GWAS). Most of the current pathway analysis methods aggregate signals from the main effects of single nucleotide polymorphisms (SNPs) in genes within a pathway without considering the effects of gene-gene interactions. However, gene-gene interactions can also have critical effects on complex diseases. Protein-protein interaction (PPI) networks have been used to define gene pairs for the gene-gene interaction tests. Incorporating the PPI information to define gene pairs for interaction tests within pathways can increase the power for pathway-based association tests. We propose a pathway association test, which aggregates the interaction signals in PPI networks within a pathway, for GWAS with case-control samples. Gene size is properly considered in the test so that genes do not contribute more to the test statistic simply due to their size. Simulation studies were performed to verify that the method is a valid test and can have more power than other pathway association tests in the presence of gene-gene interactions within a pathway under different scenarios. We applied the test to the Wellcome Trust Case Control Consortium GWAS datasets for seven common diseases. The most significant pathway is the chaperones modulate interferon signaling pathway for Crohn’s disease (p-value = 0.0003). The pathway modulates interferon gamma, which induces the JAK/STAT pathway that is involved in Crohn’s disease. Several other pathways that have functional implications for the seven diseases were also identified. The proposed test based on gene-gene interaction signals in PPI networks can be used as a complementary tool to the current existing pathway analysis methods focusing on main effects of genes. An efficient software implementing the method is freely available at http://puppi.sourceforge.net. PMID:27622767

  13. Pathway Analysis Incorporating Protein-Protein Interaction Networks Identified Candidate Pathways for the Seven Common Diseases.

    PubMed

    Lin, Peng-Lin; Yu, Ya-Wen; Chung, Ren-Hua

    2016-01-01

    Pathway analysis has become popular as a secondary analysis strategy for genome-wide association studies (GWAS). Most of the current pathway analysis methods aggregate signals from the main effects of single nucleotide polymorphisms (SNPs) in genes within a pathway without considering the effects of gene-gene interactions. However, gene-gene interactions can also have critical effects on complex diseases. Protein-protein interaction (PPI) networks have been used to define gene pairs for the gene-gene interaction tests. Incorporating the PPI information to define gene pairs for interaction tests within pathways can increase the power for pathway-based association tests. We propose a pathway association test, which aggregates the interaction signals in PPI networks within a pathway, for GWAS with case-control samples. Gene size is properly considered in the test so that genes do not contribute more to the test statistic simply due to their size. Simulation studies were performed to verify that the method is a valid test and can have more power than other pathway association tests in the presence of gene-gene interactions within a pathway under different scenarios. We applied the test to the Wellcome Trust Case Control Consortium GWAS datasets for seven common diseases. The most significant pathway is the chaperones modulate interferon signaling pathway for Crohn's disease (p-value = 0.0003). The pathway modulates interferon gamma, which induces the JAK/STAT pathway that is involved in Crohn's disease. Several other pathways that have functional implications for the seven diseases were also identified. The proposed test based on gene-gene interaction signals in PPI networks can be used as a complementary tool to the current existing pathway analysis methods focusing on main effects of genes. An efficient software implementing the method is freely available at http://puppi.sourceforge.net. PMID:27622767

  14. Infertility and miscarriage: common pathways in manifestation and management.

    PubMed

    Agenor, Angena; Bhattacharya, Sohinee

    2015-07-01

    The relationship between miscarriage and fertility is complex. While most healthcare settings treat miscarriage as a problem of subfertility in assisted reproduction units, others believe that miscarriage occurs in super-fertile women. Infertile women undergoing assisted reproduction are at a greater risk of having a miscarriage especially at an advanced age compared with women conceiving naturally. Aberrant expression of immunological factors and chromosomal abnormalities underlie both infertility and miscarriage. Common risk factors include increased maternal age, obesity, smoking, alcohol, pre-existing medical conditions and anatomical abnormalities of the reproductive system. Management pathways of both conditions may be similar with pre-implantation genetic testing and assisted reproductive technology used in both conditions. This paper discusses the synergies and differences between the two conditions in terms of their epidemiology, etiopathogenesis, risk factors and management strategies. The two conditions are related as degrees of severity of reproductive failure with common pathways in manifestation and management.

  15. Final report on the Pathway Analysis Task

    SciTech Connect

    Whicker, F.W.; Kirchner, T.B.

    1993-04-01

    The Pathway Analysis Task constituted one of several multi-laboratory efforts to estimate radiation doses to people, considering all important pathways of exposure, from the testing of nuclear devices at the Nevada Test Site (NTS). The primary goal of the Pathway Analysis Task was to predict radionuclide ingestion by residents of Utah, Nevada, and portions of seven other adjoining western states following radioactive fallout deposition from individual events at the NTS. This report provides comprehensive documentation of the activities and accomplishments of Colorado State University`s Pathway Analysis Task during the entire period of support (1979--91). The history of the project will be summarized, indicating the principal dates and milestones, personnel involved, subcontractors, and budget information. Accomplishments, both primary and auxiliary, will be summarized with general results rather than technical details being emphasized. This will also serve as a guide to the reports and open literature publications produced, where the methodological details and specific results are documented. Selected examples of results on internal dose estimates are provided in this report because the data have not been published elsewhere.

  16. The search for common pathways underlying asthma and COPD

    PubMed Central

    Kaneko, Yoshiko; Yatagai, Yohei; Yamada, Hideyasu; Iijima, Hiroki; Masuko, Hironori; Sakamoto, Tohru; Hizawa, Nobuyuki

    2013-01-01

    Recently, several genes and genetic loci associated with both asthma and chronic obstructive pulmonary disease (COPD) have been described as common susceptibility factors for the two diseases. In complex diseases such as asthma and COPD, a large number of molecular and cellular components may interact through complex networks involving gene–gene and gene–environment interactions. We sought to understand the functional and regulatory pathways that play central roles in the pathobiology of asthma and COPD and to understand the overlap between these pathways. We searched the PubMed database up to September 2012 to identify genes found to be associated with asthma, COPD, tuberculosis, or essential hypertension in at least two independent reports of candidate-gene associations or in genome-wide studies. To learn how the identified genes interact with each other and other cellular proteins, we conducted pathway-based analysis using Ingenuity Pathway Analysis software. We identified 108 genes and 58 genes that were significantly associated with asthma and COPD in at least two independent studies, respectively. These susceptibility genes were grouped into networks based on functional annotation: 12 (for asthma) and eleven (for COPD) networks were identified. Analysis of the networks for overlap between the two diseases revealed that the networks form a single complex network with 229 overlapping molecules. These overlapping molecules are significantly involved in canonical pathways including the “aryl hydrocarbon receptor signaling,” “role of cytokines in mediating communication between immune cells,” “glucocorticoid receptor signaling,” and “IL-12 signaling and production in macrophages” pathways. The Jaccard similarity index for the comparison between asthma and COPD was 0.81 for the network-level comparison, and the odds ratio was 3.62 (P < 0.0001) for the asthma/COPD pair in comparison with the tuberculosis/ essential hypertension pair. In

  17. Pathways: Service Coordination Inservice Project. Final Report.

    ERIC Educational Resources Information Center

    Rosin, Peggy; And Others

    This final report describes the implementation and outcomes of a project designed to assist Wisconsin in meeting its need for qualified and appropriately trained personnel to carry out their new roles as service coordinators in the provision of early intervention services. The project's activities included: (1) development of a set of training…

  18. Three common pathways of nephrotoxicity induced by halogenated alkenes.

    PubMed

    Cristofori, Patrizia; Sauer, Aisha V; Trevisan, Andrea

    2015-02-01

    Glutathione-dependent bioactivation is a common pathway in nephrotoxicity caused by haloalkanes and haloalkenes. Glutathione conjugation forms the link between halogenated hydrocarbons, based on the formation of an episulfonium ion (vicinal halomethanes) or a cysteine conjugate (haloalkenes). Herein, we review the metabolic pathways underlying the nephrotoxic effects of the three well-known haloalkenes trichloroethylene, tetrachloroethylene, and hexachloro-1:3-butadiene to emphasize the role of cysteine-conjugate β-lyase and the oxidative metabolism in renal toxicity. Activation by cysteine-conjugate β-lyase is the best-characterized mechanism causing toxicity due to haloalkene treatment in experimental models. However, the severity of toxicity differs considerably, with S-(1,2,2-trichlorovinyl)-L-cysteine being more toxic than S-(1,2-dichlorovinyl)-L-cysteine, which is in turn more toxic than S-(1,2,3,4,4-pentachloro-1:3-butadienyl)-L-cysteine. Moreover, two oxidative pathways involving cysteine S-conjugates (mediated by flavin-containing monooxigenase 3) and N-acetyl-L-cysteine conjugates (mediated by cytochrome P-450 3A) form derived sulfoxides, which represent alternative metabolites with toxic effects. In vitro and in vivo studies showed that sulfoxide metabolites are more toxic than cysteine-conjugate derivates. The cytochrome P-450 3A family, on the other hand, is sex specific, and its expression has only been reported in adult male rats and rabbits. In summary, haloalkenes are highly nephrotoxic in vivo and in vitro and their toxicity mechanisms are well documented experimentally. However, little information is available on their toxicity in humans, except for the carcinogenic effects established for high exposure levels of trichloroethylene and tetrachloroethylene.

  19. Autism Spectrum Disorders and Drug Addiction: Common Pathways, Common Molecules, Distinct Disorders?

    PubMed Central

    Rothwell, Patrick E.

    2016-01-01

    Autism spectrum disorders (ASDs) and drug addiction do not share substantial comorbidity or obvious similarities in etiology or symptomatology. It is thus surprising that a number of recent studies implicate overlapping neural circuits and molecular signaling pathways in both disorders. The purpose of this review is to highlight this emerging intersection and consider implications for understanding the pathophysiology of these seemingly distinct disorders. One area of overlap involves neural circuits and neuromodulatory systems in the striatum and basal ganglia, which play an established role in addiction and reward but are increasingly implicated in clinical and preclinical studies of ASDs. A second area of overlap relates to molecules like Fragile X mental retardation protein (FMRP) and methyl CpG-binding protein-2 (MECP2), which are best known for their contribution to the pathogenesis of syndromic ASDs, but have recently been shown to regulate behavioral and neurobiological responses to addictive drug exposure. These shared pathways and molecules point to common dimensions of behavioral dysfunction, including the repetition of behavioral patterns and aberrant reward processing. The synthesis of knowledge gained through parallel investigations of ASDs and addiction may inspire the design of new therapeutic interventions to correct common elements of striatal dysfunction. PMID:26903789

  20. Uncovering novel actors in astrocyte–neuron crosstalk in Parkinson’s disease: the Wnt/β-catenin signaling cascade as the common final pathway for neuroprotection and self-repair

    PubMed Central

    Marchetti, Bianca; L’Episcopo, Francesca; Morale, Maria Concetta; Tirolo, Cataldo; Testa, Nuccio; Caniglia, Salvo; Serapide, Maria Francesca; Pluchino, Stefano

    2013-01-01

    Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by progressive loss of dopaminergic (DAergic) neuronal cell bodies in the substantia nigra pars compacta and gliosis. The cause and mechanisms underlying the demise of nigrostriatal DAergic neurons are ill-defined, but interactions between genes and environmental factors are recognized to play a critical role in modulating the vulnerability to PD. Current evidence points to reactive glia as a pivotal factor in PD pathophysiology, playing both protective and destructive roles. Here, the contribution of reactive astrocytes and their ability to modulate DAergic neurodegeneration, neuroprotection and neurorepair in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model of PD will be discussed in the light of novel emerging evidence implicating wingless-type mouse mammary tumor virus integration site (Wnt)/β-catenin signaling as a strong candidate in MPTP-induced nigrostriatal DAergic plasticity. In this work, we highlight an intrinsic Wnt1/frizzled-1/β-catenin tone that critically contributes to the survival and protection of adult midbrain DAergic neurons, with potential implications for drug design or drug action in PD. The dynamic interplay between astrocyte-derived factors and neurogenic signals in MPTP-induced nigrostriatal DAergic neurotoxicity and repair will be summarized, together with recent findings showing a critical role of glia–neural stem/progenitor cell (NPC) interactions aimed at overcoming neurodegeneration and inducing neurorestoration. Understanding the intrinsic plasticity of nigrostriatal DAergic neurons and deciphering the signals facilitating the crosstalk between astrocytes, microglia, DAergic neurons and NPCs may have major implications for the role of stem cell technology in PD, and for identifying potential therapeutic targets to induce endogenous neurorepair. PMID:23461676

  1. Common pathway signature in lung and liver fibrosis.

    PubMed

    Makarev, Eugene; Izumchenko, Evgeny; Aihara, Fumiaki; Wysocki, Piotr T; Zhu, Qingsong; Buzdin, Anton; Sidransky, David; Zhavoronkov, Alex; Atala, Anthony

    2016-07-01

    Fibrosis, a progressive accumulation of extracellular matrix components, encompasses a wide spectrum of distinct organs, and accounts for an increasing burden of morbidity and mortality worldwide. Despite the tremendous clinical impact, the mechanisms governing the fibrotic process are not yet understood, and to date, no clinically reliable therapies for fibrosis have been discovered. Here we applied Regeneration Intelligence, a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in lung and liver fibrosis. In both tissues, our analysis detected major conserved signaling pathways strongly associated with fibrosis, suggesting that some of the pathways identified by our algorithm but not yet wet-lab validated as fibrogenesis related, may be attractive targets for future research. While the majority of significantly disrupted pathways were specific to histologically distinct organs, several pathways have been concurrently activated or downregulated among the hepatic and pulmonary fibrosis samples, providing new evidence of evolutionary conserved pathways that may be relevant as possible therapeutic targets. While future confirmatory studies are warranted to validate these observations, our platform proposes a promising new approach for detecting fibrosis-promoting pathways and tailoring the right therapy to prevent fibrogenesis. PMID:27267766

  2. Common pathway signature in lung and liver fibrosis

    PubMed Central

    Makarev, Eugene; Izumchenko, Evgeny; Aihara, Fumiaki; Wysocki, Piotr T.; Zhu, Qingsong; Buzdin, Anton; Sidransky, David; Zhavoronkov, Alex; Atala, Anthony

    2016-01-01

    ABSTRACT Fibrosis, a progressive accumulation of extracellular matrix components, encompasses a wide spectrum of distinct organs, and accounts for an increasing burden of morbidity and mortality worldwide. Despite the tremendous clinical impact, the mechanisms governing the fibrotic process are not yet understood, and to date, no clinically reliable therapies for fibrosis have been discovered. Here we applied Regeneration Intelligence, a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in lung and liver fibrosis. In both tissues, our analysis detected major conserved signaling pathways strongly associated with fibrosis, suggesting that some of the pathways identified by our algorithm but not yet wet-lab validated as fibrogenesis related, may be attractive targets for future research. While the majority of significantly disrupted pathways were specific to histologically distinct organs, several pathways have been concurrently activated or downregulated among the hepatic and pulmonary fibrosis samples, providing new evidence of evolutionary conserved pathways that may be relevant as possible therapeutic targets. While future confirmatory studies are warranted to validate these observations, our platform proposes a promising new approach for detecting fibrosis-promoting pathways and tailoring the right therapy to prevent fibrogenesis. PMID:27267766

  3. Diversity in Pathways to Common Childhood Disruptive Behavior Disorders

    ERIC Educational Resources Information Center

    Martel, Michelle M.; Nikolas, Molly; Jernigan, Katherine; Friderici, Karen; Nigg, Joel T.

    2012-01-01

    Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are highly comorbid, a phenomenon thought to be due to shared etiological factors and mechanisms. Little work has attempted to chart multiple-level-of-analysis pathways (i.e., simultaneously including biological, environmental, and trait influences) to ODD and…

  4. Diversity in pathways to common childhood disruptive behavior disorders.

    PubMed

    Martel, Michelle M; Nikolas, Molly; Jernigan, Katherine; Friderici, Karen; Nigg, Joel T

    2012-11-01

    Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are highly comorbid, a phenomenon thought to be due to shared etiological factors and mechanisms. Little work has attempted to chart multiple-level-of-analysis pathways (i.e., simultaneously including biological, environmental, and trait influences) to ODD and ADHD, the goal of the present investigation. 559 children/adolescents (325 boys) between the ages of 6 and 18 participated in a multi-stage, comprehensive diagnostic procedure. 148 were classified as ODD; 309 were classified as ADHD, based on parent, teacher, and clinician ratings. Children provided buccal or salivary samples of DNA, assayed for select markers in DRD4 and 5HTT. Parents completed the Alabama Parenting Questionnaire and the California Q-Sort. Children completed the Child Perception of Interparental Conflict Scale. Correlational associations consistent with multiple-level-of-analysis pathways to ODD and ADHD emerged. For ODD, children with the short allele of the 5HTT promoter polymorphism had higher neuroticism and ODD symptoms regardless of level of self-blame in relation to inter-parental conflict, whereas children without this allele had more ODD symptoms only in the context of more self-blame for inter-parental conflict. For ADHD (and ODD), children homozygous for the long allele of DRD4 120 bp insertion polymorphism had lower conscientiousness when exposed to inconsistent parenting, whereas children without this genotype were more resilient to effects of inconsistent discipline on conscientiousness. Thus, ODD and ADHD appear to demonstrate somewhat distinct correlational associations between etiological factors and mechanisms consistent with pathway models using a multiple-level-of-analysis approach.

  5. A common response to common danger? Comparison of animal and plant signaling pathways involved in cadmium sensing.

    PubMed

    Chmielowska-Bąk, Jagna; Deckert, Joanna

    2012-12-01

    Exposure to cadmium results in disturbances in cell homeostasis in all living organisms. The first response to stress factors, including cadmium, is activation of signal transduction pathways that mobilize cell defense mechanisms. The aim of this review is a comparison between the signaling network triggered by Cd in plants and animals. Despite differences in the structure and physiology of plant and animal cells, their cadmium signal transduction pathways share many common elements. These elements include signaling molecules such as ROS, Ca(2+) and NO, the involvement of phospholipase C, mitogen-activated protein kinase cascades, and activation of transcription factors. Undoubtedly, both animals and plants also possess specific signaling pathways. In case of animals, Wnt/β-catenin, sonic hedgehog and oestorgen signaling are engaged in the transduction of cadmium signal. Plant specific signal transduction pathways include signaling mediated by plant hormones. The role of ethylene and jasmonic, salicylic and abscisic acid in plant response to cadmium is also discussed.

  6. New IBD genetics: common pathways with other diseases.

    PubMed

    Lees, C W; Barrett, J C; Parkes, M; Satsangi, J

    2011-12-01

    Complex disease genetics has been revolutionised in recent years by the advent of genome-wide association (GWA) studies. The chronic inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis have seen notable successes culminating in the discovery of 99 published susceptibility loci/genes (71 Crohn's disease; 47 ulcerative colitis) to date. Approximately one-third of loci described confer susceptibility to both Crohn's disease and ulcerative colitis. Amongst these are multiple genes involved in IL23/Th17 signalling (IL23R, IL12B, JAK2, TYK2 and STAT3), IL10, IL1R2, REL, CARD9, NKX2.3, ICOSLG, PRDM1, SMAD3 and ORMDL3. The evolving genetic architecture of IBD has furthered our understanding of disease pathogenesis. For Crohn's disease, defective processing of intracellular bacteria has become a central theme, following gene discoveries in autophagy and innate immunity (associations with NOD2, IRGM, ATG16L1 are specific to Crohn's disease). Genetic evidence has also demonstrated the importance of barrier function to the development of ulcerative colitis (HNF4A, LAMB1, CDH1 and GNA12). However, when the data are analysed in more detail, deeper themes emerge including the shared susceptibility seen with other diseases. Many immune-mediated diseases overlap in this respect, paralleling the reported epidemiological evidence. However, in several cases the reported shared susceptibility appears at odds with the clinical picture. Examples include both type 1 and type 2 diabetes mellitus. In this review we will detail the presently available data on the genetic overlap between IBD and other diseases. The discussion will be informed by the epidemiological data in the published literature and the implications for pathogenesis and therapy will be outlined. This arena will move forwards very quickly in the next few years. Ultimately, we anticipate that these genetic insights will transform the landscape of common complex diseases such as IBD. PMID:21300624

  7. A Common Metric for Language Proficiency. Final Report.

    ERIC Educational Resources Information Center

    Woodford, Protase

    This is a report on a project established to develop a "common yardstick" to describe performance in one or more language skills. Descriptive scales for oral interaction were prepared as well as a general outline of scale characteristics for listening comprehension and reading. Experts in the field reviewed the project proposal and recommendations…

  8. Courtyard Commons retail addition. Phase I. Final design documentation

    SciTech Connect

    Not Available

    1981-04-25

    The project consists of a retail addition to an existing cluster of buildings located on the main commercial street in Santa Cruz, California. The existing complex is formed by two wings of one-story buildings enclosing an open courtyard now used for circulation, a coffee shop seating area, a flower stand, and access to four retail stores. The program calls for an addition of new retail space above the existing buildings constructed of eight inch concrete blocks. In order to provide for the year around use of the courtyard, the program also calls for a flexible glass cover which could be removed during the sunny warm summer days. The main requirements of the program finally, are to develop an energy efficient and cost effective design which uses natural light at its full potential for both the courtyard and interior spaces. This report includes sections of the following: overview of final design; unavailable solar design information; incremental passive design cost, energy performance analysis and results; economic analysis and results; architectural compatibility; NBSGLD output and documentation; and design development drawings.

  9. Genetic evidence for common pathways in human age-related diseases.

    PubMed

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-10-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms.

  10. VP-16 and alkylating agents activate a common metabolic pathway for suppression of DNA replication

    SciTech Connect

    Das, S.K.; Berger, N.A.

    1986-05-01

    The cytotoxic effects of etoposide (VP-16) are mediated by topoisomerase II production of protein crosslinked DNA strand breaks. Previous studies have shown that alkylating agent induced DNA damage results in expansion of dTTP pools and reduction of dCTP pools and DNA replication. Studies were conducted with V79 cells to determine whether the metabolic consequences of VP-16 treatment were similar to those induced by alkylating agents. Treatment with 0.5..mu..M VP-16 prolonged the doubling time of V79 cells from 12 to 18 hrs and caused cell volume to increase from 1.1 to 1.6 x 10/sup -12/l. 2mM caffeine completely blocked the volume increase and substantially prevented the prolongation of doubling time. 5..mu..M VP-16 reduced the rate of (/sup 3/H)TdR incorporation by 70%, whereas in the presence of 2mM caffeine, VP-16 caused only a 10% decrease in the rate of (/sup 3/H)TdR incorporation. 4 hr treatment with 5.0..mu..M VP-16 increased dTTP levels from 65 +/- 10 pmol/10/sup 6/ cells to 80 +/- 13 pmol/10/sup 6/ cells and caused dCTP level to decline from 113 +/- 23 pmol/10/sup 6/ cells to 92 +/- 17 pmol/10/sup 6/ cells. These results indicate that the metabolic consequences of VP-16 treatment are similar to alkylating agent treatment and that an increase in dTTP pools with a subsequent effect on ribonucleotide reductase may be a final common pathway by which many cytotoxic agents suppress DNA synthesis.

  11. Incontinence and psychological problems in children: a common central nervous pathway?

    PubMed

    Van Herzeele, Charlotte; Vande Walle, Johan

    2016-05-01

    Nocturnal enuresis is caused by a mismatch between the nocturnal bladder capacity and the nocturnal diuresis rate, in the presence of a deficient arousability in the majority of patients, according to the pediatric and urologic literature. Psychiatric and psychologic literature are still concentrating on the potential role of psychological factors and central nervous mechanisms in the pathogenesis, as is reflected in the DMS-5 criteria. However, research has clearly shown several important comorbidities between neuropsychological dysfunctions and nocturnal enuresis. Due to the increased comorbidity of (neuro)psychological problems, sleep problems, circadian rhythms, and enuresis, the question arises as to whether there is a possible common central pathway in the pathogenesis. It is likely that the coexistence of these problems can be attributed to a common central nervous system involvement. The specific role of the central nervous system remains unclear, but several pathways are possible. The high comorbidity between enuresis, sleep, and (neuro)psychological functioning is probably attributable to a common pathogenetic pathway, emphasizing the importance of a multidisciplinary focus in screening and treatment in children with nocturnal enuresis. PMID:26872485

  12. The cGMP/PKG pathway as a common mediator of cardioprotection: translatability and mechanism

    PubMed Central

    Inserte, Javier; Garcia-Dorado, David

    2015-01-01

    Cardiomyocyte cell death occurring during myocardial reperfusion (reperfusion injury) contributes to final infarct size after transient coronary occlusion. Different interrelated mechanisms of reperfusion injury have been identified, including alterations in cytosolic Ca2+ handling, sarcoplasmic reticulum-mediated Ca2+ oscillations and hypercontracture, proteolysis secondary to calpain activation and mitochondrial permeability transition. All these mechanisms occur during the initial minutes of reperfusion and are inhibited by intracellular acidosis. The cGMP/PKG pathway modulates the rate of recovery of intracellular pH, but has also direct effect on Ca2+ oscillations and mitochondrial permeability transition. The cGMP/PKG pathway is depressed in cardiomyocytes by ischaemia/reperfusion and preserved by ischaemic postconditioning, which importantly contributes to postconditioning protection. The present article reviews the mechanisms and consequences of the effect of ischaemic postconditioning on the cGMP/PKG pathway, the different pharmacological strategies aimed to stimulate it during myocardial reperfusion and the evidence, limitations and promise of translation of these strategies to the clinical practice. Overall, the preclinical and clinical evidence suggests that modulation of the cGMP/PKG pathway may be a therapeutic target in the context of myocardial infarction. PMID:25297462

  13. Conflicting demands on detoxification pathways influence how common brushtail possums choose their diets.

    PubMed

    Marsh, Karen J; Wallis, Ian R; McLean, Stuart; Sorensen, Jennifer S; Foley, William J

    2006-08-01

    Most herbivores eat more and survive better when they have access to a variety of foods. One explanation involves the detoxification of plant secondary metabolites (PSMs). By feeding from a variety of plants that contain different classes of PSMs, animals can use multiple detoxification pathways and presumably consume more food. Although popular, this theory is difficult to test because it requires knowledge of the detoxification pathways of each PSM in the diet. We established that common brushtail possums (Trichosurus vulpecula) use various combinations of oxidation, hydrolysis, and conjugation with glucuronic acid (GA) or glycine to detoxify six PSMs. Compared to their ingestion of a single PSM, possums ate more when offered a choice between two diets containing PSMs that require apparently independent detoxification pathways (benzoate and 1,8-cineole, benzoate and p-cymene, benzoate and orcinol, benzoate and salicin, or orcinol and 1,8-cineole). However, possums still did not eat as much of these diets as they did of a basal diet free of PSMs. This suggests that detoxification pathways are never independent, but are separated instead by degrees. In contrast, possums offered a choice of two PSMs that require competing detoxification pathways (1,8-cineole and p-cymene, 1,8-cineole and salicin, or orcinol and salicin) ate no more than when offered diets containing one of the compounds. There was an exception: even though both rutin and orcinol are detoxified via conjugation with GA, the feeding behavior of possums did not suggest competition for detoxification pathways. This implies that the supply of GA is not limiting. This study provides the first convincing evidence that herbivorous mammals can eat more by selecting mixed diets with a diversity of PSMs that make full use of their detoxification potential. It also emphasizes that other behavioral and physiological factors, such as transient food aversions, influence feeding behavior.

  14. Does a Common Pathway Transduce Symbiotic Signals in Plant–Microbe Interactions?

    PubMed Central

    Genre, Andrea; Russo, Giulia

    2016-01-01

    Recent years have witnessed major advances in our knowledge of plant mutualistic symbioses such as the rhizobium-legume symbiosis (RLS) and arbuscular mycorrhizas (AM). Some of these findings caused the revision of longstanding hypotheses, but one of the most solid theories is that a conserved set of plant proteins rules the transduction of symbiotic signals from beneficial glomeromycetes and rhizobia in a so-called common symbiotic pathway (CSP). Nevertheless, the picture still misses several elements, and a few crucial points remain unclear. How does one common pathway discriminate between – at least – two symbionts? Can we exclude that microbes other than AM fungi and rhizobia also use this pathway to communicate with their host plants? We here discuss the possibility that our current view is biased by a long-lasting focus on legumes, whose ability to develop both AM and RLS is an exception among plants and a recent innovation in their evolution; investigations in non-legumes are starting to place legume symbiotic signaling in a broader perspective. Furthermore, recent studies suggest that CSP proteins act in a wider scenario of symbiotic and non-symbiotic signaling. Overall, evidence is accumulating in favor of distinct activities for CSP proteins in AM and RLS, depending on the molecular and cellular context where they act. PMID:26909085

  15. Arbuscular Mycorrhiza–Specific Signaling in Rice Transcends the Common Symbiosis Signaling Pathway[W

    PubMed Central

    Gutjahr, Caroline; Banba, Mari; Croset, Vincent; An, Kyungsook; Miyao, Akio; An, Gynheung; Hirochika, Hirohiko; Imaizumi-Anraku, Haruko; Paszkowski, Uta

    2008-01-01

    Knowledge about signaling in arbuscular mycorrhizal (AM) symbioses is currently restricted to the common symbiosis (SYM) signaling pathway discovered in legumes. This pathway includes calcium as a second messenger and regulates both AM and rhizobial symbioses. Both monocotyledons and dicotyledons form symbiotic associations with AM fungi, and although they differ markedly in the organization of their root systems, the morphology of colonization is similar. To identify and dissect AM-specific signaling in rice (Oryza sativa), we developed molecular phenotyping tools based on gene expression patterns that monitor various steps of AM colonization. These tools were used to distinguish common SYM-dependent and -independent signaling by examining rice mutants of selected putative legume signaling orthologs predicted to be perturbed both upstream (CASTOR and POLLUX) and downstream (CCAMK and CYCLOPS) of the central, calcium-spiking signal. All four mutants displayed impaired AM interactions and altered AM-specific gene expression patterns, therefore demonstrating functional conservation of SYM signaling between distant plant species. In addition, differential gene expression patterns in the mutants provided evidence for AM-specific but SYM-independent signaling in rice and furthermore for unexpected deviations from the SYM pathway downstream of calcium spiking. PMID:19033527

  16. Does a Common Pathway Transduce Symbiotic Signals in Plant-Microbe Interactions?

    PubMed

    Genre, Andrea; Russo, Giulia

    2016-01-01

    Recent years have witnessed major advances in our knowledge of plant mutualistic symbioses such as the rhizobium-legume symbiosis (RLS) and arbuscular mycorrhizas (AM). Some of these findings caused the revision of longstanding hypotheses, but one of the most solid theories is that a conserved set of plant proteins rules the transduction of symbiotic signals from beneficial glomeromycetes and rhizobia in a so-called common symbiotic pathway (CSP). Nevertheless, the picture still misses several elements, and a few crucial points remain unclear. How does one common pathway discriminate between - at least - two symbionts? Can we exclude that microbes other than AM fungi and rhizobia also use this pathway to communicate with their host plants? We here discuss the possibility that our current view is biased by a long-lasting focus on legumes, whose ability to develop both AM and RLS is an exception among plants and a recent innovation in their evolution; investigations in non-legumes are starting to place legume symbiotic signaling in a broader perspective. Furthermore, recent studies suggest that CSP proteins act in a wider scenario of symbiotic and non-symbiotic signaling. Overall, evidence is accumulating in favor of distinct activities for CSP proteins in AM and RLS, depending on the molecular and cellular context where they act.

  17. Concurrent Ulcerative Colitis and Neurofibromatosis Type 1: The Question of a Common Pathway.

    PubMed

    Adams, William; Mitchell, Lisa; Candelaria-Santiago, Roberto; Hefner, Jody; Gramling, Joseph

    2016-02-01

    Patients with neurofibromatosis type 1 (NF1) are prone to the development of gastrointestinal stromal tumors, which may present clinically with hematochezia, obstruction, or abdominal pain. These symptoms are also commonly associated with the presentation of ulcerative colitis (UC). Within the past 5 years, there have been 2 reports of concurrent NF1 and UC and a common pathophysiologic pathway involving mast cells has been postulated. We present the case of a 15-year-old boy with a known history of NF1 who presented with 3 months of hematochezia and loose stools. A colonoscopy revealed pancolitis and histology demonstrating acute cryptitis, focal crypt abscesses, and architectural distortion consistent with UC. Due to the paucity of reported cases, the findings of both diseases in the same individual could reasonably be discounted as coincidence. However, in light of increasing reports of concurrent NF1 and UC, advances in characterizing the microenvironment within neurofibromas, and recent findings regarding potential shared genetic susceptibility, it is increasingly possible that the proposed common pathway is accurate. Our case adds to the literature and underscores the need for further investigation. PMID:26823541

  18. Alpha, beta and gamma motoneurons: functional diversity in the motor system's final pathway.

    PubMed

    Manuel, Marin; Zytnicki, Daniel

    2011-09-01

    Since their discovery in the late 19th century our conception of motoneurons has steadily evolved. Motoneurons share the same general function: they drive the contraction of muscle fibers and are the final common pathway, i.e., the seat of convergence of all the central and peripheral pathways involved in motricity. However, motoneurons innervate different types of muscular targets. Ordinary muscle fibers are subdivided into three main subtypes according to their structural and mechanical properties. Intrafusal muscle fibers located within spindles can elicit either a dynamic, or a static, action on the spindle sensory endings. No less than seven categories of motoneurons have thereby been identified on the basis of their innervation pattern. This functional diversity has hinted at a similar diversity in the inputs each motoneuron receives, as well as in the electrical, or cellular, properties of the motoneurons that match the properties of their muscle targets. The notion of the diverse properties of motoneurons has been well established by the work of many prominent neuroscientists. But in today's scientific literature, it tends to fade and motoneurons are often thought of as a homogenous group, which develop from a given population of precursor cells, and which express a common set of molecules. We first present here the historical milestones that led to the recognition of the functional diversity of motoneurons. We then review how the intrinsic electrical properties of motoneurons are precisely tuned in each category of motoneurons in order to produce an output that is adapted to the contractile properties of their specific targets.

  19. Insulin and phorbol ester stimulate conductive Na/sup +/ transport through a common pathway

    SciTech Connect

    Civan, M.M.; Peterson-Yantorno, K.; O'Brien, T.G.

    1988-02-01

    Insulin stimulates Na/sup +/ transport across frog skin, toad urinary bladder, and the distal renal nephron. This stimulation reflects an increase in apical membrane Na/sup +/ permeability and a stimulation of the basolateral membrane Na,K-exchange pump. Considerable indirect evidence has suggested that the apical natriferic effect of insulin is mediated by activation of protein kinase C. However, no direct information has been available documenting that insulin and protein kinase C indeed share a common pathway in stimulating Na/sup +/ transport across frog skin. In the present work, the authors have studied the interaction of insulin and phorbol 12-myristate 13-acetate (PMA), a documented activator of protein kinase C. Preincubation of skins with 1,2-dioctanoylglycerol, another activator of protein kinase C, increases baseline Na/sup +/ transport and reduces the subsequent natriferic response to PMA. Preincubation with PMA markedly reduces the subsequent natriferic action of insulin. This effect does not appear to primarily reflect PMA-induced internalization of insulin receptors. The insulin receptors are localized on the basolateral surface of frog skin, but the application of PMA to this surface is much less effective than mucosal treatment in reducing the response to insulin. The current results provide documentation that insulin and protein kinase C share a common pathway in stimulating Na/sup +/ transport across frog skin. The data are consistent with the concept that the natriferic effect of insulin on frog skin is, at least in part, mediated by activation of protein kinase C.

  20. Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity

    PubMed Central

    2010-01-01

    Background Obesity is a multifactorial disorder influenced by genetic and environmental factors. Animal models of obesity are required to help us understand the signaling pathways underlying this condition. Zebrafish possess many structural and functional similarities with humans and have been used to model various human diseases, including a genetic model of obesity. The purpose of this study was to establish a zebrafish model of diet-induced obesity (DIO). Results Zebrafish were assigned into two dietary groups. One group of zebrafish was overfed with Artemia (60 mg dry weight/day/fish), a living prey consisting of a relatively high amount of fat. The other group of zebrafish was fed with Artemia sufficient to meet their energy requirements (5 mg dry weight/day/fish). Zebrafish were fed under these dietary protocols for 8 weeks. The zebrafish overfed with Artemia exhibited increased body mass index, which was calculated by dividing the body weight by the square of the body length, hypertriglyceridemia and hepatosteatosis, unlike the control zebrafish. Calorie restriction for 2 weeks was applied to zebrafish after the 8-week overfeeding period. The increased body weight and plasma triglyceride level were improved by calorie restriction. We also performed comparative transcriptome analysis of visceral adipose tissue from DIO zebrafish, DIO rats, DIO mice and obese humans. This analysis revealed that obese zebrafish and mammals share common pathophysiological pathways related to the coagulation cascade and lipid metabolism. Furthermore, several regulators were identified in zebrafish and mammals, including APOH, IL-6 and IL-1β in the coagulation cascade, and SREBF1, PPARα/γ, NR1H3 and LEP in lipid metabolism. Conclusion We established a zebrafish model of DIO that shared common pathophysiological pathways with mammalian obesity. The DIO zebrafish can be used to identify putative pharmacological targets and to test novel drugs for the treatment of human obesity

  1. Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans.

    PubMed

    Dickinson, Peter J; York, Dan; Higgins, Robert J; LeCouteur, Richard A; Joshi, Nikhil; Bannasch, Danika

    2016-07-01

    Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high-grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy.

  2. Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans.

    PubMed

    Dickinson, Peter J; York, Dan; Higgins, Robert J; LeCouteur, Richard A; Joshi, Nikhil; Bannasch, Danika

    2016-07-01

    Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high-grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy. PMID:27251041

  3. Common pathways in health benefit properties of RSV in cardiovascular diseases, cancers and degenerative pathologies.

    PubMed

    Aires, Virginie; Delmas, Dominique

    2015-01-01

    Lots of epidemiological studies have put forward the beneficial effects of dietary polyphenols consumption in the prevention of diseases related to aging i.e vascular pathologies, neurodegeneration, cancers and associated inflammatory processes. Among polyphenols, resveratrol (trans-3,4',5- trihydroxystilbene, RSV), a naturally occurring stilbene widely distributed in foodstuffs such as grapes and wine, has been the most studied. Researches performed since the last decades in vitro, in animal models and in (pre)clinical studies have pointed out its pleiotropic health benefits by acting on multiple signaling pathways which go beyond its originally described direct antioxidant activity. However, its low bioavailability upon oral ingestion and lack of specificity may hamper the translation of the encouraging experimental data into human health benefits. Herein we provide an overview on the capacity of RSV to regulate oxidative stress-induced signaling and to modulate key components of signal transduction pathways which are commonly altered in cardiovascular, neurodegenerative and cancer pathologies. We also have attempted to provide a comprehensive outlook on RSV metabolism and biological activity of its main metabolites and discussed about the new strategies developed to circumvent its poor bioavailability and to improve its therapeutic efficacy, including synthesis of new derivatives and new formulations for its cell delivery. PMID:25601605

  4. Common genetic variants in Wnt signaling pathway genes as potential prognostic biomarkers for colorectal cancer.

    PubMed

    Ting, Wen-Chien; Chen, Lu-Min; Pao, Jiunn-Bey; Yang, Ying-Pi; You, Bang-Jau; Chang, Ta-Yuan; Lan, Yu-Hsuan; Lee, Hong-Zin; Bao, Bo-Ying

    2013-01-01

    Compelling evidence has implicated the Wnt signaling pathway in the pathogenesis of colorectal cancer. We assessed the use of tag single nucleotide polymorphisms (tSNPs) in adenomatous polyposis coli (APC)/β-catenin (CTNNB1) genes to predict outcomes in patients with colorectal cancer. We selected and genotyped 10 tSNP to predict common variants across entire APC and CTNNB1 genes in 282 colorectal cancer patients. The associations of these tSNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis, Cox regression model, and survival tree analysis. The 5-year overall survival rate was 68.3%. Survival tree analysis identified a higher-order genetic interaction profile consisting of the APC rs565453, CTNNB1 2293303, and APC rs1816769 that was significantly associated with overall survival. The 5-year survival overall rates were 89.2%, 66.1%, and 58.8% for the low-, medium-, and high-risk genetic profiles, respectively (log-rank P = 0.001). After adjusting for possible confounders, including age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, perineural invasion, and lymph node involvement, the genetic interaction profile remained significant. None of the studied SNPs were individually associated with distant metastasis-free survival and overall survival. Our results suggest that the genetic interaction profile among Wnt pathway SNPs might potentially increase the prognostic value in outcome prediction for colorectal cancer. PMID:23405266

  5. Cancer and Chemotherapy Contribute to Muscle Loss by Activating Common Signaling Pathways

    PubMed Central

    Barreto, Rafael; Mandili, Giorgia; Witzmann, Frank A.; Novelli, Francesco; Zimmers, Teresa A.; Bonetto, Andrea

    2016-01-01

    Cachexia represents one of the primary complications of colorectal cancer due to its effects on depletion of muscle and fat. Evidence suggests that chemotherapeutic regimens, such as Folfiri, contribute to cachexia-related symptoms. The purpose of the present study was to investigate the cachexia signature in different conditions associated with severe muscle wasting, namely Colon-26 (C26) and Folfiri-associated cachexia. Using a quantitative LC-MS/MS approach, we identified significant changes in 386 proteins in the quadriceps muscle of Folfiri-treated mice, and 269 proteins differentially expressed in the C26 hosts (p < 0.05; −1.5 ≥ fold change ≥ +1.5). Comparative analysis isolated 240 proteins that were modulated in common, with a large majority (218) that were down-regulated in both experimental settings. Interestingly, metabolic (47.08%) and structural (21.25%) proteins were the most represented. Pathway analysis revealed mitochondrial dysfunctions in both experimental conditions, also consistent with reduced expression of mediators of mitochondrial fusion (OPA-1, mitofusin-2), fission (DRP-1) and biogenesis (Cytochrome C, PGC-1α). Alterations of oxidative phosphorylation within the TCA cycle, fatty acid metabolism, and Ca2+ signaling were also detected. Overall, the proteomic signature in the presence of both chemotherapy and cancer suggests the activation of mechanisms associated with movement disorders, necrosis, muscle cell death, muscle weakness and muscle damage. Conversely, this is consistent with the inhibition of pathways that regulate nucleotide and fatty acid metabolism, synthesis of ATP, muscle and heart function, as well as ROS scavenging. Interestingly, strong up-regulation of pro-inflammatory acute-phase proteins and a more coordinated modulation of mitochondrial and lipidic metabolisms were observed in the muscle of the C26 hosts that were different from the Folfiri-treated animals. In conclusion, our results suggest that both cancer

  6. Idiopathic and heritable PAH perturb common molecular pathways, correlated with increased MSX1 expression.

    PubMed

    Austin, Eric D; Menon, Swapna; Hemnes, Anna R; Robinson, Linda R; Talati, Megha; Fox, Kelly L; Cogan, Joy D; Hamid, Rizwan; Hedges, Lora K; Robbins, Ivan; Lane, Kirk; Newman, John H; Loyd, James E; West, James

    2011-01-01

    The majority of pulmonary arterial hypertension (PAH) is not associated with BMPR2 mutation, and major risk factors for idiopathic PAH are not known. The objective of this study was to identify a gene expression signature for IPAH. To accomplish this, we used Affymetrix arrays to probe expression levels in 86 patient samples, including 22 healthy controls, 20 IPAH patients, 20 heritable PAH patients (HPAH), and 24 BMPR2 mutation carriers that were as yet unaffected (UMC). Culturing the patient cells removes the signatures of drug effects and inflammation which have made interpretation of results from freshly isolated lymphocytes problematic. We found that gene expression signatures from IPAH patients clustered either with HPAH patients or in a single distinct group. There were no groups of genes changed in IPAH that were not also changed in HPAH. HPAH, IPAH, and UMC had common changes in metabolism, actin dynamics, adhesion, cytokines, metabolism, channels, differentiation, and transcription factors. Common to IPAH and HPAH but not UMC were an upregulation of vesicle trafficking, oxidative/nitrosative stress, and cell cycle genes. The transcription factor MSX1, which is known to regulate BMP signaling, was the most upregulated gene (4×) in IPAH patients. These results suggest that IPAH cases have a shared molecular origin, which is closely related to, but distinct from, HPAH. HPAH and IPAH share the majority of altered signaling pathways, suggesting that treatments developed to target the molecular etiology of HPAH will also be effective against IPAH.

  7. Rice responds to endophytic colonization which is independent of the common symbiotic signaling pathway.

    PubMed

    Chen, Xi; Miché, Lucie; Sachs, Sabrina; Wang, Qi; Buschart, Anna; Yang, Haiyuan; Vera Cruz, Casiana M; Hurek, Thomas; Reinhold-Hurek, Barbara

    2015-10-01

    As molecular interactions of plants with N2 -fixing endophytes are largely uncharacterized, we investigated whether the common signaling pathway (CSP) shared by root nodule symbioses (RNS) and arbuscular mycorrhizal (AM) symbioses may have been recruited for the endophytic Azoarcus sp.-rice (Oryza sativa) interaction, and combined this investigation with global approaches to characterize rice root responses to endophytic colonization. Putative homologs of genes required for the CSP were analyzed for their putative role in endophytic colonization. Proteomic and suppressive subtractive hybridization (SSH) approaches were also applied, and a comparison of defense-related processes was carried out by setting up a pathosystem for flooded roots with Xanthomonas oryzae pv. oryzae strain PXO99 (Xoo). All tested genes were expressed in rice roots seedlings but not induced upon Azoarcus sp. inoculation, and the oscyclops and oscastor mutants were not impaired in endophytic colonization. Global approaches highlighted changes in rice metabolic activity and Ca(2+) -dependent signaling in roots colonized by endophytes, including some stress proteins. Marker genes for defense responses were induced to a lesser extent by the endophytes than by the pathogen, indicating a more compatible interaction. Our results thus suggest that rice roots respond to endophytic colonization by inducing metabolic shifts and signaling events, for which the CSP is not essential. PMID:26009800

  8. DELLA proteins are common components of symbiotic rhizobial and mycorrhizal signalling pathways

    PubMed Central

    Jin, Yue; Liu, Huan; Luo, Dexian; Yu, Nan; Dong, Wentao; Wang, Chao; Zhang, Xiaowei; Dai, Huiling; Yang, Jun; Wang, Ertao

    2016-01-01

    Legumes form symbiotic associations with either nitrogen-fixing bacteria or arbuscular mycorrhizal fungi. Formation of these two symbioses is regulated by a common set of signalling components that act downstream of recognition of rhizobia or mycorrhizae by host plants. Central to these pathways is the calcium and calmodulin-dependent protein kinase (CCaMK)–IPD3 complex which initiates nodule organogenesis following calcium oscillations in the host nucleus. However, downstream signalling events are not fully understood. Here we show that Medicago truncatula DELLA proteins, which are the central regulators of gibberellic acid signalling, positively regulate rhizobial symbiosis. Rhizobia colonization is impaired in della mutants and we provide evidence that DELLAs can promote CCaMK–IPD3 complex formation and increase the phosphorylation state of IPD3. DELLAs can also interact with NSP2–NSP1 and enhance the expression of Nod-factor-inducible genes in protoplasts. We show that DELLA is able to bridge a protein complex containing IPD3 and NSP2. Our results suggest a transcriptional framework for regulation of root nodule symbiosis. PMID:27514472

  9. Activation of common signaling pathways during remodeling of the heart and the bladder.

    PubMed

    Koeck, Ivonne; Burkhard, Fiona C; Monastyrskaya, Katia

    2016-02-15

    The heart and the urinary bladder are hollow muscular organs, which can be afflicted by pressure overload injury due to pathological conditions such as hypertension and bladder outlet obstruction. This increased outflow resistance induces hypertrophy, marked by dramatic changes in the organs' phenotype and function. The end result in both the heart and the bladder can be acute organ failure due to advanced fibrosis and the subsequent loss of contractility. There is emerging evidence that microRNAs (miRNAs) play an important role in the pathogenesis of heart failure and bladder dysfunction. MiRNAs are endogenous non-coding single-stranded RNAs, which regulate gene expression and control adaptive and maladaptive organ remodeling processes. This Review summarizes the current knowledge of molecular alterations in the heart and the bladder and highlights common signaling pathways and regulatory events. The miRNA expression analysis and experimental target validation done in the heart provide a valuable source of information for investigators working on the bladder and other organs undergoing the process of fibrotic remodeling. Aberrantly expressed miRNA are amendable to pharmacological manipulation, offering an opportunity for development of new therapies for cardiac and bladder hypertrophy and failure.

  10. DELLA proteins are common components of symbiotic rhizobial and mycorrhizal signalling pathways.

    PubMed

    Jin, Yue; Liu, Huan; Luo, Dexian; Yu, Nan; Dong, Wentao; Wang, Chao; Zhang, Xiaowei; Dai, Huiling; Yang, Jun; Wang, Ertao

    2016-01-01

    Legumes form symbiotic associations with either nitrogen-fixing bacteria or arbuscular mycorrhizal fungi. Formation of these two symbioses is regulated by a common set of signalling components that act downstream of recognition of rhizobia or mycorrhizae by host plants. Central to these pathways is the calcium and calmodulin-dependent protein kinase (CCaMK)-IPD3 complex which initiates nodule organogenesis following calcium oscillations in the host nucleus. However, downstream signalling events are not fully understood. Here we show that Medicago truncatula DELLA proteins, which are the central regulators of gibberellic acid signalling, positively regulate rhizobial symbiosis. Rhizobia colonization is impaired in della mutants and we provide evidence that DELLAs can promote CCaMK-IPD3 complex formation and increase the phosphorylation state of IPD3. DELLAs can also interact with NSP2-NSP1 and enhance the expression of Nod-factor-inducible genes in protoplasts. We show that DELLA is able to bridge a protein complex containing IPD3 and NSP2. Our results suggest a transcriptional framework for regulation of root nodule symbiosis. PMID:27514472

  11. Neuropathogenesis of delirium: review of current etiologic theories and common pathways.

    PubMed

    Maldonado, José R

    2013-12-01

    Delirium is a neurobehavioral syndrome caused by dysregulation of neuronal activity secondary to systemic disturbances. Over time, a number of theories have been proposed in an attempt to explain the processes leading to the development of delirium. Each proposed theory has focused on a specific mechanism or pathologic process (e.g., dopamine excess or acetylcholine deficiency theories), observational and experiential evidence (e.g., sleep deprivation, aging), or empirical data (e.g., specific pharmacologic agents' association with postoperative delirium, intraoperative hypoxia). This article represents a review of published literature and summarizes the top seven proposed theories and their interrelation. This review includes the "neuroinflammatory," "neuronal aging," "oxidative stress," "neurotransmitter deficiency," "neuroendocrine," "diurnal dysregulation," and "network disconnectivity" hypotheses. Most of these theories are complementary, rather than competing, with many areas of intersection and reciprocal influence. The literature suggests that many factors or mechanisms included in these theories lead to a final common outcome associated with an alteration in neurotransmitter synthesis, function, and/or availability that mediates the complex behavioral and cognitive changes observed in delirium. In general, the most commonly described neurotransmitter changes associated with delirium include deficiencies in acetylcholine and/or melatonin availability; excess in dopamine, norepinephrine, and/or glutamate release; and variable alterations (e.g., either a decreased or increased activity, depending on delirium presentation and cause) in serotonin, histamine, and/or γ-aminobutyric acid. In the end, it is unlikely that any one of these theories is fully capable of explaining the etiology or phenomenologic manifestations of delirium but rather that two or more of these, if not all, act together to lead to the biochemical derangement and, ultimately, to the

  12. Characterization of the cis elements in the proximal promoter regions of the anthocyanin pathway genes reveals a common regulatory logic that governs pathway regulation

    PubMed Central

    Zhu, Zhixin; Wang, Hailong; Wang, Yiting; Guan, Shan; Wang, Fang; Tang, Jingyu; Zhang, Ruijuan; Xie, Lulu; Lu, Yingqing

    2015-01-01

    Cellular activities such as compound synthesis often require the transcriptional activation of an entire pathway; however, the molecular mechanisms underlying pathway activation have rarely been explained. Here, the cis regulatory architecture of the anthocyanin pathway genes targeted by the transcription factor (TF) complex including MYB, bHLH, and WDR was systematically analysed in one species and the findings extended to others. In Ipomoea purpurea, the IpMYB1-IpbHLH2-IpWDR1 (IpMBW) complex was found to be orthologous to the PAP1-GL3-TTG1 (AtPGT) complex of Arabidopsis thaliana, and interacted with a 7-bp MYB-recognizing element (MRE) and a 6-bp bHLH-recognizing element (BRE) at the proximal promoter region of the pathway genes. There was little transcription of the gene in the absence of the MRE or BRE. The cis elements identified experimentally converged on two syntaxes, ANCNNCC for MREs and CACN(A/C/T)(G/T) for BREs, and our bioinformatic analysis showed that these were present within anthocyanin gene promoters in at least 35 species, including both gymnosperms and angiosperms. For the anthocyanin pathway, IpMBW and AtPGT recognized the interspecific promoters of both early and later genes. In A. thaliana, the seed-specific TF complex (TT2, TT8, and TTG1) may regulate all the anthocyanin pathway genes, in addition to the proanthocyanidin-specific BAN. When multiple TF complexes in the anthocyanin pathway were compared, the cis architecture played a role larger than the TF complex in determining the variation in promoter activity. Collectively, a cis logic common to the pathway gene promoters was found, and this logic is essential for the trans factors to regulate the pathway. PMID:25911741

  13. DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases

    PubMed Central

    Bettencourt, Conceição; Hensman‐Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas‐Gómez, Petra; García‐Velázquez, Lizbeth Esmeralda; Alonso‐Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J.

    2016-01-01

    Objective The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. Methods We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. Results In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10–5). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10–5) and all SCAs (p = 2.22 × 10–4) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10–5), all in the same direction as in the HD GWAS. Interpretation We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983–990 PMID:27044000

  14. Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells.

    PubMed

    Wang, L M; Keegan, A D; Li, W; Lienhard, G E; Pacini, S; Gutkind, J S; Myers, M G; Sun, X J; White, M F; Aaronson, S A

    1993-05-01

    Interleukin 4 (IL-4), insulin, and insulin-like growth factor I (IGF-I) efficiently induced DNA synthesis in the IL-3-dependent murine myeloid cell lines FDC-P1 and FDC-P2. Although these factors could not individually sustain long-term growth of these lines, a combination of IL-4 with either insulin or IGF-I did support continuous growth. The principal tyrosine-phosphorylated substrate observed in FDC cells stimulated with IL-4, previously designated 4PS, was of the same size (170 kDa) as the major substrate phosphorylated in response to insulin or IGF-I. These substrates had phosphopeptides of the same size when analyzed by digestion with Staphylococcus aureus V8 protease, and each tightly associated with the 85-kDa component of phosphatidylinositol 3-kinase after factor stimulation. IRS-1, the principal substrate phosphorylated in response to insulin or IGF-I stimulation in nonhematopoietic cells, is similar in size to 4PS. However, anti-IRS-1 antibodies failed to efficiently precipitate 4PS, and some phosphopeptides generated by V8 protease digestion of IRS-1 were distinct in size from the phosphopeptides of 4PS. Nevertheless, IL-4, insulin, and IGF-I were capable of stimulating tyrosine phosphorylation of IRS-1 in FDC cells that expressed this substrate as a result of transfection. These findings indicate that (i) IL-4, insulin, and IGF-I use signal transduction pathways in FDC lines that have at least one major feature in common, the rapid tyrosine phosphorylation of 4PS, and (ii) insulin and IGF-I stimulation of hematopoietic cell lines leads to the phosphorylation of a substrate that may be related to but is not identical to IRS-1.

  15. Gene expression data reveal common pathways that characterize the unifocal nature of ovarian cancer

    PubMed Central

    MARCHION, Douglas C.; XIONG, Yin; CHON, Hye Sook; SAWAH, Entidhar AL; ZGHEIB, Nadim BOU; RAMIREZ, Ingrid J.; ABBASI, Forough; STICKLES, Xiaomang B.; JUDSON, Patricia L.; HAKAM, Ardeshir; GONZALEZ-BOSQUET, Jesus; WENHAM, Robert M.; APTE, Sachin M.; BERGLUND, Anders E.; LANCASTER, Johnathan M.

    2013-01-01

    Objectives To evaluate the biologic validity of ovarian cancer (OVCA) screening and early detection efforts and to characterize signaling pathways associated with human cancer metastasis and patient survival. Study Design Using genome-wide expression profiling and DNA sequencing, we compared pelvic and matched extra-pelvic implants from 30 patients with advanced-stage OVCA for expression of molecular signaling pathways and p53 gene mutations. Differentially expressed pathways were further evaluated in a series of primary or early-stage versus metastatic or recurrent cancer samples from 389 ovarian, prostate, and oral cancer patients. Metastasis pathways were also evaluated for associations with survival in nine independent clinico-genomic datasets from 1,691 ovarian, breast, colon, brain, and lung cancer and leukemia patients. The inhibitory effects of one pathway (TGF-WNT) on in-vitro OVCA cell migration were studied. Results Pelvic and extra-pelvic OVCA implants demonstrated similar patterns of signaling pathway expression and identical p53 mutations. However, we identified 3 molecular pathways/cellular processes that were differentially expressed between pelvic and extra-pelvic OVCA samples and between primary/early-stage and metastatic/advanced or recurrent ovarian, oral, and prostate cancers. Furthermore, their expression was associated with overall survival from ovarian cancer (P=0.006), colon cancer (1 pathway at P=0.005), and leukemia (P=0.05). Artesunate-induced TGF-WNT pathway inhibition impaired OVCA cell migration. Conclusions Advanced-stage OVCA has a unifocal origin in the pelvis, supporting validity of early detection/screening efforts. Molecular pathways associated with extra-pelvic OVCA spread are also associated with metastasis from other human cancers and with overall patient survival. Such pathways represent appealing therapeutic targets for patients with metastatic disease. PMID:23933223

  16. Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal?##

    EPA Science Inventory

    Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal? Leon Earl Gray Jr, USEPA, ORD, NHEERL, TAD, RTB. RTP, NC, USA The shape of the dose response curve in the low dose region has been debated since th...

  17. Common Variation in Vitamin D Pathway Genes Predicts Circulating 25-Hydroxyvitamin D Levels among African Americans

    PubMed Central

    Signorello, Lisa B.; Shi, Jiajun; Cai, Qiuyin; Zheng, Wei; Williams, Scott M.; Long, Jirong; Cohen, Sarah S.; Li, Guoliang; Hollis, Bruce W.; Smith, Jeffrey R.; Blot, William J.

    2011-01-01

    Vitamin D is implicated in a wide range of health outcomes, and although environmental predictors of vitamin D levels are known, the genetic drivers of vitamin D status remain to be clarified. African Americans are a group at particularly high risk for vitamin D insufficiency but to date have been virtually absent from studies of genetic predictors of circulating vitamin D levels. Within the Southern Community Cohort Study, we investigated the association between 94 single nucleotide polymorphisms (SNPs) in five vitamin D pathway genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1) and serum 25-hydroxyvitamin D (25(OH)D) levels among 379 African American and 379 Caucasian participants. We found statistically significant associations with three SNPs (rs2298849 and rs2282679 in the GC gene, and rs10877012 in the CYP27B1 gene), although only for African Americans. A genotype score, representing the number of risk alleles across the three SNPs, alone accounted for 4.6% of the variation in serum vitamin D among African Americans. A genotype score of 5 (vs. 1) was also associated with a 7.1 ng/mL reduction in serum 25(OH)D levels and a six-fold risk of vitamin D insufficiency (<20 ng/mL) (odds ratio 6.0, p = 0.01) among African Americans. With African ancestry determined from a panel of 276 ancestry informative SNPs, we found that high risk genotypes did not cluster among those with higher African ancestry. This study is one of the first to investigate common genetic variation in relation to vitamin D levels in African Americans, and the first to evaluate how vitamin D-associated genotypes vary in relation to African ancestry. These results suggest that further evaluation of genetic contributors to vitamin D status among African Americans may help provide insights regarding racial health disparities or enable the identification of subgroups especially in need of vitamin D-related interventions. PMID:22205958

  18. Beginning at the end: Repetitive firing properties in the final common pathway

    PubMed Central

    Brownstone, Robert M.

    2016-01-01

    Since the early 20th century, it has been recognized that motoneurons must fire repetitive trains of action potentials to produce muscle contraction. In 1932, Sir John Eccles, together with Hebbel Hoff, found that action potential spike trains in motor axons were produced by “rhythmic centres”, which were within the motoneurons themselves. Two decades later, Eccles attended a Cold Spring Harbor Symposium in NY, USA entitled “The Neuron”. Two of the many notable presentations at this symposium were juxtaposed: one by Eccles from the University of Otago, Dunedin, NZL, and the other by J. Walter Woodbury and Harry Patton from the University of Washington, Seattle, USA. Both presentations included data obtained using sharp microelectrodes to study the intracellularly recorded potentials of cat motoneurons. In this review, I discuss some of the events leading up to and surrounding this jointly accomplished advance and proceed to discussion of subsequent studies over 5+ decades that have made use of intracellular recordings from motoneurons to study their repetitive firing behavior. This begins with early descriptions of primary and secondary range firing, and continues to the discovery of dendritic persistent inward currents and their relation to plateau potentials, synaptic amplification, and motoneuronal firing. Following a brief description of the possible mechanisms underlying spike frequency adaptation, I discuss the modulation of repetitive firing properties during various motor behaviors. It has become increasingly clear that the central nervous system has exquisite control of the repetitive firing of motoneurons. Eccles’ work laid the foundation for the present-day study of these processes. PMID:16725251

  19. Disability in COPD and Chronic Heart Failure Is the Skeletal Muscle the Final Common Pathway?

    PubMed Central

    DUMITRU, Luminita; ILIESCU, Alina; DINU, Horatiu; BADEA, Ruxandra; SAVULESCU, Simona; HUIDU, Simona; BERTEANU, Mihai

    2013-01-01

    ABSTRACT Chronic Obstructive Pulmonary Disease (COPD) and Chronic Heart Failure (CHF), two major causes of worldwide morbidity and mortality have important systemic components, affecting additional tissues, other than the lung or the heart, such as the skeletal muscle. Muscle function (or dysfunction) may not only influence the symptoms that limit exercise, but may contribute directly to the poor exercise performance, health status and increased healthcare utilization. The present review tries to summarize the muscular abnormalities in COPD and CHF and the mechanisms underlying these alterations, which are strikingly similar, despite the obvious differences concerning the primary impairment in these two chronic diseases. The muscles therefore represent a potential site to improve patients' functioning level and quality of life of COPD and CHF. Only one practical therapeutic intervention currently exists that can reverse some of the muscle abnormalities observed in COPD and CHF, namely exercise training, which becomes nowadays the "cornerstone" of the whole rehabilitation. PMID:24371487

  20. Common Extracellular Sensory Domains in Transmembrane Receptors for Diverse Signal Transduction Pathways in Bacteria and Archaea

    PubMed Central

    Zhulin, Igor B.; Nikolskaya, Anastasia N.; Galperin, Michael Y.

    2003-01-01

    Transmembrane receptors in microorganisms, such as sensory histidine kinases and methyl-accepting chemotaxis proteins, are molecular devices for monitoring environmental changes. We report here that sensory domain sharing is widespread among different classes of transmembrane receptors. We have identified two novel conserved extracellular sensory domains, named CHASE2 and CHASE3, that are found in at least four classes of transmembrane receptors: histidine kinases, adenylate cyclases, predicted diguanylate cyclases, and either serine/threonine protein kinases (CHASE2) or methyl-accepting chemotaxis proteins (CHASE3). Three other extracellular sensory domains were shared by at least two different classes of transmembrane receptors: histidine kinases and either diguanylate cyclases, adenylate cyclases, or phosphodiesterases. These observations suggest that microorganisms use similar conserved domains to sense similar environmental signals and transmit this information via different signal transduction pathways to different regulatory circuits: transcriptional regulation (histidine kinases), chemotaxis (methyl-accepting proteins), catabolite repression (adenylate cyclases), and modulation of enzyme activity (diguanylate cyclases and phosphodiesterases). The variety of signaling pathways using the CHASE-type domains indicates that these domains sense some critically important extracellular signals. PMID:12486065

  1. Oakland and San Francisco Create Course Pathways through Common Core Mathematics. White Paper

    ERIC Educational Resources Information Center

    Daro, Phil

    2014-01-01

    The Common Core State Standards for Mathematics (CCSS-M) set rigorous standards for each of grades 6, 7 and 8. Strategic Education Research Partnership (SERP) has been working with two school districts, Oakland Unified School District and San Francisco Unified School District, to evaluate extant policies and practices and formulate new policies…

  2. DNA repair choice defines a common pathway for recruitment of chromatin regulators

    PubMed Central

    Bennett, Gwendolyn; Papamichos-Chronakis, Manolis; Peterson, Craig L.

    2013-01-01

    DNA double-strand break (DSB) repair is essential for maintenance of genome stability. Recent work has implicated a host of chromatin regulators in the DNA damage response, and although several functional roles have been defined, the mechanisms that control their recruitment to DNA lesions remain unclear. Here, we find that efficient DSB recruitment of the INO80, SWR-C, NuA4, SWI/SNF, and RSC enzymes is inhibited by the non-homologous end joining machinery, and that their recruitment is controlled by early steps of homologous recombination. Strikingly, we find no significant role for H2A.X phosphorylation (γH2AX) in the recruitment of chromatin regulators, but rather their recruitment coincides with reduced levels of γH2AX. Our work indicates that cell cycle position plays a key role in DNA repair pathway choice and that recruitment of chromatin regulators is tightly coupled to homologous recombination. PMID:23811932

  3. Opposite phenotypes of cancer and aging arise from alternative regulation of common signaling pathways.

    PubMed

    Ukraintseva, Svetlana V; Yashin, Anatoly I

    2003-12-01

    Phenotypic features of malignant and senescent cells are in many instances opposite. Cancer cells do not "age"; their metabolic, proliferative, and growth characteristics are opposite to those observed with cellular aging (both replicative and functional). In many such characteristics cancer cells resemble embryonic cells. One can say that cancer manifests itself as a local, uncontrolled "rejuvenation" in an organism. Available evidence from human and animal studies suggests that the opposite phenotypic features of aging and cancer arise from the opposite regulation of genes participating in apoptosis/growth arrest or growth signal transduction pathways in cells. This fact may be applicable in the development of new anti-aging treatments. Genes that are contrarily regulated in cancer and aging cells (e.g., proto-oncogenes or tumor suppressors) could be candidate targets for anti-aging interventions. Their "cancer-like" regulation, if strictly controlled, might help to rejuvenate the human organism. PMID:15033776

  4. Detection of phytohormones in temperate forest fungi predicts consistent abscisic acid production and a common pathway for cytokinin biosynthesis.

    PubMed

    Morrison, Erin N; Knowles, Sarah; Hayward, Allison; Thorn, R Greg; Saville, Barry J; Emery, R J N

    2015-01-01

    The phytohormones, abscisic acid and cytokinin, once were thought to be present uniquely in plants, but increasing evidence suggests that these hormones are present in a wide variety of organisms. Few studies have examined fungi for the presence of these "plant" hormones or addressed whether their levels differ based on the nutrition mode of the fungus. This study examined 20 temperate forest fungi of differing nutritional modes (ectomycorrhizal, wood-rotting, saprotrophic). Abscisic acid and cytokinin were present in all fungi sampled; this indicated that the sampled fungi have the capacity to synthesize these two classes of phytohormones. Of the 27 cytokinins analyzed by HPLC-ESI MS/MS, seven were present in all fungi sampled. This suggested the existence of a common cytokinin metabolic pathway in fungi that does not vary among different nutritional modes. Predictions regarding the source of isopentenyl, cis-zeatin and methylthiol CK production stemming from the tRNA degradation pathway among fungi are discussed.

  5. Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common occurrence of nonmodular enzymes.

    PubMed

    Wang, Hao; Fewer, David P; Holm, Liisa; Rouhiainen, Leo; Sivonen, Kaarina

    2014-06-24

    Nonribosomal peptides and polyketides are a diverse group of natural products with complex chemical structures and enormous pharmaceutical potential. They are synthesized on modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzyme complexes by a conserved thiotemplate mechanism. Here, we report the widespread occurrence of NRPS and PKS genetic machinery across the three domains of life with the discovery of 3,339 gene clusters from 991 organisms, by examining a total of 2,699 genomes. These gene clusters display extraordinarily diverse organizations, and a total of 1,147 hybrid NRPS/PKS clusters were found. Surprisingly, 10% of bacterial gene clusters lacked modular organization, and instead catalytic domains were mostly encoded as separate proteins. The finding of common occurrence of nonmodular NRPS differs substantially from the current classification. Sequence analysis indicates that the evolution of NRPS machineries was driven by a combination of common descent and horizontal gene transfer. We identified related siderophore NRPS gene clusters that encoded modular and nonmodular NRPS enzymes organized in a gradient. A higher frequency of the NRPS and PKS gene clusters was detected from bacteria compared with archaea or eukarya. They commonly occurred in the phyla of Proteobacteria, Actinobacteria, Firmicutes, and Cyanobacteria in bacteria and the phylum of Ascomycota in fungi. The majority of these NRPS and PKS gene clusters have unknown end products highlighting the power of genome mining in identifying novel genetic machinery for the biosynthesis of secondary metabolites.

  6. Evidence for a common biological pathway linking three Parkinson's disease-causing genes: parkin, PINK1 and DJ-1.

    PubMed

    van der Merwe, Celia; Jalali Sefid Dashti, Zahra; Christoffels, Alan; Loos, Ben; Bardien, Soraya

    2015-05-01

    Parkinson's disease (PD) is characterised by the loss of dopaminergic neurons in the midbrain. Autosomal recessive, early-onset cases of PD are predominantly caused by mutations in the parkin, PINK1 and DJ-1 genes. Animal and cellular models have verified a direct link between parkin and PINK1, whereby PINK1 phosphorylates and activates parkin at the outer mitochondrial membrane, resulting in removal of dysfunctional mitochondria via mitophagy. Despite the overwhelming evidence for this interaction, few studies have been able to identify a link for DJ-1 with parkin or PINK1. The aim of this review is to summarise the functions of these three proteins, and to analyse the existing evidence for direct and indirect interactions between them. DJ-1 is able to rescue the phenotype of PINK1-knockout Drosophila models, but not of parkin-knockouts, suggesting that DJ-1 may act in a parallel pathway to that of the PINK1/parkin pathway. To further elucidate a commonality between these three proteins, bioinformatics analysis established that Miro (RHOT1) interacts with parkin and PINK1, and HSPA4 interacts with all three proteins. Furthermore, 30 transcription factors were found to be common amongst all three proteins, with many of them being involved in transcriptional regulation. Interestingly, expression of these proteins and their associated transcription factors are found to be significantly down-regulated in PD patients compared to healthy controls. In summary, this review provides insight into common pathways linking three PD-causing genes and highlights some key questions, the answers to which may provide critical insight into the disease process.

  7. Import pathways of precursor proteins into mitochondria: multiple receptor sites are followed by a common membrane insertion site

    PubMed Central

    1988-01-01

    The precursor of porin, a mitochondrial outer membrane protein, competes for the import of precursors destined for the three other mitochondrial compartments, including the Fe/S protein of the bc1- complex (intermembrane space), the ADP/ATP carrier (inner membrane), subunit 9 of the F0-ATPase (inner membrane), and subunit beta of the F1- ATPase (matrix). Competition occurs at the level of a common site at which precursors are inserted into the outer membrane. Protease- sensitive binding sites, which act before the common insertion site, appear to be responsible for the specificity and selectivity of mitochondrial protein uptake. We suggest that distinct receptor proteins on the mitochondrial surface specifically recognize precursor proteins and transfer them to a general insertion protein component (GIP) in the outer membrane. Beyond GIP, the import pathways diverge, either to the outer membrane or to translocation contact-sites, and then subsequently to the other mitochondrial compartments. PMID:2974457

  8. Ligands internalized through coated or noncoated invaginations follow a common intracellular pathway

    SciTech Connect

    Tran, D.; Carpentier, J.L.; Sawano, F.; Gorden, P.; Orci, L.

    1987-11-01

    Cholera toxic (CT) represents a class of ligands that binds preferentially to noncoated pits on the cell surface. In the present study, the authors have investigated the mechanism of endocytosis of this class of ligand and compared it to the classic coated pit mechanism. When either CT coupled to colloidal gold particles (CT-gold) or /sup 125/I-labeled CT were incubated with 3T3 L1 fibroblasts at 4/sup 0/C, both ligands bound in a preferential fashion to small noncoated pits on the cell surface. CT-gold surface-labeled cells were then incubated at 22/sup 0/C. The labeled ligand progressively moved into noncoated vesicles and a tubulovesicular compartment composed of a network of tubules and vesicles closely associated with multivesicular bodies but distinct from the Golgi complexes. The ligand next passed into multivesicular bodies. By contrast, ..cap alpha../sub 2/-macroglobulin (..cap alpha../sub 2/m)-gold initially localized preferentially to coated pits and subsequently to coated vesicles and tubulovesicular structures before associating with multivesicular bodies. To directly compare the intracellular pathway followed by CT-gold to that followed by ..cap alpha../sub 2/m, CT-gold was coincubated with ..cap alpha../sub 2/m-gold. By 10 min of incubation at 22/sup 0/C, up to 66% of tubulovesicular units contained both ligands when analyzed in serial sections. Subsequently, both ligands were colocalized in multivesicular bodies. They conclude that CT-gold endocytosed via noncoated vesicles and ..cap alpha../sub 2/m-gold endocytosed through coated vesicles subsequently associate with the same tubulovesicular units, multivesicular bodies, and lysosomes.

  9. Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways.

    PubMed

    Howe, A S; Buttenschøn, H N; Bani-Fatemi, A; Maron, E; Otowa, T; Erhardt, A; Binder, E B; Gregersen, N O; Mors, O; Woldbye, D P; Domschke, K; Reif, A; Shlik, J; Kõks, S; Kawamura, Y; Miyashita, A; Kuwano, R; Tokunaga, K; Tanii, H; Smoller, J W; Sasaki, T; Koszycki, D; De Luca, V

    2016-05-01

    The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed for three variants, TMEM132D rs7370927 (T allele: odds ratio (OR)=1.27, 95% confidence interval (CI): 1.15-1.40, P=2.49 × 10(-6)), rs11060369 (CC genotype: OR=0.65, 95% CI: 0.53-0.79, P=1.81 × 10(-5)) and COMT rs4680 (Val (G) allele: OR=1.27, 95% CI: 1.14-1.42, P=2.49 × 10(-5)) in studies with samples of European ancestry. Nominal associations that did not survive correction for multiple testing were observed for NPSR1 rs324891 (T allele: OR=1.22, 95% CI: 1.07-1.38, P=0.002), TPH1 rs1800532 (AA genotype: OR=1.46, 95% CI: 1.14-1.89, P=0.003) and HTR2A rs6313 (T allele: OR=1.19, 95% CI: 1.07-1.33, P=0.002) in studies with samples of European ancestry and for MAOA-uVNTR in female PD (low-active alleles: OR=1.21, 95% CI: 1.07-1.38, P=0.004). No significant associations were observed in the secondary analyses considering sex, agoraphobia co-morbidity and studies with samples of Asian ancestry. Although these findings highlight a few associations, PD likely involves genetic variation in a multitude of biological pathways that is diverse among populations. Future studies must

  10. Shared Genetic Factors Involved in Celiac Disease, Type 2 Diabetes and Anorexia Nervosa Suggest Common Molecular Pathways for Chronic Diseases

    PubMed Central

    Mostowy, Joanna; Montén, Caroline; Gudjonsdottir, Audur H.; Arnell, Henrik; Browaldh, Lars; Nilsson, Staffan; Agardh, Daniel

    2016-01-01

    Background and Objectives Genome-wide association studies (GWAS) have identified several genetic regions involved in immune-regulatory mechanisms to be associated with celiac disease. Previous GWAS also revealed an over-representation of genes involved in type 2 diabetes and anorexia nervosa associated with celiac disease, suggesting involvement of common metabolic pathways for development of these chronic diseases. The aim of this study was to extend these previous analyses to study the gene expression in the gut from children with active celiac disease. Material and Methods Thirty six target genes involved in type 2 diabetes and four genes associated with anorexia nervosa were investigated for gene expression in small intestinal biopsies from 144 children with celiac disease at median (range) age of 7.4 years (1.6–17.8) and from 154 disease controls at a median (range) age 11.4.years (1.4–18.3). Results A total of eleven of genes were differently expressed in celiac patients compared with disease controls of which CD36, CD38, FOXP1, SELL, PPARA, PPARG, AGT previously associated with type 2 diabetes and AKAP6, NTNG1 with anorexia nervosa remained significant after correction for multiple testing. Conclusion Shared genetic factors involved in celiac disease, type 2 diabetes and anorexia nervosa suggest common underlying molecular pathways for these diseases. PMID:27483138

  11. Dextromethorphan Addiction Mediated Through the NMDA System: Common Pathways With Alcohol?

    PubMed

    Roy, A Kenison; Hsieh, Chenen; Crapanzano, Kathleen

    2015-01-01

    Dextromethorphan, an antitussive (cough suppressant) drug of the morphinan class with sedative and dissociative properties found in cough syrup and other over-the-counter products, is also a substance of abuse, seen primarily in young adults all over the world. A case of dextromethorphan use disorder is presented in a 45-year-old women. Her repeated attempts at abstinence were unsuccessful secondary to continued intense cravings. Treatment with topiramate resulted in complete resolution of her cravings. Topiramate was chosen empirically because of a common action with dextromethorphan in the NMDA system. Genetic testing was obtained and the patient was found to be a carrier of the GRIK1 rs2832407(C:C) allele. The (C:C) allele has been associated with an increased risk of alcohol use disorder and a treatment response of patients with heavy drinking to topiramate. This case provides an opportunity to discuss personalized medicine (treatment options aided by the use of genetic testing) and the possible shared genetic susceptibility for dependence in 2 substances of abuse.

  12. Dextromethorphan Addiction Mediated Through the NMDA System: Common Pathways With Alcohol?

    PubMed

    Roy, A Kenison; Hsieh, Chenen; Crapanzano, Kathleen

    2015-01-01

    Dextromethorphan, an antitussive (cough suppressant) drug of the morphinan class with sedative and dissociative properties found in cough syrup and other over-the-counter products, is also a substance of abuse, seen primarily in young adults all over the world. A case of dextromethorphan use disorder is presented in a 45-year-old women. Her repeated attempts at abstinence were unsuccessful secondary to continued intense cravings. Treatment with topiramate resulted in complete resolution of her cravings. Topiramate was chosen empirically because of a common action with dextromethorphan in the NMDA system. Genetic testing was obtained and the patient was found to be a carrier of the GRIK1 rs2832407(C:C) allele. The (C:C) allele has been associated with an increased risk of alcohol use disorder and a treatment response of patients with heavy drinking to topiramate. This case provides an opportunity to discuss personalized medicine (treatment options aided by the use of genetic testing) and the possible shared genetic susceptibility for dependence in 2 substances of abuse. PMID:26441400

  13. Cerebellar ataxias: β-III spectrin's interactions suggest common pathogenic pathways.

    PubMed

    Perkins, Emma; Suminaite, Daumante; Jackson, Mandy

    2016-08-15

    Spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of disorders all characterised by postural abnormalities, motor deficits and cerebellar degeneration. Animal and in vitro models have revealed β-III spectrin, a cytoskeletal protein present throughout the soma and dendritic tree of cerebellar Purkinje cells, to be required for the maintenance of dendritic architecture and for the trafficking and/or stabilisation of several membrane proteins: ankyrin-R, cell adhesion molecules, metabotropic glutamate receptor-1 (mGluR1), voltage-gated sodium channels (Nav ) and glutamate transporters. This scaffold of interactions connects β-III spectrin to a wide variety of proteins implicated in the pathology of many SCAs. Heterozygous mutations in the gene encoding β-III spectrin (SPTBN2) underlie SCA type-5 whereas homozygous mutations cause spectrin associated autosomal recessive ataxia type-1 (SPARCA1), an infantile form of ataxia with cognitive impairment. Loss-of β-III spectrin function appears to underpin cerebellar dysfunction and degeneration in both diseases resulting in thinner dendrites, excessive dendritic protrusion with loss of planarity, reduced resurgent sodium currents and abnormal glutamatergic neurotransmission. The initial physiological consequences are a decrease in spontaneous activity and excessive excitation, likely to be offsetting each other, but eventually hyperexcitability gives rise to dark cell degeneration and reduced cerebellar output. Similar molecular mechanisms have been implicated for SCA1, 2, 3, 7, 13, 14, 19, 22, 27 and 28, highlighting alterations to intrinsic Purkinje cell activity, dendritic architecture and glutamatergic transmission as possible common mechanisms downstream of various loss-of-function primary genetic defects. A key question for future research is whether similar mechanisms underlie progressive cerebellar decline in normal ageing. PMID:26821241

  14. Cerebellar ataxias: β‐III spectrin's interactions suggest common pathogenic pathways

    PubMed Central

    Perkins, Emma; Suminaite, Daumante

    2016-01-01

    Abstract Spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of disorders all characterised by postural abnormalities, motor deficits and cerebellar degeneration. Animal and in vitro models have revealed β‐III spectrin, a cytoskeletal protein present throughout the soma and dendritic tree of cerebellar Purkinje cells, to be required for the maintenance of dendritic architecture and for the trafficking and/or stabilisation of several membrane proteins: ankyrin‐R, cell adhesion molecules, metabotropic glutamate receptor‐1 (mGluR1), voltage‐gated sodium channels (Nav) and glutamate transporters. This scaffold of interactions connects β‐III spectrin to a wide variety of proteins implicated in the pathology of many SCAs. Heterozygous mutations in the gene encoding β‐III spectrin (SPTBN2) underlie SCA type‐5 whereas homozygous mutations cause spectrin associated autosomal recessive ataxia type‐1 (SPARCA1), an infantile form of ataxia with cognitive impairment. Loss‐of β‐III spectrin function appears to underpin cerebellar dysfunction and degeneration in both diseases resulting in thinner dendrites, excessive dendritic protrusion with loss of planarity, reduced resurgent sodium currents and abnormal glutamatergic neurotransmission. The initial physiological consequences are a decrease in spontaneous activity and excessive excitation, likely to be offsetting each other, but eventually hyperexcitability gives rise to dark cell degeneration and reduced cerebellar output. Similar molecular mechanisms have been implicated for SCA1, 2, 3, 7, 13, 14, 19, 22, 27 and 28, highlighting alterations to intrinsic Purkinje cell activity, dendritic architecture and glutamatergic transmission as possible common mechanisms downstream of various loss‐of‐function primary genetic defects. A key question for future research is whether similar mechanisms underlie progressive cerebellar decline in normal ageing. PMID:26821241

  15. Common Intra-Cluster Competencies Needed in Selected Occupational Clusters. Health Occupations. Final Report.

    ERIC Educational Resources Information Center

    McClurg, Ronald B.

    An analysis of competencies practiced by seventeen health occupation groups was conducted to determine the extent to which commonality existed in job activities. (The groups include accredited records technician, aide/orderly, dental assistant, dental hygienist, dental lab technician, dietetic technician, licensed practical nurse, medical…

  16. Measures for the Final Common Core of Constructs. The Project on State-Level Child Outcomes.

    ERIC Educational Resources Information Center

    Child Trends, Inc., Washington, DC.

    The Project on State-Level Child Outcomes, a federal project designed to improve the measurement of child outcomes in state welfare evaluations and in other state data systems. This document provides measures for the common core of constructs that state representatives developed at the second national-level meeting of the Project's planning phase.…

  17. Determination of a Common Core of Basic Skills for Agribusiness and Natural Resources. Final Report.

    ERIC Educational Resources Information Center

    McCracken, J. David; Yoder, Edgar P.

    The purpose of the project was to identify a common core of basic skills for agribusiness and natural resources instruction in vocational education. This objective was undertaken through an inventory of 28 tasks and 28 occupational surveys. Completed task inventories were made for 28 representative occupations in agribusiness and natural…

  18. Survey of Materials Development Needs in the Less Commonly Taught Languages. Final Report.

    ERIC Educational Resources Information Center

    Stansfield, Charles W.; Galloway, Ann

    A project surveyed the instructional materials development needs of the less commonly taught languages (LCTLs) language teaching community. The national survey in 1992 covered 82 languages and surveyed approximately 1,000 language course instructors and program directors at national resource centers and universities in the United States receiving…

  19. Lysine acetylation is a common post-translational modification of key metabolic pathway enzymes of the anaerobe Porphyromonas gingivalis.

    PubMed

    Butler, Catherine A; Veith, Paul D; Nieto, Matthew F; Dashper, Stuart G; Reynolds, Eric C

    2015-10-14

    Porphyromonas gingivalis is a Gram-negative anaerobe considered to be a keystone pathogen in the development of the bacterial-associated inflammatory oral disease chronic periodontitis. Although post-translational modifications (PTMs) of proteins are commonly found to modify protein function in eukaryotes and prokaryotes, PTMs such as lysine acetylation have not been examined in P. gingivalis. Lysine acetylation is the addition of an acetyl group to a lysine which removes this amino acid's positive charge and can induce changes in a protein's secondary structure and reactivity. A proteomics based approach combining immune-affinity enrichment with high sensitivity Orbitrap mass spectrometry identified 130 lysine acetylated peptides from 92 P. gingivalis proteins. The majority of these peptides (71) were attributed to 45 proteins with predicted metabolic activity; these proteins could be mapped to several P. gingivalis metabolic pathways where enzymes catalysing sequential reactions within the same pathway were often found acetylated. In particular, the catabolic pathways of complex anaerobic fermentation of amino acids to produce energy had 12 enzymes lysine acetylated. The results suggest that lysine acetylation may be an important mechanism in metabolic regulation in P. gingivalis, which is vital for P. gingivalis survival and adaptation of its metabolism throughout infection. Statement of significance. Porphyromonas gingivalis is a keystone pathogen in the development of chronic periodontitis, an inflammatory disease of the supporting tissues of the teeth. The ability of the pathogen to induce dysbiosis and disease is related to an array of specific virulence factors and metabolic regulation that enables the bacterium to proliferate in an inflamed periodontal pocket. The mechanisms P. gingivalis uses to adapt to a changing and hostile environment are poorly understood and here we show, for the first time, that enzymes of critical metabolic pathways for energy

  20. Passive solar renovations to the Common Ground Community Restaurant. Final report

    SciTech Connect

    Not Available

    1985-01-01

    The passive solar and energy conserving renovations to the Common Ground Community Restaurant were funded primarily as a demonstration project under this program. The majority of work accomplished was (1) design and construction of a passive solar greenhouse on the existing second floor porch of the restaurant, and (2) the design and construction of energy conserving improvements to the interior of the building, consisting largely of renovating the walls and ceiling to provide an insulated space with a substantially reduced heat load.

  1. Common BRAF(V600E)-directed pathway mediates widespread epigenetic silencing in colorectal cancer and melanoma

    PubMed Central

    Fang, Minggang; Hutchinson, Lloyd; Deng, April

    2016-01-01

    During cancer development, it is well established that many genes, including tumor suppressor genes, are hypermethylated and transcriptionally repressed, a phenomenon referred to as epigenetic silencing. In general, the factors involved in, and the mechanistic basis of, epigenetic silencing during cancer development are not well understood. We have recently described an epigenetic silencing pathway, directed by the oncogenic B-Raf proto-oncogene (BRAF) variant BRAF(V600E), that mediates widespread epigenetic silencing in colorectal cancer (CRC). Notably, the BRAF(V600E) mutation is also present in 50–70% of melanomas. Here, we show that the same pathway we identified in CRC also directs epigenetic silencing of a similar set of genes in BRAF-positive melanoma. In both CRC and melanoma, BRAF(V600E) promotes epigenetic silencing through up-regulation of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G (MAFG), a transcriptional repressor with sequence-specific DNA-binding activity. The elevated concentration of MAFG drives DNA binding on the promoter. Promoter-bound MAFG recruits a set of corepressors that includes its heterodimeric partner BTB and CNC homology 1, basic leucine zipper transcription factor 1 (BACH1), the chromatin remodeling factor chromodomain helicase DNA-binding protein 8 (CHD8), and the DNA methyltransferase DNMT3B, resulting in hypermethylation and transcriptional silencing. Our results reveal a common BRAF(V600E)-directed transcriptional regulatory pathway that mediates epigenetic silencing in unrelated solid tumors and provide strong support for an instructive model of oncoprotein-directed epigenetic silencing. PMID:26787892

  2. Autophagy Competes for a Common Phosphatidylethanolamine Pool with Major Cellular PE-Consuming Pathways in Saccharomyces cerevisiae

    PubMed Central

    Wilson-Zbinden, Caroline; dos Santos, Aline Xavier da Silveira; Stoffel-Studer, Ingrid; van der Vaart, Aniek; Hofmann, Kay; Reggiori, Fulvio; Riezman, Howard; Kraft, Claudine; Peter, Matthias

    2015-01-01

    Autophagy is a highly regulated pathway that selectively degrades cellular constituents such as protein aggregates and excessive or damaged organelles. This transport route is characterized by engulfment of the targeted cargo by autophagosomes. The formation of these double-membrane vesicles requires the covalent conjugation of the ubiquitin-like protein Atg8 to phosphatidylethanolamine (PE). However, the origin of PE and the regulation of lipid flux required for autophagy remain poorly understood. Using a genetic screen, we found that the temperature-sensitive growth and intracellular membrane organization defects of mcd4-174 and mcd4-P301L mutants are suppressed by deletion of essential autophagy genes such as ATG1 or ATG7. MCD4 encodes an ethanolamine phosphate transferase that uses PE as a precursor for an essential step in the synthesis of the glycosylphosphatidylinositol (GPI) anchor used to link a subset of plasma membrane proteins to lipid bilayers. Similar to the deletion of CHO2, a gene encoding the enzyme converting PE to phosphatidylcholine (PC), deletion of ATG7 was able to restore lipidation and plasma membrane localization of the GPI-anchored protein Gas1 and normal organization of intracellular membranes. Conversely, overexpression of Cho2 was lethal in mcd4-174 cells grown at restrictive temperature. Quantitative lipid analysis revealed that PE levels are substantially reduced in the mcd4-174 mutant but can be restored by deletion of ATG7 or CHO2. Taken together, these data suggest that autophagy competes for a common PE pool with major cellular PE-consuming pathways such as the GPI anchor and PC synthesis, highlighting the possible interplay between these pathways and the existence of signals that may coordinate PE flux. PMID:25519895

  3. Germline Mutations in NFKB2 Implicate the Noncanonical NF-κB Pathway in the Pathogenesis of Common Variable Immunodeficiency

    PubMed Central

    Chen, Karin; Coonrod, Emily M.; Kumánovics, Attila; Franks, Zechariah F.; Durtschi, Jacob D.; Margraf, Rebecca L.; Wu, Wilfred; Heikal, Nahla M.; Augustine, Nancy H.; Ridge, Perry G.; Hill, Harry R.; Jorde, Lynn B.; Weyrich, Andrew S.; Zimmerman, Guy A.; Gundlapalli, Adi V.; Bohnsack, John F.; Voelkerding, Karl V.

    2013-01-01

    Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by antibody deficiency, poor humoral response to antigens, and recurrent infections. To investigate the molecular cause of CVID, we carried out exome sequence analysis of a family diagnosed with CVID and identified a heterozygous frameshift mutation, c.2564delA (p.Lys855Serfs∗7), in NFKB2 affecting the C terminus of NF-κB2 (also known as p100/p52 or p100/p49). Subsequent screening of NFKB2 in 33 unrelated CVID-affected individuals uncovered a second heterozygous nonsense mutation, c.2557C>T (p.Arg853∗), in one simplex case. Affected individuals in both families presented with an unusual combination of childhood-onset hypogammaglobulinemia with recurrent infections, autoimmune features, and adrenal insufficiency. NF-κB2 is the principal protein involved in the noncanonical NF-κB pathway, is evolutionarily conserved, and functions in peripheral lymphoid organ development, B cell development, and antibody production. In addition, Nfkb2 mouse models demonstrate a CVID-like phenotype with hypogammaglobulinemia and poor humoral response to antigens. Immunoblot analysis and immunofluorescence microscopy of transformed B cells from affected individuals show that the NFKB2 mutations affect phosphorylation and proteasomal processing of p100 and, ultimately, p52 nuclear translocation. These findings describe germline mutations in NFKB2 and establish the noncanonical NF-κB signaling pathway as a genetic etiology for this primary immunodeficiency syndrome. PMID:24140114

  4. Final Priority and Definitions; Demonstration and Training Program: Career Pathways for Individuals With Disabilities. Final priority and definitions.

    PubMed

    2015-08-01

    The Assistant Secretary for Special Education and Rehabilitative Services announces a priority designed to demonstrate promising practices in the use of career pathways to improve employment outcomes for individuals with disabilities. Specifically, this priority will establish model demonstration projects that engage State vocational rehabilitation (VR) agencies in partnerships with other entities to develop and use career pathways to help individuals with disabilities eligible for VR services, including youth with disabilities, acquire necessary marketable skills and recognized postsecondary credentials. The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2015 and later years.

  5. A common evolutionary origin for the ON- and OFF-edge motion detection pathways of the Drosophila visual system

    PubMed Central

    Shinomiya, Kazunori; Takemura, Shin-ya; Rivlin, Patricia K.; Plaza, Stephen M.; Scheffer, Louis K.; Meinertzhagen, Ian A.

    2015-01-01

    Synaptic circuits for identified behaviors in the Drosophila brain have typically been considered from either a developmental or functional perspective without reference to how the circuits might have been inherited from ancestral forms. For example, two candidate pathways for ON- and OFF-edge motion detection in the visual system act via circuits that use respectively either T4 or T5, two cell types of the fourth neuropil, or lobula plate (LOP), that exhibit narrow-field direction-selective responses and provide input to wide-field tangential neurons. T4 or T5 both have four subtypes that terminate one each in the four strata of the LOP. Representatives are reported in a wide range of Diptera, and both cell types exhibit various similarities in: (1) the morphology of their dendritic arbors; (2) their four morphological and functional subtypes; (3) their cholinergic profile in Drosophila; (4) their input from the pathways of L3 cells in the first neuropil, or lamina (LA), and by one of a pair of LA cells, L1 (to the T4 pathway) and L2 (to the T5 pathway); and (5) their innervation by a single, wide-field contralateral tangential neuron from the central brain. Progenitors of both also express the gene atonal early in their proliferation from the inner anlage of the developing optic lobe, being alone among many other cell type progeny to do so. Yet T4 receives input in the second neuropil, or medulla (ME), and T5 in the third neuropil or lobula (LO). Here we suggest that these two cell types were originally one, that their ancestral cell population duplicated and split to innervate separate ME and LO neuropils, and that a fiber crossing—the internal chiasma—arose between the two neuropils. The split most plausibly occurred, we suggest, with the formation of the LO as a new neuropil that formed when it separated from its ancestral neuropil to leave the ME, suggesting additionally that ME input neurons to T4 and T5 may also have had a common origin. PMID:26217193

  6. The School-Community Integrated Learning Pathway: Exploring a New Way to Prepare and Induct Final-Year Preservice Teachers

    ERIC Educational Resources Information Center

    Hudson, Suzanne; Hudson, Peter; Adie, Lenore

    2015-01-01

    Universities and teacher employment bodies seek new, cost-effective ways for graduating classroom-ready teachers. This study involved 32 final-year preservice teachers in an innovative school--university partnership teacher education programme titled, the School-Community Integrated Learning (SCIL) pathway. Data were collected using a five-part…

  7. Melatonin Regulates Somatotrope and Lactotrope Function Through Common and Distinct Signaling Pathways in Cultured Primary Pituitary Cells From Female Primates

    PubMed Central

    Ibáñez-Costa, Alejandro; Córdoba-Chacón, José; Gahete, Manuel D.; Kineman, Rhonda D.; Castaño, Justo P.

    2015-01-01

    Melatonin (MT) is secreted by the pineal gland and exhibits a striking circadian rhythm in its release. Depending on the species studied, some pituitary hormones also display marked circadian/seasonal patterns and rhythms of secretion. However, the precise relationship between MT and pituitary function remains controversial, and studies focusing on the direct role of MT in normal pituitary cells are limited to nonprimate species. Here, adult normal primate (baboons) primary pituitary cell cultures were used to determine the direct impact of MT on the functioning of all pituitary cell types from the pars distalis. MT increased GH and prolactin (PRL) expression/release in a dose- and time-dependent fashion, a response that was blocked by somatostatin. However, MT did not significantly affect ACTH, FSH, LH, or TSH expression/release. MT did not alter GHRH- or ghrelin-induced GH and/or PRL secretions, suggesting that MT may activate similar signaling pathways as ghrelin/GHRH. The effects of MT on GH/PRL release, which are likely mediated through MT1 receptor, involve both common (adenylyl cyclase/protein kinase A/extracellular calcium-channels) and distinct (phospholipase C/intracellular calcium-channels) signaling pathways. Actions of MT on pituitary cells also included regulation of the expression of other key components for the control of somatotrope/lactotrope function (GHRH, ghrelin, and somatostatin receptors). These results show, for the first time in a primate model, that MT directly regulates somatotrope/lactotrope function, thereby lending support to the notion that the actions of MT on these cells might substantially contribute to the define daily patterns of GH and PRL observed in primates and perhaps in humans. PMID:25545385

  8. Amphetamine and morphine may produce acute-withdrawal related hypoactivity by initially activating a common dopamine pathway.

    PubMed

    White, Wesley; White, Ilsun M

    2016-10-15

    Rats given drugs of abuse such as amphetamine or morphine show longer-term effects, that is, signs of acute withdrawal, including hypoactivity, hypophagia, and blunted affect, sometime between 12 and 24h after treatment. This research explores the possibility that signs of acute withdrawal produced by different drugs of abuse are instigated by overlapping mechanisms. The specific objectives of the research were to see if amphetamine and morphine produced longer-term hypoactivity, and to see if any longer-term hypoactivity elicited by the drugs could be blocked by SCH23390, a dopamine D1 antagonist. Six groups of rats, with eight rats in each group, were exposed to a series of five-day tests. Near light onset of Test Day 1, each animal was given control administrations, consisting of a saline treatment (1.0ml/kg) followed 30m later by a saline posttreatment, and locomotor activity was monitored for the next 24h. On Test Day 3, each animal was given experimental administrations, and locomotor activity was again monitored for 24h. Each group received only one combination of experimental administrations across tests. Experimental administrations consisted of saline, amphetamine (2.0mg/kg), or morphine (5.0mg/kg), followed by saline or SCH23390 (0.05mg/kg). All administrations were subcutaneous. Amphetamine and morphine produced longer-term hypoactivity, having similar time courses and magnitudes. SCH23390 blocked the longer-term hypoactivity produced by both drugs. Saline and SCH23390 produced no changes in longer-term activity in their own right. The time course of amphetamine-elicited longer-term hypoactivity resembled that of amphetamine-elicited longer-term hypophagia observed in a prior study. Approximately 1/4 of the animals given amphetamine or morphine did not show longer-term hypoactivity ("low withdrawal" rats). Amphetamine and morphine may initiate the cascade of events resulting in signs of acute withdrawal by producing activation in a common pathway that

  9. Pathways commonly dysregulated in mouse and human obese adipose tissue: FAT/CD36 modulates differentiation and lipogenesis

    PubMed Central

    Berger, E; Héraud, S; Mojallal, A; Lequeux, C; Weiss-Gayet, M; Damour, O; Géloën, A

    2015-01-01

    Obesity is linked to adipose tissue hypertrophy (increased adipocyte cell size) and hyperplasia (increased cell number). Comparative analyses of gene datasets allowed us to identify 1426 genes which may represent common adipose phenotype in humans and mice. Among them we identified several adipocyte-specific genes dysregulated in obese adipose tissue, involved in either fatty acid storage (acyl CoA synthase ACSL1, hormone-sensitive lipase LIPE, aquaporin 7 AQP7, perilipin PLIN) or cell adhesion (fibronectin FN1, collagens COL1A1, COL1A3, metalloprotein MMP9, or both (scavenger receptor FAT/CD36). Using real-time analysis of cell surface occupancy on xCELLigence system we developed a new method to study lipid uptake and differentiation of mouse 3T3L1 fibroblasts and human adipose stem cells. Both processes are regulated by insulin and fatty acids such as oleic acid. We showed that fatty acid addition to culture media increased the differentiation rate and was required for full differentiation into unilocular adipocytes. Significant activation of lipogenesis, i.e. lipid accumulation, by either insulin or oleic acid was monitored in times ranging from 1 to 24 h, depending on differentiation state, whereas significant effects on adipogenesis, i.e., surperimposed lipid accumulation and gene transcriptional regulations were measured after 3 to 4 d. Combination of selected times for analysis of lipid contents, cell counts, size fractionations, and gene transcriptional regulations showed that FAT/CD36 specific inhibitor AP5258 significantly increased cell survival of oleic acid-treated mouse and human adipocytes, and partially restored the transcriptional response to oleic acid in the presence of insulin through JNK pathway. Taken together, these data open new perspectives to study the molecular mechanisms commonly dysregulated in mouse and human obesity at the level of lipogenesis linked to hypertrophy and adipogenesis linked to hyperplasia. PMID:26257990

  10. Overview of Space Radiation Health Risks (Cancer, Cognition, Cardiovascular) and Potential Common Pathways Such as Senescence and Inflammation

    NASA Technical Reports Server (NTRS)

    Patel, Zarana S.; Huff, Janice L.; Simonsen, Lisa C.

    2016-01-01

    The radiation environment in space poses significant challenges to human health and is a major concern for long duration, manned space missions. Outside the Earth's protective magnetosphere, astronauts are exposed to higher levels of galactic cosmic rays, whose physical characteristics are distinct from terrestrial sources of radiation such as x-rays and gamma-rays. Galactic cosmic rays consist of high energy, high charge (HZE) particles as well as high energy protons; they impart unique biological damage as they traverse through tissue with impacts on human health that are largely unknown. Understanding the quantitative and qualitative differences in biological responses produced by galactic cosmic radiation compared to Earth-based radiation is a major focus of space radiation research and is imperative for accurate risk assessment for long duration space missions. The major health issues of concern are epithelial carcinogenesis, central nervous system effects that may result in acute (inflight) cognitive impairment and late neurological disorders, degenerative tissue effects including cardiovascular, digestive and respiratory risks as well as possible acute radiation syndromes in the event of an unshielded exposure to a large solar particle event. In this presentation, we review evidence for health risks associated with heavy ion exposure and research strategies to enable manned space flight outside low Earth orbit. We are currently focused on common risk pathways that can be targeted for mitigation via countermeasures, and senescence and inflammation are prime areas for investigation.

  11. A Common Biosynthetic Pathway Governs the Dimerization and Secretion of Inhibin and Related Transforming Growth Factor β (TGFβ) Ligands*

    PubMed Central

    Walton, Kelly L.; Makanji, Yogeshwar; Wilce, Matthew C.; Chan, Karen L.; Robertson, David M.; Harrison, Craig A.

    2009-01-01

    The assembly and secretion of transforming growth factor β superfamily ligands is dependent upon non-covalent interactions between their pro- and mature domains. Despite the importance of this interaction, little is known regarding the underlying regulatory mechanisms. In this study, the binding interface between the pro- and mature domains of the inhibin α-subunit was characterized using in vitro mutagenesis. Three hydrophobic residues near the N terminus of the prodomain (Leu30, Phe37, Leu41) were identified that, when mutated to alanine, disrupted heterodimer assembly and secretion. It is postulated that these residues mediate dimerization by interacting non-covalently with hydrophobic residues (Phe271, Ile280, Pro283, Leu338, and Val340) on the outer convex surface of the mature α-subunit. Homology modeling indicated that these mature residues are located at the interface between two β-sheets of the α-subunit and that their side chains form a hydrophobic packing core. Mutation of these residues likely disturbs the conformation of this region, thereby disrupting non-covalent interactions with the prodomain. A similar hydrophobic interface was identified spanning the pro- and mature domains of the inhibin βA-subunit. Mutation of key residues, including Ile62, Leu66, Phe329, and Pro341, across this interface was disruptive for the production of both inhibin A and activin A. In addition, mutation of Ile62 and Leu66 in the βA-propeptide reduced its ability to bind, or inhibit the activity of, activin A. Conservation of the identified hydrophobic motifs in the pro- and mature domains of other transforming growth factor β superfamily ligands suggests that we have identified a common biosynthetic pathway governing dimer assembly. PMID:19193648

  12. Cdk12 and Cdk13 regulate axonal elongation through a common signaling pathway that modulates Cdk5 expression.

    PubMed

    Chen, Hong-Ru; Lin, Guan-Ting; Huang, Chun-Kai; Fann, Ming-Ji

    2014-11-01

    Cdk12 and Cdk13 are Cdc2-related proteins that share 92% identity in their kinase domains. Using in situ hybridization and Western blot analysis, we detected the expression of Cdk12 and Cdk13 mRNAs and their proteins in developing mouse embryos, especially during development of the nervous system. We explored the roles of Cdk12 and Cdk13 in neuronal differentiation using the P19 neuronal differentiation model. Upon knockdown of Cdk12 or Cdk13, no effect on differentiated cell numbers was detected, but a substantial decrease of numbers of neurons with long neurites was identified. Similarly, knockdown of Cdk12 or Cdk13 in primarily cultured cortical neurons shortens the averaged axonal length. A microarray analysis was used to examine changes in gene expression after knockdown or overexpression of Cdk12 and we identified Cdk5 as a molecule potentially involved in mediating the effect of Cdk12 and Cdk13. Depletion of Cdk12 or Cdk13 in P19 cells significantly reduces Cdk5 expression at both the mRNA and protein levels. Expression of Cdk5 protein in the developing mouse brain is also reduced in conditional Cdk12-knockout mice in proportion to the residual amount of Cdk12 protein present. This suggests that the reduced axonal outgrowth after knockdown of Cdk12 or Cdk13 might be due to lower Cdk5 expression. Furthermore, overexpression of Cdk5 protein in P19 cells was able to partially rescue the neurite outgrowth defect observed when Cdk12 or Cdk13 is depleted. Together, these findings suggest that Cdk12 and Cdk13 regulate axonal elongation through a common signaling pathway that modulates Cdk5 expression. PMID:24999027

  13. Decreasing Electron Flux through the Cytochrome and/or Alternative Respiratory Pathways Triggers Common and Distinct Cellular Responses Dependent on Growth Conditions1[OPEN

    PubMed Central

    Kühn, Kristina; Yin, Guangkun; Duncan, Owen; Law, Simon R.; Kubiszewski-Jakubiak, Szymon; Kaur, Parwinder; Meyer, Etienne; Wang, Yan; Small, Catherine Colas des Francs; Giraud, Estelle; Narsai, Reena; Whelan, James

    2015-01-01

    Diverse signaling pathways are activated by perturbation of mitochondrial function under different growth conditions.Mitochondria have emerged as an important organelle for sensing and coping with stress in addition to being the sites of important metabolic pathways. Here, responses to moderate light and drought stress were examined in different Arabidopsis (Arabidopsis thaliana) mutant plants lacking a functional alternative oxidase (alternative oxidase1a [aox1a]), those with reduced cytochrome electron transport chain capacity (T3/T7 bacteriophage-type RNA polymerase, mitochondrial, and plastidial [rpoTmp]), and double mutants impaired in both pathways (aox1a:rpoTmp). Under conditions considered optimal for growth, transcriptomes of aox1a and rpoTmp were distinct. Under adverse growth conditions, however, transcriptome changes in aox1a and rpoTmp displayed a highly significant overlap and were indicative of a common mitochondrial stress response and down-regulation of photosynthesis. This suggests that the role of mitochondria to support photosynthesis is provided through either the alternative pathway or the cytochrome pathway, and when either pathway is inhibited, such as under environmental stress, a common, dramatic, and succinct mitochondrial signal is activated to alter energy metabolism in both organelles. aox1a:rpoTmp double mutants grown under optimal conditions showed dramatic reductions in biomass production compared with aox1a and rpoTmp and a transcriptome that was distinct from aox1a or rpoTmp. Transcript data indicating activation of mitochondrial biogenesis in aox1a:rpoTmp were supported by a proteomic analysis of over 200 proteins. Under optimal conditions, aox1a:rpoTmp plants seemed to switch on many of the typical mitochondrial stress regulators. Under adverse conditions, aox1a:rpoTmp turned off these responses and displayed a biotic stress response. Taken together, these results highlight the diverse signaling pathways activated by the

  14. Single-Cell Analysis Reveals that Insulation Maintains Signaling Specificity between Two Yeast MAPK Pathways with Common Components

    PubMed Central

    Patterson, Jesse C.; Klimenko, Evguenia S.; Thorner, Jeremy

    2014-01-01

    Eukaryotic cells use multiple mitogen-activated protein kinase (MAPK) cascades to evoke appropriate responses to external stimuli. In Saccharomyces cerevisiae, the MAPK Fus3 is activated by pheromone-binding G protein-coupled receptors to promote mating, whereas the MAPK Hog1 is activated by hyperosmotic stress to elicit the high osmolarity glycerol (HOG) response. Although these MAPK pathways share several upstream components, exposure to either pheromone or osmolyte alone triggers only the appropriate response. We used fluorescent localization- and transcription-specific reporters to assess activation of these pathways in individual cells on the minute and hour timescale, respectively. Dual activation of these two MAPK pathways occurred over a broad range of stimulant concentrations and temporal regimes in wild-type cells subjected to co-stimulation. Thus, signaling specificity is achieved through an “insulation” mechanism, not a “cross-inhibition” mechanism. Furthermore, we showed that there was a critical period during which Hog1 activity had to occur for proper insulation of the HOG pathway. PMID:20959523

  15. Final Technical Report: Genetic and Molecular Analysis of a new control pathway in assimilate partitioning.

    SciTech Connect

    Bush, Daniel, R.

    2009-03-10

    Assimilate partitioning refers to the systemic distribution of photoassimilate from sites of primary assimilation (source tissue) to import-dependent tissues and organs (sinks). One of the defining questions in this area is how plants balance source productivity with sink demand. We discovered a sucrose-sensing signal transduction pathway that controls the activity of BvSUT1, a proton-sucrose symporter in sugar beet leaf tissue. Sucrose symporters are responsible for sucrose accumulation in the phloem of many plants and, therefore, they mediate the pivotal step in the long-distance transport of photoassimilate to non-photosynthetic tissues, such as roots and seed. We previously showed that sucrose transport activity is directly proportional to the transcription rate of BvSUT1 and that symporter mRNA and protein have high rates of turnover with half-lives on the order of 2 h. We further demonstrated that symporter transcription is regulated by sucrose levels in the leaf and that sucrose-dependent regulation of BvSUT1 transcription is mediated, at least in part, by a protein phosphorylation relay pathway. The goal of the experiments during this current grant were to use genetic and molecular approaches to identify essential components of this vital regulatory system. The initial objectives were to: (1) to characterize Arabidopsis mutants we've isolated that are resistant to growth inhibition by sucrose analogues that are recognized by the sucrose-sensor, (2) to screen for loss of function mutants in BvSUT1-promoter:luciferase transgenic plants that no longer respond to sucrose accumulation in the leaf using non-destructive visualization of luciferase activity, (3) to use gel mobility-shift assays and nuclease protection experiments to identify cis elements in the symporter promoter and DNA-binding proteins that are involved in sucrose regulation of symporter expression.

  16. A Set of Activators and Repressors Control Peripheral Glucose Pathways in Pseudomonas putida To Yield a Common Central Intermediate▿

    PubMed Central

    del Castillo, Teresa; Duque, Estrella; Ramos, Juan L.

    2008-01-01

    Pseudomonas putida KT2440 channels glucose to the central Entner-Doudoroff intermediate 6-phosphogluconate through three convergent pathways. The genes for these convergent pathways are clustered in three independent regions on the host chromosome. A number of monocistronic units and operons coexist within each of these clusters, favoring coexpression of catabolic enzymes and transport systems. Expression of the three pathways is mediated by three transcriptional repressors, HexR, GnuR, and PtxS, and by a positive transcriptional regulator, GltR-2. In this study, we generated mutants in each of the regulators and carried out transcriptional assays using microarrays and transcriptional fusions. These studies revealed that HexR controls the genes that encode glucokinase/glucose 6-phosphate dehydrogenase that yield 6-phosphogluconate; the genes for the Entner-Doudoroff enzymes that yield glyceraldehyde-3-phosphate and pyruvate; and gap-1, which encodes glyceraldehyde-3-phosphate dehydrogenase. GltR-2 is the transcriptional regulator that controls specific porins for the entry of glucose into the periplasmic space, as well as the gtsABCD operon for glucose transport through the inner membrane. GnuR is the repressor of gluconate transport and gluconokinase responsible for the conversion of gluconate into 6-phosphogluconate. PtxS, however, controls the enzymes for oxidation of gluconate to 2-ketogluconate, its transport and metabolism, and a set of genes unrelated to glucose metabolism. PMID:18245293

  17. The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate autophagy via a common pathway

    PubMed Central

    Bento, Carla F.; Ashkenazi, Avraham; Jimenez-Sanchez, Maria; Rubinsztein, David C.

    2016-01-01

    Forms of Parkinson's disease (PD) are associated with lysosomal and autophagic dysfunction. ATP13A2, which is mutated in some types of early-onset Parkinsonism, has been suggested as a regulator of the autophagy–lysosome pathway. However, little is known about the ATP13A2 effectors and how they regulate this pathway. Here we show that ATP13A2 depletion negatively regulates another PD-associated gene (SYT11) at both transcriptional and post-translational levels. Decreased SYT11 transcription is controlled by a mechanism dependent on MYCBP2-induced ubiquitination of TSC2, which leads to mTORC1 activation and decreased TFEB-mediated transcription of SYT11, while increased protein turnover is regulated by SYT11 ubiquitination and degradation. Both mechanisms account for a decrease in the levels of SYT11, which, in turn, induces lysosomal dysfunction and impaired degradation of autophagosomes. Thus, we propose that ATP13A2 and SYT11 form a new functional network in the regulation of the autophagy–lysosome pathway, which is likely to contribute to forms of PD-associated neurodegeneration. PMID:27278822

  18. Pathway analysis of senescence-associated miRNA targets reveals common processes to different senescence induction mechanisms.

    PubMed

    Lafferty-Whyte, Kyle; Cairney, Claire J; Jamieson, Nigel B; Oien, Karin A; Keith, W Nicol

    2009-04-01

    Multiple mechanisms of senescence induction exist including telomere attrition, oxidative stress, oncogene expression and DNA damage signalling. The regulation of the cellular changes required to respond to these stimuli and create the complex senescent cell phenotype has many different mechanisms. MiRNAs present one mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated. In this study we investigated 12 miRNAs previously identified as senescence regulators. Using pathway analysis of their target genes we tested the relevance of miRNA regulation in the induction of senescence. Our analysis highlighted the potential of these senescence-associated miRNAs (SA-miRNAs) to regulate the cell cycle, cytoskeletal remodelling and proliferation signalling logically required to create a senescent cell. The reanalysis of publicly available gene expression data from studies exploring different senescence stimuli also revealed their potential to regulate core senescence processes, regardless of stimuli. We also identified stimulus specific apoptosis survival pathways theoretically regulated by the SA-miRNAs. Furthermore the observation that miR-499 and miR-34c had the potential to regulate all 4 of the senescence induction types we studied highlights their future potential as novel drug targets for senescence induction. PMID:19419692

  19. Molecular genetics of human growth hormone, insulin-like growth factors and their pathways in common disease.

    PubMed

    Rodriguez, Santiago; Gaunt, Tom R; Day, Ian N M

    2007-08-01

    The human growth hormone gene (GH1) and the insulin-like growth factor 1 and 2 genes (IGF1 and IGF2) encode the central elements of a key pathway influencing growth in humans. This "growth pathway" also includes transcription factors, agonists, antagonists, receptors, binding proteins, and endocrine factors that constitute an intrincate network of feedback loops. GH1 is evolutionarily coupled with other genes in linkage disequilibrium in 17q24.2, and the same applies to IGF2 in 11p15.5. In contrast, IGF1 in 12q22-24.1 is not in strong linkage disequilibrium with neighbouring genes. Knowledge of the functional architecture of these regions is important for the understanding of the combined evolution and function of GH1, IGF2 and IGF1 in relation to complex diseases. A number of mutations accounting for rare Mendelian disorders have been described in GH-IGF elements. The constellation of genes in this key pathway contains potential candidates in a number of complex diseases, including growth disorders, metabolic syndrome, diabetes (notably IGF2BP2) cardiovascular disease, and central nervous system diseases, and in longevity, aging and cancer. We review these genes and their associations with disease phenotypes, with special attention to metabolic risk traits. PMID:17534663

  20. FY08 LDRD Final Report Probabilistic Inference of Metabolic Pathways from Metagenomic Sequence Data

    SciTech Connect

    D'haeseleer, P

    2009-03-01

    Metagenomic 'shotgun' sequencing of environmental microbial communities has the potential to revolutionize microbial ecology, allowing a cultivation-independent, yet sequence-based analysis of the metabolic capabilities and functions present in an environmental sample. Although its intensive sequencing requirements are a good match for the continuously increasing bandwidth at sequencing centers, the complexity, seemingly inexhaustible novelty, and 'scrambled' nature of metagenomic data is also proving a tremendous challenge for analysis. In fact, many metagenomics projects do not go much further than providing a list of novel gene variants and over- or under-represented functional gene categories. In this project, we proposed to develop a set of novel metagenomic sequence analysis tools, including a binning method to group sequences by species, inference of phenotypes and metabolic pathways from these reconstructed species, and extraction of coarse-grained flux models. We proposed to closely collaborate with the DOE Joint Genome Institute to align these tools with their metagenomics analysis needs and the developing IMG/M metagenomics pipeline. Results would be cross-validated with simulated metagenomic data using a testing platform developed at the JGI.

  1. Final report - Microbial pathways for the reduction of mercury in saturated subsurface sediments

    SciTech Connect

    Tamar barkay; Lily Young; Gerben Zylstra

    2009-08-25

    Mercury is a component of mixed wastes that have contaminated vast areas of the deep subsurface as a result of nuclear weapon and energy production. While this mercury is mostly bound to soil constituents episodes of groundwater contamination are known in some cases resulting in potable water super saturated with Hg(0). Microbial processes that reduce Hg(II) to the elemental form Hg(0) in the saturated subsurface sediments may contribute to this problem. When we started the project, only one microbial pathway for the reduction of Hg(II), the one mediated by the mer operon in mercury resistant bacteria was known. As we had previously demonstrated that the mer mediated process occurred in highly contaminated environments (Schaefer et al., 2004), and mercury concentrations in the subsurface were reported to be low (Krabbenhoft and Babiarz, 1992), we hypothesized that other microbial processes might be active in reducing Hg(II) to Hg(0) in saturated subsurface environments. The specific goals of our projects were: (1) Investigating the potential for Hg(II) reduction under varying electron accepting conditions in subsurface sediments and relating these potential to mer gene distribution; and (2) Examining the physiological and biochemical characteristics of the interactions of anaerobic bacteria with mercury. The results are briefly summarized with references to published papers and manuscripts in preparation where details about our research can be found. Additional information may be found in copies of our published manuscripts and conference proceedings, and our yearly reports that were submitted through the RIMS system.

  2. Final Report: Investigation of Catalytic Pathways for Lignin Breakdown into Monomers and Fuels

    SciTech Connect

    Gluckstein, Jeffrey A; Hu, Michael Z.; Kidder, Michelle; McFarlane, Joanna; Narula, Chaitanya Kumar; Sturgeon, Matthew R

    2010-12-01

    Lignin is a biopolymer that comprises up to 35% of woody biomass by dry weight. It is currently underutilized compared to cellulose and hemicellulose, the other two primary components of woody biomass. Lignin has an irregular structure of methoxylated aromatic groups linked by a suite of ether and alkyl bonds which makes it difficult to degrade selectively. However, the aromatic components of lignin also make it promising as a base material for the production of aromatic fuel additives and cyclic chemical feed stocks such as styrene, benzene, and cyclohexanol. Our laboratory research focused on three methods to selectively cleave and deoxygenate purified lignin under mild conditions: acidolysis, hydrogenation and electrocatalysis. (1) Acidolysis was undertaken in CH2Cl2 at room temperature. (2) Hydrogenation was carried out by dissolving lignin and a rhodium catalyst in 1:1 water:methoxyethanol under a 1 atm H2 environment. (3) Electrocatalysis of lignin involved reacting electrically generated hydrogen atoms at a catalytic palladium cathode with lignin dissolved in a solution of aqueous methanol. In all of the experiments, the lignin degradation products were identified and quantified by gas chromatography mass spectroscopy and flame ionization detection. Yields were low, but this may have reflected the difficulty in recovering the various fractions after conversion. The homogeneous hydrogenation of lignin showed fragmentation into monomers, while the electrocatalytic hydrogenation showed production of polyaromatic hydrocarbons and substituted benzenes. In addition to the experiments, promising pathways for the conversion of lignin were assessed. Three conversion methods were compared based on their material and energy inputs and proposed improvements using better catalyst and process technology. A variety of areas were noted as needing further experimental and theoretical effort to increase the feasibility of lignin conversion to fuels.

  3. Metabolism of gambogic acid in rats: a rare intestinal metabolic pathway responsible for its final disposition.

    PubMed

    Yang, Jing; Ding, Li; Hu, Linlin; Qian, Wenjuan; Jin, Shaohong; Sun, Xiaoping; Wang, Zhenzhong; Xiao, Wei

    2011-04-01

    Gambogic acid (GA) is a promising natural anticancer candidate. Although the anticancer activity of GA has been well demonstrated, information regarding the metabolic fate of GA is limited. Previous studies suggested that GA is mainly excreted into intestinal tract in rats through bile after intravenous administration, whereas only traces appeared in the feces, suggesting that GA is metabolized extensively in the intestine. However, there has been no report about the intestinal metabolism of GA either in animals or humans. In this study, large amounts of two sulfonic acid metabolites of GA were found in the feces samples of rats after intravenous administration, and their structures were identified as 10-α sulfonic acid GA and 10-β sulfonic acid GA by comparison of the retention times and spectral data with those of synthesized reference substances using liquid chromatography-diode array detector-tandem mass spectrometry. This rare intestinal metabolic pathway mainly involves Michael addition of the sulfite ion to the 9,10 carbon-carbon double bond of α,β-unsaturated ketone. In addition, a more detailed metabolic profile in rats is proposed, according to the results of in vitro and in vivo studies. It was found that GA can be metabolized by a variety of routes, including monooxidation, hydration, glutathionylation, glucuronidation, and glucosidation in the liver of rats. These findings provide information on the major metabolic soft spot of GA in the intestine and liver of rats, which is not only useful in the future human metabolic study of this compound but also of value in the metabolic studies of GA analogs.

  4. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling.

    PubMed

    Martin, Aline; Liu, Shiguang; David, Valentin; Li, Hua; Karydis, Anastasios; Feng, Jian Q; Quarles, L Darryl

    2011-08-01

    Fibroblastic growth factor 23 (FGF23) is a circulating phosphaturic hormone. Inactivating mutations of the endopeptidase PHEX or the SIBLING protein DMP1 result in equivalent intrinsic bone mineralization defects and increased Fgf23 expression in osteocytes. The mechanisms whereby PHEX and DMP1 regulate Fgf23 expression are unknown. We examined the possibility that PHEX and DMP1 regulate Fgf23 through a common pathway by analyzing the phenotype of compound Phex and Dmp1 mutant mice (Hyp/Dmp1(-/-)). Compared to single-mutant littermates, compound-mutant Hyp/Dmp1(-/-) mice displayed nonadditive elevations of serum FGF23 (1912 ± 183, 1715 ± 178, and 1799 ± 181 pg/ml), hypophosphatemia (P(i): 6.0 ± 0.3, 5.8 ± 0.2, and 5.4 ± 0.1 mg/dl), and severity of rickets/osteomalacia (bone mineral density: -36, -36, and -30%). Microarray analysis of long bones identified gene expression profiles implicating common activation of the FGFR pathway in all the mutant groups. Furthermore, inhibiting FGFR signaling using SU5402 in Hyp- and Dmp1(-/-)-derived bone marrow stromal cells prevented the increase in Fgf23 mRNA expression (129- and 124-fold increase in Hyp and Dmp1(-/-) vs. 1.3-fold in Hyp+SU5402 and 2.5-fold in Dmp1(-/-)+SU5402, P<0.05). For all analyses, samples collected from nonmutant wild-type littermates served as controls. These findings indicate that PHEX and DMP1 control a common pathway regulating bone mineralization and FGF23 production, the latter involving activation of the FGFR signaling in osteocytes.

  5. 2014 Edition Electronic Health Record certification criteria: revision to the definition of "common Meaningful Use (MU) Data Set." Interim final rule with comment period.

    PubMed

    2013-11-01

    This interim final rule with comment period revises one paragraph in the Common Meaningful Use (MU) Data Set definition at 45 CFR 170.102 to allow more flexibility with respect to the representation of dental procedures data for electronic health record (EHR) technology testing and certification. PMID:24195145

  6. A common pathway for O-linked protein-glycosylation and synthesis of capsule in Acinetobacter baumannii.

    PubMed

    Lees-Miller, Robert G; Iwashkiw, Jeremy A; Scott, Nichollas E; Seper, Andrea; Vinogradov, Evgeny; Schild, Stefan; Feldman, Mario F

    2013-09-01

    Multi-drug resistant strains of Acinetobacter baumannii are increasingly being isolated in hospitals worldwide. Among the virulence factors identified in this bacterium there is a general O-glycosylation system that appears to be important for biofilm formation and virulence, and the capsular polysaccharide, which is essential for resistance to complement killing. In this work, we identified a locus that is responsible for the synthesis of the O-pentasaccharide found on the glycoproteins. Besides the enzymes required for the assembly of the glycan, additional proteins typically involved in polymerization and transport of capsule were identified within or adjacently to the locus. Mutagenesis of PglC, the initiating glycosyltransferase prevented the synthesis of both glycoproteins and capsule, resulting in abnormal biofilm structures and attenuated virulence in mice. These results, together with the structural analysis of A. baumannii 17978 capsular polysaccharide via NMR, demonstrated that the pentasaccharides that decorate the glycoproteins are also the building blocks for capsule biosynthesis. Two linked subunits, but not longer glycan chains, were detected on proteins via MS. The discovery of a bifurcated pathway for O-glycosylation and capsule synthesis not only provides insight into the biology of A. baumannii but also identifies potential novel candidates for intervention against this emerging pathogen.

  7. Common Genetic Pathways Regulate Organ-Specific Infection-Related Development in the Rice Blast Fungus[W

    PubMed Central

    Tucker, Sara L.; Besi, Maria I.; Galhano, Rita; Franceschetti, Marina; Goetz, Stephan; Lenhert, Steven; Osbourn, Anne; Sesma, Ane

    2010-01-01

    Magnaporthe oryzae is the most important fungal pathogen of rice (Oryza sativa). Under laboratory conditions, it is able to colonize both aerial and underground plant organs using different mechanisms. Here, we characterize an infection-related development in M. oryzae produced on hydrophilic polystyrene (PHIL-PS) and on roots. We show that fungal spores develop preinvasive hyphae (pre-IH) from hyphopodia (root penetration structures) or germ tubes and that pre-IH also enter root cells. Changes in fungal cell wall structure accompanying pre-IH are seen on both artificial and root surfaces. Using characterized mutants, we show that the PMK1 (for pathogenicity mitogen-activated protein kinase 1) pathway is required for pre-IH development. Twenty mutants with altered pre-IH differentiation on PHIL-PS identified from an insertional library of 2885 M. oryzae T-DNA transformants were found to be defective in pathogenicity. The phenotypic analysis of these mutants revealed that appressorium, hyphopodium, and pre-IH formation are genetically linked fungal developmental processes. We further characterized one of these mutants, M1373, which lacked the M. oryzae ortholog of exportin-5/Msn5p (EXP5). Mutants lacking EXP5 were much less virulent on roots, suggesting an important involvement of proteins and/or RNAs transported by EXP5 during M. oryzae root infection. PMID:20348434

  8. Common pathways toward informing policy and environmental strategies to promote health: a study of CDC's Prevention Research Centers.

    PubMed

    Neri, Elizabeth M; Stringer, Kate J; Spadaro, Antonia J; Ballman, Marie R; Grunbaum, Jo Anne

    2015-03-01

    This study examined the roles academic researchers can play to inform policy and environmental strategies that promote health and prevent disease. Prevention Research Centers (PRCs) engage in academic-community partnerships to conduct applied public health research. Interviews were used to collect data on the roles played by 32 PRCs to inform policy and environmental strategies that were implemented between September 2009 and September 2010. Descriptive statistics were calculated in SAS 9.2. A difference in roles played was observed depending on whether strategies were policy or environmental. Of the policy initiatives, the most common roles were education, research, and partnership. In contrast, the most prevalent roles the PRCs played in environmental approaches were research and providing health promotion resources. Academic research centers play various roles to help inform policy and environmental strategies.

  9. The heterogenic final cell cycle of chicken retinal Lim1 horizontal cells is not regulated by the DNA damage response pathway

    PubMed Central

    Shirazi Fard, Shahrzad; All-Ericsson, Charlotta; Hallböök, Finn

    2014-01-01

    Cells with aberrations in chromosomal ploidy are normally removed by apoptosis. However, aneuploid neurons have been shown to remain functional and active both in the cortex and in the retina. Lim1 horizontal progenitor cells in the chicken retina have a heterogenic final cell cycle, producing some cells that enter S-phase without proceeding into M-phase. The cells become heteroploid but do not undergo developmental cell death. This prompted us to investigate if the final cell cycle of these cells is under the regulation of an active DNA damage response. Our results show that the DNA damage response pathway, including γ-H2AX and Rad51 foci, is not triggered during any phase of the different final cell cycles of horizontal progenitor cells. However, chemically inducing DNA adducts or double-strand breaks in Lim1 horizontal progenitor cells activated the DNA damage response pathway, showing that the cells are capable of a functional response to DNA damage. Moreover, manipulation of the DNA damage response pathway during the final cell cycle using inhibitors of ATM/ATR, Chk1/2, and p38MAPK, neither induced apoptosis nor mitosis in the Lim1 horizontal progenitor cells. We conclude that the DNA damage response pathway is functional in the Lim1 horizontal progenitor cells, but that it is not directly involved in the regulation of the final cell cycle that gives rise to the heteroploid horizontal cell population. PMID:24247150

  10. Alternate pathways of body shape evolution translate into common patterns of locomotor evolution in two clades of lizards.

    PubMed

    Bergmann, Philip J; Irschick, Duncan J

    2010-06-01

    Body shape has a fundamental impact on organismal function, but it is unknown how functional morphology and locomotor performance and kinematics relate across a diverse array of body shapes. We showed that although patterns of body shape evolution differed considerably between lizards of the Phrynosomatinae and Lerista, patterns of locomotor evolution coincided between clades. Specifically, we found that the phrynosomatines evolved a stocky phenotype through body widening and limb shortening, whereas Lerista evolved elongation through body lengthening and limb shortening. In both clades, relative limb length played a key role in locomotor evolution and kinematic strategies, with long-limbed species moving faster and taking longer strides. In Lerista, the body axis also influenced locomotor evolution. Similar patterns of locomotor evolution were likely due to constraints on how the body can move. However, these common patterns of locomotor evolution between the two clades resulted in different kinematic strategies and levels of performance among species because of their morphological differences. Furthermore, we found no evidence that distinct body shapes are adaptations to different substrates, as locomotor kinematics did not change on loose or solid substrates. Our findings illustrate the importance of studying kinematics to understand the mechanisms of locomotor evolution and phenotype-function relationships.

  11. A pathway where polyprenyl diphosphate elongates in prenyltransferase. Insight into a common mechanism of chain length determination of prenyltransferases.

    PubMed

    Ohnuma, S; Hirooka, K; Tsuruoka, N; Yano, M; Ohto, C; Nakane, H; Nishino, T

    1998-10-01

    Prenyltransferases catalyze the consecutive condensations of isopentenyl diphosphate to produce linear polyprenyl diphosphates. Each enzyme forms the final product with a specific chain length. The product specificity of an enzyme is thought to be determined by the structure around the unknown path through which the product elongates in the enzyme. To explore the path, we introduced a few mutations at the 5th, the 8th, and/or the 11th positions before the first aspartate-rich motif of geranylgeranyl-diphosphate synthase or farnesyl-diphosphate synthase. The side chains of these amino acids are situated on the same side of an alpha-helix. In geranylgeranyl-diphosphate synthase, a single mutated enzyme (F77S) mainly produces a C25 product (Ohnuma, S.-I., Hirooka, K., Hemmi, H., Ishida, C., Ohto, C., and Nishino, T. (1996) J. Biol. Chem. 271, 18831-18837). A double mutated enzyme (L74G and F77G) mainly produces a C35 compound with significant amounts of C30 and C40. A triple mutated enzyme (I71G, L74G, and F77G) mainly produces a C40 compound with C35 and C45. Mutated farnesyl-diphosphate synthases also show similar patterns. These findings indicate that the elongating product passages on a surface of the side chains of the mutated amino acids, the original bulky amino acids had blocked the elongation, and the path is conserved in prenyltransferases. Moreover, the fact that some double and triple mutated enzymes can also form small amounts of products longer than C50 indicates that the paths in these mutated enzymes can partially access the outer surface of the enzymes.

  12. SMARTER Balanced Assessment Consortium Common Core State Standards Analysis: Eligible Content for the Summative Assessment. Final Report

    ERIC Educational Resources Information Center

    Sato, Edynn; Lagunoff, Rachel; Worth, Peter

    2011-01-01

    This report is a descriptive analysis of the Common Core State Standards (CCSS), intended to determine which content is eligible for the Smarter Balanced Assessment Consortium's end-of-year summative assessment for English language arts (ELA) and mathematics in grades 3-8 and high school. The high school standards analyzed were those in grades…

  13. Relevance of biotic pathways to the long-term regulation of nuclear waste disposal. Phase I. Final report. Vol. 4

    SciTech Connect

    McKenzie, D.H.; Cadwell, L.L.; Eberhardt, L.E.; Kennedy, W.E. Jr.; Peloquin, R.A.; Simmons, M.A.

    1984-05-01

    Licensing and regulation of commercial low-level waste (CLLW) burial facilities require that anticipated risks associated with burial sites be evaluated for the life of the facility. This work reviewed the existing capability to evaluate dose to man resulting from the potential redistribution of buried radionuclides by plants and animals that we have termed biotic transport. Through biotic transport, radionuclides can be moved to locations where they can enter exposure pathways to man. We found that predictive models currently in use did not address the long-term risks resulting from the cumulative transport of radionuclides. Although reports in the literature confirm that biotic transport phenomena are common, assessments routinely ignore the associated risks or dismiss them as insignificant without quantitative evaluation. To determine the potential impacts of biotic transport, we made order-of-magnitude estimates of the dose to man for biotic transport processes at reference arid and humid CLLW disposal sites. Estimated doses to site residents after assumed loss of institutional control were comparable to dose estimates for the intruder-agricultural scenario defined in the DEIS for 10 CFR 61 (NRC). The reported lack of potential importance of biotic transport at low-level waste sites in earlier assessment studies is not confirmed by order of magnitude estimates presented in this study. 17 references, 10 figures, 8 tables.

  14. Considerations on the role of fall-back discs in the final stages of the common envelope binary interaction

    NASA Astrophysics Data System (ADS)

    Kuruwita, Rajika L.; Staff, Jan; De Marco, Orsola

    2016-09-01

    The common envelope interaction is thought to be the gateway to all evolved compact binaries and mergers. Hydrodynamic simulations of the common envelope interaction between giant stars and their companions are restricted to the dynamical, fast, in-spiral phase. They find that the giant envelope is lifted during this phase, but remains mostly bound to the system. At the same time, the orbital separation is greatly reduced, but in most simulations it levels off at values larger than measured from observations. We conjectured that during the post-in-spiral phase the bound envelope gas will return to the system. Using hydrodynamic simulations, we generate initial conditions for our simulation that result in a fall-back disc with total mass and angular momentum in line with quantities from the simulations of Passy et al. We find that the simulated fall-back event reduces the orbital separation efficiently, but fails to unbind the gas before the separation levels off once again. We also find that more massive fall-back discs reduce the orbital separation more efficiently, but the efficiency of unbinding remains invariably very low. From these results we deduce that unless a further energy source contributes to unbinding the envelope (such as was recently tested by Nandez et al.), all common envelope interactions would result in mergers. On the other hand, additional energy sources are unlikely to help, on their own, to reduce the orbital separation. We conclude by discussing our dynamical fall-back event in the context of a thermally regulated post-common envelope phase.

  15. MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith-Magenis and fragile X syndromes.

    PubMed

    Mullegama, Sureni V; Pugliesi, Loren; Burns, Brooke; Shah, Zalak; Tahir, Raiha; Gu, Yanghong; Nelson, David L; Elsea, Sarah H

    2015-06-01

    Individuals with autism spectrum disorders (ASD) who have an identifiable single-gene neurodevelopmental disorder (NDD), such as fragile X syndrome (FXS, FMR1), Smith-Magenis syndrome (SMS, RAI1), or 2q23.1 deletion syndrome (del 2q23.1, MBD5) share phenotypic features, including a high prevalence of sleep disturbance. We describe the circadian deficits in del 2q23.1 through caregiver surveys in which we identify several frequent sleep anomalies, including night/early awakenings, coughing/snoring loudly, and difficulty falling asleep. We couple these findings with studies on the molecular analysis of the circadian deficits associated with haploinsufficiency of MBD5 in which circadian gene mRNA levels of NR1D2, PER1, PER2, and PER3 were altered in del 2q23.1 lymphoblastoid cell lines (LCLs), signifying that haploinsufficiency of MBD5 can result in dysregulation of circadian rhythm gene expression. These findings were further supported by expression microarrays of MBD5 siRNA knockdown cells that showed significantly altered expression of additional circadian rhythm signaling pathway genes. Based on the common sleep phenotypes observed in del 2q23.1, SMS, and FXS patients, we explored the possibility that MBD5, RAI1, and FMR1 function in overlapping circadian rhythm pathways. Bioinformatic analysis identified conserved putative E boxes in MBD5 and RAI1, and expression levels of NR1D2 and CRY2 were significantly reduced in patient LCLs. Circadian and mTOR signaling pathways, both associated with sleep disturbance, were altered in both MBD5 and RAI1 knockdown microarray data, overlapping with findings associated with FMR1. These data support phenotypic and molecular overlaps across these syndromes that may be exploited to provide therapeutic intervention for multiple disorders.

  16. MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith–Magenis and fragile X syndromes

    PubMed Central

    Mullegama, Sureni V; Pugliesi, Loren; Burns, Brooke; Shah, Zalak; Tahir, Raiha; Gu, Yanghong; Nelson, David L; Elsea, Sarah H

    2015-01-01

    Individuals with autism spectrum disorders (ASD) who have an identifiable single-gene neurodevelopmental disorder (NDD), such as fragile X syndrome (FXS, FMR1), Smith–Magenis syndrome (SMS, RAI1), or 2q23.1 deletion syndrome (del 2q23.1, MBD5) share phenotypic features, including a high prevalence of sleep disturbance. We describe the circadian deficits in del 2q23.1 through caregiver surveys in which we identify several frequent sleep anomalies, including night/early awakenings, coughing/snoring loudly, and difficulty falling asleep. We couple these findings with studies on the molecular analysis of the circadian deficits associated with haploinsufficiency of MBD5 in which circadian gene mRNA levels of NR1D2, PER1, PER2, and PER3 were altered in del 2q23.1 lymphoblastoid cell lines (LCLs), signifying that haploinsufficiency of MBD5 can result in dysregulation of circadian rhythm gene expression. These findings were further supported by expression microarrays of MBD5 siRNA knockdown cells that showed significantly altered expression of additional circadian rhythm signaling pathway genes. Based on the common sleep phenotypes observed in del 2q23.1, SMS, and FXS patients, we explored the possibility that MBD5, RAI1, and FMR1 function in overlapping circadian rhythm pathways. Bioinformatic analysis identified conserved putative E boxes in MBD5 and RAI1, and expression levels of NR1D2 and CRY2 were significantly reduced in patient LCLs. Circadian and mTOR signaling pathways, both associated with sleep disturbance, were altered in both MBD5 and RAI1 knockdown microarray data, overlapping with findings associated with FMR1. These data support phenotypic and molecular overlaps across these syndromes that may be exploited to provide therapeutic intervention for multiple disorders. PMID:25271084

  17. Reference gene validation for quantification of gene expression during final oocyte maturation induced by diethylstilbestrol and di-(2-ethylhexyl)-phthalate in common carp.

    PubMed

    Shi, Yanyan; Lu, Jie; Wang, Yilei; Wang, Shuhong

    2016-08-01

    Final oocyte maturation is the key step to successful spawning and fertilization. Quantitative real-time PCR (qPCR) is the technique of election to quantify the abundance of functional genes in such study. Reference gene is essential for correct interpretation of qPCR data. However, an ideal universal reference gene that is stable under all experimental circumstances has not been described. Researchers should validate their reference genes while performing qPCR analysis. The expression of 6 candidate reference genes: 18s rRNA, 28s rRNA, Cathepsin Z, Elongation factor 1-α, Glyceraldehyde-3-phosphate dehydrogenase and β-actin were investigated during final oocyte maturation induced by different compounds (DES and DEHP) in common carp (Cyprinus carpio). Four softwares (Bestkeeper, geNorm, NormFinder and RefFinder) were used to screen the most stable gene in order to evaluate their expression stability. The results revealed that EF1α was highly stable expressed when final oocyte maturation was induced by DES, while gapdh was the most stable gene when final oocyte maturation was induced by DEHP. Stable expressed reference gene selection is critical for all qPCR analysis to get accurate target gene mRNA expression information. PMID:27521935

  18. Federal Employees Health Benefits Program and Federal Employees Dental and Vision Insurance Program: eligibility for Pathway Programs participants. Interim final rule with request for comments.

    PubMed

    2014-01-01

    The U.S. Office of Personnel Management (OPM) is issuing an interim final regulation to update the Federal Employees Health Benefits Program (FEHBP) and the Federal Employees Dental and Vision Insurance Program (FEDVIP) regulations to reflect updated election opportunities for participants in the Pathways Programs. The Pathways Programs were created by Executive Order (E.O.) 13562, signed by the President on December 27, 2010, and are designed to enable the Federal Government to compete effectively for students and recent graduates by improving its recruitment efforts through internships and similar programs with Federal agencies. This interim final rule furthers these recruitment and retention efforts by providing health insurance, as well as dental and vision benefits, to eligible program participants and their families.

  19. Hormonal and transcriptional profiles highlight common and differential host responses to arbuscular mycorrhizal fungi and the regulation of the oxylipin pathway

    PubMed Central

    López-Ráez, Juan A.; Verhage, Adriaan; Fernández, Iván; García, Juan M.; Azcón-Aguilar, Concepción; Flors, Victor; Pozo, María J.

    2010-01-01

    Arbuscular mycorrhizal (AM) symbioses are mutualistic associations between soil fungi and most vascular plants. The symbiosis significantly affects the host physiology in terms of nutrition and stress resistance. Despite the lack of host range specificity of the interaction, functional diversity between AM fungal species exists. The interaction is finely regulated according to plant and fungal characters, and plant hormones are believed to orchestrate the modifications in the host plant. Using tomato as a model, an integrative analysis of the host response to different mycorrhizal fungi was performed combining multiple hormone determination and transcriptional profiling. Analysis of ethylene-, abscisic acid-, salicylic acid-, and jasmonate-related compounds evidenced common and divergent responses of tomato roots to Glomus mosseae and Glomus intraradices, two fungi differing in their colonization abilities and impact on the host. Both hormonal and transcriptional analyses revealed, among others, regulation of the oxylipin pathway during the AM symbiosis and point to a key regulatory role for jasmonates. In addition, the results suggest that specific responses to particular fungi underlie the differential impact of individual AM fungi on plant physiology, and particularly on its ability to cope with biotic stresses. PMID:20378666

  20. Protein-protein interaction and pathway analyses of top schizophrenia genes reveal schizophrenia susceptibility genes converge on common molecular networks and enrichment of nucleosome (chromatin) assembly genes in schizophrenia susceptibility loci.

    PubMed

    Luo, Xiongjian; Huang, Liang; Jia, Peilin; Li, Ming; Su, Bing; Zhao, Zhongming; Gan, Lin

    2014-01-01

    Recent genome-wide association studies have identified many promising schizophrenia candidate genes and demonstrated that common polygenic variation contributes to schizophrenia risk. However, whether these genes represent perturbations to a common but limited set of underlying molecular processes (pathways) that modulate risk to schizophrenia remains elusive, and it is not known whether these genes converge on common biological pathways (networks) or represent different pathways. In addition, the theoretical and genetic mechanisms underlying the strong genetic heterogeneity of schizophrenia remain largely unknown. Using 4 well-defined data sets that contain top schizophrenia susceptibility genes and applying protein-protein interaction (PPI) network analysis, we investigated the interactions among proteins encoded by top schizophrenia susceptibility genes. We found proteins encoded by top schizophrenia susceptibility genes formed a highly significant interconnected network, and, compared with random networks, these PPI networks are statistically highly significant for both direct connectivity and indirect connectivity. We further validated these results using empirical functional data (transcriptome data from a clinical sample). These highly significant findings indicate that top schizophrenia susceptibility genes encode proteins that significantly directly interacted and formed a densely interconnected network, suggesting perturbations of common underlying molecular processes or pathways that modulate risk to schizophrenia. Our findings that schizophrenia susceptibility genes encode a highly interconnected protein network may also provide a novel explanation for the observed genetic heterogeneity of schizophrenia, ie, mutation in any member of this molecular network will lead to same functional consequences that eventually contribute to risk of schizophrenia.

  1. Comparative Cytotoxicity and Sperm Motility Using a Computer-Aided Sperm Analysis System (CASA) for Isomers of Phthalic Acid, a Common Final Metabolite of Phthalates.

    PubMed

    Kwack, Seung Jun; Lee, Byung-Mu

    2015-01-01

    The general population is exposed to phthalates through consumer products, diet, and medical devices. Phthalic acid (PA) is a common final metabolite of phthalates, and its isomers include isophthalic acid (IPA), terephthalic acid (TPA), and phthalaldehyde (o-phthalic acid, OPA). The purpose of this study was to investigate whether PA and PA isomers exert reproductive toxicity, including altered sperm movement. In vitro cell viability assays were comparatively performed using Sertoli and liver cell lines. In animal experiments, PA or PA isomers (10, 100, or 1000 mg/kg) were administered orally to Sprague-Dawley (SD) rats, and semen samples were analyzed by computer-aided sperm analysis (CASA). PA treatment produced a significant effect on curvilinear velocity (VCL), straight-line velocity (VSL), mean velocity or average path velocity (VAP), amplitude of lateral head displacement (ALH), and frequency of head displacement or beat cross-frequency (BCF), whereas IPA, TPA, and OPA induced no marked effects. In vitro cell viability assays showed that mouse normal testis cells (TM4) and human testis cancer cells (NTERA 2 cl. D1) were more sensitive to PA and OPA than mouse liver normal cells (NCTC clone 1469) and human fetal liver cells (FL 62891). Our study suggests that PA and PA isomers specifically produced significant in vitro and in vivo reproductive toxicity, particularly sperm toxicity and testis cell cytotoxicity. Of the isomers examined, PA appeared to be the most toxic and may serve as a surrogate biomarker for reproductive toxicity following mixed exposure to phthalates.

  2. Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report

    SciTech Connect

    Duster, T.

    1998-11-01

    The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

  3. The pathways of C: from AGB stars, to the Interstellar Medium, and finally into the protoplanetary disk

    NASA Astrophysics Data System (ADS)

    Trigo-Rodriguez, J. M.; Garcia-Hernandez, D. A.

    2011-05-01

    The origin, and role of C in the formation of first solar system aggregates is described. Stellar grains evidence demonstrates that Asymptotic Giant Branch (AGB) stars were nearby to the solar nebula at the time of solar system formation. Such stars continue to burn H and He in shells that surround the C-O core. During their evolution, flashes occur in the He shell and the C, and O produced are eventually dredged up into the star's envelop and then to the stellar surface, and finally masively ejected to the interstellar medium (IM). Once in a molecular cloud, the electrophilicity of C makes this element reactable with the surrounding gas to produce different molecular species. Primitive meteorites, particularly these known as chondrites, preserved primeval materials of the disk. The abundances of short-lived radionuclides (SLN), inferred to have been present in the early solar system (ESS), are a constraint on the birth and early evolution of the solar system as their relatively short half lives do not allow the observed abundances to be explained by galactic chemical evolution processes. We present a model of a 6.5 solar masses star of solar metallicity that simultaneously match the abundances of SLNs inferred to have been present in the ESS by using a dilution factor of 1 part of AGB material per 300 parts of original solar nebula material, and taking into account a time interval between injection of SLNs and consolidation of chondrites equal to 0.53 Myr [2]. Such a polluting source does not overproduce 53Mn, as supernova models do, and only marginally affects isotopic ratios of stable elements. The AGB stars released O- and C-rich gas with important oxidizing implications to first solar system materials as recently detected in circumstellar environments [3]. REF: [1] Lada C.J. and Lada E.A. 2003. Ann. Rev. A&A. 41: 57; [2] Trigo-Rodriguez J.M. et al. 2009. MAPS 44: 627; [3] Decin L. et al. 2010. Nature 467: 64.

  4. RNA Sequencing Analysis of the msl2msl3, crl, and ggps1 Mutants Indicates that Diverse Sources of Plastid Dysfunction Do Not Alter Leaf Morphology Through a Common Signaling Pathway

    PubMed Central

    Luesse, Darron R.; Wilson, Margaret E.; Haswell, Elizabeth S.

    2015-01-01

    Determining whether individual genes function in the same or in different pathways is an important aspect of genetic analysis. As an alternative to the construction of higher-order mutants, we used contemporary expression profiling methods to perform pathway analysis on several Arabidopsis thaliana mutants, including the mscS-like (msl)2msl3 double mutant. MSL2 and MSL3 are implicated in plastid ion homeostasis, and msl2msl3 double mutants exhibit leaves with a lobed periphery, a rumpled surface, and disturbed mesophyll cell organization. Similar developmental phenotypes are also observed in other mutants with defects in a range of other chloroplast or mitochondrial functions, including biogenesis, gene expression, and metabolism. We wished to test the hypothesis that the common leaf morphology phenotypes of these mutants are the result of a characteristic nuclear expression pattern that is generated in response to organelle dysfunction. RNA-Sequencing was performed on aerial tissue of msl2msl3 geranylgeranyl diphosphate synthase 1 (ggps1), and crumpled leaf (crl) mutants. While large groups of co-expressed genes were identified in pairwise comparisons between genotypes, we were only able to identify a small set of genes that showed similar expression profiles in all three genotypes. Subsequent comparison to the previously published gene expression profiles of two other mutants, yellow variegated 2 (var2) and scabra3 (sca3), failed to reveal a common pattern of gene expression associated with superficially similar leaf morphology defects. Nor did we observe overlap between genes differentially expressed in msl2msl3, crl, and ggps1 and a previously identified retrograde core response module. These data suggest that a common retrograde signaling pathway initiated by organelle dysfunction either does not exist in these mutants or cannot be identified through transcriptomic methods. Instead, the leaf developmental defects observed in these mutants may be achieved

  5. Common fur and mystacial vibrissae parallel sensory pathways: /sup 14/C 2-deoxyglucose and WGA-HRP studies in the rat

    SciTech Connect

    Sharp, F.R.; Gonzalez, M.F.; Morgan, C.W.; Morton, M.T.; Sharp, J.W.

    1988-04-15

    Stimulation of mystacial vibrissae in rows A,B, and C increased (14C) 2-deoxyglucose (2DG) uptake in spinal trigeminal nucleus pars caudalis (Sp5c) mostly in ventral portions of laminae III-IV with less activation of II and V. Stimulation of common fur above the whiskers mainly activated lamina II, with less activation in deeper layers. The patterns of activation were compatible with an inverted head, onion skin Sp5c somatotopy. Wheatgerm Agglutinin-Horseradish Peroxidase (WGA-HRP) injections into common fur between mystacial vibrissae rows A-B and B-C led to anterograde transganglionic labeling only of Sp5c, mainly of lamina II with less label in layer V, and very sparse label in III and IV. WGA-HRP skin injections appear to primarily label small fibers, which along with larger fibers, were metabolically activated during common fur stimulation. Mystacial vibrissae stimulation increased 2DG uptake in ventral ipsilateral spinal trigeminal nuclei pars interpolaris (Sp5i) and oralis (Sp5o) and principal trigeminal sensory nucleus (Pr5). Common fur stimulation above the whiskers slightly increased 2DG uptake in ventral Sp5i, Sp5o, and possibly Pr5. The most dorsal aspect of the ventroposteromedial (VPM) nucleus of thalamus was activated contralateral to whisker stimulation. Stimulation of the common fur dorsal to the whiskers activated a region of dorsal VPM caudal to the VPM region activated during whisker stimulation. This is consistent with previous data showing that ventral whiskers and portions of the face are represented rostrally in VPM, and more dorsal whiskers and dorsal portions of the face are represented progressively more caudally in VPM. Mystacial vibrissae stimulation activated the contralateral primary sensory SI barrelfield cortex and a separate region in the second somatosensory SII cortex.

  6. Effects of leucine and citrulline versus non-essential amino acids on muscle protein synthesis in fasted rat: a common activation pathway?

    PubMed

    Le Plénier, Servane; Walrand, Stéphane; Noirt, Richard; Cynober, Luc; Moinard, Christophe

    2012-09-01

    Leucine (LEU) is recognized as a major regulator of muscle protein synthesis (MPS). Citrulline (CIT) is emerging as a potent new regulator. The aim of our study was to compare MPS modulation by CIT and LEU in food-deprived rats and to determine whether their action was driven by similar mechanisms. Rats were either freely fed (F, n = 10) or food deprived for 18 h. Food-deprived rats were randomly assigned to one of four groups and received per os, i.e., gavage, saline (S, n = 10), L: -leucine (1.35 g/kg, LEU, n = 10), L: -citrulline (1.80 g/kg CIT, n = 10) or isonitrogenous non-essential amino acids (NEAA, n = 10). After gavage, the rats were injected with a flooding dose of [(13)C] valine to determine MPS. The rats were killed 50 min after the injection of the flooding dose. Blood was collected for amino acid, glucose and insulin determinations. Tibialis anterior muscles were excised for determination of MPS and for Western blot analyses of the PI3K/Akt, mTORC1, ERK1/2/MAPK pathways and AMP kinase component. MPS was depressed by 61% in starved rats (Saline vs. Fed, P < 0.05). Administration of amino acids (NEAA, LEU or CIT) completely abolished this decrease (NEAA, CIT, LEU vs. Fed, NS). Food deprivation affected the phosphorylation status of the mTORC1 pathway and AMP kinase (Saline vs. Fed, P < 0.05). LEU and CIT administration differently stimulated the mTORC1 pathway (LEU > CIT). LEU but not CIT increased the phosphorylation of rpS6 at serine 235/236. Our findings clearly demonstrated that both CIT and LEU were able to stimulate MPS, but this effect was likely related to the nitrogen load. LEU, CIT and NEAA may have different actions on MPS in this model as they share different mTORC1 regulation capacities.

  7. Systematic Review of Micro-RNA Expression in Pre-Eclampsia Identifies a Number of Common Pathways Associated with the Disease

    PubMed Central

    Sheikh, Adam M.; Currie, Gemma; Delles, Christian

    2016-01-01

    Background Pre-eclampsia (PE) is a complex, multi-systemic condition of pregnancy which greatly impacts maternal and perinatal morbidity and mortality. MicroRNAs (miRs) are differentially expressed in PE and may be important in helping to understand the condition and its pathogenesis. Methods Case-control studies investigating expression of miRs in PE were collected through a systematic literature search. Data was extracted and compared from 58 studies to identify the most promising miRs associated with PE pathogenesis and identify areas of methodology which could account for often conflicting results. Results Some of the most frequently differentially expressed miRs in PE include miR-210, miR-223 and miR-126/126* which associate strongly with the etiological domains of hypoxia, immunology and angiogenesis. Members of the miR-515 family belonging to the imprinted chromosome 19 miR cluster with putative roles in trophoblast invasion were also found to be differentially expressed. Certain miRs appear to associate with more severe forms of PE such as miR-210 and the immune-related miR-181a and miR-15 families. Patterns of miR expression may help pinpoint key pathways (e.g. IL-6/miR-223/STAT3) and aid in untangling the heterogeneous nature of PE. The detectable presence of many PE-associated miRs in antenatal circulatory samples suggests their usefulness as predictive biomarkers. Further progress in ascertaining the clinical value of miRs and in understanding how they might contribute to pathogenesis is predicated upon resolving current methodological challenges in studies. These include differences in diagnostic criteria, cohort characteristics, sampling technique, RNA isolation and platform-dependent variation in miR profiling. Conclusion Reviewing studies of PE-associated miRs has revealed their potential as informants of underlying target genes and pathways relating to PE pathogenesis. However, the incongruity in results across current studies hampers their

  8. Hydrogen peroxide stimulation of CFTR reveals an Epac-mediated, soluble AC-dependent cAMP amplification pathway common to GPCR signalling

    PubMed Central

    Ivonnet, P; Salathe, M; Conner, G E

    2015-01-01

    BACKGROUND AND PURPOSE H2O2 is widely understood to regulate intracellular signalling. In airway epithelia, H2O2 stimulates anion secretion primarily by activating an autocrine PGE2 signalling pathway via EP4 and EP1 receptors to initiate cytic fibrosis transmembrane regulator (CFTR)-mediated Cl− secretion. This study investigated signalling downstream of the receptors activated by H2O2. EXPERIMENTAL APPROACH Anion secretion by differentiated bronchial epithelial cells was measured in Ussing chambers during stimulation with H2O2, an EP4 receptor agonist or β2-adrenoceptor agonist in the presence and absence of inhibitors of ACs and downstream effectors. Intracellular calcium ([Ca2+]I) changes were followed by microscopy using fura–2-loaded cells and PKA activation followed by FRET microscopy. KEY RESULTS Transmembrane adenylyl cyclase (tmAC) and soluble AC (sAC) were both necessary for H2O2 and EP4 receptor-mediated CFTR activation in bronchial epithelia. H2O2 and EP4 receptor agonist stimulated tmAC to increase exchange protein activated by cAMP (Epac) activity that drives PLC activation to raise [Ca2+]i via Ca2+ store release (and not entry). Increased [Ca2+]i led to sAC activation and further increases in CFTR activity. Stimulation of sAC did not depend on changes in [HCO3−]. Ca2+-activated apical KCa1.1 channels and cAMP-activated basolateral KV7.1 channels contributed to H2O2-stimulated anion currents. A similar Epac-mediated pathway was seen following β2-adrenoceptor or forskolin stimulation. CONCLUSIONS AND IMPLICATIONS H2O2 initiated a complex signalling cascade that used direct stimulation of tmACs by Gαs followed by Epac-mediated Ca2+ crosstalk to activate sAC. The Epac-mediated Ca2+ signal constituted a positive feedback loop that amplified CFTR anion secretion following stimulation of tmAC by a variety of stimuli. PMID:25220136

  9. Mutations in MAP3K1 Cause 46,XY Disorders of Sex Development and Implicate a Common Signal Transduction Pathway in Human Testis Determination

    PubMed Central

    Pearlman, Alexander; Loke, Johnny; Le Caignec, Cedric; White, Stefan; Chin, Lisa; Friedman, Andrew; Warr, Nicholas; Willan, John; Brauer, David; Farmer, Charles; Brooks, Eric; Oddoux, Carole; Riley, Bridget; Shajahan, Shahin; Camerino, Giovanna; Homfray, Tessa; Crosby, Andrew H.; Couper, Jenny; David, Albert; Greenfield, Andy; Sinclair, Andrew; Ostrer, Harry

    2010-01-01

    Investigations of humans with disorders of sex development (DSDs) resulted in the discovery of many of the now-known mammalian sex-determining genes, including SRY, RSPO1, SOX9, NR5A1, WT1, NR0B1, and WNT4. Here, the locus for an autosomal sex-determining gene was mapped via linkage analysis in two families with 46,XY DSD to the long arm of chromosome 5 with a combined, multipoint parametric LOD score of 6.21. A splice-acceptor mutation (c.634-8T>A) in MAP3K1 segregated with the phenotype in the first family and disrupted RNA splicing. Mutations were demonstrated in the second family (p.Gly616Arg) and in two of 11 sporadic cases (p.Leu189Pro, p.Leu189Arg)—18% prevalence in this cohort of sporadic cases. In cultured primary lymphoblastoid cells from family 1 and the two sporadic cases, these mutations altered the phosphorylation of the downstream targets, p38 and ERK1/2, and enhanced binding of RHOA to the MAP3K1 complex. Map3k1 within the syntenic region was expressed in the embryonic mouse gonad prior to, and after, sex determination. Thus, mutations in MAP3K1 that result in 46,XY DSD with partial or complete gonadal dysgenesis implicate this pathway in normal human sex determination. PMID:21129722

  10. Deoxycholic acid and selenium metabolite methylselenol exert common and distinct effects on cell cycle, apoptosis, and MAP kinase pathway in HCT116 human colon cancer cells.

    PubMed

    Zeng, Huawei; Botnen, James H; Briske-Anderson, Mary

    2010-01-01

    The cell growth inhibition induced by bile acid deoxycholic acid (DCA) may cause compensatory hyperproliferation of colonic epithelial cells and consequently increase colon cancer risk. On the other hand, there is increasing evidence for the efficacy of certain forms of selenium (Se) as anticancer nutrients. Methylselenol has been hypothesized to be a critical Se metabolite for anticancer activity in vivo. In this study, we demonstrated that both DCA (75-300 micromol/l) and submicromolar methylselenol inhibited colon cancer cell proliferation by up to 64% and 63%, respectively. In addition, DCA and methylselenol each increased colon cancer cell apoptosis rate by up to twofold. Cell cycle analyses revealed that DCA induced an increase in only the G1 fraction with a concomitant drop in G2 and S-phase; in contrast, methylselenol led to an increase in the G1 and G2 fractions with a concomitant drop only in the S-phase. Although both DCA and methylselenol significantly promoted apoptosis and inhibited cell growth, examination of mitogen-activated protein kinase (MAPK) pathway activation showed that DCA, but not methylselenol, induced SAPK/JNK1/2, p38 MAPK, ERK1/2 activation. Thus, our data provide, for the first time, the molecular basis for opposite effects of methylselenol and DCA on colon tumorigenesis.

  11. Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor-Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma

    PubMed Central

    Brayer, Kathryn J.; Frerich, Candace A.; Kang, Huining; Ness, Scott A.

    2015-01-01

    Adenoid Cystic Carcinoma (ACC), the second most common malignancy of salivary glands, is a rare tumor with bleak prognosis for which therapeutic targets are unavailable. We used RNA-sequencing (RNA-seq) to analyze low-quality RNA from archival, formaldehyde-fixed, paraffin-embedded samples. In addition to detecting the most common ACC translocation, t(6;9) fusing the MYB proto-oncogene to NFIB, we also detected previously unknown t(8;9) and t(8;14) translocations fusing the MYBL1 gene to the NFIB and RAD51B genes, respectively. RNA-seq provided information about gene fusions, alternative RNA splicing and gene expression signatures. Interestingly, tumors with MYB and MYBL1 translocations displayed similar gene expression profiles, and the combined MYB and MYBL1 expression correlated with outcome, suggesting that the related Myb proteins are interchangeable oncogenic drivers in ACC. Our results provide important details about the biology of ACC and illustrate how archival tissue samples can be used for detailed molecular analyses of rare tumors. PMID:26631070

  12. Interactions of external and internal H+ and Na+ with Na+/Na+ and Na+/H+ exchange of rabbit red cells: evidence for a common pathway.

    PubMed

    Morgan, K; Canessa, M

    1990-12-01

    We have studied the kinetic properties of rabbit red cell (RRBC) Na+/Na+ and Na+/H+ exchanges (EXC) in order to define whether or not both transport functions are conducted by the same molecule. The strategy has been to determine the interactions of Na+ and H+ at the internal (i) and external (o) sites for both exchanges modes. RRBC containing varying Nai and Hi were prepared by nystatin and DIDS treatment of acid-loaded cells. Na+/Na+ EXC was measured as Nao-stimulated Na+ efflux and Na+/H+ EXC as Nao-stimulated H+ efflux and delta pHo-stimulated Na+ influx into acid-loaded cells. The activation of Na+/Na+ EXC by Nao at pHi 7.4 did not follow simple hyperbolic kinetics. Testing of different kinetic models to obtain the best fit for the experimental data indicated the presence of high (Km 2.2 mM) and low affinity (Km 108 mM) sites for a single- or two-carrier system. The activation of Na+/H+ EXC by Nao (pHi 6.6, Nai less than 1 mM) also showed high (Km 11 mM) and low (Km 248 mM) affinity sites. External H+ competitively inhibited Na+/Na+ EXC at the low affinity Nao site (KH 52 nM) while internally H+ were competitive inhibitors (pK 6.7) at low Nai and allosteric activators (pK 7.0) at high Nai. Na+/H+ EXC was also inhibited by acid pHo and allosterically activated by Hi (pK 6.4). We also established the presence of a Nai regulatory site which activates Na+/H+ and Na+/Na+ EXC modifying the affinity for Nao of both pathways. At low Nai, Na+/Na+ EXC was inhibited by acid pHi and Na+/H+ stimulated but at high Nai, Na+/Na+ EXC was stimulated and Na+/H+ inhibited being the sum of both pathways kept constant. Both exchange modes were activated by two classes of Nao sites, cis-inhibited by external Ho, allosterically modified by the binding of H+ to a Hi regulatory site and regulated by Nai. These findings are consistent with Na+/Na+ EXC being a mode of operation of the Na+/H+ exchanger. Na+/H+ EXC was partially inhibited (80-100%) by dimethyl-amiloride (DMA) but basal or

  13. RNA-sequencing of Cercospora beticola DMI-sensitive and -resistant isolates after treatment with tetraconazole identifies common and contrasting pathway induction.

    PubMed

    Bolton, Melvin D; Ebert, Malaika K; Faino, Luigi; Rivera-Varas, Viviana; de Jonge, Ronnie; Van de Peer, Yves; Thomma, Bart P H J; Secor, Gary A

    2016-07-01

    Cercospora beticola causes Cercospora leaf spot of sugar beet. Cercospora leaf spot management measures often include application of the sterol demethylation inhibitor (DMI) class of fungicides. The reliance on DMIs and the consequent selection pressures imposed by their widespread use has led to the emergence of resistance in C. beticola populations. Insight into the molecular basis of tetraconazole resistance may lead to molecular tools to identify DMI-resistant strains for fungicide resistance management programs. Previous work has shown that expression of the gene encoding the DMI target enzyme (CYP51) is generally higher and inducible in DMI-resistant C. beticola field strains. In this study, we extended the molecular basis of DMI resistance in this pathosystem by profiling the transcriptional response of two C. beticola strains contrasting for resistance to tetraconazole. A majority of the genes in the ergosterol biosynthesis pathway were induced to similar levels in both strains with the exception of CbCyp51, which was induced several-fold higher in the DMI-resistant strain. In contrast, a secondary metabolite gene cluster was induced in the resistance strain, but repressed in the sensitive strain. Genes encoding proteins with various cell membrane fortification processes were induced in the resistance strain. Site-directed and ectopic mutants of candidate DMI-resistance genes all resulted in significantly higher EC50 values than the wild-type strain, suggesting that the cell wall and/or membrane modified as a result of the transformation process increased resistance to tetraconazole. Taken together, this study identifies important cell membrane components and provides insight into the molecular events underlying DMI resistance in C. beticola. PMID:27112724

  14. Common Cold

    MedlinePlus

    ... nose, coughing - everyone knows the symptoms of the common cold. It is probably the most common illness. In ... avoid colds. There is no cure for the common cold. For relief, try Getting plenty of rest Drinking ...

  15. Down syndrome and Alzheimer's disease: Common pathways, common goals.

    PubMed

    Hartley, Dean; Blumenthal, Thomas; Carrillo, Maria; DiPaolo, Gilbert; Esralew, Lucille; Gardiner, Katheleen; Granholm, Ann-Charlotte; Iqbal, Khalid; Krams, Michael; Lemere, Cynthia; Lott, Ira; Mobley, William; Ness, Seth; Nixon, Ralph; Potter, Huntington; Reeves, Roger; Sabbagh, Marwan; Silverman, Wayne; Tycko, Benjamin; Whitten, Michelle; Wisniewski, Thomas

    2015-06-01

    In the United States, estimates indicate there are between 250,000 and 400,000 individuals with Down syndrome (DS), and nearly all will develop Alzheimer's disease (AD) pathology starting in their 30s. With the current lifespan being 55 to 60 years, approximately 70% will develop dementia, and if their life expectancy continues to increase, the number of individuals developing AD will concomitantly increase. Pathogenic and mechanistic links between DS and Alzheimer's prompted the Alzheimer's Association to partner with the Linda Crnic Institute for Down Syndrome and the Global Down Syndrome Foundation at a workshop of AD and DS experts to discuss similarities and differences, challenges, and future directions for this field. The workshop articulated a set of research priorities: (1) target identification and drug development, (2) clinical and pathological staging, (3) cognitive assessment and clinical trials, and (4) partnerships and collaborations with the ultimate goal to deliver effective disease-modifying treatments.

  16. Down syndrome and Alzheimer's disease: Common pathways, common goals

    PubMed Central

    Hartley, Dean; Blumenthal, Thomas; Carrillo, Maria; DiPaolo, Gilbert; Esralew, Lucille; Gardiner, Katheleen; Granholm, Ann-Charlotte; Iqbal, Khalid; Krams, Michael; Lemere, Cynthia; Lott, Ira; Mobley, William; Ness, Seth; Nixon, Ralph; Potter, Huntington; Reeves, Roger; Sabbagh, Marwan; Silverman, Wayne; Tycko, Benjamin; Whitten, Michelle; Wisniewski, Thomas

    2016-01-01

    In the United States, estimates indicate there are between 250,000 and 400,000 individuals with Down syndrome (DS), and nearly all will develop Alzheimer's disease (AD) pathology starting in their 30s. With the current lifespan being 55 to 60 years, approximately 70% will develop dementia, and if their life expectancy continues to increase, the number of individuals developing AD will concomitantly increase. Pathogenic and mechanistic links between DS and Alzheimer's prompted the Alzheimer's Association to partner with the Linda Crnic Institute for Down Syndrome and the Global Down Syndrome Foundation at a workshop of AD and DS experts to discuss similarities and differences, challenges, and future directions for this field. The workshop articulated a set of research priorities: (1) target identification and drug development, (2) clinical and pathological staging, (3) cognitive assessment and clinical trials, and (4) partnerships and collaborations with the ultimate goal to deliver effective disease-modifying treatments. PMID:25510383

  17. Common murre restoration monitoring in the Barren Islands, Alaska, 1993. Restoration project 93049. Exxon Valdez oil spill restoration project final report

    SciTech Connect

    Roseneau, D.G.; Kettle, A.B.; Byrd, G.V.

    1995-06-01

    This report summarizes the results of the second year of common murre (Uria aalge) restoration monitoring work conducted in the northern Gulf of Alaska for the Exxon Valdez Oil Spill Trustee Council. Information on population numbers, nesting chronology, and productivity of murres were collected by U.S. Fish and Wildlife Service (FWS) biologists at the injured East of Amatuli Island - Light Rock and Nord Island - Northwest Islet colonies in the Barren Islands during the 1993 breeding season. These data are presented and statistically compared with information reported in the 1989-1992 FWS murre damage assessment and restoration studies.

  18. Cofunctional Subpathways Were Regulated by Transcription Factor with Common Motif, Common Family, or Common Tissue

    PubMed Central

    Su, Fei; Shang, Desi; Xu, Yanjun; Feng, Li; Yang, Haixiu; Liu, Baoquan; Su, Shengyang; Chen, Lina; Li, Xia

    2015-01-01

    Dissecting the characteristics of the transcription factor (TF) regulatory subpathway is helpful for understanding the TF underlying regulatory function in complex biological systems. To gain insight into the influence of TFs on their regulatory subpathways, we constructed a global TF-subpathways network (TSN) to analyze systematically the regulatory effect of common-motif, common-family, or common-tissue TFs on subpathways. We performed cluster analysis to show that the common-motif, common-family, or common-tissue TFs that regulated the same pathway classes tended to cluster together and contribute to the same biological function that led to disease initiation and progression. We analyzed the Jaccard coefficient to show that the functional consistency of subpathways regulated by the TF pairs with common motif, common family, or common tissue was significantly greater than the random TF pairs at the subpathway level, pathway level, and pathway class level. For example, HNF4A (hepatocyte nuclear factor 4, alpha) and NR1I3 (nuclear receptor subfamily 1, group I, member 3) were a pair of TFs with common motif, common family, and common tissue. They were involved in drug metabolism pathways and were liver-specific factors required for physiological transcription. In short, we inferred that the cofunctional subpathways were regulated by common-motif, common-family, or common-tissue TFs. PMID:26688819

  19. Screening douglas-fir for rapid early growth in common-garden tests in spain. Forest Service general technical report (Final)

    SciTech Connect

    Hernandez, G.T.; Alonso, G.V.; Arribas, G.P.; Jenkinson, J.L.

    1993-08-01

    Douglas-firs from 91 seed sources in North America were evaluated after 5 and 6 years in 15 common-garden tests in the mountainous regions of northwest and north central Spain. Analyses of tallest trees showed that most of the sources of highest potential for reforestation in Spain are found in regions where the Pacific Ocean air mass dominates climate. Fast growers came from coastal slopes of the Coast Ranges from northwest California to the Georgia Strait of southwest British Columbia and inland slopes of the Olympic Mountains and Coast and Cascade Ranges facing the Puget Trough in western Washington and Willamette Valley in northwest Oregon. Slow growers came from latitudes south of 44 deg and north of 50 deg, high altitudes west of the crest of the Cascade Ranges, and regions east of the crest where the continental air mass dominated climate.

  20. Common Cold

    MedlinePlus

    ... News & Events Volunteer NIAID > Health & Research Topics > Common Cold Skip Website Tools Website Tools Print this page ... Help people who are suffering from the common cold by volunteering for NIAID clinical studies on ClinicalTrials. ...

  1. Common Sense: Using Common Finals to Measure Postsecondary Student Learning

    ERIC Educational Resources Information Center

    Chingos, Matthew M.

    2013-01-01

    College completion rates in the U.S. are stubbornly low despite the large and rising returns to a college degree. Efforts to increase student success in college have largely ignored a potentially key factor: the instruction that students receive in the sequence of courses that add up to a college education. Improving the quality of instruction may…

  2. Clays, common

    USGS Publications Warehouse

    Virta, R.L.

    1998-01-01

    Part of a special section on the state of industrial minerals in 1997. The state of the common clay industry worldwide for 1997 is discussed. Sales of common clay in the U.S. increased from 26.2 Mt in 1996 to an estimated 26.5 Mt in 1997. The amount of common clay and shale used to produce structural clay products in 1997 was estimated at 13.8 Mt.

  3. Functional analysis of the final steps of the 1-deoxy-D-xylulose 5-phosphate (DXP) pathway to isoprenoids in plants using virus-induced gene silencing.

    PubMed

    Page, Jonathan E; Hause, Gerd; Raschke, Maja; Gao, Wenyun; Schmidt, Jürgen; Zenk, Meinhart H; Kutchan, Toni M

    2004-04-01

    Isoprenoid biosynthesis in plant plastids occurs via the 1-deoxy-d-xylulose 5-phosphate (DXP) pathway. We used tobacco rattle virus (TRV) to posttranscriptionally silence the expression of the last two enzymes of this pathway, the IspG-encoded (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (HDS) and the IspH-encoded isopentenyl/dimethylallyl diphosphate synthase (IDDS), as well as isopentenyl/dimethylallyl diphosphate isomerase (IDI), the enzyme that interconverts IPP and DMAPP. TRV-IspG and TRV-IspH infected Nicotiana benthamiana plants had albino leaves that contained less than 4% of the chlorophyll and carotenoid pigments of control leaves. We applied [(13)C]DXP and [(14)C]DXP to silenced leaves and found that 2-C-methyl-d-erythritol 2,4-cyclodiphosphate accumulated in plants blocked at HDS while DXP, (E)-4-hydroxy-3-methylbut-2-enyl phosphate and (E)-2-methylbut-2-ene-1,4-diol accumulated in IDDS-blocked plants. Albino leaves from IspG- and IspH-silenced plants displayed a disorganized palisade mesophyll, reduced cuticle, fewer plastids, and disrupted thylakoid membranes. These findings demonstrate the participation of HDS and IDDS in the DXP pathway in plants, and support the view that plastid isoprenoid biosynthesis is metabolically and physically segregated from the mevalonate pathway. IDI-silenced plants had mottled white-pale green leaves with disrupted tissue and plastid structure, and showed an 80% reduction in pigments compared to controls. IPP pyrophosphatase activity was higher in chloroplasts isolated from IDI-silenced plants than in control plant chloroplasts. We suggest that a low level of isoprenoid biosynthesis via the DXP pathway can occur without IDI but that this enzyme is required for full function of the DXP pathway.

  4. Student Commons

    ERIC Educational Resources Information Center

    Gordon, Douglas

    2010-01-01

    Student commons are no longer simply congregation spaces for students with time on their hands. They are integral to providing a welcoming environment and effective learning space for students. Many student commons have been transformed into spaces for socialization, an environment for alternative teaching methods, a forum for large group meetings…

  5. An introductory review of parallel independent component analysis (p-ICA) and a guide to applying p-ICA to genetic data and imaging phenotypes to identify disease-associated biological pathways and systems in common complex disorders.

    PubMed

    Pearlson, Godfrey D; Liu, Jingyu; Calhoun, Vince D

    2015-01-01

    Complex inherited phenotypes, including those for many common medical and psychiatric diseases, are most likely underpinned by multiple genes contributing to interlocking molecular biological processes, along with environmental factors (Owen et al., 2010). Despite this, genotyping strategies for complex, inherited, disease-related phenotypes mostly employ univariate analyses, e.g., genome wide association. Such procedures most often identify isolated risk-related SNPs or loci, not the underlying biological pathways necessary to help guide the development of novel treatment approaches. This article focuses on the multivariate analysis strategy of parallel (i.e., simultaneous combination of SNP and neuroimage information) independent component analysis (p-ICA), which typically yields large clusters of functionally related SNPs statistically correlated with phenotype components, whose overall molecular biologic relevance is inferred subsequently using annotation software suites. Because this is a novel approach, whose details are relatively new to the field we summarize its underlying principles and address conceptual questions regarding interpretation of resulting data and provide practical illustrations of the method. PMID:26442095

  6. A carbon source-responsive promoter element necessary for activation of the isocitrate lyase gene ICL1 is common to genes of the gluconeogenic pathway in the yeast Saccharomyces cerevisiae.

    PubMed Central

    Schöler, A; Schüller, H J

    1994-01-01

    The expression of yeast genes encoding gluconeogenic enzymes depends strictly on the carbon source available in the growth medium. We have characterized the control region of the isocitrate lyase gene ICL1, which is derepressed more than 200-fold after transfer of cells from fermentative to nonfermentative growth conditions. Deletion analysis of the ICL1 promoter led to the identification of an upstream activating sequence element, UASICL1 (5' CATTCATCCG 3'), necessary and sufficient for conferring carbon source-dependent regulation on a heterologous reporter gene. Similar sequence motifs were also found in the upstream regions of coregulated genes involved in gluconeogenesis. This carbon source-responsive element (CSRE) interacts with a protein factor, designated Ang1 (activator of nonfermentative growth), detectable only in extracts derived from derepressed cells. Gene activation mediated by the CSRE requires the positively acting derepression genes CAT1 (= SNF1 and CCR1) and CAT3 (= SNF4). In the respective mutants, Ang1-CSRE interaction was no longer observed under repressing or derepressing conditions. Since binding of Ang1 factor to the CSRE could be competed for by an upstream sequence derived from the fructose-1,6-bisphosphatase gene FBP1, we propose that the CSRE functions as a UAS element common to genes of the gluconeogenic pathway. Images PMID:8196607

  7. Common cold

    MedlinePlus

    ... been tried for colds, such as vitamin C, zinc supplements, and echinacea. Talk to your health care ... nih.gov/pubmed/22962927 . Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic ...

  8. Multiple pathways regulate shoot branching

    PubMed Central

    Rameau, Catherine; Bertheloot, Jessica; Leduc, Nathalie; Andrieu, Bruno; Foucher, Fabrice; Sakr, Soulaiman

    2015-01-01

    Shoot branching patterns result from the spatio-temporal regulation of axillary bud outgrowth. Numerous endogenous, developmental and environmental factors are integrated at the bud and plant levels to determine numbers of growing shoots. Multiple pathways that converge to common integrators are most probably involved. We propose several pathways involving not only the classical hormones auxin, cytokinins and strigolactones, but also other signals with a strong influence on shoot branching such as gibberellins, sugars or molecular actors of plant phase transition. We also deal with recent findings about the molecular mechanisms and the pathway involved in the response to shade as an example of an environmental signal controlling branching. We propose the TEOSINTE BRANCHED1, CYCLOIDEA, PCF transcription factor TB1/BRC1 and the polar auxin transport stream in the stem as possible integrators of these pathways. We finally discuss how modeling can help to represent this highly dynamic system by articulating knowledges and hypothesis and calculating the phenotype properties they imply. PMID:25628627

  9. Crystallization Pathways in Biomineralization

    NASA Astrophysics Data System (ADS)

    Weiner, Steve; Addadi, Lia

    2011-08-01

    A crystallization pathway describes the movement of ions from their source to the final product. Cells are intimately involved in biological crystallization pathways. In many pathways the cells utilize a unique strategy: They temporarily concentrate ions in intracellular membrane-bound vesicles in the form of a highly disordered solid phase. This phase is then transported to the final mineralization site, where it is destabilized and crystallizes. We present four case studies, each of which demonstrates specific aspects of biological crystallization pathways: seawater uptake by foraminifera, calcite spicule formation by sea urchin larvae, goethite formation in the teeth of limpets, and guanine crystal formation in fish skin and spider cuticles. Three representative crystallization pathways are described, and aspects of the different stages of crystallization are discussed. An in-depth understanding of these complex processes can lead to new ideas for synthetic crystallization processes of interest to materials science.

  10. Common Standards for All

    ERIC Educational Resources Information Center

    Principal, 2010

    2010-01-01

    About three-fourths of the states have already adopted the Common Core State Standards, which were designed to provide more clarity about and consistency in what is expected of student learning across the country. However, given the brief time since the standards' final release in June, questions persist among educators, who will have the…

  11. Common Pyraloidea species of Dominica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Forty-six adult crambid moths of the superfamily Pyraloidea from Dominica are illustrated and identified. These images are a tool for the identification of large, common species in the Caribbean. The Caribbean is a common entry and pathway of invasive species to southeastern United States....

  12. Career pathways in research: pharmaceutical.

    PubMed

    Kenkre, J E; Foxcroft, D R

    The pharmaceutical pathway is the final article in this series on career pathways and highlights opportunities for nurses within associated industries. This pathway shows that nurses can use their nursing qualifications, combined with their knowledge, skills and expertise, to develop a career within another sphere of employment.

  13. Making the Common Good Common

    ERIC Educational Resources Information Center

    Chase, Barbara

    2011-01-01

    How are independent schools to be useful to the wider world? Beyond their common commitment to educate their students for meaningful lives in service of the greater good, can they educate a broader constituency and, thus, share their resources and skills more broadly? Their answers to this question will be shaped by their independence. Any…

  14. Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1.

    PubMed

    Zhai, Jinbin; Lin, Hong; Julien, Jean-Pierre; Schlaepfer, William W

    2007-12-15

    Mutations in neurofilament light (NFL) subunit and small heat-shock protein B1 (HSPB1) cause autosomal-dominant axonal Charcot-Marie-Tooth disease type 2E (CMT2E) and type 2F (CMT2F). Previous studies have shown that CMT mutations in NFL and HSPB1 disrupt NF assembly and cause aggregation of NFL protein. In this study, we investigate the role of aggregation of NFL protein in the neurotoxicity of CMT mutant NFL and CMT mutant HSPB1 in motor neurons. We find that expression of CMT mutant NFL leads to progressive degeneration and loss of neuronal viability of cultured motor neurons. Degenerating motor neurons show fragmentation and loss of neuritic processes associated with disruption of NF network and aggregation of NFL protein. Co-expression of wild-type HSPB1 diminishes aggregation of CMT mutant NFL, induces reversal of CMT mutant NFL aggregates and reduces CMT mutant NFL-induced loss of motor neuron viability. Like CMT mutant NFL, expression of S135F CMT mutant HSPB1 also leads to progressive degeneration of motor neurons with disruption of NF network and aggregation of NFL protein. Further studies show that wild-type and S135F mutant HSPB1 associate with wild-type and CMT mutant NFL and that S135F mutant HSPB1 has dominant effect on disruption of NF assembly and aggregation of NFL protein. Finally, we show that deletion of NFL markedly reduces degeneration and loss of motor neuron viability induced by S135F mutant HSPB1. Together, our data support the view that disruption of NF network with aggregation of NFL is a common triggering event of motor neuron degeneration in CMT2E and CMT2F disease.

  15. Studies of transport pathways of Th, U, rare earths, Ra-228, and Ra-226 from soil to plants and farm animals: Final progress report, 1983-1988

    SciTech Connect

    Linsalata, P

    1988-07-01

    This report consists of three parts. Part 1 discusses a field study conducted in an area of enhanced, natural radioactivity to assess the soil to edible vegetable concentration ratios (CR = concentration in dry vegetable/concentration in dry soil) of Th-232, Th-230, Ra-226, Ra-228, and the light rare earth elements (REE's), La, Ce, and Nd. Twenty-eight soil, and approximately 42 vegetable samples consisting of relatively equal numbers of seven varieties, were obtained from 11 farms on the Pocos de Caldas Plateau in the state of Minas Gerais, Brazil. This region is the site of a major natural analogue study to assess the mobilization and retardation processes affecting thorium and the REE's at the Morro do Ferro ore body, and uranium series radionuclides at the Osamu Utsumi open pit uranium mine. Thorium (IV) serves as a chemical analogue for quadrivalent plutonium, the light REE's (III) as chemical analogues for trivalent americium and curium, and uranium (VI) as an analogue for transuranics with stable oxidation states above IV, e.g., Pu(VI). Part 2 includes our final measurement results for naturally occurring light rare earth elements (REE's include La, Ce, Nd, and SM), U-series and Th-series radionuclides in adult farm animal tissues, feeds and soils. Our findings on soil-to-tissue concentration ratios (CR's) and the comparative behavior of these elements in farm animals raised under natural conditions by local farmers are presented. Part 3 summarizes our findings to date on the distribution and mobilization of Th-232, light rare earth elements (LREE), U-238 and Ra-228 in the MF basin. Estimates of first order, present day, mobilization rate constants resulting from ground water solubilization and seepage/stream transport are calculated using revised inventory estimates for the occurrence of these elements in the ore body and annual flux estimates for the transport of these elements away from the ore body. 151 refs., 20 figs., 40 tabs.

  16. Development of fruit color in Solanaceae: a story of two biosynthetic pathways.

    PubMed

    Dhar, Manoj K; Sharma, Rupali; Koul, Archana; Kaul, Sanjana

    2015-05-01

    This review highlights the major differences between the regulation of two important pathways namely anthocyanin and carotenoid pathways, responsible for fruit color generation in Solanaceae mediated by transcription factors (TFs). The anthocyanin pathway is regulated by a common set of TFs (MYB, MYC and WD40) belonging to specific families of DNA-binding proteins. Their regulation is aimed at controlling the type and amount of pigments produced and the physiological conditions (like pH) at which they are finally stored. In the carotenoid pathway, the color diversity depends on the quantity of pigment produced and the point where the pathway is arrested. TFs in the latter case are accordingly found to influence the sequestration and degradation of these pigments, which determines their final concentration in the tissue. TFs (phytochrome interacting factors, MADS-BOX, HB-ZIP and B-ZIP) also regulate important rate-determining steps, which decide the direction in which the pathway proceeds and the point at which it is terminated. In the absence of a clear pattern of TF-mediated regulation, it is suggested that the carotenoid pathway is more significantly influenced by other regulatory methods which need to be explored. It is expected that common factors affecting these pathways are the ones acting much before the initiation of the biosynthesis of respective pigments.

  17. Common tester platform concept.

    SciTech Connect

    Hurst, Michael James

    2008-05-01

    This report summarizes the results of a case study on the doctrine of a common tester platform, a concept of a standardized platform that can be applicable across the broad spectrum of testing requirements throughout the various stages of a weapons program, as well as across the various weapons programs. The common tester concept strives to define an affordable, next-generation design that will meet testing requirements with the flexibility to grow and expand; supporting the initial development stages of a weapons program through to the final production and surveillance stages. This report discusses a concept investing key leveraging technologies and operational concepts combined with prototype tester-development experiences and practical lessons learned gleaned from past weapons programs.

  18. Technology Pathway Partnership Final Scientific Report

    SciTech Connect

    Hall, John C. Dr.; Godby, Larry A.

    2012-04-26

    This report covers the scientific progress and results made in the development of high efficiency multijunction solar cells and the light concentrating non-imaging optics for the commercial generation of renewable solar energy. During the contract period the efficiency of the multijunction solar cell was raised from 36.5% to 40% in commercially available fully qualified cells. In addition significant strides were made in automating production process for these cells in order to meet the costs required to compete with commercial electricity. Concurrent with the cells effort Boeing also developed a non imaging optical systems to raise the light intensity at the photovoltaic cell to the rage of 800 to 900 suns. Solar module efficiencies greater than 30% were consistently demonstrated. The technology and its manufacturing were maturated to a projected price of < $0.015 per kWh and demonstrated by automated assembly in a robotic factory with a throughput of 2 MWh/yr. The technology was demonstrated in a 100 kW power plant erected at California State University Northridge, CA.

  19. The MST/Hippo Pathway and Cell Death: A Non-Canonical Affair

    PubMed Central

    Fallahi, Emma; O’Driscoll, Niamh A.; Matallanas, David

    2016-01-01

    The MST/Hippo signalling pathway was first described over a decade ago in Drosophila melanogaster and the core of the pathway is evolutionary conserved in mammals. The mammalian MST/Hippo pathway regulates organ size, cell proliferation and cell death. In addition, it has been shown to play a central role in the regulation of cellular homeostasis and it is commonly deregulated in human tumours. The delineation of the canonical pathway resembles the behaviour of the Hippo pathway in the fly where the activation of the core kinases of the pathway prevents the proliferative signal mediated by the key effector of the pathway YAP. Nevertheless, several lines of evidence support the idea that the mammalian MST/Hippo pathway has acquired new features during evolution, including different regulators and effectors, crosstalk with other essential signalling pathways involved in cellular homeostasis and the ability to actively trigger cell death. Here we describe the current knowledge of the mechanisms that mediate MST/Hippo dependent cell death, especially apoptosis. We include evidence for the existence of complex signalling networks where the core proteins of the pathway play a central role in controlling the balance between survival and cell death. Finally, we discuss the possible involvement of these signalling networks in several human diseases such as cancer, diabetes and neurodegenerative disorders. PMID:27322327

  20. Final focus nomenclature

    SciTech Connect

    Erickson, R.

    1986-08-08

    The formal names and common names for all devices in the final focus system of the SLC are listed. The formal names consist of a device type designator, microprocessor designator, and a four-digit unit number. (LEW)

  1. The last common bilaterian ancestor

    NASA Technical Reports Server (NTRS)

    Erwin, Douglas H.; Davidson, Eric H.

    2002-01-01

    Many regulatory genes appear to be utilized in at least superficially similar ways in the development of particular body parts in Drosophila and in chordates. These similarities have been widely interpreted as functional homologies, producing the conventional view of the last common protostome-deuterostome ancestor (PDA) as a complex organism that possessed some of the same body parts as modern bilaterians. Here we discuss an alternative view, in which the last common PDA had a less complex body plan than is frequently conceived. This reconstruction alters expectations for Neoproterozoic fossil remains that could illustrate the pathways of bilaterian evolution.

  2. Common Cause Failure Modeling

    NASA Technical Reports Server (NTRS)

    Hark, Frank; Britton, Paul; Ring, Rob; Novack, Steven D.

    2015-01-01

    Common Cause Failures (CCFs) are a known and documented phenomenon that defeats system redundancy. CCFS are a set of dependent type of failures that can be caused by: system environments; manufacturing; transportation; storage; maintenance; and assembly, as examples. Since there are many factors that contribute to CCFs, the effects can be reduced, but they are difficult to eliminate entirely. Furthermore, failure databases sometimes fail to differentiate between independent and CCF (dependent) failure and data is limited, especially for launch vehicles. The Probabilistic Risk Assessment (PRA) of NASA's Safety and Mission Assurance Directorate at Marshall Space Flight Center (MFSC) is using generic data from the Nuclear Regulatory Commission's database of common cause failures at nuclear power plants to estimate CCF due to the lack of a more appropriate data source. There remains uncertainty in the actual magnitude of the common cause risk estimates for different systems at this stage of the design. Given the limited data about launch vehicle CCF and that launch vehicles are a highly redundant system by design, it is important to make design decisions to account for a range of values for independent and CCFs. When investigating the design of the one-out-of-two component redundant system for launch vehicles, a response surface was constructed to represent the impact of the independent failure rate versus a common cause beta factor effect on a system's failure probability. This presentation will define a CCF and review estimation calculations. It gives a summary of reduction methodologies and a review of examples of historical CCFs. Finally, it presents the response surface and discusses the results of the different CCFs on the reliability of a one-out-of-two system.

  3. Common Cause Failure Modeling

    NASA Technical Reports Server (NTRS)

    Hark, Frank; Britton, Paul; Ring, Rob; Novack, Steven D.

    2016-01-01

    Common Cause Failures (CCFs) are a known and documented phenomenon that defeats system redundancy. CCFS are a set of dependent type of failures that can be caused by: system environments; manufacturing; transportation; storage; maintenance; and assembly, as examples. Since there are many factors that contribute to CCFs, the effects can be reduced, but they are difficult to eliminate entirely. Furthermore, failure databases sometimes fail to differentiate between independent and CCF (dependent) failure and data is limited, especially for launch vehicles. The Probabilistic Risk Assessment (PRA) of NASA's Safety and Mission Assurance Directorate at Marshal Space Flight Center (MFSC) is using generic data from the Nuclear Regulatory Commission's database of common cause failures at nuclear power plants to estimate CCF due to the lack of a more appropriate data source. There remains uncertainty in the actual magnitude of the common cause risk estimates for different systems at this stage of the design. Given the limited data about launch vehicle CCF and that launch vehicles are a highly redundant system by design, it is important to make design decisions to account for a range of values for independent and CCFs. When investigating the design of the one-out-of-two component redundant system for launch vehicles, a response surface was constructed to represent the impact of the independent failure rate versus a common cause beta factor effect on a system's failure probability. This presentation will define a CCF and review estimation calculations. It gives a summary of reduction methodologies and a review of examples of historical CCFs. Finally, it presents the response surface and discusses the results of the different CCFs on the reliability of a one-out-of-two system.

  4. Common stemness regulators of embryonic and cancer stem cells.

    PubMed

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-10-26

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.

  5. Common stemness regulators of embryonic and cancer stem cells

    PubMed Central

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-01-01

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies. PMID:26516408

  6. [Common anemias in neonatology].

    PubMed

    Humbert, J; Wacker, P

    1999-01-28

    We describe the four most common groups of neonatal anemia and their treatments, with particular emphasis on erythropoietin therapy. The hemolytic anemias include the ABO incompatibility (much more frequent, nowadays, than the Rh incompatibility, which has nearly disappeared following the use of anti-D immunoglobulin in postpartum Rh-negative mothers), hereditary spherocytosis and G-6-PD deficiency. Among hypoplastic anemias, that caused by Parvovirus B19 predominates, by far, over Diamond-Blackfan anemia, alpha-thalassemia and the rare sideroblastic anemias. "Hemorrhagic" anemias occur during twin-to-twin transfusions, or during feto-maternal transfusions. Finally, the multifactorial anemia of prematurity develops principally as a result of the rapid expansion of the blood volume in this group of patients. Erythropoietin therapy, often at doses much higher than those used in the adult, should be seriously considered in most cases of non-hypoplastic neonatal anemias, to minimise maximally the use of transfusions.

  7. Molecular pathways in dystonia

    PubMed Central

    Bragg, D. Cristopher; Armata, Ioanna A.; Nery, Flavia C.; Breakefield, Xandra O.; Sharma, Nutan

    2011-01-01

    The hereditary dystonias comprise a set of diseases defined by a common constellation of motor deficits. These disorders are most likely associated with different molecular etiologies, many of which have yet to be elucidated. Here we discuss recent advances in three forms of hereditary dystonia, DYT1, DYT6 and DYT16, which share a similar clinical picture: onset in childhood or adolescence, progressive spread of symptoms with generalized involvement of body regions and a steady state affliction without treatment. Unlike DYT1, the genes responsible for DYT6 and DYT16 have only recently been identified, with relatively little information about the function of the encoded proteins. Nevertheless, recent data suggest that these proteins may fit together within interacting pathways involved in dopaminergic signaling, transcriptional regulation, and cellular stress responses. This review focuses on these molecular pathways, highlighting potential common themes among these dystonias which may serve as areas for future research. PMID:21134457

  8. WikiPathways: capturing the full diversity of pathway knowledge

    PubMed Central

    Kutmon, Martina; Riutta, Anders; Nunes, Nuno; Hanspers, Kristina; Willighagen, Egon L.; Bohler, Anwesha; Mélius, Jonathan; Waagmeester, Andra; Sinha, Sravanthi R.; Miller, Ryan; Coort, Susan L.; Cirillo, Elisa; Smeets, Bart; Evelo, Chris T.; Pico, Alexander R.

    2016-01-01

    WikiPathways (http://www.wikipathways.org) is an open, collaborative platform for capturing and disseminating models of biological pathways for data visualization and analysis. Since our last NAR update, 4 years ago, WikiPathways has experienced massive growth in content, which continues to be contributed by hundreds of individuals each year. New aspects of the diversity and depth of the collected pathways are described from the perspective of researchers interested in using pathway information in their studies. We provide updates on extensions and services to support pathway analysis and visualization via popular standalone tools, i.e. PathVisio and Cytoscape, web applications and common programming environments. We introduce the Quick Edit feature for pathway authors and curators, in addition to new means of publishing pathways and maintaining custom pathway collections to serve specific research topics and communities. In addition to the latest milestones in our pathway collection and curation effort, we also highlight the latest means to access the content as publishable figures, as standard data files, and as linked data, including bulk and programmatic access. PMID:26481357

  9. [Detecting shared pathways linked to rheumatoid arthritis with other autoimmune diseases in a in silico analysis].

    PubMed

    Zheng, W-Y; Zheng, W-X; Hua, L

    2016-01-01

    Pathway-based analysis approach has exploded in use during the last several years. It is successful in recognizing additional biological insight of disease and finding groupings of risk genes that represent disease developing processes. Therefore, shared pathways, with pleiotropic effects, are important for understanding similar pathogenesis and indicating the common genetic origin of certain diseases. Here, we present a pathway analysis to reveal the potential disease associations between RA and three potential RA-related autoimmune diseases: psoriasis, diabetes mellitus, type 1 (T1D) and systemic lupus erythematosus (SLE). First, a comprehensive knowledge mining of public databases is performed to discover risk genes associated with RA, T1D, SLE and psoriasis; then by enrichment test of these genes, disease-related risk pathways are detected to recognize the pathways common for RA and three other diseases. Finally, the underlying disease associations are evaluated with the association rules mining method. In total, we identify multiple RA risk pathways with significant pleiotropic effects, the most unsurprising of which are the immunology related pathways. Meanwhile for the first time we highlight the involvement of the viral myocarditis pathway related to cardiovascular disease (CVD) in autoimmune diseases such as RA, psoriasis, T1D and SLE. Further Association rule mining results validate the strong association between RA and T1D and RA and SLE. It is clear that pleiotropy is a common property of pathways associated with disease traits. We provide novel pathway associations among RA and three autoimmune diseases. These results ascertain that there are shared genetic risk profiles that predispose individuals to autoimmune diseases. PMID:27414792

  10. No Common Opinion on the Common Core

    ERIC Educational Resources Information Center

    Henderson, Michael B.; Peterson, Paul E.; West, Martin R.

    2015-01-01

    According to the three authors of this article, the 2014 "EdNext" poll yields four especially important new findings: (1) Opinion with respect to the Common Core has yet to coalesce. The idea of a common set of standards across the country has wide appeal, and the Common Core itself still commands the support of a majority of the public.…

  11. The design of PC/MISI, a PC-based common user interface to remote information storage and retrieval systems. Presentation visuals. M.S. Thesis Final Report, 1 Jul. 1985 - 31 Dec. 1987

    NASA Technical Reports Server (NTRS)

    Dominick, Wayne D. (Editor); Hall, Philip P.

    1985-01-01

    This Working Paper Series entry represents a collection of presentation visuals associated with the companion report entitled, The Design of PC/MISI, a PC-Based Common User Interface to Remote Information Storage and Retrieval Systems, USL/DBMS NASA/RECON Working Paper Series report number DBMS.NASA/RECON-15. The paper discusses the following: problem definition; the PC solution; the goals of system design; the design description; future considerations, the research environment; conclusions.

  12. Common Cause Failure Modeling

    NASA Technical Reports Server (NTRS)

    Hark, Frank; Britton, Paul; Ring, Robert; Novack, Steven

    2015-01-01

    Space Launch System (SLS) Agenda: Objective; Key Definitions; Calculating Common Cause; Examples; Defense against Common Cause; Impact of varied Common Cause Failure (CCF) and abortability; Response Surface for various CCF Beta; Takeaways.

  13. Nutrient Sensing Mechanisms and Pathways

    PubMed Central

    Efeyan, Alejo; Comb, William C.; Sabatini, David M.

    2015-01-01

    PREFACE The ability to sense and respond to fluctuations in environmental nutrient levels is a requisite for life. Nutrient scarcity is a selective pressure that has shaped the evolution of most cellular processes. Different pathways that detect intracellular and extracellular levels of sugars, amino acids and lipids, and surrogate metabolites, are then integrated and coordinated at the organismal level via hormonal signals. During food abundance, nutrient sensing pathways engage anabolism and storage, and scarcity triggers homeostatic mechanisms, like the mobilization of internal stores through mechanisms such as autophagy. Nutrient sensing pathways are commonly deregulated in human metabolic diseases. PMID:25592535

  14. Vestibular pathways involved in cognition

    PubMed Central

    Hitier, Martin; Besnard, Stephane; Smith, Paul F.

    2014-01-01

    Recent discoveries have emphasized the role of the vestibular system in cognitive processes such as memory, spatial navigation and bodily self-consciousness. A precise understanding of the vestibular pathways involved is essential to understand the consequences of vestibular diseases for cognition, as well as develop therapeutic strategies to facilitate recovery. The knowledge of the “vestibular cortical projection areas”, defined as the cortical areas activated by vestibular stimulation, has dramatically increased over the last several years from both anatomical and functional points of view. Four major pathways have been hypothesized to transmit vestibular information to the vestibular cortex: (1) the vestibulo-thalamo-cortical pathway, which probably transmits spatial information about the environment via the parietal, entorhinal and perirhinal cortices to the hippocampus and is associated with spatial representation and self-versus object motion distinctions; (2) the pathway from the dorsal tegmental nucleus via the lateral mammillary nucleus, the anterodorsal nucleus of the thalamus to the entorhinal cortex, which transmits information for estimations of head direction; (3) the pathway via the nucleus reticularis pontis oralis, the supramammillary nucleus and the medial septum to the hippocampus, which transmits information supporting hippocampal theta rhythm and memory; and (4) a possible pathway via the cerebellum, and the ventral lateral nucleus of the thalamus (perhaps to the parietal cortex), which transmits information for spatial learning. Finally a new pathway is hypothesized via the basal ganglia, potentially involved in spatial learning and spatial memory. From these pathways, progressively emerges the anatomical network of vestibular cognition. PMID:25100954

  15. Vestibular pathways involved in cognition.

    PubMed

    Hitier, Martin; Besnard, Stephane; Smith, Paul F

    2014-01-01

    Recent discoveries have emphasized the role of the vestibular system in cognitive processes such as memory, spatial navigation and bodily self-consciousness. A precise understanding of the vestibular pathways involved is essential to understand the consequences of vestibular diseases for cognition, as well as develop therapeutic strategies to facilitate recovery. The knowledge of the "vestibular cortical projection areas", defined as the cortical areas activated by vestibular stimulation, has dramatically increased over the last several years from both anatomical and functional points of view. Four major pathways have been hypothesized to transmit vestibular information to the vestibular cortex: (1) the vestibulo-thalamo-cortical pathway, which probably transmits spatial information about the environment via the parietal, entorhinal and perirhinal cortices to the hippocampus and is associated with spatial representation and self-versus object motion distinctions; (2) the pathway from the dorsal tegmental nucleus via the lateral mammillary nucleus, the anterodorsal nucleus of the thalamus to the entorhinal cortex, which transmits information for estimations of head direction; (3) the pathway via the nucleus reticularis pontis oralis, the supramammillary nucleus and the medial septum to the hippocampus, which transmits information supporting hippocampal theta rhythm and memory; and (4) a possible pathway via the cerebellum, and the ventral lateral nucleus of the thalamus (perhaps to the parietal cortex), which transmits information for spatial learning. Finally a new pathway is hypothesized via the basal ganglia, potentially involved in spatial learning and spatial memory. From these pathways, progressively emerges the anatomical network of vestibular cognition.

  16. Common Career Technical Core: Common Standards, Common Vision for CTE

    ERIC Educational Resources Information Center

    Green, Kimberly

    2012-01-01

    This article provides an overview of the National Association of State Directors of Career Technical Education Consortium's (NASDCTEc) Common Career Technical Core (CCTC), a state-led initiative that was created to ensure that career and technical education (CTE) programs are consistent and high quality across the United States. Forty-two states,…

  17. Education, Psychology, and Social Science: Common Pathways for Teaching Peace.

    ERIC Educational Resources Information Center

    Stomfay-Stitz, Aline M.

    This paper explores the contributions of several disciplines of the social sciences to peace education and peace psychology and focuses on positive gains in several aspects of peace education and conflict resolution witnessed by the researcher in over 10 years of work. The paper contains the following sections: (1) Introduction; (2) "Definitions…

  18. IDENTIFICATION OF COMMON GENES AND PATHWAYS REGULATED BY PPARÁ ACTIVATORS

    EPA Science Inventory

    Exposure to peroxisome proliferator chemicals (PPC) leads to alterations in the balance between hepatocyte growth and apoptosis, increases in liver to body weights (LW/BW) and liver tumors. There is strong evidence that PPC cause many of their effects related to carcinogenesis th...

  19. MPW : the metabolic pathways database.

    SciTech Connect

    Selkov, E., Jr.; Grechkin, Y.; Mikhailova, N.; Selkov, E.; Mathematics and Computer Science; Russian Academy of Sciences

    1998-01-01

    The Metabolic Pathways Database (MPW) (www.biobase.com/emphome.html/homepage. html.pags/pathways.html) a derivative of EMP (www.biobase.com/EMP) plays a fundamental role in the technology of metabolic reconstructions from sequenced genomes under the PUMA (www.mcs.anl.gov/home/compbio/PUMA/Production/ ReconstructedMetabolism/reconstruction.html), WIT (www.mcs.anl.gov/home/compbio/WIT/wit.html ) and WIT2 (beauty.isdn.msc.anl.gov/WIT2.pub/CGI/user.cgi) systems. In October 1997, it included some 2800 pathway diagrams covering primary and secondary metabolism, membrane transport, signal transduction pathways, intracellular traffic, translation and transcription. In the current public release of MPW (beauty.isdn.mcs.anl.gov/MPW), the encoding is based on the logical structure of the pathways and is represented by the objects commonly used in electronic circuit design. This facilitates drawing and editing the diagrams and makes possible automation of the basic simulation operations such as deriving stoichiometric matrices, rate laws, and, ultimately, dynamic models of metabolic pathways. Individual pathway diagrams, automatically derived from the original ASCII records, are stored as SGML instances supplemented by relational indices. An auxiliary database of compound names and structures, encoded in the SMILES format, is maintained to unambiguously connect the pathways to the chemical structures of their intermediates.

  20. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging

    PubMed Central

    Steelman, Linda S.; Chappell, William H.; Abrams, Stephen L.; Kempf, C. Ruth; Long, Jacquelyn; Laidler, Piotr; Mijatovic, Sanja; Maksimovic-Ivanic, Danijela; Stivala, Franca; Mazzarino, Maria C.; Donia, Marco; Fagone, Paolo; Malaponte, Graziella; Nicoletti, Ferdinando; Libra, Massimo; Milella, Michele; Tafuri, Agostino; Bonati, Antonio; Bäsecke, Jörg; Cocco, Lucio; Evangelisti, Camilla; Martelli, Alberto M.; Montalto, Giuseppe; Cervello, Melchiorre; McCubrey, James A.

    2011-01-01

    Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health. PMID:21422497

  1. Clerkship pathway

    PubMed Central

    MacLellan, Anne-Marie; Brailovsky, Carlos; Miller, François; Leboeuf, Sylvie

    2012-01-01

    Abstract Objective To identify factors that help predict success for international medical graduates (IMGs) who train in Canadian residency programs and pass the Canadian certification examinations. Design A retrospective analysis of 58 variables in the files of IMGs who applied to the Collège des médecins du Québec between 2000 and 2008. Setting Quebec. Participants Eight hundred ten IMGs who applied to the Collège des médecins du Québec through either the “equivalency pathway” (ie, starting training at a residency level) or the “clerkship pathway” (ie, relearning at the level of a medical student in the last 2 years of the MD diploma). Main outcome measures Success factors in achieving certification. Data were analyzed using descriptive statistics and ANOVA (analysis of variance). Results International medical graduates who chose the “clerkship pathway” had greater success on certification examinations than those who started at the residency level did. Conclusion There are several factors that influence IMGs’ success on certification examinations, including integration issues, the acquisition of clinical decision-making skills, and the varied educational backgrounds. These factors perhaps can be better addressed by a regular clerkship pathway, in which IMGs benefit from learner-centred teaching and have more time for reflection on and understanding of the North American approach to medical education. The clerkship pathway is a useful strategy for assuring the integration of IMGs in the North American health care system. A 2-year relearning period in medical school at a clinical clerkship level deserves careful consideration. PMID:22859630

  2. Pathway-based network analysis of myeloma tumors: monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and multiple myeloma.

    PubMed

    Dong, L; Chen, C Y; Ning, B; Xu, D L; Gao, J H; Wang, L L; Yan, S Y; Cheng, S

    2015-01-01

    Although many studies have been carried out on monoclonal gammopathy of unknown significances (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM), their classification and underlying pathogenesis are far from elucidated. To discover the relationships among MGUS, SMM, and MM at the transcriptome level, differentially expressed genes in MGUS, SMM, and MM were identified by the rank product method, and then co-expression networks were constructed by integrating the data. Finally, a pathway-network was constructed based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and the relationships between the pathways were identified. The results indicated that there were 55, 78, and 138 pathways involved in the myeloma tumor developmental stages of MGUS, SMM, and MM, respectively. The biological processes identified therein were found to have a close relationship with the immune system. Processes and pathways related to the abnormal activity of DNA and RNA were also present in SMM and MM. Six common pathways were found in the whole process of myeloma tumor development. Nine pathways were shown to participate in the progression of MGUS to SMM, and prostate cancer was the sole pathway that was involved only in MGUS and MM. Pathway-network analysis might provide a new indicator for the developmental stage diagnosis of myeloma tumors. PMID:26345890

  3. Common Interventional Radiology Procedures

    MedlinePlus

    ... of common interventional techniques is below. Common Interventional Radiology Procedures Angiography An X-ray exam of the ... into the vertebra. Copyright © 2016 Society of Interventional Radiology. All rights reserved. 3975 Fair Ridge Drive • Suite ...

  4. How Common Is the Common Core?

    ERIC Educational Resources Information Center

    Thomas, Amande; Edson, Alden J.

    2014-01-01

    Since the introduction of the Common Core State Standards for Mathematics (CCSSM) in 2010, stakeholders in adopting states have engaged in a variety of activities to understand CCSSM standards and transition from previous state standards. These efforts include research, professional development, assessment and modification of curriculum resources,…

  5. Badges: A Common Currency for Learning

    ERIC Educational Resources Information Center

    Bowen, Kyle; Thomas, Andrea

    2014-01-01

    Digital Badges--icons that can represent skills and achievements at a more fine-grained level than a degree--give colleges and universities a new way to document learning outcomes and to map the pathways students follow to earn a degree. They also provide a common currency to denote learning outcomes and give employers a visual representation and…

  6. The New Common School.

    ERIC Educational Resources Information Center

    Glenn, Charles L.

    1987-01-01

    Horace Mann's goal of creating a common school that brings our society's children together in mutual respect and common learning need not be frustrated by residential segregation and geographical separation of the haves and have-nots. Massachusetts' new common school vision boasts a Metro Program for minority students, 80 magnet schools, and…

  7. Knowledge representation for commonality

    NASA Technical Reports Server (NTRS)

    Yeager, Dorian P.

    1990-01-01

    Domain-specific knowledge necessary for commonality analysis falls into two general classes: commonality constraints and costing information. Notations for encoding such knowledge should be powerful and flexible and should appeal to the domain expert. The notations employed by the Commonality Analysis Problem Solver (CAPS) analysis tool are described. Examples are given to illustrate the main concepts.

  8. Canonical Commonality Analysis.

    ERIC Educational Resources Information Center

    Leister, K. Dawn

    Commonality analysis is a method of partitioning variance that has advantages over more traditional "OVA" methods. Commonality analysis indicates the amount of explanatory power that is "unique" to a given predictor variable and the amount of explanatory power that is "common" to or shared with at least one predictor variable. This paper outlines…

  9. "Common synthetic scaffolds" in the synthesis of structurally diverse natural products.

    PubMed

    Anagnostaki, Elissavet E; Zografos, Alexandros L

    2012-09-01

    Selected natural products have long been considered as desirable targets for total synthesis due to their unique biological properties and their challenging structural complexity. Laboratory synthesis of natural compounds usually relies on target-oriented synthesis, involving the production, isolation and purification of successive intermediates, requiring multiple steps to arrive to the final product. A far more economical approach using common synthetic scaffolds that can be readily transformed through biomimetic-like pathways to a range of structurally diverse natural products has been evolved in the last decade, leading synthesis to new directions. This tutorial review critically presents the hallmarks in this field.

  10. Conserved genetic pathways associated with microphthalmia, anophthalmia, and coloboma.

    PubMed

    Reis, Linda M; Semina, Elena V

    2015-06-01

    The human eye is a complex organ whose development requires extraordinary coordination of developmental processes. The conservation of ocular developmental steps in vertebrates suggests possible common genetic mechanisms. Genetic diseases involving the eye represent a leading cause of blindness in children and adults. During the last decades, there has been an exponential increase in genetic studies of ocular disorders. In this review, we summarize current success in identification of genes responsible for microphthalmia, anophthalmia, and coloboma (MAC) phenotypes, which are associated with early defects in embryonic eye development. Studies in animal models for the orthologous genes identified overlapping phenotypes for most factors, confirming the conservation of their function in vertebrate development. These animal models allow for further investigation of the mechanisms of MAC, integration of various identified genes into common developmental pathways and finally, provide an avenue for the development and testing of therapeutic interventions.

  11. Using the attract method to identify core pathways in juvenile idiopathic arthritis.

    PubMed

    Li, J S; Gao, X L; Liu, Y R; Dong, Y

    2016-01-01

    The aim of this study was to identify core pathways associated with juvenile idiopathic arthritis (JIA) using the attract method. Kyoto Encyclopedia of Genes and Genomes pathways were determined using the GSEA-ANOVA method, based on the gene expression data of JIA. Syn-expression groups within core attractor pathways were identified by hierarchical clustering. Correlated sets of genes exhibiting highly similar profiles to the syn-expression groups were identified and each correlated set was subjected to a gene ontology functional enrichment analysis to discover potentially shared biological themes. Based on a false-discovery rate < 0.05, we identified 11 significant pathways were identified as potential attractors. Flag genes or uninformative genes were removed and 5 discriminative pathways: the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were identified. A final set of syn-expression groups with a consistent trend of relative expression of pathway-related genes was obtained; that is, the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were composed of 2, 2, 1, 2, and 3 clusters, respectively. Genes in each correlated set shared common roles, and changes at the pathway level were more likely to be real. In light of these, the attract method was able to on expand important context to find distinguishing expression patterns within pathways. This paper predicted that the functional themes involved in protein synthesis (such as proteasome, ribosome, spliceosome) were closely related to the progression of JIA, which might contribute to the detection of therapy target for JIA. PMID:27525947

  12. The evolution of fungal metabolic pathways.

    PubMed

    Wisecaver, Jennifer H; Slot, Jason C; Rokas, Antonis

    2014-12-01

    Fungi contain a remarkable range of metabolic pathways, sometimes encoded by gene clusters, enabling them to digest most organic matter and synthesize an array of potent small molecules. Although metabolism is fundamental to the fungal lifestyle, we still know little about how major evolutionary processes, such as gene duplication (GD) and horizontal gene transfer (HGT), have interacted with clustered and non-clustered fungal metabolic pathways to give rise to this metabolic versatility. We examined the synteny and evolutionary history of 247,202 fungal genes encoding enzymes that catalyze 875 distinct metabolic reactions from 130 pathways in 208 diverse genomes. We found that gene clustering varied greatly with respect to metabolic category and lineage; for example, clustered genes in Saccharomycotina yeasts were overrepresented in nucleotide metabolism, whereas clustered genes in Pezizomycotina were more common in lipid and amino acid metabolism. The effects of both GD and HGT were more pronounced in clustered genes than in their non-clustered counterparts and were differentially distributed across fungal lineages; specifically, GD, which was an order of magnitude more abundant than HGT, was most frequently observed in Agaricomycetes, whereas HGT was much more prevalent in Pezizomycotina. The effect of HGT in some Pezizomycotina was particularly strong; for example, we identified 111 HGT events associated with the 15 Aspergillus genomes, which sharply contrasts with the 60 HGT events detected for the 48 genomes from the entire Saccharomycotina subphylum. Finally, the impact of GD within a metabolic category was typically consistent across all fungal lineages, whereas the impact of HGT was variable. These results indicate that GD is the dominant process underlying fungal metabolic diversity, whereas HGT is episodic and acts in a category- or lineage-specific manner. Both processes have a greater impact on clustered genes, suggesting that metabolic gene clusters

  13. An algorithm for linear metabolic pathway alignment.

    PubMed

    Chen, Ming; Hofestaedt, Ralf

    2005-01-01

    Metabolic pathway alignment represents one of the most powerful tools for comparative analysis of metabolism. It involves recognition of metabolites common to a set of functionally-related metabolic pathways, interpretation of biological evolution processes and determination of alternative metabolic pathways. Moreover, it is of assistance in function prediction and metabolism modeling. Although research on genomic sequence alignment is extensive, the problem of aligning metabolic pathways has received less attention. We are motivated to develop an algorithm of metabolic pathway alignment to reveal the similarities between metabolic pathways. A new definition of the metabolic pathway is introduced. The algorithm has been implemented into the PathAligner system; its web-based interface is available at http://bibiserv.techfak.uni-bielefeld.de/pathaligner/.

  14. Final Report

    SciTech Connect

    Normanly, J.

    1999-11-29

    The primary goal was the characterization of tryptophan (Trp)-independent biosynthesis of the auxin indole-3-acetic acid (IAA). Our work and that of others indicates that indole is a precursor to IAA in a Trp-independent pathway and the objectives of this grant have been the isolation of indole-metabolizing genes from Arabidopsis.

  15. Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile

    PubMed Central

    Mercken, Evi M.; Crosby, Seth D.; Lamming, Dudley W.; JeBailey, Lellean; Krzysik-Walker, Susan; Villareal, Dennis; Capri, Miriam; Franceschi, Claudio; Zhang, Yongqing; Becker, Kevin; Sabatini, David M.; de Cabo, Rafael; Fontana, Luigi

    2013-01-01

    Summary Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR-induced dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis and inflammation. Furthermore, our data identifies promising pathways for therapeutic targets to combat age-related diseases and promote health in humans. PMID:23601134

  16. Collateral Pathways in Portal Hypertension

    PubMed Central

    Sharma, Malay; Rameshbabu, Chittapuram S.

    2012-01-01

    Presence of portosystemic collateral veins (PSCV) is common in portal hypertension due to cirrhosis. Physiologically, normal portosystemic anastomoses exist which exhibit hepatofugal flow. With the development of portal hypertension, transmission of backpressure leads to increased flow in these patent normal portosystemic anastomoses. In extrahepatic portal vein obstruction collateral circulation develops in a hepatopetal direction and portoportal pathways are frequently found. The objective of this review is to illustrate the various PSCV and portoportal collateral vein pathways pertinent to portal hypertension in liver cirrhosis and EHPVO. PMID:25755456

  17. Final Report

    SciTech Connect

    DeTar, Carleton

    2012-12-10

    This document constitutes the Final Report for award DE-FC02-06ER41446 as required by the Office of Science. It summarizes accomplishments and provides copies of scientific publications with significant contribution from this award.

  18. Final Report

    SciTech Connect

    Gurney, Kevin R.

    2015-01-12

    This document constitutes the final report under DOE grant DE-FG-08ER64649. The organization of this document is as follows: first, I will review the original scope of the proposed research. Second, I will present the current draft of a paper nearing submission to Nature Climate Change on the initial results of this funded effort. Finally, I will present the last phase of the research under this grant which has supported a Ph.D. student. To that end, I will present the graduate student’s proposed research, a portion of which is completed and reflected in the paper nearing submission. This final work phase will be completed in the next 12 months. This final workphase will likely result in 1-2 additional publications and we consider the results (as exemplified by the current paper) high quality. The continuing results will acknowledge the funding provided by DOE grant DE-FG-08ER64649.

  19. Conceptualizing an Information Commons.

    ERIC Educational Resources Information Center

    Beagle, Donald

    1999-01-01

    Concepts from Strategic Alignment, a technology-management theory, are used to discuss the Information Commons as a new service-delivery model in academic libraries. The Information Commons, as a conceptual, physical, and instructional space, involves an organizational realignment from print to the digital environment. (Author)

  20. Campus Common Law

    ERIC Educational Resources Information Center

    Bakken, Gordon Morris

    1976-01-01

    Discusses the legal principle of common law as it applies to the personnel policies of colleges and universities in an attempt to define the parameters of campus common law and to clarify its relationship to written university policies and relevant state laws. (JG)

  1. Evolution of the TOR pathway.

    PubMed

    van Dam, Teunis J P; Zwartkruis, Fried J T; Bos, Johannes L; Snel, Berend

    2011-10-01

    The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and provide a practical framework on which experimental evidence can be compared between species. Here we performed phylogenetic analyses on the components of the TOR pathway and determined their point of invention. We find that the two TOR complexes and a large part of the TOR pathway originated before the Last Eukaryotic Common Ancestor and form a core to which new inputs have been added during animal evolution. In addition, we provide insight into how duplications and sub-functionalization of the S6K, RSK, SGK and PKB kinases shaped the complexity of the TOR pathway. In yeast we identify novel AGC kinases that are orthologous to the S6 kinase. These results demonstrate how a vital signaling pathway can be both highly conserved and flexible in eukaryotes.

  2. Communication and common interest.

    PubMed

    Godfrey-Smith, Peter; Martínez, Manolo

    2013-01-01

    Explaining the maintenance of communicative behavior in the face of incentives to deceive, conceal information, or exaggerate is an important problem in behavioral biology. When the interests of agents diverge, some form of signal cost is often seen as essential to maintaining honesty. Here, novel computational methods are used to investigate the role of common interest between the sender and receiver of messages in maintaining cost-free informative signaling in a signaling game. Two measures of common interest are defined. These quantify the divergence between sender and receiver in their preference orderings over acts the receiver might perform in each state of the world. Sampling from a large space of signaling games finds that informative signaling is possible at equilibrium with zero common interest in both senses. Games of this kind are rare, however, and the proportion of games that include at least one equilibrium in which informative signals are used increases monotonically with common interest. Common interest as a predictor of informative signaling also interacts with the extent to which agents' preferences vary with the state of the world. Our findings provide a quantitative description of the relation between common interest and informative signaling, employing exact measures of common interest, information use, and contingency of payoff under environmental variation that may be applied to a wide range of models and empirical systems.

  3. Clathrin-Independent Pathways of Endocytosis

    PubMed Central

    Mayor, Satyajit; Parton, Robert G.; Donaldson, Julie G.

    2014-01-01

    There are many pathways of endocytosis at the cell surface that apparently operate at the same time. With the advent of new molecular genetic and imaging tools, an understanding of the different ways by which a cell may endocytose cargo is increasing by leaps and bounds. In this review we explore pathways of endocytosis that occur in the absence of clathrin. These are referred to as clathrin-independent endocytosis (CIE). Here we primarily focus on those pathways that function at the small scale in which some have distinct coats (caveolae) and others function in the absence of specific coated intermediates. We follow the trafficking itineraries of the material endocytosed by these pathways and finally discuss the functional roles that these pathways play in cell and tissue physiology. It is likely that these pathways will play key roles in the regulation of plasma membrane area and tension and also control the availability of membrane during cell migration. PMID:24890511

  4. Activation of ERK and JNK signaling pathways by mycotoxin citrinin in human cells

    SciTech Connect

    Chang, C.-H.; Yu, F.-Y.; Wang, L.-T.; Lin, Y.-S.; Liu, B.-H.

    2009-06-15

    Mycotoxin citrinin (CTN) is commonly found in foods and feeds that are contaminated/inoculated with Penicillium, Aspergillus and Monascus species. The exposure of human embryonic kidney (HEK293) and HeLa cells to CTN resulted in a dose-dependent increase in the phosphorylation of two major mitogen-activated protein kinases (MAPKs), ERK1/2 and JNK. In HEK293 cultures, the administering of CTN increased both the mRNA and protein levels of egr-1, c-fos and c-jun genes; additionally, the ERK1/2 pathway contributed to the upregulation of Egr-1 and c-Fos protein expression. CTN treatment also induced the transcription activity of Egr-1 and AP-1 proteins, as evidenced by luciferase reporter assays. Bioinformatic analyses indicated two genes Gadd45{beta} and MMP3 have Egr-1 and AP-1 response elements in their promoters, respectively. Furthermore, co-exposure of HEK293 cells to CTN and MAPK pathway inhibitors demonstrated that CTN increased the levels of Gadd45{beta} mRNA through ERK1/2 signaling pathway and up-regulated the MMP3 transcripts majorly via JNK pathway. Finally, CTN-triggered caspase 3 activity was significantly reduced in the presence of MAPK inhibitors. Our results suggest that CTN positively regulates ERK1/2 and JNK pathways as well as their downstream effectors in human cells; activated MAPK pathways are also involved in CTN-induced apoptosis.

  5. AIP's Career Pathways Project

    NASA Astrophysics Data System (ADS)

    Avila, Jose

    2014-03-01

    The American Institute of Physics (AIP) Career Pathways Project, funded by the National Science Foundation, aims to increase the number of undergraduates going into STEM careers. The main purposes of this project are to show students the professional opportunities for a STEM career, understand what departments can do to better prepare physics bachelor's degree recipients to enter the workforce, understand what students can do to better prepare themselves, and develop resources based on these findings. I was chosen by the Society of Physics Students (SPS) to be the 2013 summer intern of the AIP's Career Pathways Project. In this talk I will discuss several resources I worked on with the Statistical Research Center of the American Institute of Physics and SPS. These resources include how to write a resume and cover letter, how to perform an informational interview, common job titles for physics bachelors, how to find career information in physics and STEM, how to search and use job postings, and how to network.

  6. Evolutionarily conserved Δ25(27)-olefin ergosterol biosynthesis pathway in the alga Chlamydomonas reinhardtii

    PubMed Central

    Miller, Matthew B.; Haubrich, Brad A.; Wang, Qian; Snell, William J.; Nes, W. David

    2012-01-01

    Ergosterol is the predominant sterol of fungi and green algae. Although the biosynthetic pathway for sterol synthesis in fungi is well established and is known to use C24-methylation-C24 (28)-reduction (Δ24(28)-olefin pathway) steps, little is known about the sterol pathway in green algae. Previous work has raised the possibility that these algae might use a novel pathway because the green alga Chlamydomonas reinhardtii was shown to possess a mevalonate-independent methylerythritol 4-phosphate not present in fungi. Here, we report that C. reinhardtii synthesizes the protosterol cycloartenol and converts it to ergosterol (C24β-methyl) and 7-dehydroporiferasterol (C24β-ethyl) through a highly conserved sterol C24- methylation-C25-reduction (Δ25(27)-olefin) pathway that is distinct from the well-described acetate-mevalonate pathway to fungal lanosterol and its conversion to ergosterol by the Δ24 (28)-olefin pathway. We isolated and characterized 23 sterols by a combination of GC-MS and proton nuclear magnetic resonance spectroscopy analysis from a set of mutant, wild-type, and 25-thialanosterol-treated cells. The structure and stereochemistry of the final C24-alkyl sterol side chains possessed different combinations of 24β-methyl/ethyl groups and Δ22(23)E and Δ25 (27)-double bond constructions. When incubated with [methyl-2H3]methionine, cells incorporated three (into ergosterol) or five (into 7-dehydroporiferasterol) deuterium atoms into the newly biosynthesized 24β-alkyl sterols, consistent only with a Δ25 (27)-olefin pathway. Thus, our findings demonstrate that two separate isoprenoid-24-alkyl sterol pathways evolved in fungi and green algae, both of which converge to yield a common membrane insert ergosterol. PMID:22591742

  7. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2004-01-01

    Part of the 2003 industrial minerals review. The legislation, production, and consumption of common clay and shale are discussed. The average prices of the material and outlook for the market are provided.

  8. ACS: ALMA Common Software

    NASA Astrophysics Data System (ADS)

    Chiozzi, Gianluca; Šekoranja, Matej

    2013-02-01

    ALMA Common Software (ACS) provides a software infrastructure common to all ALMA partners and consists of a documented collection of common patterns and components which implement those patterns. The heart of ACS is based on a distributed Component-Container model, with ACS Components implemented as CORBA objects in any of the supported programming languages. ACS provides common CORBA-based services such as logging, error and alarm management, configuration database and lifecycle management. Although designed for ALMA, ACS can and is being used in other control systems and distributed software projects, since it implements proven design patterns using state of the art, reliable technology. It also allows, through the use of well-known standard constructs and components, that other team members whom are not authors of ACS easily understand the architecture of software modules, making maintenance affordable even on a very large project.

  9. Barry Commoner Assails Petrochemicals

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1973

    1973-01-01

    Discusses Commoner's ideas on the social value of the petrochemical industry and his suggestions for curtailment or elimination of its productive operation to produce a higher environmental quality for mankind at a relatively low loss in social benefit. (CC)

  10. Genomic Data Commons launches

    Cancer.gov

    The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

  11. Medicolegal Implications of Common Rhinologic Medications.

    PubMed

    Poetker, David M; Smith, Timothy L

    2015-10-01

    As otolaryngologists, we prescribe many medications to our patients. The objective of this article is to review the potential side effects and medicolegal risks of the common medications used to treat chronic rhinosinusitis. The authors evaluate some of the common side effects as well as the published literature on the lawsuits associated with those medications. Finally, the authors review the informed consent discussion and opportunities to improve patient care and decrease the risk of litigation.

  12. Common Metrics for Human-Robot Interaction

    NASA Technical Reports Server (NTRS)

    Steinfeld, Aaron; Lewis, Michael; Fong, Terrence; Scholtz, Jean; Schultz, Alan; Kaber, David; Goodrich, Michael

    2006-01-01

    This paper describes an effort to identify common metrics for task-oriented human-robot interaction (HRI). We begin by discussing the need for a toolkit of HRI metrics. We then describe the framework of our work and identify important biasing factors that must be taken into consideration. Finally, we present suggested common metrics for standardization and a case study. Preparation of a larger, more detailed toolkit is in progress.

  13. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2011-01-01

    The article discusses the latest developments in the global common clay and shale industry, particularly in the U.S. It claims that common clay and shale is mainly used in the manufacture of heavy clay products like brick, flue tile and sewer pipe. The main producing states in the U.S. include North Carolina, New York and Oklahoma. Among the firms that manufacture clay and shale-based products are Mid America Brick & Structural Clay Products LLC and Boral USA.

  14. Common skin conditions.

    PubMed Central

    Ridley, M.; Safranek, M.

    1992-01-01

    Four common conditions: acne, psoriasis, eczema and urticaria are considered. Guidance is given on appropriate topical and systematic treatment for the different types and degrees of these conditions, with notes on management in general and criteria for referral to hospital outpatient departments. Where there are different types of the condition, with varying aetiology, for example in urticaria and eczema, management of the common types is outlined. PMID:1345156

  15. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2006-01-01

    At present, 150 companies produce common clay and shale in 41 US states. According to the United States Geological Survey (USGS), domestic production in 2005 reached 24.8 Mt valued at $176 million. In decreasing order by tonnage, the leading producer states include North Carolina, Texas, Alabama, Georgia and Ohio. For the whole year, residential and commercial building construction remained the major market for common clay and shale products such as brick, drain tile, lightweight aggregate, quarry tile and structural tile.

  16. Final Words

    ERIC Educational Resources Information Center

    Bers, Trudy

    2012-01-01

    This final chapter provides observations about institutional research in community colleges derived from the preceding chapters and the issue editors' own experiences. Taken as a whole, the chapters in this issue, as well as the editors' experiences, suggest several observations about institutional research in community colleges. These include the…

  17. Use of international data sets to evaluate and validate pathway assessment models applicable to exposure and dose reconstruction at DOE facilities. Monthly progress reports and final report, October--December 1994

    SciTech Connect

    Hoffman, F.O.

    1995-04-01

    The objective of Task 7.lD was to (1) establish a collaborative US-USSR effort to improve and validate our methods of forecasting doses and dose commitments from the direct contamination of food sources, and (2) perform experiments and validation studies to improve our ability to predict rapidly and accurately the long-term internal dose from the contamination of agricultural soil. At early times following an accident, the direct contamination of pasture and food stuffs, particularly leafy vegetation and grain, can be of great importance. This situation has been modeled extensively. However, models employed then to predict the deposition, retention and transport of radionuclides in terrestrial environments employed concepts and data bases that were more than a decade old. The extent to which these models have been tested with independent data sets was limited. The data gathered in the former-USSR (and elsewhere throughout the Northern Hemisphere) offered a unique opportunity to test model predictions of wet and dry deposition, agricultural foodchain bioaccumulation, and short- and long-term retention, redistribution, and resuspension of radionuclides from a variety of natural and artificial surfaces. The current objective of this project is to evaluate and validate pathway-assessment models applicable to exposure and dose reconstruction at DOE facilities through use of international data sets. This project incorporates the activity of Task 7.lD into a multinational effort to evaluate models and data used for the prediction of radionuclide transfer through agricultural and aquatic systems to humans. It also includes participation in two studies, BIOMOVS (BIOspheric MOdel Validation Study) with the Swedish National Institute for Radiation Protection and VAMP (VAlidation of Model Predictions) with the International Atomic Energy Agency, that address testing the performance of models of radionuclide transport through foodchains.

  18. Power system commonality study

    NASA Astrophysics Data System (ADS)

    Littman, Franklin D.

    1992-07-01

    A limited top level study was completed to determine the commonality of power system/subsystem concepts within potential lunar and Mars surface power system architectures. A list of power system concepts with high commonality was developed which can be used to synthesize power system architectures which minimize development cost. Examples of potential high commonality power system architectures are given in this report along with a mass comparison. Other criteria such as life cycle cost (which includes transportation cost), reliability, safety, risk, and operability should be used in future, more detailed studies to select optimum power system architectures. Nineteen potential power system concepts were identified and evaluated for planetary surface applications including photovoltaic arrays with energy storage, isotope, and nuclear power systems. A top level environmental factors study was completed to assess environmental impacts on the identified power system concepts for both lunar and Mars applications. Potential power system design solutions for commonality between Mars and lunar applications were identified. Isotope, photovoltaic array (PVA), regenerative fuel cell (RFC), stainless steel liquid-metal cooled reactors (less than 1033 K maximum) with dynamic converters, and in-core thermionic reactor systems were found suitable for both lunar and Mars environments. The use of SP-100 thermoelectric (TE) and SP-100 dynamic power systems in a vacuum enclosure may also be possible for Mars applications although several issues need to be investigated further (potential single point failure of enclosure, mass penalty of enclosure and active pumping system, additional installation time and complexity). There are also technical issues involved with development of thermionic reactors (life, serviceability, and adaptability to other power conversion units). Additional studies are required to determine the optimum reactor concept for Mars applications. Various screening

  19. Common Cause Failure Modes

    NASA Technical Reports Server (NTRS)

    Wetherholt, Jon; Heimann, Timothy J.; Anderson, Brenda

    2011-01-01

    High technology industries with high failure costs commonly use redundancy as a means to reduce risk. Redundant systems, whether similar or dissimilar, are susceptible to Common Cause Failures (CCF). CCF is not always considered in the design effort and, therefore, can be a major threat to success. There are several aspects to CCF which must be understood to perform an analysis which will find hidden issues that may negate redundancy. This paper will provide definition, types, a list of possible causes and some examples of CCF. Requirements and designs from NASA projects will be used in the paper as examples.

  20. Commonality based interoperability

    NASA Astrophysics Data System (ADS)

    Moulton, Christine L.; Hepp, Jared J.; Harrell, John

    2016-05-01

    What interoperability is and why the Army wants it between systems is easily understood. Enabling multiple systems to work together and share data across boundaries in a co-operative manner will benefit the warfighter by allowing for easy access to previously hard-to-reach capabilities. How to achieve interoperability is not as easy to understand due to the numerous different approaches that accomplish the goal. Commonality Based Interoperability (CBI) helps establish how to achieve the goal by extending the existing interoperability definition. CBI is not an implementation, nor is it an architecture; it is a definition of interoperability with a foundation of establishing commonality between systems.

  1. Nanoparticle hardness controls the internalization pathway for drug delivery

    NASA Astrophysics Data System (ADS)

    Li, Ye; Zhang, Xianren; Cao, Dapeng

    2015-01-01

    Nanoparticle (NP)-based drug delivery systems offer fundamental advantages over current therapeutic agents that commonly display a longer circulation time, lower toxicity, specific targeted release, and greater bioavailability. For successful NP-based drug delivery it is essential that the drug-carrying nanocarriers can be internalized by the target cells and transported to specific sites, and the inefficient internalization of nanocarriers is often one of the major sources for drug resistance. In this work, we use the dissipative particle dynamics simulation to investigate the effect of NP hardness on their internalization efficiency. Three simplified models of NP platforms for drug delivery, including polymeric NP, liposome and solid NP, are designed here to represent increasing nanocarrier hardness. Simulation results indicate that NP hardness controls the internalization pathway for drug delivery. Rigid NPs can enter the cell by a pathway of endocytosis, whereas for soft NPs the endocytosis process can be inhibited or frustrated due to wrapping-induced shape deformation and non-uniform ligand distribution. Instead, soft NPs tend to find one of three penetration pathways to enter the cell membrane via rearranging their hydrophobic and hydrophilic segments. Finally, we show that the interaction between nanocarriers and drug molecules is also essential for effective drug delivery.

  2. The Common Good in Classical Political Philosophy

    ERIC Educational Resources Information Center

    Lewis, V. Bradley

    2006-01-01

    The term "common good" names the end (or final cause) of political and social life in the tradition of moral thought that owes its main substance to Aristotle and St. Thomas Aquinas. It names a genuine good ("bonum honestum") and not merely an instrumental or secondary good defeasible in the face of particular goods. However, at the same time, it…

  3. Common Educational Proficiency Assessment (CEPA) in English

    ERIC Educational Resources Information Center

    Coombe, Christine; Davidson, Peter

    2014-01-01

    The Common Educational Proficiency Assessment (CEPA) is a large-scale, high-stakes, English language proficiency/placement test administered in the United Arab Emirates to Emirati nationals in their final year of secondary education or Grade 12. The purpose of the CEPA is to place students into English classes at the appropriate government…

  4. The final step of the ethylene biosynthesis pathway in turnip tops (Brassica rapa): molecular characterization of the 1-aminocyclopropane-1-carboxylate oxidase BrACO1 throughout zygotic embryogenesis and germination of heterogeneous seeds.

    PubMed

    Del Carmen Rodríguez-Gacio, María; Nicolás, Carlos; Matilla, Angel Jesús

    2004-05-01

    In a previous report from the present authors, it was shown that the 1-aminocyclopropane-1-carboxylate (ACC) oxidation may play a crucial role during zygotic embryogenesis of turnip tops seeds. The present study was performed to elucidate the contribution of the silique-wall and seeds in ethylene production during this developmental process. ACC content in the silique wall is only higher than in seeds during the middle phases of zygotic embryogenesis. The ACC-oxidase (ACO) activity peaks in the silique-wall and seeds during the onset of embryogenesis, declining gradually afterwards, being undetectable during desiccation period. Using reverse transcriptase-polymerase chain reaction, one cDNA clone coding for an ACO and called BrACO1, was isolated. The deduced protein for BrACO1 has a molecular weight of 36.8 kDa and a high homology with other crucifer ACOs. The heterologous expression of this cDNA confirmed that BrACO1 is an ACO. The expression of this gene was high during the first phases of silique-wall development, low during the middle phases and undetectable during desiccation. By contrast, BrACO1 transcript was accumulated only in the earliest phases of seed embryogenesis and may participate in the highest ACO activity and ethylene production by seeds at the beginning of embryogenesis. Finally, in this work a correlation between the heterogeneity of Brassica rapa L. cv. Rapa seeds and the ability to oxidize the ACC to ethylene has been demonstrated.

  5. Final Report

    SciTech Connect

    Marchant, Gary E.

    2013-04-23

    This is the final report of a two year project entitled "Governing Nanotechnology Risks and Benefits in the Transition to Regulation: Innovative Public and Private Approaches." This project examined the role of new governance or "soft law" mechanisms such as codes of conduct, voluntary programs and partnership agreements to manage the risks of emerging technologies such as nanotechnology. A series of published or in publication papers and book chapters are attached.

  6. Final Report

    SciTech Connect

    R. Paul Drake

    2001-11-30

    This final report describes work involving 22 investigators from 11 institutions to explore the dynamics present in supernova explosions by means of experiments on the Omega laser. The specific experiments emphasized involved the unstable expansion of a spherical capsule and the coupling of perturbations at a first interface to a second interface by means of a strong shock. Both effects are present in supernovae. The experiments were performed at Omega and the computer simulations were undertaken at several institutions. B139

  7. Solving Common Mathematical Problems

    NASA Technical Reports Server (NTRS)

    Luz, Paul L.

    2005-01-01

    Mathematical Solutions Toolset is a collection of five software programs that rapidly solve some common mathematical problems. The programs consist of a set of Microsoft Excel worksheets. The programs provide for entry of input data and display of output data in a user-friendly, menu-driven format, and for automatic execution once the input data has been entered.

  8. Common food allergies.

    PubMed

    McKevith, Brigid; Theobald, Hannah

    The incidence of allergic disease, including food allergy, appears to be increasing in the UK (Gupta et al 2003). Although any food has the potential to cause an allergic reaction, certain foods are more common causes of allergy than others. If diagnosed, food allergy is manageable. Correct diagnosis is important to ensure optimal management and a nutritionally balanced diet.

  9. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2003-01-01

    Part of the 2002 industrial minerals review. The production, consumption, and price of shale and common clay in the U.S. during 2002 are discussed. The impact of EPA regulations on brick and structural clay product manufacturers is also outlined.

  10. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2001-01-01

    Part of the 2000 annual review of the industrial minerals sector. A general overview of the common clay and shale industry is provided. In 2000, U.S. production increased by 5 percent, while sales or use declined to 23.6 Mt. Despite the slowdown in the economy, no major changes are expected for the market.

  11. Math, Literacy, & Common Standards

    ERIC Educational Resources Information Center

    Education Week, 2012

    2012-01-01

    Nearly every state has signed on to use the Common Core State Standards as a framework for teaching English/language arts and mathematics to students. Translating them for the classroom, however, requires schools, teachers, and students to change the way they approach teaching and learning. This report examines the progress some states have made…

  12. Common Carrier Services.

    ERIC Educational Resources Information Center

    Federal Communications Commission, Washington, DC.

    This bulletin outlines the Federal Communications Commission's (FCC) responsibilities in regulating the interstate and foreign common carrier communication via electrical means. Also summarized are the history, technological development, and current capabilities and prospects of telegraph, wire telephone, radiotelephone, satellite communications,…

  13. Common Carrier Services.

    ERIC Educational Resources Information Center

    Federal Communications Commission, Washington, DC.

    After outlining the Federal Communications Commission's (FCC) responsibility for regulating interstate common carrier communication (non-broadcast communication whose carriers are required by law to furnish service at reasonable charges upon request), this information bulletin reviews the history, technological development, and current…

  14. Pleasure: the common currency.

    PubMed

    Cabanac, M

    1992-03-21

    At present as physiologists studying various homeostatic behaviors, such as thermoregulatory behavior and food and fluid intake, we have no common currency that allows us to equate the strength of the motivational drive that accompanies each regulatory need, in terms of how an animal or a person will choose to satisfy his needs when there is a conflict between two or more of them. Yet the behaving organism must rank his priorities and needs a common currency to achieve the ranking (McFarland & Sibly, 1975, Phil. Trans. R. Soc. Lond. 270 Biol 265-293). A theory is proposed here according to which pleasure is this common currency. The perception of pleasure, as measured operationally and quantitatively by choice behavior (in the case of animals), or by the rating of the intensity of pleasure or displeasure (in the case of humans) can serve as such a common currency. The tradeoffs between various motivations would thus be accomplished by simple maximization of pleasure. In what follows, the scientific work arising recently on this subject, with be reviewed briefly and our recent experimental findings will be presented. This will serve as the support for the theoretical position formulated in this essay.

  15. Common Dermatoses of Infancy

    PubMed Central

    Gora, Irv

    1986-01-01

    Within the pediatric population of their practices, family physicians frequently encounter infants with skin rashes. This article discusses several of the more common rashes of infancy: atopic dermatitis, cradle cap, diaper dermatitis and miliaria. Etiology, clinical picture and possible approaches to treatment are presented. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7 PMID:21267297

  16. Space station commonality analysis

    NASA Technical Reports Server (NTRS)

    1988-01-01

    This study was conducted on the basis of a modification to Contract NAS8-36413, Space Station Commonality Analysis, which was initiated in December, 1987 and completed in July, 1988. The objective was to investigate the commonality aspects of subsystems and mission support hardware while technology experiments are accommodated on board the Space Station in the mid-to-late 1990s. Two types of mission are considered: (1) Advanced solar arrays and their storage; and (2) Satellite servicing. The point of departure for definition of the technology development missions was a set of missions described in the Space Station Mission Requirements Data Base. (MRDB): TDMX 2151 Solar Array/Energy Storage Technology; TDMX 2561 Satellite Servicing and Refurbishment; TDMX 2562 Satellite Maintenance and Repair; TDMX 2563 Materials Resupply (to a free-flyer materials processing platform); TDMX 2564 Coatings Maintenance Technology; and TDMX 2565 Thermal Interface Technology. Issues to be addressed according to the Statement of Work included modularity of programs, data base analysis interactions, user interfaces, and commonality. The study was to consider State-of-the-art advances through the 1990s and to select an appropriate scale for the technology experiments, considering hardware commonality, user interfaces, and mission support requirements. The study was to develop evolutionary plans for the technology advancement missions.

  17. Common Magnets, Unexpected Polarities

    ERIC Educational Resources Information Center

    Olson, Mark

    2013-01-01

    In this paper, I discuss a "misconception" in magnetism so simple and pervasive as to be typically unnoticed. That magnets have poles might be considered one of the more straightforward notions in introductory physics. However, the magnets common to students' experiences are likely different from those presented in educational…

  18. Common File Formats.

    PubMed

    Mills, Lauren

    2014-03-21

    An overview of the many file formats commonly used in bioinformatics and genome sequence analysis is presented, including various data file formats, alignment file formats, and annotation file formats. Example workflows illustrate how some of the different file types are typically used.

  19. Pleasure: the common currency.

    PubMed

    Cabanac, M

    1992-03-21

    At present as physiologists studying various homeostatic behaviors, such as thermoregulatory behavior and food and fluid intake, we have no common currency that allows us to equate the strength of the motivational drive that accompanies each regulatory need, in terms of how an animal or a person will choose to satisfy his needs when there is a conflict between two or more of them. Yet the behaving organism must rank his priorities and needs a common currency to achieve the ranking (McFarland & Sibly, 1975, Phil. Trans. R. Soc. Lond. 270 Biol 265-293). A theory is proposed here according to which pleasure is this common currency. The perception of pleasure, as measured operationally and quantitatively by choice behavior (in the case of animals), or by the rating of the intensity of pleasure or displeasure (in the case of humans) can serve as such a common currency. The tradeoffs between various motivations would thus be accomplished by simple maximization of pleasure. In what follows, the scientific work arising recently on this subject, with be reviewed briefly and our recent experimental findings will be presented. This will serve as the support for the theoretical position formulated in this essay. PMID:12240693

  20. Navagating the Common Core

    ERIC Educational Resources Information Center

    McShane, Michael Q.

    2014-01-01

    This article presents a debate over the Common Core State Standards Initiative as it has rocketed to the forefront of education policy discussions around the country. The author contends that there is value in having clear cross state standards that will clarify the new online and blended learning that the growing use of technology has provided…

  1. Information Commons to Go

    ERIC Educational Resources Information Center

    Bayer, Marc Dewey

    2008-01-01

    Since 2004, Buffalo State College's E. H. Butler Library has used the Information Commons (IC) model to assist its 8,500 students with library research and computer applications. Campus Technology Services (CTS) plays a very active role in its IC, with a centrally located Computer Help Desk and a newly created Application Support Desk right in the…

  2. Common conversion factors.

    PubMed

    2001-05-01

    This appendix presents tables of some of the more common conversion factors for units of measure used throughout Current Protocols manuals, as well as prefixes indicating powers of ten for SI units. Another table gives conversions between temperatures on the Celsius (Centigrade) and Fahrenheit scales. PMID:18770653

  3. Common file formats.

    PubMed

    Leonard, Shonda A; Littlejohn, Timothy G; Baxevanis, Andreas D

    2007-01-01

    This appendix discusses a few of the file formats frequently encountered in bioinformatics. Specifically, it reviews the rules for generating FASTA files and provides guidance for interpreting NCBI descriptor lines, commonly found in FASTA files. In addition, it reviews the construction of GenBank, Phylip, MSF and Nexus files. PMID:18428774

  4. A Language in Common.

    ERIC Educational Resources Information Center

    1963

    This collection of articles reprinted from the "London Times Literary Supplement" indicates the flexibility of English as a common literary language in its widespread use outside the United States and England. Major articles present the thesis that English provides an artistic medium which is enriched through colloquial idioms in the West Indies…

  5. COMMON LISP: The language

    SciTech Connect

    Steele, G.L. Jr.

    1984-01-01

    This book describes COMMON LISP,which is becoming the industry and government standard AI language. Topics covered include the following: data types; scope and extent; type specifiers; program structure; predicates; control structure; macros; declarations; symbols; packages; numbers; characters; sequences; lists; hash tables; arrays; strings; structures; the evaluator; streams; input/output; file system interface; and errors.

  6. IL-1α Counteract TGF-β Regulated Genes and Pathways in Human Fibroblasts.

    PubMed

    Koskela von Sydow, Anita; Janbaz, Chris; Kardeby, Caroline; Repsilber, Dirk; Ivarsson, Mikael

    2016-07-01

    Dysregulated wound healing is commonly associated with excessive fibrosis. Connective tissue growth factor (CTGF/CCN2) is characteristically overexpressed in fibrotic diseases and stimulated by transforming growth factor-β (TGF-β) in dermal fibroblasts. We previously showed that interleukin-1 (IL-1α) counteracts TGF-β-stimulated CTGF mRNA and protein expression in these cells. The aim of this study was to explore the effects of IL-1α on further genes and pathways in TGF-β regulated fibroblasts. Transcriptional microarray and multiple comparison analysis showed that the antagonizing effects of IL-1α was much more prominent than the synergistic effects, both with respect to number of genes and extent of changes in gene expression. Moreover, comparing canonical pathways by gene set enrichment analysis and the Ingenuity Pathway Analysis tool revealed that IL-1α counteracted TGF-β in the top six most confident pathways regulated by both cytokines. Interferon and IL-1 signaling, as well as two pathways involved in apoptosis signaling were suppressed by TGF-β and activated by IL-1α. Pathways involving actin remodeling and focal adhesion dynamics were activated by TGF-β and suppressed by IL-1α. Analyzing upstream regulators in part corroborate the comparison of canonical pathways and added cell cycle regulators as another functional group regulated by IL-1α. Finally, gene set enrichment analysis of fibrosis-related genes indicated that IL-1 moderately counteracts the collective effect of TGF-β on these genes. Microarray results were validated by qPCR. Taken together, the results indicate prominent antagonistic effects of IL-1α on TGF-β regulated interferon signaling, as well as on a wide variety of other genes and pathways in fibroblasts. J. Cell. Biochem. 117: 1622-1632, 2016. © 2015 Wiley Periodicals, Inc.

  7. Pathways for virus assembly around nucleic acids

    PubMed Central

    Perlmutter, Jason D; Perkett, Matthew R

    2014-01-01

    Understanding the pathways by which viral capsid proteins assemble around their genomes could identify key intermediates as potential drug targets. In this work we use computer simulations to characterize assembly over a wide range of capsid protein-protein interaction strengths and solution ionic strengths. We find that assembly pathways can be categorized into two classes, in which intermediates are either predominantly ordered or disordered. Our results suggest that estimating the protein-protein and the protein-genome binding affinities may be sufficient to predict which pathway occurs. Furthermore, the calculated phase diagrams suggest that knowledge of the dominant assembly pathway and its relationship to control parameters could identify optimal strategies to thwart or redirect assembly to block infection. Finally, analysis of simulation trajectories suggests that the two classes of assembly pathways can be distinguished in single molecule fluorescence correlation spectroscopy or bulk time resolved small angle x-ray scattering experiments. PMID:25036288

  8. Curcumin inhibits transforming growth factor-β1-induced EMT via PPARγ pathway, not Smad pathway in renal tubular epithelial cells.

    PubMed

    Li, Rui; Wang, Yunman; Liu, Yujun; Chen, Qijing; Fu, Wencheng; Wang, Hao; Cai, Hui; Peng, Wen; Zhang, Xuemei

    2013-01-01

    Tubulointerstitial fibrosis (TIF) is the final common pathway in the end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is considered a major contributor to the TIF by increasing the number of myofibroblasts. Curcumin, a polyphenolic compound derived from rhizomes of Curcuma, has been shown to possess potent anti-fibrotic properties but the mechanism remains elusive. We found that curcumin inhibited the EMT as assessed by reduced expression of α-SMA and PAI-1, and increased E-cadherin in TGF-β1 treated proximal tubular epithelial cell HK-2 cells. Both of the conventional TGF-β1/Smad pathway and non-Smad pathway were investigated. Curcumin reduced TGF-β receptor type I (TβR-I) and TGF-β receptor type II (TβR II), but had no effect on phosphorylation of Smad2 and Smad3. On the other hand, in non-Smad pathway curcumin reduced TGF-β1-induced ERK phosphorylation and PPARγ phosphorylation, and promoted nuclear translocation of PPARγ. Further, the effect of curcumin on α-SMA, PAI-1, E-cadherin, TβR I and TβR II were reversed by ERK inhibitor U0126 or PPARγ inhibitor BADGE, or PPARγ shRNA. Blocking PPARγ signaling pathway by inhibitor BADGE or shRNA had no effect on the phosphorylation of ERK whereas the suppression of ERK signaling pathway inhibited the phosphorylation of PPARγ. We conclude that curcumin counteracted TGF-β1-induced EMT in renal tubular epithelial cells via ERK-dependent and then PPARγ-dependent pathway.

  9. Common Magnets, Unexpected Polarities

    NASA Astrophysics Data System (ADS)

    Olson, Mark

    2013-11-01

    In this paper, I discuss a "misconception" in magnetism so simple and pervasive as to be typically unnoticed. That magnets have poles might be considered one of the more straightforward notions in introductory physics. However, the magnets common to students' experiences are likely different from those presented in educational contexts. This leads students, in my experience, to frequently and erroneously attribute magnetic poles based on geometric associations rather than actual observed behavior. This polarity discrepancy can provide teachers the opportunity to engage students in authentic inquiry about objects in their daily experiences. I've found that investigation of the magnetic polarities of common magnets provides a productive context for students in which to develop valuable and authentic scientific inquiry practices.

  10. Common Anorectal Disorders

    PubMed Central

    Foxx-Orenstein, Amy E.; Umar, Sarah B.; Crowell, Michael D.

    2014-01-01

    Anorectal disorders result in many visits to healthcare specialists. These disorders include benign conditions such as hemorrhoids to more serious conditions such as malignancy; thus, it is important for the clinician to be familiar with these disorders as well as know how to conduct an appropriate history and physical examination. This article reviews the most common anorectal disorders, including hemorrhoids, anal fissures, fecal incontinence, proctalgia fugax, excessive perineal descent, and pruritus ani, and provides guidelines on comprehensive evaluation and management. PMID:24987313

  11. Final Report

    SciTech Connect

    R Paul Drake

    2004-01-12

    OAK-B135 This is the final report from the project Hydrodynamics by High-Energy-Density Plasma Flow and Hydrodynamics and Radiation Hydrodynamics with Astrophysical Applications. This project supported a group at the University of Michigan in the invention, design, performance, and analysis of experiments using high-energy-density research facilities. The experiments explored compressible nonlinear hydrodynamics, in particular at decelerating interfaces, and the radiation hydrodynamics of strong shock waves. It has application to supernovae, astrophysical jets, shock-cloud interactions, and radiative shock waves.

  12. 'Historicising common sense'.

    PubMed

    Millstone, Noah

    2012-12-01

    This essay is an expanded set of comments on the social psychology papers written for the special issue on History and Social Psychology. It considers what social psychology, and particularly the theory of social representations, might offer historians working on similar problems, and what historical methods might offer social psychology. The social history of thinking has been a major theme in twentieth and twenty-first century historical writing, represented most recently by the genre of 'cultural history'. Cultural history and the theory of social representations have common ancestors in early twentieth-century social science. Nevertheless, the two lines of research have developed in different ways and are better seen as complementary than similar. The theory of social representations usefully foregrounds issues, like social division and change over time, that cultural history relegates to the background. But for historians, the theory of social representations seems oddly fixated on comparing the thought styles associated with positivist science and 'common sense'. Using historical analysis, this essay tries to dissect the core opposition 'science : common sense' and argues for a more flexible approach to comparing modes of thought.

  13. Common HEP UNIX Environment

    NASA Astrophysics Data System (ADS)

    Taddei, Arnaud

    After it had been decided to design a common user environment for UNIX platforms among HEP laboratories, a joint project between DESY and CERN had been started. The project consists in 2 phases: 1. Provide a common user environment at shell level, 2. Provide a common user environment at graphical level (X11). Phase 1 is in production at DESY and at CERN as well as at PISA and RAL. It has been developed around the scripts originally designed at DESY Zeuthen improved and extended with a 2 months project at CERN with a contribution from DESY Hamburg. It consists of a set of files which are customizing the environment for the 6 main shells (sh, csh, ksh, bash, tcsh, zsh) on the main platforms (AIX, HP-UX, IRIX, SunOS, Solaris 2, OSF/1, ULTRIX, etc.) and it is divided at several "sociological" levels: HEP, site, machine, cluster, group of users and user with some levels which are optional. The second phase is under design and a first proposal has been published. A first version of the phase 2 exists already for AIX and Solaris, and it should be available for all other platforms, by the time of the conference. This is a major collective work between several HEP laboratories involved in the HEPiX-scripts and HEPiX-X11 working-groups.

  14. Common Geometry Module

    2005-01-01

    The Common Geometry Module (CGM) is a code library which provides geometry functionality used for mesh generation and other applications. This functionality includes that commonly found in solid modeling engines, like geometry creation, query and modification; CGM also includes capabilities not commonly found in solid modeling engines, like geometry decomposition tools and support for shared material interfaces. CGM is built upon the ACIS solid modeling engine, but also includes geometry capability developed beside and onmore » top of ACIS. CGM can be used as-is to provide geometry functionality for codes needing this capability. However, CGM can also be extended using derived classes in C++, allowing the geometric model to serve as the basis for other applications, for example mesh generation. CGM is supported on Sun Solaris, SGI, HP, IBM, DEC, Linux and Windows NT platforms. CGM also indudes support for loading ACIS models on parallel computers, using MPI-based communication. Future plans for CGM are to port it to different solid modeling engines, including Pro/Engineer or SolidWorks. CGM is being released into the public domain under an LGPL license; the ACIS-based engine is available to ACIS licensees on request.« less

  15. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  16. Role of care pathways in interprofessional teamwork.

    PubMed

    Scaria, Minimol Kulakkottu

    2016-08-24

    Cohesive interprofessional teamwork is essential to successful healthcare services. Interprofessional teamwork is the means by which different healthcare professionals - with diverse knowledge, skills and talents - collaborate to achieve a common goal. Several interventions are available to improve teamwork in the healthcare setting. This article explores the role of care pathways in improving interprofessional teamwork. Care pathways enhance teamwork by promoting coordination, collaboration, communication and decision making to achieve optimal healthcare outcomes. They result in improved staff knowledge, communication, documentation and interprofessional relations. Care pathways also contribute to patient-centred care and increase patient satisfaction.

  17. Role of care pathways in interprofessional teamwork.

    PubMed

    Scaria, Minimol Kulakkottu

    2016-08-24

    Cohesive interprofessional teamwork is essential to successful healthcare services. Interprofessional teamwork is the means by which different healthcare professionals - with diverse knowledge, skills and talents - collaborate to achieve a common goal. Several interventions are available to improve teamwork in the healthcare setting. This article explores the role of care pathways in improving interprofessional teamwork. Care pathways enhance teamwork by promoting coordination, collaboration, communication and decision making to achieve optimal healthcare outcomes. They result in improved staff knowledge, communication, documentation and interprofessional relations. Care pathways also contribute to patient-centred care and increase patient satisfaction. PMID:27641591

  18. Common rodent procedures.

    PubMed

    Klaphake, Eric

    2006-05-01

    Rodents are commonly owned exotic animal pets that may be seen by veterinary practitioners. Although most owners presenting their animals do care about their pets, they may not be aware of the diagnostic possibilities and challenges that can be offered by rodents to the veterinarian. Understanding clinical anatomy, proper hand-ling technique, realistic management of emergency presentations,correct and feasible diagnostic sampling, anesthesia, and humane euthanasia procedures is important to enhancing the doctor-client-patient relationship, especially when financial constraints may be imposed by the owner. PMID:16759953

  19. Pathway modulators and inhibitors.

    PubMed

    Smith, John A

    2009-07-01

    Inhibitors of specific cellular pathways are useful for investigating the roles of proteins of unknown function, and for selectively inhibiting a protein in complex pathways to uncover its relationships to other proteins in this and other interacting pathways. This appendix provides links to Web sites that describe cellular processes and pathways along with the various classes of inhibitors, numerous references, downloadable diagrams, and technical tips.

  20. Social Justice and the Environmental Commons.

    PubMed

    Flanagan, Constance A; Byington, Rachel; Gallay, Erin; Sambo, Allison

    2016-01-01

    In this chapter, we build on the scholarship on youth civic engagement by turning attention to the environmental commons as a space for political action. We begin with a definition of the term and arguments about ways that social justice is implied in it. Following that, we raise several psychological challenges to motivating action on behalf of the environmental commons and discuss the critical experiences and actions that can defy those challenges. Finally, drawing from Ostrom's empirical evidence opposing a tragedy of the commons, we discuss practices consistent with a social justice approach that nurture in younger generations an identification with and commitment to the environmental commons and discuss how this orientation would benefit human beings, democracies, and the earth. PMID:27474427

  1. Social Justice and the Environmental Commons.

    PubMed

    Flanagan, Constance A; Byington, Rachel; Gallay, Erin; Sambo, Allison

    2016-01-01

    In this chapter, we build on the scholarship on youth civic engagement by turning attention to the environmental commons as a space for political action. We begin with a definition of the term and arguments about ways that social justice is implied in it. Following that, we raise several psychological challenges to motivating action on behalf of the environmental commons and discuss the critical experiences and actions that can defy those challenges. Finally, drawing from Ostrom's empirical evidence opposing a tragedy of the commons, we discuss practices consistent with a social justice approach that nurture in younger generations an identification with and commitment to the environmental commons and discuss how this orientation would benefit human beings, democracies, and the earth.

  2. Final Vowel-Consonant-e.

    ERIC Educational Resources Information Center

    Burmeister, Lou E.

    The utility value of the final vowel-consonant-e phonic generalization was examined using 2,715 common English words. When the vowel was defined as a single-vowel, the consonant as a single-consonant, and the final e as a single-e the generalization was found to be highly useful, contrary to other recent findings. Using the total sample of 2,715…

  3. Common pediatric epilepsy syndromes.

    PubMed

    Park, Jun T; Shahid, Asim M; Jammoul, Adham

    2015-02-01

    Benign rolandic epilepsy (BRE), childhood idiopathic occipital epilepsy (CIOE), childhood absence epilepsy (CAE), and juvenile myoclonic epilepsy (JME) are some of the common epilepsy syndromes in the pediatric age group. Among the four, BRE is the most commonly encountered. BRE remits by age 16 years with many children requiring no treatment. Seizures in CAE also remit at the rate of approximately 80%; whereas, JME is considered a lifelong condition even with the use of antiepileptic drugs (AEDs). Neonates and infants may also present with seizures that are self-limited with no associated psychomotor disturbances. Benign familial neonatal convulsions caused by a channelopathy, and inherited in an autosomal dominant manner, have a favorable outcome with spontaneous resolution. Benign idiopathic neonatal seizures, also referred to as "fifth-day fits," are an example of another epilepsy syndrome in infants that carries a good prognosis. BRE, CIOE, benign familial neonatal convulsions, benign idiopathic neonatal seizures, and benign myoclonic epilepsy in infancy are characterized as "benign" idiopathic age-related epilepsies as they have favorable implications, no structural brain abnormality, are sensitive to AEDs, have a high remission rate, and have no associated psychomotor disturbances. However, sometimes selected patients may have associated comorbidities such as cognitive and language delay for which the term "benign" may not be appropriate.

  4. Common Variable Immunodeficiency.

    PubMed

    Saikia, Biman; Gupta, Sudhir

    2016-04-01

    Common variable immunodeficiency (CVID) is the most common primary immunodeficiency of young adolescents and adults which also affects the children. The disease remains largely under-diagnosed in India and Southeast Asian countries. Although in majority of cases it is sporadic, disease may be inherited in a autosomal recessive pattern and rarely, in autosomal dominant pattern. Patients, in addition to frequent sino-pulmonary infections, are also susceptible to various autoimmune diseases and malignancy, predominantly lymphoma and leukemia. Other characteristic lesions include lymphocytic and granulomatous interstitial lung disease, and nodular lymphoid hyperplasia of gut. Diagnosis requires reduced levels of at least two immunoglobulin isotypes: IgG with IgA and/or IgM and impaired specific antibody response to vaccines. A number of gene mutations have been described in CVID; however, these genetic alterations account for less than 20% of cases of CVID. Flow cytometry aptly demonstrates a disturbed B cell homeostasis with reduced or absent memory B cells and increased CD21(low) B cells and transitional B cell populations. Approximately one-third of patients with CVID also display T cell functional defects. Immunoglobulin therapy remains the mainstay of treatment. Immunologists and other clinicians in India and other South East Asian countries need to be aware of CVID so that early diagnosis can be made, as currently, majority of these patients still go undiagnosed. PMID:26868026

  5. Final Report

    SciTech Connect

    Ananth Devulapalli

    2009-06-30

    Ohio Supercomputer Center (OSC) is a junior partner in the project titled Common HEC I/O Forwarding Scalability Layer. The goal of this project is to design and implement an open platform for scalable I/O forwarding for the next generation leadership class machines. These machines are going to be made up of hundreds of thousands of nodes, and current distributed file system architectures cannot scale to such large number of clients due to problems caused by large fan-in. One solution to that problem is to add another layer of machines between the file servers and the clients, which can intermediate the I/O requests. Not only does it reduce the fan-in problem at the file servers, but this additional layer of indirection also allows architectural flexibility, like the ability to support heterogeneous networks and file systems.

  6. Final Report

    SciTech Connect

    Webb, Robert C.; Kamon, Teruki; Toback, David; Safonov, Alexei; Dutta, Bhaskar; Dimitri, Nanopoulos; Pope, Christopher; White, James

    2013-11-18

    Overview The High Energy Physics Group at Texas A&M University is submitting this final report for our grant number DE-FG02-95ER40917. This grant has supported our wide range of research activities for over a decade. The reports contained here summarize the latest work done by our research team. Task A (Collider Physics Program): CMS & CDF Profs. T. Kamon, A. Safonov, and D. Toback co-lead the Texas A&M (TAMU) collider program focusing on CDF and CMS experiments. Task D: Particle Physics Theory Our particle physics theory task is the combined effort of Profs. B. Dutta, D. Nanopoulos, and C. Pope. Task E (Underground Physics): LUX & NEXT Profs. R. Webb and J. White(deceased) lead the Xenon-based underground research program consisting of two main thrusts: the first, participation in the LUX two-phase xenon dark matter search experiment and the second, detector R&D primarily aimed at developing future detectors for underground physics (e.g. NEXT and LZ).

  7. EPR Correlations, Bell Inequalities and Common Cause Systems

    NASA Astrophysics Data System (ADS)

    Hofer-Szabó, Gábor

    2014-03-01

    Standard common causal explanations of the EPR situation assume a so-called joint common cause system that is a common cause for all correlations. However, the assumption of a joint common cause system together with some other physically motivated assumptions concerning locality and no-conspiracy results in various Bell inequalities. Since Bell inequalities are violated for appropriate measurement settings, a local, non-conspiratorial joint common causal explanation of the EPR situation is ruled out. But why do we assume that a common causal explanation of a set of correlation consists in finding a joint common cause system for all correlations and not just in finding separate common cause systems for the different correlations? What are the perspectives of a local, non-conspiratorial separate common causal explanation for the EPR scenario? And finally, how do Bell inequalities relate to the weaker assumption of separate common cause systems?

  8. System Safety Common Cause Analysis

    1992-03-10

    The COMCAN fault tree analysis codes are designed to analyze complex systems such as nuclear plants for common causes of failure. A common cause event, or common mode failure, is a secondary cause that could contribute to the failure of more than one component and violates the assumption of independence. Analysis of such events is an integral part of system reliability and safety analysis. A significant common cause event is a secondary cause common tomore » all basic events in one or more minimal cut sets. Minimal cut sets containing events from components sharing a common location or a common link are called common cause candidates. Components share a common location if no barrier insulates any one of them from the secondary cause. A common link is a dependency among components which cannot be removed by a physical barrier (e.g.,a common energy source or common maintenance instructions).« less

  9. Common Control System Vulnerability

    SciTech Connect

    Trent Nelson

    2005-12-01

    The Control Systems Security Program and other programs within the Idaho National Laboratory have discovered a vulnerability common to control systems in all sectors that allows an attacker to penetrate most control systems, spoof the operator, and gain full control of targeted system elements. This vulnerability has been identified on several systems that have been evaluated at INL, and in each case a 100% success rate of completing the attack paths that lead to full system compromise was observed. Since these systems are employed in multiple critical infrastructure sectors, this vulnerability is deemed common to control systems in all sectors. Modern control systems architectures can be considered analogous to today's information networks, and as such are usually approached by attackers using a common attack methodology to penetrate deeper and deeper into the network. This approach often is composed of several phases, including gaining access to the control network, reconnaissance, profiling of vulnerabilities, launching attacks, escalating privilege, maintaining access, and obscuring or removing information that indicates that an intruder was on the system. With irrefutable proof that an external attack can lead to a compromise of a computing resource on the organization's business local area network (LAN), access to the control network is usually considered the first phase in the attack plan. Once the attacker gains access to the control network through direct connections and/or the business LAN, the second phase of reconnaissance begins with traffic analysis within the control domain. Thus, the communications between the workstations and the field device controllers can be monitored and evaluated, allowing an attacker to capture, analyze, and evaluate the commands sent among the control equipment. Through manipulation of the communication protocols of control systems (a process generally referred to as ''reverse engineering''), an attacker can then map out the

  10. Apoptosis pathways and neuroblastoma therapy.

    PubMed

    Fulda, S

    2009-01-01

    Evasion of apoptosis, the cell's intrinsic death program, is a hallmark of human cancers including neuroblastoma. Also, failure to undergo apoptosis may cause treatment resistance, since the cytotoxic activity of anticancer therapies commonly used in the clinic, e.g. chemotherapy, gamma-irradiation or immunotherapy, is predominantly mediated by triggering apoptosis in tumor cells. Therefore, a better understanding of the signaling pathways and molecules that govern apoptosis in neuroblastoma cells is expected to open new avenues for the design of molecular targeted therapies for neuroblastoma.

  11. Common hyperspectral image database design

    NASA Astrophysics Data System (ADS)

    Tian, Lixun; Liao, Ningfang; Chai, Ali

    2009-11-01

    This paper is to introduce Common hyperspectral image database with a demand-oriented Database design method (CHIDB), which comprehensively set ground-based spectra, standardized hyperspectral cube, spectral analysis together to meet some applications. The paper presents an integrated approach to retrieving spectral and spatial patterns from remotely sensed imagery using state-of-the-art data mining and advanced database technologies, some data mining ideas and functions were associated into CHIDB to make it more suitable to serve in agriculture, geological and environmental areas. A broad range of data from multiple regions of the electromagnetic spectrum is supported, including ultraviolet, visible, near-infrared, thermal infrared, and fluorescence. CHIDB is based on dotnet framework and designed by MVC architecture including five main functional modules: Data importer/exporter, Image/spectrum Viewer, Data Processor, Parameter Extractor, and On-line Analyzer. The original data were all stored in SQL server2008 for efficient search, query and update, and some advance Spectral image data Processing technology are used such as Parallel processing in C#; Finally an application case is presented in agricultural disease detecting area.

  12. Accepted Common Interest Community (CIC) Proposals.

    PubMed

    2014-01-01

    These are the 18 accepted proposals for the three Common Interest Community (CIC) sessions at IAYT's Symposium on Yoga Therapy and Research (SYTAR), June 5-8, 2014, in Austin, Texas and published in the Final Program Guide and CIC Works for SYTAR 2014. The sessions were CIC#1 Rehab Professionals: Bridging the Past with the Future and CIC#2a & CIC#2b Mental, Emotional and Spiritual Health. PMID:25645135

  13. COMMON ENVELOPE: ENTHALPY CONSIDERATION

    SciTech Connect

    Ivanova, N.; Chaichenets, S.

    2011-04-20

    In this Letter, we discuss a modification to the criterion for the common envelope (CE) event to result in envelope dispersion. We emphasize that the current energy criterion for the CE phase is not sufficient for an instability of the CE, nor for an ejection. However, in some cases, stellar envelopes undergo stationary mass outflows, which are likely to occur during the slow spiral-in stage of the CE event. We propose the condition for such outflows, in a manner similar to the currently standard {alpha}{sub CE}{lambda}-prescription but with an addition of P/{rho} term in the energy balance equation, accounting therefore for the enthalpy of the envelope rather than merely the gas internal energy. This produces a significant correction, which might help to dispense with an unphysically high value of energy efficiency parameter during the CE phase, currently required in the binary population synthesis studies to make the production of low-mass X-ray binaries with a black hole companion to match the observations.

  14. Advances in Targeting Signal Transduction Pathways

    PubMed Central

    McCubrey, James A.; Steelman, Linda S.; Chappell, William H.; Sun, Lin; Davis, Nicole M.; Abrams, Stephen L.; Franklin, Richard A.; Cocco, Lucio; Evangelisti, Camilla; Chiarini, Francesca; Martelli, Alberto M.; Libra, Massimo; Candido, Saverio; Ligresti, Giovanni; Malaponte, Grazia; Mazzarino, Maria C.; Fagone, Paolo; Donia, Marco; Nicoletti, Ferdinando; Polesel, Jerry; Talamini, Renato; Bäsecke, Jörg; Mijatovic, Sanja; Maksimovic-Ivanic, Danijela; Milella, Michele; Tafuri, Agostino; Dulińska-Litewka, Joanna; Laidler, Piotr; D'Assoro, Antonio B.; Drobot, Lyudmyla; Umezawa, Kazuo; Montalto, Giuseppe; Cervello, Melchiorre; Demidenko, Zoya N.

    2012-01-01

    Over the past few years, significant advances have occurred in both our understanding of the complexity of signal transduction pathways as well as the isolation of specific inhibitors which target key components in those pathways. Furthermore critical information is being accrued regarding how genetic mutations can affect the sensitivity of various types of patients to targeted therapy. Finally, genetic mechanisms responsible for the development of resistance after targeted therapy are being discovered which may allow the creation of alternative therapies to overcome resistance. This review will discuss some of the highlights over the past few years on the roles of key signaling pathways in various diseases, the targeting of signal transduction pathways and the genetic mechanisms governing sensitivity and resistance to targeted therapies. PMID:23455493

  15. [Controls of the plant endomembrane-secretory pathway]. Final report

    SciTech Connect

    Not Available

    1991-12-31

    These studies are focused on elucidating the molecular structure of plant cell membranes with special reference to cell surface glycoproteins. The studies reported herein include use of monoclonal antibodies to characterize cell surface epitopes, construction of cDNA libraries of cell surface proteins, isolation of plant cell mutants by flow cytometry, detection of beta-glucouronidase marker enzyme systems in plants, expression go VSVG (the major envelope glycoprotein of Vesicular Stomatis Virus) in plant cells, and control of gene expression of cell membrane glycoproteins.(DT)

  16. GED 21st Century Learning Pathways Pilots. Final Report

    ERIC Educational Resources Information Center

    Rutschow, Elizabeth Zachry; Grossman, Amanda; Cullinan, Dan

    2014-01-01

    For the nearly 39 million U.S. adults who do not have a high school diploma, the General Educational Development (GED) programs and exam have served as the main avenue for improving individuals' skills and helping them earn a high school credential. However, few students who start these programs ever get this credential, and even fewer advance to…

  17. FY2003 LDRD Final Annual Report Article: Pathogen Pathway Project

    SciTech Connect

    Fitch, J P; McCutchen-Maloney, S L

    2003-11-10

    Understanding virulence mechanisms of bacterial pathogens is vital to anticipating biological threats and to improving detectors, vaccines, and treatments. This project will characterize factors responsible for virulence of Yersinia pestis, the causative agent of plague and a biothreat agent, which has an inducible Type III secretion virulence mechanism also found in other animal, plant, and human pathogens. Our approach relies on genomic and proteomic characterization of Y. pestis in addition to a bioinformatic infrastructure. Scientific and technical capabilities developed in this project can be applied to other microbes of interest. This work will establish a significant new direction for biodefense at LLNL and expand our national and international scientific collaborations.

  18. Final Technical Report - Mechanisms and pathways controlling genomic instability

    SciTech Connect

    Dynan, William S.

    2013-05-31

    This project used model organisms, the zebrafish and the Japanese medaka fish to investigate the effects of low-dose radiation exposure on the vertebrate embryo. Endpoints measured included apoptotic cell death, aging, and oxidative stress.

  19. Threads of common knowledge.

    PubMed

    Icamina, P

    1993-04-01

    Indigenous knowledge is examined as it is affected by development and scientific exploration. The indigenous culture of shamanism, which originated in northern and southeast Asia, is a "political and religious technique for managing societies through rituals, myths, and world views." There is respect for the natural environment and community life as a social common good. This world view is still practiced by many in Latin America and in Colombia specifically. Colombian shamanism has an environmental accounting system, but the Brazilian government has established its own system of land tenure and political representation which does not adequately represent shamanism. In 1992 a conference was held in the Philippines by the International Institute for Rural Reconstruction and IDRC on sustainable development and indigenous knowledge. The link between the two is necessary. Unfortunately, there are already examples in the Philippines of loss of traditional crop diversity after the introduction of modern farming techniques and new crop varieties. An attempt was made to collect species, but without proper identification. Opposition was expressed to the preservation of wilderness preserves; the desire was to allow indigenous people to maintain their homeland and use their time-tested sustainable resource management strategies. Property rights were also discussed during the conference. Of particular concern was the protection of knowledge rights about biological diversity or pharmaceutical properties of indigenous plant species. The original owners and keepers of the knowledge must retain access and control. The research gaps were identified and found to be expansive. Reference was made to a study of Mexican Indian children who knew 138 plant species while non-Indian children knew only 37. Sometimes there is conflict of interest where foresters prefer timber forests and farmers desire fuelwood supplies and fodder and grazing land, which is provided by shrubland. Information

  20. Threads of common knowledge.

    PubMed

    Icamina, P

    1993-04-01

    Indigenous knowledge is examined as it is affected by development and scientific exploration. The indigenous culture of shamanism, which originated in northern and southeast Asia, is a "political and religious technique for managing societies through rituals, myths, and world views." There is respect for the natural environment and community life as a social common good. This world view is still practiced by many in Latin America and in Colombia specifically. Colombian shamanism has an environmental accounting system, but the Brazilian government has established its own system of land tenure and political representation which does not adequately represent shamanism. In 1992 a conference was held in the Philippines by the International Institute for Rural Reconstruction and IDRC on sustainable development and indigenous knowledge. The link between the two is necessary. Unfortunately, there are already examples in the Philippines of loss of traditional crop diversity after the introduction of modern farming techniques and new crop varieties. An attempt was made to collect species, but without proper identification. Opposition was expressed to the preservation of wilderness preserves; the desire was to allow indigenous people to maintain their homeland and use their time-tested sustainable resource management strategies. Property rights were also discussed during the conference. Of particular concern was the protection of knowledge rights about biological diversity or pharmaceutical properties of indigenous plant species. The original owners and keepers of the knowledge must retain access and control. The research gaps were identified and found to be expansive. Reference was made to a study of Mexican Indian children who knew 138 plant species while non-Indian children knew only 37. Sometimes there is conflict of interest where foresters prefer timber forests and farmers desire fuelwood supplies and fodder and grazing land, which is provided by shrubland. Information

  1. FINAL REPORT

    SciTech Connect

    PETER, GARY F.

    2014-07-16

    of biomass samples imaged with all three methods, and using common analytical software to quantify parameters from the three dimensional images. In addition to the proposed experiments, we conducted imaging studies with a novel TOF-SIMS instrument available through collaborations with the AMOLF goup led by Ron Heeren at the FOM Institute in Amersterdam, Netherlands. ToF-SIMS was used to image intact cross sections of Populus stems with high spatial resolution, chemically selectivity. ToF-SIMS images were correlated with fluorescence microscopy which allowed for more positive ion identification.

  2. Final report

    SciTech Connect

    Dobbs, Fred C.

    2003-01-15

    species of flagellates, Spumella sp. and Bodo sp. (identifications are tentative) were isolated from South Oyster sediments by repetitive serial dilution/extinction method. Protistan cells were cultured with Cereal leaf Prescott medium and pelleted by centrifugation. Protistan DNAs were extracted with a DNA extraction kit (Sigma Co.) and the sequencing of their SSrDNA is underway. Finally, to follow up on our collaboration of Dr. Bill Johnson (Univ. of Utah), one of the co-PIs under the same NABIR umbrella, we are pleased to report we have successfully tested antibody-ferrographic capture of protists (See previous year's report for more background). Polyclonal FITC-conjugated antibody specific for a flagellate, Spumella sp., was produced by Rockland Inc., and we now are able to enumerate that species using ferrographic capture. There are, however, some issues of non-specific staining that remain to be resolved.

  3. Subpathway Analysis based on Signaling-Pathway Impact Analysis of Signaling Pathway

    PubMed Central

    Li, Xianbin; Shen, Liangzhong; Shang, Xuequn; Liu, Wenbin

    2015-01-01

    Pathway analysis is a common approach to gain insight from biological experiments. Signaling-pathway impact analysis (SPIA) is one such method and combines both the classical enrichment analysis and the actual perturbation on a given pathway. Because this method focuses on a single pathway, its resolution generally is not very high because the differentially expressed genes may be enriched in a local region of the pathway. In the present work, to identify cancer-related pathways, we incorporated a recent subpathway analysis method into the SPIA method to form the “sub-SPIA method.” The original subpathway analysis uses the k-clique structure to define a subpathway. However, it is not sufficiently flexible to capture subpathways with complex structure and usually results in many overlapping subpathways. We therefore propose using the minimal-spanning-tree structure to find a subpathway. We apply this approach to colorectal cancer and lung cancer datasets, and our results show that sub-SPIA can identify many significant pathways associated with each specific cancer that other methods miss. Based on the entire pathway network in the Kyoto Encyclopedia of Genes and Genomes, we find that the pathways identified by sub-SPIA not only have the largest average degree, but also are more closely connected than those identified by other methods. This result suggests that the abnormality signal propagating through them might be responsible for the specific cancer or disease. PMID:26207919

  4. Targeting RTK Signaling Pathways in Cancer

    PubMed Central

    Regad, Tarik

    2015-01-01

    The RAS/MAP kinase and the RAS/PI3K/AKT pathways play a key role in the regulation of proliferation, differentiation and survival. The induction of these pathways depends on Receptor Tyrosine Kinases (RTKs) that are activated upon ligand binding. In cancer, constitutive and aberrant activations of components of those pathways result in increased proliferation, survival and metastasis. For instance, mutations affecting RTKs, Ras, B-Raf, PI3K and AKT are common in perpetuating the malignancy of several types of cancers and from different tissue origins. Therefore, these signaling pathways became prime targets for cancer therapy. This review aims to provide an overview about the most frequently encountered mutations, the pathogenesis that results from such mutations and the known therapeutic strategies developed to counteract their aberrant functions. PMID:26404379

  5. Endocytic pathways and endosomal trafficking: a primer.

    PubMed

    Elkin, Sarah R; Lakoduk, Ashley M; Schmid, Sandra L

    2016-05-01

    This brief overview of endocytic trafficking is written in honor of Renate Fuchs, who retires this year. In the mid-1980s, Renate pioneered studies on the ion-conducting properties of the recently discovered early and late endosomes and the mechanisms governing endosomal acidification. As described in this review, after uptake through one of many mechanistically distinct endocytic pathways, internalized proteins merge into a common early/sorting endosome. From there they again diverge along distinct sorting pathways, back to the cell surface, on to the trans-Golgi network or across polarized cells. Other transmembrane receptors are packaged into intraluminal vesicles of late endosomes/multivesicular bodies that eventually fuse with and deliver their content to lysosomes for degradation. Endosomal acidification, in part, determines sorting along this pathway. We describe other sorting machinery and mechanisms, as well as the rab proteins and phosphatidylinositol lipids that serve to dynamically define membrane compartments along the endocytic pathway. PMID:26861668

  6. Minimal distortion pathways in polyhedral rearrangements.

    PubMed

    Casanova, David; Cirera, Jordi; Llunell, Miquel; Alemany, Pere; Avnir, David; Alvarez, Santiago

    2004-02-18

    A definition of minimum distortion paths between two polyhedra in terms of continuous shape measures (CShM) is presented. A general analytical expression deduced for such pathways makes use of one parameter, the minimum distortion constant, that can be easily obtained through the CShM methodology and is herein tabulated for pairs of polyhedra having four to eight vertexes. The work presented here also allows us to obtain representative model molecular structures along the interconversion pathways. Several commonly used polytopal rearrangement pathways are shown to be in fact minimum distortion pathways: the spread path leading from the tetrahedron to the square, the Berry pseudorotation that interconverts a square pyramid and a trigonal bipyramid, and the Bailar twist for the interconversion of the octahedron and the trigonal prism. Examples of applications to the analysis of the stereochemistries of several families of metal complexes are presented. PMID:14871107

  7. Modularized TGFbeta-Smad Signaling Pathway

    NASA Technical Reports Server (NTRS)

    Li, Yongfeng; Wang, M.; Carra, C.; Cucinotta, F. A.

    2011-01-01

    The Transforming Growth Factor beta (TGFbeta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. It can be induced by several factors, including ionizing radiation. It is regulated by Smads in a negative feedback loop through promoting increases in the regulatory Smads in the cell nucleus, and subsequent expression of inhibitory Smad, Smad7 to form a ubiquitin ligase with Smurf targeting active TGF receptors for degradation. In this work, we proposed a mathematical model to study the radiation-induced Smad-regulated TGF signaling pathway. By modularization, we are able to analyze each module (subsystem) and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, along the TGF signaling pathway is discussed by mathematical analysis and numerical simulation.

  8. Role of Hemichannels in CNS Inflammation and the Inflammasome Pathway.

    PubMed

    Kim, Yuri; Davidson, Joanne O; Gunn, Katherine C; Phillips, Anthony R; Green, Colin R; Gunn, Alistair J

    2016-01-01

    Neurodegenerative, cardiovascular, and metabolic disorders, once triggered, share a number of common features, including sustained inflammatory cell activation and vascular disruption. These shared pathways are induced independently of any genetic predisposition to the disease or the precise external stimulus. Glial cells respond to injury with an innate immune response that includes release of proinflammatory cytokines and chemokines. Vascular endothelial cells may also be affected, leading to opening of the blood-brain barrier that facilitates invasion by circulating inflammatory cells. Inflammation can trigger acute neural injury followed by chronic inflammation that plays a key role in neurodegenerative conditions. Gap junction channels normally allow direct cell-to-cell communication. They are formed by the docking of two hemichannels, one contributed by each of the neighboring cells. While the opening probability of these channels is tightly controlled under resting conditions, hemichannels can open in response to injury or inflammatory factors, forming a large, relatively nonselective membrane pore. In this review, we consider the CNS immune system from the perspective that modulating connexin hemichannel opening can prevent tissue damage arising from excessive and uncontrolled inflammation. We discuss connexin channel roles in microglia, astrocytes, and endothelial cells in both acute and chronic inflammatory conditions, and in particular describe the role of connexin hemichannels in the inflammasome pathway where they contribute to both its activation and its spread to neighboring cells. Finally, we describe the benefits of hemichannel block in animal models of brain injury. PMID:27038371

  9. Dynamic optimization identifies optimal programmes for pathway regulation in prokaryotes.

    PubMed

    Bartl, Martin; Kötzing, Martin; Schuster, Stefan; Li, Pu; Kaleta, Christoph

    2013-01-01

    To survive in fluctuating environmental conditions, microorganisms must be able to quickly react to environmental challenges by upregulating the expression of genes encoding metabolic pathways. Here we show that protein abundance and protein synthesis capacity are key factors that determine the optimal strategy for the activation of a metabolic pathway. If protein abundance relative to protein synthesis capacity increases, the strategies shift from the simultaneous activation of all enzymes to the sequential activation of groups of enzymes and finally to a sequential activation of individual enzymes along the pathway. In the case of pathways with large differences in protein abundance, even more complex pathway activation strategies with a delayed activation of low abundance enzymes and an accelerated activation of high abundance enzymes are optimal. We confirm the existence of these pathway activation strategies as well as their dependence on our proposed constraints for a large number of metabolic pathways in several hundred prokaryotes.

  10. Quantifying the economic competitiveness of cellulosic biofuel pathways under uncertainty and regional sensitivity

    NASA Astrophysics Data System (ADS)

    Brown, Tristan R.

    The revised Renewable Fuel Standard requires the annual blending of 16 billion gallons of cellulosic biofuel by 2022 from zero gallons in 2009. The necessary capacity investments have been underwhelming to date, however, and little is known about the likely composition of the future cellulosic biofuel industry as a result. This dissertation develops a framework for identifying and analyzing the industry's likely future composition while also providing a possible explanation for why investment in cellulosic biofuels capacity has been low to date. The results of this dissertation indicate that few cellulosic biofuel pathways will be economically competitive with petroleum on an unsubsidized basis. Of five cellulosic biofuel pathways considered under 20-year price forecasts with volatility, only two achieve positive mean 20-year net present value (NPV) probabilities. Furthermore, recent exploitation of U.S. shale gas reserves and the subsequent fall in U.S. natural gas prices have negatively impacted the economic competitiveness of all but two of the cellulosic biofuel pathways considered; only two of the five pathways achieve substantially higher 20-year NPVs under a post-shale gas economic scenario relative to a pre-shale gas scenario. The economic competitiveness of cellulosic biofuel pathways with petroleum is reduced further when considered under price uncertainty in combination with realistic financial assumptions. This dissertation calculates pathway-specific costs of capital for five cellulosic biofuel pathway scenarios. The analysis finds that the large majority of the scenarios incur costs of capital that are substantially higher than those commonly assumed in the literature. Employment of these costs of capital in a comparative TEA greatly reduces the mean 20-year NPVs for each pathway while increasing their 10-year probabilities of default to above 80% for all five scenarios. Finally, this dissertation quantifies the economic competitiveness of six

  11. JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny

    PubMed Central

    2012-01-01

    Background It has been reported that the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway regulates erythropoietin (EPO)-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival have also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the function of EPO activation of JAK-STAT and PI3K/AKT pathways in the development of erythroid progenitors from hematopoietic CD34+ progenitor cells, as well as to distinguish early EPO target genes in human erythroid progenitors during ontogeny. Methods Hematopoietic CD34+ progenitor cells, isolated from fetal and adult hematopoietic tissues, were differentiated into erythroid progenitor cells. We have used microarray analysis to examine JAK-STAT and PI3K/AKT related genes, as well as broad gene expression modulation in these human erythroid progenitor cells. Results In microarray studies, a total of 1755 genes were expressed in fetal liver, 3844 in cord blood, 1770 in adult bone marrow, and 1325 genes in peripheral blood-derived erythroid progenitor cells. The erythroid progenitor cells shared 1011 common genes. Using the Ingenuity Pathways Analysis software, we evaluated the network pathways of genes linked to hematological system development, cellular growth and proliferation. The KITLG, EPO, GATA1, PIM1 and STAT3 genes represent the major connection points in the hematological system development linked genes. Some JAK-STAT signaling pathway-linked genes were steadily upregulated throughout ontogeny (PIM1, SOCS2, MYC, PTPN11), while others were downregulated (PTPN6, PIAS, SPRED2). In addition, some JAK-STAT pathway related genes are differentially expressed only in some stages of ontogeny (STATs, GRB2, CREBB). Beside the continuously upregulated (AKT1, PPP2CA, CHUK, NFKB1) and downregulated (FOXO1, PDPK1, PIK3CG) genes in the PI3K-AKT signaling pathway, we also observed intermittently regulated gene expression

  12. Final report

    SciTech Connect

    Weissman, Jon B

    2006-04-30

    computational resources in order to use the service, and the user need not be concerned with performance tuning. This can all be done by the service provider. We believe that the next dominant paradigm for high performance computing will be based on high-end network services. Putting high performance applications on-line will create a new generation of community services. Community services have several features which make their deployment challenging: (i) they must provide high performance, (ii) they are resource intensive, and (iii) they may be built upon a large existing code base. Many groups have built significant infrastructure for providing domain-specific high-end services [6][8][12][14][22][24][27][31][32]. However, this process is labor-intensive and time-consuming as evidenced by the development time required to build many of these systems. The reason is that these systems are all built from the ground-up with little existing infrastructure to utilize. Providing efficient, reliable, secure, and scalable services requires significant run-time infrastructure and middleware (Figure 1). The goal of this project is to develop general-purpose middleware to support the rapid deployment of high-end community services. In this proposal, we will focus on scalable middleware in support of resource management and reliability. We also propose a system architecture that integrates the middleware components. Our middleware and system architecture will be designed to accommodate and integrate middleware solutions for security and user interface1 developed by other groups. We will produce middleware that can be leveraged by community services running in clusters, supercomputers, and in Grids. One of the novel aspects of our approach is that the tension between resource sharing for the 'common good' and resource monopolization for the 'individual good' is significantly reduced. To increase the impact of this project, the middleware will be integrated into a widely used implementation

  13. Metabolome-scale de novo pathway reconstruction using regioisomer-sensitive graph alignments

    PubMed Central

    Yamanishi, Yoshihiro; Tabei, Yasuo; Kotera, Masaaki

    2015-01-01

    Motivation: Recent advances in mass spectrometry and related metabolomics technologies have enabled the rapid and comprehensive analysis of numerous metabolites. However, biosynthetic and biodegradation pathways are only known for a small portion of metabolites, with most metabolic pathways remaining uncharacterized. Results: In this study, we developed a novel method for supervised de novo metabolic pathway reconstruction with an improved graph alignment-based approach in the reaction-filling framework. We proposed a novel chemical graph alignment algorithm, which we called PACHA (Pairwise Chemical Aligner), to detect the regioisomer-sensitive connectivities between the aligned substructures of two compounds. Unlike other existing graph alignment methods, PACHA can efficiently detect only one common subgraph between two compounds. Our results show that the proposed method outperforms previous descriptor-based methods or existing graph alignment-based methods in the enzymatic reaction-likeness prediction for isomer-enriched reactions. It is also useful for reaction annotation that assigns potential reaction characteristics such as EC (Enzyme Commission) numbers and PIERO (Enzymatic Reaction Ontology for Partial Information) terms to substrate–product pairs. Finally, we conducted a comprehensive enzymatic reaction-likeness prediction for all possible uncharacterized compound pairs, suggesting potential metabolic pathways for newly predicted substrate–product pairs. Contact: maskot@bio.titech.ac.jp PMID:26072478

  14. Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea

    PubMed Central

    Barberán, Sara; Martín-Durán, José M.; Cebrià, Francesc

    2016-01-01

    The EGFR pathway is an essential signaling system in animals, whose core components are the epidermal growth factors (EGF ligands) and their trans-membrane tyrosine kinase receptors (EGFRs). Despite extensive knowledge in classical model organisms, little is known of the composition and function of the EGFR pathway in most animal lineages. Here, we have performed an extensive search for the presence of EGFRs and EGF ligands in representative species of most major animal clades, with special focus on the planarian Schmidtea mediterranea. With the exception of placozoans and cnidarians, we found that the EGFR pathway is potentially present in all other analyzed animal groups, and has experienced frequent independent expansions. We further characterized the expression domains of the EGFR/EGF identified in S. mediterranea, revealing a wide variety of patterns and localization in almost all planarian tissues. Finally, functional experiments suggest an interaction between one of the previously described receptors, Smed-egfr-5, and the newly found ligand Smed-egf-6. Our findings provide the most comprehensive overview to date of the EGFR pathway, and indicate that the last common metazoan ancestor had an initial complement of one EGFR and one putative EGF ligand, which was often expanded or lost during animal evolution. PMID:27325311

  15. Coordinating towards a Common Good

    NASA Astrophysics Data System (ADS)

    Santos, Francisco C.; Pacheco, Jorge M.

    2010-09-01

    Throughout their life, humans often engage in collective endeavors ranging from family related issues to global warming. In all cases, the tragedy of the commons threatens the possibility of reaching the optimal solution associated with global cooperation, a scenario predicted by theory and demonstrated by many experiments. Using the toolbox of evolutionary game theory, I will address two important aspects of evolutionary dynamics that have been neglected so far in the context of public goods games and evolution of cooperation. On one hand, the fact that often there is a threshold above which a public good is reached [1, 2]. On the other hand, the fact that individuals often participate in several games, related to the their social context and pattern of social ties, defined by a social network [3, 4, 5]. In the first case, the existence of a threshold above which collective action is materialized dictates a rich pattern of evolutionary dynamics where the direction of natural selection can be inverted compared to standard expectations. Scenarios of defector dominance, pure coordination or coexistence may arise simultaneously. Both finite and infinite population models are analyzed. In networked games, cooperation blooms whenever the act of contributing is more important than the effort contributed. In particular, the heterogeneous nature of social networks naturally induces a symmetry breaking of the dilemmas of cooperation, as contributions made by cooperators may become contingent on the social context in which the individual is embedded. This diversity in context provides an advantage to cooperators, which is particularly strong when both wealth and social ties follow a power-law distribution, providing clues on the self-organization of social communities. Finally, in both situations, it can be shown that individuals no longer play a defection dominance dilemma, but effectively engage in a general N-person coordination game. Even if locally defection may seem

  16. Pathways from Poverty.

    ERIC Educational Resources Information Center

    Baldwin, Barbara, Ed.

    1995-01-01

    Articles in this theme issue are based on presentations at the Pathways from Poverty Workshop held in Albuquerque, New Mexico, on May 18-25, 1995. The event aimed to foster development of a network to address rural poverty issues in the Western Rural Development Center (WRDC) region. Articles report on outcomes from the Pathways from Poverty…

  17. Career Pathways in Indiana

    ERIC Educational Resources Information Center

    McCaskey, Steve; Johnson, Tricia

    2010-01-01

    The revisions to the Carl D. Perkins Career and Technical Education Act of 2006 require that career and technical education (CTE) programs provide students with a clear pathway from secondary to postsecondary education, and into high-wage, high-skill and high-demand careers. States nationwide are developing programs, called career pathways, to…

  18. Building clinical pathways.

    PubMed

    Leininger, S M

    1998-01-01

    TQM principles change the work environment so that point-of-service personnel can improve health care delivery to patients. The clinical pathway process starts with the principles of TQM. In the era of managed care, health care resources can be managed effectively using a clinical pathway. The multidisciplinary team has the opportunity to improve the health care services provided to patients.

  19. Essential Role of TGF-β/Smad Pathway on Statin Dependent Vascular Smooth Muscle Cell Regulation

    PubMed Central

    Rodríguez-Vita, Juan; Sánchez-Galán, Eva; Santamaría, Beatriz; Sánchez-López, Elsa; Rodrigues-Díez, Raquel; Blanco-Colio, Luís Miguel; Egido, Jesús; Ortiz, Alberto; Ruiz-Ortega, Marta

    2008-01-01

    Background The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins) exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-β (TGF-β) in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-β/Smad pathway in atherosclerosis and vascular cells. Methodology In cultured vascular smooth muscle cells (VSMCs) statins enhanced Smad pathway activation caused by TGF-β. In addition, statins upregulated TGF-β receptor type II (TRII), and increased TGF-β synthesis and TGF-β/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-β induced apoptosis and increased TGF-β-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-β/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. Conclusions Statins enhance TGF-β/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-β/Smad pathway is essential for statins-dependent actions in VSMCs. PMID:19088845

  20. Committee Handbook for Common Learning.

    ERIC Educational Resources Information Center

    Burton, Sharon; And Others

    This manual on general education and common learning was prepared by and for the Dallas County Community College District's (DCCCD's) Committees for Common Learning (CCL's), which have been charged with reviewing the DCCCD's general education curriculum and degree requirements and making recommendations concerning common learning requirements and…

  1. Culture and the Common School

    ERIC Educational Resources Information Center

    Feinberg, Walter

    2007-01-01

    This essay addresses the question: given the flattening out of the cultural hierarchy that was the vestige of colonialism and nation-building, is there anything that might be uniquely common about the common school in this postmodern age? By "uniquely common" I do not mean those subjects that all schools might teach, such as reading or arithmetic.…

  2. Common Core State Standards 101

    ERIC Educational Resources Information Center

    Rothman, Robert

    2013-01-01

    The Common Core State Standards (CCSS) represent the first time that nearly every state has set common expectations for what students should know and be able to do. In the past, each state set its own standards, and the results varied widely. And while states collectively developed these common standards, decisions about the curriculum and…

  3. Conference Summary Final Remarks

    NASA Astrophysics Data System (ADS)

    Greiner, Walter

    2007-05-01

    Finally we come to the last talk. The end of the Conference is near! I try to reflect on an interesting Conference, with many different - diverse - topics and 5 parallel afternoon sessions. How to solve this difficulty? I do it my way and present a selection of what I personally found interesting. I illustrate these topics with the help of slides which are borrowed from various speakers at the conference. There are outstanding problems, which will also find attention and interest if explained to non-nuclear physicists, common people. I will address four such topics which were were discussed at this conference: Heavy-Ion Cancer Therapy Extension of the Periodic Table - Superheavy Elements Nuclear Astrophysics Hot compressed elementary matter - Production - Phases

  4. Leading the Common Core State Standards: From Common Sense to Common Practice

    ERIC Educational Resources Information Center

    Dunkle, Cheryl A.

    2012-01-01

    Many educators agree that we already know how to foster student success, so what is keeping common sense from becoming common practice? The author provides step-by-step guidance for overcoming the barriers to adopting the Common Core State Standards (CCSS) and achieving equity and excellence for all students. As an experienced teacher and…

  5. Updating the Wnt pathways

    PubMed Central

    Yu, Jia; Virshup, David M.

    2014-01-01

    In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

  6. Remodeling of Calcium Entry Pathways in Cancer.

    PubMed

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2016-01-01

    Ca(2+) entry pathways play important roles in control of many cellular functions, including long-term proliferation, migration and cell death. In recent years, it is becoming increasingly clear that, in some types of tumors, remodeling of Ca(2+) entry pathways could contribute to cancer hallmarks such as excessive proliferation, cell migration and invasion as well as resistance to cell death or survival. In this chapter we briefly review findings related to remodeling of Ca(2+) entry pathways in cancer with emphasis on the mechanisms that contribute to increased store-operated Ca(2+) entry (SOCE) and store-operated currents (SOCs) in colorectal cancer cells. Finally, since SOCE appears critically involved in colon tumorogenesis, the inhibition of SOCE by aspirin and other NSAIDs and its possible contribution to colon cancer chemoprevention is reviewed.

  7. Remodeling of Calcium Entry Pathways in Cancer.

    PubMed

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2016-01-01

    Ca(2+) entry pathways play important roles in control of many cellular functions, including long-term proliferation, migration and cell death. In recent years, it is becoming increasingly clear that, in some types of tumors, remodeling of Ca(2+) entry pathways could contribute to cancer hallmarks such as excessive proliferation, cell migration and invasion as well as resistance to cell death or survival. In this chapter we briefly review findings related to remodeling of Ca(2+) entry pathways in cancer with emphasis on the mechanisms that contribute to increased store-operated Ca(2+) entry (SOCE) and store-operated currents (SOCs) in colorectal cancer cells. Finally, since SOCE appears critically involved in colon tumorogenesis, the inhibition of SOCE by aspirin and other NSAIDs and its possible contribution to colon cancer chemoprevention is reviewed. PMID:27161240

  8. A pathway to academic accreditation

    SciTech Connect

    Seitz, M.R.

    1994-09-01

    The pathways to successfully accrediting programs through a partnership with a local college can be convoluted and offer many dead ends. Those pathways can be made straighter and have fewer false starts by following a plan that has worked. Accreditation of courses and programs can add credibility and prestige to a program. The process can be facilitated by following a basic plan such as the one outlined. The discussion will track the preliminary activities that form the ground work for the beginning of the accreditation process through final approval by a college`s State Board of trustees or regents. On the road to approval, the packaging of courses for presentation, the formulation and composition of an advisory committee, the subsequent use of the advisors, presentation to the faculty committees, the presentation to the college`s governing board of trustees or regents, and final approval by the State Board are covered. An important benefit of accreditation is the formation of a partnership with the local college. Teaming with a local college to provide an accredited certificate in a field of employee training is an excellent opportunity to establish an educational partnership within the local community that will be of benefit to the participating entities. It also represents a training/retraining opportunity in direct support of the US Department of Energy`s current missions of partnership and localization. The accredited modules can be taught where appropriate by college personnel or loaned instructors from the work site. By using the company employees who are working with the topics covered in the modules, the courses are kept up-to-date.

  9. MOLECULAR PATHWAYS: JAK/STAT PATHWAY: MUTATIONS, INHIBITORS, AND RESISTANCE

    PubMed Central

    Quintás-Cardama, Alfonso; Verstovsek, Srdan

    2016-01-01

    Aberrant activation of the JAK/STAT pathway has been reported in a variety of disease states, including inflammatory conditions, hematologic malignancies, and solid tumors. For instance, a large proportion of patients with myeloproliferative neoplasms (MPNs) carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of the pathogenesis of MPNs and it has facilitated the development of therapeutics capable of suppressing the constitutive activation of the JAK/STAT pathway, now recognized as a common underlying biological abnormality in MPNs. Ruxolitinib is an oral JAK1 and JAK2 inhibitor that has recently been approved for the treatment of myelofibrosis and has been tested against other hematologic malignancies. A series of agents with different specificities against different members of the JAK family of proteins is currently undergoing evaluation in clinical trials for patients with MPNs, lymphoma, and solid tumors such as breast or pancreatic cancer. Despite their significant clinical activity exhibited in myelofibrosis, some patients fail to respond or progress during JAK kinase inhibitor therapy. Recent reports have shed light into the mechanisms of resistance to JAK kinase inhibitor therapy. Several approaches hold promise to overcome such resistance. PMID:23406773

  10. Hepatic haemangioma: common and uncommon imaging features.

    PubMed

    Klotz, T; Montoriol, P-F; Da Ines, D; Petitcolin, V; Joubert-Zakeyh, J; Garcier, J-M

    2013-09-01

    The haemangioma, the most common non-cystic hepatic lesion, most often discovered by chance, may in certain situations raise diagnostic problems in imaging. In this article, the authors first demonstrate that the radiological appearance of the hepatic haemangioma, in its typical form, is closely related to three known histological sub-types. They then show that certain atypical features should be known in order to establish a diagnosis. They also observe the potential interactions between the haemangioma, an active vascular lesion, and the adjacent hepatic parenchyma. Finally, they discuss the specific paediatric features of hepatic haemangiomas and illustrate the case of a hepatic angiosarcoma.

  11. Constructing the Commons: Practical Projects To Build the Information Commons.

    ERIC Educational Resources Information Center

    Lee, Daniel R.

    2003-01-01

    Describes several projects aimed at building the Information Commons, including: Knowledge Conservancy plans to create a database of all freely available digitized content; the Universal Library, a project with the long-term goal of providing free, online access to all books; and several projects of the Creative Commons intended to build a robust…

  12. How Common is Common Use Facilities at Airports

    NASA Astrophysics Data System (ADS)

    Barbeau, Addison D.

    This study looked at common use airports across the country and at the implementation of common use facailities at airports. Common use consists of several elements that maybe installed at an airport. One of the elements is the self-service kiosks that allow passengers to have a faster check-in process, therefore moving them more quickly within the airport. Another element is signage and the incorporation of each airline's logo. Another aspect of common useis an airport regaining control of terminal gates by reducing the number of gates that are exclusively leased to a specific air carrier. This research focused on the current state of the common use facilities across the United States and examines the advantages and disadvantages of this approach. The research entailed interviews with personnel at a wide range of airports and found that each airport is in a different stage of implementation; some have fully implemented the common use concept while others are in the beginning stages of implementation. The questions were tailored to determine what the advantages and disadvantages are of a common use facility. The most common advantages reported included flexibility and cost. In the commom use system the airport reserves the right to move any airline to a different gate at any time for any reason. In turn, this helps reduce gates delays at that facility. For the airports that were interviewed no major disadvantages were reported. One down side of common use facilities for the airport involved is the major capital cost that is required to move to a common use system.

  13. Discovery of Unclustered Fungal Indole Diterpene Biosynthetic Pathways through Combinatorial Pathway Reassembly in Engineered Yeast.

    PubMed

    Tang, Man-Cheng; Lin, Hsiao-Ching; Li, Dehai; Zou, Yi; Li, Jian; Xu, Wei; Cacho, Ralph A; Hillenmeyer, Maureen E; Garg, Neil K; Tang, Yi

    2015-11-01

    The structural diversity and biological activities of fungal indole diterpenes (IDTs) are generated in large part by the IDT cyclases (IDTCs). Identifying different IDTCs from IDT biosynthetic pathways is therefore important toward understanding how these enzymes introduce chemical diversity from a common linear precursor. However, IDTCs involved in the cyclization of the well-known aflavinine subgroup of IDTs have not been discovered. Here, using Saccharomyces cerevisiae as a heterologous host and a phylogenetically guided enzyme mining approach, we combinatorially assembled IDT biosynthetic pathways using IDTCs homologues identified from different fungal hosts. We identified the genetically standalone IDTCs involved in the cyclization of aflavinine and anominine and produced new IDTs not previously isolated. The cyclization mechanisms of the new IDTCs were proposed based on the yeast reconstitution results. Our studies demonstrate heterologous pathway assembly is a useful tool in the reconstitution of unclustered biosynthetic pathways.

  14. Different routes, same pathways: Molecular mechanisms under silver ion and nanoparticle exposures in the soil sentinel Eisenia fetida.

    PubMed

    Novo, Marta; Lahive, Elma; Díez-Ortiz, María; Matzke, Marianne; Morgan, Andrew J; Spurgeon, David J; Svendsen, Claus; Kille, Peter

    2015-10-01

    Use of nanotechnology products is increasing; with silver (Ag) nanoparticles particularly widely used. A key uncertainty surrounding the risk assessment of AgNPs is whether their effects are driven through the same mechanism of action that underlies the toxic effects of Ag ions. We present the first full transcriptome study of the effects of Ag ions and NPs in an ecotoxicological model soil invertebrate, the earthworm Eisenia fetida. Gene expression analyses indicated similar mechanisms for both silver forms with toxicity being exerted through pathways related to ribosome function, sugar and protein metabolism, molecular stress, disruption of energy production and histones. The main difference seen between Ag ions and NPs was associated with potential toxicokinetic effects related to cellular internalisation and communication, with pathways related to endocytosis and cilia being significantly enriched. These results point to a common final toxicodynamic response, but initial internalisation driven by different exposure routes and toxicokinetic mechanisms. PMID:26204059

  15. The Whole Genome Sequence of Sphingobium chlorophenolicum L-1: Insights into the Evolution of the Pentachlorophenol Degradation Pathway

    SciTech Connect

    Copley, Shelley D.; Rokicki, Joseph; Turner, Pernilla; Daligault, Hajnalka E.; Nolan, Matt; Land, Miriam L

    2012-01-01

    Sphingobium chlorophenolicum Strain L-1 can mineralize the toxic pesticide pentachlorophenol (PCP). We have sequenced the genome of S. chlorophenolicum Strain L-1. The genome consists of a primary chromosome that encodes most of the genes for core processes, a secondary chromosome that encodes primarily genes that appear to be involved in environmental adaptation, and a small plasmid. The genes responsible for degradation of PCP are found on chromosome 2. We have compared the genomes of S. chlorophenolicum Strain L-1 and Sphingobium japonicum, a closely related Sphingomonad that degrades lindane. Our analysis suggests that the genes encoding the first three enzymes in the PCP degradation pathway were acquired via two different horizontal gene transfer events, and the genes encoding the final two enzymes in the pathway were acquired from the most recent common ancestor of these two bacteria.

  16. Pathways to hydrogen as an energy carrier.

    PubMed

    Sigfusson, Thorsteinn I

    2007-04-15

    When hydrogen is used as an alternative energy carrier, it is very important to understand the pathway from the primary energy source to the final use of the carrier. This involves, for example, the understanding of greenhouse gas emissions associated with the production of hydrogen and throughout the lifecycle of a given utilization pathway as well as various energy or exergy efficiencies and aspects involved. This paper which is based on a talk given at the Royal Society in London assesses and reviews the various production pathways for hydrogen with emphasis on emissions, energy use and energy efficiency. The paper also views some aspects of the breaking of the water molecule and examines some new emerging physical evidence which could pave the way to a new and more feasible pathway. A special attention will be given to the use of the renewable energy pathway. As an example of a hydrogen society that could be based on renewable primary energy, the paper describes the hydrogen society experiments in Iceland as well as unconventional hydrogen obtained from geothermal gases. In the light of our experience, attempts will be made to shed light upon drivers as well as obstacles in the development of a hydrogen society.

  17. Uncovering common bacterial skin infections.

    PubMed

    Napierkowski, Daria

    2013-03-10

    The four most common bacterial skin infections are impetigo, erysipelas, cellulitis, and folliculitis. This article summarizes current information about the etiology, clinical presentation, diagnosis, prevention, treatment, and implications for primary care practice needed to effectively diagnose and treat common bacterial skin infections. PMID:23361375

  18. Building on the Common Core

    ERIC Educational Resources Information Center

    Conley, David T.

    2011-01-01

    The Common Core State Standards, released in June 2010, offer an opportunity to shift education away from shallow, test-prep instruction and toward a focus on key cognitive skills, writes Conley. Two consortia of states are now developing common assessments to measure these standards--assessments that will be designed to capture deeper, more…

  19. The Tragedy of the Commons

    ERIC Educational Resources Information Center

    Short, Daniel

    2016-01-01

    The tragedy of the commons is one of the principal tenets of ecology. Recent developments in experiential computer-based simulation of the tragedy of the commons are described. A virtual learning environment is developed using the popular video game "Minecraft". The virtual learning environment is used to experience first-hand depletion…

  20. The Common Core Takes Hold

    ERIC Educational Resources Information Center

    Rothman, Robert

    2014-01-01

    A survey administered in the spring of 2013 by the Center on Education Policy (CEP) inquired into the implementation of Common Core State Standards at that time. Based on self-reports by state officials, the survey found that curricula aligned to the common core were already being taught in at least some districts or grade levels. All states…

  1. Understanding Common Core State Standards

    ERIC Educational Resources Information Center

    Kendall, John S.

    2011-01-01

    Now that the Common Core standards are coming to just about every school, what every school leader needs is a straightforward explanation that lays out the benefits of the Common Core in plain English, provides a succinct overview, and gets everyone thinking about how to transition to this promising new paradigm. This handy, inexpensive booklet…

  2. Remedies for Common Cold Symptoms

    PubMed Central

    Miller, Penny F.

    1991-01-01

    Individuals suffering from intolerable symptoms of the common cold can now be advised of safe and effective products for symptomatic relief. This article describes and discusses four categories of drugs used to treat the common cold. To simplify the product selection process for family physicians, suggestions are included for possible ingredients for treatments of specific cold symptoms. PMID:21234087

  3. The common ancestry of life

    PubMed Central

    2010-01-01

    Background It is common belief that all cellular life forms on earth have a common origin. This view is supported by the universality of the genetic code and the universal conservation of multiple genes, particularly those that encode key components of the translation system. A remarkable recent study claims to provide a formal, homology independent test of the Universal Common Ancestry hypothesis by comparing the ability of a common-ancestry model and a multiple-ancestry model to predict sequences of universally conserved proteins. Results We devised a computational experiment on a concatenated alignment of universally conserved proteins which shows that the purported demonstration of the universal common ancestry is a trivial consequence of significant sequence similarity between the analyzed proteins. The nature and origin of this similarity are irrelevant for the prediction of "common ancestry" of by the model-comparison approach. Thus, homology (common origin) of the compared proteins remains an inference from sequence similarity rather than an independent property demonstrated by the likelihood analysis. Conclusion A formal demonstration of the Universal Common Ancestry hypothesis has not been achieved and is unlikely to be feasible in principle. Nevertheless, the evidence in support of this hypothesis provided by comparative genomics is overwhelming. Reviewers this article was reviewed by William Martin, Ivan Iossifov (nominated by Andrey Rzhetsky) and Arcady Mushegian. For the complete reviews, see the Reviewers' Report section. PMID:21087490

  4. OSTA commonality analysis, volume 2

    NASA Technical Reports Server (NTRS)

    Stolarik, E. G.

    1981-01-01

    The 13 OSTA disciplines are examined and the applications being performed under each discipline and the parameter requirements associated with the various applications are identified. It contains a variety of printouts from the commonality database built using DRS on the Vax. It also shows commonality of parameter requirements by discipline and by application.

  5. Diversity in Biosynthetic Pathways of Galactolipids in the Light of Endosymbiotic Origin of Chloroplasts.

    PubMed

    Sato, Naoki; Awai, Koichiro

    2016-01-01

    Cyanobacteria and chloroplasts perform oxygenic photosynthesis, and share a common origin. Galactolipids are present in the photosynthetic membranes of both cyanobacteria and chloroplasts, but the biosynthetic pathways of the galactolipids are significantly different in the two systems. In this minireview, we explain the history of the discovery of the cyanobacterial pathway, and present a probable scenario of the evolution of the two pathways.

  6. Testing effects for common versus proper names.

    PubMed

    Sensenig, Amanda E; Littrell-Baez, Megan K; Delosh, Edward L

    2011-08-01

    The present study examines the testing effect as a function of item meaningfulness. In Experiments 1 and 2 participants studied lists of words that could serve as proper names or occupations (e.g., Mr Baker or baker), with the items given in a name context for one group and an occupation context for a second group. During an intervening phase participants restudied some items and were given a cued recall test (Experiment 1) or a free recall test (Experiment 2) on other items. On a final free recall test memory was better for tested items than studied items in both the name and occupation contexts. Experiment 3 followed the same procedure as Experiment 1, except that participants studied lists of proper names that do not have alternative uses in the English language (e.g., Mr Anderson) or studied concrete nouns (e.g., letter). Tested items were better remembered on a final test than studied items, and there was no interaction with type of study material. These results show that the testing effect extends to proper names, material that is commonly assumed to differ from common names on several dimensions. PMID:21919593

  7. Pathways to chromothripsis.

    PubMed

    Ivkov, Robert; Bunz, Fred

    2015-01-01

    Chromothripsis is a recently recognized mode of genetic instability that generates chromosomes with strikingly large numbers of segmental re-arrangements. While the characterization of these derivative chromosomes has provided new insights into the processes by which cancer genomes can evolve, the underlying signaling events and molecular mechanisms remain unknown. In medulloblastomas, chromothripsis has been observed to occur in the context of mutational inactivation of p53 and activation of the canonical Hedgehog (Hh) pathway. Recent studies have illuminated mechanistic links between these 2 signaling pathways, including a novel PTCH1 homolog that is regulated by p53. Here, we integrate this new pathway into a hypothetical model for the catastrophic DNA breakage that appears to trigger profound chromosomal rearrangements. PMID:26178348

  8. Clinical Pathway for Thyroidectomy.

    PubMed

    Villar del Moral, Jesús María; Soria Aledo, Víctor; Colina Alonso, Alberto; Flores Pastor, Benito; Gutiérrez Rodríguez, María Teresa; Ortega Serrano, Joaquín; Parra Hidalgo, Pedro; Ros López, Susana

    2015-05-01

    Clinical pathways are care plans applicable to patient care procedures that present variations in practice and a predictable clinical course. They are designed not as a substitute for clinical judgment, but rather as a means to improve the effectiveness and efficiency of the procedures. This clinical pathway is the result of a collaborative work of the Sections of Endocrine Surgery and Quality Management of the Spanish Association of Surgeons. It attempts to provide a framework for standardizing the performance of thyroidectomy, the most frequently performed operation in endocrine surgery. Along with the usual documents of clinical pathways (temporary matrix, variance tracking and information sheets, assessment indicators and a satisfaction questionnaire) it includes a review of the scientific evidence around different aspects of pre, intra and postoperative management. Among others, antibiotic and antithrombotic prophylaxis, preoperative preparation in hyperthyroidism, intraoperative neuromonitoring and systems for obtaining hemostasis are included, along with management of postoperative hypocalcemia. PMID:25732107

  9. Clinical Pathway for Thyroidectomy.

    PubMed

    Villar del Moral, Jesús María; Soria Aledo, Víctor; Colina Alonso, Alberto; Flores Pastor, Benito; Gutiérrez Rodríguez, María Teresa; Ortega Serrano, Joaquín; Parra Hidalgo, Pedro; Ros López, Susana

    2015-05-01

    Clinical pathways are care plans applicable to patient care procedures that present variations in practice and a predictable clinical course. They are designed not as a substitute for clinical judgment, but rather as a means to improve the effectiveness and efficiency of the procedures. This clinical pathway is the result of a collaborative work of the Sections of Endocrine Surgery and Quality Management of the Spanish Association of Surgeons. It attempts to provide a framework for standardizing the performance of thyroidectomy, the most frequently performed operation in endocrine surgery. Along with the usual documents of clinical pathways (temporary matrix, variance tracking and information sheets, assessment indicators and a satisfaction questionnaire) it includes a review of the scientific evidence around different aspects of pre, intra and postoperative management. Among others, antibiotic and antithrombotic prophylaxis, preoperative preparation in hyperthyroidism, intraoperative neuromonitoring and systems for obtaining hemostasis are included, along with management of postoperative hypocalcemia.

  10. Final cook temperature monitoring

    NASA Astrophysics Data System (ADS)

    Stewart, John; Matthews, Michael; Glasco, Marc

    2006-04-01

    Fully cooked, ready-to-eat products represent one of the fastest growing markets in the meat and poultry industries. Modern meat cooking facilities typically cook chicken strips and nuggets at rates of 6000 lbs per hour, and it is a critical food safety issue to ensure the products on these lines are indeed fully cooked. Common practice now employs oven technicians to constantly measure final cook temperature with insertion-type thermocouple probes. Prior research has demonstrated that thermal imagery of chicken breasts and other products can be used to predict core temperature of products leaving an oven. In practice, implementation of a system to monitor core temperature can be difficult for several reasons. First, a wide variety of products are typically produced on the same production line and the system must adapt to all products. Second, the products can be often hard to find because they often leave the process in random order and may be touching or even overlapping. Another issue is finite measurement time which is typically only a few seconds. Finally, the system is subjected to a rigorous sanitation cycle and must hold up under wash down conditions. To address these problems, a calibrated 320x240 micro-bolometer camera was used to monitor the temperature of formed, breaded poultry products on a fully cooked production line for a period of one year. The study addressed the installation and operation of the system as well as the development of algorithms used to identify the product on a cluttered conveyor belt. It also compared the oven tech insertion probe measurements to the non-contact monitoring system performance.

  11. The Secretory Pathway Kinases

    PubMed Central

    Sreelatha, Anju; Kinch, Lisa N.; Tagliabracci, Vincent S.

    2015-01-01

    Protein phosphorylation is a nearly universal post-translation modification involved in a plethora of cellular events. Even though phosphorylation of extracellular proteins had been observed, the identity of the kinases that phosphorylate secreted proteins remained a mystery until recently. Advances in genome sequencing and genetic studies have paved the way for the discovery of a new class of kinases that localize within the endoplasmic reticulum, Golgi apparatus and the extracellular space. These novel kinases phosphorylate proteins and proteoglycans in the secretory pathway and appear to regulate various extracellular processes. Mutations in these kinases cause human disease, thus underscoring the biological importance of phosphorylation within the secretory pathway. PMID:25862977

  12. Common Variants for Heart Failure

    PubMed Central

    Shen, Shutong; Tao, Lichan; Wang, Xiuzhi; Kong, Xiangqing; Li, Xinli

    2015-01-01

    Heart failure (HF) is a common disease with high morbidity and mortality; however, none of the drugs available are now entirely optimal for the treatment of HF. In addition to various clinical diseases and environment influences, genetic factors also contribute to the development and progression of HF. Identifying the common variants for HF by genome-wide association studies will facilitate the understanding of pathophysiological mechanisms underlying HF. This review summarizes the recently identified common variants for HF risk and outcome and discusses their implications for the clinic therapy. PMID:26085806

  13. Common-offset ray tracing

    SciTech Connect

    Jannaud, L.R.

    1994-12-31

    In the SMART method, exact traveltimes, used as input of reflection tomography, are computed by tracing rays that are reflected on interpreted migrated events. Since picking migrated events is easier in common offset migrated images than in common shot migrated images, a common offset raytracing has been developed. It is based on a continuation method in the source position-shooting angle domain. It consists in following in this domain iso-offset lines and determining the points of these lines corresponding to the actual sources. It allows the user to compute all the arrivals even for complex media at a low computational cost.

  14. Verb-Final Typology

    ERIC Educational Resources Information Center

    Ogihara, Saeko

    2010-01-01

    This dissertation is a typological study of verb-final languages, the purpose of which is to examine various grammatical phenomena in verb-final languages to discover whether there are correlations between the final position of the verb and other aspects of grammar. It examines how finality of the verb interacts with argument coding in simple…

  15. A Chaperone-Assisted Degradation Pathway Targets Kinetochore Proteins to Ensure Genome Stability

    PubMed Central

    Kriegenburg, Franziska; Jakopec, Visnja; Poulsen, Esben G.; Nielsen, Sofie Vincents; Roguev, Assen; Krogan, Nevan; Gordon, Colin; Fleig, Ursula; Hartmann-Petersen, Rasmus

    2014-01-01

    Cells are regularly exposed to stress conditions that may lead to protein misfolding. To cope with this challenge, molecular chaperones selectively target structurally perturbed proteins for degradation via the ubiquitin-proteasome pathway. In mammals the co-chaperone BAG-1 plays an important role in this system. BAG-1 has two orthologues, Bag101 and Bag102, in the fission yeast Schizosaccharomyces pombe. We show that both Bag101 and Bag102 interact with 26S proteasomes and Hsp70. By epistasis mapping we identify a mutant in the conserved kinetochore component Spc7 (Spc105/Blinkin) as a target for a quality control system that also involves, Hsp70, Bag102, the 26S proteasome, Ubc4 and the ubiquitin-ligases Ubr11 and San1. Accordingly, chromosome missegregation of spc7 mutant strains is alleviated by mutation of components in this pathway. In addition, we isolated a dominant negative version of the deubiquitylating enzyme, Ubp3, as a suppressor of the spc7-23 phenotype, suggesting that the proteasome-associated Ubp3 is required for this degradation system. Finally, our data suggest that the identified pathway is also involved in quality control of other kinetochore components and therefore likely to be a common degradation mechanism to ensure nuclear protein homeostasis and genome integrity. PMID:24497846

  16. Conversion of KEGG metabolic pathways to SBGN maps including automatic layout

    PubMed Central

    2013-01-01

    Background Biologists make frequent use of databases containing large and complex biological networks. One popular database is the Kyoto Encyclopedia of Genes and Genomes (KEGG) which uses its own graphical representation and manual layout for pathways. While some general drawing conventions exist for biological networks, arbitrary graphical representations are very common. Recently, a new standard has been established for displaying biological processes, the Systems Biology Graphical Notation (SBGN), which aims to unify the look of such maps. Ideally, online repositories such as KEGG would automatically provide networks in a variety of notations including SBGN. Unfortunately, this is non‐trivial, since converting between notations may add, remove or otherwise alter map elements so that the existing layout cannot be simply reused. Results Here we describe a methodology for automatic translation of KEGG metabolic pathways into the SBGN format. We infer important properties of the KEGG layout and treat these as layout constraints that are maintained during the conversion to SBGN maps. Conclusions This allows for the drawing and layout conventions of SBGN to be followed while creating maps that are still recognizably the original KEGG pathways. This article details the steps in this process and provides examples of the final result. PMID:23953132

  17. The Use of Inhibitors to Study Endocytic Pathways of Gene Carriers: Optimization and Pitfalls

    PubMed Central

    Vercauteren, Dries; Vandenbroucke, Roosmarijn E; Jones, Arwyn T; Rejman, Joanna; Demeester, Joseph; De Smedt, Stefaan C; Sanders, Niek N; Braeckmans, Kevin

    2009-01-01

    Nonviral gene complexes can enter mammalian cells through different endocytic pathways. For efficient optimization of the gene carrier it is important to profile its cellular uptake, because this largely determines its intracellular processing and subsequent transfection efficiency. Most of the current information on uptake of these gene-delivery vehicles is based on data following the use of chemical inhibitors of endocytic pathways. Here, we have performed a detailed characterization of four commonly used endocytosis inhibitors [chlorpromazine, genistein, methyl-β-cyclodextrin (MβCD), and potassium depletion] on cell viability and endocytosis in five well-described cell lines. We found that chlorpromazine and to a lesser extent MβCD significantly decreased cell viability of some cell lines even after short incubation periods and at concentrations that are routinely used to inhibit endocytosis. Through analyzing the uptake and subcellular distribution of two fluorescent endocytic probes transferrin and lactosylceramide (LacCer) that are reported to enter cells via clathrin-dependent (CDE) and clathrin-independent (CIE) mechanisms, respectively, we showed poor specificity of these agents for inhibiting distinct endocytic pathways. Finally, we demonstrate that any inhibitory effects are highly cell line dependent. Overall, the data question the significance of performing endocytosis studies with these agents in the absence of very stringent controls. PMID:20010917

  18. Adolescents' theories of the commons.

    PubMed

    Flanagan, Constance; Gallay, Erin

    2014-01-01

    Drawing from research on civic engagement and environmental commitment, we make a case for the processes inherent in how adolescents' ideas about the commons (those things that bind a polity together) develop. Engagement in the public realm with a plethora of perspectives and a goal of finding common ground is fundamental. Adolescents participate in the public realm through mini-polities (e.g., schools, community organizations). Practices in those settings can reinforce or challenge dominant political narratives. Special attention is given to the natural environment as a commons that transcends generations and to the opportunities in schools and in community partnerships that enable adolescents to realize their interdependence with nature and to author decisions about the commons.

  19. Variance Components: Partialled vs. Common.

    ERIC Educational Resources Information Center

    Curtis, Ervin W.

    1985-01-01

    A new approach to partialling components is used. Like conventional partialling, this approach orthogonalizes variables by partitioning the scores or observations. Unlike conventional partialling, it yields a common component and two unique components. (Author/GDC)

  20. Muscle Cramp - A Common Pain

    MedlinePlus

    ... Osteopathic Manipulative Treatment Becoming a DO Video Library Muscle Cramp – A Common Pain Page Content Has a ... body’s natural tendency toward self-healing. Causes of Muscle Cramps Unfortunately, cramps can occur anywhere, anytime to ...

  1. Genomic Data Commons launches - TCGA

    Cancer.gov

    The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

  2. 6 Common Cancers - Lung Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents ... for Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the ...

  3. Adolescents' theories of the commons.

    PubMed

    Flanagan, Constance; Gallay, Erin

    2014-01-01

    Drawing from research on civic engagement and environmental commitment, we make a case for the processes inherent in how adolescents' ideas about the commons (those things that bind a polity together) develop. Engagement in the public realm with a plethora of perspectives and a goal of finding common ground is fundamental. Adolescents participate in the public realm through mini-polities (e.g., schools, community organizations). Practices in those settings can reinforce or challenge dominant political narratives. Special attention is given to the natural environment as a commons that transcends generations and to the opportunities in schools and in community partnerships that enable adolescents to realize their interdependence with nature and to author decisions about the commons. PMID:24851345

  4. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  5. 6 Common Cancers - Breast Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  6. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  7. Pathways to School Success

    ERIC Educational Resources Information Center

    University of Pittsburgh Office of Child Development, 2012

    2012-01-01

    In 2006, the University of Pittsburgh Office of Child Development began implementing a multi-year school readiness project in several area schools. Evidence from both research and the field point to several key elements that foster school readiness and create pathways to school success for all children. This paper presents components of a…

  8. Dexter energy transfer pathways.

    PubMed

    Skourtis, Spiros S; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M; Beratan, David N

    2016-07-19

    Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor-acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways.

  9. Pathways to Prosperity

    ERIC Educational Resources Information Center

    Symonds, William C.

    2012-01-01

    Symonds, director of the Pathways to Prosperity Project, asserts that the current U.S. system of preparing students for successful adult lives fails too many youth. Citing data showing that only 40 percent of young Americans earn an associate's or bachelor's degree by age 27--and that many employers say they see candidates who don't have…

  10. Common circuit design in fly and mammalian motion vision.

    PubMed

    Borst, Alexander; Helmstaedter, Moritz

    2015-08-01

    Motion-sensitive neurons have long been studied in both the mammalian retina and the insect optic lobe, yet striking similarities have become obvious only recently. Detailed studies at the circuit level revealed that, in both systems, (i) motion information is extracted from primary visual information in parallel ON and OFF pathways; (ii) in each pathway, the process of elementary motion detection involves the correlation of signals with different temporal dynamics; and (iii) primary motion information from both pathways converges at the next synapse, resulting in four groups of ON-OFF neurons, selective for the four cardinal directions. Given that the last common ancestor of insects and mammals lived about 550 million years ago, this general strategy seems to be a robust solution for how to compute the direction of visual motion with neural hardware.

  11. Common circuit design in fly and mammalian motion vision.

    PubMed

    Borst, Alexander; Helmstaedter, Moritz

    2015-08-01

    Motion-sensitive neurons have long been studied in both the mammalian retina and the insect optic lobe, yet striking similarities have become obvious only recently. Detailed studies at the circuit level revealed that, in both systems, (i) motion information is extracted from primary visual information in parallel ON and OFF pathways; (ii) in each pathway, the process of elementary motion detection involves the correlation of signals with different temporal dynamics; and (iii) primary motion information from both pathways converges at the next synapse, resulting in four groups of ON-OFF neurons, selective for the four cardinal directions. Given that the last common ancestor of insects and mammals lived about 550 million years ago, this general strategy seems to be a robust solution for how to compute the direction of visual motion with neural hardware. PMID:26120965

  12. Casuistry as common law morality.

    PubMed

    Paulo, Norbert

    2015-12-01

    This article elaborates on the relation between ethical casuistry and common law reasoning. Despite the frequent talk of casuistry as common law morality, remarks on this issue largely remain at the purely metaphorical level. The article outlines and scrutinizes Albert Jonsen and Stephen Toulmin's version of casuistry and its basic elements. Drawing lessons for casuistry from common law reasoning, it is argued that one generally has to be faithful to ethical paradigms. There are, however, limitations for the binding force of paradigms. The most important limitations--the possibilities of overruling and distinguishing paradigm norms--are similar in common law and in casuistry, or so it is argued. These limitations explain why casuistry is not necessarily overly conservative and conventional, which is one line of criticism to which casuists can now better respond. Another line of criticism has it that the very reasoning from case to case is extremely unclear in casuistry. I suggest a certain model of analogical reasoning to address this critique. All my suggestions to understand and to enhance casuistry make use of common law reasoning whilst remaining faithful to Jonsen and Toulmin's main ideas and commitments. Further developed along these lines, casuistry can appropriately be called "common law morality." PMID:26576963

  13. Casuistry as common law morality.

    PubMed

    Paulo, Norbert

    2015-12-01

    This article elaborates on the relation between ethical casuistry and common law reasoning. Despite the frequent talk of casuistry as common law morality, remarks on this issue largely remain at the purely metaphorical level. The article outlines and scrutinizes Albert Jonsen and Stephen Toulmin's version of casuistry and its basic elements. Drawing lessons for casuistry from common law reasoning, it is argued that one generally has to be faithful to ethical paradigms. There are, however, limitations for the binding force of paradigms. The most important limitations--the possibilities of overruling and distinguishing paradigm norms--are similar in common law and in casuistry, or so it is argued. These limitations explain why casuistry is not necessarily overly conservative and conventional, which is one line of criticism to which casuists can now better respond. Another line of criticism has it that the very reasoning from case to case is extremely unclear in casuistry. I suggest a certain model of analogical reasoning to address this critique. All my suggestions to understand and to enhance casuistry make use of common law reasoning whilst remaining faithful to Jonsen and Toulmin's main ideas and commitments. Further developed along these lines, casuistry can appropriately be called "common law morality."

  14. Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits.

    PubMed

    Ulirsch, Jacob C; Nandakumar, Satish K; Wang, Li; Giani, Felix C; Zhang, Xiaolan; Rogov, Peter; Melnikov, Alexandre; McDonel, Patrick; Do, Ron; Mikkelsen, Tarjei S; Sankaran, Vijay G

    2016-06-01

    Genome-wide association studies (GWAS) have successfully identified thousands of associations between common genetic variants and human disease phenotypes, but the majority of these variants are non-coding, often requiring genetic fine-mapping, epigenomic profiling, and individual reporter assays to delineate potential causal variants. We employ a massively parallel reporter assay (MPRA) to simultaneously screen 2,756 variants in strong linkage disequilibrium with 75 sentinel variants associated with red blood cell traits. We show that this assay identifies elements with endogenous erythroid regulatory activity. Across 23 sentinel variants, we conservatively identified 32 MPRA functional variants (MFVs). We used targeted genome editing to demonstrate endogenous enhancer activity across 3 MFVs that predominantly affect the transcription of SMIM1, RBM38, and CD164. Functional follow-up of RBM38 delineates a key role for this gene in the alternative splicing program occurring during terminal erythropoiesis. Finally, we provide evidence for how common GWAS-nominated variants can disrupt cell-type-specific transcriptional regulatory pathways. PMID:27259154

  15. 75 FR 52218 - Common Crop Insurance Regulations; Apple Crop Insurance Provisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-25

    ... Federal Crop Insurance Corporation 7 CFR Part 457 RIN 0563-AC10 Common Crop Insurance Regulations; Apple...: The Federal Crop Insurance Corporation (FCIC) finalizes the Common Crop Insurance Regulations, Apple... 48 FR 29115, June 24, 1983. Executive Order 12988 This final rule has been reviewed in...

  16. 77 FR 22467 - Common Crop Insurance Regulations; Fresh Market Tomato (Dollar Plan) Crop Provisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-16

    ... Federal Crop Insurance Corporation 7 CFR Part 457 RIN 0563-AC32 Common Crop Insurance Regulations; Fresh...: Final rule. SUMMARY: The Federal Crop Insurance Corporation (FCIC) finalizes the Common Crop Insurance... provide policy changes and clarify existing policy provisions to better meet the needs of...

  17. Activation of the Complement Classical Pathway (C1q Binding) by Mesophilic Aeromonas hydrophila Outer Membrane Protein

    PubMed Central

    Merino, Susana; Nogueras, Maria Mercedes; Aguilar, Alicia; Rubires, Xavier; Albertí, Sebastian; Benedí, Vicente Javier; Tomás, Juan M.

    1998-01-01

    The mechanism of killing of Aeromonas hydrophila serum-sensitive strains in nonimmune serum by the complement classical pathway has been studied. The bacterial cell surface component that binds C1q more efficiently was identified as a major outer membrane protein of 39 kDa, presumably the porin II described by D. Jeanteur, N. Gletsu, F. Pattus, and J. T. Buckley (Mol. Microbiol. 6:3355–3363, 1992), of these microorganisms. We have demonstrated that the purified form of porin II binds C1q and activates the classical pathway in an antibody-independent manner, with the subsequent consumption of C4 and reduction of the serum total hemolytic activity. Activation of the classical pathway has been observed in human nonimmune serum and agammaglobulinemic serum (both depleted of factor D). Binding of C1q to other components of the bacterial outer membrane, in particular to rough lipopolysaccharide, could not be demonstrated. Activation of the classical pathway by this lipopolysaccharide was also much less efficient than activation by the outer membrane protein. The strains possessing O-antigen lipopolysaccharide bind less C1q than the serum-sensitive strains, because the outer membrane protein is less accessible, and are resistant to complement-mediated killing. Finally, a similar or identical outer membrane protein (presumably porin II) that binds C1q was shown to be present in strains from the most common mesophilic Aeromonas O serogroups. PMID:9673268

  18. Porphyrin Binding to Gun4 Protein, Facilitated by a Flexible Loop, Controls Metabolite Flow through the Chlorophyll Biosynthetic Pathway.

    PubMed

    Kopečná, Jana; Cabeza de Vaca, Israel; Adams, Nathan B P; Davison, Paul A; Brindley, Amanda A; Hunter, C Neil; Guallar, Victor; Sobotka, Roman

    2015-11-20

    In oxygenic phototrophs, chlorophylls, hemes, and bilins are synthesized by a common branched pathway. Given the phototoxic nature of tetrapyrroles, this pathway must be tightly regulated, and an important regulatory role is attributed to magnesium chelatase enzyme at the branching between the heme and chlorophyll pathway. Gun4 is a porphyrin-binding protein known to stimulate in vitro the magnesium chelatase activity, but how the Gun4-porphyrin complex acts in the cell was unknown. To address this issue, we first performed simulations to determine the porphyrin-docking mechanism to the cyanobacterial Gun4 structure. After correcting crystallographic loop contacts, we determined the binding site for magnesium protoporphyrin IX. Molecular modeling revealed that the orientation of α6/α7 loop is critical for the binding, and the magnesium ion held within the porphyrin is coordinated by Asn-211 residue. We also identified the basis for stronger binding in the Gun4-1 variant and for weaker binding in the W192A mutant. The W192A-Gun4 was further characterized in magnesium chelatase assay showing that tight porphyrin binding in Gun4 facilitates its interaction with the magnesium chelatase ChlH subunit. Finally, we introduced the W192A mutation into cells and show that the Gun4-porphyrin complex is important for the accumulation of ChlH and for channeling metabolites into the chlorophyll biosynthetic pathway.

  19. Systematic tracking of dysregulated modules identifies disrupted pathways in narcolepsy

    PubMed Central

    Liu, Zhenhua; Zhao, Jiali; Tan, Yinyin; Tang, Minglu; Li, Guanzhen

    2015-01-01

    Objective: The objective of this work is to identify disrupted pathways in narcolepsy according to systematically tracking the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. Here, we performed systematic identification and comparison of modules across normal and narcolepsy conditions by integrating PPI and gene-expression data. Methods: Firstly, normal and narcolepsy PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, modules in PPI network were explored by clique-merging algorithm and we identified altered modules using a maximum weight bipartite matching and in non-increasing order. Finally, pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test to illuminate the biological pathways in narcolepsy. Results: Our analyses revealed that 235 altered modules were identified by comparing modules in normal and narcolepsy PPI network. Pathway functional enrichment analysis of disrupted module genes showed 59 disrupted pathways within threshold P < 0.001. The most significant five disrupted pathways were: oxidative phosphorylation, T cell receptor signaling pathway, cell cycle, Alzheimer’s disease and focal adhesion. Conclusions: We successfully identified disrupted pathways and these pathways might be potential biological processes for treatment and etiology mechanism in narcolepsy. PMID:26309600

  20. Drug-Path: a database for drug-induced pathways.

    PubMed

    Zeng, Hui; Qiu, Chengxiang; Cui, Qinghua

    2015-01-01

    Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches.

  1. The GPM Common Calibrated Brightness Temperature Product

    NASA Technical Reports Server (NTRS)

    Stout, John; Berg, Wesley; Huffman, George; Kummerow, Chris; Stocker, Erich

    2005-01-01

    The Global Precipitation Measurement (GPM) project will provide a core satellite carrying the GPM Microwave Imager (GMI) and will use microwave observations from a constellation of other satellites. Each partner with a satellite in the constellation will have a calibration that meets their own requirements and will decide on the format to archive their brightness temperature (Tb) record in GPM. However, GPM multi-sensor precipitation algorithms need to input intercalibrated Tb's in order to avoid differences among sensors introducing artifacts into the longer term climate record of precipitation. The GPM Common Calibrated Brightness Temperature Product is intended to address this problem by providing intercalibrated Tb data, called "Tc" data, where the "c" stands for common. The precipitation algorithms require a Tc file format that is both generic and flexible enough to accommodate the different passive microwave instruments. The format will provide detailed information on the processing history in order to allow future researchers to have a record of what was done. The format will be simple, including the main items of scan time, latitude, longitude, and Tc. It will also provide spacecraft orientation, spacecraft location, orbit, and instrument scan type (cross-track or conical). Another simplification is to store data in real numbers, avoiding the ambiguity of scaled data. Finally, units and descriptions will be provided in the product. The format is built on the concept of a swath, which is a series of scans that have common geolocation and common scan geometry. Scan geometry includes pixels per scan, sensor orientation, scan type, and incidence angles. The Tc algorithm and data format are being tested using the pre-GPM Precipitation Processing System (PPS) software to generate formats and 1/0 routines. In the test, data from SSM/I, TMI, AMSR-E, and WindSat are being processed and written as Tc products.

  2. Common themes in microbial pathogenicity revisited.

    PubMed Central

    Finlay, B B; Falkow, S

    1997-01-01

    Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics. PMID

  3. Garlic for the common cold.

    PubMed

    Lissiman, Elizabeth; Bhasale, Alice L; Cohen, Marc

    2014-01-01

    Background Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four.Objectives To determine whether garlic (Allium sativum) is effective for the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments.Search methods We searched CENTRAL (2014, Issue 7),OLDMEDLINE (1950 to 1965),MEDLINE (January 1966 to July week 5, 2014), EMBASE(1974 to August 2014) and AMED (1985 to August 2014).Selection criteria Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment.Data collection and analysis Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data.Main results In this updated review, we identified eight trials as potentially relevant from our searches. Again, only one trial met the inclusion criteria.This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily)for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. Authors' conclusions

  4. Garlic for the common cold.

    PubMed

    Lissiman, Elizabeth; Bhasale, Alice L; Cohen, Marc

    2014-11-11

    Background Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four.Objectives To determine whether garlic (Allium sativum) is effective for the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments.Search methods We searched CENTRAL (2014, Issue 7),OLDMEDLINE (1950 to 1965),MEDLINE (January 1966 to July week 5, 2014), EMBASE(1974 to August 2014) and AMED (1985 to August 2014).Selection criteria Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment.Data collection and analysis Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data.Main results In this updated review, we identified eight trials as potentially relevant from our searches. Again, only one trial met the inclusion criteria.This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily)for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. Authors' conclusions

  5. Laparoscopic common bile duct exploration.

    PubMed

    Vecchio, Rosario; MacFadyen, Bruce V

    2002-04-01

    In recent years, laparoscopic common bile duct exploration has become the procedure of choice in the management of choledocholithiasis in several laparoscopic centers. The increasing interest for this laparoscopic approach is due to the development of instrumentation and technique, allowing the procedure to be performed safely, and it is also the result of the revised role of endoscopic retrograde cholangiopancreatography, which has been questioned because of its cost, risk of complications and effectiveness. Many surgeons, however, are still not familiar with this technique. In this article we discuss the technique and results of laparoscopic common bile duct exploration. Both the laparoscopic transcystic approach and choledochotomy are discussed, together with the results given in the literature. When one considers the costs, morbidity, mortality and the time required before the patient can return to work, it would appear that laparoscopic cholecystectomy with common bile duct exploration is more favorable than open surgery or laparoscopic cholecystectomy with preoperative or postoperative endoscopic sphincterotomy. However, the technique requires advanced laparoscopic skills, including suturing, knot tying, the use of a choledochoscope, guidewire, dilators and balloon stone extractor. Although laparoscopic common bile duct exploration appears to be the most cost-effective method to treat common bile duct stones, it should be emphasized that this procedure is very challenging, and it should be performed by well-trained laparoscopic surgeons with experience in biliary surgery. PMID:11981684

  6. Creative Commons and Why It Should Be More Commonly Understood

    ERIC Educational Resources Information Center

    Johnson, Doug

    2009-01-01

    Authors, videographers, musicians, photographers, and almost anyone who creates materials and makes them publicly available has an alternative to standard copyright licensing: Creative Commons (CC). It is a tool that helps the creator display a licensing mark. The creator can assign a variety of rights for others to use his work--rights that are…

  7. Surveying the Commons: Current Implementation of Information Commons Web sites

    ERIC Educational Resources Information Center

    Leeder, Christopher

    2009-01-01

    This study assessed the content of 72 academic library Information Commons (IC) Web sites using content analysis, quantitative assessment and qualitative surveys of site administrators to analyze current implementation by the academic library community. Results show that IC Web sites vary widely in content, design and functionality, with few…

  8. Sharing Common Ground: Texas and the Common Core State Standards

    ERIC Educational Resources Information Center

    Vasinda, Sheri; Grote-Garcia, Stephanie; Durham, Patricia

    2013-01-01

    When browsing through professional catalogs or attending national conferences, one cannot help but notice the growing emphasis on the Common Core State Standards (CCSS). So, what does this mean for Texas teachers? As part of a special four-part series in our Texas Journal of Literacy Education, a special task force from the TALE Board will share…

  9. Non-canonical pathway network modelling and ubiquitination site prediction through homology modelling of NF-κB.

    PubMed

    Ghosh, Sayantan; Febin Prabhu Dass, J

    2016-04-25

    Given the fact that NF-κB stays as a dormant molecule in the cytoplasm in steady state, one common step in all the metabolic activities comprising NF-κB is its activation. Consequently there are two pathways of interest related to NF-κB activation: Canonical and alternate. Both the pathways involve ubiquitination of its repressors, that is to say ubiquitination of I-κB by NEMO/IKK-α/IKK-β complex in case of NF-κB1 and that of p100 by IKK-α homodimer in case of NF-κB2. This paper attempts to figure out the ubiquitination sites in alternate pathway of NF-κB activation using a purely computational approach. We initiated the work by acquiring the genes involved in NF kappa B alternate pathway through Agilent literature search. For this we employed the Cytoscape and STRING database. Secondly, the MSA was built using the sequences obtained through BLAST search, and the results were used to update the original sequence list, which was further refined using HMMER. Structural alignment was achieved via Modeller libraries. The final model has been refined using loop_model and asses_dope functions of Modeller. Ubiquitination site is predicted to be comprised of residues 'SPECLDLLVDS' between sites 178 and 188, both positions inclusive. Unlike the classical pathway, due to absence of parallel studies for p100/RelB, a quality match could not be performed, but future studies are in pipeline to replicate the methodology for NF-κB1 activation and compare the results with existing observations. The study can be used to understand the cofactors involved and ubiquitination sites employed during the activation process during drug designing activities. The methodology can be easily scaled and adapted for classical pathway as well. PMID:26784652

  10. Governing for the Common Good.

    PubMed

    Ruger, Jennifer Prah

    2015-12-01

    The proper object of global health governance (GHG) should be the common good, ensuring that all people have the opportunity to flourish. A well-organized global society that promotes the common good is to everyone's advantage. Enabling people to flourish includes enabling their ability to be healthy. Thus, we must assess health governance by its effectiveness in enhancing health capabilities. Current GHG fails to support human flourishing, diminishes health capabilities and thus does not serve the common good. The provincial globalism theory of health governance proposes a Global Health Constitution and an accompanying Global Institute of Health and Medicine that together propose to transform health governance. Multiple lines of empirical research suggest that these institutions would be effective, offering the most promising path to a healthier, more just world.

  11. Governing for the Common Good.

    PubMed

    Ruger, Jennifer Prah

    2015-12-01

    The proper object of global health governance (GHG) should be the common good, ensuring that all people have the opportunity to flourish. A well-organized global society that promotes the common good is to everyone's advantage. Enabling people to flourish includes enabling their ability to be healthy. Thus, we must assess health governance by its effectiveness in enhancing health capabilities. Current GHG fails to support human flourishing, diminishes health capabilities and thus does not serve the common good. The provincial globalism theory of health governance proposes a Global Health Constitution and an accompanying Global Institute of Health and Medicine that together propose to transform health governance. Multiple lines of empirical research suggest that these institutions would be effective, offering the most promising path to a healthier, more just world. PMID:26122555

  12. Wnt and lithium: a common destiny in the therapy of nervous system pathologies?

    PubMed

    Meffre, Delphine; Grenier, Julien; Bernard, Sophie; Courtin, Françoise; Dudev, Todor; Shackleford, Ghjuvan'Ghjacumu; Jafarian-Tehrani, Mehrnaz; Massaad, Charbel

    2014-04-01

    Wnt signaling is required for neurogenesis, the fate of neural progenitors, the formation of neuronal circuits during development, neuron positioning and polarization, axon and dendrite development and finally for synaptogenesis. This signaling pathway is also implicated in the generation and differentiation of glial cells. In this review, we describe the mechanisms of action of Wnt signaling pathways and their implication in the development and correct functioning of the nervous system. We also illustrate how a dysregulated Wnt pathway could lead to psychiatric, neurodegenerative and demyelinating pathologies. Lithium, used for the treatment of bipolar disease, inhibits GSK3β, a central enzyme of the Wnt/β-catenin pathway. Thus, lithium could, to some extent, mimic Wnt pathway. We highlight the possible dialogue between lithium therapy and modulation of Wnt pathway in the treatment of the diseases of the nervous system.

  13. Genome-Wide Pathway Analysis Identifies Genetic Pathways Associated with Psoriasis.

    PubMed

    Aterido, Adrià; Julià, Antonio; Ferrándiz, Carlos; Puig, Lluís; Fonseca, Eduardo; Fernández-López, Emilia; Dauden, Esteban; Sánchez-Carazo, José Luís; López-Estebaranz, José Luís; Moreno-Ramírez, David; Vanaclocha, Francisco; Herrera, Enrique; de la Cueva, Pablo; Dand, Nick; Palau, Núria; Alonso, Arnald; López-Lasanta, María; Tortosa, Raül; García-Montero, Andrés; Codó, Laia; Gelpí, Josep Lluís; Bertranpetit, Jaume; Absher, Devin; Capon, Francesca; Myers, Richard M; Barker, Jonathan N; Marsal, Sara

    2016-03-01

    Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P < 0.05). These findings provide insights into the biological mechanisms associated with psoriasis susceptibility.

  14. Genome-Wide Pathway Analysis Identifies Genetic Pathways Associated with Psoriasis.

    PubMed

    Aterido, Adrià; Julià, Antonio; Ferrándiz, Carlos; Puig, Lluís; Fonseca, Eduardo; Fernández-López, Emilia; Dauden, Esteban; Sánchez-Carazo, José Luís; López-Estebaranz, José Luís; Moreno-Ramírez, David; Vanaclocha, Francisco; Herrera, Enrique; de la Cueva, Pablo; Dand, Nick; Palau, Núria; Alonso, Arnald; López-Lasanta, María; Tortosa, Raül; García-Montero, Andrés; Codó, Laia; Gelpí, Josep Lluís; Bertranpetit, Jaume; Absher, Devin; Capon, Francesca; Myers, Richard M; Barker, Jonathan N; Marsal, Sara

    2016-03-01

    Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P < 0.05). These findings provide insights into the biological mechanisms associated with psoriasis susceptibility. PMID:26743605

  15. AIP Career Pathways

    NASA Astrophysics Data System (ADS)

    Palchak, Amanda

    2012-02-01

    American Institute of Physics (AIP) Career Pathways is a new project funded by the National Science Foundation. One of the goals of AIP Career Pathways is to prepare students to compete for Science, Technology, Engineering, and Mathematics (STEM) careers with a bachelor's degree in physics. In order to do so, I reviewed and compiled useful resources on finding a STEM career with a bachelor's degree in physics. These resources not only supply the job seeker with job postings in STEM careers but also provide them with information on resumes, interviewing skills, and networking. Recently at the 2011 Industrial Physics Forum, I interviewed companies in the private sector to obtain a unique perspective on what types of skills potential employers expect an applicant to posses with a bachelor's degree in physics. Ultimately, these components will be used as supplements at student career workshops held at annual Society of Physics Students Zone Meetings.

  16. Pathways of tau fibrillization.

    PubMed

    Kuret, Jeff; Chirita, Carmen N; Congdon, Erin E; Kannanayakal, Theresa; Li, Guibin; Necula, Mihaela; Yin, Haishan; Zhong, Qi

    2005-01-01

    New methods for analyzing tau fibrillization have yielded insights into the biochemical transitions involved in the process. Here we review the parallels between the sequential progression of tau fibrillization observed macroscopically in Alzheimer's disease (AD) lesions and the pathway of tau aggregation observed in vitro with purified tau preparations. In addition, pharmacological agents for further dissection of fibrillization mechanism and lesion formation are discussed. PMID:15615636

  17. The design of a common lunar lander

    NASA Technical Reports Server (NTRS)

    Driggers, Dan; Hearrell, Sean; Key, Kevin; Le, Brian; Love, Glen; Mcmullen, Rob; Messec, Scott; Ruhnke, Jim

    1991-01-01

    The Austin Cynthesis Corporation was formed to respond to a Request for Proposal for the design of a Common Lunar Lander (CLL) capable of carrying lightweight (less than 500 kg), unspecified payload to the moon. This Final Design Report Document includes information on the requirements for the design project; the ideas proposed as solutions to the design problem; the work which has been completed in support of the design effort; justifications, validations, and verifications of decisions made during the project; and suggestions for future work to be done in support of the project. A project schedule, including current status of the items included on the schedule, as well as cost and management summaries is also included.

  18. The evolutionary pathway to obligate scavenging in Gyps vultures.

    PubMed

    Dermody, Brian J; Tanner, Colby J; Jackson, Andrew L

    2011-01-01

    The evolutionary pathway to obligate scavenging in Gyps vultures remains unclear. We propose that communal roosting plays a central role in setting up the information transfer network critical for obligate scavengers in ephemeral environments and that the formation of a flotilla-like foraging group is a likely strategy for foraging Gyps vultures. Using a spatial, individual-based, optimisation model we find that the communal roost is critical for establishing the information network that enables information transfer owing to the spatial-concentration of foragers close to the roost. There is also strong selection pressure for grouping behaviour owing to the importance of maintaining network integrity and hence information transfer during foraging. We present a simple mechanism for grouping, common in many animal species, which has the added implication that it negates the requirement for roost-centric information transfer. The formation of a flotilla-like foraging group also improves foraging efficiency through the reduction of overlapping search paths. Finally, we highlight the importance of consideration of information transfer mechanisms in order to maximise the success of vulture reintroduction programmes.

  19. Physiology of central pathways.

    PubMed

    Cullen, K E

    2016-01-01

    The relative simplicity of the neural circuits that mediate vestibular reflexes is well suited for linking systems and cellular levels of analyses. Notably, a distinctive feature of the vestibular system is that neurons at the first central stage of sensory processing in the vestibular nuclei are premotor neurons; the same neurons that receive vestibular-nerve input also send direct projections to motor pathways. For example, the simplicity of the three-neuron pathway that mediates the vestibulo-ocular reflex leads to the generation of compensatory eye movements within ~5ms of a head movement. Similarly, relatively direct pathways between the labyrinth and spinal cord control vestibulospinal reflexes. A second distinctive feature of the vestibular system is that the first stage of central processing is strongly multimodal. This is because the vestibular nuclei receive inputs from a wide range of cortical, cerebellar, and other brainstem structures in addition to direct inputs from the vestibular nerve. Recent studies in alert animals have established how extravestibular signals shape these "simple" reflexes to meet the needs of current behavioral goal. Moreover, multimodal interactions at higher levels, such as the vestibular cerebellum, thalamus, and cortex, play a vital role in ensuring accurate self-motion and spatial orientation perception. PMID:27638060

  20. 76 FR 44776 - Provisions Common to Registered Entities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-27

    ... part 40 Provisions Common to Registered Entities, 75 FR 67282 (Nov. 2, 2010). The Commission's final... mandatory clearing; 75 FR 67277 (Nov. 2, 2010)). Paragraph (j)(2)(ii) refers to `` otional amounts, quantity... Registered Entities, 75 FR 57282 (Nov. 2, 2010). In this regard, the Commission continues to view its...

  1. Luminosities for Final Flash Stars

    NASA Astrophysics Data System (ADS)

    Hinkle, Kenneth; Joyce, Richard; Lebzelter, Thomas

    2010-08-01

    A brief yet common evolutionary process is a post-AGB final episode of helium shell burning. This occurs after a low mass star has ejected a planetary nebula and has started on the white dwarf track. Seven stars are now classified with varying degrees of certainty as one of these ``final flash'' objects. Two of these have actually been observed to eject a shell of gas first as a pseudo-photosphere and then as a thick dust envelope. The dust envelopes are expanding at ~100 km s^-1. We propose AO imaging of the circumstellar shells to measure changes from images recorded a decade or more ago. From these changes we will determine geometric parallaxes and hence luminosities. The luminosity will be compared to stellar evolution models. In an additional challenge to models we will calibrate the He I emission line flux and through this the mass loss rate from the fast stellar wind.

  2. Uncommon illness from common infections.

    PubMed Central

    Christian, C. L.

    1988-01-01

    Individual common infectious agents such as EBV, CMV and HBV have well characterized relationships to a variety of acute and chronic disease states; the host and/or environment variables underlying this clinical heterogeneity are not known. Given the high frequency of these viral infections in the general population, there should be a cautious interpretation of antiviral serological data. PMID:3332514

  3. Common sleep disorders in children.

    PubMed

    Carter, Kevin A; Hathaway, Nathanael E; Lettieri, Christine F

    2014-03-01

    Up to 50% of children will experience a sleep problem. Early identification of sleep problems may prevent negative consequences, such as daytime sleepiness, irritability, behavioral problems, learning difficulties, motor vehicle crashes in teenagers, and poor academic performance. Obstructive sleep apnea occurs in 1% to 5% of children. Polysomnography is needed to diagnose the condition because it may not be detected through history and physical examination alone. Adenotonsillectomy is the primary treatment for most children with obstructive sleep apnea. Parasomnias are common in childhood; sleepwalking, sleep talking, confusional arousals, and sleep terrors tend to occur in the first half of the night, whereas nightmares are more common in the second half of the night. Only 4% of parasomnias will persist past adolescence; thus, the best management is parental reassurance and proper safety measures. Behavioral insomnia of childhood is common and is characterized by a learned inability to fall and/or stay asleep. Management begins with consistent implementation of good sleep hygiene practices, and, in some cases, use of extinction techniques may be appropriate. Delayed sleep phase disorder is most common in adolescence, presenting as difficulty falling asleep and awakening at socially acceptable times. Treatment involves good sleep hygiene and a consistent sleep-wake schedule, with nighttime melatonin and/or morning bright light therapy as needed. Diagnosing restless legs syndrome in children can be difficult; management focuses on trigger avoidance and treatment of iron deficiency, if present. PMID:24695508

  4. Common Issues in Professional Behavior

    ERIC Educational Resources Information Center

    Janosik, Steven M.

    2007-01-01

    Most conversations about ethics and professional behavior involve case studies and hypothetical situations. This study identifies and examines the most common concerns in professional behavior as reported by 303 student affairs practitioners in the field. Differences by gender, years of experience, organizational level, institutional type, and…

  5. Common Core: Solve Math Problems

    ERIC Educational Resources Information Center

    Strom, Erich

    2012-01-01

    The new common core standards for mathematics demand that students (and teachers!) exhibit deeper conceptual understanding. That's music to the ears of education professor John Tapper, who says teachers have overemphasized teaching procedures--and getting right answers. In his new book, "Solving for Why," he makes a powerful case for moving beyond…

  6. The Academic Common Market. 1976.

    ERIC Educational Resources Information Center

    Southern Regional Education Board, Atlanta, GA.

    The Academic Common Market is an interstate agreement among Southern states for sharing academic programs. Participating states are able to make arrangements for their residents who qualify for admission to enroll in specific programs in other states on an in-state tuition basis. Thus far, the arrangements have been limited to unusual graduate…

  7. Technology: Technology and Common Sense

    ERIC Educational Resources Information Center

    Van Horn, Royal

    2004-01-01

    The absence of common sense in the world of technology continues to amaze the author. Things that seem so logical to just aren nott for many people. The installation of Voice-over IP (VoIP, with IP standing for Internet Protocol) in many school districts is a good example. Schools have always had trouble with telephones. Many districts don't even…

  8. Common Ground: Expanding Our Horizons.

    ERIC Educational Resources Information Center

    McDevitt, Michele J.

    In "Common Ground: Dialogue, Understanding, and the Teaching of Composition," Kurt Spellmeyer seeks to familiarize students and teachers with the linguistic and cultural no-man's-land separating them. Reinstating the value of two writing conventions often used by traditional students--expressive and commonplaces--can help expand on the horizons of…

  9. Common Environmental Terms: A Glossary.

    ERIC Educational Resources Information Center

    Studdard, Gloria J.

    This glossary is designed fo r students learning and writing about environmental conditions, problems, and solutions. Not primarily intended for use by scientists and technicians, the glossary contains over 400 common terms that are helpful in understanding the environmental literature of today. (MA)

  10. "Common Core Implementation Best Practices"

    ERIC Educational Resources Information Center

    Martin, Carmel

    2014-01-01

    This document presents the testimony of Carmel Martin, Executive Vice President for Policy at the Center for American Progress, delivered at the New York State Office of the Governor Common Core Implementation Panel on Wednesday, February 19, 2014. In this statement, Martin began by saying that The Center for American Progress believes that this…

  11. Common Core: Victory Is Yours!

    ERIC Educational Resources Information Center

    Fink, Jennifer L. W.

    2012-01-01

    In this article, the author discusses how to implement the Common Core State Standards in the classroom. She presents examples and activities that will leave teachers feeling "rosy" about tackling the new standards. She breaks down important benchmarks and shows how other teachers are doing the Core--and loving it!

  12. Common Core: Rx for Change

    ERIC Educational Resources Information Center

    Jaeger, Paige

    2012-01-01

    When David Coleman, one of the authors of the Common Core State Standards (CCSS), spoke to New York educators, he stated that over the last forty years 8th grade reading scores have been flat. Despite doubling expenditures on classroom instruction, there has been little growth. Most educators are aware that what worked for the students of the…

  13. The Common Core Math Standards

    ERIC Educational Resources Information Center

    Wurman, Ze'ev; Wilson, W. Stephen

    2012-01-01

    More than 40 states have now signed onto the Common Core standards in English language arts and math, which have been both celebrated as a tremendous advance and criticized as misguided and for bearing the heavy thumbprint of the federal government. This article presents an interview with Ze'ev Wurman and W. Stephen Wilson. Wurman, who was a U.S.…

  14. Community Commons Program Development Manual.

    ERIC Educational Resources Information Center

    Culp, Kieta Osteen

    Community Commons (CC) is a collaborative partnership among Brevard Community College (BCC) (Florida) and over 40 social service organizations and agencies in Florida dedicated to providing education, job training, social services, recreation, and a drug free environment to communities of low income families. The project specifically seeks to…

  15. Common Chemicals around the House.

    ERIC Educational Resources Information Center

    Katz, David A., Comp.; O'Brien, Thomas, Comp.

    1991-01-01

    Lists 46 household chemicals readily available at local stores by common name, chemical name, chemical formula, and typical commercial source. Suggests that school budgetary constraints can be eased by this practice and that students can become more chemically literate as consumers. (JJK)

  16. Common Core: Fact vs. Fiction

    ERIC Educational Resources Information Center

    Greene, Kim

    2012-01-01

    Despite students' interest in informational text, it has played second fiddle in literacy instruction for years. Now, though, nonfiction is getting its turn in the spotlight. The Common Core State Standards require that students become thoughtful consumers of complex, informative texts--taking them beyond the realm of dry textbooks and…

  17. Objectification in Common Sense Thinking

    ERIC Educational Resources Information Center

    Markova, Ivana

    2012-01-01

    In epistemologies of both scientific and common sense thinking "objectification" characterizes the formation of knowledge and concepts, yet in each case its meaning is different. In the former, objectification in acquiring knowledge refers to the individual's rationalistic reification of an object or of another person and to disengagement or…

  18. Common Practices in Adventure Programming.

    ERIC Educational Resources Information Center

    Johanson, Karl M., Ed.

    The goals of this manual are to raise the level of safety, environmental awareness, and quality in outdoor adventure education, and to encourage the development of skilled, knowledgeable outdoor leaders through the compilation and dissemination of common practices and information. Other goals are to provide information for programs to use as a…

  19. Pathway and Resource Overview (Presentation)

    SciTech Connect

    Ruth, M. F.

    2009-11-16

    This presentation provides information about hydrogen pathway analysis, which is analysis of the total levelized cost (including return on investment). Well-to-wheels (WTW) energy use, and WTW emissions for hydrogen production, delivery, and distribution pathways.

  20. Evolution of the parathyroid hormone family and skeletal formation pathways.

    PubMed

    Danks, Janine A; D'Souza, Damian G; Gunn, Haley J; Milley, Kristi M; Richardson, Samantha J

    2011-01-01

    Bone is considered to be a feature of higher vertebrates and one of the features that was required for the movement from water onto land. But there are a number of evolutionarily important species that have cartilaginous skeletons, including sharks. Both bony and cartilaginous fish are believed to have a common ancestor who had a bony skeleton. A number of factors and pathways have been shown to be involved in the development and maintenance of bony skeleton including the Wnt pathway and the parathyroid hormone gene family. The study of these pathways and factors in cartilaginous animals may shed light on the evolution of the vertebrate skeleton. PMID:21074535

  1. Common sense and the common morality in theory and practice.

    PubMed

    Daly, Patrick

    2014-06-01

    The unfinished nature of Beauchamp and Childress's account of the common morality after 34 years and seven editions raises questions about what is lacking, specifically in the way they carry out their project, more generally in the presuppositions of the classical liberal tradition on which they rely. Their wide-ranging review of ethical theories has not provided a method by which to move beyond a hypothetical approach to justification or, on a practical level regarding values conflict, beyond a questionable appeal to consensus. My major purpose in this paper is to introduce the thought of Bernard Lonergan as offering a way toward such a methodological breakthrough. In the first section, I consider Beauchamp and Childress's defense of their theory of the common morality. In the second, I relate a persisting vacillation in their argument regarding the relative importance of reason and experience to a similar tension in classical liberal theory. In the third, I consider aspects of Lonergan's generalized empirical method as a way to address problems that surface in the first two sections of the paper: (1) the structural relation of reason and experience in human action; and (2) the importance of theory for practice in terms of what Lonergan calls "common sense" and "general bias." PMID:24526573

  2. Common sense and the common morality in theory and practice.

    PubMed

    Daly, Patrick

    2014-06-01

    The unfinished nature of Beauchamp and Childress's account of the common morality after 34 years and seven editions raises questions about what is lacking, specifically in the way they carry out their project, more generally in the presuppositions of the classical liberal tradition on which they rely. Their wide-ranging review of ethical theories has not provided a method by which to move beyond a hypothetical approach to justification or, on a practical level regarding values conflict, beyond a questionable appeal to consensus. My major purpose in this paper is to introduce the thought of Bernard Lonergan as offering a way toward such a methodological breakthrough. In the first section, I consider Beauchamp and Childress's defense of their theory of the common morality. In the second, I relate a persisting vacillation in their argument regarding the relative importance of reason and experience to a similar tension in classical liberal theory. In the third, I consider aspects of Lonergan's generalized empirical method as a way to address problems that surface in the first two sections of the paper: (1) the structural relation of reason and experience in human action; and (2) the importance of theory for practice in terms of what Lonergan calls "common sense" and "general bias."

  3. Lipedema: A Relatively Common Disease with Extremely Common Misconceptions

    PubMed Central

    Herbst, Karen L.

    2016-01-01

    Lipedema, or adiposis dolorosa, is a common adipose tissue disorder that is believed to affect nearly 11% of adult women worldwide. It is characterized most commonly by disproportionate adipocyte hypertrophy of the lower extremities, significant tenderness to palpation, and a failure to respond to extreme weight loss modalities. Women with lipedema report a rapid growth of the lipedema subcutaneous adipose tissue in the setting of stress, surgery, and/or hormonal changes. Women with later stages of lipedema have a classic “column leg” appearance, with masses of nodular fat, easy bruising, and pain. Despite this relatively common disease, there are few physicians who are aware of it. As a result, patients are often misdiagnosed with lifestyle-induced obesity, and/or lymphedema, and subjected to unnecessary medical interventions and fat-shaming. Diagnosis is largely clinical and based on criteria initially established in 1951. Treatment of lipedema is effective and includes lymphatic support, such as complete decongestive therapy, and specialized suction lipectomy to spare injury to lymphatic channels and remove the diseased lipedema fat. With an incidence that may affect nearly 1 in 9 adult women, it is important to generate appropriate awareness, conduct additional research, and identify better diagnostic and treatment modalities for lipedema so these women can obtain the care that they need and deserve. PMID:27757353

  4. On the origin of metabolic pathways

    NASA Technical Reports Server (NTRS)

    Lazcano, A.; Miller, S. L.; Bada, J. L. (Principal Investigator)

    1999-01-01

    The heterotrophic theory of the origin of life is the only proposal available with experimental support. This comes from the ease of prebiotic synthesis under strongly reducing conditions. The prebiotic synthesis of organic compounds by reduction of CO(2) to monomers used by the first organisms would also be considered an heterotrophic origin. Autotrophy means that the first organisms biosynthesized their cell constituents as well as assembling them. Prebiotic synthetic pathways are all different from the biosynthetic pathways of the last common ancestor (LCA). The steps leading to the origin of the metabolic pathways are closer to prebiotic chemistry than to those in the LCA. There may have been different biosynthetic routes between the prebiotic and the LCAs that played an early role in metabolism but have disappeared from extant organisms. The semienzymatic theory of the origin of metabolism proposed here is similar to the Horowitz hypothesis but includes the use of compounds leaking from preexisting pathways as well as prebiotic compounds from the environment.

  5. Crowding in the S-cone pathway.

    PubMed

    Coates, Daniel R; Chung, Susana T L

    2016-05-01

    The spatial extent of interference from nearby object or contours (the critical spacing of "crowding") has been thoroughly characterized across the visual field, typically using high contrast achromatic stimuli. However, attempts to link this measure with known properties of physiological pathways have been inconclusive. The S-cone pathway, with its ease of psychophysical isolation and known anatomical characteristics, offers a unique tool to gain additional insights into crowding. In this study, we measured the spatial extent of crowding in the S-cone pathway at several retinal locations using a chromatic adaptation paradigm. S-cone crowding was evident and extensive, but its spatial extent changed less markedly as a function of retinal eccentricity than the extent found using traditional achromatic stimuli. However, the spatial extent agreed with that of low contrast achromatic stimuli matched for isolated resolvability. This suggests that common cortical mechanisms mediate the crowding effect in the S-cone and achromatic pathway, but contrast is an important factor. The low contrast of S-cone stimuli makes S-cone vision more acuity-limited than crowding-limited.

  6. Pathway Analysis: State of the Art

    PubMed Central

    García-Campos, Miguel A.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2015-01-01

    Pathway analysis is a set of widely used tools for research in life sciences intended to give meaning to high-throughput biological data. The methodology of these tools settles in the gathering and usage of knowledge that comprise biomolecular functioning, coupled with statistical testing and other algorithms. Despite their wide employment, pathway analysis foundations and overall background may not be fully understood, leading to misinterpretation of analysis results. This review attempts to comprise the fundamental knowledge to take into consideration when using pathway analysis as a hypothesis generation tool. We discuss the key elements that are part of these methodologies, their capabilities and current deficiencies. We also present an overview of current and all-time popular methods, highlighting different classes across them. In doing so, we show the exploding diversity of methods that pathway analysis encompasses, point out commonly overlooked caveats, and direct attention to a potential new class of methods that attempt to zoom the analysis scope to the sample scale. PMID:26733877

  7. Overfill of common piggyback admixture solutions.

    PubMed

    Kleinberg, M L; Chang, P

    1984-10-01

    The average final volume of 23 commonly used piggyback solutions was determined. Polyvinyl chloride (PVC) containers filled with 0.9% sodium chloride injection or 5% dextrose injection in 50 ml and 100 ml sizes were used for 20 of the piggybacks. A total of ten samples of each drug and dose were measured by draining the entire contents into a graduated cylinder and measuring the volume. The mean volumes, standard deviations, and ranges for each drug and dose were calculated. The volume found in each sample exceeded the volume in the original PVC container by at least 20% in the 50 ml size and 11% in the 100 ml size. The greatest percentage volume difference was 62% in the 50 ml size and 28% in the 100 ml size. The FasPak and the two Viaflex Plus Ready-To-Use containers, which did not require the use of the 50 and 100 ml PVC containers, had a percentage volume difference of 2.6%, 2.2%, and 3.4%, respectively. This information demonstrates the fact that the final volumes of some piggyback admixtures are significantly greater than that which may be presumed from the admixture label. PMID:10268316

  8. Pathways with PathWhiz

    PubMed Central

    Pon, Allison; Jewison, Timothy; Su, Yilu; Liang, Yongjie; Knox, Craig; Maciejewski, Adam; Wilson, Michael; Wishart, David S.

    2015-01-01

    PathWhiz (http://smpdb.ca/pathwhiz) is a web server designed to create colourful, visually pleasing and biologically accurate pathway diagrams that are both machine-readable and interactive. As a web server, PathWhiz is accessible from almost any place and compatible with essentially any operating system. It also houses a public library of pathways and pathway components that can be easily viewed and expanded upon by its users. PathWhiz allows users to readily generate biologically complex pathways by using a specially designed drawing palette to quickly render metabolites (including automated structure generation), proteins (including quaternary structures, covalent modifications and cofactors), nucleic acids, membranes, subcellular structures, cells, tissues and organs. Both small-molecule and protein/gene pathways can be constructed by combining multiple pathway processes such as reactions, interactions, binding events and transport activities. PathWhiz's pathway replication and propagation functions allow for existing pathways to be used to create new pathways or for existing pathways to be automatically propagated across species. PathWhiz pathways can be saved in BioPAX, SBGN-ML and SBML data exchange formats, as well as PNG, PWML, HTML image map or SVG images that can be viewed offline or explored using PathWhiz's interactive viewer. PathWhiz has been used to generate over 700 pathway diagrams for a number of popular databases including HMDB, DrugBank and SMPDB. PMID:25934797

  9. Image-decrypting common path interferometer

    NASA Astrophysics Data System (ADS)

    Glueckstad, Jesper

    1999-03-01

    A new scheme for parallel optical decryption and the display of encrypted image information is presented. The scheme is based on a common path interferometer configuration providing a simple and robust optical setup. Images are encrypted directly during recording by use of a combined phase encoding and phase scrambling method. The encoding and encryption does not require sophisticated, iterative and time consuming optimization algorithms. Pixels are independently encoded and encrypted by use of a simple look-up table technique that can be performed in milliseconds on a standard personal computer. Optical decryption can subsequently be implemented in the common path interferometer by use of single phase or if desired a combined phase/amplitude key. An advantage of the presented method is that the encrypted image may selectively require recording and decryption of phase values or amplitude values or a combination thereof. Another advantage is that decryption is performed in a plane adjacent to the encrypted mask or an equivalent plane whereby generation of speckles in the decrypted image is strongly suppressed. Finally, there is no requirement of positioning a decrypting mask or spatial light modulator in the optical Fourier plane whereby an accurate three dimensional positioning requirement can be avoided.

  10. Identification of hub genes and pathways associated with hepatocellular carcinoma based on network strategy

    PubMed Central

    Liu, Jun; Hua, Ping; Hui, Li; Zhang, Li-Li; Hu, Zhen; Zhu, Ying-Wei

    2016-01-01

    The objective of this study was to identify hub genes and pathways associated with hepatocellular carcinoma (HCC) by centrality analysis of a co-expression network. A co-expression network based on differentially expressed (DE) genes of HCC was constructed using the Differentially Co-expressed Genes and Links (DCGL) package. Centrality analyses, for centrality of degree, clustering coefficient, closeness, stress and betweenness for the co-expression network were performed to identify hub genes, and the hub genes were combined together to overcome inconsistent results. Enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Finally, validation of hub genes was conducted utilizing reverse transcription-polymerase chain reaction (RT-PCR) analysis. In total, 260 DE genes between normal controls and HCC patients were obtained and a co-expression network with 154 nodes and 326 edges was constructed. From this, 13 hub genes were identified according to degree, clustering coefficient, closeness, stress and betweenness centrality analysis. It was found that reelin (RELN), potassium voltage-gated channel subfamily J member 10 (KCNJ10) and neural cell adhesion molecule 1 (NCAM1) were common hub genes across the five centralities, and the results of RT-PCR analysis for RELN, KCNJ10 and NCAM1 were consistent with the centrality analyses. Pathway enrichment analysis of DE genes showed that cell cycle, metabolism of xenobiotics by cytochrome P450 and p53 signaling pathway were the most significant pathways. This study may contribute to understanding the molecular pathogenesis of HCC and provide potential biomarkers for its early detection and effective therapies. PMID:27703495

  11. 77 FR 35691 - Update to Electronic Common Technical Document Module 1

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-14

    ... HUMAN SERVICES Food and Drug Administration Update to Electronic Common Technical Document Module 1... (FDA) is announcing the following meeting: Update to Electronic Common Technical Document Module 1. The topic to be discussed is final documentation of the Electronic Common Technical Document (eCTD) Module...

  12. Dynamics of the surgical microbiota along the cardiothoracic surgery pathway

    PubMed Central

    Romano-Bertrand, Sara; Frapier, Jean-Marc; Calvet, Brigitte; Colson, Pascal; Albat, Bernard; Parer, Sylvie; Jumas-Bilak, Estelle

    2015-01-01

    Human skin associated microbiota are increasingly described by culture-independent methods that showed an unexpected diversity with variation correlated with several pathologies. A role of microbiota disequilibrium in infection occurrence is hypothesized, particularly in surgical site infections. We study the diversities of operative site microbiota and its dynamics during surgical pathway of patients undergoing coronary-artery by-pass graft (CABG). Pre-, per-, and post-operative samples were collected from 25 patients: skin before the surgery, superficially and deeply during the intervention, and healing tissues. Bacterial diversity was assessed by DNA fingerprint using 16S rRNA gene PCR and Temporal Temperature Gel Electrophoresis (TTGE). The diversity of Operational Taxonomic Units (OTUs) at the surgical site was analyzed according to the stage of surgery. From all patients and samples, we identified 147 different OTUs belonging to the 6 phyla Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, Cyanobacteria, and Fusobacteria. High variations were observed among patients but common themes can be observed. The Firmicutes dominated quantitatively but were largely encompassed by the Proteobacteria regarding the OTUs diversity. The genera Propionibacterium and Staphylococcus predominated on the preoperative skin, whereas very diverse Proteobacteria appeared selected in peri-operative samples. The resilience in scar skin was partial with depletion in Actinobacteria and Firmicutes and increase of Gram-negative bacteria. Finally, the thoracic operative site presents an unexpected bacterial diversity, which is partially common to skin microbiota but presents particular dynamics. We described a complex bacterial community that gathers pathobionts and bacteria deemed to be environmental, opportunistic pathogens and non-pathogenic bacteria. These data stress to consider surgical microbiota as a “pathobiome” rather than a reservoir of individual potential

  13. Fragmentation Pathways in the Uracil Radical Cation

    SciTech Connect

    Zhou, Congyi; Matsika, Spiridoula; Kotur, Marija; Weinacht, Thomas C.

    2012-08-24

    We investigate pathways for fragmentation in the uracil radical cation using ab initio electronic structure calculations. We focus on the main fragments produced in pump–probe dissociative ionization experiments. These are fragments with mass to charge ratios (m/z) of 69, 28, 41, and 42. Barriers to dissociation along the ground ionic surface are reported, which provide an estimate of the energetic requirements for the production of the main fragments. Finally, direct and sequential fragmentation mechanisms have been analyzed, and it is concluded that sequential fragmentation after production of fragment with m/z 69 is the dominant mechanism for the production of the smaller fragments.

  14. Pathways: Strategies for Susceptibility Genes in SLE

    PubMed Central

    Kelley, James M.; Edberg, Jeffrey C.; Kimberly, Robert P.

    2010-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disorder marked by an inappropriate immune response to nuclear antigens. Recent whole genome association and more focused studies have revealed numerous genes implicated in this disease process, including ITGAM, Fc gamma receptors, complement components, C-reactive protein, and others. One common feature of these molecules is their involvement in the immune opsonins pathway and phagocytic clearing of nuclear antigens and apoptotic debris which provide excessive exposure of lupus-related antigens to immune cells. Analysis of gene-gene interactions in the opsonin pathway and its relationship to SLE may provide a systems-based approach to identify additional candidate genes associated with disease able to account for a larger part of lupus susceptibility. PMID:20144911

  15. Common modules: A success story

    NASA Astrophysics Data System (ADS)

    Morrow, Walter B., Jr.

    1988-06-01

    During the late 1960s and early 1970s, the U.S. military found far-infrared or thermal imaging systems very useful as night vision devices because of ready application as troop-carried, combat vehicle-mounted, and aircraft-mounted systems. The rapid proliferation of applications posed a serious financial problem, yet clearly solved critical needs. The development and acquisition process for each system's development, purchase, and maintenance was both lengthy and expensive. Therefore, an investigative committee was formed in 1971 within the Center for Night Vision and Electro-Optics to analyze the problems and develop the design concept for Common Modules. This report focuses on the detector modules and develops cost benefits accrued to date and expected to accrue in the Army's future as a result of common module development and implementation.

  16. Common criteria for usability review.

    PubMed

    Nassar, Victor

    2012-01-01

    The propose of this paper is to present a literature review, in a grouping of common criteria for usability approaches of Bastien and Scapin (1993), Nielsen (1994), Shnneiderman(1998), Dix et al (1998), Preece et al (2005) and ISO 9241-110 (2006). After establishment of prerequisites for knowledge of the general characteristics of the users who will use the system, are defined and explained the criteria in common: consistency, user control, ease of learning, flexibility, errors management, reduction of excess and visibility system status. Although there is no determination as to which criteria should be considered when developing an interface and each author presents some specificity in their approach, it is observed that there is equivalence in the measures adopted usability. PMID:22316859

  17. Common Perspectives in Qualitative Research.

    PubMed

    Flannery, Marie

    2016-07-01

    The primary purpose of this column is to focus on several common core concepts that are foundational to qualitative research. Discussion of these concepts is at an introductory level and is designed to raise awareness and understanding of several conceptual foundations that undergird qualitative research. Because of the variety of qualitative approaches, not all concepts are relevant to every design and tradition. However, foundational aspects were selected for highlighting. PMID:27314194

  18. Perioperative risk assessment. Common misconceptions.

    PubMed

    Mishriki, Y Y

    1989-04-01

    Proper assessment of the preoperative patient is a blend of the art and science of medicine. The body of literature dealing with the various facets of this assessment has grown in the past few years. Unfortunately, this core of knowledge is neither well taught to residents-in-training nor well appreciated by many practicing physicians. Thus, evaluation of the surgical patient is often guided by personal anecdotes and unjustified assumptions. Seven common misconceptions are addressed in this article. PMID:2648378

  19. Improving carbon fixation pathways

    SciTech Connect

    Ducat, DC; Silver, PA

    2012-08-01

    A recent resurgence in basic and applied research on photosynthesis has been driven in part by recognition that fulfilling future food and energy requirements will necessitate improvements in crop carbon-fixation efficiencies. Photosynthesis in traditional terrestrial crops is being reexamined in light of molecular strategies employed by photosynthetic microbes to enhance the activity of the Calvin cycle. Synthetic biology is well-situated to provide original approaches for compartmentalizing and enhancing photosynthetic reactions in a species independent manner. Furthermore, the elucidation of alternative carbon-fixation routes distinct from the Calvin cycle raises possibilities that novel pathways and organisms can be utilized to fix atmospheric carbon dioxide into useful materials.

  20. Common morality and moral reform.

    PubMed

    Wallace, K A

    2009-01-01

    The idea of moral reform requires that morality be more than a description of what people do value, for there has to be some measure against which to assess progress. Otherwise, any change is not reform, but simply difference. Therefore, I discuss moral reform in relation to two prescriptive approaches to common morality, which I distinguish as the foundational and the pragmatic. A foundational approach to common morality (e.g., Bernard Gert's) suggests that there is no reform of morality, but of beliefs, values, customs, and practices so as to conform with an unchanging, foundational morality. If, however, there were revision in its foundation (e.g., in rationality), then reform in morality itself would be possible. On a pragmatic view, on the other hand, common morality is relative to human flourishing, and its justification consists in its effectiveness in promoting flourishing. Morality is dependent on what in fact does promote human flourishing and therefore, could be reformed. However, a pragmatic approach, which appears more open to the possibility of moral reform, would need a more robust account of norms by which reform is measured.

  1. Common Avionics Display Processor (CADP)

    NASA Astrophysics Data System (ADS)

    Farley, Paul E.

    1995-06-01

    The 1970s saw the start of a trend towards integrated digital avionics. In the 1980s, the Air Force's Pave Pillar initiative defined centralized digital processing as the cost- effective approach to tactical avionics. The avionics systems of the two advanced aircraft presently under development, a fixed-wing tactical fighter and an armed scout/reconnaissance helicopter, were based on this architecture. Both platforms relied upon custom, single-purpose hardware and software to generate images for their advanced multifunctional flat panel cockpit displays. The technology to generate real-time synthetic images with common data and signal processors was not available during the development of the platforms. Harris IR&D investigations have focused on an approach that Harris GASD has named the Common Avionics Display Processor (CADP). This programmable device can generate sophisticated images or perform sensor image manipulation and processing. The Common Avionics Display Processor is a general purpose image synthesizer. It consists of software and hardware components configured at run time by a downloaded program. The CADP offers two advantages over custom, special purpose devices. First, it solves a class of problems, not a single one. It can generate many types of images, from alphanumeric to sensor simulation. Only one module type is required for any of these functions. Second, as program schedules become shorter, traditional hardware design time becomes the delivery limiting task. Because both the software and hardware components are programmable at run time, the CADP can adapt to changing requirements without redesign.

  2. Scientific Research: Commodities or Commons?

    NASA Astrophysics Data System (ADS)

    Vermeir, Koen

    2013-10-01

    Truth is for sale today, some critics claim. The increased commodification of science corrupts it, scientific fraud is rampant and the age-old trust in science is shattered. This cynical view, although gaining in prominence, does not explain very well the surprising motivation and integrity that is still central to the scientific life. Although scientific knowledge becomes more and more treated as a commodity or as a product that is for sale, a central part of academic scientific practice is still organized according to different principles. In this paper, I critically analyze alternative models for understanding the organization of knowledge, such as the idea of the scientific commons and the gift economy of science. After weighing the diverse positive and negative aspects of free market economies of science and gift economies of science, a commons structured as a gift economy seems best suited to preserve and take advantage of the specific character of scientific knowledge. Furthermore, commons and gift economies promote the rich social texture that is important for supporting central norms of science. Some of these basic norms might break down if the gift character of science is lost. To conclude, I consider the possibility and desirability of hybrid economies of academic science, which combine aspects of gift economies and free market economies. The aim of this paper is to gain a better understanding of these deeper structural challenges faced by science policy. Such theoretical reflections should eventually assist us in formulating new policy guidelines.

  3. George Combe and common sense.

    PubMed

    Dyde, Sean

    2015-06-01

    This article examines the history of two fields of enquiry in late eighteenth- and early nineteenth-century Scotland: the rise and fall of the common sense school of philosophy and phrenology as presented in the works of George Combe. Although many previous historians have construed these histories as separate, indeed sometimes incommensurate, I propose that their paths were intertwined to a greater extent than has previously been given credit. The philosophy of common sense was a response to problems raised by Enlightenment thinkers, particularly David Hume, and spurred a theory of the mind and its mode of study. In order to succeed, or even to be considered a rival of these established understandings, phrenologists adapted their arguments for the sake of engaging in philosophical dispute. I argue that this debate contributed to the relative success of these groups: phrenology as a well-known historical subject, common sense now largely forgotten. Moreover, this history seeks to question the place of phrenology within the sciences of mind in nineteenth-century Britain.

  4. Treating urinary tract stones: common questions about a common problem.

    PubMed

    Monga, Manoj

    2010-08-01

    Urinary stones are a common and costly problem. Although shockwave lithotripsy is the mainstay of treatment for stones, a number of other surgical tools and approaches may be beneficial to some patients. Newer diagnostic techniques and technologies are improving our ability to determine the size, location, and composition of stones and, thus, our approach to treatment. And an increased focus on diet and metabolism is helping patients prevent stone formation. This article reviews the current approaches to diagnosing and treating urologic stones and answers questions primary care physicians often ask about this topic.

  5. Developmental pathways in colon cancer

    PubMed Central

    Bertrand, Fred E.; Angus, C. William; Partis, William J.; Sigounas, George

    2012-01-01

    A hallmark of cancer is reactivation/alteration of pathways that control cellular differentiation during developmental processes. Evidence indicates that WNT, Notch, BMP and Hedgehog pathways have a role in normal epithelial cell differentiation, and that alterations in these pathways accompany establishment of the tumorigenic state. Interestingly, there is recent evidence that these pathways are intertwined at the molecular level, and these nodes of intersection may provide opportunities for effective targeted therapies. This review will highlight the role of the WNT, Notch, BMP and Hedgehog pathways in colon cancer. PMID:23032367

  6. Descending pathways to the spinal cord: a comparative study of 22 mammals.

    PubMed

    Nudo, R J; Masterton, R B

    1988-11-01

    In order to estimate the qualitative commonalities and range of variation among major descending spinal pathways relevant to mankind's ancestral lineage, the supraspinal cell groups originating fibers descending directly to the spinal cord were examined in 22 mammalian species. In a standardized retrograde tract-tracing procedure, flakes of raw HRP were applied directly to the freshly cut fibers of the spinal cord after it had been hemisected at the C1-C2 junction. After a 72-hour survival period, brain and spinal cord tissues were processed by conventional HRP-processing techniques. This procedure was performed on 94 individual animals. Of this total, 41 individual cases were eliminated by a rigorous culling procedure. The results are based on 53 individuals representing 15 species selected for their successive kinship with mankind and seven species in two other lineages selected for the convergence of their visual or sensorimotor systems with anthropoids. The 22 species represent 19 genera, 14 families, eight orders, and two subclasses of Mammalia. The results show that at least 27 supraspinal cell groups, each containing intensely labeled cells, can be readily identified in each of the species. Despite vast quantitative differences in cell number and cell size, this qualitative uniformity among the relatively large number of diverse taxa suggests that the same pathways were probably present in the extinct ancestors throughout mankind's mammalian lineage and are probably still present in extant viviparous mammals as well. If so, these pathways are as old in phylogenetic history as the last common ancestor of marsupial and placental mammals--dating from the late Jurassic to early Cretaceous, perhaps 145-120 million years ago. Further comparison of the results with similar experimental findings in members of other vertebrate classes supports the notion that several of these same pathways can be traced to even more remote ancestry, with some possibly as old as the

  7. Descending pathways to the spinal cord: a comparative study of 22 mammals.

    PubMed

    Nudo, R J; Masterton, R B

    1988-11-01

    In order to estimate the qualitative commonalities and range of variation among major descending spinal pathways relevant to mankind's ancestral lineage, the supraspinal cell groups originating fibers descending directly to the spinal cord were examined in 22 mammalian species. In a standardized retrograde tract-tracing procedure, flakes of raw HRP were applied directly to the freshly cut fibers of the spinal cord after it had been hemisected at the C1-C2 junction. After a 72-hour survival period, brain and spinal cord tissues were processed by conventional HRP-processing techniques. This procedure was performed on 94 individual animals. Of this total, 41 individual cases were eliminated by a rigorous culling procedure. The results are based on 53 individuals representing 15 species selected for their successive kinship with mankind and seven species in two other lineages selected for the convergence of their visual or sensorimotor systems with anthropoids. The 22 species represent 19 genera, 14 families, eight orders, and two subclasses of Mammalia. The results show that at least 27 supraspinal cell groups, each containing intensely labeled cells, can be readily identified in each of the species. Despite vast quantitative differences in cell number and cell size, this qualitative uniformity among the relatively large number of diverse taxa suggests that the same pathways were probably present in the extinct ancestors throughout mankind's mammalian lineage and are probably still present in extant viviparous mammals as well. If so, these pathways are as old in phylogenetic history as the last common ancestor of marsupial and placental mammals--dating from the late Jurassic to early Cretaceous, perhaps 145-120 million years ago. Further comparison of the results with similar experimental findings in members of other vertebrate classes supports the notion that several of these same pathways can be traced to even more remote ancestry, with some possibly as old as the

  8. Cultural pathways through universal development.

    PubMed

    Greenfield, Patricia M; Keller, Heidi; Fuligni, Andrew; Maynard, Ashley

    2003-01-01

    We focus our review on three universal tasks of human development: relationship formation, knowledge acquisition, and the balance between autonomy and relatedness at adolescence. We present evidence that each task can be addressed through two deeply different cultural pathways through development: the pathways of independence and interdependence. Whereas core theories in developmental psychology are universalistic in their intentions, they in fact presuppose the independent pathway of development. Because the independent pathway is therefore well-known in psychology, we focus a large part of our review on empirically documenting the alternative, interdependent pathway for each developmental task. We also present three theoretical approaches to culture and development: the ecocultural, the sociohistorical, and the cultural values approach. We argue that an understanding of cultural pathways through human development requires all three approaches. We review evidence linking values (cultural values approach), ecological conditions (ecocultural approach), and socialization practices (sociohistorical approach) to cultural pathways through universal developmental tasks. PMID:12415076

  9. Pathway analysis with next-generation sequencing data.

    PubMed

    Zhao, Jinying; Zhu, Yun; Boerwinkle, Eric; Xiong, Momiao

    2015-04-01

    Although pathway analysis methods have been developed and successfully applied to association studies of common variants, the statistical methods for pathway-based association analysis of rare variants have not been well developed. Many investigators observed highly inflated false-positive rates and low power in pathway-based tests of association of rare variants. The inflated false-positive rates and low true-positive rates of the current methods are mainly due to their lack of ability to account for gametic phase disequilibrium. To overcome these serious limitations, we develop a novel statistic that is based on the smoothed functional principal component analysis (SFPCA) for pathway association tests with next-generation sequencing data. The developed statistic has the ability to capture position-level variant information and account for gametic phase disequilibrium. By intensive simulations, we demonstrate that the SFPCA-based statistic for testing pathway association with either rare or common or both rare and common variants has the correct type 1 error rates. Also the power of the SFPCA-based statistic and 22 additional existing statistics are evaluated. We found that the SFPCA-based statistic has a much higher power than other existing statistics in all the scenarios considered. To further evaluate its performance, the SFPCA-based statistic is applied to pathway analysis of exome sequencing data in the early-onset myocardial infarction (EOMI) project. We identify three pathways significantly associated with EOMI after the Bonferroni correction. In addition, our preliminary results show that the SFPCA-based statistic has much smaller P-values to identify pathway association than other existing methods. PMID:24986826

  10. Signaling Pathways in Thyroid Cancer and Their Therapeutic Implications

    PubMed Central

    Jin, Shan; Borkhuu, Oyungerel; Bao, Wuyuntu; Yang, Yun-Tian

    2016-01-01

    Thyroid cancer is a common malignancy of endocrine system, and has now become the fastest increasing cancer among all the malignancies. The development, progression, invasion, and metastasis are closely associated with multiple signaling pathways and the functions of related molecules, such as Src, Janus kinase (JAK)-signal transducers and activators of transcription (STAT), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, NF-κB, thyroid stimulating hormone receptor (TSHR), Wnt-β-catenin and Notch signaling pathways. Each of the signaling pathways could exert its function singly or through network with other pathways. These pathways could cooperate, promote, antagonize, or interact with each other to form a complex network for the regulation. Dysfunction of this network could increase the development, progression, invasion, and metastasis of thyroid cancer. Inoperable thyroid cancer still has a poor prognosis. However, signaling pathway-related targeted therapies offer the hope of longer quality of meaningful life for this small group of patients. Signaling pathway-related targets provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. In the present work, the advances in these signaling pathways and targeted treatments of thyroid cancer were reviewed. PMID:26985248

  11. Pathway Analysis for Drug Repositioning Based on Public Database Mining

    PubMed Central

    2015-01-01

    Sixteen FDA-approved drugs were investigated to elucidate their mechanisms of action (MOAs) and clinical functions by pathway analysis based on retrieved drug targets interacting with or affected by the investigated drugs. Protein and gene targets and associated pathways were obtained by data-mining of public databases including the MMDB, PubChem BioAssay, GEO DataSets, and the BioSystems databases. Entrez E-Utilities were applied, and in-house Ruby scripts were developed for data retrieval and pathway analysis to identify and evaluate relevant pathways common to the retrieved drug targets. Pathways pertinent to clinical uses or MOAs were obtained for most drugs. Interestingly, some drugs identified pathways responsible for other diseases than their current therapeutic uses, and these pathways were verified retrospectively by in vitro tests, in vivo tests, or clinical trials. The pathway enrichment analysis based on drug target information from public databases could provide a novel approach for elucidating drug MOAs and repositioning, therefore benefiting the discovery of new therapeutic treatments for diseases. PMID:24460210

  12. Signaling Pathways in Melanogenesis

    PubMed Central

    D’Mello, Stacey A. N.; Finlay, Graeme J.; Baguley, Bruce C.; Askarian-Amiri, Marjan E.

    2016-01-01

    Melanocytes are melanin-producing cells found in skin, hair follicles, eyes, inner ear, bones, heart and brain of humans. They arise from pluripotent neural crest cells and differentiate in response to a complex network of interacting regulatory pathways. Melanins are pigment molecules that are endogenously synthesized by melanocytes. The light absorption of melanin in skin and hair leads to photoreceptor shielding, thermoregulation, photoprotection, camouflage and display coloring. Melanins are also powerful cation chelators and may act as free radical sinks. Melanin formation is a product of complex biochemical events that starts from amino acid tyrosine and its metabolite, dopa. The types and amounts of melanin produced by melanocytes are determined genetically and are influenced by a variety of extrinsic and intrinsic factors such as hormonal changes, inflammation, age and exposure to UV light. These stimuli affect the different pathways in melanogenesis. In this review we will discuss the regulatory mechanisms involved in melanogenesis and explain how intrinsic and extrinsic factors regulate melanin production. We will also explain the regulatory roles of different proteins involved in melanogenesis. PMID:27428965

  13. Signaling Pathways in Melanogenesis.

    PubMed

    D'Mello, Stacey A N; Finlay, Graeme J; Baguley, Bruce C; Askarian-Amiri, Marjan E

    2016-01-01

    Melanocytes are melanin-producing cells found in skin, hair follicles, eyes, inner ear, bones, heart and brain of humans. They arise from pluripotent neural crest cells and differentiate in response to a complex network of interacting regulatory pathways. Melanins are pigment molecules that are endogenously synthesized by melanocytes. The light absorption of melanin in skin and hair leads to photoreceptor shielding, thermoregulation, photoprotection, camouflage and display coloring. Melanins are also powerful cation chelators and may act as free radical sinks. Melanin formation is a product of complex biochemical events that starts from amino acid tyrosine and its metabolite, dopa. The types and amounts of melanin produced by melanocytes are determined genetically and are influenced by a variety of extrinsic and intrinsic factors such as hormonal changes, inflammation, age and exposure to UV light. These stimuli affect the different pathways in melanogenesis. In this review we will discuss the regulatory mechanisms involved in melanogenesis and explain how intrinsic and extrinsic factors regulate melanin production. We will also explain the regulatory roles of different proteins involved in melanogenesis. PMID:27428965

  14. The Reactome pathway Knowledgebase

    PubMed Central

    Fabregat, Antonio; Sidiropoulos, Konstantinos; Garapati, Phani; Gillespie, Marc; Hausmann, Kerstin; Haw, Robin; Jassal, Bijay; Jupe, Steven; Korninger, Florian; McKay, Sheldon; Matthews, Lisa; May, Bruce; Milacic, Marija; Rothfels, Karen; Shamovsky, Veronica; Webber, Marissa; Weiser, Joel; Williams, Mark; Wu, Guanming; Stein, Lincoln; Hermjakob, Henning; D'Eustachio, Peter

    2016-01-01

    The Reactome Knowledgebase (www.reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations—an extended version of a classic metabolic map, in a single consistent data model. Reactome functions both as an archive of biological processes and as a tool for discovering unexpected functional relationships in data such as gene expression pattern surveys or somatic mutation catalogues from tumour cells. Over the last two years we redeveloped major components of the Reactome web interface to improve usability, responsiveness and data visualization. A new pathway diagram viewer provides a faster, clearer interface and smooth zooming from the entire reaction network to the details of individual reactions. Tool performance for analysis of user datasets has been substantially improved, now generating detailed results for genome-wide expression datasets within seconds. The analysis module can now be accessed through a RESTFul interface, facilitating its inclusion in third party applications. A new overview module allows the visualization of analysis results on a genome-wide Reactome pathway hierarchy using a single screen page. The search interface now provides auto-completion as well as a faceted search to narrow result lists efficiently. PMID:26656494

  15. A Novel Testosterone Catabolic Pathway in Bacteria ▿ ‡

    PubMed Central

    Leu, Yann-Lii; Wang, Po-Hsiang; Shiao, Ming-Shi; Ismail, Wael; Chiang, Yin-Ru

    2011-01-01

    Forty years ago, Coulter and Talalay (A. W. Coulter and P. Talalay, J. Biol. Chem. 243:3238–3247, 1968) established the oxygenase-dependent pathway for the degradation of testosterone by aerobes. The oxic testosterone catabolic pathway involves several oxygen-dependent reactions and is not available for anaerobes. Since then, a variety of anaerobic bacteria have been described for the ability to degrade testosterone in the absence of oxygen. Here, a novel, oxygenase-independent testosterone catabolic pathway in such organisms is described. Steroidobacter denitrificansDSMZ18526 was shown to be capable of degrading testosterone in the absence of oxygen and was selected as the model organism in this study. In a previous investigation, we identified the initial intermediates involved in an anoxic testosterone catabolic pathway, most of which are identical to those of the oxic pathway demonstrated in Comamonas testosteroni. In this study, five additional intermediates of the anoxic pathway were identified. We demonstrated that subsequent steps of the anoxic pathway greatly differ from those of the established oxic pathway, which suggests that a novel pathway for testosterone catabolism is present. In the proposed anoxic pathway, a reduction reaction occurs at C-4 and C-5 of androsta-1,4-diene-3,17-dione, the last common intermediate of both the oxic and anoxic pathways. After that, a novel hydration reaction occurs and a hydroxyl group is thus introduced to the C-1α position of C19steroid substrates. To our knowledge, an enzymatic hydration reaction occurring at the A ring of steroid compounds has not been reported before. PMID:21725000

  16. hiPathDB: a human-integrated pathway database with facile visualization

    PubMed Central

    Yu, Namhee; Seo, Jihae; Rho, Kyoohyoung; Jang, Yeongjun; Park, Jinah; Kim, Wan Kyu; Lee, Sanghyuk

    2012-01-01

    One of the biggest challenges in the study of biological regulatory networks is the systematic organization and integration of complex interactions taking place within various biological pathways. Currently, the information of the biological pathways is dispersed in multiple databases in various formats. hiPathDB is an integrated pathway database that combines the curated human pathway data of NCI-Nature PID, Reactome, BioCarta and KEGG. In total, it includes 1661 pathways consisting of 8976 distinct physical entities. hiPathDB provides two different types of integration. The pathway-level integration, conceptually a simple collection of individual pathways, was achieved by devising an elaborate model that takes distinct features of four databases into account and subsequently reformatting all pathways in accordance with our model. The entity-level integration creates a single unified pathway that encompasses all pathways by merging common components. Even though the detailed molecular-level information such as complex formation or post-translational modifications tends to be lost, such integration makes it possible to investigate signaling network over the entire pathways and allows identification of pathway cross-talks. Another strong merit of hiPathDB is the built-in pathway visualization module that supports explorative studies of complex networks in an interactive fashion. The layout algorithm is optimized for virtually automatic visualization of the pathways. hiPathDB is available at http://hiPathDB.kobic.re.kr. PMID:22123737

  17. Extending the Shared Socioeconomic Pathways for sub-national impacts, adaptation, and vulnerability studies

    SciTech Connect

    Absar, Syeda Mariya; Preston, Benjamin L.

    2015-05-25

    The exploration of alternative socioeconomic futures is an important aspect of understanding the potential consequences of climate change. While socioeconomic scenarios are common and, at times essential, tools for the impact, adaptation and vulnerability and integrated assessment modeling research communities, their approaches to scenario development have historically been quite distinct. However, increasing convergence of impact, adaptation and vulnerability and integrated assessment modeling research in terms of scales of analysis suggests there may be value in the development of a common framework for socioeconomic scenarios. The Shared Socioeconomic Pathways represents an opportunity for the development of such a common framework. However, the scales at which these global storylines have been developed are largely incommensurate with the sub-national scales at which impact, adaptation and vulnerability, and increasingly integrated assessment modeling, studies are conducted. Our objective for this study was to develop sub-national and sectoral extensions of the global SSP storylines in order to identify future socioeconomic challenges for adaptation for the U.S. Southeast. A set of nested qualitative socioeconomic storyline elements, integrated storylines, and accompanying quantitative indicators were developed through an application of the Factor-Actor-Sector framework. Finally, in addition to revealing challenges and opportunities associated with the use of the SSPs as a basis for more refined scenario development, this study generated sub-national storyline elements and storylines that can subsequently be used to explore the implications of alternative subnational socioeconomic futures for the assessment of climate change impacts and adaptation.

  18. Personalized Pathways to Success

    ERIC Educational Resources Information Center

    Westover, Jay

    2012-01-01

    The term "college and career ready" has become widely used as a result of the proposed Elementary and Secondary Education Act (ESEA) reauthorization and Common Core State Standards movement. As schools move toward what may be considered a moral and economic imperative for the nation's students, it is essential that they first identify the gaps of…

  19. Assessment of relative potential for Legionella species or surrogates inhalation exposure from common water uses.

    PubMed

    Hines, Stephanie A; Chappie, Daniel J; Lordo, Robert A; Miller, Brian D; Janke, Robert J; Lindquist, H Alan; Fox, Kim R; Ernst, Hiba S; Taft, Sarah C

    2014-06-01

    The Legionella species have been identified as important waterborne pathogens in terms of disease morbidity and mortality. Microbial exposure assessment is a tool that can be utilized to assess the potential of Legionella species inhalation exposure from common water uses. The screening-level exposure assessment presented in this paper developed emission factors to model aerosolization, quantitatively assessed inhalation exposures of aerosolized Legionella species or Legionella species surrogates while evaluating two generalized levels of assumed water concentrations, and developed a relative ranking of six common in-home uses of water for potential Legionella species inhalation exposure. Considerable variability in the calculated exposure dose was identified between the six identified exposure pathways, with the doses differing by over five orders of magnitude in each of the evaluated exposure scenarios. The assessment of exposure pathways that have been epidemiologically associated with legionellosis transmission (ultrasonic and cool mist humidifiers) produced higher estimated inhalation exposure doses than pathways where epidemiological evidence of transmission has been less strong (faucet and shower) or absent (toilets and therapy pool). With consideration of the large uncertainties inherent in the exposure assessment process used, a relative ranking of exposure pathways from highest to lowest exposure doses was produced using culture-based measurement data and the assumption of constant water concentration across exposure pathways. In this ranking, the ultrasonic and cool mist humidifier exposure pathways were estimated to produce the highest exposure doses, followed by the shower and faucet exposure pathways, and then the toilet and therapy pool exposure pathways.

  20. Sampled Longest Common Prefix Array

    NASA Astrophysics Data System (ADS)

    Sirén, Jouni

    When augmented with the longest common prefix (LCP) array and some other structures, the suffix array can solve many string processing problems in optimal time and space. A compressed representation of the LCP array is also one of the main building blocks in many compressed suffix tree proposals. In this paper, we describe a new compressed LCP representation: the sampled LCP array. We show that when used with a compressed suffix array (CSA), the sampled LCP array often offers better time/space trade-offs than the existing alternatives. We also show how to construct the compressed representations of the LCP array directly from a CSA.

  1. Multiple order common path spectrometer

    NASA Technical Reports Server (NTRS)

    Newbury, Amy B. (Inventor)

    2010-01-01

    The present invention relates to a dispersive spectrometer. The spectrometer allows detection of multiple orders of light on a single focal plane array by splitting the orders spatially using a dichroic assembly. A conventional dispersion mechanism such as a defraction grating disperses the light spectrally. As a result, multiple wavelength orders can be imaged on a single focal plane array of limited spectral extent, doubling (or more) the number of spectral channels as compared to a conventional spectrometer. In addition, this is achieved in a common path device.

  2. Common genetic and epigenetic syndromes.

    PubMed

    Adams, Darius J; Clark, David A

    2015-04-01

    Cytogenetic anomalies should be considered in individuals with multiple congenital anomalies. DNA methylation analysis is the most sensitive initial test in evaluating for Prader-Willi and Angelman syndromes. The timely identification of cytogenetic anomalies allows for prompt initiation of early intervention services to maximize the potential of every individual as they grow older. Although many of these conditions are rare, keeping them in mind can have a profound impact on the clinical course of affected individuals. This article reviews some of the more common genetic syndromes. PMID:25836705

  3. Improved patient pathways can prevent overcrowding.

    PubMed

    Emeny, Russell; Vincent, Connolly

    2013-03-01

    Emergency department (ED) crowding is a common problem throughout the western world. Not only does crowding create a miserable environment for patients, and to considerable stress and poor job satisfaction among staff, it can also lead EDs to breach the four-hour standard and other care quality indicators. In addition, crowding in EDs correlates with increases in patient mortality, rates of admission, lengths of inpatient stay and costs. This article argues that crowding is best tackled by the consistent application of eight principles, derived from various guidance, to emergency patient pathways, particularly those in acute settings. PMID:23586168

  4. Structured career pathways in academic primary care.

    PubMed

    Foy, Robbie; Eccles, Martin

    2008-02-01

    Research in primary care has much to offer researchers and ultimately efforts to improve population health and health care. There is a need for capacity building and efforts to improve the science of research in this field. This article outlines a relatively structured career pathway for primary care researchers and offers advice on opportunities and commonly encountered pitfalls. It is largely based upon the authors' experiences and personal reflections as medically trained researchers but many of the implications and lessons are relevant to other clinical and research disciplines.

  5. Vet Centers. Final rule.

    PubMed

    2016-03-01

    The Department of Veterans Affairs (VA) adopts as final an interim final rule that amends its medical regulation that governs Vet Center services. The National Defense Authorization Act for Fiscal Year 2013 (the 2013 Act) requires Vet Centers to provide readjustment counseling services to broader groups of veterans, members of the Armed Forces, including a member of a reserve component of the Armed Forces, and family members of such veterans and members. This final rule adopts as final the regulatory criteria to conform to the 2013 Act, to include new and revised definitions. PMID:26934755

  6. Genetic variants in DNA repair pathways are not associated with disease progression among multiple myeloma patients.

    PubMed

    Thyagarajan, Bharat; Arora, Mukta; Guan, Weihua; Barcelo, Helene; Jackson, Scott; Kumar, Shaji; Gertz, Morie

    2013-11-01

    DNA damage induced by high dose melphalan and autologous transplantation is repaired by the nucleotide excision repair (NER) and base excision repair (BER) pathways. We evaluated the association between single nucleotide polymorphisms (SNPs) (n=311) in the NER and BER pathways and disease progression in 695 multiple myeloma patients who underwent autologous transplantation. None of the SNPs were associated with disease progression. Pathway based analyses showed that the NER pathway had a borderline association with disease progression (p=0.09). These findings suggest that common variation in the NER and BER pathways do not substantially influence disease progression in multiple myeloma patients.

  7. Inelastic final-state interaction

    SciTech Connect

    Suzuki, Mahiko; Suzuki, Mahiko

    2007-10-29

    The final-state interaction in multichannel decay processes is systematically studied with application to B decay in mind. Since the final-state interaction is intrinsically interwoven with the decay interaction in this case, no simple phase theorem like"Watson's theorem" holds for experimentally observed final states. We first examine in detail the two-channel problem as a toy-model to clarify the issues and to remedy common mistakes made in earlier literature. Realistic multichannel problems are too challenging for quantitative analysis. To cope with mathematical complexity, we introduce a method of approximation that is applicable to the case where one prominent inelastic channel dominates over all others. We illustrate this approximation method in the amplitude of the decay B to pi K fed by the intermediate states of a charmed meson pair. Even with our approximation we need more accurate information of strong interactions than we have now. Nonetheless we are able to obtain some insight in the issue and draw useful conclusions on general features on the strong phases.

  8. High pressure common rail injection system modeling and control.

    PubMed

    Wang, H P; Zheng, D; Tian, Y

    2016-07-01

    In this paper modeling and common-rail pressure control of high pressure common rail injection system (HPCRIS) is presented. The proposed mathematical model of high pressure common rail injection system which contains three sub-systems: high pressure pump sub-model, common rail sub-model and injector sub-model is a relative complicated nonlinear system. The mathematical model is validated by the software Matlab and a virtual detailed simulation environment. For the considered HPCRIS, an effective model free controller which is called Extended State Observer - based intelligent Proportional Integral (ESO-based iPI) controller is designed. And this proposed method is composed mainly of the referred ESO observer, and a time delay estimation based iPI controller. Finally, to demonstrate the performances of the proposed controller, the proposed ESO-based iPI controller is compared with a conventional PID controller and ADRC. PMID:27012440

  9. The Common Communication Interface (CCI)

    SciTech Connect

    Shipman, Galen M; Atchley, Scott; Dillow, David A; Geoffray, Patrick; Bosilca, George; Squyres, Jeffrey M; Minnich, Ronald

    2011-01-01

    There are many APIs for connecting and exchanging data between network peers. Each interface varies wildly based on metrics including performance, portability, and complexity. Specifically, many interfaces make design or implementation choices emphasizing some of the more desirable metrics (e.g., performance) while sacrificing others (e.g., portability). As a direct result, software developers building large, network-based applications are forced to choose a specific network API based on a complex, multi-dimensional set of criteria. Such trade-offs inevitably result in an interface that fails to deliver some desirable features. In this paper, we introduce a novel interface that both supports many features that have become standard (or otherwise generally expected) in other communication interfaces, and strives to export a small, yet powerful, interface. This new interface draws upon years of experience from network-oriented software development best practices to systems-level implementations. The goal is to create a relatively simple, high-level communication interface with low barriers to adoption while still providing important features such as scalability, resiliency, and performance. The result is the Common Communications Interface (CCI): an intuitive API that is portable, efficient, scalable, and robust to meet the needs of network-intensive applications common in HPC and cloud computing.

  10. Common Skin Rashes in Children.

    PubMed

    Allmon, Amanda; Deane, Kristen; Martin, Kari L

    2015-08-01

    Because childhood rashes may be difficult to differentiate by appearance alone, it is important to consider the entire clinical presentation to help make the appropriate diagnosis. Considerations include the appearance and location of the rash; the clinical course; and associated symptoms, such as pruritus or fever. A fever is likely to occur with roseola, erythema infectiosum (fifth disease), and scarlet fever. Pruritus sometimes occurs with atopic dermatitis, pityriasis rosea, erythema infectiosum, molluscum contagiosum, and tinea infection. The key feature of roseola is a rash presenting after resolution of a high fever, whereas the distinguishing features in pityriasis rosea are a herald patch and a bilateral and symmetric rash in a Christmas tree pattern. The rash associated with scarlet fever usually develops on the upper trunk, then spreads throughout the body, sparing the palms and soles. Impetigo is a superficial bacterial infection that most commonly affects the face and extremities of children. Erythema infectiosum is characterized by a viral prodrome followed by the "slapped cheek" facial rash. Flesh-colored or pearly white papules with central umbilication occur with molluscum contagiosum, a highly contagious viral infection that usually resolves without intervention. Tinea is a common fungal skin infection in children that affects the scalp, body, groin, feet, hands, or nails. Atopic dermatitis is a chronic, relapsing inflammatory skin condition that may present with a variety of skin changes. PMID:26280141

  11. Management of common sleep disorders.

    PubMed

    Ramar, Kannan; Olson, Eric J

    2013-08-15

    Sleep disorders are common and affect sleep quality and quantity, leading to increased morbidity. Patients with sleep disorders can be categorized as those who cannot sleep, those who will not sleep, those with excessive daytime sleepiness, and those with increased movements during sleep. Insomnia, defined as difficulty initiating or maintaining sleep that results in daytime impairment, is diagnosed using history findings and treated with cognitive behavior therapy, with or without sleep hypnotics. Restless legs syndrome is characterized by an urge to move the legs that worsens with rest, is relieved by movement, and often occurs in the evening or at night. Restless legs syndrome is treated based on the frequency of symptoms. Narcolepsy is characterized by excessive sleepiness, cataplexy, hypnagogic or hypnopompic hallucinations, and sleep paralysis. It is diagnosed using a sleep log or actigraphy, followed by overnight polysomnography and a multiple sleep latency test. Narcolepsy is treated with stimulants, such as modafinil; selective serotonin reuptake inhibitors; or gamma hydroxybutyric acid (sodium oxybate). Patients with snoring and witnessed apneas may have obstructive sleep apnea, which is diagnosed using overnight polysomnography. Continuous positive airway pressure is the most common and effective treatment for obstructive sleep apnea. Rapid eye movement sleep behavior disorder is characterized by increased muscle tone during rapid eye movement sleep, resulting in the patient acting out dreams with possible harmful consequences. It is diagnosed based on history and polysomnography findings, and treated with environmental safety measures and melatonin or clonazepam.

  12. ALMA Common Software - UTFSM Group

    NASA Astrophysics Data System (ADS)

    Araya, M.; Avarias, J.; Mora, M.; Tobar, R.

    The ACS-UTFSM Group was created as a distributed systems research team on astronomical and non-astronomical applications on the year 2004. The choice of the ALMA Common Software framework (ACS) as the development platform came from the experience gained during summerjobs at ESO observatories. After three years of informal contributions to ACS development, the team presented a technology exchange initiative to the ALMA-CONICYT Fund 2006, which was granted in 2007. Through the past years, the UTFSM helped the ACS team with "nice-to-have" applications and testing. Currently the ACS-UTFSM is involved in several contributions to ACS, and the development of a flexible telescope control system (gTCS) framework which aims to encapsulate common requirements and will provide a uniform software. In preparation for this challenging objective, several small projects are currently being developed. The other interesting edge of the team work is the technology transfer initiatives. Several inter-universities collaborations are flourishing (PUC, UCN, UV) after the first ACS Workshop held at the UTFSM this year. Today three former team members are working at NRAO's ALMA Test Facility in Socorro, New Mexico. Two other students will have a summer job next year to work in ALMA related development.

  13. Common ecology quantifies human insurgency.

    PubMed

    Bohorquez, Juan Camilo; Gourley, Sean; Dixon, Alexander R; Spagat, Michael; Johnson, Neil F

    2009-12-17

    Many collective human activities, including violence, have been shown to exhibit universal patterns. The size distributions of casualties both in whole wars from 1816 to 1980 and terrorist attacks have separately been shown to follow approximate power-law distributions. However, the possibility of universal patterns ranging across wars in the size distribution or timing of within-conflict events has barely been explored. Here we show that the sizes and timing of violent events within different insurgent conflicts exhibit remarkable similarities. We propose a unified model of human insurgency that reproduces these commonalities, and explains conflict-specific variations quantitatively in terms of underlying rules of engagement. Our model treats each insurgent population as an ecology of dynamically evolving, self-organized groups following common decision-making processes. Our model is consistent with several recent hypotheses about modern insurgency, is robust to many generalizations, and establishes a quantitative connection between human insurgency, global terrorism and ecology. Its similarity to financial market models provides a surprising link between violent and non-violent forms of human behaviour. PMID:20016600

  14. Management of common sleep disorders.

    PubMed

    Ramar, Kannan; Olson, Eric J

    2013-08-15

    Sleep disorders are common and affect sleep quality and quantity, leading to increased morbidity. Patients with sleep disorders can be categorized as those who cannot sleep, those who will not sleep, those with excessive daytime sleepiness, and those with increased movements during sleep. Insomnia, defined as difficulty initiating or maintaining sleep that results in daytime impairment, is diagnosed using history findings and treated with cognitive behavior therapy, with or without sleep hypnotics. Restless legs syndrome is characterized by an urge to move the legs that worsens with rest, is relieved by movement, and often occurs in the evening or at night. Restless legs syndrome is treated based on the frequency of symptoms. Narcolepsy is characterized by excessive sleepiness, cataplexy, hypnagogic or hypnopompic hallucinations, and sleep paralysis. It is diagnosed using a sleep log or actigraphy, followed by overnight polysomnography and a multiple sleep latency test. Narcolepsy is treated with stimulants, such as modafinil; selective serotonin reuptake inhibitors; or gamma hydroxybutyric acid (sodium oxybate). Patients with snoring and witnessed apneas may have obstructive sleep apnea, which is diagnosed using overnight polysomnography. Continuous positive airway pressure is the most common and effective treatment for obstructive sleep apnea. Rapid eye movement sleep behavior disorder is characterized by increased muscle tone during rapid eye movement sleep, resulting in the patient acting out dreams with possible harmful consequences. It is diagnosed based on history and polysomnography findings, and treated with environmental safety measures and melatonin or clonazepam. PMID:23944726

  15. Common Skin Rashes in Children.

    PubMed

    Allmon, Amanda; Deane, Kristen; Martin, Kari L

    2015-08-01

    Because childhood rashes may be difficult to differentiate by appearance alone, it is important to consider the entire clinical presentation to help make the appropriate diagnosis. Considerations include the appearance and location of the rash; the clinical course; and associated symptoms, such as pruritus or fever. A fever is likely to occur with roseola, erythema infectiosum (fifth disease), and scarlet fever. Pruritus sometimes occurs with atopic dermatitis, pityriasis rosea, erythema infectiosum, molluscum contagiosum, and tinea infection. The key feature of roseola is a rash presenting after resolution of a high fever, whereas the distinguishing features in pityriasis rosea are a herald patch and a bilateral and symmetric rash in a Christmas tree pattern. The rash associated with scarlet fever usually develops on the upper trunk, then spreads throughout the body, sparing the palms and soles. Impetigo is a superficial bacterial infection that most commonly affects the face and extremities of children. Erythema infectiosum is characterized by a viral prodrome followed by the "slapped cheek" facial rash. Flesh-colored or pearly white papules with central umbilication occur with molluscum contagiosum, a highly contagious viral infection that usually resolves without intervention. Tinea is a common fungal skin infection in children that affects the scalp, body, groin, feet, hands, or nails. Atopic dermatitis is a chronic, relapsing inflammatory skin condition that may present with a variety of skin changes.

  16. Common contact sensitizers in Delhi.

    PubMed

    Singhal, V; Reddy, B S

    2000-07-01

    Seventy-five patients of both sexes with clinically suspected contact dermatitis were patch tested with the Indian Standard Series and indigenous antigens. The results were compared with the data from other centers. Most of these patients were young adults between 20 and 39 yrs old with the mean age of 36.63 +/- 5.6 yrs. Their occupational profiles included household workers (17.33%), masons (10.66%), farmers (6.66%), factory workers (4%), medical personnel (4%), lab workers (2.66%), and miscellaneous (17.33%). Itching and burning were two of the most common complaints, and chronic dermatitis was the predominant morphologic pattern of the lesions observed. Frequent sites involved included the hands (40.83%), airborne type (22.44%), hands and feet (12.24%), feet (12.24%), face (10.2%), and neck (2.04%). Patch test analysis of these patients revealed that, out of 75 subjects tested, 49 (65.3%) reacted to one or more allergens. Parthenium (20%) is the most common contact sensitizer followed by potassium dichromate (16%), xanthium (13.33%), nickel sulphate (12%), chrysanthemum (8%), mercaptobenzothiazole, and garlic (6.66% each). These findings are in broad conformity with those in other reports. We concluded that the Indian Standard Series of antigens with the addition of a few more (such as garlic, onion and chlorheximide of local relevance) is suitable for detecting the allergens responsible for the contact dermatitis prevailing in this region. PMID:10935340

  17. Precise generation of systems biology models from KEGG pathways

    PubMed Central

    2013-01-01

    Background The KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG REACTION. Therefore, the pathways can be extended with an enormous amount of information and provide a foundation for initial structural modeling approaches. As a drawback, KGML-formatted KEGG pathways are primarily designed for visualization purposes and often omit important details for the sake of a clear arrangement of its entries. Thus, a direct conversion into systems biology models would produce incomplete and erroneous models. Results Here, we present a precise method for processing and converting KEGG pathways into initial metabolic and signaling models encoded in the standardized community pathway formats SBML (Levels 2 and 3) and BioPAX (Levels 2 and 3). This method involves correcting invalid or incomplete KGML content, creating complete and valid stoichiometric reactions, translating relations to signaling models and augmenting the pathway content with various information, such as cross-references to Entrez Gene, OMIM, UniProt ChEBI, and many more. Finally, we compare several existing conversion tools for KEGG pathways and show that the conversion from KEGG to BioPAX does not involve a loss of information, whilst lossless translations to SBML can only be performed using SBML Level 3, including its recently proposed qualitative models and groups extension packages. Conclusions Building correct BioPAX and SBML signaling models from the KEGG database is a unique characteristic of the proposed method. Further, there is no other approach that is able to appropriately construct metabolic models from KEGG pathways, including correct reactions with stoichiometry. The resulting initial models, which contain valid and comprehensive SBML or BioPAX code and a multitude of cross-references, lay the foundation to facilitate further modeling steps. PMID:23433509

  18. Pathways of Antigen Processing

    PubMed Central

    Blum, Janice S.; Wearsch, Pamela A.; Cresswell, Peter

    2014-01-01

    T cell recognition of antigen presenting cells depends on their expression of a spectrum of peptides bound to Major Histocompatibility Complex class I (MHC-I) and class II (MHC-II) molecules. Conversion of antigens from pathogens or transformed cells into MHC-I and MHC-II-bound peptides is critical for mounting protective T cell responses, and similar processing of self proteins is necessary to establish and maintain tolerance. Cells use a variety of mechanisms to acquire protein antigens, from translation in the cytosol to variations on the theme of endocytosis, and to degrade them once acquired. In this review we highlight the aspects of MHC-I and MHC-II biosynthesis and assembly that have evolved to intersect these pathways and sample the peptides that are produced. PMID:23298205

  19. Summer 2014 Pathways Report

    NASA Technical Reports Server (NTRS)

    Hand, Zachary

    2014-01-01

    Over the summer I had the exciting opportunity to work for NASA at the Kennedy Space Center as a Mission Assurance Engineering intern. When I was offered a position in mission assurance for the Safety and Mission Assurance directorate's Launch Services Division, I didn't really know what I would be doing, but I knew it would be an excellent opportunity to learn and grow professionally. In this report I will provide some background information on the Launch Services Division, as well as detail my duties and accomplishments during my time as an intern. Additionally, I will relate the significance of my work experience to my current academic work and future career goals. This report contains background information on Mission Assurance Engineering, a description of my duties and accomplishments over the summer of 2014, and relates the significance of my work experience to my school work and future career goals. It is a required document for the Pathways program.

  20. [Implementing clinical pathways: some practical notes].

    PubMed

    Raggi, F; Montella, M T; Lazzari, C; Ciotti, E; Longanesi, A; Nardacchione, V; Bernardi, R; Cacciari, P

    2012-01-01

    The traditional biomedical paradigm is no longer a guarantee of quality for health care, facing increasingly difficult challenges caused by chronic diseases and increasingly fragmented resources that current healthcare systems are dealing with. Health care organizations, considered to be the most complex enterprises of the modern era, must be able to focus on the flow of patients, integrating primary and secondary care through tools such as the Integrated Care Pathways (ICP). This brief discussion attempts to define the ICP its purposes, the elements that characterize it, its limitations and the mechanisms to push for a successful implementation. In order to highlight the elements and basic steps for the creation of an ICP, the authors have compared five different clinical pathways, whose implementation they have contributed to. The comparison was made using two grids: the first showing the essential elements for the definition of lCP and the second one with features that can facilitate their effectiveness. The conclusions of the work show what, pursuing the construction of a pathway, we must never forget: to analyze the gap between the clinical-care activities performed and the theoretical framework provided by the evidence; to see the barriers to change that may impede the implementation; to involve all actors in the system, with particular attention to patients and their associations, and finally to provide a plan for information and education, addressed to health professionals and patients as well. PMID:22755502

  1. Nonmonotonic Dose Response Curves (NMDRCs) Common after Estrogen or Androgen Signaling Pathway Disruption: Fact or Falderal?

    EPA Science Inventory

    EDCs appear to induce some effects that do not appear to display a threshold (apparent Linear No Threshold responses) NMDRCs for EDCs Biologically plausible Occur frequently in vitro, but these are generally not relevant to in vivo effects and do not occur at low concentrations ...

  2. Behavioral and Physiological Neural Network Analyses: A Common Pathway toward Pattern Recognition and Prediction

    ERIC Educational Resources Information Center

    Ninness, Chris; Lauter, Judy L.; Coffee, Michael; Clary, Logan; Kelly, Elizabeth; Rumph, Marilyn; Rumph, Robin; Kyle, Betty; Ninness, Sharon K.

    2012-01-01

    Using 3 diversified datasets, we explored the pattern-recognition ability of the Self-Organizing Map (SOM) artificial neural network as applied to diversified nonlinear data distributions in the areas of behavioral and physiological research. Experiment 1 employed a dataset obtained from the UCI Machine Learning Repository. Data for this study…

  3. Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

    PubMed Central

    An, S.S.; Bai, T.R.; Bates, J.H.T.; Black, J.L.; Brown, R.H.; Brusasco, V.; Chitano, P.; Deng, L.; Dowell, M.; Eidelman, D.H.; Fabry, B.; Fairbank, N.J.; Ford, L.E.; Fredberg, J.J.; Gerthoffer, W.T.; Gilbert, S.H.; Gosens, R.; Gunst, S.J.; Halayko, A.J.; Ingram, R.H.; Irvin, C.G.; James, A.L.; Janssen, L.J.; King, G.G.; Knight, D.A.; Lauzon, A.M.; Lakser, O.J.; Ludwig, M.S.; Lutchen, K.R.; Maksym, G.N.; Martin, J.G.; Mauad, T.; McParland, B.E.; Mijailovich, S.M.; Mitchell, H.W.; Mitchell, R.W.; Mitzner, W.; Murphy, T.M.; Paré, P.D.; Pellegrino, R.; Sanderson, M.J.; Schellenberg, R.R.; Seow, C.Y.; Silveira, P.S.P.; Smith, P.G.; Solway, J.; Stephens, N.L.; Sterk, P.J.; Stewart, A.G.; Tang, D.D.; Tepper, R.S.; Tran, T.; Wang, L.

    2008-01-01

    Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling. Anti-inflammatory therapy, however, does not “cure” asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM. In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored. PMID:17470619

  4. Reading for Meaning in Dyslexic and Young Children: Distinct Neural Pathways but Common Endpoints

    ERIC Educational Resources Information Center

    Schulz, Enrico; Maurer, Urs; van der Mark, Sanne; Bucher, Kerstin; Brem, Silvia; Martin, Ernst; Brandeis, Daniel

    2009-01-01

    Developmental dyslexia is a highly prevalent and specific disorder of reading acquisition characterised by impaired reading fluency and comprehension. We have previously identified fMRI- and ERP-based neural markers of impaired sentence reading in dyslexia that indicated both deviant basic word processing and deviant semantic incongruency…

  5. Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes.

    PubMed

    Scheen, André J; Van Gaal, Luc F

    2014-11-01

    The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent inflammation, abnormal hormone secretion, and various metabolic disturbances that contribute to insulin resistance and insulin secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that leads to cardiovascular disease, liver pathologies, and cancer. Despite the importance of weight control strategies in the prevention and management of type 2 diabetes, long-term results from lifestyle or drug interventions are generally disappointing. Furthermore, most of the classic glucose-lowering drugs have a side-effect of weight gain, which renders the management of most overweight or obese people with type 2 diabetes even more challenging. Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns. The gastrointestinal lipase inhibitor orlistat was the only anti-obesity drug available until the recent US, but not European, launch of phentermine-controlled-release topiramate and lorcaserin. Improved knowledge about bodyweight regulation opens new prospects for the potential use of peptides derived from the gut or the adipose tissue. Combination therapy will probably be necessary to avoid compensatory mechanisms and potentiate initial weight loss while avoiding weight regain. New glucose-lowering treatments, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic drugs by promoting weight loss while improving glucose control. In this Review, we explore the overlapping pathophysiology and also how various treatments can, alone or in combination, combat the dual burden of obesity and type 2 diabetes.

  6. Nitrone spin traps and a nitroxide antioxidant inhibit a common pathway of thymocyte apoptosis.

    PubMed Central

    Slater, A F; Nobel, C S; Maellaro, E; Bustamante, J; Kimland, M; Orrenius, S

    1995-01-01

    Oxidative stress has recently been suggested to be a mediator of apoptotic cell death [Buttke and Sandstrom (1994) Immunology Today 15, 7-10], although evidence that this phenomenon is a widespread component of apoptosis is lacking. When rat thymocytes were exposed to the glucocorticoid methylprednisolone (MPS), a progressive increase in intracellular peroxides and a decrease in glutathione (GSH) were observed to accompany the onset of apoptosis. Using Percoll density gradients to isolate subpopulations of thymocytes at different stages of apoptosis, the increase in peroxide content was found to be restricted to apoptotic cells, while a significant depletion of GSH and reduced protein thiol was detected in both pre-apoptotic and fully apoptotic cells. To investigate the biological significance of these redox changes, the free radical spin traps 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) and 3,3,5,5-tetramethyl-1-pyrroline-1-oxide (TMPO), and the related nitroxide-radical antioxidant 2,2,6,6-tetramethyl-1-piperidinyl-1-oxyl (TEMPO) were tested as inhibitors of thymocyte apoptosis. The cell shrinkage and DNA fragmentation induced by four different initiators of apoptosis were reduced by each compound. TEMPO inhibition of both etoposide- and MPS-induced thymocyte DNA fragmentation was also found to correlate with an increase in intracellular GSH, providing support for the proposal that its antioxidant properties were responsible for the observed protective activity. We conclude that some form of intracellular oxidation (here measured indirectly by changes in intracellular GSH and peroxide levels) is required during thymocyte apoptosis even when this process is initiated by an agent that does not exert a direct oxidant action. Images Figure 2 Figure 4 PMID:7702573

  7. Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes.

    PubMed

    Scheen, André J; Van Gaal, Luc F

    2014-11-01

    The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent inflammation, abnormal hormone secretion, and various metabolic disturbances that contribute to insulin resistance and insulin secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that leads to cardiovascular disease, liver pathologies, and cancer. Despite the importance of weight control strategies in the prevention and management of type 2 diabetes, long-term results from lifestyle or drug interventions are generally disappointing. Furthermore, most of the classic glucose-lowering drugs have a side-effect of weight gain, which renders the management of most overweight or obese people with type 2 diabetes even more challenging. Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns. The gastrointestinal lipase inhibitor orlistat was the only anti-obesity drug available until the recent US, but not European, launch of phentermine-controlled-release topiramate and lorcaserin. Improved knowledge about bodyweight regulation opens new prospects for the potential use of peptides derived from the gut or the adipose tissue. Combination therapy will probably be necessary to avoid compensatory mechanisms and potentiate initial weight loss while avoiding weight regain. New glucose-lowering treatments, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic drugs by promoting weight loss while improving glucose control. In this Review, we explore the overlapping pathophysiology and also how various treatments can, alone or in combination, combat the dual burden of obesity and type 2 diabetes. PMID:24731666

  8. Coping with Perceived Peer Stress: Gender-Specific and Common Pathways to Symptoms of Psychopathology

    ERIC Educational Resources Information Center

    Sontag, Lisa M.; Graber, Julia A.

    2010-01-01

    This study investigated gender differences in the moderating and mediating effects of responses to stress on the association between perceived peer stress and symptoms of psychopathology. A sample of 295 middle school students (63.7% female; M[subscript age] = 12.39 years, SD = 0.99) completed self-report surveys on stress, coping, and behavioral…

  9. Differential Role of Inhibition in Habituation of Two Independent Afferent Pathways to a Common Motor Output

    ERIC Educational Resources Information Center

    Bristol, Adam S.; Carew, Thomas J.

    2005-01-01

    Many studies of the neural mechanisms of learning have focused on habituation, a simple form of learning in which a response decrements with repeated stimulation. In the siphon-elicited siphon withdrawal reflex (S-SWR) of the marine mollusk "Aplysia," the prevailing view is that homosynaptic depression of primary sensory afferents underlies…

  10. Transformation and removal pathways of four common PPCP/EDCs in soil.

    PubMed

    Dodgen, L K; Li, J; Wu, X; Lu, Z; Gan, J J

    2014-10-01

    Pharmaceutical and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs) enter the soil environment via irrigation with treated wastewater, groundwater recharge, and land application of biosolids. The transformation and fate of PPCP/EDCs in soil affects their potential for plant uptake and groundwater pollution. This study examined four PPCP/EDCs (bisphenol A, diclofenac, naproxen, and 4-nonylphenol) in soil by using (14)C-labeling and analyzing mineralization, extractable residue, bound residue, and formation of transformation products. At the end of 112 d of incubation, the majority of (14)C-naproxen and (14)C-diclofenac was mineralized to (14)CO2, while a majority of (14)C-bisphenol A and (14)Cnonylphenol was converted to bound residue. After 112 d, the estimated half-lives of the parent compounds were only 1.4-5.4 d. However a variety of transformation products were found and several for bisphenol A and diclofenac were identified, suggesting the need to consider degradation intermediates in soils impacted by PPCP/EDCs.

  11. Production of bulk chemicals via novel metabolic pathways in microorganisms.

    PubMed

    Shin, Jae Ho; Kim, Hyun Uk; Kim, Dong In; Lee, Sang Yup

    2013-11-01

    Metabolic engineering has been playing important roles in developing high performance microorganisms capable of producing various chemicals and materials from renewable biomass in a sustainable manner. Synthetic and systems biology are also contributing significantly to the creation of novel pathways and the whole cell-wide optimization of metabolic performance, respectively. In order to expand the spectrum of chemicals that can be produced biotechnologically, it is necessary to broaden the metabolic capacities of microorganisms. Expanding the metabolic pathways for biosynthesizing the target chemicals requires not only the enumeration of a series of known enzymes, but also the identification of biochemical gaps whose corresponding enzymes might not actually exist in nature; this issue is the focus of this paper. First, pathway prediction tools, effectively combining reactions that lead to the production of a target chemical, are analyzed in terms of logics representing chemical information, and designing and ranking the proposed metabolic pathways. Then, several approaches for potentially filling in the gaps of the novel metabolic pathway are suggested along with relevant examples, including the use of promiscuous enzymes that flexibly utilize different substrates, design of novel enzymes for non-natural reactions, and exploration of hypothetical proteins. Finally, strain optimization by systems metabolic engineering in the context of novel metabolic pathways constructed is briefly described. It is hoped that this review paper will provide logical ways of efficiently utilizing 'big' biological data to design and develop novel metabolic pathways for the production of various bulk chemicals that are currently produced from fossil resources. PMID:23280013

  12. Production of bulk chemicals via novel metabolic pathways in microorganisms.

    PubMed

    Shin, Jae Ho; Kim, Hyun Uk; Kim, Dong In; Lee, Sang Yup

    2013-11-01

    Metabolic engineering has been playing important roles in developing high performance microorganisms capable of producing various chemicals and materials from renewable biomass in a sustainable manner. Synthetic and systems biology are also contributing significantly to the creation of novel pathways and the whole cell-wide optimization of metabolic performance, respectively. In order to expand the spectrum of chemicals that can be produced biotechnologically, it is necessary to broaden the metabolic capacities of microorganisms. Expanding the metabolic pathways for biosynthesizing the target chemicals requires not only the enumeration of a series of known enzymes, but also the identification of biochemical gaps whose corresponding enzymes might not actually exist in nature; this issue is the focus of this paper. First, pathway prediction tools, effectively combining reactions that lead to the production of a target chemical, are analyzed in terms of logics representing chemical information, and designing and ranking the proposed metabolic pathways. Then, several approaches for potentially filling in the gaps of the novel metabolic pathway are suggested along with relevant examples, including the use of promiscuous enzymes that flexibly utilize different substrates, design of novel enzymes for non-natural reactions, and exploration of hypothetical proteins. Finally, strain optimization by systems metabolic engineering in the context of novel metabolic pathways constructed is briefly described. It is hoped that this review paper will provide logical ways of efficiently utilizing 'big' biological data to design and develop novel metabolic pathways for the production of various bulk chemicals that are currently produced from fossil resources.

  13. Pathways to psychosis in cannabis abuse.

    PubMed

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

    2015-04-01

    Cannabis has been implicated as a risk factor for the development of schizophrenia, but the exact biological mechanisms remain unclear. In this review, we attempt to understand the neurobiological pathways that link cannabis use to schizophrenia. This has been an area of great debate; despite similarities between cannabis users and schizophrenia patients, the evidence is not sufficient to establish cause-and-effect. There have been advances in the understanding of the mechanisms of cannabis dependence as well as the role of the cannabinoid system in the development of psychosis and schizophrenia. The neurobiological mechanisms associated with the development of psychosis and effects from cannabis use may be similar but remain elusive. In order to better understand these associations, this paper will show common neurobiological and neuroanatomical changes as well as common cognitive dysfunction in cannabis users and patients of schizophrenia. We conclude that epidemiologic evidence highlights potential causal links; however, neurobiological evidence for causality remains weak. PMID:23491968

  14. Pathways to psychosis in cannabis abuse.

    PubMed

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

    2015-04-01

    Cannabis has been implicated as a risk factor for the development of schizophrenia, but the exact biological mechanisms remain unclear. In this review, we attempt to understand the neurobiological pathways that link cannabis use to schizophrenia. This has been an area of great debate; despite similarities between cannabis users and schizophrenia patients, the evidence is not sufficient to establish cause-and-effect. There have been advances in the understanding of the mechanisms of cannabis dependence as well as the role of the cannabinoid system in the development of psychosis and schizophrenia. The neurobiological mechanisms associated with the development of psychosis and effects from cannabis use may be similar but remain elusive. In order to better understand these associations, this paper will show common neurobiological and neuroanatomical changes as well as common cognitive dysfunction in cannabis users and patients of schizophrenia. We conclude that epidemiologic evidence highlights potential causal links; however, neurobiological evidence for causality remains weak.

  15. Common sense in nuclear energy

    SciTech Connect

    Hoyle, F.; Hoyle, G.

    1980-01-01

    Public concern about energy resource exhaustion is noted to have developed only after the means (nuclear power) for avoiding this disaster became available and the negative implications of a nuclear society became a focus for anxiety. Ironically, collapse of conventional energy supplies could lead to the nuclear confrontation which anti-nuclear forces claim as the inevitable outcome of nuclear power. A review of the risks, environmental impacts, and political implications of the major energy sources concludes that emotion, not common sense, has made nuclear energy an unpopular option. While the problems of proliferation, radiation protection, waste management, and accident prevention are far from trivial, they will respond to technological improvements and responsible control policies. An historical tradition of fearing new, poorly understood technologies is seen in the reaction to railroads during the early 19th Century. (DCK)

  16. Common questions in veterinary toxicology.

    PubMed

    Bates, N; Rawson-Harris, P; Edwards, N

    2015-05-01

    Toxicology is a vast subject. Animals are exposed to numerous drugs, household products, plants, chemicals, pesticides and venomous animals. In addition to the individual toxicity of the various potential poisons, there is also the question of individual response and, more importantly, of species differences in toxicity. This review serves to address some of the common questions asked when dealing with animals with possible poisoning, providing evidence where available. The role of emetics, activated charcoal and lipid infusion in the management of poisoning in animals, the toxic dose of chocolate, grapes and dried fruit in dogs, the use of antidotes in paracetamol poisoning, timing of antidotal therapy in ethylene glycol toxicosis and whether lilies are toxic to dogs are discussed. PMID:25728477

  17. [The patient pathway, an essential element of the care project].

    PubMed

    Despiau, Frédéric; Bombail, Marie; Le Duff, Gérard; Peoc'h, Nadia; Labatut, Raymonde; Ceaux, Christine

    2015-05-01

    Constructing an innovative care project in oncology, common to two healthcare institutions with different statuses, was a challenge for the directors of nursing of the Claudius-Regaud Institute and Toulouse university hospital. The patient care pathway was a major organisational element of the project, keyto ensuring high quality patient care, from the diagnosis through to the personalised post-cancer plan. PMID:26126375

  18. Cassini's Grand Finale: The Final Orbits

    NASA Astrophysics Data System (ADS)

    Spilker, Linda; Edgington, Scott

    2016-04-01

    The Cassini-Huygens mission, a joint collaboration between NASA, ESA and the Italian Space Agency, is approaching its last year of operations after nearly 12 years in orbit around Saturn. Cassini will send back its final bits of unique data on September 15th, 2017 as it plunges into Saturn's atmosphere, vaporizing and satisfying planetary protection requirements. Before that time Cassini will continue its legacy of exploration and discovery with 12 close flybys of Titan in 2016 and 2017 that will return new science data as well as sculpt the inclinations and periods of the final orbits. Even though all of our close icy satellite flybys, including those of Enceladus, are now completed, numerous Voyager-class flybys (<100,000 km) of Mimas and Enceladus remain as well as some of our best flybys of the tiny ring moons. Cassini will also continue to study seasonal and temporal changes in the system as northern summer solstice approaches. In November 2016 Cassini will transition to a series of orbits with peripases just outside Saturn's F ring. These 20 orbits will include close flybys of some tiny ring moons and excellent views of the F ring and outer A ring. The 126th and final close flyby of Titan will propel Cassini across Saturn's main rings and into its final orbits. Cassini's Grand Finale, starting in April 2017, is comprised of 22 orbits at an inclination of 63 degrees. Cassini will repeatedly dive between the innermost rings and the upper atmosphere of the planet providing insights into fundamental questions unattainable during the rest of the mission. Cassini will be the first spacecraft to explore this region. These close orbits provide the highest resolution observations of both the rings and Saturn, and direct in situ sampling of the ring particles, composition, plasma, Saturn's exosphere and the innermost radiation belts. Saturn's gravitational field will be measured to unprecedented accuracy, providing information on the interior structure of the planet

  19. De Novo Discovery of Mutated Driver Pathways in Cancer

    NASA Astrophysics Data System (ADS)

    Vandin, Fabio; Upfal, Eli; Raphael, Benjamin J.

    Next-generation DNA sequencing technologies are enabling genome-wide measurements of somatic mutations in large numbers of cancer patients. A major challenge in interpretation of this data is to distinguish functional driver mutations that are important for cancer development from random, passenger mutations. A common approach to identify driver mutations is to find genes that are mutated at significant frequency in a large cohort of cancer genomes. This approach is confounded by the observation that driver mutations target multiple cellular signaling and regulatory pathways. Thus, each cancer patient may exhibit a different combination of mutations that are sufficient to perturb the necessary pathways. However, the current understanding of the somatic mutational process of cancer [3,5,6] places two additional constraints on the expected patterns of somatic mutations in a cancer pathway. First, an important cancer pathway should be perturbed in a large number of patients. Thus we expect that with genome-wide measurements of somatic mutations a driver pathway will exhibit high coverage, where most patients will have a mutation in some gene in the pathway. Second, since driver mutations are relatively rare and typically a single driver mutation is sufficient to perturb a pathway, a reasonable assumption is that most patients have a single driver mutation in a pathway. Thus, the genes in a driver pathway exhibit a pattern of mutually exclusive driver mutations, where driver mutations are observed in exactly one gene in the pathway in each patient. There are numerous examples of sets of mutually exclusive mutations [5,6].

  20. 75 FR 59622 - Supplemental Determination for Renewable Fuels Produced Under the Final RFS2 Program From Canola Oil

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... produced from canola oil, the delayed RINs provision will only be applicable to this pathway. \\1\\ 75 FR... Generation for New Pathways In a Notice of Proposed Rulemaking (NPRM) published on July 20, 2010 (75 FR 42238... new RIN-generating pathway to Table 1 to Sec. 80.1426. For the RFS2 final rule (75 FR 14670),...

  1. Influence of Berry-Polyphenols on Receptor Signaling and Cell-Death Pathways: Implications for Breast Cancer Prevention

    PubMed Central

    Aiyer, Harini S; Warri, Anni M; Woode, Denzel R; Hilakivi-Clarke, Leena; Clarke, Robert

    2012-01-01

    Breast cancer is the most commonly diagnosed cancer among women worldwide. Many women have become more aware of the benefits of increasing fruit consumption, as part of a healthy lifestyle, for the prevention of cancer. The mechanisms by which fruits, including berries, prevent breast cancer can be partially explained by exploring their interactions with pathways known influence cell-proliferation and evasion of cell-death. Two receptor pathways- estrogen receptor (ER) and tyrosine kinase receptors, especially the epidermal growth factor receptor (EGFR) family- are drivers of cell-proliferation and play a significant role in the development of both primary and recurrent breast cancer. There is strong evidence to show that several phytochemicals present in berries such as cyanidin, delphinidin, quercetin, kaempferol, ellagic acid, resveratrol and pterostilbene, interact with and alter the effects of these pathways. Further, they also induce cell death (apoptosis and autophagy) via their influence on kinase signaling. In this review, we summarize in vitro data regarding the interaction of berry polyphenols with the specific receptors and the mechanisms by which they induce cell death. Further, we also present in vivo data of primary breast cancer prevention by individual compounds and whole berries. Finally, we present a possible role for berries and berry compounds in the prevention of breast cancer and our perspective on the areas that require further research. PMID:22300613

  2. Revealing Deactivation Pathways Hidden in Time-Resolved Photoelectron Spectra

    PubMed Central

    Ruckenbauer, Matthias; Mai, Sebastian; Marquetand, Philipp; González, Leticia

    2016-01-01

    Time-resolved photoelectron spectroscopy is commonly employed with the intention to monitor electronic excited-state dynamics occurring in a neutral molecule. With the help of theory, we show that when excited-state processes occur on similar time scales the different relaxation pathways are completely obscured in the total photoionization signal recorded in the experiment. Using non-adiabatic molecular dynamics and Dyson norms, we calculate the photoionization signal of cytosine and disentangle the transient contributions originating from the different deactivation pathways of its tautomers. In the simulations, the total signal from the relevant keto and enol tautomers can be decomposed into contributions either from the neutral electronic state populations or from the distinct mechanistic pathways across the multiple potential surfaces. The lifetimes corresponding to these contributions cannot be extracted from the experiment, thereby illustrating that new experimental setups are necessary to unravel the intricate non-adiabatic pathways occurring in polyatomic molecules after irradiation by light. PMID:27762396

  3. Mycobacterial shikimate pathway enzymes as targets for drug design.

    PubMed

    Ducati, R G; Basso, L A; Santos, D S

    2007-03-01

    The aetiological agent of tuberculosis (TB), Mycobacterium tuberculosis, is responsible for millions of deaths annually. The increasing prevalence of the disease, the emergence of multidrug-resistant strains, and the devastating effect of human immunodeficiency virus co-infection have led to an urgent need for the development of new and more efficient antimycobacterial drugs. Since the shikimate pathway is present and essential in algae, higher plants, bacteria, and fungi, but absent from mammals, the gene products of the common pathway might represent attractive targets for the development of new antimycobacterial agents. In this review we describe studies on shikimate pathway enzymes, including enzyme kinetics and structural data. We have focused on mycobacterial shikimate pathway enzymes as potential targets for the development of new anti-TB agents.

  4. Clinical development of phosphatidylinositol-3 kinase pathway inhibitors.

    PubMed

    Arteaga, Carlos L

    2010-01-01

    The PI3K pathway is the most commonly altered in human cancer. Several recent phase I studies with therapeutic inhibitors of this pathway have shown that pharmacological inhibition of PI3K in humans is feasible and overall well tolerated. Furthermore, there has already been clinical evidence of anti-tumor activity in patients with advanced cancer. The intensity and duration of PI3K inhibition required for an antitumor effect and the optimal pharmacodynamic biomarker(s) of pathway inactivation remain to be established. Preclinical and early clinical data support focusing on trials with PI3K inhibitors that are at a minimum enriched with patients with alterations in this signaling pathway. These inhibitors are likely to be more effective in combination with established and other novel molecular therapies.

  5. Oscillatory Dynamics of the Extracellular Signal-regulated Kinase Pathway

    SciTech Connect

    Shankaran, Harish; Wiley, H. S.

    2010-12-01

    The extracellular signal-regulated kinase (ERK) pathway is a central signaling pathway in development and disease and is regulated by multiple negative and positive feedback loops. Recent studies have shown negative feedback from ERK to upstream regulators can give rise to biochemical oscillations with a periodicity of between 15-30 minutes. Feedback due to the stimulated transcription of negative regulators of the ERK pathway can also give rise to transcriptional oscillations with a periodicity of 1-2h. The biological significance of these oscillations is not clear, but recent evidence suggests that transcriptional oscillations participate in developmental processes, such as somite formation. Biochemical oscillations are more enigmatic, but could provide a mechanism for encoding different types of inputs into a common signaling pathway.

  6. The MORPH Algorithm: Ranking Candidate Genes for Membership in Arabidopsis and Tomato Pathways[C][W

    PubMed Central

    Tzfadia, Oren; Amar, David; Bradbury, Louis M.T.; Wurtzel, Eleanore T.; Shamir, Ron

    2012-01-01

    Closing gaps in our current knowledge about biological pathways is a fundamental challenge. The development of novel computational methods along with high-throughput experimental data carries the promise to help in the challenge. We present an algorithm called MORPH (for module-guided ranking of candidate pathway genes) for revealing unknown genes in biological pathways. The method receives as input a set of known genes from the target pathway, a collection of expression profiles, and interaction and metabolic networks. Using machine learning techniques, MORPH selects the best combination of data and analysis method and outputs a ranking of candidate genes predicted to belong to the target pathway. We tested MORPH on 230 known pathways in Arabidopsis thaliana and 93 known pathways in tomato (Solanum lycopersicum) and obtained high-quality cross-validation results. In the photosynthesis light reactions, homogalacturonan biosynthesis, and chlorophyll biosynthetic pathways of Arabidopsis, genes ranked highly by MORPH were recently verified to be associated with these pathways. MORPH candidates ranked for the carotenoid pathway from Arabidopsis and tomato are derived from pathways that compete for common precursors or from pathways that are coregulated with or regulate the carotenoid biosynthetic pathway. PMID:23204403

  7. Distinct Effects of p19 RNA Silencing Suppressor on Small RNA Mediated Pathways in Plants

    PubMed Central

    Kontra, Levente; Tavazza, Mario; Lucioli, Alessandra; Tavazza, Raffaela; Moxon, Simon; Medzihradszky, Anna; Burgyán, József

    2016-01-01

    RNA silencing is one of the main defense mechanisms employed by plants to fight viruses. In change, viruses have evolved silencing suppressor proteins to neutralize antiviral silencing. Since the endogenous and antiviral functions of RNA silencing pathway rely on common components, it was suggested that viral suppressors interfere with endogenous silencing pathway contributing to viral symptom development. In this work, we aimed to understand the effects of the tombusviral p19 suppressor on endogenous and antiviral silencing during genuine virus infection. We showed that ectopically expressed p19 sequesters endogenous small RNAs (sRNAs) in the absence, but not in the presence of virus infection. Our presented data question the generalized model in which the sequestration of endogenous sRNAs by the viral suppressor contributes to the viral symptom development. We further showed that p19 preferentially binds the perfectly paired ds-viral small interfering RNAs (vsiRNAs) but does not select based on their sequence or the type of the 5’ nucleotide. Finally, co-immunoprecipitation of sRNAs with AGO1 or AGO2 from virus-infected plants revealed that p19 specifically impairs vsiRNA loading into AGO1 but not AGO2. Our findings, coupled with the fact that p19-expressing wild type Cymbidium ringspot virus (CymRSV) overcomes the Nicotiana benthamiana silencing based defense killing the host, suggest that AGO1 is the main effector of antiviral silencing in this host-virus combination. PMID:27711201

  8. DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes.

    PubMed

    Cohen, Isadora S; Bar, Carmit; Paz-Elizur, Tamar; Ainbinder, Elena; Leopold, Karoline; de Wind, Niels; Geacintov, Nicholas; Livneh, Zvi

    2015-02-18

    DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells. PMID:25589543

  9. DNA lesion identity drives choice of damage tolerance pathway in murine cell chromosomes

    PubMed Central

    Cohen, Isadora S.; Bar, Carmit; Paz-Elizur, Tamar; Ainbinder, Elena; Leopold, Karoline; de Wind, Niels; Geacintov, Nicholas; Livneh, Zvi

    2015-01-01

    DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells. PMID:25589543

  10. Transcriptomic Analyses in Zebrafish Cancer Models for Global Gene Expression and Pathway Discovery.

    PubMed

    Huang, Xiaoqian; Agrawal, Ira; Li, Zhen; Zheng, Weiling; Lin, Qingsong; Gong, Zhiyuan

    2016-01-01

    The past decade has witnessed a remarkable advancement of the zebrafish model in cancer research. With the rapid development of genomic tools, it is increasingly feasible to perform genome-wide analyses to identify changes associated with cancer in a wide array of model organisms. These genomic tools, particularly transcriptomic analyses using DNA microarray and RNA sequencing platforms, have now become widely used in zebrafish cancer models to uncover novel biology and common molecular pathways underlying hepatocellular carcinoma, intrahepatic cholangiocarcinoma, melanoma, embryonal rhabdomyosarcoma (ERMS), T cell acute lymphoblastic leukemia (T-ALL), Ewing's sarcoma and glioma. An important finding from these studies is the high similarity and conservation of molecular pathways that underlie cancer in complementary zebrafish models and their human counterparts. Finally, these transcriptomic tools have also proven effective in the development and the validation of specific assays for chemical compound screening. In the future, other genomic tools, such as epigenetic, proteomic and metabolomic tools will likely be incorporated into zebrafish cancer studies, further refining our understanding of cancer. PMID:27165353

  11. Modeling Protein Expression and Protein Signaling Pathways

    PubMed Central

    Telesca, Donatello; Müller, Peter; Kornblau, Steven M.; Suchard, Marc A.; Ji, Yuan

    2015-01-01

    High-throughput functional proteomic technologies provide a way to quantify the expression of proteins of interest. Statistical inference centers on identifying the activation state of proteins and their patterns of molecular interaction formalized as dependence structure. Inference on dependence structure is particularly important when proteins are selected because they are part of a common molecular pathway. In that case, inference on dependence structure reveals properties of the underlying pathway. We propose a probability model that represents molecular interactions at the level of hidden binary latent variables that can be interpreted as indicators for active versus inactive states of the proteins. The proposed approach exploits available expert knowledge about the target pathway to define an informative prior on the hidden conditional dependence structure. An important feature of this prior is that it provides an instrument to explicitly anchor the model space to a set of interactions of interest, favoring a local search approach to model determination. We apply our model to reverse-phase protein array data from a study on acute myeloid leukemia. Our inference identifies relevant subpathways in relation to the unfolding of the biological process under study. PMID:26246646

  12. Pathway and Network Analysis in Proteomics

    PubMed Central

    Wu, Xiaogang; Hasan, Mohammad Al; Chen, Jake Yue

    2014-01-01

    Proteomics is inherently a systems science that studies not only measured protein and their expressions in a cell, but also the interplay of proteins, protein complexes, signaling pathways, and network modules. There is a rapid accumulation of Proteomics data in recent years. However, Proteomics data are highly variable, with results being sensitive to data preparation methods, sample condition, instrument types, and analytical method. To address this challenge in Proteomics data analysis, we review common approaches developed to incorporate biological function and network topological information. We categorize existing tools into four categories: tools with basic functional information and little topological features (e.g., GO category analysis), tools with rich functional information and little topological features (e.g., GSEA), tools with basic functional information and rich topological features (e.g., Cytoscape), and tools with rich functional information and rich topological features (e.g., PathwayExpress). We review the general application potential of these tools to Proteomics. In addition, we also review tools that can achieve automated learning of pathway modules and features, and tools that help perform integrated network visual analytics. PMID:24911777

  13. 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.

  14. Ribosomopathies: how a common root can cause a tree of pathologies.

    PubMed

    Danilova, Nadia; Gazda, Hanna T

    2015-09-01

    Defects in ribosome biogenesis are associated with a group of diseases called the ribosomopathies, of which Diamond-Blackfan anemia (DBA) is the most studied. Ribosomes are composed of ribosomal proteins (RPs) and ribosomal RNA (rRNA). RPs and multiple other factors are necessary for the processing of pre-rRNA, the assembly of ribosomal subunits, their export to the cytoplasm and for the final assembly of subunits into a ribosome. Haploinsufficiency of certain RPs causes DBA, whereas mutations in other factors cause various other ribosomopathies. Despite the general nature of their underlying defects, the clinical manifestations of ribosomopathies differ. In DBA, for example, red blood cell pathology is especially evident. In addition, individuals with DBA often have malformations of limbs, the face and various organs, and also have an increased risk of cancer. Common features shared among human DBA and animal models have emerged, such as small body size, eye defects, duplication or overgrowth of ectoderm-derived structures, and hematopoietic defects. Phenotypes of ribosomopathies are mediated both by p53-dependent and -independent pathways. The current challenge is to identify differences in response to ribosomal stress that lead to specific tissue defects in various ribosomopathies. Here, we review recent findings in this field, with a particular focus on animal models, and discuss how, in some cases, the different phenotypes of ribosomopathies might arise from differences in the spatiotemporal expression of the affected genes. PMID:26398160

  15. Ribosomopathies: how a common root can cause a tree of pathologies

    PubMed Central

    Danilova, Nadia; Gazda, Hanna T.

    2015-01-01

    ABSTRACT Defects in ribosome biogenesis are associated with a group of diseases called the ribosomopathies, of which Diamond-Blackfan anemia (DBA) is the most studied. Ribosomes are composed of ribosomal proteins (RPs) and ribosomal RNA (rRNA). RPs and multiple other factors are necessary for the processing of pre-rRNA, the assembly of ribosomal subunits, their export to the cytoplasm and for the final assembly of subunits into a ribosome. Haploinsufficiency of certain RPs causes DBA, whereas mutations in other factors cause various other ribosomopathies. Despite the general nature of their underlying defects, the clinical manifestations of ribosomopathies differ. In DBA, for example, red blood cell pathology is especially evident. In addition, individuals with DBA often have malformations of limbs, the face and various organs, and also have an increased risk of cancer. Common features shared among human DBA and animal models have emerged, such as small body size, eye defects, duplication or overgrowth of ectoderm-derived structures, and hematopoietic defects. Phenotypes of ribosomopathies are mediated both by p53-dependent and -independent pathways. The current challenge is to identify differences in response to ribosomal stress that lead to specific tissue defects in various ribosomopathies. Here, we review recent findings in this field, with a particular focus on animal models, and discuss how, in some cases, the different phenotypes of ribosomopathies might arise from differences in the spatiotemporal expression of the affected genes. PMID:26398160

  16. Kinetic insulation as an effective mechanism for achieving pathway specificity in intracellular signaling networks

    PubMed Central

    Behar, Marcelo; Dohlman, Henrik G.; Elston, Timothy C.

    2007-01-01

    Intracellular signaling pathways that share common components often elicit distinct physiological responses. In most cases, the biochemical mechanisms responsible for this signal specificity remain poorly understood. Protein scaffolds and cross-inhibition have been proposed as strategies to prevent unwanted cross-talk. Here, we report a mechanism for signal specificity termed “kinetic insulation.” In this approach signals are selectively transmitted through the appropriate pathway based on their temporal profile. In particular, we demonstrate how pathway architectures downstream of a common component can be designed to efficiently separate transient signals from signals that increase slowly over time. Furthermore, we demonstrate that upstream signaling proteins can generate the appropriate input to the common pathway component regardless of the temporal profile of the external stimulus. Our results suggest that multilevel signaling cascades may have evolved to modulate the temporal profile of pathway activity so that stimulus information can be efficiently encoded and transmitted while ensuring signal specificity. PMID:17913886

  17. Modulation of neurotrophic signaling pathways by polyphenols

    PubMed Central

    Moosavi, Fatemeh; Hosseini, Razieh; Saso, Luciano; Firuzi, Omidreza

    2016-01-01

    Polyphenols are an important class of phytochemicals, and several lines of evidence have demonstrated their beneficial effects in the context of a number of pathologies including neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. In this report, we review the studies on the effects of polyphenols on neuronal survival, growth, proliferation and differentiation, and the signaling pathways involved in these neurotrophic actions. Several polyphenols including flavonoids such as baicalein, daidzein, luteolin, and nobiletin as well as nonflavonoid polyphenols such as auraptene, carnosic acid, curcuminoids, and hydroxycinnamic acid derivatives including caffeic acid phentyl ester enhance neuronal survival and promote neurite outgrowth in vitro, a hallmark of neuronal differentiation. Assessment of underlying mechanisms, especially in PC12 neuronal-like cells, reveals that direct agonistic effect on tropomyosin receptor kinase (Trk) receptors, the main receptors of neurotrophic factors including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) explains the action of few polyphenols such as 7,8-dihydroxyflavone. However, several other polyphenolic compounds activate extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt pathways. Increased expression of neurotrophic factors in vitro and in vivo is the mechanism of neurotrophic action of flavonoids such as scutellarin, daidzein, genistein, and fisetin, while compounds like apigenin and ferulic acid increase cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation. Finally, the antioxidant activity of polyphenols reflected in the activation of Nrf2 pathway and the consequent upregulation of detoxification enzymes such as heme oxygenase-1 as well as the contribution of these effects to the neurotrophic activity have also been discussed. In conclusion, a better understanding of the neurotrophic effects of polyphenols and

  18. 'Focus on Marshall' Features Final External Tank Rollout

    NASA Video Gallery

    Gumbo, Mardi Gras parades and external tanks. All three share a common bond - they are all New Orleans staples. But for one, it's the final send-off, highlighted on the August episode of "Focus on ...

  19. Allergic Disease and Autoimmune Effectors Pathways

    PubMed Central

    Rottem, Menachem; Gershwin, M. Eric; Shoenfeld, Yehuda

    2002-01-01

    Allergy and autoimmunity result from dysregulation of the immune system. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest possible common pathogenetic effector pathways. This review illustrates the concomitant presentation of these conditions and the potential relationship or common mechanism in some cases, by looking at the key elements that regulate the immune response in both allergic and autoimmunite conditions: mast cells, antibodies, T cells, cytokines, and genetic determinants. The parallel appearance of allergic and autoimmune conditions in the some patients may reveal that such aberrations of the immune system have a common pathophysiologic mechanism. Mast cells, which play a key role in allergic reactions, and the wealth of inflammatory mediators they express, make it likely that they have profound effects on many autoimmune processes. Activation of protein kinases by inflammatory cytokines and environmental stresses may contribute to both allergic and autoimmune diseases. The presence of autoantibodies in some allergic conditions suggests an autoimmune basis for these conditions. Because of the central role T cells play in immune reactivity, the T-cell receptor (TCR) loci have long been considered important candidates for common disease susceptibility within the immune system such as asthma, atopy, and autoimmunity. Immunomodulation is the key to a successful treatment of allergic and autoimmune conditions. PMID:12885156

  20. Common musculoskeletal problems in the performing artist.

    PubMed

    Hansen, Pamela A; Reed, Kristi

    2006-11-01

    In this chapter we touched on a wide variety of unique musculoskeletal conditions in the musician and dancer. We outlined generalized methods of evaluation that stress the importance of the interdisciplinary approach in this highly specialized patient population and stressed the importance of specific involvement of the music or dance instructor in evaluation and management. We sought to emphasize the need to refer to specialized care early when in doubt of diagnosis or when usual first-line treatments fail. We gave examples of specific injury patterns common in these subgroups and suggestions for early management. Finally, we described some general principals for prevention of musculoskeletal injury in this group. A physician treating the performing artist must always keep in mind that in this unique patient population, their occupation is not only a means of earning a living, it is their passion. Artists make great sacrifice both physically and mentally to bring the world such immeasurable beauty. It is our responsibility to care for them in the most comprehensive and compassionate manner possible while informing them as honestly as possible about their treatment options.