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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. Novel Paradigms for Dialysis Vascular Access: Downstream Vascular Biology–Is There a Final Common Pathway?

    PubMed Central

    2013-01-01

    Summary Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development. PMID:23990166

  5. Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis.

    PubMed

    Vanderhorst, V G; Holstege, G

    1995-08-28

    The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made to localize and quantify the retrogradely labeled neurons in the caudal medullary lateral tegmentum. These injections were combined with spinal hemisections to distinguish between neurons having ipsi-or contralaterally descending axons. The NRA-lumbosacral fibers descend almost exclusively contralaterally, but neurons in areas surrounding the NRA project mainly ipsilaterally. In an anterograde tracing study, injections of WGA-HRP or tritiated leucine were made in the region of the NRA to determine the NRA targets in the lumbosarcral cord. Hemisections in C2 made it possible to distinguish between NRA projections and projections from neurons in the adjoining lateral tegmentum. The results show delicate NRA projections to distinct lumbosacral motoneuronal cell groups innervating specific hindlimb muscles (iliopsoas, adductors, and hamstrings) as well as axial muscles (medial longissimus and proximal tail muscles). The projection is bilateral, with a contralateral predominance. Ipsilaterally terminating fibers are derived from NRA neurons whose axons cross the midline at the level of the obex, descend through the contralateral spinal white matter, and recross at the level of termination. A conceptual description is presented in which the periaqueductal gray-NRA-lumbosacral projections form the final common pathway for lordosis in the cat. PMID:7499541

  6. The behavioural final common path.

    PubMed

    McFarland, D J; Sibly, R M

    1975-05-15

    In this paper it is argued that any model of the motivational (i.e. reversible) processes governing the behaviour of an animal can be represented by means of isoclines in a multidimensional 'causal-factor space'. The argument is axiomatic, based upon the two prime assumptions: that (1) it is always possible to classify the behavioural repertoire of a species in such a way that the classes are mutually exclusive in the sense that the members of different classes cannot occur simultaneously, and (2) these incompatible actions are uniquely determined by a particular set of causal factors. The isoclines join all points in the space which present a given 'degree of competitiveness' of a particular 'candidate' for overt behavioural expression. The competition between candidates is an inevitable consequence of the fact that animals cannot 'do more than one thing at a time', and is envisaged as taking place in the behavioural final common path. An empirical method of determining the motivational state (i.e. point in causal-factor space) is outlined. This is a 'relative' method, independent of the arbitrary calibration of the axes of the causal-factor space. It is shown that an arbitrary scale of measurement along any two axes of the causal-factor space is all that is necessary for empirical determination of the shape of a motivational isocline. Experiments in which this method has been applied to the measurement of hunger and thirst in doves are outlined, and the results are discussed in terms of their implications for motivation theory in general. PMID:239416

  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. No oculomotor plant, no final common path.

    PubMed

    Miller, Joel

    2003-12-01

    The assumption that there is an oculomotor plant, a fixed relationship between motoneuron firing rate and eye position, is disproved by brainstem recording studies showing that this relationship depends on which supernuclear subsystem determines firing rate. But it remains possible that there is a final common path (FCP), a fixed relationship between firing rate and muscle force. But then, brainstem recording studies predict that lateral rectus (LR) forces (and probably medial rectus (MR) forces, as well) will be higher in converged than in unconverged gaze for a given eye position. We recently measured these forces and found that they are slightly lower in convergence, disproving the FCP hypothesis. Thus, even the relationship between motoneuron firing rate and muscle force is under supernuclear control. What peripheral oculomotor articulations could vary the relationship of firing rate to muscle force?: (1) Actively movable EOM pulleys could alter oculorotary muscle force for a given oculorotory innervation by altering muscle lengths. (2) 'Outer' motoneurons may function as gamma efferents in conjunction with palisade endings and non-twitch global EOM fibers. (3) Complex nonlinear interactions likely arise among both parallel and serially connected muscle fibers. PMID:14730457

  10. 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…

  11. A systems biology approach reveals common metastatic pathways in osteosarcoma

    PubMed Central

    2012-01-01

    Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest-path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models

  12. 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

  13. 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. PMID:26238301

  14. 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

  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. 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

  17. 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

  18. 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

  19. 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…

  20. Diversity in Pathways to Common Childhood Disruptive Behavior Disorders

    PubMed Central

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

    2014-01-01

    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 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 120bp 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. PMID:22584505

  1. An Effective Method to Identify Shared Pathways and Common Factors among Neurodegenerative Diseases

    PubMed Central

    Li, Ping; Nie, Yaling; Yu, Jingkai

    2015-01-01

    Groups of distinct but related diseases often share common symptoms, which suggest likely overlaps in underlying pathogenic mechanisms. Identifying the shared pathways and common factors among those disorders can be expected to deepen our understanding for them and help designing new treatment strategies effected on those diseases. Neurodegeneration diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), were taken as a case study in this research. Reported susceptibility genes for AD, PD and HD were collected and human protein-protein interaction network (hPPIN) was used to identify biological pathways related to neurodegeneration. 81 KEGG pathways were found to be correlated with neurodegenerative disorders. 36 out of the 81 are human disease pathways, and the remaining ones are involved in miscellaneous human functional pathways. Cancers and infectious diseases are two major subclasses within the disease group. Apoptosis is one of the most significant functional pathways. Most of those pathways found here are actually consistent with prior knowledge of neurodegenerative diseases except two cell communication pathways: adherens and tight junctions. Gene expression analysis showed a high probability that the two pathways were related to neurodegenerative diseases. A combination of common susceptibility genes and hPPIN is an effective method to study shared pathways involved in a group of closely related disorders. Common modules, which might play a bridging role in linking neurodegenerative disorders and the enriched pathways, were identified by clustering analysis. The identified shared pathways and common modules can be expected to yield clues for effective target discovery efforts on neurodegeneration. PMID:26575483

  2. UVA1 radiation triggers two different final apoptotic pathways.

    PubMed

    Godar, D E

    1999-01-01

    Because ultraviolet-A1 (UVA1; 340-400 nm) radiation is used therapeutically, this in vitro study addressed the question "how does it work?" To begin addressing this question, UVA1 radiation was first established to reduce the survival of transformed T and B lymphocytes in a linear dose-dependent manner using clonogenic reproductive assays, and that cell death occurs by apoptosis using transmission electron microscopy, Annexin V, and flow cytometry. The primary mechanism was determined to be immediate pre-programmed cell death, an apoptotic mechanism that does not require protein synthesis post-insult, by quantifying the apoptotic cells over time in the absence or presence of a translation inhibitor. To explore how UVA1 radiation induces immediate pre-programmed cell death apoptosis, reactive oxygen species and mitochondrial activity were altered during exposure using a variety of agents, while a specific fluorescent probe, 5,5',6,6'tetrachloro- 1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide, was used to examine mitochondrial transmembrane depolarization. To show that UVA1 mediates singlet-oxygen damage to the mitochondrial membranes, X-rays, UVB (290-320 nm), 8-methoxypsoralen and UVA, vitamin K3, anti-Fas antibody, and blocking antibody were the negative controls, while rose bengal or protoporphyrin IX with visible light were the positive controls. Cyclosporine A, which inhibits the mitochondrial megapore from opening, was used with singlet-oxygen and superoxide-anion generators to distinguish between the two final apoptotic pathways. The collective results show that UVA1 radiation primarily mediates singlet-oxygen damage triggering immediate pre-programmed cell death apoptosis (T < 20 min) by immediately opening the cyclosporine A-sensitive ("S" site) mitochondrial megapore, while superoxide anions initiate another cyclosporine A-insensitive ("P" site) final apoptotic pathway. PMID:9886256

  3. 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.

  4. 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.

  5. The biological pathway and effect of PCBs on common terns in Lake Michigan.

    PubMed

    Ward, Michael P; Jablonski, Cindi; Semel, Brad; Soucek, David

    2010-11-01

    Poly-chlorinated biphenyls (PCBs) have been recognized as a significant contaminant in the Great Lakes ecosystem. Although PCBs are implicated in the reduced survival and reproductive success of several piscivorous bird species, the biological pathway in which PCBs bioaccumulate remains largely unknown. This study investigates the two most likely biological pathways, suggested via research on Great Lakes sport fish, by which PCBs would be acquired by common terns (Sterna hirundo), a piscivorous species of conservation concern. The first proposed pathway is through atmospheric deposition of PCBs which are subsequently acquired by filter-feeding fish (e.g., alewives, Alosa pseudoharengus). An alternative pathway is via the biodeposits of zebra mussels which are consumed by shallow water fish (e.g., round gobies, Neogobius melanostromus). Because common terns breed in near-shore sites where concentrations of zebra mussels are found, as well as forage in more pelagic environments it is possible that either or both pathways may be contributing to their PCB exposure. Field experiments and stable isotope analyses suggest the most likely pathway by which terns are exposed to PCBs is via alewives, similar to how apex predators such as lake trout acquire PCBs. Biodeposits from zebra mussels do not appear to be a significant factor in PCB accumulation in terns. We quantified extremely poor parental attentiveness during incubation. Although we cannot determine whether poor parental attentiveness alone or in combination with PCB contamination led to low hatching success, accumulation of PCBs appears to have significant impacts on the overall reproductive success of common terns. PMID:20725777

  6. 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

  7. Common and overlapping oncogenic pathways contribute to the evolution of acute myeloid leukemias

    PubMed Central

    Kvinlaug, Brynn T; Chan, Wai-In; Bullinger, Lars; Ramaswami, Mukundhan; Sears, Christopher; Foster, Donna; Lazic, Stanley E; Okabe, Rachel; Benner, Axel; Lee, Benjamin H; De Silva, Inusha; Valk, Peter JM; Delwel, Ruud; Armstrong, Scott A; Döhner, Hartmut; Gilliland, D Gary; Huntly, Brian JP

    2011-01-01

    Fusion oncogenes in acute myeloid leukemia (AML) promote self-renewal from committed progenitors, thereby linking transformation and self-renewal pathways. Like most cancers, AML is a genetically and biologically heterogeneous disease, but it is unclear whether transformation results from common or overlapping genetic programs acting downstream of multiple mutations, or by the engagement of unique genetic programs acting cooperatively downstream of individual mutations. This distinction is important, because the involvement of common programs would imply the existence of common molecular targets to treat AML, no matter which fusion oncogenes are involved. Here we demonstrate that the ability to promote self-renewal is a generalized property of leukemia-associated oncogenes. Disparate oncogenes initiated overlapping transformation and self-renewal gene expression programs, the common elements of which were defined in established leukemia stem cells from an animal model as well as from a large cohort of patients with differing AML subtypes, where they strongly predicted pathobiological character. Notably, individual genes commonly activated in these programs could partially phenocopy the self-renewal function of leukemia-associated oncogenes in committed murine progenitors. Further, they could generate AML following expression in murine bone marrow. In summary, our findings reveal the operation of common programs of self-renewal and transformation downstream of leukemia-associated oncogenes, suggesting mechanistically common therapeutic approaches to AML are likely to be possible, regardless of the identity of the driver oncogene involved. PMID:21505102

  8. 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

  9. Kidney and eye diseases: common risk factors, etiological mechanisms, and pathways.

    PubMed

    Wong, Chee Wai; Wong, Tien Yin; Cheng, Ching-Yu; Sabanayagam, Charumathi

    2014-06-01

    Chronic kidney disease is an emerging health problem worldwide. The eye shares striking structural, developmental, and genetic pathways with the kidney, suggesting that kidney disease and ocular disease may be closely linked. A growing number of studies have found associations of chronic kidney disease with age-related macular degeneration, diabetic retinopathy, glaucoma, and cataract. In addition, retinal microvascular parameters have been shown to be predictive of chronic kidney disease. Chronic kidney disease shares common vascular risk factors including diabetes, hypertension, smoking, and obesity, and pathogenetic mechanisms including inflammation, oxidative stress, endothelial dysfunction, and microvascular dysfunction, with ocular diseases supporting the 'Common Soil Hypothesis.' In this review, we present major epidemiological evidence for these associations and explore underlying pathogenic mechanisms and common risk factors for kidney and ocular disease. Understanding the link between kidney and ocular disease can lead to the development of new treatment and screening strategies for both diseases. PMID:24336029

  10. 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. PMID:26909085

  11. 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

  12. 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

  13. 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.

  14. Common-Lymphoid-Progenitor-Independent Pathways of Innate and T Lymphocyte Development.

    PubMed

    Ghaedi, Maryam; Steer, Catherine A; Martinez-Gonzalez, Itziar; Halim, Timotheus Y F; Abraham, Ninan; Takei, Fumio

    2016-04-19

    All lymphocytes are thought to develop from common lymphoid progenitors (CLPs). However, lymphoid-primed multipotent progenitors (LMPPs) are more efficient than CLPs in differentiating into T cells and group 2 innate lymphoid cells (ILC2s). Here, we have divided LMPPs into CD127(-) (LMPP-s) and CD127(+) (LMPP+s) subsets and compared them with Ly6D(-) and Ly6D(+) CLPs. Adult LMPP+s differentiated into T cells and ILCs more rapidly and efficiently than other progenitors in transplantation assays. The development of T cells and ILC2s is highly active in the neonatal period. Neonatal CLPs are rare and, unlike prominent neonatal LMPP+s, do not efficiently differentiate into T cells and ILC2s. ILC2s generated in the neonatal period are long lived and persist in adult tissues. These results suggest that some ILCs and T cells may develop from LMPP+s via CLP-independent pathways. PMID:27068476

  15. BRCA1 and BRCA2: different roles in a common pathway of genome protection

    PubMed Central

    Roy, Rohini; Chun, Jarin; Powell, Simon N.

    2016-01-01

    The proteins encoded by the two major breast cancer susceptibility genes, BRCA1 and BRCA2, work in a common pathway of genome protection. However, the two proteins work at different stages in the DNA damage response (DDR) and in DNA repair. BRCA1 is a pleiotropic DDR protein that functions in both checkpoint activation and DNA repair, whereas BRCA2 is a mediator of the core mechanism of homologous recombination. The links between the two proteins are not well understood, but they must exist to explain the marked similarity of human cancer susceptibility that arises with germline mutations in these genes. As discussed here, the proteins work in concert to protect the genome from double-strand DNA damage during DNA replication. PMID:22193408

  16. 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

  17. 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

  18. Insulin and phorbol ester stimulate conductive Na+ transport through a common pathway.

    PubMed Central

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

    1988-01-01

    Insulin stimulates Na+ transport across frog skin, toad urinary bladder, and the distal renal nephron. This stimulation reflects an increase in apical membrane Na+ 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+ transport across frog skin. In the present work, we 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+ 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. Preincubation with D-sphingosine, an inhibitor of protein kinase C, also reduces the natriferic action of insulin. The current results provide documentation that insulin and protein kinase C share a common pathway in stimulating Na+ 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. Images PMID:3277184

  19. Advanced glycation end-products: a common pathway in diabetes and age-related erectile dysfunction.

    PubMed

    Neves, D

    2013-08-01

    Reactive derivatives of non-enzymatic glucose-protein condensation reactions integrate a heterogeneous group of irreversible adducts called advanced glycation end-products (AGEs). Numerous studies have investigated the role of the AGEs in cardiovascular system; however, its contribution to erectile dysfunction (ED) that is an early manifestation of cardiovascular disease has been less intensively investigated. This review summarizes the most recent advances concerning AGEs effects in the cavernous tissue of the penis and in ED onset, particularly on diabetes and aging, conditions that not only favor AGEs formation, but also increase risk of developing ED. The specific contribution of AGE on intra- and extracellular deposition of insoluble complexes, interference in activity of endothelial nitric oxide (NO) synthase, NO bioavailability, endothelial-dependent vasodilatation, as well as molecular pathways activated by receptor of AGEs are presented. Finally, the interventional actions that prevent AGEs formation, accumulation or activity in the cavernous tissue and that include nutritional pattern modulation, nutraceuticals, exercise, therapeutic strategies (statins, anti-diabetics, inhibitors of phosphodiesterase-5, anti-hypertensive drugs) and inhibitors of AGEs formation and crosslink breakers, are discussed. From this review, we conclude that despite the experiments conducted in animal models pointing to the AGE/RAGE axis as a potential interventional target with respect to ED associated with diabetes and aging, the clinical data have been very disappointing and, until now, did not provide evidence of benefits of treatments directed to AGE inactivation. PMID:23822116

  20. Pandora, a PAthway and Network DiscOveRy Approach based on common biological evidence

    PubMed Central

    Zhang, Kelvin Xi; Ouellette, B. F. Francis

    2010-01-01

    Motivation: Many biological phenomena involve extensive interactions between many of the biological pathways present in cells. However, extraction of all the inherent biological pathways remains a major challenge in systems biology. With the advent of high-throughput functional genomic techniques, it is now possible to infer biological pathways and pathway organization in a systematic way by integrating disparate biological information. Results: Here, we propose a novel integrated approach that uses network topology to predict biological pathways. We integrated four types of biological evidence (protein–protein interaction, genetic interaction, domain–domain interaction and semantic similarity of Gene Ontology terms) to generate a functionally associated network. This network was then used to develop a new pathway finding algorithm to predict biological pathways in yeast. Our approach discovered 195 biological pathways and 31 functionally redundant pathway pairs in yeast. By comparing our identified pathways to three public pathway databases (KEGG, BioCyc and Reactome), we observed that our approach achieves a maximum positive predictive value of 12.8% and improves on other predictive approaches. This study allows us to reconstruct biological pathways and delineates cellular machinery in a systematic view. Availability: The method has been implemented in Perl and is available for downloading from http://www.oicr.on.ca/research/ouellette/pandora. It is distributed under the terms of GPL (http://opensource.org/licenses/gpl-2.0.php) Contact: francis@oicr.on.ca Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20031970

  1. 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

  2. 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

  3. 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

  4. Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis

    PubMed Central

    Smith, Steven B.; Dampier, William; Tozeren, Aydin; Brown, James R.; Magid-Slav, Michal

    2012-01-01

    Background Pandemic and seasonal respiratory viruses are a major global health concern. Given the genetic diversity of respiratory viruses and the emergence of drug resistant strains, the targeted disruption of human host-virus interactions is a potential therapeutic strategy for treating multi-viral infections. The availability of large-scale genomic datasets focused on host-pathogen interactions can be used to discover novel drug targets as well as potential opportunities for drug repositioning. Methods/Results In this study, we performed a large-scale analysis of microarray datasets involving host response to infections by influenza A virus, respiratory syncytial virus, rhinovirus, SARS-coronavirus, metapneumonia virus, coxsackievirus and cytomegalovirus. Common genes and pathways were found through a rigorous, iterative analysis pipeline where relevant host mRNA expression datasets were identified, analyzed for quality and gene differential expression, then mapped to pathways for enrichment analysis. Possible repurposed drugs targets were found through database and literature searches. A total of 67 common biological pathways were identified among the seven different respiratory viruses analyzed, representing fifteen laboratories, nine different cell types, and seven different array platforms. A large overlap in the general immune response was observed among the top twenty of these 67 pathways, adding validation to our analysis strategy. Of the top five pathways, we found 53 differentially expressed genes affected by at least five of the seven viruses. We suggest five new therapeutic indications for existing small molecules or biological agents targeting proteins encoded by the genes F3, IL1B, TNF, CASP1 and MMP9. Pathway enrichment analysis also identified a potential novel host response, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway, which is known to be involved in the progression of neurodegenerative Parkinson's disease. Conclusions Our study

  5. 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

  6. 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

  7. 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...

  8. TGF-β stimulation in human and murine cells reveals commonly affected biological processes and pathways at transcription level

    PubMed Central

    2014-01-01

    Background The TGF-β signaling pathway is a fundamental pathway in the living cell, which plays a key role in many central cellular processes. The complex and sometimes contradicting mechanisms by which TGF-β yields phenotypic effects are not yet completely understood. In this study we investigated and compared the transcriptional response profile of TGF-β1 stimulation in different cell types. For this purpose, extensive experiments are performed and time-course microarray data are generated in human and mouse parenchymal liver cells, human mesenchymal stromal cells and mouse hematopoietic progenitor cells at different time points. We applied a panel of bioinformatics methods on our data to uncover common patterns in the dynamic gene expression response in respective cells. Results Our analysis revealed a quite variable and multifaceted transcriptional response profile of TGF-β1 stimulation, which goes far beyond the well-characterized classical TGF-β1 signaling pathway. Nonetheless, we could identify several commonly affected processes and signaling pathways across cell types and species. In addition our analysis suggested an important role of the transcription factor EGR1, which appeared to have a conserved influence across cell-types and species. Validation via an independent dataset on A549 lung adenocarcinoma cells largely confirmed our findings. Network analysis suggested explanations, how TGF-β1 stimulation could lead to the observed effects. Conclusions The analysis of dynamical transcriptional response to TGF-β treatment experiments in different human and murine cell systems revealed commonly affected biological processes and pathways, which could be linked to TGF-β1 via network analysis. This helps to gain insights about TGF-β pathway activities in these cell systems and its conserved interactions between the species and tissue types. PMID:24886091

  9. Wingless and its signalling pathway have common and separable functions during tracheal development.

    PubMed

    Llimargas, M

    2000-10-01

    The Drosophila tracheal tree consists of a tubular network of epithelial branches that constitutes the respiratory system. Groups of tracheal cells migrate towards stereotyped directions while they acquire specific tracheal fates. This work shows that the wingless/WNT signalling pathway is needed within the tracheal cells for the formation of the dorsal trunk and for fusion of the branches. These functions are achieved through the regulation of target genes, such as spalt in the dorsal trunk and escargot in the fusion cells. The pathway also aids tracheal invagination and helps guide the ganglionic branch. Moreover the wingless/WNT pathway displays antagonistic interactions with the DPP (decapentaplegic) pathway, which regulates branching along the dorsoventral axis. Remarkably, the wingless gene itself, acting through its canonical pathway, seems not to be absolutely required for all these tracheal functions. However, the artificial overexpression of wingless in tracheal cells mimics the overexpression of a constitutively activated armadillo protein. The results suggest that another gene product, possibly a WNT, could help to trigger the wingless cascade in the developing tracheae. PMID:11003840

  10. Tom20 and Tom22 share the common signal recognition pathway in mitochondrial protein import.

    PubMed

    Yamano, Koji; Yatsukawa, Yoh-Ichi; Esaki, Masatoshi; Hobbs, Alyson E Aiken; Jensen, Robert E; Endo, Toshiya

    2008-02-15

    Precise targeting of mitochondrial precursor proteins to mitochondria requires receptor functions of Tom20, Tom22, and Tom70 on the mitochondrial surface. Tom20 is a major import receptor that recognizes preferentially mitochondrial presequences, and Tom70 is a specialized receptor that recognizes presequence-less inner membrane proteins. The cytosolic domain of Tom22 appears to function as a receptor in cooperation with Tom20, but how its substrate specificity differs from that of Tom20 remains unclear. To reveal possible differences in substrate specificities between Tom20 and Tom22, if any, we deleted the receptor domain of Tom20 or Tom22 in mitochondria in vitro by introducing cleavage sites for a tobacco etch virus protease between the receptor domains and transmembrane segments of Tom20 and Tom22. Then mitochondria without the receptor domain of Tom20 or Tom22 were analyzed for their abilities to import various mitochondrial precursor proteins targeted to different mitochondrial subcompartments in vitro. The effects of deletion of the receptor domains on the import of different mitochondrial proteins for different import pathways were quite similar between Tom20 and Tom22. Therefore Tom20 and Tom22 are apparently involved in the same step or sequential steps along the same pathway of targeting signal recognition in import. PMID:18063580

  11. 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…

  12. 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

  13. Common pathological processes and transcriptional pathways in Alzheimer's disease and type 2 diabetes.

    PubMed

    Jones, Allan; Kulozik, Philipp; Ostertag, Anke; Herzig, Stephan

    2009-01-01

    Numerous epidemiological and experimental studies have established a strong connection between type 2 diabetes and the risk of the development of Alzheimer's disease. Indeed, several pathological features have been identified as common denominators of diabetic and Alzheimer's patients, including insulin resistance, dyslipidemia and inflammation, suggesting a close connection between the two disorders. Here we review common metabolic and inflammatory processes implicated in the pathogenesis of both disorders. In particular, the role of critical transcriptional checkpoints in the control of cellular metabolism, insulin sensitivity, and inflammation will be emphasized in this context. These transcriptional regulators hold great promise as new therapeutic targets in the potentially combined treatment of type 2 diabetes and Alzheimer's disease in the future. PMID:19387113

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

    PubMed Central

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

    2014-01-01

    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. PMID:24927540

  15. Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand Skill

    PubMed Central

    Brandler, William M.; Morris, Andrew P.; Evans, David M.; Scerri, Thomas S.; Kemp, John P.; Timpson, Nicholas J.; St Pourcain, Beate; Smith, George Davey; Ring, Susan M.; Stein, John; Monaco, Anthony P.; Talcott, Joel B.; Fisher, Simon E.; Webber, Caleb; Paracchini, Silvia

    2013-01-01

    Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10−9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development. PMID:24068947

  16. A common pathway of nitric oxide release from AZD3582 and glyceryl trinitrate.

    PubMed

    Berndt, Georg; Grosser, Nina; Hoogstraate, Janet; Schröder, Henning

    2004-02-01

    4-(Nitrooxy)-butyl-(S)-2-(6-methoxy-2-naphthyl)-propanoate (AZD3582) is a cyclooxygenase (COX)-inhibiting nitric oxide donator (CINOD). It donates nitric oxide (NO) in biological systems through as yet unidentified mechanisms. cGMP, a marker of intracellularly generated NO, was increased up to 27-fold over basal levels by AZD3582 (1-30microM) in LLC-PK1 kidney epithelial cells. A 5h pretreatment with glyceryl tinitrate (GTN, 0.1-1microM) attenuated the cGMP response to a subsequent challenge with AZD3582 or GTN. Similarly, AZD3582 (10-30microM) pretreatment reduced the increase in cGMP on subsequent incubation with AZD3582 or GTN. In contrast, cGMP stimulation by SIN-1, which releases NO independently of enzymatic catalysis, remained unimpaired in cells pretreated with GTN or AZD3582. Our results demonstrate that AZD3582 decreases the sensitivity of the guanylyl cyclase/cGMP system to GTN and vice versa. This suggests that bioactivation pathways for organic nitrates, which involve enzymatic catalysis, may be responsible for NO donation from AZD3582. PMID:14757506

  17. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma

    PubMed Central

    Perry, Jennifer A.; Kiezun, Adam; Tonzi, Peter; Van Allen, Eliezer M.; Carter, Scott L.; Baca, Sylvan C.; Cowley, Glenn S.; Bhatt, Ami S.; Rheinbay, Esther; Pedamallu, Chandra Sekhar; Helman, Elena; Taylor-Weiner, Amaro; McKenna, Aaron; DeLuca, David S.; Lawrence, Michael S.; Ambrogio, Lauren; Sougnez, Carrie; Sivachenko, Andrey; Walensky, Loren D.; Wagle, Nikhil; Mora, Jaume; de Torres, Carmen; Lavarino, Cinzia; Dos Santos Aguiar, Simone; Yunes, Jose Andres; Brandalise, Silvia Regina; Mercado-Celis, Gabriela Elisa; Melendez-Zajgla, Jorge; Cárdenas-Cardós, Rocío; Velasco-Hidalgo, Liliana; Roberts, Charles W. M.; Garraway, Levi A.; Rodriguez-Galindo, Carlos; Gabriel, Stacey B.; Lander, Eric S.; Golub, Todd R.; Orkin, Stuart H.; Getz, Gad; Janeway, Katherine A.

    2014-01-01

    Osteosarcoma is the most common primary bone tumor, yet there have been no substantial advances in treatment or survival in three decades. We examined 59 tumor/normal pairs by whole-exome, whole-genome, and RNA-sequencing. Only the TP53 gene was mutated at significant frequency across all samples. The mean nonsilent somatic mutation rate was 1.2 mutations per megabase, and there was a median of 230 somatic rearrangements per tumor. Complex chains of rearrangements and localized hypermutation were detected in almost all cases. Given the intertumor heterogeneity, the extent of genomic instability, and the difficulty in acquiring a large sample size in a rare tumor, we used several methods to identify genomic events contributing to osteosarcoma survival. Pathway analysis, a heuristic analytic algorithm, a comparative oncology approach, and an shRNA screen converged on the phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway as a central vulnerability for therapeutic exploitation in osteosarcoma. Osteosarcoma cell lines are responsive to pharmacologic and genetic inhibition of the PI3K/mTOR pathway both in vitro and in vivo. PMID:25512523

  18. Comprehensive analysis of migration pathways (CAMP): Contaminant migration pathways at confined dredged material-disposal facilities. Final report

    SciTech Connect

    Brannon, J.M.; Pennington, J.C.; Gunnison, D.; Myers, T.E.

    1990-09-01

    A confined disposal facility (CDF) is a diked enclosure having either permeable or low-permeable walls that are used to retain dredged material solids. There are two types of CDFs are located within the influence of normal tidal or other water fluctuations. This report identifies and documents key contaminant mobility processes and pathways operative in CDFs under varying operational and environmental conditions. It also summarizes what is known about contaminant migration, cycling, and mobilization pathways, provides information on models and assessment techniques, and identifies areas for which insufficient information is available. The present information does not permit evaluations of the relative significance of contaminant migration pathways from a CDF. Pathways involving movement of large masses of water, such as CDF effluent, leaching through permeable dikes, or leaching through the dredged material, have the greatest potential for moving significant quantities of contaminants out of the CDF. Pathways such as volatilization may also result in movement of substantial amounts of volatile organic contaminants from CDFs. The relative importance of contaminant cycling and mobilization pathways to net mass balance has not been determined, but available information on each of the contaminant migration, cycling, and mobilization pathways is summarized in the report. Where possible, methods have been provided for making rough estimates of contaminant mass movement via pathways.

  19. 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

  20. 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

  1. Coping with perceived peer stress: gender-specific and common pathways to symptoms of psychopathology.

    PubMed

    Sontag, Lisa M; Graber, Julia A

    2010-11-01

    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(age) = 12.39 years, SD = 0.99) completed self-report surveys on stress, coping, and behavioral problems. Involuntary responses to stress (e.g., physiological arousal, intrusive thoughts, impulsive action) mediated the association between perceived stress and anxiety/depression and aggression for girls and for boys. Disengagement coping (e.g., denial, avoidance) partially mediated the association between peer stress and anxiety/depression for boys and for girls. In contrast, disengagement coping mediated the association between peer stress and overt aggression for boys only. Finally, engagement coping (e.g., problem solving, emotion regulation, cognitive restructuring) buffered the indirect effect of peer stress on symptoms of psychopathology for girls only. Implications for prevention and intervention efforts are discussed. PMID:20718534

  2. Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC-1α-dependent pathway

    PubMed Central

    Lin, Kuan-Ting; Hsu, Shih-Lan; Wang, Feng-Sheng; Chou, Chen-Kung; Lee, Kuen-Haur; Tsou, Ann-Ping; Lai, Jin-Mei; Yeh, Sheau-Farn; Huang, Chi-Ying F.

    2015-01-01

    PGC-1α, a major metabolic regulator of gluconeogenesis and lipogenesis, is strongly induced to coactivate Hepatitis B virus (HBV) gene expression in the liver of fasting mice. We found that 8-Br-cAMP and glucocorticoids synergistically induce PGC-1α and its downstream targets, including PEPCK and G6Pase. Also, HBV core promoter activity was synergistically enhanced by 8-Br-cAMP and glucocorticoids. Graptopetalum paraguayense (GP), a herbal medicine, is commonly used in Taiwan to treat liver disorders. Partially purified fraction of GP (named HH-F3) suppressed 8-Br-cAMP/glucocorticoid-induced G6Pase, PEPCK and PGC-1α expression and suppressed HBV core promoter activity. HH-F3 blocked HBV core promoter activity via inhibition of PGC-1α expression. Ectopically expressed PGC-1α rescued HH-F3-inhibited HBV surface antigen expression, HBV mRNA production, core protein levels, and HBV replication. HH-F3 also inhibited fatty acid synthase (FASN) expression and decreased lipid accumulation by down-regulating PGC-1α. Thus, HH-F3 can inhibit HBV replication, gluconeogenesis and lipogenesis by down-regulating PGC-1α. Our study indicates that targeting PGC-1α may be a therapeutic strategy for treatment of HBV infections. HH-F3 may have potential use for the treatment of chronic hepatitis B patients with associated metabolic syndrome. PMID:25762623

  3. 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

  4. Common pathways regulate Type III TGFβ receptor-dependent cell invasion in epicardial and endocardial cells.

    PubMed

    Clark, Cynthia R; Robinson, Jamille Y; Sanchez, Nora S; Townsend, Todd A; Arrieta, Julian A; Merryman, W David; Trykall, David Z; Olivey, Harold E; Hong, Charles C; Barnett, Joey V

    2016-06-01

    Epithelial-Mesenchymal Transformation (EMT) and the subsequent invasion of epicardial and endocardial cells during cardiac development is critical to the development of the coronary vessels and heart valves. The transformed cells give rise to cardiac fibroblasts and vascular smooth muscle cells or valvular interstitial cells, respectively. The Type III Transforming Growth Factor β (TGFβR3) receptor regulates EMT and cell invasion in both cell types, but the signaling mechanisms downstream of TGFβR3 are not well understood. Here we use epicardial and endocardial cells in in vitro cell invasion assays to identify common mechanisms downstream of TGFβR3 that regulate cell invasion. Inhibition of NF-κB activity blocked cell invasion in epicardial and endocardial cells. NF-κB signaling was found to be dysregulated in Tgfbr3(-/-) epicardial cells which also show impaired cell invasion in response to ligand. TGFβR3-dependent cell invasion is also dependent upon Activin Receptor-Like Kinase (ALK) 2, ALK3, and ALK5 activity. A TGFβR3 mutant that contains a threonine to alanine substitution at residue 841 (TGFβR3-T841A) induces ligand-independent cell invasion in both epicardial and endocardial cells in vitro. These findings reveal a role for NF-κB signaling in the regulation of epicardial and endocardial cell invasion and identify a mutation in TGFβR3 which stimulates ligand-independent signaling. PMID:26970186

  5. Insulin sensitizes FGF21 in glucose and lipid metabolisms via activating common AKT pathway.

    PubMed

    Yu, Dan; Ye, Xianlong; Wu, Qiang; Li, Shujie; Yang, Yongbi; He, Jinjiao; Liu, Yunye; Zhang, Xiaoyu; Yuan, Qingyan; Liu, Mingyao; Li, Deshan; Ren, Guiping

    2016-06-01

    Previous studies reveal that fibroblast growth factor 21 (FGF21) sensitizes insulin to achieve a synergy in regulating glucose metabolism. Here, we report that insulin sensitizes FGF21 in regulating both glucose and lipid metabolisms. db/db diabetic mice were subcutaneously administrated once a day for 6 weeks. Effective dose of insulin (1 U) could control blood glucose level of the db/db mice for maximum of 2 h, increased the body weight of the db/db mice and did not improve serum lipid parameters. In contrast, effective dose of FGF21 (0.5 mg/kg) could maintain blood glucose of the db/db mice at normal level for at least 24 h, repressed the weight gain of the mice and significantly improved lipid parameters. Ineffective doses of FGF21 (0.125 mg/kg) and insulin had no effect on blood glucose level of the db/db mice after 24 h administration, body weight or lipid parameters. However, combination of the two ineffective doses could maintain blood glucose level of the db/db mice for at least 24 h, suppressed weight gain and significantly improved lipid parameters. These results suggest that insulin sensitizes FGF21 in regulating both glucose and lipid metabolism. The results aimed to study the molecular basis of FGF21 sensitization indicates that combination of the two ineffective doses increased the mRNA expression of glut1, glut4, β-Klotho, sirt1, pgc-1α, ucp-1 and AKT phosphorylation, decreased fasn. The results demonstrate that insulin sensitizes FGF21 through elevating the phosphorylation of common gene Akt and amplifying FGF21 downstream signaling, including increasing expression of glut1 sirt1, pgc-1α, ucp-1, and decreasing fasn expression. In summary, we reports herein for the first time that insulin sensitizes FGF21 to achieve a synergy in regulating glucose and lipid metabolism. Along with previous studies, we conclude that the synergistic effect between FGF21 and insulin is realized through mutual sensitization. PMID:26607153

  6. A database of common-cause events for risk and reliability applications. Final report

    SciTech Connect

    Fleming, K.N.; Rao, S.B.

    1992-06-01

    This report documents a common cause event database and updates an earlier version of a database that was published as EPRI report NP-3967 in June 1985. The purposes of this report are to provide more information on the original set of common cause events, to expand on both the number of events and the coverage of different component types, and to provide guidance in how to use the database to support applied risk and reliability evaluations such as the ongoing individual plant examination (IPE). Included in this report are descriptions and analyses of events that were found to be of potential importance in a common cause analysis, statistical information from which to estimate common cause failure probabilities, and examples of how the information can be used to support a plant-specific probabilistic risk assessment (PRA) or reliability evaluation, according to the PRA Procedures for Common Cause Analysis documented in NUREG/CR-4780. That procedures guide, which was developed under joint sponsorship of EPRI and the US Nuclear Regulatory Commission, was supported by EPRI research project RP2169-4.

  7. Less-Commonly Taught Languages in Selected Elementary and Secondary Schools in California. Final Report.

    ERIC Educational Resources Information Center

    Padilla, Amado M.; Sung, Hyekyung

    The report summarizes results of an evaluative study of selected state-funded elementary and secondary school programs for less commonly taught languages (LCTLs) in California. Fourteen projects at 19 school sites received a maximum of 4 years of funding to offer instruction in Japanese, Chinese (Mandarin and Cantonese), Korean, and Russian. The…

  8. 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…

  9. 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…

  10. 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.…

  11. The NKG2008 GPS campaign - final transformation results and a new common Nordic reference frame

    NASA Astrophysics Data System (ADS)

    Häkli, P.; Lidberg, M.; Jivall, L.; Nørbech, T.; Tangen, O.; Weber, M.; Pihlak, P.; Aleksejenko, I.; Paršeliunas, E.

    2016-03-01

    The NKG 2008 GPS campaign was carried out in September 28 - October 4, 2008. The purpose was to establish a common reference frame in the Nordic- Baltic-Arctic region, and to improve and update the transformations from the latest global ITRF reference frame to the national ETRS89 realizations of the Nordic/Baltic countries. Postglacial rebound in the Fennoscandian area causes intraplate deformations up to about 10 mm/yr to the Eurasian tectonic plate which need to be taken into account in order to reach centimetre level accuracies in the transformations. We discuss some possible alternatives and present the most applicable transformation strategy. The selected transformation utilizes the de facto transformation recommended by the EUREF but includes additional intraplate corrections and a new common Nordic-Baltic reference frame to serve the requirements of the Nordic/Baltic countries. To correct for the intraplate deformations in the Nordic-Baltic areawe have used the commonNordic deformation model NKG RF03vel. The new common reference frame, NKG ETRF00, was aligned to ETRF2000 at epoch 2000.0 in order to be close to the national ETRS89 realizations and to coincide with the land uplift epoch of the national height systems. We present here the realization of the NKG ETRF00 and transformation formulae together with the parameters to transform from global ITRF coordinates to Nordic/Baltic realizations of the ETRS89.

  12. 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

  13. Synergy between Common γ Chain Family Cytokines and IL-18 Potentiates Innate and Adaptive Pathways of NK Cell Activation

    PubMed Central

    Nielsen, Carolyn M.; Wolf, Asia-Sophia; Goodier, Martin R.; Riley, Eleanor M.

    2016-01-01

    Studies to develop cell-based therapies for cancer and other diseases have consistently shown that purified human natural killer (NK) cells secrete cytokines and kill target cells after in vitro culture with high concentrations of cytokines. However, these assays poorly reflect the conditions that are likely to prevail in vivo in the early stages of an infection and have been carried out in a wide variety of experimental systems, which has led to contradictions within the literature. We have conducted a detailed kinetic and dose–response analysis of human NK cell responses to low concentrations of IL-12, IL-15, IL-18, IL-21, and IFN-α, alone and in combination, and their potential to synergize with IL-2. We find that very low concentrations of both innate and adaptive common γ chain cytokines synergize with equally low concentrations of IL-18 to drive rapid and potent NK cell CD25 and IFN-γ expression; IL-18 and IL-2 reciprocally sustain CD25 and IL-18Rα expression in a positive feedback loop; and IL-18 synergizes with FcγRIII (CD16) signaling to augment antibody-dependent cellular cytotoxicity. These data indicate that NK cells can be rapidly activated by very low doses of innate cytokines and that the common γ chain cytokines have overlapping but distinct functions in combination with IL-18. Importantly, synergy between multiple signaling pathways leading to rapid NK cell activation at very low cytokine concentrations has been overlooked in prior studies focusing on single cytokines or simple combinations. Moreover, although the precise common γ chain cytokines available during primary and secondary infections may differ, their synergy with both IL-18 and antigen–antibody immune complexes underscores their contribution to NK cell activation during innate and adaptive responses. IL-18 signaling potentiates NK cell effector function during innate and adaptive immune responses by synergy with IL-2, IL-15, and IL-21 and immune complexes. PMID:27047490

  14. Systems analysis of human brain gene expression: mechanisms for HIV-associated neurocognitive impairment and common pathways with Alzheimer’s disease

    PubMed Central

    2013-01-01

    Background Human Immunodeficiency Virus-1 (HIV) infection frequently results in neurocognitive impairment. While the cause remains unclear, recent gene expression studies have identified genes whose transcription is dysregulated in individuals with HIV-association neurocognitive disorder (HAND). However, the methods for interpretation of such data have lagged behind the technical advances allowing the decoding genetic material. Here, we employ systems biology methods novel to the field of NeuroAIDS to further interrogate extant transcriptome data derived from brains of HIV + patients in order to further elucidate the neuropathogenesis of HAND. Additionally, we compare these data to those derived from brains of individuals with Alzheimer’s disease (AD) in order to identify common pathways of neuropathogenesis. Methods In Study 1, using data from three brain regions in 6 HIV-seronegative and 15 HIV + cases, we first employed weighted gene co-expression network analysis (WGCNA) to further explore transcriptome networks specific to HAND with HIV-encephalitis (HIVE) and HAND without HIVE. We then used a symptomatic approach, employing standard expression analysis and WGCNA to identify networks associated with neurocognitive impairment (NCI), regardless of HIVE or HAND diagnosis. Finally, we examined the association between the CNS penetration effectiveness (CPE) of antiretroviral regimens and brain transcriptome. In Study 2, we identified common gene networks associated with NCI in both HIV and AD by correlating gene expression with pre-mortem neurocognitive functioning. Results Study 1: WGCNA largely corroborated findings from standard differential gene expression analyses, but also identified possible meta-networks composed of multiple gene ontology categories and oligodendrocyte dysfunction. Differential expression analysis identified hub genes highly correlated with NCI, including genes implicated in gliosis, inflammation, and dopaminergic tone. Enrichment

  15. 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…

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

    PubMed

    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

  17. 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

  18. In Search for a Common Pathway for Health Issues in Men--the Sign of a Holmesian Deduction.

    PubMed

    Aoun, Fouad; Albisinni, Simone; Chemaly, Anthony Kallas; Zanaty, Marc; Roumeguère, Thierry

    2016-01-01

    The evidence for the existence of a common pathway for health issues in men is presented in this review. Several epidemiological studies have shown that conditions like cardiovascular diseases (CVD), metabolic syndrome, diabetes, lower urinary tract symptom (LUTS), erectile dysfunction (ED), prostate cancer, hypogonadism, depression and suicide can be associated as risk factors for each other. Thus, the risk of CVD is significantly increased in men with metabolic syndrome, ED, hypogonadism, prostate cancer and/or LUTS. In addition, the above mentioned conditions are more prevalent in atherosclerotic patients. In addition, growing evidence indicates that low androgen levels can cause metabolic syndrome. In addition, obesity, dyslipidaemia and diabetes can further reduce androgen levels potentiating their adverse effect. Low testosterone levels are also associated with a higher incidence of aggressive prostate cancer on biopsy and on definitive pathology, and lower probability of abiraterone response in the metastatic setting. Several recent studies point towards diffuse endothelial dysfunction and dysregulated pro-inflammatory state as the biological link between all these disorders. Our current hypothesis is that oxidative stress caused by these dysfunctions explains the pathogenesis of each of these conditions. PMID:26838191

  19. 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.

  20. The Oncolytic Poxvirus JX-594 Selectively Replicates in and Destroys Cancer Cells Driven by Genetic Pathways Commonly Activated in Cancers

    PubMed Central

    Parato, Kelley A; Breitbach, Caroline J; Le Boeuf, Fabrice; Wang, Jiahu; Storbeck, Chris; Ilkow, Carolina; Diallo, Jean-Simon; Falls, Theresa; Burns, Joseph; Garcia, Vanessa; Kanji, Femina; Evgin, Laura; Hu, Kang; Paradis, Francois; Knowles, Shane; Hwang, Tae-Ho; Vanderhyden, Barbara C; Auer, Rebecca; Kirn, David H; Bell, John C

    2012-01-01

    Oncolytic viruses are generally designed to be cancer selective on the basis of a single genetic mutation. JX-594 is a thymidine kinase (TK) gene-inactivated oncolytic vaccinia virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) and lac-Z transgenes that is designed to destroy cancer cells through replication-dependent cell lysis and stimulation of antitumoral immunity. JX-594 has demonstrated a favorable safety profile and reproducible tumor necrosis in a variety of solid cancer types in clinical trials. However, the mechanism(s) responsible for its cancer-selectivity have not yet been well described. We analyzed the replication of JX-594 in three model systems: primary normal and cancer cells, surgical explants, and murine tumor models. JX-594 replication, transgene expression, and cytopathic effects were highly cancer-selective, and broad spectrum activity was demonstrated. JX-594 cancer-selectivity was multi-mechanistic; replication was activated by epidermal growth factor receptor (EGFR)/Ras pathway signaling, cellular TK levels, and cancer cell resistance to type-I interferons (IFNs). These findings confirm a large therapeutic index for JX-594 that is driven by common genetic abnormalities in human solid tumors. This appears to be the first description of multiple selectivity mechanisms, both inherent and engineered, for an oncolytic virus. These findings have implications for oncolytic viruses in general, and suggest that their cancer targeting is a complex and multifactorial process. PMID:22186794

  1. Aggregation-triggering segments of SOD1 fibril formation support a common pathway for familial and sporadic ALS.

    PubMed

    Ivanova, Magdalena I; Sievers, Stuart A; Guenther, Elizabeth L; Johnson, Lisa M; Winkler, Duane D; Galaleldeen, Ahmad; Sawaya, Michael R; Hart, P John; Eisenberg, David S

    2014-01-01

    ALS is a terminal disease of motor neurons that is characterized by accumulation of proteinaceous deposits in affected cells. Pathological deposition of mutated Cu/Zn superoxide dismutase (SOD1) accounts for ∼20% of the familial ALS (fALS) cases. However, understanding the molecular link between mutation and disease has been difficult, given that more than 140 different SOD1 mutants have been observed in fALS patients. In addition, the molecular origin of sporadic ALS (sALS) is unclear. By dissecting the amino acid sequence of SOD1, we identified four short segments with a high propensity for amyloid fibril formation. We find that fALS mutations in these segments do not reduce their propensity to form fibrils. The atomic structures of two fibril-forming segments from the C terminus, (101)DSVISLS(107) and (147)GVIGIAQ(153), reveal tightly packed β-sheets with steric zipper interfaces characteristic of the amyloid state. Based on these structures, we conclude that both C-terminal segments are likely to form aggregates if available for interaction. Proline substitutions in (101)DSVISLS(107) and (147)GVIGIAQ(153) impaired nucleation and fibril growth of full-length protein, confirming that these segments participate in aggregate formation. Our hypothesis is that improper protein maturation and incompletely folded states that render these aggregation-prone segments available for interaction offer a common molecular pathway for sALS and fALS. PMID:24344300

  2. Aggregation-triggering segments of SOD1 fibril formation support a common pathway for familial and sporadic ALS

    PubMed Central

    Ivanova, Magdalena I.; Sievers, Stuart A.; Guenther, Elizabeth L.; Johnson, Lisa M.; Winkler, Duane D.; Galaleldeen, Ahmad; Sawaya, Michael R.; Hart, P. John; Eisenberg, David S.

    2014-01-01

    ALS is a terminal disease of motor neurons that is characterized by accumulation of proteinaceous deposits in affected cells. Pathological deposition of mutated Cu/Zn superoxide dismutase (SOD1) accounts for ∼20% of the familial ALS (fALS) cases. However, understanding the molecular link between mutation and disease has been difficult, given that more than 140 different SOD1 mutants have been observed in fALS patients. In addition, the molecular origin of sporadic ALS (sALS) is unclear. By dissecting the amino acid sequence of SOD1, we identified four short segments with a high propensity for amyloid fibril formation. We find that fALS mutations in these segments do not reduce their propensity to form fibrils. The atomic structures of two fibril-forming segments from the C terminus, 101DSVISLS107 and 147GVIGIAQ153, reveal tightly packed β-sheets with steric zipper interfaces characteristic of the amyloid state. Based on these structures, we conclude that both C-terminal segments are likely to form aggregates if available for interaction. Proline substitutions in 101DSVISLS107 and 147GVIGIAQ153 impaired nucleation and fibril growth of full-length protein, confirming that these segments participate in aggregate formation. Our hypothesis is that improper protein maturation and incompletely folded states that render these aggregation-prone segments available for interaction offer a common molecular pathway for sALS and fALS. PMID:24344300

  3. Maternally Derived Egg Hormones, Antibodies and Antimicrobial Proteins: Common and Different Pathways of Maternal Effects in Japanese Quail

    PubMed Central

    Okuliarova, Monika; Kankova, Zuzana; Bertin, Aline; Leterrier, Christine; Mostl, Erich; Zeman, Michal

    2014-01-01

    Avian eggs contain a variety of maternally-derived substances that can influence the development and performance of offspring. The levels of these egg compounds vary in relation to environmental and genetic factors, but little is known about whether there are correlative links between maternal substances in the egg underlying common and different pathways of maternal effects. In the present study, we investigated genetically determined variability and mutually adjusted deposition of sex hormones (testosterone-T, androstenedione-A4 and progesterone-P4), antibodies (IgY) and antimicrobial proteins (lysozyme) in eggs of Japanese quail (Coturnix japonica). We used different genetic lines that were independently selected for yolk T concentrations, duration of tonic immobility and social reinstatement behaviour, since both selections for behavioural traits (fearfulness and social motivation, respectively) produced considerable correlative responses in yolk androgen levels. A higher selection potential was found for increased rather than decreased yolk T concentrations, suggesting that there is a physiological minimum in egg T levels. Line differences in yolk IgY concentrations were manifested within each selection experiment, but no consistent inter-line pattern between yolk IgY and T was revealed. On the other hand, a consistent inverse inter-line pattern was recorded between yolk IgY and P4 in both selections for behavioural traits. In addition, selections for contrasting fearfulness and social motivation were associated with changes in albumen lysozyme concentrations and an inverse inter-line pattern between the deposition of yolk IgY and albumen lysozyme was found in lines selected for the level of social motivation. Thus, our results demonstrate genetically-driven changes in deposition of yolk T, P4, antibodies and albumen lysozyme in the egg. This genetic variability can partially explain mutually adjusted maternal deposition of sex hormones and immune

  4. Decreasing electron flux through the cytochrome and/or alternative respiratory pathways triggers common and distinct cellular responses dependent on growth conditions.

    PubMed

    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

  5. A common muscarinic pathway for diapause recovery in the distantly related nematode species Caenorhabditis elegans and Ancylostoma caninum

    PubMed Central

    Tissenbaum, Heidi A.; Hawdon, John; Perregaux, Melissa; Hotez, Peter; Guarente, Leonard; Ruvkun, Gary

    2000-01-01

    Converging TGF-β and insulin-like neuroendocrine signaling pathways regulate whether Caenorhabditis elegans develops reproductively or arrests at the dauer larval stage. We examined whether neurotransmitters act in the dauer entry or recovery pathways. Muscarinic agonists promote recovery from dauer arrest induced by pheromone as well as by mutations in the TGF-β pathway. Dauer recovery in these animals is inhibited by the muscarinic antagonist atropine. Muscarinic agonists do not induce dauer recovery of either daf-2 or age-1 mutant animals, which have defects in the insulin-like signaling pathway. These data suggest that a metabotropic acetylcholine signaling pathway activates an insulin-like signal during C. elegans dauer recovery. Analogous and perhaps homologous cholinergic regulation of mammalian insulin release by the autonomic nervous system has been noted. In the parasitic nematode Ancylostoma caninum, the dauer larval stage is the infective stage, and recovery to the reproductive stage normally is induced by host factors. Muscarinic agonists also induce and atropine potently inhibits in vitro recovery of A. caninum dauer arrest. We suggest that host or parasite insulin-like signals may regulate recovery of A. caninum and could be potential targets for antihelminthic drugs. PMID:10618440

  6. 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

  7. 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

  8. 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

  9. 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

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

    PubMed

    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

  11. 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

  12. PATHWAYS: A Human Support System Model for Integrated Handicapped Children and Their Families. Final Report.

    ERIC Educational Resources Information Center

    Carlson, Nancy A., Ed.

    The final report discusses achievements of a 3 year project to demonstrate the feasibility and effectiveness of integrating young handicapped children into existing early childhood programs. The project is conceptualized from a socioecological model, operationalized as a technical assistance support system, and located within an interdisciplinary…

  13. Mitochondria-focused gene expression profile reveals common pathways and CPT1B dysregulation in both rodent stress model and human subjects with PTSD

    PubMed Central

    Zhang, L; Li, H; Hu, X; Benedek, D M; Fullerton, C S; Forsten, R D; Naifeh, J A; Li, X; Wu, H; Benevides, K N; Le, T; Smerin, S; Russell, D W; Ursano, R J

    2015-01-01

    Posttraumatic stress disorder (PTSD), a trauma-related mental disorder, is associated with mitochondrial dysfunction in the brain. However, the biologic approach to identifying the mitochondria-focused genes underlying the pathogenesis of PTSD is still in its infancy. Previous research, using a human mitochondria-focused cDNA microarray (hMitChip3) found dysregulated mitochondria-focused genes present in postmortem brains of PTSD patients, indicating that those genes might be PTSD-related biomarkers. To further test this idea, this research examines profiles of mitochondria-focused gene expression in the stressed-rodent model (inescapable tail shock in rats), which shows characteristics of PTSD-like behaviors and also in the blood of subjects with PTSD. This study found that 34 mitochondria-focused genes being upregulated in stressed-rat amygdala. Ten common pathways, including fatty acid metabolism and peroxisome proliferator-activated receptors (PPAR) pathways were dysregulated in the amygdala of the stressed rats. Carnitine palmitoyltransferase 1B (CPT1B), an enzyme in the fatty acid metabolism and PPAR pathways, was significantly over-expressed in the amygdala (P<0.007) and in the blood (P<0.01) of stressed rats compared with non-stressed controls. In human subjects with (n=28) or without PTSD (n=31), significant over-expression of CPT1B in PTSD was also observed in the two common dysregulated pathways: fatty acid metabolism (P=0.0027, false discovery rate (FDR)=0.043) and PPAR (P=0.006, FDR=0.08). Quantitative real-time polymerase chain reaction validated the microarray findings and the CPT1B result. These findings indicate that blood can be used as a specimen in the search for PTSD biomarkers in fatty acid metabolism and PPAR pathways, and, in addition, that CPT1B may contribute to the pathology of PTSD. PMID:26080315

  14. 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.

  15. Conotruncal Heart Defects and Common Variants in Maternal and Fetal Genes in Folate, Homocysteine and Transsulfuration Pathways

    PubMed Central

    Hobbs, Charlotte A.; Cleves, Mario A.; MacLeod, Stewart L.; Erickson, Stephen W.; Tang, Xinyu; Li, Jingyun; Li, Ming; Nick, Todd; Malik, Sadia

    2014-01-01

    Background We investigated the association between conotruncal heart defects (CTDs) and maternal and fetal single nucleotide polymorphisms (SNPs) in 60 genes in the folate, homocysteine and pathways. We also investigated whether periconceptional maternal folic acid supplementation modified associations between CTDs and SNPs. Methods Participants were enrolled in the National Birth Defects Prevention Study between 1997 and 2007. DNA samples from 616 case-parental triads affected by CTDs and 1,645 control-parental triads were genotyped using an Illumina® Golden Gate custom SNP panel. A hybrid design analysis, optimizing data from case and control trios, was used to identify maternal and fetal SNPs associated with CTDs. Results Among 921 SNPs, 17 maternal and 17 fetal SNPs had a Bayesian false-discovery probability (BFDP) of <0.8. Ten of the 17 maternal SNPs and 2 of the 17 fetal SNPs were found within the glutamate-cysteine ligase, catalytic subunit (GCLC) gene. Fetal SNPs with the lowest BFDP (rs2612101, rs2847607, rs2847326, rs2847324) were found within the thymidylate synthetase (TYMS) gene. Additional analyses indicated that the risk of CTDs associated with candidate SNPs was modified by periconceptional folic acid supplementation. Nineteen maternal and 9 fetal SNPs had BFDP <0.8 for gene-by-environment (GxE) interactions with maternal folic acid supplementation. Conclusions These results support previous studies suggesting that maternal and fetal SNPs within folate, homocysteine and transsulfuration pathways are associated with CTD risk. Maternal use of supplements containing folic acid may modify the impact of SNPs on the developing heart. PMID:24535845

  16. 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.

  17. 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.

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

    PubMed Central

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

    2011-01-01

    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 (Pi: 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.—Martin, A., Liu, S., David, V., Li, H., Karydis, A., Feng, J. Q., Quarles, L. D. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway. PMID:21507898

  19. 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.

  20. 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

  1. A common mechanism involving the TORC1 pathway can lead to amphotericin B-persistence in biofilm and planktonic Saccharomyces cerevisiae populations

    PubMed Central

    Bojsen, Rasmus; Regenberg, Birgitte; Gresham, David; Folkesson, Anders

    2016-01-01

    Fungal infections are an increasing clinical problem. Decreased treatment effectiveness is associated with biofilm formation and drug recalcitrance is thought to be biofilm specific. However, no systematic investigations have tested whether resistance mechanisms are shared between biofilm and planktonic populations. We performed multiplexed barcode sequencing (Bar-seq) screening of a pooled collection of gene-deletion mutants cultivated as biofilm and planktonic cells. Screening for resistance to the ergosterol-targeting fungicide amphotericin B (AmB) revealed that the two growth modes had significant overlap in AmB-persistent mutants. Mutants defective in sterol metabolism, ribosome biosynthesis, and the TORC1 and Ras pathways showed increased persistence when treated with AmB. The ras1, ras2 and tor1 mutants had a high-persister phenotype similar to wild-type biofilm and planktonic cells exposed to the TORC1 pathway inhibitor rapamycin. Inhibition of TORC1 with rapamycin also increased the proportion of persisters in Candida albicans and Candida glabrata. We propose that decreased TORC1-mediated induction of ribosome biosynthesis via Ras can lead to formation of AmB-persister cells regardless of whether the cells are in planktonic or biofilm growth mode. Identification of common pathways leading to growth mode-independent persister formation is important for developing novel strategies for treating fungal infections. PMID:26903175

  2. 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

  3. Common and Divergent Immune Response Signaling Pathways Discovered in Peripheral Blood Mononuclear Cell Gene Expression Patterns in Presymptomatic and Clinically Apparent Malaria†

    PubMed Central

    Ockenhouse, Christian F.; Hu, Wan-chung; Kester, Kent E.; Cummings, James F.; Stewart, Ann; Heppner, D. Gray; Jedlicka, Anne E.; Scott, Alan L.; Wolfe, Nathan D.; Vahey, Maryanne; Burke, Donald S.

    2006-01-01

    Using genome-wide expression profiles from persons either experimentally challenged with malaria-infected mosquitoes or naturally infected with Plasmodium falciparum malaria, we present details of the transcriptional changes that occur with infection and that either are commonly shared between subjects with presymptomatic and clinically apparent malaria or distinguish these two groups. Toll-like receptor signaling through NF-κB pathways was significantly upregulated in both groups, as were downstream genes that function in phagocytosis and inflammation, including the cytokines tumor necrosis factor alpha, gamma interferon (IFN-γ), and interleukin-1β (IL-1β). The molecular program derived from these signatures illuminates the closely orchestrated interactions that regulate gene expression by transcription factors such as IRF-1 in the IFN-γ signal transduction pathway. Modulation of transcripts in heat shock and glycolytic enzyme genes paralleled the intensity of infection. Major histocompatibility complex class I molecules and genes involved in class II antigen presentation are significantly induced in 90% of malaria-infected persons regardless of group. Differences between early presymptomatic infection and natural infection involved genes that regulate the induction of apoptosis through mitogen-activated protein (MAP) kinases and signaling pathways through the endogenous pyrogen IL-1β, a major inducer of fever. The induction of apoptosis in peripheral blood mononuclear cells from patients with naturally acquired infection impacted the mitochondrial control of apoptosis and the activation of MAP kinase pathways centered around MAPK14 (p38α and p38β). Our findings confirm and extend findings regarding aspects of the earliest responses to malaria infection at the molecular level, which may be informative in elucidating how innate and adaptive immune responses may be modulated in different stages of infection. PMID:16988231

  4. Common Variants at 10 Genomic Loci Influence Hemoglobin A1C Levels via Glycemic and Nonglycemic Pathways

    PubMed Central

    Soranzo, Nicole; Sanna, Serena; Wheeler, Eleanor; Gieger, Christian; Radke, Dörte; Dupuis, Josée; Bouatia-Naji, Nabila; Langenberg, Claudia; Prokopenko, Inga; Stolerman, Elliot; Sandhu, Manjinder S.; Heeney, Matthew M.; Devaney, Joseph M.; Reilly, Muredach P.; Ricketts, Sally L.

    2010-01-01

    storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c. PMID:20858683

  5. 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. PMID:25271084

  6. 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.

  7. 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.

  8. Dead-end intermediates in the enterobacterial common antigen pathway induce morphological defects in Escherichia coli by competing for undecaprenyl phosphate.

    PubMed

    Jorgenson, Matthew A; Kannan, Suresh; Laubacher, Mary E; Young, Kevin D

    2016-04-01

    Bacterial morphology is determined primarily by the architecture of the peptidoglycan (PG) cell wall, a mesh-like layer that encases the cell. To identify novel mechanisms that create or maintain cell shape in Escherichia coli, we used flow cytometry to screen a transposon insertion library and identified a wecE mutant that altered cell shape, causing cells to filament and swell. WecE is a sugar aminotransferase involved in the biosynthesis of enterobacterial common antigen (ECA), a non-essential outer membrane glycolipid of the Enterobacteriaceae. Loss of wecE interrupts biosynthesis of ECA and causes the accumulation of the undecaprenyl pyrophosphate-linked intermediate ECA-lipid II. The wecE shape defects were reversed by: (i) preventing initiation of ECA biosynthesis, (ii) increasing the synthesis of the lipid carrier undecaprenyl phosphate (Und-P), (iii) diverting Und-P to PG synthesis or (iv) promoting Und-P recycling. The results argue that the buildup of ECA-lipid II sequesters part of the pool of Und-P, which, in turn, adversely affects PG synthesis. The data strongly suggest there is competition for a common pool of Und-P, whose proper distribution to alternate metabolic pathways is required to maintain normal cell shape in E. coli. PMID:26593043

  9. Laryngeal cancer risk and common single nucleotide polymorphisms in nucleotide excision repair pathway genes ERCC1, ERCC2, ERCC3, ERCC4, ERCC5 and XPA.

    PubMed

    Lu, Baocai; Li, Jing; Gao, Qingzu; Yu, Wenfa; Yang, Qinghui; Li, Xiaoyu

    2014-05-25

    Because the molecular mechanisms underlying the development of laryngeal cancer are not well understood, we conducted a case-control study to determine the association between eight common SNPs in NER pathway genes and risk of laryngeal cancer, and the association between genetic polymorphisms and environmental factors. A 1:1 matched case-control study of 176 cases and 176 controls was conducted. Laryngeal cancer cases were more likely to smoke and drink (all P values<0.05). Subjects with the ERCC1 rs11615 CC genotype and C allele had an increased risk of laryngeal cancer. Similarly, individuals with the ERCC5 rs17655 GG genotype and G allele had an increased risk of laryngeal cancer. Gene-gene interaction analysis showed that subjects carrying ERCC1 rs11615 C allele and XPG/ERCC5 rs17655 G allele had a greatly increased risk of breast cancer. Stratified analysis revealed that the interaction between polymorphisms of ERCC1 rs11615 and ERCC5 rs17655 and smoking on cancer risk was statistically significant, and ERCC1 rs11615 polymorphisms also had a significant interaction with drinking habit. In conclusion, our study suggests that ERCC1 rs11615 and ERCC5 rs17655 polymorphisms are associated with increased risk of laryngeal cancer, and that they confer more risk among smokers and drinkers. PMID:24582975

  10. 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

  11. Dissection of the interferon gamma-MHC class II signal transduction pathway reveals that type I and type II interferon systems share common signalling component(s).

    PubMed Central

    Loh, J E; Chang, C H; Fodor, W L; Flavell, R A

    1992-01-01

    We have used a herpes virus thymidine kinase (HSV-TK) based metabolic selection system to isolate mutants defective in the interferon gamma mediated induction of the MHC class II promoter. All the mutations act in trans and result in no detectable induction of MHC and invariant chain (Ii) gene expression. Scatchard analysis indicates that the mutants have a normal number of surface IFN gamma receptors with the same affinity constant. The mutants fall into two broad categories. One class of mutants is still able to induce MHC class I, IRF-1, 9-27, 1-8 and GBP genes by IFN gamma. A second class of mutants is defective for the IFN gamma induction of all the genes tested; surprisingly, the IFN alpha/beta induction of MHC class I, 9-27, ISG54 and ISG15 genes is also defective in these mutants, although different members of this class can be discriminated by the response of the GBP and IRF-1 genes to type I interferons. These data demonstrate that the signalling pathways of both type I and type II interferon systems share common signal transduction component(s). These mutants will be useful for the study of IFN gamma regulation of class II genes and Ii chain, and to elucidate molecular components of type I and type II interferon signal transduction. Images PMID:1314162

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

    PubMed Central

    Beilina, Alexandria; Rudenko, Iakov N.; Kaganovich, Alice; Civiero, Laura; Chau, Hien; Kalia, Suneil K.; Kalia, Lorraine V.; Lobbestael, Evy; Chia, Ruth; Ndukwe, Kelechi; Ding, Jinhui; Nalls, Mike A.; Olszewski, Maciej; Hauser, David N.; Kumaran, Ravindran; Lozano, Andres M.; Baekelandt, Veerle; Greene, Lois E.; Taymans, Jean-Marc; Greggio, Elisa; Cookson, Mark R.; Nalls, Mike A.; Plagnol, Vincent; Martinez, Maria; Hernandez, Dena G; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simón-Sánchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M A; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M; Brockmann, Kathrin; Brooks, Janet; Burn, David J; Charlesworth, Gavin; Chen, Honglei; Chong, Sean; Clarke, Carl E; Cookson, Mark R; Cooper, J Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T; van Dijk, Karin D; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gibbs, J Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Ómar; Harris, Clare; van Hilten, Jacobus J; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E; Huttenlocher, Johanna; Illig, Thomas; München, Helmholtz Zentrum; Jónsson, Pálmi V; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; München, Helmholtz Zentrum; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R; Morrison, Karen E; Mudanohwo, Ese; O’Sullivan, Sean S; Pearson, Justin; Perlmutter, Joel S; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C A; Stefánsson, Hreinn; Steinberg, Stacy; Stockton, Joanna D; Strange, Amy; Talbot, Kevin; Tanner, Carlie M; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J; Uitterlinden, André G; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H; Winder-Rhodes, Sophie; Stefánsson, Kári; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Singleton, Andrew B; Wood, Nicholas W; Chinnery, Patrick F; Arepalli, Sampath; Cookson, Mark R; Dillman, Allissa; Ferrucci, Luigi; Gibbs, J Raphael; Hernandez, Dena G; Johnson, Robert; Longo, Dan L; Majounie, Elisa; Nalls, Michael A; O’Brien, Richard; Singleton, Andrew B; Traynor, Bryan J; Troncoso, Juan; van der Brug, Marcel; Zielke, H Ronald; Zonderman, Alan B

    2014-01-01

    Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein–protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G–associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy–lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms. PMID:24510904

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Common and biased signaling pathways of the chemokine receptor CCR7 elicited by its ligands CCL19 and CCL21 in leukocytes.

    PubMed

    Hauser, Mark A; Legler, Daniel F

    2016-06-01

    Chemokines are pivotal regulators of cell migration during continuous immune surveillance, inflammation, homeostasis, and development. Chemokine binding to their 7-transmembrane domain, G-protein-coupled receptors causes conformational changes that elicit intracellular signaling pathways to acquire and maintain an asymmetric architectural organization and a polarized distribution of signaling molecules necessary for directional cell migration. Leukocytes rely on the interplay of chemokine-triggered migration modules to promote amoeboid-like locomotion. One of the most important chemokine receptors for adaptive immune cell migration is the CC-chemokine receptor CCR7. CCR7 and its ligands CCL19 and CCL21 control homing of T cells and dendritic cells to areas of the lymph nodes where T cell priming and the initiation of the adaptive immune response occur. Moreover, CCR7 signaling also contributes to T cell development in the thymus and to lymphorganogenesis. Although the CCR7-CCL19/CCL21 axis evolved to benefit the host, inappropriate regulation or use of these proteins can contribute or cause pathobiology of chronic inflammation, tumorigenesis, and metastasis, as well as autoimmune diseases. Therefore, it appears as the CCR7-CCL19/CCL21 axis is tightly regulated at numerous intersections. Here, we discuss the multiple regulatory mechanism of CCR7 signaling and its influence on CCR7 function. In particular, we focus on the functional diversity of the 2 CCR7 ligands, CCL19 and CCL21, as well as on their impact on biased signaling. The understanding of the molecular determinants of biased signaling and the multiple layers of CCR7 regulation holds the promise for potential future therapeutic intervention. PMID:26729814

  2. Insulin-like growth factor-II, phosphatidylinositol 3-kinase, nuclear factor-kappaB and inducible nitric-oxide synthase define a common myogenic signaling pathway.

    PubMed

    Kaliman, P; Canicio, J; Testar, X; Palacín, M; Zorzano, A

    1999-06-18

    Insulin-like growth factors (IGFs) are potent inducers of skeletal muscle differentiation and phosphatidylinositol (PI) 3-kinase activity is essential for this process. Here we show that IGF-II induces nuclear factor-kappaB (NF-kappaB) and nitric-oxide synthase (NOS) activities downstream from PI 3-kinase and that these events are critical for myogenesis. Differentiation of rat L6E9 myoblasts with IGF-II transiently induced NF-kappaB DNA binding activity, inducible nitric-oxide synthase (iNOS) expression, and nitric oxide (NO) production. IGF-II-induced iNOS expression and NO production were blocked by NF-kappaB inhibition. Both NF-kappaB and NOS activities were essential for IGF-II-induced terminal differentiation (myotube formation and expression of skeletal muscle proteins: myosin heavy chain, GLUT 4, and caveolin 3), which was totally blocked by NF-kappaB or NOS inhibitors in rat and human myoblasts. Moreover, the NOS substrate L-Arg induced myogenesis in the absence of IGFs in both rat and human myoblasts, and this effect was blocked by NOS inhibition. Regarding the mechanisms involved in IGF-II activation of NF-kappaB, PI 3-kinase inhibition prevented NF-kappaB activation, iNOS expression, and NO production. Moreover, IGF-II induced, through a PI 3-kinase-dependent pathway, a decrease in IkappaB-alpha protein content that correlated with a decrease in the amount of IkappaB-alpha associated with p65 NF-kappaB. PMID:10364173

  3. 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

  4. Targeted ablation of secretin-producing cells in transgenic mice reveals a common differentiation pathway with multiple enteroendocrine cell lineages in the small intestine.

    PubMed

    Rindi, G; Ratineau, C; Ronco, A; Candusso, M E; Tsai, M; Leiter, A B

    1999-09-01

    The four cell types of gut epithelium, enteroendocrine cells, enterocytes, Paneth cells and goblet cells, arise from a common totipotent stem cell located in the mid portion of the intestinal gland. The secretin-producing (S) cell is one of at least ten cell types belonging to the diffuse neuroendocrine system of the gut. We have examined the developmental relationship between secretin cells and other enteroendocrine cell types by conditional ablation of secretin cells in transgenic mice expressing herpes simplex virus 1 thymidine kinase (HSVTK). Ganciclovir-treated mice showed markedly increased numbers of apoptotic cells at the crypt-villus junction. Unexpectedly, ganciclovir treatment induced nearly complete ablation of enteroendocrine cells expressing cholecystokinin and peptide YY/glucagon (L cells) as well as secretin cells, suggesting a close developmental relationship between these three cell types. In addition, ganciclovir reduced the number of enteroendocrine cells producing gastric inhibitory polypeptide, substance-P, somatostatin and serotonin. During recovery from ganciclovir treatment, the enteroendocrine cells repopulated the intestine in normal numbers, suggesting that a common early endocrine progenitor was spared. Expression of BETA2, a basic helix-loop-helix protein essential for differentiation of secretin and cholecystokinin cells was examined in the proximal small intestine. BETA2 expression was seen in all enteroendocrine cells and not seen in nonendocrine cells. These results suggest that most small intestinal endocrine cells are developmentally related and that a close developmental relationship exists between secretin-producing S cells and cholecystokinin-producing and L type enteroendocrine cells. In addition, our work shows the existence of a multipotent endocrine-committed cell type and locates this hybrid multipotent cell type to a region of the intestine populated by relatively immature cells. PMID:10457023

  5. Common Space, Common Time, Common Work

    ERIC Educational Resources Information Center

    Shank, Melody J.

    2005-01-01

    The most valued means of support and learning cited by new teachers at Poland Regional High School in rural Maine are the collegial interactions that common workspace, common planning time, and common tasks make possible. The school has used these everyday structures to enable new and veteran teachers to converse about curricular and pedagogical…

  6. The signalling pathways of interleukin-6 and gamma interferon converge by the activation of different transcription factors which bind to common responsive DNA elements.

    PubMed Central

    Yuan, J; Wegenka, U M; Lütticken, C; Buschmann, J; Decker, T; Schindler, C; Heinrich, P C; Horn, F

    1994-01-01

    Interleukin-6 (IL-6) and gamma interferon (IFN-gamma) induce a partially overlapping set of genes, including the genes for interferon regulatory factor 1 (IRF-1), intercellular adhesion molecule 1 (ICAM-1), and the acute-phase protein alpha 2-macroglobulin. We report here that the rat alpha 2-macroglobulin promoter is activated by IFN-gamma in human hepatoma (HepG2) cells and that the IFN-gamma response element maps to the same site previously defined as the acute-phase response element (APRE), which binds the IL-6-activated transcription factor APRF (acute-phase response factor). As was reported for fibroblasts, the IFN-gamma-regulated transcription factor GAF is phosphorylated at tyrosine after IFN-gamma treatment of HepG2 cells. IFN-gamma posttranslationally activates a protein which specifically binds to the alpha 2-macroglobulin APRE. This protein is shown to be identical or closely related to GAF. Although APRF and GAF are shown to represent different proteins, their binding sequence specificities are very similar. APRF and GAF bind equally well to the APRE sequences of various acute-phase protein genes as well as to the IFN-gamma response elements of the IRF-1, ICAM-1, and other IFN-gamma-inducible genes. Transient transfection analysis revealed that the IFN-gamma response elements of the IRF-1 and ICAM-1 promoters are able to confer responsiveness to both IFN-gamma and IL-6 onto a heterologous promoter. Therefore, APRF and GAF are likely to be involved in the transcriptional induction of these immediate-early genes by IL-6 and IFN-gamma, respectively. Taken together, these results demonstrate that two functionally distinct hormones, IL-6 and IFN-gamma, act through common regulatory elements to which different transcription factors sharing almost the same sequence specificity bind. Images PMID:7509445

  7. 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. PMID:25510383

  8. 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

  9. 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

  10. Common Schools for Common Education.

    ERIC Educational Resources Information Center

    Callan, Eamonn

    1995-01-01

    A vision of common education for citizens of a liberal democracy warrants faith in common schools as an instrument of social good. Some kinds of separate schooling are not inconsistent with common schooling and are even desirable. Equal respect, as defined by J. Rawls, is a basis for common education. (SLD)

  11. 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.

  12. 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. ...

  13. Common Cold

    MedlinePlus

    ... coughing - everyone knows the symptoms of the common cold. It is probably the most common illness. In ... people in the United States suffer 1 billion colds. You can get a cold by touching your ...

  14. Ida-1, the Caenorhabditis elegans Orthologue of Mammalian Diabetes Autoantigen IA-2, Potentially Acts as a Common Modulator between Parkinson’s Disease and Diabetes: Role of Daf-2/Daf-16 Insulin Like Signalling Pathway

    PubMed Central

    Fatima, Soobiya; Haque, Rizwanul; Jadiya, Pooja; Shamsuzzama; Kumar, Lalit; Nazir, Aamir

    2014-01-01

    The lack of cure to age associated Parkinson’s disease (PD) has been challenging the efforts of researchers as well as health care providers. Recent evidences suggest that diabetic patients tend to show a higher future risk for PD advocating a strong correlation between PD and Diabetes, thus making it intriguing to decipher common genetic cues behind these ailments. We carried out studies on ida-1, the C. elegans orthologue of mammalian type-1 diabetes auto-antigen IA-2 towards achieving its functional workup vis-à-vis various associated endpoints of PD and Diabetes. Employing transgenic C. elegans strain expressing “human” alpha synuclein (NL5901) under normal and increased glucose concentrations, we studied aggregation of alpha synuclein, content of dopamine, expression of dopamine transporter, content of reactive oxygen species, locomotor activity, nuclear translocation of FOXO transcription factor Daf-16, and quantification of Daf2/Daf-16 mRNA. Our findings indicate that ida-1 affords protection in the studied disease conditions as absence of ida-1 resulted in higher alpha-synuclein aggregation under conditions that mimic the blood glucose levels of diabetic patients. We also observed reduced dopamine content, decreased motility, defective Daf-16 translocation and reduced expression of Daf-2 and Daf-16. Our studies establish important function of ida-1 as a modulator in Daf-2/Daf-16 insulin like signalling pathway thus possibly being a common link between PD and Diabetes. PMID:25469508

  15. Proteomic analysis of common bean seed with storage protein deficiency reveals up-regulation of sulfur-rich proteins and starch and raffinose metabolic enzymes, and down-regulation of the secretory pathway.

    PubMed

    Marsolais, Frédéric; Pajak, Agnieszka; Yin, Fuqiang; Taylor, Meghan; Gabriel, Michelle; Merino, Diana M; Ma, Vanessa; Kameka, Alexander; Vijayan, Perumal; Pham, Hai; Huang, Shangzhi; Rivoal, Jean; Bett, Kirstin; Hernández-Sebastià, Cinta; Liu, Qiang; Bertrand, Annick; Chapman, Ralph

    2010-06-16

    A deficiency in major seed storage proteins is associated with a nearly two-fold increase in sulfur amino acid content in genetically related lines of common bean (Phaseolus vulgaris). Their mature seed proteome was compared by an approach combining label-free quantification by spectral counting, 2-DE, and analysis of selective extracts. Lack of phaseolin, phytohemagglutinin and arcelin was mainly compensated by increases in legumin, alpha-amylase inhibitors and mannose lectin FRIL. Along with legumin, albumin-2, defensin and albumin-1 were major contributors to the elevated sulfur amino acid content. Coordinate induction of granule-bound starch synthase I, starch synthase II-2 and starch branching enzyme were associated with minor alteration of starch composition, whereas increased levels of UDP-glucose 4-epimerase were correlated with a 30% increase in raffinose content. Induction of cell division cycle protein 48 and ubiquitin suggested enhanced ER-associated degradation. This was not associated with a classical unfolded protein response as the levels of ER HSC70-cognate binding protein were actually reduced in the mutant. Repression of rab1 GTPase was consistent with decreased traffic through the secretory pathway. Collectively, these results have implications for the nutritional quality of common bean, and provide information on the pleiotropic phenotype associated with storage protein deficiency in a dicotyledonous seed. PMID:20353836

  16. 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.

  17. 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.

  18. 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…

  19. 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

  20. 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

  1. 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 Central

    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

  2. Coal-liquids distillation-tower corrosion. Chloride pathways in the Wilsonville, Alabama SRC-1 pilot plant when processing a high-chloride coal. Final report

    SciTech Connect

    Davis, B.H.; Saguees, A.; Thomas, G.A.; Baumert, K.L.

    1985-01-01

    The Wilsonville pilot plant experienced severe corrosion (> 1,000 mils/year) in the atmospheric fractionation column when processing a high-chloride (0.25 wt. %) coal. The operators found that the addition of sodium carbonate to the coal feed greatly reduced this corrosion but designers of a commercial plant could not use this corrosion control method. Hence, it was necessary to define the chloride pathway through the process. Samples collected during a brief operation without carbonate addition permitted a tentative conclusion about the chloride pathway. To provide a more definite pathway, the plant was operated for a three week period with a high chloride coal and samples were collected daily at more than 20 crucial sample points. Analysis of these samples clearly defined that the chloride pathway to the atmospheric fractionator was in the highest boiling distillate stream from the vacuum distillation column. A processing change near the mid-point of the three week run provided a marker to trace chloride through the process and provided further support for the pathway. Amines provide a transport mechanism for the chloride and provide, in addition, through thermal dissociation and recombination in fractionation columns, a mechanism for concentrating chlorides in a narrow region in the columns.

  3. Common cold

    MedlinePlus

    ... are the most common reason that children miss school and parents miss work. Parents often get colds ... other children. A cold can spread quickly through schools or daycares. Colds can occur at any time ...

  4. 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

  5. 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…

  6. 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....

  7. Analysis of common bean expressed sequence tags identifies sulfur metabolic pathways active in seed and sulfur-rich proteins highly expressed in the absence of phaseolin and major lectins

    PubMed Central

    2011-01-01

    Background A deficiency in phaseolin and phytohemagglutinin is associated with a near doubling of sulfur amino acid content in genetically related lines of common bean (Phaseolus vulgaris), particularly cysteine, elevated by 70%, and methionine, elevated by 10%. This mostly takes place at the expense of an abundant non-protein amino acid, S-methyl-cysteine. The deficiency in phaseolin and phytohemagglutinin is mainly compensated by increased levels of the 11S globulin legumin and residual lectins. Legumin, albumin-2, defensin and albumin-1 were previously identified as contributing to the increased sulfur amino acid content in the mutant line, on the basis of similarity to proteins from other legumes. Results Profiling of free amino acid in developing seeds of the BAT93 reference genotype revealed a biphasic accumulation of gamma-glutamyl-S-methyl-cysteine, the main soluble form of S-methyl-cysteine, with a lag phase occurring during storage protein accumulation. A collection of 30,147 expressed sequence tags (ESTs) was generated from four developmental stages, corresponding to distinct phases of gamma-glutamyl-S-methyl-cysteine accumulation, and covering the transitions to reserve accumulation and dessication. Analysis of gene ontology categories indicated the occurrence of multiple sulfur metabolic pathways, including all enzymatic activities responsible for sulfate assimilation, de novo cysteine and methionine biosynthesis. Integration of genomic and proteomic data enabled the identification and isolation of cDNAs coding for legumin, albumin-2, defensin D1 and albumin-1A and -B induced in the absence of phaseolin and phytohemagglutinin. Their deduced amino acid sequences have a higher content of cysteine than methionine, providing an explanation for the preferential increase of cysteine in the mutant line. Conclusion The EST collection provides a foundation to further investigate sulfur metabolism and the differential accumulation of sulfur amino acids in seed

  8. Network representations and methods for the analysis of chemical and biochemical pathways

    PubMed Central

    Sandefur, Conner I.; Mincheva, Maya; Schnell, Santiago

    2013-01-01

    Systems biologists increasingly use network representations to investigate biochemical pathways and their dynamic behaviours. In this critical review, we discuss four commonly used network representations of chemical and biochemical pathways. We illustrate how some of these representations reduce network complexity but result in the ambiguous representation of biochemical pathways. We also examine the current theoretical approaches available to investigate the dynamic behaviour of chemical and biochemical networks. Finally, we describe how the critical chemical and biochemical pathways responsible for emergent dynamic behaviour can be identified using network mining and functional mapping approaches. PMID:23857078

  9. 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…

  10. Targeting the Hedgehog Pathway in Pediatric Medulloblastoma

    PubMed Central

    Huang, Sherri Y.; Yang, Jer-Yen

    2015-01-01

    Medulloblastoma (MB), a primitive neuroectomal tumor of the cerebellum, is the most common malignant pediatric brain tumor. The cause of MB is largely unknown, but aberrant activation of Hedgehog (Hh) pathway is responsible for ~30% of MB. Despite aggressive treatment with surgical resection, radiation and chemotherapy, 70%–80% of pediatric medulloblastoma cases can be controlled, but most treated patients suffer devastating side effects. Therefore, developing a new effective treatment strategy is urgently needed. Hh signaling controls transcription of target genes by regulating activities of the three Glioma-associated oncogene (Gli1-3) transcription factors. In this review, we will focus on current clinical treatment options of MB and discuss mechanisms of drug resistance. In addition, we will describe current known molecular pathways which crosstalk with the Hedgehog pathway both in the context of medulloblastoma and non-medulloblastoma cancer development. Finally, we will introduce post-translational modifications that modulate Gli1 activity and summarize the positive and negative regulations of the Hh/Gli1 pathway. Towards developing novel combination therapies for medulloblastoma treatment, current information on interacting pathways and direct regulation of Hh signaling should prove critical. PMID:26512695

  11. 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.

  12. 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.

  13. 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.

  14. 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

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

    PubMed

    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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. [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

  1. 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

  2. WikiPathways: capturing the full diversity of pathway knowledge.

    PubMed

    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

  3. 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.…

  4. 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

  5. Inflammatory pathways in spondyloarthritis.

    PubMed

    Hreggvidsdottir, Hulda S; Noordenbos, Troy; Baeten, Dominique L

    2014-01-01

    Spondyloarthritis is the second most common form of chronic inflammatory arthritis and a unique hallmark of the disease is pathologic new bone formation. Several cytokine pathways have been genetically associated with ankylosing spondylitis (AS), the prototypic subtype of SpA, and additional evidence from human and animal studies support a role of these pathways in the disease. TNF has a key role in SpA as blockade significantly reduces inflammation and destruction, however the treatment does not halt new bone formation. New insights into the TNF pathway were recently obtained from an animal model specifically overexpressing the transmembrane form of TNF. This model leads to axial and peripheral new bone formation which is not seen in soluble TNF overexpression models, indicating different pathogenic roles of soluble and transmembrane TNF in arthritis development. Besides TNF, the IL-23/IL-17 axis is emerging as an important inflammatory pathway in SpA, as a SNP in the IL-23R locus has been associated with developing AS, mice overexpressing IL-23 develop SpA-like features and IL-17 blockade has been shown to be efficacious for AS patients in a phase II trial. In this review, we focus on the cytokine pathways that have recently been genetically associated with SpA, i.e. TNF, IL-1, IL-6 and IL-23/IL-17. We review the current genetic, experimental and human in vivo data available and discuss how these different pathways are involved in the pathophysiology of SpA. Additionally, we discuss how these pathways relate to the pathogenic new bone formation in SpA. PMID:23969080

  6. Social Ecology of South Commons. Final Report on Work Completed for the Office of Child Development, Planning Grant OCD-CB-486 (6/1/73-3/3/74).

    ERIC Educational Resources Information Center

    Pellow, Deborah; Bedger, Jean E.

    The purpose of this research is to determine if it is possible to build an inner-city community with socioeconomic and racial mix and have it work. The findings from a study carried out in the Near Southside Chicago community of South Commons, built in the late 50's are presented. Methodology included informal conversations, interviews with adult…

  7. 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.

  8. Migraine and Common Morbidities

    MedlinePlus

    ... headaches . Home > Migraine and Common Morbidities Print Email Migraine and Common Morbidities ACHE Newsletter Sign up for ... newsletter by entering your e-mail address below. Migraine and Common Morbidities For many patients, migraine is ...

  9. 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.

  10. 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

  11. 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,…

  12. 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

  13. 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…

  14. 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...

  15. 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.

  16. 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 ...

  17. 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,…

  18. 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…

  19. 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…

  20. The Common Core.

    ERIC Educational Resources Information Center

    Boyer, Ernest L.

    Current curricula in institutions of higher education are criticized in this speech for their lack of a common core of education. Several possibilities for developing such a common core include education centered around our common heritage and the challenges of the present. It is suggested that all students must be introduced to the events,…

  1. 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.

  2. Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

    PubMed Central

    Samuel, Varman T.; Shulman, Gerald I.

    2012-01-01

    Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance. PMID:22385956

  3. Targeting pathways downstream of KRAS in lung adenocarcinoma.

    PubMed

    Zhu, Zehua; Golay, Hadrien G; Barbie, David A

    2014-08-01

    Oncogenic KRAS activation is responsible for the most common genetic subtype of lung cancer. Although many of the major downstream signaling pathways that KRAS engages have been defined, these discoveries have yet to translate into effective targeted therapy. Much of the current focus has been directed at inhibiting the activation of RAF/MAPK and PI3K/AKT signaling, but clinical trials combining multiple different agents that target these pathways have failed to show significant activity. In this article, we will discuss the evidence for RAF and PI3K as key downstream RAS effectors, as well as the RAL guanine exchange factor, which is equally essential for transformation. Furthermore, we will delineate alternative pathways, including cytokine activation and autophagy, which are co-opted by oncogenic RAS signaling and also represent attractive targets for therapy. Finally, we will present strategies for combining inhibitors of these downstream KRAS signaling pathways in a rational fashion, as multitargeted therapy will be required to achieve a cure. PMID:25303301

  4. Targeting pathways downstream of KRAS in lung adenocarcinoma

    PubMed Central

    Zhu, Zehua; Golay, Hadrien G; Barbie, David A

    2014-01-01

    Oncogenic KRAS activation is responsible for the most common genetic subtype of lung cancer. Although many of the major downstream signaling pathways that KRAS engages have been defined, these discoveries have yet to translate into effective targeted therapy. Much of the current focus has been directed at inhibiting the activation of RAF/MAPK and PI3K/AKT signaling, but clinical trials combining multiple different agents that target these pathways have failed to show significant activity. In this article, we will discuss the evidence for RAF and PI3K as key downstream RAS effectors, as well as the RAL guanine exchange factor, which is equally essential for transformation. Furthermore, we will delineate alternative pathways, including cytokine activation and autophagy, which are co-opted by oncogenic RAS signaling and also represent attractive targets for therapy. Finally, we will present strategies for combining inhibitors of these downstream KRAS signaling pathways in a rational fashion, as multitargeted therapy will be required to achieve a cure. PMID:25303301

  5. The Evolution of Fungal Metabolic Pathways

    PubMed Central

    Rokas, Antonis

    2014-01-01

    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

  6. 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

  7. 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

  8. Effects of vegetation of radon transport processes in soil: The origins and pathways of {sup 222}Rn entering into basement structures. Final report, March 15, 1987--May 15, 1993

    SciTech Connect

    Borak, T.B.

    1992-08-01

    The entry rate of {sup 22}Rn into a basement structure was measured continuously. These measurements demonstrated that radon entry did not vanish even when the structure was slightly pressurized. This persistent entry has been determined to be dominated by diffusion through the floor and walls and a combination of diffusion and convection through the floor-wall joint. The highest indoor radon concentrations occurred during calm periods when the pressure differentials between the inside and outside of the structure were small. The objectives of this work were to identify the origins of the radon and investigate the entry pathways. The radon could originate either in the concrete or in the soil surrounding the structure. Entry pathways into the basement were through the concrete floor and walls as well as through the floor-wall joint. The contributions of the origins and entry pathways were determined by continuously measuring the radon entry rate into the basement, using a trace gas system, and the flux density through portions of the floor and walls. Radon entry through the floor-wall joint could be controlled using a baseboard barrier system. Results indicated that, during calm conditions with wind speeds less than 1 m s{sup {minus}1}, 25 % of the radon enters through the floor-wall joint and 75 % enters through the concrete. About 30 % of the radon originated in the concrete floor and walls. A method for in-situ determination of the diffusion length and emanation fraction of radon in concrete was developed. For the concrete used in the structure, the average diffusion length and emanation fraction were 27{plus_minus}4 cm and 0.19{plus_minus}0.02 respectively.

  9. 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

  10. Common Genetic Influences Underlie Comorbidity of Migraine and Endometriosis

    PubMed Central

    Nyholt, Dale R.; Gillespie, Nathan G.; Merikangas, Kathleen R.; Treloar, Susan A.; Martin, Nicholas G.; Montgomery, Grant W.

    2009-01-01

    We examined the co-occurrence of migraine and endometriosis within the largest known collection of families containing multiple women with surgically confirmed endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic female twin pairs. Within the endometriosis families, a significantly increased risk of migrainous headache was observed in women with endometriosis compared to women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]: 1.12–2.21, P = 0.009). Bivariate heritability analyses indicated no evidence for common environmental factors influencing either migraine or endometriosis but significant genetic components for both traits, with heritability estimates of 69 and 49%, respectively. Importantly, a significant additive genetic correlation (rG = 0.27, 95% CI: 0.06–0.47) and bivariate heritability (h2 = 0.17, 95% CI: 0.08–0.27) was observed between migraine and endometriosis. Controlling for the personality trait neuroticism made little impact on this association. These results confirm the previously reported comorbidity between migraine and endometriosis and indicate common genetic influences completely explain their co-occurrence within individuals. Given pharmacological treatments for endometriosis typically target hormonal pathways and a number of findings provide support for a relationship between hormonal variations and migraine, hormone-related genes and pathways are highly plausible candidates for both migraine and endometriosis. Therefore, taking into account the status of both migraine and endometriosis may provide a novel opportunity to identify the genes underlying them. Finally, we propose that the analysis of such genetically correlated comorbid traits can increase power to detect genetic risk loci through the use of more specific, homogenous and heritable phenotypes. PMID:18636479

  11. Common Conditions in Newborns

    MedlinePlus

    ... Prenatal Baby Bathing & Skin Care Breastfeeding Crying & Colic Diapers & Clothing Feeding & Nutrition Preemie Sleep Teething & Tooth Care Toddler Preschool Gradeschool Teen Young Adult Healthy Children > Ages & Stages > Baby > Common Conditions in ...

  12. 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.

  13. 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.

  14. 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)

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

    PubMed Central

    Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

    2016-01-01

    Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins. PMID:26959016

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Experimental evolution reveals hidden diversity in evolutionary pathways

    PubMed Central

    Lind, Peter A; Farr, Andrew D; Rainey, Paul B

    2015-01-01

    Replicate populations of natural and experimental organisms often show evidence of parallel genetic evolution, but the causes are unclear. The wrinkly spreader morph of Pseudomonas fluorescens arises repeatedly during experimental evolution. The mutational causes reside exclusively within three pathways. By eliminating these, 13 new mutational pathways were discovered with the newly arising WS types having fitnesses similar to those arising from the commonly passaged routes. Our findings show that parallel genetic evolution is strongly biased by constraints and we reveal the genetic bases. From such knowledge, and in instances where new phenotypes arise via gene activation, we suggest a set of principles: evolution proceeds firstly via pathways subject to negative regulation, then via promoter mutations and gene fusions, and finally via activation by intragenic gain-of-function mutations. These principles inform evolutionary forecasting and have relevance to interpreting the diverse array of mutations associated with clinically identical instances of disease in humans. DOI: http://dx.doi.org/10.7554/eLife.07074.001 PMID:25806684

  6. 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…

  7. 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…

  8. 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.

  9. 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…

  10. 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…

  11. 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,…

  12. Human Commonalities and Art

    ERIC Educational Resources Information Center

    Passmore, Kaye

    2008-01-01

    Educator Ernest Boyer believed that well-educated students should do more than master isolated facts. They should understand the "connectedness of things." He suggested organizing curriculum thematically around eight commonalities shared by people around the world. In the book "The Basic School: A Community for Learning," Boyer recommends that…

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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…

  18. The Common Denominator

    ERIC Educational Resources Information Center

    Grimes, Nikki

    2005-01-01

    An author and a poet Nikki Grimes uses her art to reach across differences such as race and culture, and show the commonality of human experience. She uses the power of her poetry to break down racial barriers, shatter cultural stereotypes, and forge community.

  19. Mathematics: Common Curriculum Goals.

    ERIC Educational Resources Information Center

    Oregon State Dept. of Education, Salem.

    This document defines what are considered to be the essentials in a strong mathematics program for the state of Oregon for grades K-12. The common curriculum goals are organized into nine content strands: (1) number and numeration; (2) appropriate computational skills; (3) problem solving; (4) geometry and visualization skills; (5) measurement;…

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. The Commonalities in Bacterial Effector Inhibition of Apoptosis.

    PubMed

    Robinson, Keith S; Aw, Rochelle

    2016-08-01

    Antiapoptotic pathways of the host cell play integral roles in bacterial pathogenesis, with inhibition of those pathways resulting in halted disease pathology. Certain pathogens have developed elegant mechanisms to modulate the fate of the host cell, many of which target novel pathways that are poorly understood in the context of the cell biology. Bacterial pathogenesis research not only promotes the understanding of the role of antiapoptotic pathways in bacterial infection, but has a broader context in understanding the epitome of human disease, that is, developing the understanding of tumorigenic or inflammatory pathways. Here we review host antiapoptotic signalling pathways manipulated by translocated bacterial effectors that propagate the disease state, drawing common parallels and showing the novel differences. PMID:27117049

  5. Common Rail Injection System Development

    SciTech Connect

    Electro-Motive,

    2005-12-30

    The collaborative research program between the Department of energy and Electro-Motive Diesels, Inc. on the development of common rail fuel injection system for locomotive diesel engines that can meet US EPA Tier 2 exhaust emissions has been completed. This final report summarizes the objectives of the program, work scope, key accomplishments and research findings. The major objectives of this project encompassed identification of appropriate injection strategies by using advanced analytical tools, development of required prototype hardware/controls, investigations of fuel spray characteristics including cavitation phenomena, and validation of hareware using a single-cylinder research locomotive diesel engine. Major milestones included: (1) a detailed modeling study using advanced mathematical models - several various injection profiles that show simultaneous reduction of NOx and particulates on a four stroke-cycle locomotive diesel engine were identified; (2) development of new common rail fuel injection hardware capable of providing these injection profiles while meeting EMD engine and injection performance specifications. This hardware was developed together with EMD's current fuel injection component supplier. (3) Analysis of fuel spray characteristics. Fuel spray numerical studies and high speed photographic imaging analyses were performed. (4) Validation of new hardware and fuel injection profiles. EMD's single-cylinder research diesel engine located at Argonne National Laboratory was used to confirm emissions and performacne predictions. These analytical ane experimental investigations resulted in optimized fuel injection profiles and engine operating conditions that yield reductions in NOx emissions from 7.8 g/bhp-hr to 5.0 g/bhp-hr at full (rated) load. Additionally, hydrocarbon and particulate emissions were reduced considerably when compared to baseline Tier I levels. The most significant finding from the injection optimization process was a 2% to 3

  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. PMID:26629874

  7. Commonly missed orthopedic problems.

    PubMed

    Ballas, M T; Tytko, J; Mannarino, F

    1998-01-15

    When not diagnosed early and managed appropriately, common musculoskeletal injuries may result in long-term disabling conditions. Anterior cruciate ligament tears are some of the most common knee ligament injuries. Slipped capital femoral epiphysis may present with little or no hip pain, and subtle or absent physical and radiographic findings. Femoral neck stress fractures, if left untreated, may result in avascular necrosis, refractures and pseudoarthrosis. A delay in diagnosis of scaphoid fractures may cause early wrist arthrosis if nonunion results. Ulnar collateral ligament tears are a frequently overlooked injury in skiers. The diagnosis of Achilles tendon rupture is missed as often as 25 percent of the time. Posterior tibial tendon tears may result in fixed bony planus if diagnosis is delayed, necessitating hindfoot fusion rather than simple soft tissue repair. Family physicians should be familiar with the initial assessment of these conditions and, when appropriate, refer patients promptly to an orthopedic surgeon. PMID:9456991

  8. Common drive unit

    NASA Technical Reports Server (NTRS)

    Ellis, R. C.; Fink, R. A.; Moore, E. A.

    1987-01-01

    The Common Drive Unit (CDU) is a high reliability rotary actuator with many versatile applications in mechanism designs. The CDU incorporates a set of redundant motor-brake assemblies driving a single output shaft through differential. Tachometers provide speed information in the AC version. Operation of both motors, as compared to the operation of one motor, will yield the same output torque with twice the output speed.

  9. 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

  10. 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.

  11. Common Geometry Module

    Energy Science and Technology Software Center (ESTSC)

    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

  12. 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.

  13. '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. PMID:23135802

  14. 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

  15. Signaling pathways mediating alcohol effects.

    PubMed

    Ron, Dorit; Messing, Robert O

    2013-01-01

    Ethanol's effects on intracellular signaling pathways contribute to acute effects of ethanol as well as to neuroadaptive responses to repeated ethanol exposure. In this chapter we review recent discoveries that demonstrate how ethanol alters signaling pathways involving several receptor tyrosine kinases and intracellular tyrosine and serine-threonine kinases, with consequences for regulation of cell surface receptor function, gene expression, protein translation, neuronal excitability and animal behavior. We also describe recent work that demonstrates a key role for ethanol in regulating the function of scaffolding proteins that organize signaling complexes into functional units. Finally, we review recent exciting studies demonstrating ethanol modulation of DNA and histone modification and the expression of microRNAs, indicating epigenetic mechanisms by which ethanol regulates neuronal gene expression and addictive behaviors. PMID:21877259

  16. Developmental pathways of motor dysfunction.

    PubMed

    Kleven, Gale A; Bellinger, Seanceray A

    2015-05-01

    Recent evidence has revealed unique patterns of behavioral development after prenatal insult similar to those outlined in studies of adult metabolic dysfunction after prenatal malnutrition. The hallmark features of this Developmental Pathway include a prenatal insult to the nervous system (environmental or genetic) followed by a period of Silent Vulnerability, where no or few functional deficits are observed, and finally emergence of later dysfunction. Possible mechanisms leading to later dysfunction from prenatal insult may include secondary or cascade effects due to the timing of prenatal insults relative to later developing structures in the brain. Methods best employed to study the mechanisms of these pathways are microgenetic and longitudinal designs that include behavioral assessment during the prenatal period of development, and animal models such as the guinea pig. PMID:25864561

  17. Temporal Identification of Dysregulated Genes and Pathways in Clear Cell Renal Cell Carcinoma Based on Systematic Tracking of Disrupted Modules

    PubMed Central

    Wang, Shao-Mei; Sun, Ze-Qiang; Li, Hong-Yun; Wang, Jin; Liu, Qing-Yong

    2015-01-01

    Objective. The objective of this work is to identify dysregulated genes and pathways of ccRCC temporally according to systematic tracking of the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. Methods. Firstly, normal and ccRCC PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, we identified altered modules using maximum weight bipartite matching and ranked them in nonincreasing order. Finally, gene compositions of altered modules were analyzed, and pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test. Results. We obtained 136, 576, 693, and 531 disrupted modules of ccRCC stages I, II, III, and IV, respectively. Gene composition analyses of altered modules revealed that there were 56 common genes (such as MAPK1, CCNA2, and GSTM3) existing in the four stages. Besides pathway enrichment analysis identified 5 common pathways (glutathione metabolism, cell cycle, alanine, aspartate, and glutamate metabolism, arginine and proline metabolism, and metabolism of xenobiotics by cytochrome P450) across stages I, II, III, and IV. Conclusions. We successfully identified dysregulated genes and pathways of ccRCC in different stages, and these might be potential biological markers and processes for treatment and etiology mechanism in ccRCC. PMID:26543493

  18. 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…

  19. 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

  20. 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. PMID:25658216

  1. 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

  2. Commonly used gastrointestinal drugs.

    PubMed

    Aggarwal, Annu; Bhatt, Mohit

    2014-01-01

    This chapter reviews the spectrum and mechanisms of neurologic adverse effects of commonly used gastrointestinal drugs including antiemetics, promotility drugs, laxatives, antimotility drugs, and drugs for acid-related disorders. The commonly used gastrointestinal drugs as a group are considered safe and are widely used. A range of neurologic complications are reported following use of various gastrointestinal drugs. Acute neurotoxicities, including transient akathisias, oculogyric crisis, delirium, seizures, and strokes, can develop after use of certain gastrointestinal medications, while disabling and pervasive tardive syndromes are described following long-term and often unsupervised use of phenothiazines, metoclopramide, and other drugs. In rare instances, some of the antiemetics can precipitate life-threatening extrapyramidal reactions, neuroleptic malignant syndrome, or serotonin syndrome. In contrast, concerns about the cardiovascular toxicity of drugs such as cisapride and tegaserod have been grave enough to lead to their withdrawal from many world markets. Awareness and recognition of the neurotoxicity of gastrointestinal drugs is essential to help weigh the benefit of their use against possible adverse effects, even if uncommon. Furthermore, as far as possible, drugs such as metoclopramide and others that can lead to tardive dyskinesias should be used for as short time as possible, with close clinical monitoring and patient education. PMID:24365343

  3. Neurophysiology and itch pathways.

    PubMed

    Schmelz, Martin

    2015-01-01

    As we all can easily differentiate the sensations of itch and pain, the most straightforward neurophysiologic concept would consist of two specific pathways that independently encode itch and pain. Indeed, a neuronal pathway for histamine-induced itch in the peripheral and central nervous system has been described in animals and humans, and recently several non-histaminergic pathways for itch have been discovered in rodents that support a dichotomous concept differentiated into a pain and an itch pathway, with both pathways being composed of different "flavors." Numerous markers and mediators have been found that are linked to itch processing pathways. Thus, the delineation of neuronal pathways for itch from pain pathways seemingly proves that all sensory aspects of itch are based on an itch-specific neuronal pathway. However, such a concept is incomplete as itch can also be induced by the activation of the pain pathway in particular when the stimulus is applied in a highly localized spatial pattern. These opposite views reflect the old dispute between specificity and pattern theories of itch. Rather than only being of theoretic interest, this conceptual problem has key implication for the strategy to treat chronic itch as key therapeutic targets would be either itch-specific pathways or unspecific nociceptive pathways. PMID:25861773

  4. The structure of common-envelope remnants

    NASA Astrophysics Data System (ADS)

    Hall, Philip D.

    2015-05-01

    evolved stars. These formulae can be used to better compute the outcome of common-envelope evolution with rapid evolution codes. We find that the new formulae are necessary for accurate predictions of the properties of post-common envelope systems. Finally, we use detailed remnant models of massive stars to investigate whether hydrogen may be retained after a common-envelope phase to the point of core-collapse and so be observable in supernovae. We find that this is possible and thus common-envelope evolution may contribute to the formation of Type IIb supernovae.

  5. Common herbal remedies.

    PubMed

    Turkoski, B B

    2000-01-01

    Herbal remedies are becoming increasingly popular as people seek more effective, natural, or safer methods for treating a variety of complaints. As a result, nurses in every setting may expect to see increased numbers of patients who are using herbal products. When patients assume that the nurses will be critical of their use of herbals, they may withhold such information to avoid unpleasantness. This could place patients at risk for adverse effects, drug interactions, and complications related to ineffective treatment. Nurses who are knowledgeable about herbal products and who are open to discussion about these products can provide information and advice about safe use. The discussion in this article addresses actions, possible benefits, and dangers of the most common herbal products. Guidelines for assessing and teaching clients about herbal use are included. PMID:11062629

  6. CPL: Common Pipeline Library

    NASA Astrophysics Data System (ADS)

    ESO CPL Development Team

    2014-02-01

    The Common Pipeline Library (CPL) is a set of ISO-C libraries that provide a comprehensive, efficient and robust software toolkit to create automated astronomical data reduction pipelines. Though initially developed as a standardized way to build VLT instrument pipelines, the CPL may be more generally applied to any similar application. The code also provides a variety of general purpose image- and signal-processing functions, making it an excellent framework for the creation of more generic data handling packages. The CPL handles low-level data types (images, tables, matrices, strings, property lists, etc.) and medium-level data access methods (a simple data abstraction layer for FITS files). It also provides table organization and manipulation, keyword/value handling and management, and support for dynamic loading of recipe modules using programs such as EsoRex (ascl:1504.003).

  7. System Safety Common Cause Analysis

    Energy Science and Technology Software Center (ESTSC)

    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

  8. 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?

  9. 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

  10. 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.

  11. Relevant Networks involving the p53 Signalling Pathway in Renal Cell Carcinoma

    PubMed Central

    Villaamil, V. Medina; Gallego, G. Aparicio; Caínzos, I. Santamarina; Ruvira, L. Valbuena; Valladares-Ayerbes, M.; Aparicio, L. M. Antón

    2011-01-01

    Introduction: Renal cell carcinoma is the most common type of kidney cancer. A better understanding of the critical pathways and interactions associated with alterations in renal function and renal tumour properties is required. Our final goal is to combine the knowledge provided by a regulatory network with experimental observations provided by the dataset. Methods: In this study, a systems biology approach was used, integrating immunohistochemistry protein expression profiles and protein interaction information with the STRING and MeV bioinformatics tools. A group consisting of 80 patients with renal cell carcinoma was studied. The expression of selected markers was assessed using tissue microarray technology on immunohistochemically stained slides. The immunohistochemical data of the molecular factors studied were analysed using a parametric statistical test, Pearson’s correlation coefficient test. Results: Bioinformatics analysis of tumour samples resulted in 2 protein networks. The first network consists of proteins involved in the angiogenesis pathway and the apoptosis suppressor, BCL2, and includes both positive and negative correlations. The second network shows a negative interaction between the p53 tumour suppressor protein and the glucose transporter type 4. Conclusion: The comprehensive pathway network will help us to realise the cooperative behaviours among pathways. Regulation of metabolic pathways is an important role of p53. The pathway involving the tumour suppressor gene p53 could regulate tumour angiogenesis. Further investigation of the proteins that interact with this pathway in this type of tumour may provide new strategies for cancer therapies to specifically inhibit the molecules that play crucial roles in tumour progression. PMID:23675247

  12. 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

  13. Proteomic Analysis of Cerebellum in Common Marmoset Exposed to Methylmercury.

    PubMed

    Shao, Yueting; Yamamoto, Megumi; Figeys, Daniel; Ning, Zhibin; Chan, Hing Man

    2015-07-01

    The cerebellum is known as the major target regions of methylmercury (MeHg) toxicity, but the mechanisms are still not fully understood. We studied the effects of MeHg exposure in the cerebellum of common marmoset (Callithrix jacchus) using a shotgun proteomic approach with liquid chromatography coupled to mass spectrometry. A total of 1000 common proteins were identified in all samples, and 102 proteins were significantly differentially expressed in the cerebellum of common marmoset with orally dosed MeHg (1.5 mg MeHg/kg body weight for 2 weeks) compared with those of the control group. Functional enrichment analysis and pathway predictions showed that the differentially expressed proteins were involved in carbohydrate derivative metabolic process, ion transport including synaptic transmission, cell development, and calcium signaling pathway. Cellular component enrichment analysis showed that they were mainly distributed in plasma membrane, excitatory synapse, and synaptic membrane. These results indicate that synaptic transmission and calcium signaling pathways are the core functions affected by MeHg. We found a total of 21 novel proteins affected by MeHg in synaptic transmission and calcium signaling pathways. DLG4: (PSD95) and MIR-19A/MIR-19B were found to be potential key targets leading to the multiple effects of MeHg neurotoxicity. These results show the global effects of MeHg on cellular functions and pathways leading to neurological deficits in common marmoset. PMID:25809596

  14. 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.

  15. 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

  16. The Common Land Model.

    NASA Astrophysics Data System (ADS)

    Dai, Yongjiu; Zeng, Xubin; Dickinson, Robert E.; Baker, Ian; Bonan, Gordon B.; Bosilovich, Michael G.; Denning, A. Scott; Dirmeyer, Paul A.; Houser, Paul R.; Niu, Guoyue; Oleson, Keith W.; Schlosser, C. Adam; Yang, Zong-Liang

    2003-08-01

    The Common Land Model (CLM) was developed for community use by a grassroots collaboration of scientists who have an interest in making a general land model available for public use and further development. The major model characteristics include enough unevenly spaced layers to adequately represent soil temperature and soil moisture, and a multilayer parameterization of snow processes; an explicit treatment of the mass of liquid water and ice water and their phase change within the snow and soil system; a runoff parameterization following the TOPMODEL concept; a canopy photosynthesis-conductance model that describes the simultaneous transfer of CO2 and water vapor into and out of vegetation; and a tiled treatment of the subgrid fraction of energy and water balance. CLM has been extensively evaluated in offline mode and coupling runs with the NCAR Community Climate Model (CCM3). The results of two offline runs, presented as examples, are compared with observations and with the simulation of three other land models [the Biosphere-Atmosphere Transfer Scheme (BATS), Bonan's Land Surface Model (LSM), and the 1994 version of the Chinese Academy of Sciences Institute of Atmospheric Physics LSM (IAP94)].

  17. Common approaches for adolescents.

    PubMed

    1998-01-01

    A South-South program organized by JOICFP provided an excellent opportunity for the exchange of experiences in the field of adolescent reproductive health (RH) between Mexico and the Philippines. Alfonso Lopez Juarez, executive director, Mexican Foundation for Family Planning (MEXFAM), shared MEXFAM's experiences with field personnel and GO-NGO representatives related to JOICFP's RH-oriented project in the Philippines while in the country from November 16 to 21. The program was also effective for identifying common issues and effective approaches to adolescent health issues and communicating with youth on RH and sexual health. The exchange was supported by the Hoken Kaikan Foundation and organized by JOICFP in collaboration with UNFPA-Manila and the Commission on Population (POPCOM). Lopez shared some of the lessons of MEXFAM's decade-long Gente Joven IEC program on adolescent health with GO and NGO representatives at a forum held on November 18. The event was opened by Dr. Carmencita Reodica, secretary, Department of Health (DOH). He then moved to the project sites of Balayan and Malvar municipalities of Batangas Province, where he spoke with field staff and demonstrated MEXFAM's approach in classroom situations with young people. Lopez also observed various adolescent activities such as group work with peer facilitators. "I am pleased that we can share some applicable experiences and learn from each other's projects," commented Lopez. PMID:12348336

  18. 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.

  19. 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

  20. PATHWAYS - ELECTRON TUNNELING PATHWAYS IN PROTEINS

    NASA Technical Reports Server (NTRS)

    Beratan, D. N.

    1994-01-01

    The key to understanding the mechanisms of many important biological processes such as photosynthesis and respiration is a better understanding of the electron transfer processes which take place between metal atoms (and other groups) fixed within large protein molecules. Research is currently focused on the rate of electron transfer and the factors that influence it, such as protein composition and the distance between metal atoms. Current models explain the swift transfer of electrons over considerable distances by postulating bridge-mediated tunneling, or physical tunneling pathways, made up of interacting bonds in the medium around and between donor and acceptor sites. The program PATHWAYS is designed to predict the route along which electrons travel in the transfer processes. The basic strategy of PATHWAYS is to begin by recording each possible path element on a connectivity list, including in each entry which two atoms are connected and what contribution the connection would make to the overall rate if it were included in a pathway. The list begins with the bonded molecular structure (including the backbone sequence and side chain connectivity), and then adds probable hydrogen bond links and through-space contacts. Once this list is completed, the program runs a tree search from the donor to the acceptor site to find the dominant pathways. The speed and efficiency of the computer search offers an improvement over manual techniques. PATHWAYS is written in FORTRAN 77 for execution on DEC VAX series computers running VMS. The program inputs data from four data sets and one structure file. The software was written to input BIOGRAF (old format) structure files based on x-ray crystal structures and outputs ASCII files listing the best pathways and BIOGRAF vector files containing the paths. Relatively minor changes could be made in the input format statements for compatibility with other graphics software. The executable and source code are included with the

  1. 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.

  2. 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

  3. 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…

  4. Air Research Program: Key Pathways research track

    EPA Science Inventory

    The pathways research track applies animal, cellular, and human studies to discern whether there is a common molecular mechanism (e.g. production of oxidative stress, phosphatase inhibition, disruption of iron homeostasis) through which air pollutants induce toxicity of air pollu...

  5. HOW COMMON IS RSI?

    PubMed Central

    Palmer, Keith T; Reading, Isabel; Calnan, Michael; Coggon, David

    2013-01-01

    Objective Statistics from Labour Force Surveys are widely quoted as evidence for the scale of occupational illness in Europe. However, occupational attribution depends on whether participants believe their health problem is caused or aggravated by work, and personal beliefs may be unreliable. We assessed the potential for error for work-associated arm pain. Methods We mailed a questionnaire to working-aged adults, randomly chosen from five British general practices. We asked about: occupational activities; mental health; self-rated health; arm pain; and beliefs about its causation. Those in work (n = 1769) were asked about activities likely to cause arm pain, from which we derived a variable for exposure to any ‘arm-straining’ occupational activity. We estimated the relative risk (RR) from arm-straining activity, using a modified Cox model, and derived the population attributable fraction (PAF). We compared the proportion of arm pain cases reporting their symptom as caused or made worse by work with the calculated PAF, overall and for subsets defined by demographic and other characteristics. Results Arm pain in the past year was more common in the 1,143 subjects who reported exposure to arm-straining occupational activity (RR 1.2, 95% confidence interval 1.1 to 1.5). In the study sample as a whole, 53.9% of 817 cases reported their arm pain as work-associated, whereas the PAF for arm-straining occupational activity was only 13.9%. The ratio of cases reported as work-related to the calculated attributable number was substantially higher below 50 years (5.4) than at older ages (3.0) and higher in those with worse self-rated and mental health. Conclusions Counting people with arm pain which they believe to be work-related can overestimate the number of cases attributable to work substantially. This casts doubt on the validity of a major source of information used by European Governments to evaluate their occupational health strategies. PMID:18056747

  6. 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

  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. 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

  9. 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

  10. Antidromic Atrioventricular Reciprocating Tachycardia Using a Concealed Retrograde Conducting Left Lateral Accessory Pathway.

    PubMed

    Gonzalez, Jaime E; Zipse, Matthew M; Nguyen, Duy T; Sauer, William H

    2016-03-01

    Atrioventricular reciprocating tachycardia is a common cause of undifferentiated supraventricular tachycardia. In patients with manifest or concealed accessory pathways, it is imperative to assess for the presence of other accessory pathways. Multiple accessory pathways are present in 4% to 10% of patients and are more common in patients with structural heart disease. In rare cases, multiple accessory pathways can act as the anterograde and retrograde limbs of the tachycardia. PMID:26920167

  11. Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway.

    PubMed

    Huang, Nanxin; Chen, Dong; Wu, Xiyan; Chen, Xianjun; Zhang, Xuesi; Niu, Jianqin; Shen, Hai-Ying; Xiao, Lan

    2016-07-01

    Aspirin, one of the most commonly used anti-inflammatory drugs, has been recently reported to display multiple effects in the central nervous system (CNS), including neuroprotection and upregulation of ciliary neurotrophic factor (CNTF) expression in astrocytes. Although it was most recently reported that aspirin could promote the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) after white matter lesion, the underlying mechanisms remain unclear. To dissect the effects of aspirin on oligodendroglial development and explore possible mechanisms, we here demonstrated the following: (i) in vitro treatment of aspirin on OPC cultures significantly increased the number of differentiated oligodendrocytes (OLs) but had no effect on the number of proliferative OPCs, indicating that aspirin can promote OPC differentiation but not proliferation; (ii) in vivo treatment of aspirin on neonatal (P3) rats for 4 days led to a nearly twofold increase in the expression of myelin basic protein (MBP), devoid of change in OPC proliferaion, in the corpus callosum (CC); (iii) finally, aspirin treatment increased the phosphorylation level of β-catenin and counteracted Wnt signaling pathway synergist QS11-induced suppression on OPC differentiation. Together, our data show that aspirin can directly target oligodendroglial lineage cells and promote their differentiation through inhibition of Wnt/β-catenin signaling pathway. These findings suggest that aspirin may be a novel candidate for the treatment of demyelinating diseases. PMID:26059811

  12. 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

  13. Light-Mediated Remote Control of Signaling Pathways

    PubMed Central

    Priestman, Melanie A.; Lawrence, David S.

    2009-01-01

    Summary Cell signaling networks display an extraordinary range of temporal and spatial plasticity. Our programmatic approach focuses on the construction of intracellular probes, including sensors, inhibitors, and functionally unique proteins that can be temporally and spatially controlled by the investigator even after they have entered the cell. We have designed and evaluated protein kinase sensors that furnish a fluorescent readout upon phosphorylation. In addition, since the sensors are inert (i.e. cannot be phosphorylated) until activated by light, they can be carried through the various stages of any given cell-based behavior without being consumed. Using this strategy, we have shown that PKCβ is essential for nuclear envelope breakdown and thus the transition from prophase to metaphase in actively dividing cells. Photoactivatable proteins furnish the means to initiate cellular signaling pathways with a high degree of spatial and temporal control. We have used this approach to demonstrate that cofilin serves as a component of the steering apparatus of the cell. Finally, inhibitors are commonly used to assess the participation of specific enzymes in signaling pathways that control cellular behavior. We have constructed a photo-deactivatable inhibitor, an inhibitory species that can be switched off with light. In the absence of light, the target enzyme is inactive due to the presence of the potent inhibitory molecule. Upon photolysis, the inhibitory molecule is destroyed and enzymatic activity is released. PMID:19765679

  14. The Wnt pathway: emerging anticancer strategies.

    PubMed

    Gupta, Aman; Verma, Anukriti; Mishra, Ashutosh K; Wadhwa, Gulshan; Sharma, Sanjeev K; Jain, Chakresh K

    2013-05-01

    The canonical Wnt cascade has emerged as a critical regulator of cancer cells. Activation of the Wnt signaling pathway has also been associated with stem cell, thus raising the possibility of its role in embryogenesis and in the proliferation of malignant cancer cells. Wnt pathway has been reported to be involved in normal physiological processes in adult animals and integrally associated with cancer cell growth and maintenance, thus has been harnessed to devise strategies for anticancer therapy. The presence or absence of some members in this pathway, such as β-catenin, Axin or APC, has been found to involve in different types of tumors in human beings. Dysregulation of the canonical Wnt/β-catenin signaling pathway, mostly by inactivating mutations of the APC tumor suppressor, or oncogenic mutations of β-catenin, has been implicated in colorectal tumorigenesis. Further, elevated levels of β-catenin protein, a hallmark of activated canonical Wnt pathway, have been significantly observed in common forms of human malignancies, indicating that activation of the Wnt pathway may play an important role in tumor development and hence could be a crucial consideration for drug development. The paper discusses the potential therapeutic and diagnostic strategies directing on Wnt pathways on the basis of recent patents and their analysis. PMID:23432158

  15. 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

  16. 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

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

    PubMed

    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

  18. 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

  19. Concomitant Wolff-Parkinson-White and Atrioventricular Nodal Reentrant Tachycardia: Which Pathway to Ablate?

    PubMed Central

    Sarsam, Sinan; Sidiqi, Ibrahim; Shah, Dipak; Zughaib, Marcel

    2015-01-01

    Patient: Male, 54 Final Diagnosis: WPW and AVNRT Symptoms: Palpitations • shorthness of breath Medication: — Clinical Procedure: EP Study/Radiofrequency Ablation Specialty: Cardiology Objective: Rare co-existance of disease or pathology Background: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common form of supraventricular tachycardia. In contrast, Wolff-Parkinson-White (WPW) pattern consists of an accessory pathway, which may result in the development of ventricular arrhythmias. Frequent tachycardia caused by AVNRT and accessory pathways may play a role in left ventricular systolic dysfunction. Case Report: A 54-year-old man presented with palpitations and acute decompensated congestive heart failure. His baseline EKG showed Wolff-Parkinson-White (WPW) pattern. While hospitalized, he had an episode of atrioventricular nodal reentrant tachycardia (AVNRT). He underwent radiofrequency catheter ablation for AVNRT, and his accessory pathway was also ablated even though its conduction was found to be weak. He was clinically doing well on follow-up visit, with resolution of his heart failure symptoms and normalization of left ventricular function on echocardiography. Conclusions: This case raises the question whether the accessory pathway plays a role in the development of systolic dysfunction, and if there is any role for ablation in patients with asymptomatic WPW pattern. PMID:26655223

  20. 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

  1. 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.

  2. COMMONALITIES IN METABOLISM OF ARSENICALS

    EPA Science Inventory

    Elucidating the pathway of inorganic arsenic metabolism shows that some of methylated arsenicals formed as intermediates and products are reactive and toxic species. Hence, methylated arsenicals likely mediate at least some of the toxic and carcinogenic effects associated with e...

  3. 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.

  4. 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…

  5. [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)

  6. 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.

  7. 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…

  8. 6 Common Cancers - Skin Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Skin Cancer Past Issues / Spring 2007 Table of Contents For ... AP Photo/Herald-Mail, Kevin G. Gilbert Skin Cancer Skin cancer is the most common form of ...

  9. 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

  10. Analyzing Commonality In A System

    NASA Technical Reports Server (NTRS)

    Pacheco, Alfred; Pool, Kevin

    1988-01-01

    Cost decreased by use of fewer types of parts. System Commonality Analysis Tool (SCAT) computer program designed to aid managers and engineers in identifying common, potentially common, and unique components of system. Incorporates three major functions: program for creation and maintenance of data base, analysis of commonality, and such system utilities as host-operating-system commands and loading and unloading of data base. Produces reports tabulating maintenance, initial configurations, and expected total costs. Written in FORTRAN 77.

  11. 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).

  12. 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.…

  13. 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…

  14. 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…

  15. 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…

  16. Final Report

    SciTech Connect

    Wessels, B. W.

    2002-08-02

    Final report for program on the study of structure and properties of epitaxial oxide films. The defect structure of epitaxial oxide thin films was investigated. Both binary and complex oxides were studied. Epitaxial oxides were synthesized by organometallic chemical vapor deposition (OMCVD). This technique has been found to be highly versatile for the synthesis of a wide range of epitaxial oxide including dielectrics, ferroelectrics and high T{sub c} superconductors. Systems investigated include the binary oxides ZnO and TiO{sub 2} and ferroelectric oxides BaTiO{sub 3}, BaSrTiO{sub 3} and KNbO{sub 3}. Techniques used to evaluate the defect structure included deep level transient spectroscopy (DLTS), photocapacitance spectroscopy, and photoluminescence (PL) spectroscopy. High purity, stoichiometric oxide films were deposited and their defect structure evaluated. Epitaxial ZnO was deposited at temperatures as low as 250 C. PL indicated only near band edge ultraviolet emission showing that both extrinsic and intrinsic point defects could be significantly lowered in OMCVD derived thin films compared to that of the bulk. This presumably was a result of low deposition temperatures and high purity starting materials. Ferroelectric oxides epitaxial thin films of BaTiO{sub 3} and the solid solution BaSrTiO{sub 3} were synthesized and the defect structure determined. Photocapacitance spectroscopy was developed to quantify electrically active defects in the oxides. Defects with concentrations as low as 10{sup 14} cm{sup -3} were observed and their properties determined. A new model was developed for the electronic transport properties of intrinsic and extrinsic BaTiO{sub 3}. A transport model was proposed whereby conduction in La doped films occurs via hopping in localized states within a pseudogap formed between a lower Hubbard band and the conduction band edge. The influence of the size effect on the ferroelectric phase transition in the thin films was investigated. The

  17. Detection of driver pathways using mutated gene network in cancer.

    PubMed

    Li, Feng; Gao, Lin; Ma, Xiaoke; Yang, Xiaofei

    2016-06-21

    Distinguishing driver pathways has been extensively studied because they are critical for understanding the development and molecular mechanisms of cancers. Most existing methods for driver pathways are based on high coverage as well as high mutual exclusivity, with the underlying assumption that mutations are exclusive. However, in many cases, mutated driver genes in the same pathways are not strictly mutually exclusive. Based on this observation, we propose an index for quantifying mutual exclusivity between gene pairs. Then, we construct a mutated gene network for detecting driver pathways by integrating the proposed index and coverage. The detection of driver pathways on the mutated gene network consists of two steps: raw pathways are obtained using a CPM method, and the final driver pathways are selected using a strict testing strategy. We apply this method to glioblastoma and breast cancers and find that our method is more accurate than state-of-the-art methods in terms of enrichment of KEGG pathways. Furthermore, the detected driver pathways intersect with well-known pathways with moderate exclusivity, which cannot be discovered using the existing algorithms. In conclusion, the proposed method provides an effective way to investigate driver pathways in cancers. PMID:27118146

  18. 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.

  19. Fanconi Anemia: A Signal Transduction and DNA Repair Pathway

    PubMed Central

    Kupfer, Gary M.

    2013-01-01

    Fanconi anemia (FA) is a fascinating, rare genetic disorder marked by congenital defects, bone marrow failure, and cancer susceptibility. Research in recent years has led to the elucidation of FA as a DNA repair disorder and involved multiple pathways as well as having wide applicability to common cancers, including breast, ovarian, and head and neck. This review will describe the clinical aspects of FA as well as the current state of its molecular pathophysiology. In particular, work from the Kupfer laboratory will be described that demonstrates how the FA pathway interacts with multiple DNA repair pathways, including the mismatch repair system and signal transduction pathway of the DNA damage response. PMID:24348213

  20. Transformation pathways of liposomes.

    PubMed

    Hotani, H

    1984-09-01

    Liposomes undergoing transformation were observed by dark-field light microscopy in order to study the role of lipid in morphogenesis of biological vesicular structures. Liposomes were found to transform sequentially in a well-defined manner through one of several transformation pathways. A circular biconcave form was an initial shape in all the pathways and it transformed into a stable thin flexible filament or small spheres via a variety of regularly shaped vesicles which possessed geometrical symmetry. The transformation was reversible up to a certain point in each pathway. Osmotic pressure was found to be the driving force for the transformations. Biological membrane vesicles such as trypsinized red cell ghosts also transformed by similar pathways. PMID:6548263

  1. 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

  2. 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

  3. Secretory Pathway of Trypanosomatid Parasites

    PubMed Central

    McConville, Malcolm J.; Mullin, Kylie A.; Ilgoutz, Steven C.; Teasdale, Rohan D.

    2002-01-01

    The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs. PMID:11875130

  4. 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.

  5. 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

  6. 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.

  7. Competence across Europe: Highest Common Factor or Lowest Common Denominator?

    ERIC Educational Resources Information Center

    Winterton, Jonathan

    2009-01-01

    Purpose: The purpose of this article is to explore diversity in competence models across Europe and consider the extent to which there is sufficient common ground for a common European approach to underpin the European Qualifications Framework. Design/methodology/approach: The paper uses a literature review and interviews with policy makers.…

  8. 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…

  9. Lunar and Martian hardware commonality

    NASA Technical Reports Server (NTRS)

    Davis, Hubert P.; Johnson, Robert E.; Phillips, Paul G.; Spear, Donald S.; Stump, William R.; Williams, Franklin U.

    1986-01-01

    A number of different hardware elements were examined for possible Moon/Mars program commonality. These include manned landers; cargo landers, a trans-Mars injection (TMI) stage, traverse vehicles, unmanned surface rovers, habitation modules, and power supplies. Preliminary analysis indicates that it is possible to build a common two-stage manned lander. A single-stage, reusable lander may be practical for the lunar cast, but much less so for the Martian case, and commonality may therefore exist only at the subsystem level. A modified orbit transfer vehicle was examined as a potential cargo lander. Potential cargoes to various destinations were calculated for a Shuttle external tank sized TMI stage. A nuclear powered, long range traverse vehicle was conceptually designed and commonality is considered feasible. Short range, unmanned rovers can be made common without great effort. A surface habitation module may be difficult to make common due to difficulties in landing certain shapes on the Martian surface with aerobraking landers. Common nuclear power sources appear feasible. High temperature radiators appear easy to make common. Low temperature radiators may be difficult to make common. In most of these cases, Martian requirements determine the design.

  10. Identifying Branched Metabolic Pathways by Merging Linear Metabolic Pathways

    NASA Astrophysics Data System (ADS)

    Heath, Allison P.; Bennett, George N.; Kavraki, Lydia E.

    This paper presents a graph-based algorithm for identifying complex metabolic pathways in multi-genome scale metabolic data. These complex pathways are called branched pathways because they can arrive at a target compound through combinations of pathways that split compounds into smaller ones, work in parallel with many compounds, and join compounds into larger ones. While most previous work has focused on identifying linear metabolic pathways, branched metabolic pathways predominate in metabolic networks. Automatic identification of branched pathways has a number of important applications in areas that require deeper understanding of metabolism, such as metabolic engineering and drug target identification. Our algorithm utilizes explicit atom tracking to identify linear metabolic pathways and then merges them together into branched metabolic pathways. We provide results on two well-characterized metabolic pathways that demonstrate that this new merging approach can efficiently find biologically relevant branched metabolic pathways with complex structures.

  11. 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.

  12. Delineating the Biosynthesis of Gentamicin X2, the Common Precursor of the Gentamicin C Antibiotic Complex

    PubMed Central

    Huang, Chuan; Huang, Fanglu; Moison, Eileen; Guo, Junhong; Jian, Xinyun; Duan, Xiaobo; Deng, Zixin; Leadlay, Peter F.; Sun, Yuhui

    2015-01-01

    Summary Gentamicin C complex is a mixture of aminoglycoside antibiotics used worldwide to treat severe Gram-negative bacterial infections. Despite its clinical importance, the enzymology of its biosynthetic pathway has remained obscure. We report here insights into the four enzyme-catalyzed steps that lead from the first-formed pseudotrisaccharide gentamicin A2 to gentamicin X2, the last common intermediate for all components of the C complex. We have used both targeted mutations of individual genes and reconstitution of portions of the pathway in vitro to show that the secondary alcohol function at C-3″ of A2 is first converted to an amine, catalyzed by the tandem operation of oxidoreductase GenD2 and transaminase GenS2. The amine is then specifically methylated by the S-adenosyl-l-methionine (SAM)-dependent N-methyltransferase GenN to form gentamicin A. Finally, C-methylation at C-4″ to form gentamicin X2 is catalyzed by the radical SAM-dependent and cobalamin-dependent enzyme GenD1. PMID:25641167

  13. Genomic Gene Clustering Analysis of Pathways in Eukaryotes

    PubMed Central

    Lee, Jennifer M.; Sonnhammer, Erik L.L.

    2003-01-01

    Genomic clustering of genes in a pathway is commonly found in prokaryotes due to transcriptional operons, but these are not present in most eukaryotes. Yet, there might be clustering to a lesser extent of pathway members in eukaryotic genomes, that assist coregulation of a set of functionally cooperating genes. We analyzed five sequenced eukaryotic genomes for clustering of genes assigned to the same pathway in the KEGG database. Between 98% and 30% of the analyzed pathways in a genome were found to exhibit significantly higher clustering levels than expected by chance. In descending order by the level of clustering, the genomes studied were Saccharomyces cerevisiae, Homo sapiens, Caenorhabditis elegans, Arabidopsis thaliana, and Drosophila melanogaster. Surprisingly, there is not much agreement between genomes in terms of which pathways are most clustered. Only seven of 69 pathways found in all species were significantly clustered in all five of them. This species-specific pattern of pathway clustering may reflect adaptations or evolutionary events unique to a particular lineage. We note that although operons are common in C. elegans, only 58% of the pathways showed significant clustering, which is less than in human. Virtually all pathways in S. cerevisiae showed significant clustering. PMID:12695325

  14. 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

  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. 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

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

    PubMed Central

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

    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. PMID:22179583

  18. 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

  19. 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

  20. 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

  1. Connecticut's Common Core of Learning.

    ERIC Educational Resources Information Center

    Connecticut State Dept. of Education, Hartford. Bureau of Curriculum and Instruction.

    Since its adoption in January 1987, Connecticut's Common Core of Learning has set the standard of an educated citizen for the state, and the five 1991-1995 Statewide Educational Goals for Students incorporate its policy on the skills, knowledge and attitudes that are expected of Connecticut's public secondary school graduates. The Common Core…

  2. 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.

  3. 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…

  4. 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…

  5. Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production.

    PubMed

    Kang, Aram; George, Kevin W; Wang, George; Baidoo, Edward; Keasling, Jay D; Lee, Taek Soon

    2016-03-01

    Branched C5 alcohols are promising biofuels with favorable combustion properties. A mevalonate (MVA)-based isoprenoid biosynthetic pathway for C5 alcohols was constructed in Escherichia coli using genes from several organisms, and the pathway was optimized to achieve over 50% theoretical yield. Although the MVA pathway is energetically less efficient than the native methylerythritol 4-phosphate (MEP) pathway, implementing the MVA pathway in bacterial hosts such as E. coli is advantageous due to its lack of endogenous regulation. The MVA and MEP pathways intersect at isopentenyl diphosphate (IPP), the direct precursor to isoprenoid-derived C5 alcohols and initial precursor to longer chain terpenes, which makes independent regulation of the pathways difficult. In pursuit of the complete "decoupling" of the MVA pathway from native cellular regulation, we designed novel IPP-bypass MVA pathways for C5 alcohol production by utilizing promiscuous activities of two enzymes, phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA). These bypass pathways have reduced energetic requirements, are further decoupled from intrinsic regulation, and are free from IPP-related toxicity. In addition to these benefits, we demonstrate that reduced aeration rate has less impact on the bypass pathway than the original MVA pathway. Finally, we showed that performance of the bypass pathway was primarily determined by the activity of PMD. We designed PMD mutants with improved activity and demonstrated titer increases in the mutant strains. These modified pathways would be a good platform for industrial production of isopentenol and related chemicals such as isoprene. PMID:26708516

  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 of Transport Protein Evolution: Recent Advances

    PubMed Central

    Lam, Vincent H.; Lee, Jong-Hoon; Silverio, Abe; Chan, Henry; Gomolplitinant, Kenny M.; Povolotsky, Tatyana L.; Orlova, Ekaterina; Sun, Eric I.; Welliver, Carl H.; Saier, Milton H.

    2014-01-01

    We herein report recent advances in our understanding of transport protein evolution. The Drug-Metabolite Transporter (DMT) superfamily (TC# 2.A.7) arose from a 2TMS precursor to give 4TMS proteins which then added one and duplicated to give 10. The proposed pathway is 2 –> 4 –> 5 –> 10. This superfamily provides a rare example where all proposed topological intermediates in this evolutionary pathway have been identified in current protein databases. Another family, the Oligopeptide Transporter (OPT) family (TC# 2.A.67), also started with a 2 TMS peptide precursor, but it followed the pathway: Only 16 and 17 TMS OPT family members have been identified in current databases. The TRIC family of K+ channels, characterized in animals, arose via the pathway: where the seventh TMS was added c-terminally to the 6 TMS precursor that resulted from a 3 TMS duplication. Surprisingly, animal TRIC channels proved to have numerous 7 TMS homologues in prokaryotes, none of which had been identified previously. We found that two families of integral membrane proteins gave rise to multiple current topological types. Members of the SdpC killer factor immunity protein family, SdpI (TC# 9.A.32) probably arose via the pathway: while members of the Heme Handling Protein (HHP) Family (TC# 9.B.14) arose via the pathway: Predictions are also made for an evolutionary pathway giving rise to the seven topological types of P-type ATPases so far identified in the P-ATPase superfamily. Finally, the ubiquitous CDF carriers (TC# 1.A.4) of 6TMSs probably gave rise to CRAC channels of 4TMSs by loss of the first two TMSs an unusual example of retroevolution. PMID:21194372

  8. Embryonic myogenesis pathways in muscle regeneration.

    PubMed

    Zhao, Po; Hoffman, Eric P

    2004-02-01

    Embryonic myogenesis involves the staged induction of myogenic regulatory factors and positional cues that dictate cell determination, proliferation, and differentiation into adult muscle. Muscle is able to regenerate after damage, and muscle regeneration is generally thought to recapitulate myogenesis during embryogenesis. There has been considerable progress in the delineation of myogenesis pathways during embryogenesis, but it is not known whether the same signaling pathways are relevant to muscle regeneration in adults. Here, we defined the subset of embryogenesis pathways induced in muscle regeneration using a 27 time-point in vivo muscle regeneration series. The embryonic Wnt (Wnt1, 3a, 7a, 11), Shh pathway, and the BMP (BMP2, 4, 7) pathway were not induced during muscle regeneration. Moreover, antagonists of Wnt signaling, sFRP1, sFRP2, and sFRP4 (secreted frizzled-related proteins) were significantly up-regulated, suggesting active inhibition of the Wnt pathway. The pro-differentiation FGFR4 pathway was transiently expressed at day 3, commensurate with expression of MyoD, Myogenin, Myf5, and Pax7. Protein verification studies showed fibroblast growth factor receptor 4 (FGFR4) protein to be strongly expressed in differentiating myoblasts and newly formed myotubes. We present evidence that FGF6 is likely the key ligand for FGFR4 during muscle regeneration, and further suggest that FGF6 is released from necrotic myofibers where it is then sequestered by basal laminae. We also confirmed activation of Notch1 in the regenerating muscle. Finally, known MyoD coactivators (MEF2A, p/CIP, TCF12) and repressors (Twist, Id2) were strongly induced at appropriate time points. Taken together, our results suggest that embryonic positional signals (Wnt, Shh, and BMP) are not induced in postnatal muscle regeneration, whereas cell-autonomous factors (Pax7, MRFs, FGFR4) involving muscle precursor proliferation and differentiation are recapitulated by muscle regeneration. PMID

  9. Bacterial Fatty Acid Synthesis and its Relationships with Polyketide Synthetic Pathways

    PubMed Central

    Cronan, John E.; Thomas, Jacob

    2014-01-01

    This review presents the most thoroughly studied bacterial fatty acid synthetic pathway, that of Escherichia coli and then discusses the exceptions to the E. coli pathway present in other bacteria. The known interrelationships between the fatty acid and polyketide synthetic pathways are also assessed, mainly in the Streptomyces group of bacteria. Finally, we present a compendium of methods for analysis of bacterial fatty acid synthetic pathways. PMID:19362649

  10. 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

  11. Pathways to chromothripsis

    PubMed Central

    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

  12. Common variable immunodeficiency: etiological and treatment issues.

    PubMed

    Deane, Sean; Selmi, Carlo; Naguwa, Stanley M; Teuber, Suzanne S; Gershwin, M Eric

    2009-01-01

    One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients. PMID:19571563

  13. Common Variable Immunodeficiency: Etiological and Treatment Issues

    PubMed Central

    Deane, Sean; Selmi, Carlo; Naguwa, Stanley M.; Teuber, Suzanne S.; Gershwin, M. Eric

    2009-01-01

    One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients. PMID:19571563

  14. Concordant Signaling Pathways Produced by Pesticide Exposure in Mice Correspond to Pathways Identified in Human Parkinson's Disease

    PubMed Central

    Gollamudi, Seema; Johri, Ashu; Calingasan, Noel Y.; Yang, Lichuan; Elemento, Olivier; Beal, M. Flint

    2012-01-01

    Parkinson's disease (PD) is a neurodegenerative disease in which the etiology of 90 percent of the patients is unknown. Pesticide exposure is a major risk factor for PD, and paraquat (PQ), pyridaben (PY) and maneb (MN) are amongst the most widely used pesticides. We studied mRNA expression using transcriptome sequencing (RNA-Seq) in the ventral midbrain (VMB) and striatum (STR) of PQ, PY and paraquat+maneb (MNPQ) treated mice, followed by pathway analysis. We found concordance of signaling pathways between the three pesticide models in both the VMB and STR as well as concordance in these two brain areas. The concordant signaling pathways with relevance to PD pathogenesis were e.g. axonal guidance signaling, Wnt/β-catenin signaling, as well as pathways not previously linked to PD, e.g. basal cell carcinoma, human embryonic stem cell pluripotency and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Human PD pathways previously identified by expression analysis, concordant with VMB pathways identified in our study were axonal guidance signaling, Wnt/β-catenin signaling, IL-6 signaling, ephrin receptor signaling, TGF-β signaling, PPAR signaling and G-protein coupled receptor signaling. Human PD pathways concordant with the STR pathways in our study were Wnt/β-catenin signaling, axonal guidance signaling and G-protein coupled receptor signaling. Peroxisome proliferator activated receptor delta (Ppard) and G-Protein Coupled Receptors (GPCRs) were common genes in VMB and STR identified by network analysis. In conclusion, the pesticides PQ, PY and MNPQ elicit common signaling pathways in the VMB and STR in mice, which are concordant with known signaling pathways identified in human PD, suggesting that these pathways contribute to the pathogenesis of idiopathic PD. The analysis of these networks and pathways may therefore lead to improved understanding of disease pathogenesis, and potential novel therapeutic targets. PMID:22563483

  15. 6 Common Cancers - Lung Cancer

    MedlinePlus

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

  16. 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 ...

  17. 6 Common Cancers - Breast Cancer

    MedlinePlus

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

  18. Misconceptions about Acne Still Common

    MedlinePlus

    ... gov/medlineplus/news/fullstory_157613.html Misconceptions About Acne Still Common Skin condition isn't caused by ... of negative and mistaken beliefs about people with acne, a new study finds. Researchers showed photos of ...

  19. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

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

  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. 6 Common Cancers - Prostate Cancer

    MedlinePlus

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

  2. 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 ...

  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. Common Skin Diseases in Children

    PubMed Central

    Taradash, J. B.

    1976-01-01

    Six common pediatric skin problems are discussed through the use of case histories. Problems of differential diagnosis are outlined, and the various steps and pitfalls in therapy itemized. PMID:21308018

  5. 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 ( ...

  6. 6 Common Cancers - Lung Cancer

    MedlinePlus

    ... Bar 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 next ...

  7. 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

  8. 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

  9. 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…

  10. 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…

  11. 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. PMID:27382185

  12. Hedgehog Pathway Inhibition.

    PubMed

    Sekulic, Aleksandar; Von Hoff, Daniel

    2016-02-25

    The hedgehog (Hh) signaling pathway is aberrantly activated in a majority of basal cell carcinomas (BCC). Vismodegib and sonidegib are targeted inhibitors of Smoothened (SMO). Both drugs are approved for use in locally advanced BCC (laBCC), with vismodegib also approved for metastatic BCC (mBCC). PMID:26919418

  13. 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

  14. 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. PMID:26130661

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

    PubMed Central

    Zeng, Hui; 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. Database URL: http://www.cuilab.cn/drugpath PMID:26130661

  16. Cell signalling pathways underlying induced pluripotent stem cell reprogramming

    PubMed Central

    Hawkins, Kate; Joy, Shona; McKay, Tristan

    2014-01-01

    Induced pluripotent stem (iPS) cells, somatic cells reprogrammed to the pluripotent state by forced expression of defined factors, represent a uniquely valuable resource for research and regenerative medicine. However, this methodology remains inefficient due to incomplete mechanistic understanding of the reprogramming process. In recent years, various groups have endeavoured to interrogate the cell signalling that governs the reprogramming process, including LIF/STAT3, BMP, PI3K, FGF2, Wnt, TGFβ and MAPK pathways, with the aim of increasing our understanding and identifying new mechanisms of improving safety, reproducibility and efficiency. This has led to a unified model of reprogramming that consists of 3 stages: initiation, maturation and stabilisation. Initiation of reprogramming occurs in almost all cells that receive the reprogramming transgenes; most commonly Oct4, Sox2, Klf4 and cMyc, and involves a phenotypic mesenchymal-to-epithelial transition. The initiation stage is also characterised by increased proliferation and a metabolic switch from oxidative phosphorylation to glycolysis. The maturation stage is considered the major bottleneck within the process, resulting in very few “stabilisation competent” cells progressing to the final stabilisation phase. To reach this stage in both mouse and human cells, pre-iPS cells must activate endogenous expression of the core circuitry of pluripotency, comprising Oct4, Sox2, and Nanog, and thus reach a state of transgene independence. By the stabilisation stage, iPS cells generally use the same signalling networks that govern pluripotency in embryonic stem cells. These pathways differ between mouse and human cells although recent work has demonstrated that this is context dependent. As iPS cell generation technologies move forward, tools are being developed to interrogate the process in more detail, thus allowing a greater understanding of this intriguing biological phenomenon. PMID:25426259

  17. NODAL PATHWAY GENES ARE DOWNREGULATED IN FACIAL ASYMMETRY

    PubMed Central

    Nicot, Romain; Hottenstein, Molly; Raoul, Gwenael; Ferri, Joel; Horton, Michael; Tobias, John W.; Barton, Elisabeth; Gelé, Patrick; Sciote, James J.

    2014-01-01

    Purpose Facial asymmetry is a common comorbid condition in patients with jaw deformation malocclusion. Heritability of malocclusion is advancing rapidly, but very little is known regarding genetic contributions to asymmetry. This study identifies differences in expression of key asymmetry-producing genes which are down regulated in facial asymmetry patients. Material and Methods Masseter muscle samples were collected during BSSO orthognathic surgery to correct skeletal-based malocclusion. Patients were classified as Class II or III and open or deep bite malocclusion with or without facial asymmetry. Muscle samples were analyzed for gene expression differences on Affymetrix HT2.0 microarray global expression chips. Results Overall gene expression was different for asymmetric patients compared to other malocclusion classifications by principal component analysis (P<0.05). We identified differences in the nodal signaling pathway (NSP) which promotes development of mesoderm and endoderm and left-right patterning during embryogenesis. Nodal and Lefty expression was 1.39–1.84 fold greater (P<3.41×10−5) whereas integral membrane Nodal-modulators Nomo1,2,3 were −5.63 to −5.81 (P<3.05×10−4) less in asymmetry subjects. Fold differences among intracellular pathway members were negative in the range of −7.02 to −2.47 (P<0.003). Finally Pitx2, a upstream effector of Nodal known to influence the size of type II skeletal muscle fibers was also significantly decreased in facial asymmetry (P<0.05). Conclusions When facial asymmetry is part of skeletal malocclusion there are decreases of NSP genes in masseter muscle. This data suggests that the NSP is down regulated to help promote development of asymmetry. Pitx2 expression differences also contributed to both skeletal and muscle development in this condition. PMID:25364968

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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…

  3. Common Ground: Finding Commonalities in Diverse Musical Material

    ERIC Educational Resources Information Center

    Gault, Brent

    2006-01-01

    The article focuses on teaching commonalities in diverse musical genres. Teachers need to relate the musical activities performed in class to music that students experience in the world around them since they understand music in relation to history and culture. A key to selecting high-quality musical examples is to find music pieces that contain…

  4. 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…

  5. Perturbations to the hedgehog pathway in sea urchin embryos.

    PubMed

    Warner, Jacob F; McClay, David R

    2014-01-01

    The Hedgehog pathway has been shown to be an important developmental signaling pathway in many organisms (Ingham and McMahon. Genes Dev 15:3059-3087, 2001). Recently that work has been extended to developing echinoderm embryos (Walton et al. Dev Biol 331(1):26-37, 2009). Here we describe several methods to perturb the Hedgehog signaling pathway in the sea urchin. These include microinjection of Morpholinos and mRNA constructs as well as treatments with small molecule inhibitors. Finally we provide simple methods for assaying Hedgehog phenotypes in the sea urchin embryo. PMID:24567217

  6. 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

  7. Common Emergencies in Pet Birds.

    PubMed

    Stout, Jane D

    2016-05-01

    Treating avian emergencies can be a challenging task. Pet birds often mask signs of illness until they are critically ill and require quick initiation of supportive care with minimal handling to stabilize them. This article introduces the clinician to common avian emergency presentations and details initial therapeutics and diagnostics that can be readily performed in the small-animal emergency room. Common disease presentations covered include respiratory and extrarespiratory causes of dyspnea, gastrointestinal signs, reproductive disease, neurologic disorders, trauma, and toxin exposure. The duration and severity of the avian patient's disease and the clinician's initiation of appropriate therapy often determines clinical outcome. PMID:26948267

  8. Systematic tracking of altered modules identifies disrupted pathways in teratozoospermia.

    PubMed

    Huang, Z Q; Wang, G X; Jiang, X L; Tian, E P; Yao, W L; Zeng, T

    2016-01-01

    The objective of this study was to identify disrupted pathways in teratozoospermia by systematically tracking dysregulated modules in reweighted protein-protein interaction (PPI) networks. We inferred and reweighted the PPI networks of normal and teratozoospermia groups based on Spearman correlation coefficients. Modules in the PPI networks were explored via a clique-merging algorithm and altered modules were identified based on maximum weight bipartite matching. Furthermore, pathway-enrichment analyses of genes in altered modules were performed by Database for Annotation, Visualization, and Integrated Discovery (DAVID) to illuminate the biological pathways in teratozoospermia. A total of 20,102 genes were screened from the expression profile. We explored 2406 and 2101 modules in normal and disease PPI networks, respectively. Moreover, we obtained 875 altered modules by comparing modules in normal and teratozoospermia PPI networks. At P < 0.01, the genes involved in 2855 interactions with score changes >1 were mainly enriched in 66 pathways and the genes in altered modules were enriched in 71 pathways. The activity genes (missed and added genes in the disrupted modules) were enriched in 41 common pathways. There were 36 mutual enriched pathways under the five different conditions. Moreover, the cell cycle pathway was disrupted in the first 10 pathways of each condition. This study provides a powerful biomarker discovery platform to better understand the progression of teratozoospermia by systematically tracking dysregulated modules. This method uncovered potential diagnostic and therapeutic targets of teratozoospermia. This information might lead to improved monitoring and treatment of teratozoospermia. PMID:27173237

  9. 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

  10. 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.

  11. Does Training Affect Growth? Answers to Common Questions.

    ERIC Educational Resources Information Center

    Daly, Robin M.; Bass, Shona; Caine, Dennis; Howe, Warren

    2002-01-01

    Adolescent athletes may be at risk of restricted growth and delayed maturation when combining intense training with insufficient energy intake. Because catch-up growth commonly occurs with reduced training, final adult stature is generally not compromised. However, in athletes with long-term, clinically delayed maturation, catch-up growth may be…

  12. 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...

  13. Dispositional Statements on Student Teacher Evaluation Instruments: Commonalities across Institutions

    ERIC Educational Resources Information Center

    Young, Alice; Wilkins, Elizabeth

    2008-01-01

    The purpose of this study was to investigate summative student teacher evaluation instruments to determine the most common dispositions evaluated by teacher preparatory programs. Thirty-two (32) final student teaching instruments were purposely selected from across the United States and examined. Thirteen disposition categories emerged from the…

  14. 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.

  15. 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. PMID:21931786

  16. Master Regulators, Regulatory Networks, and Pathways of Glioblastoma Subtypes

    PubMed Central

    Bozdag, Serdar; Li, Aiguo; Baysan, Mehmet; Fine, Howard A

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common malignant brain tumor. GBM samples are classified into subtypes based on their transcriptomic and epigenetic profiles. Despite numerous studies to better characterize GBM biology, a comprehensive study to identify GBM subtype- specific master regulators, gene regulatory networks, and pathways is missing. Here, we used FastMEDUSA to compute master regulators and gene regulatory networks for each GBM subtype. We also ran Gene Set Enrichment Analysis and Ingenuity Pathway Analysis on GBM expression dataset from The Cancer Genome Atlas Project to compute GBM- and GBM subtype-specific pathways. Our analysis was able to recover some of the known master regulators and pathways in GBM as well as some putative novel regulators and pathways, which will aide in our understanding of the unique biology of GBM subtypes. PMID:25368508

  17. 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

  18. 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…

  19. Common Types of Heart Defects

    MedlinePlus

    ... American Heart area Search by State SELECT YOUR LANGUAGE Español (Spanish) 简体中文 (Traditional Chinese) 繁体中文 (Simplified Chinese) ... heart defect, treatment options and expected results. The descriptions and pictures of common heart defects that follow ...

  20. Common problems in gastrointestinal radiology

    SciTech Connect

    Thompson, W.M.

    1989-01-01

    This book covers approximately 70 common diagnostic problems in gastro-intestinal radiology. Each problem, includes a short illustrated case history, a discussion of the radiologic findings, a general discussion of the case, the differential diagnosis, a description of the management of the problem or procedure used, and, where appropriate, the results of the therapy suggested.

  1. "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…

  2. 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…

  3. 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…

  4. 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…

  5. 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.…

  6. 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!

  7. The Common Vision. Reviews: Books.

    ERIC Educational Resources Information Center

    Chattin-McNichols, John

    1998-01-01

    Reviews Marshak's book describing the work of educators Maria Montessori, Rudolf Steiner, Aurobindo Ghose, and Inayat Khan. Maintains that the book gives clear, concise information on each educator and presents a common vision for children and their education; also maintains that it gives theoretical and practical information and discusses…

  8. 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…

  9. 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…

  10. 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…

  11. 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

  12. Common Protocols for Shared Communities.

    ERIC Educational Resources Information Center

    Bull, Glen; Bull, Gina; Sigmon, Tim

    1997-01-01

    Although it is becoming easier to share materials via the Internet, the process is still not transparent, especially when cross-platform transfers are involved. This article reviews common protocols and discusses several utilities and strategies for exchanging information online. Includes a table listing transfer and compression protocols, common…

  13. 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…

  14. Common Ground: Opportunities and Possibilities.

    ERIC Educational Resources Information Center

    Kraft, M. Katherine; Muck, Randolph; Bazemore, Gordon

    2001-01-01

    Wraps up a theme issue that explores the common ground between the restorative justice and community justice movements and examines their effect on substance-abusing youth and the communities in which they reside. Suggests that restorative justice programs may help adolescent treatment providers in their adoption of practices to promote change and…

  15. Leadership in Education: Five Commonalities.

    ERIC Educational Resources Information Center

    Goldberg, Marc A.

    2001-01-01

    Reflecting on 43 interviews with eminent educational leaders from all backgrounds and political stripes, the author isolates five common characteristics: a bedrock belief in their work's usefulness, courage to swim upstream on behalf of their beliefs, possession of a social conscience, seriousness of purpose, and situational mastery. (MLH)

  16. Interaction of SecB with intermediates along the folding pathway of maltose-binding protein.

    PubMed Central

    Diamond, D. L.; Strobel, S.; Chun, S. Y.; Randall, L. L.

    1995-01-01

    SecB, a molecular chaperone involved in protein export in Escherichia coli, displays the remarkable ability to selectively bind many different polypeptide ligands whose only common feature is that of being nonnative. The selectivity is explained in part by a kinetic partitioning between the folding of a polypeptide and its association with SecB. SecB has no affinity for native, stably folded polypeptides but interacts tightly with polypeptides that are nonnative. In order to better understand the nature of the binding, we have examined the interaction of SecB with intermediates along the folding pathway of maltose-binding protein. Taking advantage of forms of maltose-binding protein that are altered in their folding properties, we show that the first intermediate in folding, represented by the collapsed state, binds to SecB, and that the polypeptide remains active as a ligand until it crosses the final energy barrier to attain the native state. PMID:7549876

  17. Alternative Respiratory Pathway

    PubMed Central

    Siedow, James N.; Girvin, Mark E.

    1980-01-01

    Oxygen uptake during the first hours of imbibition in intact soybean and mung bean seeds showed a marked sensitivity to potassium cyanide but was unaffected by addition of either salicylhydroxamic acid or propyl gallate. However O2 uptake by finely ground seed particles was very sensitive to the addition of either compound. The results indicated that O2 uptake in intact, imbibing seeds was associated with a cyanide-sensitive process, most probably mitochondrial mediated respiration, and not the result of the cyanide-insensitive lipoxygenase activity which was readily detectable in ground seed particles. The antioxidant propyl gallate was found to inhibit specifically alternative pathway electron transfer in isolated mung bean mitochondria. Half-maximal inhibition occurred with 2 to 5 micromolar propyl gallate. Kinetic analysis indicated that propyl gallate inhibition of the alternative pathway occurred at, or very near, the site of inhibition of the alternative pathway by salicylhydroxamic acid. A high level of lipoxygenase activity was found to be associated with washed mitochondria isolated from a variety of etiolated plant tissues. Most of this lipoxygenase activity could be eliminated from mung bean mitochondria if the mitochondria were purified on a discontinuous sucrose gradient. This indicated that the mitochondrial-associated activity was probably the result of nonspecific adsorption of lipoxygenase onto the mitochondrial membranes during isolation. PMID:16661259

  18. 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

  19. 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.

  20. Linking multiple pathogenic pathways in Alzheimer's disease.

    PubMed

    Bou Khalil, Rami; Khoury, Elie; Koussa, Salam

    2016-06-22

    Alzheimer's disease (AD) is a chronic neurodegenerative disorder presenting as progressive cognitive decline with dementia that does not, to this day, benefit from any disease-modifying drug. Multiple etiologic pathways have been explored and demonstrate promising solutions. For example, iron ion chelators, such as deferoxamine, are a potential therapeutic solution around which future studies are being directed. Another promising domain is related to thrombin inhibitors. In this minireview, a common pathophysiological pathway is suggested for the pathogenesis of AD to prove that all these mechanisms converge onto the same cascade of neuroinflammatory events. This common pathway is initiated by the presence of vascular risk factors that induce brain tissue hypoxia, which leads to endothelial cell activation. However, the ensuing hypoxia stimulates the production and release of reactive oxygen species and pro-inflammatory proteins. Furthermore, the endothelial activation may become excessive and dysfunctional in predisposed individuals, leading to thrombin activation and iron ion decompartmentalization. The oxidative stress that results from these modifications in the neurovascular unit will eventually lead to neuronal and glial cell death, ultimately leading to the development of AD. Hence, future research in this field should focus on conducting trials with combinations of potentially efficient treatments, such as the combination of intranasal deferoxamine and direct thrombin inhibitors. PMID:27354962

  1. 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

  2. N-Acetylgalactosamine Utilization Pathway and Regulon in Proteobacteria

    PubMed Central

    Leyn, Semen A.; Gao, Fang; Yang, Chen; Rodionov, Dmitry A.

    2012-01-01

    We used a comparative genomics approach to reconstruct the N-acetyl-d-galactosamine (GalNAc) and galactosamine (GalN) utilization pathways and transcriptional regulons in Proteobacteria. The reconstructed GalNAc/GalN utilization pathways include multiple novel genes with specific functional roles. Most of the pathway variations were attributed to the amino sugar transport, phosphorylation, and deacetylation steps, whereas the downstream catabolic enzymes in the pathway were largely conserved. The predicted GalNAc kinase AgaK, the novel variant of GalNAc-6-phosphate deacetylase AgaAII and the GalN-6-phosphate deaminase AgaS from Shewanella sp. ANA-3 were validated in vitro using individual enzymatic assays and reconstitution of the three-step pathway. By using genetic techniques, we confirmed that AgaS but not AgaI functions as the main GalN-6-P deaminase in the GalNAc/GalN utilization pathway in Escherichia coli. Regulons controlled by AgaR repressors were reconstructed by bioinformatics in most proteobacterial genomes encoding GalNAc pathways. Candidate AgaR-binding motifs share a common sequence with consensus CTTTC that was found in multiple copies and arrangements in regulatory regions of aga genes. This study provides comprehensive insights into the common and distinctive features of the GalNAc/GalN catabolism and its regulation in diverse Proteobacteria. PMID:22711537

  3. 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.

  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. 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

  6. 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…

  7. Pathway-based approaches to the treatment of inflammatory bowel disease.

    PubMed

    Bamias, Giorgos; Pizarro, Theresa T; Cominelli, Fabio

    2016-01-01

    Crohn's disease and ulcerative colitis, collectively termed inflammatory bowel disease (IBD), are immunologic disorders that represent the prototypes of chronic intestinal inflammation. Their pathogenesis involves the dysregulated interaction between the intestinal microbiota and the gut-associated mucosal immune system that takes place when genetically predisposed individuals are exposed to detrimental environmental triggers. In recent years, the therapeutic dogma in IBD has shifted away from the administration of nonspecific immunosuppressives toward a pathway-based approach. In this review, we present an outlook of IBD treatment based on this new conceptual approach. Firstly, we will provide an overview of the major aspects of IBD pathogenesis with emphasis on specific pathway-based defects. Secondly, we will examine in detail the development of novel therapeutic approaches that can be used to target genetics, dysbiosis, the epithelial barrier, proinflammatory cytokines, and leukocyte trafficking. Most of these strategies are still in the developmental phase, but promising approaches include fecal microbiota transplantation as a means to correct IBD-related dysbiosis; administration of modified phosphatidylcholine to enhance the function of the intestinal mucous and tighten the defective epithelial barrier; the reduction of over-reactive proinflammatory pathways through the blockade of novel, nontumor necrosis factor inflammatory mediators via monoclonal antibodies against the common p40 chain of interleukin (IL-12) and IL-23, Janus kinase inhibitors, or antisense oligonucleotides against inhibitors of the immunosuppressive cytokine transforming growth factor-β1; and finally, inhibition of leukocyte trafficking to the gut via neutralization of the gut-specific α4β7 integrin. Availability of such diverse treatment modalities with specific pathway-based targets will increase the therapeutic options for patients with IBD. PMID:26408803

  8. Pathways with PathWhiz.

    PubMed

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

    2015-07-01

    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. 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

  10. Pathway Analysis of Smoking Quantity in Multiple GWAS Identifies Cholinergic and Sensory Pathways

    PubMed Central

    Harari, Oscar; Wang, Jen-Chyong; Bucholz, Kathleen; Edenberg, Howard J.; Heath, Andrew; Martin, Nicholas G.; Pergadia, Michele L.; Montgomery, Grant; Schrage, Andrew; Bierut, Laura J.; Madden, Pamela F.; Goate, Alison M.

    2012-01-01

    Cigarette smoking is a common addiction that increases the risk for many diseases, including lung cancer and chronic obstructive pulmonary disease. Genome-wide association studies (GWAS) have successfully identified and validated several susceptibility loci for nicotine consumption and dependence. However, the trait variance explained by these genes is only a small fraction of the estimated genetic risk. Pathway analysis complements single marker methods by including biological knowledge into the evaluation of GWAS, under the assumption that causal variants lie in functionally related genes, enabling the evaluation of a broad range of signals. Our approach to the identification of pathways enriched for multiple genes associated with smoking quantity includes the analysis of two studies and the replication of common findings in a third dataset. This study identified pathways for the cholinergic receptors, which included SNPs known to be genome-wide significant; as well as novel pathways, such as genes involved in the sensory perception of smell, that do not contain any single SNP that achieves that stringent threshold. PMID:23227220

  11. 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

  12. Common skin conditions during pregnancy.

    PubMed

    Tunzi, Marc; Gray, Gary R

    2007-01-15

    Common skin conditions during pregnancy generally can be separated into three categories: hormone-related, preexisting, and pregnancy-specific. Normal hormone changes during pregnancy may cause benign skin conditions including striae gravidarum (stretch marks); hyperpigmentation (e.g., melasma); and hair, nail, and vascular changes. Preexisting skin conditions (e.g., atopic dermatitis, psoriasis, fungal infections, cutaneous tumors) may change during pregnancy. Pregnancy-specific skin conditions include pruritic urticarial papules and plaques of pregnancy, prurigo of pregnancy, intrahepatic cholestasis of pregnancy, pemphigoid gestationis, impetigo herpetiformis, and pruritic folliculitis of pregnancy. Pruritic urticarial papules and plaques of pregnancy are the most common of these disorders. Most skin conditions resolve postpartum and only require symptomatic treatment. However, there are specific treatments for some conditions (e.g., melasma, intrahepatic cholestasis of pregnancy, impetigo herpetiformis, pruritic folliculitis of pregnancy). Antepartum surveillance is recommended for patients with intrahepatic cholestasis of pregnancy, impetigo herpetiformis, and pemphigoid gestationis. PMID:17263216

  13. 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

  14. 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.

  15. 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. PMID:25921681

  16. 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.

  17. The Common Geometry Module (CGM).

    SciTech Connect

    Tautges, Timothy James

    2004-12-01

    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 on 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 includes 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.

  18. PML Surfs into HIPPO Tumor Suppressor Pathway

    PubMed Central

    Strano, Sabrina; Fausti, Francesca; Di Agostino, Silvia; Sudol, Marius; Blandino, Giovanni

    2013-01-01

    Growth arrest, inhibition of cell proliferation, apoptosis, senescence, and differentiation are the most characterized effects of a given tumor suppressor response. It is becoming increasingly clear that tumor suppression results from the integrated and synergistic activities of different pathways. This implies that tumor suppression includes linear, as well as lateral, crosstalk signaling. The latter may happen through the concomitant involvement of common nodal proteins. Here, we discuss the role of Promyelocytic leukemia protein (PML) in functional cross-talks with the HIPPO and the p53 family tumor suppressor pathways. PML, in addition to its own anti-tumor activity, contributes to the assembly of an integrated and superior network that may be necessary for the maximization of the tumor suppressor response to diverse oncogenic insults. PMID:23459691

  19. An evolutionary approach for searching metabolic pathways.

    PubMed

    Gerard, Matias F; Stegmayer, Georgina; Milone, Diego H

    2013-11-01

    Searching metabolic pathways that relate two compounds is a common task in bioinformatics. This is of particular interest when trying, for example, to discover metabolic relations among compounds clustered with a data mining technique. Search strategies find sequences to relate two or more states (compounds) using an appropriate set of transitions (reactions). Evolutionary algorithms carry out the search guided by a fitness function and explore multiple candidate solutions using stochastic operators. In this work we propose an evolutionary algorithm for searching metabolic pathways between two compounds. The operators and fitness function employed are described and the effect of mutation rate is studied. Performance of this algorithm is compared with two classical search strategies. Source code and dataset are available at http://sourceforge.net/projects/sourcesinc/files/eamp/ PMID:24209916

  20. Studying lipids involved in the endosomal pathway.

    PubMed

    Bissig, Christin; Johnson, Shem; Gruenberg, Jean

    2012-01-01

    Endosomes along the degradation pathway exhibit a multivesicular appearance and differ in their lipid compositions. Association of proteins to specific membrane lipids and presumably also lipid-lipid interactions contribute to the formation of functional membrane platforms that regulate endosome biogenesis and function. This chapter provides a brief review of the functions of endosomal lipids in the degradation pathway, a discussion of techniques that allow studying lipid-based mechanisms and a selection of step-by-step protocols for in vivo and in vitro methods commonly used to study lipid roles in endocytosis. The techniques described here have been used to elucidate the function of the late endosomal lipid lysobisphosphatidic acid and allow the monitoring of lipid distribution, levels and dynamics, as well as the characterization of lipid-binding partners. PMID:22325596

  1. 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.

  2. 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

  3. 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

  4. Improving Carbon Fixation Pathways

    PubMed Central

    Ducat, Daniel C.

    2012-01-01

    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 alternative pathways and organisms can be utilized to fix atmospheric carbon dioxide into useful materials. PMID:22647231

  5. Growth hormone signaling pathways.

    PubMed

    Carter-Su, Christin; Schwartz, Jessica; Argetsinger, Lawrence S

    2016-06-01

    Over 20years ago, our laboratory showed that growth hormone (GH) signals through the GH receptor-associated tyrosine kinase JAK2. We showed that GH binding to its membrane-bound receptor enhances binding of JAK2 to the GHR, activates JAK2, and stimulates tyrosyl phosphorylation of both JAK2 and GHR. The activated JAK2/GHR complex recruits a variety of signaling proteins, thereby initiating multiple signaling pathways and cellular responses. These proteins and pathways include: 1) Stat transcription factors implicated in the expression of multiple genes, including the gene encoding insulin-like growth factor 1; 2) Shc adapter proteins that lead to activation of the grb2-SOS-Ras-Raf-MEK-ERK1,2 pathway; 3) insulin receptor substrate proteins implicated in the phosphatidylinositol-3-kinase and Akt pathway; 4) signal regulatory protein α, a transmembrane scaffold protein that recruits proteins including the tyrosine phosphatase SHP2; and 5) SH2B1, a scaffold protein that can activate JAK2 and enhance GH regulation of the actin cytoskeleton. Our recent work has focused on the function of SH2B1. We have shown that SH2B1β is recruited to and phosphorylated by JAK2 in response to GH. SH2B1 localizes to the plasma membrane, cytoplasm and focal adhesions; it also cycles through the nucleus. SH2B1 regulates the actin cytoskeleton and promotes GH-dependent motility of RAW264.7 macrophages. Mutations in SH2B1 have been found in humans exhibiting severe early-onset childhood obesity and insulin resistance. These mutations impair SH2B1 enhancement of GH-induced macrophage motility. As SH2B1 is expressed ubiquitously and is also recruited to a variety of receptor tyrosine kinases, our results raise the possibility that effects of SH2B1 on the actin cytoskeleton in various cell types, including neurons, may play a role in regulating body weight. PMID:26421979

  6. 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.

  7. The Reactome pathway knowledgebase.

    PubMed

    Croft, David; Mundo, Antonio Fabregat; Haw, Robin; Milacic, Marija; Weiser, Joel; Wu, Guanming; Caudy, Michael; Garapati, Phani; Gillespie, Marc; Kamdar, Maulik R; Jassal, Bijay; Jupe, Steven; Matthews, Lisa; May, Bruce; Palatnik, Stanislav; Rothfels, Karen; Shamovsky, Veronica; Song, Heeyeon; Williams, Mark; Birney, Ewan; Hermjakob, Henning; Stein, Lincoln; D'Eustachio, Peter

    2014-01-01

    Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation. PMID:24243840

  8. Sequential activation of metabolic pathways: a dynamic optimization approach.

    PubMed

    Oyarzún, Diego A; Ingalls, Brian P; Middleton, Richard H; Kalamatianos, Dimitrios

    2009-11-01

    The regulation of cellular metabolism facilitates robust cellular operation in the face of changing external conditions. The cellular response to this varying environment may include the activation or inactivation of appropriate metabolic pathways. Experimental and numerical observations of sequential timing in pathway activation have been reported in the literature. It has been argued that such patterns can be rationalized by means of an underlying optimal metabolic design. In this paper we pose a dynamic optimization problem that accounts for time-resource minimization in pathway activation under constrained total enzyme abundance. The optimized variables are time-dependent enzyme concentrations that drive the pathway to a steady state characterized by a prescribed metabolic flux. The problem formulation addresses unbranched pathways with irreversible kinetics. Neither specific reaction kinetics nor fixed pathway length are assumed.In the optimal solution, each enzyme follows a switching profile between zero and maximum concentration, following a temporal sequence that matches the pathway topology. This result provides an analytic justification of the sequential activation previously described in the literature. In contrast with the existent numerical approaches, the activation sequence is proven to be optimal for a generic class of monomolecular kinetics. This class includes, but is not limited to, Mass Action, Michaelis-Menten, Hill, and some Power-law models. This suggests that sequential enzyme expression may be a common feature of metabolic regulation, as it is a robust property of optimal pathway activation. PMID:19412635

  9. 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

  10. 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. PMID:24681377

  11. 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

  12. Epidermis is a pivotal site of at least four secondary metabolic pathways in Catharanthus roseus aerial organs.

    PubMed

    Mahroug, Samira; Courdavault, Vincent; Thiersault, Martine; St-Pierre, Benoit; Burlat, Vincent

    2006-05-01

    Catharanthus roseus produces a wide range of secondary metabolites, some of which present high therapeutic values such as antitumoral monoterpenoid indole alkaloids (MIAs), vinblastine and vincristine, and the hypotensive MIA, ajmalicine. We have recently shown that a complex multicellular organisation of the MIA biosynthetic pathway occurred in C. roseus aerial organs. In particular, the final steps of both the secoiridoid-monoterpene and indole pathways specifically occurred in the epidermis of leaves and petals. Chorismate is the common precursor of indole and phenylpropanoid pathways. In an attempt to better map the spatio-temporal organisation of diverse secondary metabolisms in Catharanthus roseus aerial organs, we studied the expression pattern of genes encoding enzymes of the phenylpropanoid pathway (phenylalanine ammonia-lyase [PAL, E.C. 4.3.1.5], cinnamate 4-hydroxylase [C4H, E.C. 1.14.13.11] and chalcone synthase [CHS, E.C. 2.3.1.74]). In situ hybridisation experiments revealed that CrPAL and CrC4H were specifically localised to lignifying xylem, whereas CrPAL, CrC4H and CrCHS were specifically expressed in the flavonoid-rich upper epidermis. Interestingly, these three genes were co-expressed in the epidermis (at least the upper, adaxial one) together with three MIA-related genes, indicating that single epidermis cells were capable of concomitantly producing a wide range of diverse secondary metabolites (e.g. flavonoïds, indoles, secoiridoid-monoterpenes and MIAs). These results, and data showing co-accumulation of flavonoids and alkaloids in single cells of C. roseus cell lines, indicated the spatio-temporal feasibility of putative common regulation mechanisms for the expression of these genes involved in at least four distinct secondary metabolisms. PMID:16322983

  13. 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.

  14. The Chordin Morphogenetic Pathway.

    PubMed

    De Robertis, Edward M; Moriyama, Yuki

    2016-01-01

    The ancestral Chordin/bone morphogenetic protein (BMP) signaling pathway that establishes dorsal-ventral (D-V) patterning in animal development is one of the best understood morphogenetic gradients, and is established by multiple proteins that interact with each other in the extracellular space-including several BMPs, Chordin, Tolloid, Ont-1, Crossveinless-2, and Sizzled. The D-V gradient is adjusted redundantly by regulating the synthesis of its components, by direct protein-protein interactions between morphogens, and by long-range diffusion. The entire embryo participates in maintaining the D-V BMP gradient, so that for each action in the dorsal side there is a reaction in the ventral side. A gradient of Chordin is formed in the extracellular matrix that separates ectoderm from endomesoderm, called Brachet's cleft in Xenopus. The Chordin/BMP pathway is self-organizing and able to scale pattern in the dorsal half of bisected embryos or in Spemann dorsal lip transplantation experiments. PMID:26970622

  15. Pathways of lateral spreading.

    PubMed

    Jacobi, U; Schanzer, S; Weigmann, H-J; Patzelt, A; Vergou, T; Sterry, W; Lademann, J

    2011-01-01

    In the case of topically applied substances, usually both lateral spreading and competitive penetration into the skin occur in parallel. In the present study, the pathways of lateral spreading were studied quantitatively and visually. The local distribution and lateral spreading of the UV filter substance butyl methoxydibenzoylmethane applied in an o/w emulsion was studied on the forearm and the back. The tape stripping procedure was used to determine the recovery rates inside and outside the area of application. The skin characteristics of transepidermal water loss, pH value, hydration of the stratum corneum and sebum rate were determined at both anatomic sites. Photography and laser scanning microscopy were used to visually investigate the lateral spreading of topically applied dyes. On the back, a preferred direction of lateral spreading parallel to the body axis was observed. This result was caused by differences in the network of furrows. The furrows functioned as a pathway for lateral spreading, whereas the follicles formed a reservoir for the topically applied substance. PMID:21455016

  16. The Reactome pathway Knowledgebase.

    PubMed

    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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. Caffeine and the common cold.

    PubMed

    Smith, A; Thomas, M; Perry, K; Whitney, H

    1997-01-01

    An experiment was carried out to determine whether caffeinated and decaffeinated coffee removed the malaise (reduced alertness, slower psychomotor performance) associated with having a common cold. One hundred volunteers were tested when healthy and 46 returned to the laboratory when they developed colds. Those subjects who remained healthy were then recalled as a control group. On the second visit subjects carried out two sessions, one pre-drink and another an hour after the drink. Subjects were randomly assigned to one of the following three conditions, caffeinated coffee (1.5 mg/kg caffeine/body weight), decaffeinated coffee or fruit juice. Subjects with colds reported decreased alertness and were slower at performing psychomotor tasks. Caffeine increased the alertness and performance of the colds subjects to the same level as the healthy group and decaffeinated coffee also led to an improvement. These results suggest that drugs which increase alertness can remove the malaise associated with the common cold, and that increased stimulation of the sensory afferent nerves may also be beneficial. PMID:9443519

  6. 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.

  7. Common hematological disorders in children.

    PubMed

    Bansal, Deepak; Totadri, Sidharth

    2014-01-01

    It is common for primary care physicians to be faced with children with hematological disorders in everyday practice. The article seeks to provide realistic information for the first-contact physician in handling common hematological diseases in children. Practical step-wise approach to understanding and investigating anemia and bleeding disorders is illustrated. Requirement of iron in normal children and management of iron deficiency anemia (IDA) and thalassemia is explained. The gold standard for IDA continues to be ferrous sulphate which has good bioavailability and is inexpensive. There is emerging concept of delayed clamping of umbilical cord at birth, particularly in regions with widespread IDA, to augment iron stores in infancy. Typical case scenarios of children with immune thrombocytopenia (ITP) and hemophilia are provided to facilitate the understanding of management in day to day practice. The vital role of the medical practitioner in shared care of patients with acute lymphoblastic leukemia and febrile neutropenia is emphasized. A risk based treatment algorithm for febrile neutropenia is provided. PMID:23934100

  8. Inverse Common-Reflection-Surface

    NASA Astrophysics Data System (ADS)

    Perroud, H.; Tygel, M.; Freitas, L.

    2010-12-01

    The Common-Reflection-Surface (CRS) stack method is a powerful tool to produce high-quality stacked images of multicoverage seismic data. As a result of the CRS stack, not only a stacked section, but also a number of attributes defined at each point of that section, are produced. In this way, one can think of the CRS stack method as a transformation from data space to attribute space. Being a purely kinematic method, the CRS stack lacks amplitude information that can be useful for many purposes. Here we propose to fill this gap by means of a combined use of a zero-offset section (that could be a short-offset or amplitude-corrected stacked section) and common midpoint gather. We present an algorithm for an inverse CRS transformation, namely one that (approximately) transforms the CRS attributes back to data space. First synthetic tests provide satisfying results for the two simple cases of single dipping-plane and single circular reflectors with a homogeneous overburden, and provide estimates of the range of applicability, in both midpoint and offset directions. We further present an application for interpolating missing traces in a near-surface, high-resolution seismic experiment, conducted in the alluvial plain of the river Gave de Pau, near Assat, southern France, showing its ability to build coherent signals, where recording was not available. A somewhat unexpected good feature of the algorithm, is that it seems capable to reconstruct signals even in muted parts of the section.

  9. 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

  10. DNA/SNLA commonality program

    SciTech Connect

    Keller, D. V.; Watts, A. J.; Rice, D. A.; Powe, J.; Beezhold, W.

    1980-01-01

    The purpose of the Commonality program, initiated by DNA in 1978, was to evaluate e-beam material testing procedures and techniques by comparing material stress and spall data from various US and UK e-beam facilities and experimenters. As part of this joint DNA/SNL/UK Commonality effort, Sandia and Ktech used four different electron-beam machines to investigate various aspects of e-beam energy deposition in three materials. The deposition duration and the deposition profiles were varied, and the resulting stresses were measured. The materials studied were: (1) a low-Z material (A1), (2) a high-Z material (Ta), and (3) a typical porous material, a cermet. Aluminium and tantalum were irradiated using the DNA Blackjack 3 accelerator (60 ns pulse width), the DNA Blackjack 3' accelerator (30 ns pulse width), and the SNLA REHYD accelerator (100 ns pulse width). Propagating stresses were measured using x-cut quartz gauges, carbon gauges, and laser interferometry techniques. Data to determine the influence of deposition duration were obtained over a wide range of energy loadings. The cermet material was studied using the SNLA REHYD and HERMES II accelerators. The e-beam from REHYD generated propagating stresses which were monitored with quartz gauges as a function of sample thickness and energy loadings. The HERMES II accelerator was used to uniformly heat the cermet to determine the Grueneisen parameter and identify the incipient spall condition. Results of these experiments are presented.

  11. Evolution of a common controller

    NASA Astrophysics Data System (ADS)

    Powell, D.; Barbour, D.; Gilbreath, G.

    2012-06-01

    Precedent has shown common controllers must strike a balance between the desire for an integrated user interface design by human factors engineers and support of project-specific data requirements. A common user-interface requires the project-specific data to conform to an internal representation, but project-specific customization is impeded by the implicit rules introduced by the internal data representation. Space and Naval Warfare Systems Center Pacific (SSC Pacific) developed the latest version of the Multi-robot Operator Control Unit (MOCU) to address interoperability, standardization, and customization issues by using a modular, extensible, and flexible architecture built upon a sharedworld model. MOCU version 3 provides an open and extensible operator-control interface that allows additional functionality to be seamlessly added with software modules while providing the means to fully integrate the information into a layered game-like user interface. MOCU's design allows it to completely decouple the human interface from the core management modules, while still enabling modules to render overlapping regions of the screen without interference or a priori knowledge of other display elements, thus allowing more flexibility in project-specific customization.

  12. Common questions about Barrett esophagus.

    PubMed

    Zimmerman, Thomas G

    2014-01-15

    Barrett esophagus is a precancerous metaplasia of the esophagus that is more common in patients with chronic reflux symptoms, although it also occurs in patients without symptomatic reflux. Other risk factors include smoking, male sex, obesity, white race, hiatal hernia, and increasing age (particularly older than 50 years). Although Barrett esophagus is a risk factor for esophageal adenocarcinoma, its management and the need for screening or surveillance endoscopy are debatable. The annual incidence of progression to esophageal cancer is 0.12% to 0.33%; progression is more common in patients with high-grade dysplasia and long-segment Barrett esophagus. Screening endoscopy should be considered for patients with multiple risk factors, and those who have lesions with high-grade dysplasia should undergo endoscopic mucosal resection or other endoscopic procedures to remove the lesions. Although the cost-effectiveness is questionable, patients with nondysplastic Barrett esophagus can be followed with endoscopic surveillance. Lowgrade dysplasia should be monitored or eradicated via endoscopy. Although there is no evidence that medical or surgical therapies to reduce acid reflux prevent neoplastic progression, proton pump inhibitors can be used to help control reflux symptoms. PMID:24444576

  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. 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 ...

  16. RASS SOT Webinar - Nonmonotonic Dose Response Curves (NMDRCs) Common after Estrogen or Androgen Signaling Pathway Disruption

    EPA Science Inventory

    The presentation provides the listening and viewing audience with Dr Gray's scientific information on the relevance of nonmonotonic dose response curves to the risk assessment of estrogenic and androgenic chemicals

  17. 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…

  18. 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…

  19. 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…

  20. 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…

  1. 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. PMID:24997388

  2. Investigating ROS sources in male infertility: a common end for numerous pathways.

    PubMed

    Lavranos, G; Balla, M; Tzortzopoulou, A; Syriou, V; Angelopoulou, R

    2012-11-01

    Reactive oxygen species (ROS) are active byproducts of aerobic metabolism. Although they are constantly produced during normal cellular activities in the mitochondria, their action is counteracted by inherent antioxidant systems. This equilibrium is distorted in the case of acute or chronic inflammation, which results in increased ROS production and, ultimately, oxidative stress. In sperm, ROS are produced by both spermatozoa and circulating leucocytes and may be part of normal adaptive reactions, such as the capacitation process. However, a number of external toxicants may also contribute to ROS production in the testis and epididymis, leading to a decrease in sperm viability and motility and, therefore, an increased onset of the male factor of infertility. Such pro-oxidative conditions include, among others, exposure to radiation, extreme temperature, certain drugs, toxins, heavy metals, smoking and biological hazards. The current review paper summarizes the available evidence incriminating ROS and oxidative stress as the underlying pathophysiological mechanism leading to the onset of reproductive toxicity in each of these settings. PMID:22749934

  3. Transformation and Removal Pathways of Four Common PPCP/EDCs in Soil

    PubMed Central

    Dodgen, LK; Li, J; Wu, X; Lu, Z; Gan, JJ

    2014-01-01

    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 14C-labeling and analyzing mineralization, extractable residue, bound residue, and formation of transformation products. At the end of 112 d of incubation, the majority of 14C-naproxen and 14C-diclofenac was mineralized to 14CO2, while a majority of 14C-bisphenol A and 14C-nonylphenol 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. PMID:24997388

  4. 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

  5. Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity

    PubMed Central

    Angoa-Pérez, Mariana; Kane, Michael J.; Briggs, Denise I.; Sykes, Catherine E.; Shah, Mrudang M.; Francescutti, Dina M.; Rosenberg, David R.; Thomas, David M.; Kuhn, Donald M.

    2012-01-01

    Neuropsychiatric disorders characterized by behavioral disinhibition, including disorders of compulsivity (e.g., obsessive-compulsive disorder; OCD) and impulse-control (e.g., impulsive aggression), are severe, highly prevalent and chronically disabling. Treatment options for these diseases are extremely limited. The pathophysiological bases of disorders of behavioral disinhibition are poorly understood but it has been suggested that serotonin dysfunction may play a role. Mice lacking the gene encoding brain tryptophan hydroxylase 2 (Tph2−/−), the initial and rate-limiting enzyme in the synthesis of serotonin, were tested in numerous behavioral assays that are well known for their utility in modeling human neuropsychiatric diseases. Mice lacking Tph2 (and brain 5HT) show intense compulsive and impulsive behaviors to include extreme aggression. The impulsivity is motor in form and not cognitive because Tph2−/− mice show normal acquisition and reversal learning on a spatial learning task. Restoration of 5HT levels by treatment of Tph2−/− mice with its immediate precursor 5-hydroxytryptophan attenuated compulsive and impulsive-aggressive behaviors. Surprisingly, in Tph2−/− mice, the lack of 5HT was not associated with anxiety-like behaviors. The results indicate that 5HT mediates behavioral disinhibition in the mammalian brain independent of anxiogenesis. PMID:22443164

  6. Purinergic signaling: a common pathway for neural and mesenchymal stem cell maintenance and differentiation

    PubMed Central

    Cavaliere, Fabio; Donno, Claudia; D’Ambrosi, Nadia

    2015-01-01

    Extracellular ATP, related nucleotides and adenosine are among the earliest signaling molecules, operating in virtually all tissues and cells. Through their specific receptors, namely purinergic P1 for nucleosides and P2 for nucleotides, they are involved in a wide array of physiological effects ranging from neurotransmission and muscle contraction to endocrine secretion, vasodilation, immune response, and fertility. The purinergic system also participates in the proliferation and differentiation of stem cells from different niches. In particular, both mesenchymal stem cells (MSCs) and neural stem cells are endowed with several purinergic receptors and ecto-nucleotide metabolizing enzymes, and release extracellular purines that mediate autocrine and paracrine growth/proliferation, pro- or anti-apoptotic processes, differentiation-promoting effects and immunomodulatory actions. Here, we discuss the often opposing roles played by ATP and adenosine in adult neurogenesis in both physiological and pathological conditions, as well as in adipogenic and osteogenic MSC differentiation. We also focus on how purinergic ligands produced and released by transplanted stem cells can be regarded as ideal candidates to mediate the crosstalk with resident stem cell niches, promoting cell growth and survival, regulating inflammation and, therefore, contributing to local tissue homeostasis and repair. PMID:26082684

  7. 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

  8. Molecular pathways of chronic kidney disease progression.

    PubMed

    Bienaimé, Frank; Canaud, Guillaume; El Karoui, Khalil; Gallazzini, Morgan; Terzi, Fabiola

    2016-04-01

    Chronic kidney disease is characterized by the progressive loss of functional nephrons. This loss means that the remaining nephrons are put under stress and are forced to adapt in order to maintain kidney function. Over the time, the strains imposed by these adaptations result in a vicious circle in which the loss of damaged nephrons results in the damage of the so far healthy nephrons. Hence, the rate of chronic kidney disease progression depends on the ability of the remaining nephrons to cope with stress. This article reviews the molecular pathways involved in the compensation and deterioration process after nephron reduction. In particular, we examine the role of mammalian target of rapamycin complex (mTORC)/serine-threonine protein kinase AKT, epidermal growth factor receptor (EGFR) and unfolded protein response pathways, as well as the pleiotropic function of Lipocalin 2. We also discuss the dual role played by some of these pathways in acute and chronic kidney disease. Finally, the relevance of these experimental finding to human chronic kidney disease is discussed. PMID:26972095

  9. 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.

  10. 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

  11. The Peroxide Pathway

    NASA Technical Reports Server (NTRS)

    McNeal, Curtis I., Jr.; Anderson, William

    1999-01-01

    NASA's current focus on technology roadmaps as a tool for guiding investment decisions leads naturally to a discussion of NASA's roadmap for peroxide propulsion system development. NASA's new Second Generation Space Transportation System roadmap calls for an integrated Reusable Upper-Stage (RUS) engine technology demonstration in the FY03/FY04 time period. Preceding this integrated demonstration are several years of component developments and subsystem technology demonstrations. NASA and the Air Force took the first steps at developing focused upper stage technologies with the initiation of the Upper Stage Flight Experiment with Orbital Sciences in December 1997. A review of this program's peroxide propulsion development is a useful first step in establishing the peroxide propulsion pathway that could lead to a RUS demonstration in 2004.

  12. Pathways Intern Work Report

    NASA Technical Reports Server (NTRS)

    Midulla, Laura P.

    2014-01-01

    For the spring of 2014, I continued my position at NASA as a Pathways Engineering Student Trainee in the Engineering and Technology Directorate (NE), in the Test, Operations & Support Software Engineering Branch of the Control and Data Systems Division. The Control and Data Systems Division provides control, monitor, checkout, processing, display, and simulation capabilities to support vehicle element testing, checkout and launch. In addition the division provides significant leadership associated with engineering processes and Information Technology Security management. My assignment during this semester was to continue to support the Engineering Information Technology (IT) Security team, providing IT Security support to the Ground Systems Development and Operations Spaceport Command & Control System and Ground Systems, NE Labs and other systems.

  13. The Relationship between Vocational Interests, Self-Efficacy, and Achievement in the Prediction of Educational Pathways

    ERIC Educational Resources Information Center

    Patrick, Lyn; Care, Esther; Ainley, Mary

    2011-01-01

    The influence of vocational interest, self-efficacy beliefs, and academic achievement on choice of educational pathway is described for a cohort of Australian students. Participants were 189 students aged 14-15 years, who were considering either academic or applied learning pathways and subject choices for the final 3 years of secondary school.…

  14. Pathways of iron absorption.

    PubMed

    Conrad, Marcel E; Umbreit, Jay N

    2002-01-01

    Iron is vital for all living organisms but excess iron can be lethal because it facilitates free radical formation. Thus iron absorption is carefully regulated to maintain an equilibrium between absorption and body loss of iron. In countries where meat is a significant part of the diet, most body iron is derived from dietary heme because heme binds few of the dietary chelators that bind inorganic iron. Uptake of heme into enterocytes occurs as a metalloporphyrin in an endosomal process. Intracellular iron is released from heme by heme oxygenase to enter plasma as inorganic iron. Ferric iron is absorbed via a beta(3) integrin and mobilferrin pathway (IMP) which is unshared with other nutritional metals. Ferrous iron uptake is facilitated by a DMT-1 pathway which is shared with manganese. In the iron deficient gut, large quantities of both mobilferrin and DMT-1 are found in goblet cells and intraluminal mucins suggesting that they are secreted with mucin into the intestinal lumen to bind iron to facilitate uptake by the cells. In the cytoplasm, IMP and DMT associate in a large protein complex called paraferritin which serves as a ferrireductase. Paraferritin solublizes iron binding proteins and reduces iron to make iron available for production of iron containing proteins such as heme. Iron uptake by intestinal absorptive cells is regulated by the iron concentration within the cell. Except in hemochromatosis it remains in equilibrium with total body stores via transferrin receptors on the basolateral membrane of absorptive cells. Increased intracellular iron either up-regulates or satiates iron binding proteins on regulatory proteins to alter their location in the intestinal mucosa. PMID:12547224

  15. 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

  16. Developmental Programming, a Pathway to Disease.

    PubMed

    Padmanabhan, Vasantha; Cardoso, Rodolfo C; Puttabyatappa, Muraly

    2016-04-01

    Accumulating evidence suggests that insults occurring during the perinatal period alter the developmental trajectory of the fetus/offspring leading to long-term detrimental outcomes that often culminate in adult pathologies. These perinatal insults include maternal/fetal disease states, nutritional deficits/excess, stress, lifestyle choices, exposure to environmental chemicals, and medical interventions. In addition to reviewing the various insults that contribute to developmental programming and the benefits of animal models in addressing underlying mechanisms, this review focuses on the commonalities in disease outcomes stemming from various insults, the convergence of mechanistic pathways via which various insults can lead to common outcomes, and identifies the knowledge gaps in the field and future directions. PMID:26859334

  17. 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)

  18. 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

  19. CLL: Common Leukemia; Uncommon Presentations.

    PubMed

    Lad, Deepesh; Malhotra, Pankaj; Varma, Neelam; Sachdeva, Manupdesh Singh; Das, Ashim; Srinivasan, Radhika; Bal, Amanjit; Khadwal, Alka; Prakash, Gaurav; Suri, Vikas; Kumari, Savita; Jain, Sanjay; Varma, Subhash

    2016-09-01

    We report here a series of ten patients with uncommon presentations and associations of chronic lymphocytic leukemia (CLL) not reported hitherto or occasionally reported in literature. The first two cases describe unusual causes of abdominal distension in CLL and unusual sites infiltration by CLL. The next two cases illustrate occurrence of CLL in association with other hematological malignancies. Cases five and six describe unusual infections and their impact on CLL. Cases seven and eight depict associations of rare non-hematological autoimmune conditions with CLL. The last two cases describe transformation at unusual sites. This series of ten cases illustrates how a common leukemia like CLL can present in different forms and how despite so much progress in understanding of this leukemia so little is known of such presentations. PMID:27429518

  20. Work and common psychiatric disorders.

    PubMed

    Henderson, M; Harvey, S B; Overland, S; Mykletun, A; Hotopf, M

    2011-05-01

    Psychiatric disorders are now the most common reason for long-term sickness absence. The associated loss in productivity and the payment of disability benefits places a substantial burden on the economies of many developed countries. The occupational dysfunction associated with psychiatric disorders can also lead to poverty and social isolation. As a result the area of work and psychiatric disorders is a high priority for policymakers. There are two main agendas: for many researchers and clinicians the focus is on the need to overcome stigma and ensure people with severe psychiatric disorders have meaningful work; however the public health agenda predominantly relates to the more common disorders such as depression and anxiety, which contribute a greater burden of disability benefits and pensions. In this review we attempt to address this second agenda. The relatively sparse evidence available reveals a complex field with significant interplay between medical, psychological social and cultural factors. Sick leave can be a 'process' as well as an 'event'. In this review we propose a staged model where different risk and protective factors contribute to the onset of psychiatric disorders in the working population, the onset of short-term sickness absence, and the transition from short- to long-term absence. We also examine strategies to manage psychiatric disorder in the workforce with a view towards returning the employee to work. Our aim in this review is to highlight the complexity of the area, to stimulate debate and to identify important gaps in knowledge where further research might benefit both patients and wider society. PMID:21558098

  1. 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

  2. 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

  3. 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. PMID:24929454

  4. A common biological mechanism in cancer and Alzheimer’s disease?

    PubMed Central

    Behrens, Maria I; Lendon, Corinne; Roe, Catherine M.

    2009-01-01

    Cancer and Alzheimer’s disease (AD) are two common disorders for which the final pathophysiological mechanism is not yet clearly defined. In a prospective longitudinal study we have previously shown an inverse association between AD and cancer, such that the rate of developing cancer in general with time was significantly slower in participants with AD, while participants with a history of cancer had a slower rate of developing AD. In cancer, cell regulation mechanisms are disrupted with augmentation of cell survival and/or proliferation, whereas conversely, AD is associated with increased neuronal death, either caused by, or concomitant with, beta amyloid (Aβ) and tau deposition. The possibility that perturbations of mechanisms involved in cell survival/death regulation could be involved in both disorders is discussed. Genetic polymorphisms, DNA methylation or other mechanisms that induce changes in activity of molecules with key roles in determining the decision to “repair and live”- or “die” could be involved in the pathogenesis of the two disorders. As examples, the role of p53, Pin1 and the Wnt signaling pathway are discussed as potential candidates that, speculatively, may explain inverse associations between AD and cancer. PMID:19519301

  5. Study on the standard architecture for geoinformation common services

    NASA Astrophysics Data System (ADS)

    Zha, Z.; Zhang, L.; Wang, C.; Jiang, J.; Huang, W.

    2014-04-01

    The construction of platform for geoinformation common services was completed or on going in in most provinces and cities in these years in China, and the platforms plays an important role in the economic and social activities. Geoinfromation and geoinfromation based services are the key issues in the platform. The standards on geoinormation common services play as bridges among the users, systems and designers of the platform. The standard architecture for geoinformation common services is the guideline for designing and using the standard system in which the standards integrated to each other to promote the development, sharing and services of geoinformation resources. To establish the standard architecture for geoinformation common services is one of the tasks of "Study on important standards for geonformation common services and management of public facilities in city". The scope of the standard architecture is defined, such as data or information model, interoperability interface or service, information management. Some Research work on the status of international standards of geoinormation common services in organization and countries, like ISO/TC 211, OGC and other countries or unions like USA, EU, Japan have done. Some principles are set up to evaluate the standard, such as availability, suitability and extensible ability. Then the development requirement and practical situation are analyzed, and a framework of the standard architecture for geoinformation common services are proposed. Finally, a summary and prospects of the geoinformation standards are made.

  6. 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.

  7. 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

  8. Itch and pain differences and commonalities.

    PubMed

    Schmelz, Martin

    2015-01-01

    Pain and itch are generally regarded antagonistic as painful stimuli such as scratching suppresses itch. Moreover, inhibition of pain processing by opioids generates itch further supporting their opposing role. Separate specific pathways for itch and pain processing have been uncovered, and several molecular markers have been established in mice that identify neurons involved in the processing of histaminergic and non-histaminergic itch on primary afferent and spinal level. These results are in agreement with the specificity theory for itch and might suggest that pain and itch should be investigated separately on the level of neurons, mediators, and mechanisms. However, in addition to broadly overlapping mediators of itch and pain, there is also evidence for overlapping functions in primary afferents: nociceptive primary afferents can provoke itch when activated very locally in the epidermis, and sensitization of both nociceptors and pruriceptors has been found following local nerve growth factor application in volunteers. Thus, also mechanisms that underlie the development of chronic itch and pain including spontaneous activity and sensitization of primary afferents as well as spinal cord sensitization may well overlap to a great extent. Rather than separating itch and pain, research concepts should therefore address the common mechanisms. Such an approach appears most appropriate for clinical conditions of neuropathic itch and pain and also chronic inflammatory conditions. While itch researchers can benefit from the large body of information of the pain field, pain researchers will find behavioral readouts of spontaneous itch much simpler than those for spontaneous pain in animals and the skin as source of the pruritic activity much more accessible even in patients. PMID:25846624

  9. The nuclear factor-kappaB-interleukin-6 signalling pathway mediating vascular inflammation.

    PubMed

    Brasier, Allan R

    2010-05-01

    Vascular inflammation is a common pathophysiological response to diverse cardiovascular disease processes, including atherosclerosis, myocardial infarction, congestive heart failure, and aortic aneurysms/dissection. Inflammation is an ordered process initiated by vascular injury that produces enhanced leucocyte adherence, chemotaxis, and finally activation in situ. This process is coordinated by local secretion of adhesion molecules, chemotactic factors, and cytokines whose expression is the result of vascular injury-induced signal transduction networks. A wide variety of mediators of the vascular injury response have been identified; these factors include vasoactive peptides (angiotensin II, Ang II), CD40 ligands, oxidized cholesterol, and advanced glycation end-products. Downstream, the nuclear factor-kappaB (NF-kappaB) transcription factor performs an important signal integration step, responding to mediators of vascular injury in a stimulus-dependent and cell type-specific manner. The ultimate consequence of NF-kappaB signalling is the activation of inflammatory genes including adhesion molecules and chemotaxins. However, clinically, the hallmark of vascular NF-kappaB activation is the production of interleukin-6 (IL-6), whose local role in vascular inflammation is relatively unknown. The recent elucidation for the role of the IL-6 signalling pathway in Ang II-induced vascular inflammation as one that controls monocyte activation as well as its diverse signalling mechanism will be reviewed. These new discoveries further our understanding for the important role of the NF-kappaB-IL-6 signalling pathway in the process of vascular inflammation. PMID:20202975

  10. 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

  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. 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

  13. The Harvard Catalyst Common Reciprocal IRB Reliance Agreement

    PubMed Central

    Winkler, Sabune J.; Witte, Elizabeth; Bierer, Barbara E.

    2014-01-01

    Reduction of duplicative Institutional Review Board (IRB) review for multi-institutional studies is a desirable goal to improve IRB efficiency while enhancing human subject protections. Here we describe the Harvard Catalyst Master Reciprocal Common IRB Reliance Agreement (MRA), a system that provides a legal framework for IRB reliance, with the potential to streamline IRB review processes and reduce administrative burden and barriers to collaborative, multi-institutional research. The MRA respects the legal autonomy of the signatory institutions while offering a pathway to eliminate duplicative IRB review when appropriate. The Harvard Catalyst MRA provides a robust and flexible model for reciprocal reliance that is both adaptable and scalable. PMID:25196592

  14. Constitution and common law in bioethics.

    PubMed

    Santosuosso, A

    2001-10-01

    In recent years legal intervention in bioethical matters has increased notably following various paths: court decisions, parliamentary acts, codes of conduct and solemn declarations (i.e. European Bioethics Convention, 1997, or the UNESCO Genome Declaration, 1997). Body and liberty, as a question of fundamental legal rights, are constitutionalized along two paths. The former is vertical (a text created at central level is open to ratification and domestic implementation to finally become the rule in concrete cases). The latter is, above all, horizontal. It is characterized by the existence at world level of a number of centres and institutions, with the judiciary and judge-made law playing a major role. The most important new rights and freedoms in bioethics have been recognized in this ever-changing and troubled environment. The horizontal way has the great advantage of considering the differences as a resource and not as a limit. In the case law on bioethics a sort of jurisprudential model seems to be at work, that goes some way toward a judge-made law at a universal level. Cases such as Cruzan, Bland and Massimo held the fundamental concept of self-determination with surprising similarity. But we don't know if one of them has influenced the others, always supposing that the judges were aware of them. Today's first duty is to raise the consciousness of judges as to how common their problems are and how often their rulings are similar to each other's. PMID:12058772

  15. Common Data Elements for Muscle Biopsy Reporting

    PubMed Central

    Dastgir, Jahannaz; Rutkowski, Anne; Alvarez, Rachel; Cossette, Stacy A.; Yan, Ke; Hoffmann, Raymond G.; Sewry, Caroline; Hayashi, Yukiko K.; Goebel, Hans-Hilmar; Bonnemann, Carsten; Lawlor, Michael W.

    2016-01-01

    Context There is no current standard among myopathologists for reporting muscle biopsy findings. The National Institute of Neurological Disorders and Stroke has recently launched a common data element (CDE) project to standardize neuromuscular data collected in clinical reports and to facilitate their use in research. Objective To develop a more-uniform, prospective reporting tool for muscle biopsies, incorporating the elements identified by the CDE project, in an effort to improve reporting and educational resources. Design The variation in current biopsy reporting practice was evaluated through a study of 51 muscle biopsy reports from self-reported diagnoses of genetically confirmed or undiagnosed muscle disease from the Congenital Muscle Disease International Registry. Two reviewers independently extracted data from deidentified reports and entered them into the revised CDE format to identify what was missing and whether or not information provided on the revised CDE report (complete/incomplete) could be successfully interpreted by a neuropathologist. Results Analysis of the data highlighted showed (1) inconsistent reporting of key clinical features from referring physicians, and (2) considerable variability in the reporting of pertinent positive and negative histologic findings by pathologists. Conclusions We propose a format for muscle-biopsy reporting that includes the elements in the CDE checklist and a brief narrative comment that interprets the data in support of a final interpretation. Such a format standardizes cataloging of pathologic findings across the spectrum of muscle diseases and serves emerging clinical care and research needs with the expansion of genetic-testing therapeutic trials. PMID:26132600

  16. 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. PMID:17097480

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

    PubMed Central

    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. PMID:26904079

  18. Mouse hippocampal phosphorylation footprint induced by generalized seizures: Focus on ERK, mTORC1 and Akt/GSK-3 pathways.

    PubMed

    Gangarossa, Giuseppe; Sakkaki, Sophie; Lory, Philippe; Valjent, Emmanuel

    2015-12-17

    Exacerbated hippocampal activity has been associated to critical modifications of the intracellular signaling pathways. We have investigated rapid hippocampal adaptive responses induced by maximal electroshock seizure (MES). Here, we demonstrate that abnormal and exacerbated hippocampal activity induced by MES triggers specific and temporally distinct patterns of phosphorylation of extracellular signal-related kinase (ERK), mammalian target of rapamycin complex (mTORC) and Akt/glycogen synthase kinase-3 (Akt/GSK-3) pathways in the mouse hippocampus. While the ERK pathway is transiently activated, the mTORC1 cascade follows a rapid inhibition followed by a transient activation. This rebound of mTORC1 activity leads to the selective phosphorylation of p70S6K, which is accompanied by an enhanced phosphorylation of the ribosomal subunit S6. In contrast, the Akt/GSK-3 pathway is weakly altered. Finally, MES triggers a rapid upregulation of several plasticity-associated genes as a consequence exacerbated hippocampal activity. The results reported in the present study are reminiscent of the one observed in other models of generalized seizures, thus defining a common molecular footprint induced by intense and aberrant hippocampal activities. PMID:26545981

  19. Diagnosing Common Benign Skin Tumors.

    PubMed

    Higgins, James C; Maher, Michael H; Douglas, Mark S

    2015-10-01

    Patients will experience a wide range of skin growths and changes over their lifetime. Family physicians should be able to distinguish potentially malignant from benign skin tumors. Most lesions can be diagnosed on the basis of history and clinical examination. Lesions that are suspicious for malignancy, those with changing characteristics, symptomatic lesions, and those that cause cosmetic problems may warrant medical therapy, a simple office procedure (e.g., excision, cryosurgery, laser ablation), or referral. Acrochordons are extremely common, small, and typically pedunculated benign neoplasms. Simple scissor or shave excision, electrodesiccation, or cryosurgery can be used for treatment. Sebaceous hyperplasia presents as asymptomatic, discrete, soft, pale yellow, shiny bumps on the forehead or cheeks, or near hair follicles. Except for cosmesis, they have no clinical significance. Lipomas are soft, flesh-colored nodules that are easily moveable under the overlying skin. Keratoacanthomas are rapidly growing, squamoproliferative benign tumors that resemble squamous cell carcinomas. Early simple excision is recommended. Pyogenic granuloma is a rapidly growing nodule that bleeds easily. Treatment includes laser ablation or shave excision with electrodesiccation of the base. Dermatofibromas are an idiopathic benign proliferation of fibroblasts. No treatment is required unless there is a change in size or color, bleeding, or irritation from trauma. Epidermal inclusion cysts can be treated by simple excision with removal of the cyst and cyst wall. Seborrheic keratoses and cherry angiomas generally do not require treatment. PMID:26447443

  20. Common questions about wound care.

    PubMed

    Worster, Brooke; Zawora, Michelle Q; Hsieh, Christine

    2015-01-15

    Lacerations, abrasions, burns, and puncture wounds are common in the outpatient setting. Because wounds can quickly become infected, the most important aspect of treating a minor wound is irrigation and cleaning. There is no evidence that antiseptic irrigation is superior to sterile saline or tap water. Occlusion of the wound is key to preventing contamination. Suturing, if required, can be completed up to 24 hours after the trauma occurs, depending on the wound site. Tissue adhesives are equally effective for low-tension wounds with linear edges that can be evenly approximated. Although patients are often instructed to keep their wounds covered and dry after suturing, they can get wet within the first 24 to 48 hours without increasing the risk of infection. There is no evidence that prophylactic antibiotics improve outcomes for most simple wounds. Tetanus toxoid should be administered as soon as possible to patients who have not received a booster in the past 10 years. Superficial mild wound infections can be treated with topical agents, whereas deeper mild and moderate infections should be treated with oral antibiotics. Most severe infections, and moderate infections in high-risk patients, require initial parenteral antibiotics. Severe burns and wounds that cover large areas of the body or involve the face, joints, bone, tendons, or nerves should generally be referred to wound care specialists. PMID:25591209