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Sample records for atypical kinase implicated

  1. Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases and atypical protein kinase C.

    Science.gov (United States)

    Yoshimitsu, Yuji; Oishi, Shinya; Miyagaki, Jun; Inuki, Shinsuke; Ohno, Hiroaki; Fujii, Nobutaka

    2011-09-15

    Sphingosine kinases (SphKs) are oncogenic enzymes that regulate the critical balance between ceramide and sphingosine-1-phosphate. Much effort has been dedicated to develop inhibitors against these enzymes. Naturally occurring pachastrissamine (jaspine B) and all its stereoisomers were prepared and evaluated for their inhibitory effects against SphKs. All eight stereoisomers exhibited moderate to potent inhibitory activity against SphK1 and SphK2. Inhibitory effects were profiled against protein kinase C (PKC) isoforms by in vitro experiments. Atypical PKCs (PKCζ and PKCι) were inhibited by several pachastrissamine stereoisomers. The improved activity over N,N-dimethylsphingosine suggests that the cyclic scaffold in pachastrissamines facilitates potential favorable interactions with SphKs and PKCs.

  2. Atypical (RIO) protein kinases from Haemonchus contortus--promise as new targets for nematocidal drugs.

    Science.gov (United States)

    Campbell, Bronwyn E; Boag, Peter R; Hofmann, Andreas; Cantacessi, Cinzia; Wang, Conan K; Taylor, Paul; Hu, Min; Sindhu, Zia-Ud-Din; Loukas, Alex; Sternberg, Paul W; Gasser, Robin B

    2011-01-01

    Almost nothing is known about atypical kinases in multicellular organisms, including parasites. Supported by information and data available for the free-living nematode, Caenorhabditis elegans, and other eukaryotes, the present article describes three RIO kinase genes, riok-1, riok-2 and riok-3, from Haemonchus contortus, one of the most important parasitic nematodes of small ruminants. Analyses of these genes and their products predict that they each play critical roles in the developmental pathways of parasitic nematodes. The findings of this review indicate prospects for functional studies of these genes in C. elegans (as a surrogate) and opportunities for the design of a novel class of nematode-specific inhibitors of RIO kinases. The latter aspect is of paramount importance, given the serious problems linked to anthelmintic resistance in parasitic nematode populations of livestock. PMID:21262337

  3. Tv-RIO1 – an atypical protein kinase from the parasitic nematode Trichostrongylus vitrinus

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    Sternberg Paul W

    2008-09-01

    Full Text Available Abstract Background Protein kinases are key enzymes that regulate a wide range of cellular processes, including cell-cycle progression, transcription, DNA replication and metabolic functions. These enzymes catalyse the transfer of phosphates to serine, threonine and tyrosine residues, thus playing functional roles in reversible protein phosphorylation. There are two main groups, namely eukaryotic protein kinases (ePKs and atypical protein kinases (aPKs; RIO kinases belong to the latter group. While there is some information about RIO kinases and their roles in animals, nothing is known about them in parasites. This is the first study to characterise a RIO1 kinase from any parasite. Results A full-length cDNA (Tv-rio-1 encoding a RIO1 protein kinase (Tv-RIO1 was isolated from the economically important parasitic nematode Trichostrongylus vitrinus (Order Strongylida. The uninterrupted open reading frame (ORF of 1476 nucleotides encoded a protein of 491 amino acids, containing the characteristic RIO1 motif LVHADLSEYNTL. Tv-rio-1 was transcribed at the highest level in the third-stage larva (L3, and a higher level in adult females than in males. Comparison with homologues from other organisms showed that protein Tv-RIO1 had significant homology to related proteins from a range of metazoans and plants. Amino acid sequence identity was most pronounced in the ATP-binding motif, active site and metal binding loop. Phylogenetic analyses of selected amino acid sequence data revealed Tv-RIO1 to be most closely related to the proteins in the species of Caenorhabditis. A structural model of Tv-RIO1 was constructed and compared with the published crystal structure of RIO1 of Archaeoglobus fulgidus (Af-Rio1. Conclusion This study provides the first insights into the RIO1 protein kinases of nematodes, and a foundation for further investigations into the biochemical and functional roles of this molecule in biological processes in parasitic nematodes.

  4. An atypical kinase under balancing selection confers broad-spectrum disease resistance in Arabidopsis.

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    Carine Huard-Chauveau

    Full Text Available The failure of gene-for-gene resistance traits to provide durable and broad-spectrum resistance in an agricultural context has led to the search for genes underlying quantitative resistance in plants. Such genes have been identified in only a few cases, all for fungal or nematode resistance, and encode diverse molecular functions. However, an understanding of the molecular mechanisms of quantitative resistance variation to other enemies and the associated evolutionary forces shaping this variation remain largely unknown. We report the identification, map-based cloning and functional validation of QRX3 (RKS1, Resistance related KinaSe 1, conferring broad-spectrum resistance to Xanthomonas campestris (Xc, a devastating worldwide bacterial vascular pathogen of crucifers. RKS1 encodes an atypical kinase that mediates a quantitative resistance mechanism in plants by restricting bacterial spread from the infection site. Nested Genome-Wide Association mapping revealed a major locus corresponding to an allelic series at RKS1 at the species level. An association between variation in resistance and RKS1 transcription was found using various transgenic lines as well as in natural accessions, suggesting that regulation of RKS1 expression is a major component of quantitative resistance to Xc. The co-existence of long lived RKS1 haplotypes in A. thaliana is shared with a variety of genes involved in pathogen recognition, suggesting common selective pressures. The identification of RKS1 constitutes a starting point for deciphering the mechanisms underlying broad spectrum quantitative disease resistance that is effective against a devastating and vascular crop pathogen. Because putative RKS1 orthologous have been found in other Brassica species, RKS1 provides an exciting opportunity for plant breeders to improve resistance to black rot in crops.

  5. Elevated rates of atypical handedness in paedophilia: Theory and implications

    Science.gov (United States)

    Fazio, Rachel L.; Lykins, Amy D.; Cantor, James M.

    2014-01-01

    Multiple factors determine handedness including genetics, prenatal stress and post-natal environmental conditions. Atypical handedness, whether manifest as increased sinistrality or decreased strength of lateral preference, has been noted in a wide variety of populations with neuropathology. Those with atypical sexual preferences, specifically paedophilia, also manifest reduced rates of right-handedness. This paper uses the largest sample of phallometrically assessed men to date to establish the pattern of atypical handedness in paedophilia. Specifically, whereas prior research has largely characterized participants dichotomously as right-handed or non-right-handed and/or used self-report of writing hand, this paper expands upon such reports by using the Edinburgh Handedness Inventory's laterality quotient. Participants' handedness and phallometrically assessed sexual preference were analyzed both as continuous and categorical variables, and the responses of those scoring in the range of ambiguous-handedness were evaluated to ascertain whether they were ambiguously handed or more accurately described as mixed-handed. Results indicated those producing scores in the range of ambiguous-handedness demonstrated response patterns consistent with ambiguous-handedness, rather than mixed-handedness. Paedophiles demonstrated high rates of non-right-handedness primarily manifested as sinistrality, whereas those who had a sexual preference for pubescent children evidenced increased ambiguous-handedness. Results support a view of ambiguous-handedness as less pathological than previously hypothesized, and of a neurodevelopmental origin of paraphilic sexual preferences. PMID:24666135

  6. hCINAP is an atypical mammalian nuclear adenylate kinase with an ATPase motif: Structural and functional studies

    OpenAIRE

    Drakou, Christina E.; Malekkou, Anna; Hayes, Joseph M.; Carsten W Lederer; Leonidas, Demetres D.; Oikonomakos, Nikos G.; Lamond, Angus I.; Santama, Niovi; Zographos, Spyros E.

    2012-01-01

    Human coilin interacting nuclear ATPase protein (hCINAP) directly interacts with coilin, a marker protein of Cajal Bodies (CBs), nuclear organelles involved in the maturation of small nuclear ribonucleoproteins UsnRNPs and snoRNPs. hCINAP has previously been designated as an adenylate kinase (AK6), but is very atypical as it exhibits unusually broad substrate specificity, structural features characteristic of ATPase/GTPase proteins (Walker motifs A and B) and also intrinsic ATPase activity. D...

  7. The role of the atypical kinases ABC1K7 and ABC1K8 in abscisic acid responses

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    Anna eManara

    2016-03-01

    Full Text Available The ABC1K family of atypical kinases (activity of bc1 complex kinase is represented in bacteria, archaea and eukaryotes. In plants they regulate diverse physiological processes in the chloroplasts and mitochondria, but their precise functions are poorly defined. ABC1K7 and ABC1K8 are probably involved in oxidative stress responses, isoprenyl lipid synthesis and distribution of iron within chloroplasts. Because reactive oxygen species take part in abscisic acid (ABA-mediated processes, we investigated the functions of ABC1K7 and ABC1K8 during germination, stomatal movement and leaf senescence. Both genes were upregulated by ABA treatment and some ABA-responsive physiological processes were affected in abc1k7 and abc1k8 mutants. Germination was more severely affected by ABA, osmotic stress and salt stress in the single and double mutants; the stomatal aperture was smaller in the mutants under standard growth conditions and was not further reduced by exogenous ABA application; ABA-induced senescence symptoms were more severe in the leaves of the single and double mutants compared to wild type leaves. Taken together, our results suggest that ABC1K7 and ABC1K8 might be involved in the cross-talk between ABA and ROS signaling.

  8. Optic Atrophy in a Patient With Atypical Pantothenate Kinase-Associated Neurodegeneration.

    Science.gov (United States)

    Han, Jinu; Kim, Do Wook; Lee, Chul-Ho; Han, Sueng-Han

    2016-06-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive neurodegeneration with brain iron accumulation and characterized by extrapyramidal signs, vision loss, and intellectual decline. PKAN is caused by mutations in the PANK2 gene, which codes for a mitochondrial enzyme that phosphorylates vitamin B5 in the first reaction of the coenzyme A biosynthetic pathway. Visual failure in this disorder is typically due to pigmentary retinopathy. Yet our patient, a 13-year-old girl with PKAN, developed bilateral optic atrophy and the appearance of the retina and electroretinography were normal. Optic atrophy is a rare finding in patients with PKAN. It is important for the clinician to consider PKAN in the differential diagnosis of patients presenting with signs of extrapyramidal dysfunction, cognitive decline, and vision loss because of optic atrophy. PMID:26828840

  9. hCINAP is an atypical mammalian nuclear adenylate kinase with an ATPase motif: structural and functional studies.

    Science.gov (United States)

    Drakou, Christina E; Malekkou, Anna; Hayes, Joseph M; Lederer, Carsten W; Leonidas, Demetres D; Oikonomakos, Nikos G; Lamond, Angus I; Santama, Niovi; Zographos, Spyros E

    2012-01-01

    Human coilin interacting nuclear ATPase protein (hCINAP) directly interacts with coilin, a marker protein of Cajal Bodies (CBs), nuclear organelles involved in the maturation of small nuclear ribonucleoproteins UsnRNPs and snoRNPs. hCINAP has previously been designated as an adenylate kinase (AK6), but is very atypical as it exhibits unusually broad substrate specificity, structural features characteristic of ATPase/GTPase proteins (Walker motifs A and B) and also intrinsic ATPase activity. Despite its intriguing structure, unique properties and cellular localization, the enzymatic mechanism and biological function of hCINAP have remained poorly characterized. Here, we offer the first high-resolution structure of hCINAP in complex with the substrate ADP (and dADP), the structure of hCINAP with a sulfate ion bound at the AMP binding site, and the structure of the ternary complex hCINAP-Mg(2+) ADP-Pi. Induced fit docking calculations are used to predict the structure of the hCINAP-Mg(2+) ATP-AMP ternary complex. Structural analysis suggested a functional role for His79 in the Walker B motif. Kinetic analysis of mutant hCINAP-H79G indicates that His79 affects both AK and ATPase catalytic efficiency and induces homodimer formation. Finally, we show that in vivo expression of hCINAP-H79G in human cells is toxic and drastically deregulates the number and appearance of CBs in the cell nucleus. Our findings suggest that hCINAP may not simply regulate nucleotide homeostasis, but may have broader functionality, including control of CB assembly and disassembly in the nucleus of human cells. PMID:22038794

  10. Typical Versus Atypical Anorexia Nervosa Among Adolescents: Clinical Characteristics and Implications for ICD-11.

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    Silén, Yasmina; Raevuori, Anu; Jüriloo, Elisabeth; Tainio, Veli-Matti; Marttunen, Mauri; Keski-Rahkonen, Anna

    2015-09-01

    There is scant research on the clinical utility of differentiating International Classification of Diseases (ICD) 10 diagnoses F50.0 anorexia nervosa (typical AN) and F50.1 atypical anorexia. We reviewed systematically records of 47 adolescents who fulfilled criteria for ICD-10 F50.0 (n = 34) or F50.1 (n = 13), assessing the impact of diagnostic subtype, comorbidity, background factors and treatment choices on recovery. Atypical AN patients were significantly older (p = 0.03), heavier (minimum body mass index 16.7 vs 15.1 kg/m(2) , p = 0.003) and less prone to comorbidities (38% vs 71%, p = 0.04) and had shorter, less intensive and less costly treatments than typical AN patients. The diagnosis of typical versus atypical AN was the sole significant predictor of treatment success: recovery from atypical AN was 4.3 times (95% confidence interval [1.1, 17.5]) as likely as recovery from typical AN. Overall, our findings indicate that a broader definition of AN may dilute the prognostic value of the diagnosis, and therefore, ICD-11 should retain its distinction between typical and atypical AN. PMID:26010207

  11. Typical Versus Atypical Anorexia Nervosa Among Adolescents: Clinical Characteristics and Implications for ICD-11.

    Science.gov (United States)

    Silén, Yasmina; Raevuori, Anu; Jüriloo, Elisabeth; Tainio, Veli-Matti; Marttunen, Mauri; Keski-Rahkonen, Anna

    2015-09-01

    There is scant research on the clinical utility of differentiating International Classification of Diseases (ICD) 10 diagnoses F50.0 anorexia nervosa (typical AN) and F50.1 atypical anorexia. We reviewed systematically records of 47 adolescents who fulfilled criteria for ICD-10 F50.0 (n = 34) or F50.1 (n = 13), assessing the impact of diagnostic subtype, comorbidity, background factors and treatment choices on recovery. Atypical AN patients were significantly older (p = 0.03), heavier (minimum body mass index 16.7 vs 15.1 kg/m(2) , p = 0.003) and less prone to comorbidities (38% vs 71%, p = 0.04) and had shorter, less intensive and less costly treatments than typical AN patients. The diagnosis of typical versus atypical AN was the sole significant predictor of treatment success: recovery from atypical AN was 4.3 times (95% confidence interval [1.1, 17.5]) as likely as recovery from typical AN. Overall, our findings indicate that a broader definition of AN may dilute the prognostic value of the diagnosis, and therefore, ICD-11 should retain its distinction between typical and atypical AN.

  12. Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake

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    Daphna D.J. Habets

    2012-09-01

    Full Text Available Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/ long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-λ knockout mice the roles of atypical PKCs (PKC-ζ and PKC-λ in regulating cardiac glucose and fatty acid uptake. Results: Neither insulin-stimulated nor AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC-λ ablation in cardiomyocytes. In contrast, myristoylated PKC-ζ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty acid uptake by >80% in both wild-type and PKC-λ-knockout cardiomyocytes. In PKC-λ knockout cardiomyocytes, PKC-ζ is the sole remaining atypical PKC isoform, and its expression level is not different from wild-type cardiomyocytes, in which it contributes to 29% and 17% of total atypical PKC expression and phosphorylation, respectively. Conclusion: Taken together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated glucose uptake into the heart, as well as for insulin-stimulated and AMPK-mediated fatty acid uptake. However, the residual PKC-ζ activity in PKC-λ-knockout cardiomyocytes is sufficient to allow optimal stimulation of glucose and fatty acid uptake, indicating that atypical PKCs are necessary but not rate-limiting in the regulation of cardiac substrate uptake and that PKC-λ and PKC-ζ have interchangeable functions in these processes.

  13. Activation of Plant Immune Responses by a Gain-of-Function Mutation in an Atypical Receptor-Like Kinase1[C][W][OA

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    Bi, Dongling; Cheng, Yu Ti; Li, Xin; Zhang, Yuelin

    2010-01-01

    Arabidopsis (Arabidopsis thaliana) suppressor of npr1-1, constitutive1 (snc1) contains a gain-of-function mutation in a Toll/interleukin receptor-nucleotide binding site-leucine-rich repeat Resistance (R) protein and it has been a useful tool for dissecting R-protein-mediated immunity. Here we report the identification and characterization of snc4-1D, a semidominant mutant with snc1-like phenotypes. snc4-1D constitutively expresses defense marker genes PR1, PR2, and PDF1.2, and displays enhanced pathogen resistance. Map-based cloning of SNC4 revealed that it encodes an atypical receptor-like kinase with two predicted extracellular glycerophosphoryl diester phosphodiesterase domains. The snc4-1D mutation changes an alanine to threonine in the predicted cytoplasmic kinase domain. Wild-type plants transformed with the mutant snc4-1D gene displayed similar phenotypes as snc4-1D, suggesting that the mutation is a gain-of-function mutation. Epistasis analysis showed that NON-RACE-SPECIFIC DISEASE RESISTANCE1 is required for the snc4-1D mutant phenotypes. In addition, the snc4-1D mutant phenotypes are partially suppressed by knocking out MAP KINASE SUBSTRATE1, a positive defense regulator associated with MAP KINASE4. Furthermore, both the morphology and constitutive pathogen resistance of snc4-1D are partially suppressed by blocking jasmonic acid synthesis, suggesting that jasmonic acid plays an important role in snc4-1D-mediated resistance. Identification of snc4-1D provides us a unique genetic system for analyzing the signal transduction pathways downstream of receptor-like kinases. PMID:20508139

  14. Serotonin type-1D receptor stimulation of A-type K(+) channel decreases membrane excitability through the protein kinase A- and B-Raf-dependent p38 MAPK pathways in mouse trigeminal ganglion neurons.

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    Zhao, Xianyang; Zhang, Yuan; Qin, Wenjuan; Cao, Junping; Zhang, Yi; Ni, Jianqiang; Sun, Yangang; Jiang, Xinghong; Tao, Jin

    2016-08-01

    Although recent studies have implicated serotonin 5-HT1B/D receptors in the nociceptive sensitivity of primary afferent neurons, the underlying molecular and cellular mechanisms remain unclear. In this study, we identified a novel functional role of the 5-HT1D receptor subtype in regulating A-type potassium (K(+)) currents (IA) as well as membrane excitability in small trigeminal ganglion (TG) neurons. We found that the selective activation of 5-HT1D, rather than 5-HT1B, receptors reversibly increased IA, while the sustained delayed rectifier K(+) current was unaffected. The 5-HT1D-mediated IA increase was associated with a depolarizing shift in the voltage dependence of inactivation. Blocking G-protein signaling with pertussis toxin or by intracellular application of a selective antibody raised against Gαo or Gβ abolished the 5-HT1D effect on IA. Inhibition of protein kinase A (PKA), but not of phosphatidylinositol 3-kinase or protein kinase C, abolished the 5-HT1D-mediated IA increase. Analysis of phospho-p38 (p-p38) revealed that activation of 5-HT1D, but not 5-HT1B, receptors significantly activated p38, while p-ERK and p-JNK were unaffected. The p38 MAPK inhibitor SB203580, but not its inactive analogue SB202474, and inhibition of B-Raf blocked the 5-HT1D-mediated IA response. Functionally, we observed a significantly decreased action potential firing rate induced by the 5-HT1D receptors; pretreatment with 4-aminopyridine abolished this effect. Taken together, these results suggest that the activation of 5-HT1D receptors selectively enhanced IA via the Gβγ of the Go-protein, PKA, and the sequential B-Raf-dependent p38 MAPK signaling cascade. This 5-HT1D receptor effect may contribute to neuronal hypoexcitability in small TG neurons. PMID:27156838

  15. Emplacement age and tectonic implications of the Xilinhot A-type granite in Inner Mongolia, China

    Institute of Scientific and Technical Information of China (English)

    SHI Guanghai; MIAO Laicheng; ZHANG Fuqing; JIAN Ping; FAN Weiming; LIU Dunyi

    2004-01-01

    A new rock type of granite, approximate 45 km2 in area and located about 10 km south of Xilinhot, Inner Mongolia, was found in the Sunitezuoqi (or called Suzuoqi)-Xilinhot tectonic belt and identified as an A-type mia- rolitic intrusion. The pluton has miarolitic structure and is composed chiefly of perthite, quartz, euhedral albite and potassium feldspar. Various types of textures occur in the pluton, such as perthitie, graphic and myrmekite textures. Only quartz is found in miarolitic cavity. This A-type granite with seagull-shaped REE patterns and obvious negative Eu anomaly (δEu = 0.24-0.28) is high in SiO2 (76%-77%), K and Na (Na2O + K2O = 7.75%-8.15%) and low in Ca (CaO = 0.20%-0.22%), Fe and Mg. Both petrographical observations and chemical compositions indicate that it is an A-type granite. Zircon SHRIMP U-Pb analyses indicate that this A-type granite was emplaced at 276 ( 2 Ma and coeval with the same type of granites in the adjacent areas. Therefore, it suggests that this pluton was likely formed in a post-orogenic extensional setting and probably related to break-off of subducted slabs in Central Asian Orogenic Belt (CAOB), which indicate that the Sunitezuoqi-Xilinhot belt was tectonically evolved into post-orogenic stage since early Permian.

  16. The Structure of Lombricine Kinase: Implications for Phosphagen Conformational Changes

    Energy Technology Data Exchange (ETDEWEB)

    Bush, D. Jeffrey; Kirillova, Olga; Clark, Shawn A.; Davulcu, Omar; Fabiola, Felcy; Xie, Qing; Somasundaram, Thayumanasamy; Ellington, W. Ross; Chapman, Michael S. (Oregon HSU); (FSU)

    2012-05-29

    Lombricine kinase is a member of the phosphagen kinase family and a homolog of creatine and arginine kinases, enzymes responsible for buffering cellular ATP levels. Structures of lombricine kinase from the marine worm Urechis caupo were determined by x-ray crystallography. One form was crystallized as a nucleotide complex, and the other was substrate-free. The two structures are similar to each other and more similar to the substrate-free forms of homologs than to the substrate-bound forms of the other phosphagen kinases. Active site specificity loop 309-317, which is disordered in substrate-free structures of homologs and is known from the NMR of arginine kinase to be inherently dynamic, is resolved in both lombricine kinase structures, providing an improved basis for understanding the loop dynamics. Phosphagen kinases undergo a segmented closing on substrate binding, but the lombricine kinase ADP complex is in the open form more typical of substrate-free homologs. Through a comparison with prior complexes of intermediate structure, a correlation was revealed between the overall enzyme conformation and the substrate interactions of His{sup 178}. Comparative modeling provides a rationale for the more relaxed specificity of these kinases, of which the natural substrates are among the largest of the phosphagen substrates.

  17. Host Signal Transduction and Protein Kinases Implicated in Legionella Infection

    OpenAIRE

    Hempstead, Andrew D.; Isberg, Ralph R.

    2013-01-01

    Modulation of the phosphorylation status of proteins by both kinases and phosphatases plays an important role in cellular signal transduction. Challenge of host cells by Legionella pneumophila manipulates the phosphorylation state of multiple host factors. These changes play roles in bacterial uptake, vacuole modification, cellular survival, and the immune response. In addition to modification by host cell kinases in response to the bacterium, L. pneumophila translocates bacterial kinases int...

  18. Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake

    DEFF Research Database (Denmark)

    Habets, Daphna D J; Luiken, Joost J F P; Ouwens, Margriet;

    2012-01-01

    cardiac glucose and fatty acid uptake. Results: Neither insulin-stimulated nor AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC-¿ ablation in cardiomyocytes. In contrast, myristoylated PKC-¿ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty...... and phosphorylation, respectively. Conclusion: Taken together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated glucose uptake into the heart, as well as for insulin-stimulated and AMPK-mediated fatty acid uptake. However, the residual PKC-¿ activity in PKC-¿-knockout cardiomyocytes is sufficient...

  19. Structure-function analysis of STRUBBELIG, an Arabidopsis atypical receptor-like kinase involved in tissue morphogenesis.

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    Prasad Vaddepalli

    Full Text Available Tissue morphogenesis in plants requires the coordination of cellular behavior across clonally distinct histogenic layers. The underlying signaling mechanisms are presently being unraveled and are known to include the cell surface leucine-rich repeat receptor-like kinase STRUBBELIG in Arabidopsis. To understand better its mode of action an extensive structure-function analysis of STRUBBELIG was performed. The phenotypes of 20 EMS and T-DNA-induced strubbelig alleles were assessed and homology modeling was applied to rationalize their possible effects on STRUBBELIG protein structure. The analysis was complemented by phenotypic, cell biological, and pharmacological investigations of a strubbelig null allele carrying genomic rescue constructs encoding fusions between various mutated STRUBBELIG proteins and GFP. The results indicate that STRUBBELIG accepts quite some sequence variation, reveal the biological importance for the STRUBBELIG N-capping domain, and reinforce the notion that kinase activity is not essential for its function in vivo. Furthermore, individual protein domains of STRUBBELIG cannot be related to specific STRUBBELIG-dependent biological processes suggesting that process specificity is mediated by factors acting together with or downstream of STRUBBELIG. In addition, the evidence indicates that biogenesis of a functional STRUBBELIG receptor is subject to endoplasmic reticulum-mediated quality control, and that an MG132-sensitive process regulates its stability. Finally, STRUBBELIG and the receptor-like kinase gene ERECTA interact synergistically in the control of internode length. The data provide genetic and molecular insight into how STRUBBELIG regulates intercellular communication in tissue morphogenesis.

  20. Clinical implications and histological correlation of atypical glandular cells found in cervicovaginal smears

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    Beliza Loos

    2014-08-01

    Full Text Available Introduction: Atypical glandular cells (AGC are carriers of insufficient nuclear abnormalities for the diagnosis of adenocarcinoma, but exceed the criteria for classification as reactive glandular cells. This is an uncommon diagnosis, which may be associated with neoplastic lesions. Objective: To evaluate the clinical significance of primary cytological diagnosis of AGC through correlation with results of subsequent cyto-histologic examination. Materials and methods: 10 years retrospective study based on cervical cytologic results indicating AGC, classified as "possibly non-neoplastic" or "cannot exclude high-grade intraepithelial lesion". It was performed cyto-histopathological correlation in cases that were submitted to subsequent histopathological examination up to two years after cervical cytology analysis. Results: AGC were reported in 380 (0.06% exams, providing 160 cases with subsequent biopsy. 85 (53.1% of these, presented benign changes and 75 (46.9% neoplastic lesions. From 114 "possibly non-neoplastic" cytological results, 71 (62.3% had benign histological changes, and 43 (37.7% neoplastic lesions, corresponding to a negative predictive value (NPV of 62.3%. In contrast, among the 46 AGC "cannot exclude high-grade intraepithelial lesion" results, 14 (30.4% presented benign changes and 32 (69.6% neoplastic lesions (positive predictive value [PPV] = 69.6%. Discussion: The high rate of cancer associated with the diagnosis of AGC reassures the importance of recognizing these atypical cells in pap smears. The classification of "possibly non-neoplastic" and "cannot exclude high-grade intraepithelial lesion" may suggest the origin of cytological changes. Conclusion: Our results reinforce the importance of adequate follow-up of patients with AGC diagnosis on cervical cytology.

  1. Crystal structure of LpxK, the 4'-kinase of lipid A biosynthesis and atypical P-loop kinase functioning at the membrane interface.

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    Emptage, Ryan P; Daughtry, Kelly D; Pemble, Charles W; Raetz, Christian R H

    2012-08-01

    In Gram-negative bacteria, the hydrophobic anchor of the outer membrane lipopolysaccharide is lipid A, a saccharolipid that plays key roles in both viability and pathogenicity of these organisms. The tetraacyldisaccharide 4'-kinase (LpxK) of the diverse P-loop-containing nucleoside triphosphate hydrolase superfamily catalyzes the sixth step in the biosynthetic pathway of lipid A, and is the only known P-loop kinase to act upon a lipid substrate at the membrane. Here, we report the crystal structures of apo- and ADP/Mg(2+)-bound forms of Aquifex aeolicus LpxK to a resolution of 1.9 Å and 2.2 Å, respectively. LpxK consists of two α/β/α sandwich domains connected by a two-stranded β-sheet linker. The N-terminal domain, which has most structural homology to other family members, is responsible for catalysis at the P-loop and positioning of the disaccharide-1-phosphate substrate for phosphoryl transfer on the inner membrane. The smaller C-terminal domain, a substructure unique to LpxK, helps bind the nucleotide substrate and Mg(2+) cation using a 25° hinge motion about its base. Activity was severely reduced in alanine point mutants of conserved residues D138 and D139, which are not directly involved in ADP or Mg(2+) binding in our structures, indicating possible roles in phosphoryl acceptor positioning or catalysis. Combined structural and kinetic studies have led to an increased understanding of the enzymatic mechanism of LpxK and provided the framework for structure-based antimicrobial design. PMID:22826246

  2. Atypical Depression

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    Erhan Ertekin

    2013-09-01

    Full Text Available Atypical depression is defined as a specifier of major depressive disorder. Columbia criteria for atypical depression are commonly used to make a diagnosis. Female sex, onset at early age, chronic course, and higher rate of comorbidity (especially anxiety disorder and bipolar disorder is noteworthy in atypical depression. Although, the atypical depression seems to support the familial genetic transition, there is not any specific study supporting these data. In the treatment of atypical depression, monoamine oxidase inhibitors are reported to be more effective than tricyclic antidepressants. In recent studies, selective serotonin reuptake inhibitors have also proven to be efficient.

  3. Targeting atypical protein kinase C iota reduces viability in glioblastoma stem-like cells via a notch signaling mechanism.

    Science.gov (United States)

    Phillips, Emma; Lang, Verena; Bohlen, Jonathan; Bethke, Frederic; Puccio, Laura; Tichy, Diana; Herold-Mende, Christel; Hielscher, Thomas; Lichter, Peter; Goidts, Violaine

    2016-10-15

    In a previous study, Protein Kinase C iota (PRKCI) emerged as an important candidate gene for glioblastoma (GBM) stem-like cell (GSC) survival. Here, we show that PKCι is overexpressed and activated in patient derived GSCs compared with normal neural stem cells and normal brain lysate, and that silencing of PRKCI in GSCs causes apoptosis, along with loss of clonogenicity and reduced proliferation. Notably, PRKCI silencing reduces tumor growth in vivo in a xenograft mouse model. PKCι has been intensively studied as a therapeutic target in non-small cell lung cancer, resulting in the identification of an inhibitor, aurothiomalate (ATM), which disrupts the PKCι/ERK signaling axis. However, we show that, although sensitive to pharmacological inhibition via a pseudosubstrate peptide inhibitor, GSCs are much less sensitive to ATM, suggesting that PKCι acts along a different signaling axis in GSCs. Gene expression profiling of PRKCI-silenced GSCs revealed a novel role of the Notch signaling pathway in PKCι mediated GSC survival. A proximity ligation assay showed that Notch1 and PKCι are in close proximity in GSCs. Targeting PKCι in the context of Notch signaling could be an effective way of attacking the GSC population in GBM. PMID:27299852

  4. Perspectives on the rhythm-grammar link and its implications for typical and atypical language development.

    Science.gov (United States)

    Gordon, Reyna L; Jacobs, Magdalene S; Schuele, C Melanie; McAuley, J Devin

    2015-03-01

    This paper reviews the mounting evidence for shared cognitive mechanisms and neural resources for rhythm and grammar. Evidence for a role of rhythm skills in language development and language comprehension is reviewed here in three lines of research: (1) behavioral and brain data from adults and children, showing that prosody and other aspects of timing of sentences influence online morpho-syntactic processing; (2) comorbidity of impaired rhythm with grammatical deficits in children with language impairment; and (3) our recent work showing a strong positive association between rhythm perception skills and expressive grammatical skills in young school-age children with typical development. Our preliminary follow-up study presented here revealed that musical rhythm perception predicted variance in 6-year-old children's production of complex syntax, as well as online reorganization of grammatical information (transformation); these data provide an additional perspective on the hierarchical relations potentially shared by rhythm and grammar. A theoretical framework for shared cognitive resources for the role of rhythm in perceiving and learning grammatical structure is elaborated on in light of potential implications for using rhythm-emphasized musical training to improve language skills in children. PMID:25773612

  5. Crystal Structure of Pyridoxal Kinase from the Escherichia coli pdxK Gene: Implications for the Classification of Pyridoxal Kinases

    OpenAIRE

    Safo, Martin K.; Musayev, Faik N.; di Salvo, Martino L.; Hunt, Sharyn; Claude, Jean-Baptiste; Schirch, Verne

    2006-01-01

    The pdxK and pdxY genes have been found to code for pyridoxal kinases, enzymes involved in the pyridoxal phosphate salvage pathway. Two pyridoxal kinase structures have recently been published, including Escherichia coli pyridoxal kinase 2 (ePL kinase 2) and sheep pyridoxal kinase, products of the pdxY and pdxK genes, respectively. We now report the crystal structure of E. coli pyridoxal kinase 1 (ePL kinase 1), encoded by a pdxK gene, and an isoform of ePL kinase 2. The structures were deter...

  6. Crystal structure of pyridoxal kinase from the Escherichia coli pdxK gene: implications for the classification of pyridoxal kinases.

    Science.gov (United States)

    Safo, Martin K; Musayev, Faik N; di Salvo, Martino L; Hunt, Sharyn; Claude, Jean-Baptiste; Schirch, Verne

    2006-06-01

    The pdxK and pdxY genes have been found to code for pyridoxal kinases, enzymes involved in the pyridoxal phosphate salvage pathway. Two pyridoxal kinase structures have recently been published, including Escherichia coli pyridoxal kinase 2 (ePL kinase 2) and sheep pyridoxal kinase, products of the pdxY and pdxK genes, respectively. We now report the crystal structure of E. coli pyridoxal kinase 1 (ePL kinase 1), encoded by a pdxK gene, and an isoform of ePL kinase 2. The structures were determined in the unliganded and binary complexes with either MgATP or pyridoxal to 2.1-, 2.6-, and 3.2-A resolutions, respectively. The active site of ePL kinase 1 does not show significant conformational change upon binding of either pyridoxal or MgATP. Like sheep PL kinase, ePL kinase 1 exhibits a sequential random mechanism. Unlike sheep pyridoxal kinase, ePL kinase 1 may not tolerate wide variation in the size and chemical nature of the 4' substituent on the substrate. This is the result of differences in a key residue at position 59 on a loop (loop II) that partially forms the active site. Residue 59, which is His in ePL kinase 1, interacts with the formyl group at C-4' of pyridoxal and may also determine if residues from another loop (loop I) can fill the active site in the absence of the substrate. Both loop I and loop II are suggested to play significant roles in the functions of PL kinases.

  7. Cooperation between c-Met and focal adhesion kinase family members in medulloblastoma and implications for therapy

    OpenAIRE

    Guessous, Fadila; Yang, Yanzhi; Johnson, Elizabeth; Marcinkiewicz, Lukasz; Smith, Matthew; Zhang, Ying; Kofman, Alexander; Schiff, David; Christensen, James; Abounader, Roger

    2011-01-01

    We previously demonstrated the involvement of the tyrosine kinase receptor c-Met in medulloblastoma malignancy. The nonreceptor tyrosine kinases FAK and Pyk2, are key players in the progression of different cancers. However, their role in medulloblastoma malignancy is not well understood. In this study, using a protein array approach, we found that c-Met phosphorylates FAK and Pyk2 in medulloblastoma cells. We therefore studied the interactions between c-Met and FAK/Pyk2 and their implication...

  8. 3C 57 as an atypical radio-loud quasar: implications for the radio-loud/radio-quiet dichotomy

    Science.gov (United States)

    Sulentic, J. W.; Martínez-Carballo, M. A.; Marziani, P.; del Olmo, A.; Stirpe, G. M.; Zamfir, S.; Plauchu-Frayn, I.

    2015-06-01

    Lobe-dominated radio-loud (LD RL) quasars occupy a restricted domain in the 4D Eigenvector 1 (4DE1) parameter space which implies restricted geometry/physics/kinematics for this subclass compared to the radio-quiet (RQ) majority of quasars. We discuss how this restricted domain for the LD RL parent population supports the notion for a RQ-RL dichotomy among type 1 sources. 3C 57 is an atypical RL quasar that shows both uncertain radio morphology and falls in a region of 4DE1 space where RL quasars are rare. We present new radio flux and optical spectroscopic measures designed to verify its atypical optical/UV spectroscopic behaviour and clarify its radio structure. The former data confirms that 3C 57 falls off the 4DE1 quasar `main sequence' with both extreme optical Fe II emission (R_{Fe II} ˜ 1) and a large C IV λ1549 profile blueshift (˜-1500 km s-1). These parameter values are typical of extreme Population A sources which are almost always RQ. New radio measures show no evidence for flux change over a 50+ year time-scale consistent with compact steep-spectrum (or young LD) over core-dominated morphology. In the 4DE1 context where LD RL are usually low L/LEdd quasars, we suggest that 3C 57 is an evolved RL quasar (i.e. large blackhole mass) undergoing a major accretion event leading to a rejuvenation reflected by strong Fe II emission, perhaps indicating significant heavy metal enrichment, high bolometric luminosity for a low-redshift source and resultant unusually high Eddington ratio giving rise to the atypical C IV λ1549.

  9. 3C 57 as an Atypical Radio-Loud Quasar: Implications for the Radio-Loud/Radio-Quiet Dichotomy

    CERN Document Server

    Sulentic, J W; Marziani, P; del Olmo, A; Stirpe, G M; Zamfir, S; Plauchu-Frayn, I

    2015-01-01

    Lobe-dominated radio-loud (LD RL) quasars occupy a restricted domain in the 4D Eigenvector 1 (4DE1) parameter space which implies restricted geometry/physics/kinematics for this subclass compared to the radio-quiet (RQ) majority of quasars. We discuss how this restricted domain for the LD RL parent population supports the notion for a RQ-RL dichotomy among Type 1 sources. 3C 57 is an atypical RL quasar that shows both uncertain radio morphology and falls in a region of 4DE1 space where RL quasars are rare. We present new radio flux and optical spectroscopic measures designed to verify its atypical optical/UV spectroscopic behaviour and clarify its radio structure. The former data confirms that 3C 57 falls off the 4DE1 quasar "main sequence" with both extreme optical FeII emission (R_{FeII} ~ 1) and a large CIV 1549 profile blueshift (~ -1500 km/s). These parameter values are typical of extreme Population A sources which are almost always RQ. New radio measures show no evidence for flux change over a 50+ year ...

  10. Mutational analysis of residues implicated in the interaction between protein kinase CK2 and peptide substrates

    DEFF Research Database (Denmark)

    Sarno, S; Vaglio, P; Marin, O;

    1997-01-01

    Sixteen derivatives of the optimal peptide substrate RRRA-DDSDDDDD in which aspartic acids were singly or multiply substituted by alanine have been assayed for their phosphorylation efficiency by either wild type protein kinase CK2 or CK2 alpha mutants defective in substrate recognition. With wild...... substitutions tend to have a more than additive effect even if they affect individually dispensable aspartic acids; thus, double, triple, and quintuple substitutions at positions n - 2 and -1, and n + 2, +4, and +5 had detrimental consequences comparable to those observed with substitutions at n + 1 and n + 3....... However, if the suboptimal substrate RRRA-AASDDDDD was used, the single mutants K49A, K71A, K77A, R80A, and H160A also exhibited Km values significantly higher than those of wild type CK2. Kinetic analysis with singly substituted derivatives of peptide RRRA-DDSDDDDD revealed that K49 is implicated in the...

  11. Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress

    Directory of Open Access Journals (Sweden)

    Kwang eChoi

    2011-07-01

    Full Text Available Suicide is a serious public health issue that results from an interaction between multiple risk factors including individual vulnerabilities to complex feelings of hopelessness, fear and stress. Although kinase genes have been implicated in fear and stress, including the consolidation and extinction of fearful memories, expression profiles of those genes in the brain of suicide victims are less clear. Using gene expression microarray data from the Online Stanley Genomics Database (www.stanleygenomics.org and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK, the cyclin-dependent kinase (CDK, the mitogen-activated protein kinase (MAPK, and the protein kinase C (PKC in the prefrontal cortex (PFC of mood disorder patients died with suicide (n=45 and without suicide (N=38. We also investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (n=46. The expression levels of CAMK2B, CDK5, MAPK9, and PRKCI were increased in the PFC of suicide victims as compared to non-suicide controls (FDR-adjusted p < 0.05, fold change > 1.1. Those genes also showed changes in expression pattern during the postnatal development (FDR-adjusted p < 0.05. These results suggest that multiple kinase genes undergo age-dependent changes in normal brains as well as pathological changes in suicide brains. These findings may provide an important link to protein kinases known to be important for the development of fear memory, stress-associated neural plasticity and up-regulation in the PFC of suicide victims. More research is needed to better understand the functional role of these kinase genes that may be associated with the pathophysiology of suicide.

  12. Transforming growth factor-β1 induces cell cycle arrest by activating atypical cyclin-dependent kinase 5 through up-regulation of Smad3-dependent p35 expression in human MCF10A mammary epithelial cells.

    Science.gov (United States)

    Park, Seong Ji; Yang, Sun Woo; Kim, Byung-Chul

    2016-04-01

    Cyclin-dependent kinases (Cdks) play important roles in control of cell division. Cdk5 is an atypical member of Cdk family with non-cyclin-like regulatory subunit, p35, but its role in cell cycle progression is still unclear. In the present study, we investigated the role of Cdk5/p35 on transforming growth factor-β1 (TGF-β1)-induced cell cycle arrest. In human MCF10A mammary epithelial cells, TGF-β1 induced cell cycle arrest at G1 phase and increased p27KIP1 expression. Interestingly, pretreatment with roscovitine, an inhibitor of Cdk5, or transfection with small interfering (si) RNAs specific to Cdk5 and p35 significantly attenuated the TGF-β1-induced p27KIP1 expression and cell cycle arrest. TGF-β1 increased Cdk5 activity via up-regulation of p35 gene at transcriptional level, and these effects were abolished by transfection with Smad3 siRNA or infection of adenovirus carrying Smad3 mutant at the C-tail (3SA). Chromatin immunoprecipitation assay further revealed that wild type Smad3, but not mutant Smad3 (3SA), binds to the region of the p35 promoter region (-1000--755) in a TGF-β1-dependent manner. These results for the first time demonstrate a role of Cdk5/p35 in the regulation of cell cycle progression modulated by TGF-β1.

  13. Acute rhabdomyolysis associated with atypical Guillain-Barré syndrome.

    OpenAIRE

    Scott, A. J.; Duncan, R; Henderson, L.; Jamal, G A; Kennedy, P G

    1991-01-01

    We report a patient with atypical Guillain-Barré syndrome associated with acute rhabdomyolysis. Rhabdomyolysis may be the cause of elevation of creatine kinase sometimes seen in patients with Guillain-Barré syndrome.

  14. The frequencies and clinical implications of mutations in 33 kinase-related genes in locally advanced rectal cancer: a pilot study.

    LENUS (Irish Health Repository)

    Abdul-Jalil, Khairun I

    2014-08-01

    Locally advanced rectal cancer (LARC: T3\\/4 and\\/or node-positive) is treated with preoperative\\/neoadjuvant chemoradiotherapy (CRT), but responses are not uniform. The phosphatidylinositol 3-kinase (PI3K), MAP kinase (MAPK), and related pathways are implicated in rectal cancer tumorigenesis. Here, we investigated the association between genetic mutations in these pathways and LARC clinical outcomes.

  15. Oxidized, magnetite-series, rapakivi-type granites of Carajás, Brazil: Implications for classification and petrogenesis of A-type granites

    Science.gov (United States)

    Dall'Agnol, Roberto; de Oliveira, Davis Carvalho

    2007-02-01

    The varying geochemical and petrogenetic nature of A-type granites is a controversial issue. The oxidized, magnetite-series A-type granites, defined by Anderson and Bender [Anderson, J.L., Bender, E.E., 1989. Nature and origin of Proterozoic A-type granitic magmatism in the southwestern United States of America. Lithos 23, 19-52.], are the most problematic as they do not strictly follow the original definition of A-type granites, and approach calc-alkaline and I-type granites in some aspects. The oxidized Jamon suite A-type granites of the Carajás province of the Amazonian craton are compared with the magnetite-series granites of Laurentia, and other representative A-type granites, including Finnish rapakivi and Lachlan Fold Belt A-type granites, as well as with calc-alkaline, I-type orogenic granites. The geochemistry and petrogenesis of different groups of A-types granites are discussed with an emphasis on oxidized A-type granites in order to define their geochemical signatures and to clarify the processes involved in their petrogenesis. Oxidized A-type granites are clearly distinguished from calc-alkaline Cordilleran granites not only regarding trace element composition, as previously demonstrated, but also in their major element geochemistry. Oxidized A-type granites have high whole-rock FeO t/(FeO t + MgO), TiO 2/MgO, and K 2O/Na 2O and low Al 2O 3 and CaO compared to calc-alkaline granites. The contrast of Al 2O 3 contents in these two granite groups is remarkable. The CaO/(FeO t + MgO + TiO 2) vs. CaO + Al 2O 3 and CaO/(FeO t + MgO + TiO 2) vs. Al 2O 3 diagrams are proposed to distinguish A-type and calc-alkaline granites. Whole-rock FeO t/(FeO t + MgO) and the FeO t/(FeO t + MgO) vs. Al 2O 3 and FeO t/(FeO t + MgO) vs. Al 2O 3/(K 2O/Na 2O) diagrams are suggested for discrimination of oxidized and reduced A-type granites. Experimental data indicate that, besides pressure, the nature of A-type granites is dependent of ƒO 2 conditions and the water content

  16. Multiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer

    Institute of Scientific and Technical Information of China (English)

    Keum-Jin; Yang; Jongsun; Park

    2010-01-01

    3-phosphoinositide-dependent protein kinase-1(PDK1) is a central mediator of cellular signaling between phosphoinositide-3 kinase and various intracellular serine/threonine kinases,including protein kinase B,p70 ribosomal S6 kinase,serum and glucocorticoid-inducible kinase,and protein kinase C.PDK1 activates members of the AGC family of protein kinases by phosphorylating serine/threonine residues in the activation loop.Here,we review the regulatory mechanisms of PDK1 and its roles in cancer.PDK1 is activated by autophosphorylation in the activation loop and other serine residues,as well as by phosphorylation of Tyr-9 and Tyr-373/376.Src appears to recognize PDK1 following tyrosine phosphorylation.The role of heat shock protein 90 in regulating PDK1 stability and PDK1-Src complex formation are also discussed.Furthermore,we summarize the subcellular distribution of PDK1.Finally,an important role for PDK1 in cancer chemotherapy is proposed.In conclusion,a better understanding of its molecular regulatory mechanisms in various signaling pathways will help to explain how PDK1 acts as an oncogenic kinase in various cancers,and will contribute to the development of novel cancer chemotherapies.

  17. Detection of Human Papillomavirus among Women with Atypical Squamous Cells of Undetermined Significance Referred to Colposcopy: Implications for Clinical Management in Low and MiddleIncome Countries.

    Science.gov (United States)

    de Abreu, Andre Lp; Gimenes, Fabricia; Malaguti, Natalia; Pereira, Monalisa W; Uchimura, Nelson S; Consolaro, Marcia El

    2016-01-01

    To determine the prevalence of human papillomavirus (HPV) among women with atypical squamous cells of undetermined significance (ASC-US) referred to colposcopy and the implications for clinical management in low- and middle-income countries (LMIC), the present study was conducted. We included 200 women living in Maringa÷Brazil referred to colposcopy service between August 2012 and March 2013 due to an abnormal cytology from ASC-US until high-grade intraepithelial lesion (HSIL). HPV was detected and genotyped by polymerase chain reaction (PCR). The mean age was 36.8±10.5 years, and women with and without ASC-US had similar mean ages (37.4±11.5 and 36.4±9.96 years, respectively). The highest prevalence of ASC-US occurred at 20-24 years (40%). HPV-DNA was positive in 164 (82.0%) women.Of the 57 women with ASC-US, 30 (52.6%) were HPV-DNA-positive and 21 (70%) were high-risk HPV-positive (HR-HPV); the latter was similar to women without ASC-US (76.9%) but with other abnormal cytological findings present. Our data demonstrated that performing tests for HR-HPV can be used for management of women with ASC-US to support the decision of which women should be referred for an immediate or later colposcopy. The same conclusions can be applied to other LMICs for which HPV testing for primary screening has not been adopted. PMID:27510023

  18. Association of Neoproterozoic A- and I-type Granites in South China: Implications for Generation of A-type Granites in A Subduction-related Environment

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xin-fu; ZHOU Mei-fu; LI Jian-wei; WU Fu-yuan

    2008-01-01

    @@ Neoproterozoic magmatism in the Yangtze Block of South China produced voluminous S- and I-type granites, and sparse A-type granites. The Daxiangling A-type granitic pluton is spatially associated with the Shimian I-type pluton at the western margin of the Yangtze Block. Both plutons have similar SHRIMP zircon U-Pb ages of~800 Ma and are slightly younger than the tonalite-trondhjemite-granodiorite (TTG) gneisses in the area.

  19. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jennifer M A Tullet

    2014-02-01

    Full Text Available The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK, which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be

  20. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    Science.gov (United States)

    Tullet, Jennifer M A; Araiz, Caroline; Sanders, Matthew J; Au, Catherine; Benedetto, Alexandre; Papatheodorou, Irene; Clark, Emily; Schmeisser, Kathrin; Jones, Daniel; Schuster, Eugene F; Thornton, Janet M; Gems, David

    2014-02-01

    The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be evolutionarily conserved

  1. Substrate-specific reorganization of the conformational ensemble of CSK implicates novel modes of kinase function.

    Directory of Open Access Journals (Sweden)

    Michael A Jamros

    Full Text Available Protein kinases use ATP as a phosphoryl donor for the posttranslational modification of signaling targets. It is generally thought that the binding of this nucleotide induces conformational changes leading to closed, more compact forms of the kinase domain that ideally orient active-site residues for efficient catalysis. The kinase domain is oftentimes flanked by additional ligand binding domains that up- or down-regulate catalytic function. C-terminal Src kinase (Csk is a multidomain tyrosine kinase that is up-regulated by N-terminal SH2 and SH3 domains. Although the X-ray structure of Csk suggests the enzyme is compact, X-ray scattering studies indicate that the enzyme possesses both compact and open conformational forms in solution. Here, we investigated whether interactions with the ATP analog AMP-PNP and ADP can shift the conformational ensemble of Csk in solution using a combination of small angle x-ray scattering and molecular dynamics simulations. We find that binding of AMP-PNP shifts the ensemble towards more extended rather than more compact conformations. Binding of ADP further shifts the ensemble towards extended conformations, including highly extended conformations not adopted by the apo protein, nor by the AMP-PNP bound protein. These ensembles indicate that any compaction of the kinase domain induced by nucleotide binding does not extend to the overall multi-domain architecture. Instead, assembly of an ATP-bound kinase domain generates further extended forms of Csk that may have relevance for kinase scaffolding and Src regulation in the cell.

  2. Investigation of the flexibility of protein kinases implicated in the pathology of Alzheimer's disease.

    Science.gov (United States)

    Mazanetz, Michael P; Laughton, Charles A; Fischer, Peter M

    2014-01-01

    The pathological characteristics of Alzheimer's Disease (AD) have been linked to the activity of three particular kinases--Glycogen Synthase Kinase 3β (GSK3β), Cyclin-Dependent Kinase 5 (CDK5) and Extracellular-signal Regulated Kinase 2 (ERK2). As a consequence, the design of selective, potent and drug-like inhibitors of these kinases is of particular interest. Structure-based design methods are well-established in the development of kinase inhibitors. However, progress in this field is limited by the difficulty in obtaining X-ray crystal structures suitable for drug design and by the inability of this method to resolve highly flexible regions of the protein that are crucial for ligand binding. To address this issue, we have undertaken a study of human protein kinases CDK5/p25, CDK5, ERK2 and GSK3β using both conventional molecular dynamics (MD) and the new Active Site Pressurisation (ASP) methodology, to look for kinase-specific patterns of flexibility that could be leveraged for the design of selective inhibitors. ASP was used to examine the intrinsic flexibility of the ATP-binding pocket for CDK5/p25, CDK5 and GSK3β where it is shown to be capable of inducing significant conformational changes when compared with X-ray crystal structures. The results from these experiments were used to quantify the dynamics of each protein, which supported the observations made from the conventional MD simulations. Additional information was also derived from the ASP simulations, including the shape of the ATP-binding site and the rigidity of the ATP-binding pocket. These observations may be exploited in the design of selective inhibitors of GSK3β, CDK5 and ERK2. PMID:24983862

  3. Differential role of human choline kinase α and β enzymes in lipid metabolism: Implications in cancer onset and treatment

    OpenAIRE

    Gallego Ortega, David; Ramírez de Molina, Ana; Ramos, Maria Angeles; Valdés Mora, Fátima; Barderas, Maria Gonzalez; Sarmentero Estrada, Jacinto; Lacal, Juan Carlos

    2009-01-01

    Background The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of 1phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKα and ChoKβ isoforms, the first one with two different variants of splicing. Recently ChoKα has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. Howev...

  4. Investigation of the Flexibility of Protein Kinases Implicated in the Pathology of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Michael P. Mazanetz

    2014-06-01

    Full Text Available The pathological characteristics of Alzheimer’s Disease (AD have been linked to the activity of three particular kinases—Glycogen Synthase Kinase 3β (GSK3β, Cyclin-Dependent Kinase 5 (CDK5 and Extracellular-signal Regulated Kinase 2 (ERK2. As a consequence, the design of selective, potent and drug-like inhibitors of these kinases is of particular interest. Structure-based design methods are well-established in the development of kinase inhibitors. However, progress in this field is limited by the difficulty in obtaining X-ray crystal structures suitable for drug design and by the inability of this method to resolve highly flexible regions of the protein that are crucial for ligand binding. To address this issue, we have undertaken a study of human protein kinases CDK5/p25, CDK5, ERK2 and GSK3β using both conventional molecular dynamics (MD and the new Active Site Pressurisation (ASP methodology, to look for kinase-specific patterns of flexibility that could be leveraged for the design of selective inhibitors. ASP was used to examine the intrinsic flexibility of the ATP-binding pocket for CDK5/p25, CDK5 and GSK3β where it is shown to be capable of inducing significant conformational changes when compared with X-ray crystal structures. The results from these experiments were used to quantify the dynamics of each protein, which supported the observations made from the conventional MD simulations. Additional information was also derived from the ASP simulations, including the shape of the ATP-binding site and the rigidity of the ATP-binding pocket. These observations may be exploited in the design of selective inhibitors of GSK3β, CDK5 and ERK2.

  5. Characterisation of a K390R ITK kinase dead transgenic mouse--implications for ITK as a therapeutic target.

    Directory of Open Access Journals (Sweden)

    Angela Deakin

    Full Text Available Interleukin-2 inducible tyrosine kinase (ITK is expressed in T cells and plays a critical role in signalling through the T cell receptor. Evidence, mainly from knockout mice, has suggested that ITK plays a particularly important function in Th2 cells and this has prompted significant efforts to discover ITK inhibitors for the treatment of allergic disease. However, ITK is known to have functions outside of its kinase domain and in general kinase knockouts are often not good models for the behaviour of small molecule inhibitors. Consequently we have developed a transgenic mouse where the wild type Itk allele has been replaced by a kinase dead Itk allele containing an inactivating K390R point mutation (Itk-KD mice. We have characterised the immune phenotype of these naive mice and their responses to airway inflammation. Unlike Itk knockout (Itk-/- mice, T-cells from Itk-KD mice can polymerise actin in response to CD3 activation. The lymph nodes from Itk-KD mice showed more prominent germinal centres than wild type mice and serum antibody levels were significantly abnormal. Unlike the Itk-/-, γδ T cells in the spleens of the Itk-KD mice had an impaired ability to secrete Th2 cytokines in response to anti-CD3 stimulation whilst the expression of ICOS was not significantly different to wild type. However ICOS expression is markedly increased on αβCD3+ cells from the spleens of naïve Itk-KD compared to WT mice. The Itk-KD mice were largely protected from inflammatory symptoms in an Ovalbumin model of airway inflammation. Consequently, our studies have revealed many similarities but some differences between Itk-/-and Itk-KD transgenic mice. The abnormal antibody response and enhanced ICOS expression on CD3+ cells has implications for the consideration of ITK as a therapeutic target.

  6. Mapping the residues of protein kinase CK2 implicated in substrate recognition

    DEFF Research Database (Denmark)

    Sarno, S; Boldyreff, B; Marin, O;

    1995-01-01

    Six mutants of protein kinase CK2 alpha subunit in which basic residues have been mutated into alanines were assayed for their capability to phosphorylate the peptide RRRADDSDDDDD. Two mutants (R228A and R278K279R280A) behaved more or less as alpha wild type and one (H160,166A) was nearly inactive...

  7. AKT (protein kinase B) is implicated in meiotic maturation of porcine oocytes.

    Science.gov (United States)

    Kalous, Jaroslav; Kubelka, Michal; Solc, Petr; Susor, Andrej; Motlík, Jan

    2009-10-01

    The aim of this study was to investigate the involvement of the serine/threonine protein kinase AKT (also called protein kinase B) in the control of meiosis of porcine denuded oocytes (DOs) matured in vitro. Western blot analysis revealed that the two principal AKT phosphorylation sites, Ser473 and Thr308, are phosphorylated at different stages of meiosis. In freshly isolated germinal vesicle (GV)-stage DOs, Ser473 was already phosphorylated. After the onset of oocyte maturation, the intensity of the Ser473 phosphorylation increased, however, which declined sharply when DOs underwent GV breakdown (GVBD) and remained at low levels in metaphase I- and II-stage (MI- and MII-stage). In contrast, phosphorylation of Thr308 was increased by the time of GVBD and reached maximum at MI-stage. A peak of AKT activity was noticed around GVBD and activity of AKT declined at MI-stage. To assess the role of AKT during meiosis, porcine DOs were cultured in 50 microM SH-6, a specific inhibitor of AKT. In SH-6-treated DOs, GVBD was not inhibited; on the contrary, a significant acceleration of meiosis resumption was observed. The dynamics of the Ser473 phosphorylation was not affected; however, phosphorylation of Thr308 was reduced, AKT activity was diminished at the time of GVBD, and meiotic progression was arrested in early MI-stage. Moreover, the activity of the cyclin-dependent kinase 1 (CDK1) and MAP kinase declined when SH-6-treated DOs underwent GVBD, indicating that AKT activity is involved in the regulation of CDK1 and MAP kinase. These results suggest that activity of AKT is not essential for induction of GVBD in porcine oocytes but plays a substantial role during progression of meiosis to MI/MII-stage.

  8. The Late Cretaceous I- and A-type granite association of southeast China: Implications for the origin and evolution of post-collisional extensional magmatism

    Science.gov (United States)

    Zhao, Jiao-Long; Qiu, Jian-Sheng; Liu, Liang; Wang, Rui-Qiang

    2016-01-01

    We present new geochronological, mineralogical, and geochemical data for granitic plutons that crop out within the Zhoushan archipelago, northeastern coastal Zhejiang Province, in order to constrain their origin, and the genetic relationship between the I- and A-type granites. These granites can be divided into two groups: (1) the northern I-type Putuoshan (PTS) and Dadong'ao (DDA) plutons; and (2) the southern A-type Daqingshan (DQS), Taohuadao (THD), and Xiazhidao (XZD) plutons. Zircon LA-ICP-MS U-Pb dating yielded ages of 98-96 Ma for the northern I-type plutons and 89-86 Ma for the southern A-type plutons. All of these granites are highly siliceous, K-rich, and have similar total alkali and total rare earth element (REE) abundances. However, there are also geochemical differences between the I-type and the A-type granites. The northern I-type alkali-feldspar granites are high-K calc-alkaline, metaluminous to mildly peraluminous, contain low concentrations of the high field strength elements (HFSE; e.g., Nb, Ta, Zr, and Hf), and have low Ga/Al ratios (2.04-2.44). In contrast, the southern A-type granites are peralkaline and F-rich, and have lower CaO and Al2O3 concentrations, and higher Fe2O3T and HFSE concentrations and Ga/Al ratios (3.25-3.86). Meanwhile, they have slightly higher heavy REE (HREE) concentrations, and are more depleted in Ba, Sr, P, Ti, and Eu than the northern I-type granites. Both the I- and A-type granites have homogeneous whole-rock Nd and highly variable zircon Hf isotopic compositions. Of note, the southern peralkaline A-type granites appear to have more radiogenic Nd and Hf isotope compositions than the northern I-type granites. The present data, together with the results of a previous study on mafic enclaves within the PTS pluton, suggest that the northern I-type alkali-feldspar granites were generated by mixing of mantle-derived material with crustal-derived magmas that formed by dehydration melting of mica-bearing basaltic rocks

  9. Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment.

    Directory of Open Access Journals (Sweden)

    David Gallego-Ortega

    Full Text Available BACKGROUND: The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKalpha and ChoKbeta isoforms, the first one with two different variants of splicing. Recently ChoKalpha has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKbeta in carcinogenesis has been reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we compare the in vitro and in vivo properties of ChoKalpha1 and ChoKbeta in lipid metabolism, and their potential role in carcinogenesis. Both ChoKalpha1 and ChoKbeta showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKbeta display an ethanolamine kinase role, ChoKalpha1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKalpha1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKbeta overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKalpha1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKbeta mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKalpha1 than ChoKbeta. CONCLUSION/SIGNIFICANCE: This study represents the first evidence of the distinct metabolic role of ChoKalpha and ChoKbeta isoforms, suggesting different physiological roles and implications in human

  10. Creatine-Kinase- and Exercise-Related Muscle Damage Implications for Muscle Performance and Recovery

    OpenAIRE

    Baird, Marianne F.; Graham, Scott M.; Baker, Julien S.; Bickerstaff, Gordon F.

    2012-01-01

    The appearance of creatine kinase (CK) in blood has been generally considered to be an indirect marker of muscle damage, particularly for diagnosis of medical conditions such as myocardial infarction, muscular dystrophy, and cerebral diseases. However, there is controversy in the literature concerning its validity in reflecting muscle damage as a consequence of level and intensity of physical exercise. Nonmodifiable factors, for example, ethnicity, age, and gender, can also affect enzyme tiss...

  11. Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population.

    Directory of Open Access Journals (Sweden)

    Jianming Ying

    Full Text Available Anaplastic lymphoma kinase (ALK rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.Tissue microarray (TMA was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH, real-time polymerase chain reaction (qRT-PCR, target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.Among the tested cases, 2 (0.44% CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1. One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.

  12. The Plasticity of Oncogene Addiction: Implications for Targeted Therapies Directed to Receptor Tyrosine Kinases

    Directory of Open Access Journals (Sweden)

    Vinochani Pillay

    2009-05-01

    Full Text Available A common mutation of the epidermal growth factor receptor (EGFR in glioblastoma multiforme (GBM is an extracellular truncation known as the de2-7 EGFR (or EGFRvIII. Hepatocyte growth factor (HGF is the ligand for the receptor tyrosine kinase (RTK c-Met, and this signaling axis is often active in GBM. The expression of the HGF/c-Met axis or de2-7 EGFR independently enhances GBMgrowth and invasiveness, particularly through the phosphatidylinositol-3 kinase/pAkt pathway. Using RTK arrays, we show that expression of de2-7 EGFR in U87MG GBM cells leads to the coactivation of several RTKs, including platelet-derived growth factor receptor β and c-Met. A neutralizing antibody to HGF (AMG102 did not inhibit de2-7 EGFR-mediated activation of c-Met, demonstrating that it is ligand-independent. Therapy for parental U87MG xenografts with AMG 102 resulted in significant inhibition of tumor growth, whereas U87MG.Δ2-7 xenografts were profoundly resistant. Treatment of U87MG.Δ2-7 xenografts with panitumumab, an anti-EGFR antibody, only partially inhibited tumor growth as xenografts rapidly reverted to the HGF/c-Met signaling pathway. Cotreatment with panitumumab and AMG 102 prevented this escape leading to significant tumor inhibition through an apoptotic mechanism, consistent with the induction of oncogenic shock. This observation provides a rationale for using panitumumab and AMG 102 in combination for the treatment of GBM patients. These results illustrate that GBM cells can rapidly change the RTK driving their oncogene addiction if the alternate RTK signals through the same downstream pathway. Consequently, inhibition of a dominant oncogene by targeted therapy can alter the hierarchy of RTKs resulting in rapid therapeutic resistance.

  13. Atypical charles bonnet syndrome.

    Science.gov (United States)

    Arun, Priti; Jain, Rajan; Tripathi, Vaibhav

    2013-10-01

    Charles Bonnet syndrome (CBS) is not uncommon disorder. It may not present with all typical symptoms and intact insight. Here, a case of atypical CBS is reported where antipsychotics were not effective. Patient improved completely after restoration of vision.

  14. Oxygen and neodymium isotope evidence for source diversity in Cretaceous anorogenic granites from Namibia and implications for A-type granite genesis

    Science.gov (United States)

    Trumbull, A.-type granite genesis R. B.; Harris, C.; Frindt, S.; Wigand, M.

    2004-03-01

    Many of the early Cretaceous intrusive complexes in the Damaraland of west-central Namibia are silicic in composition. Although all have trace element characteristics typical for the so-called A-type granites, major differences in alkali/aluminum ratios and isotopic compositions require diverse magma sources. This paper presents Nd and O isotope data from the five largest silicic complexes (Paresis, Erongo, Brandberg, Cape Cross, Gross Spitzkoppe) that provide new constraints on the nature of crustal and mantle sources involved, and their relative proportions. The Paresis complex has an isotopic signature ( δ18O=+9‰, ɛNd 130 Ma=-21) indicating a crustal component similar to Mesoproterozoic gneisses of the Angola craton. The other complexes have isotope variations ( δ18O from +8.1‰ to +10.7‰ and ɛNd 130 Ma from -1 to -9) that can be explained by a binary mixing model between a mantle and crustal component. More importantly, this same mixing line also fits the Nd-O isotope variations reported from the mafic Okenyenya and Messum complexes, and from rhyodacites in the southern Etendeka volcanic sequence. The uniformity of the crustal component implied by this mixing model suggests lower crustal material, in contrast to the geologic complexity of the Neoproterozoic Damara Belt presently exposed at the surface. This is consistent with the isotopic data, and we interpret the crustal component to be lower crustal metametasediments that were dehydrated and perhaps melt-depleted by generation of the S-type granites, which are widespread in the Damara Belt. The mantle component is interpreted to be dominated by the Tristan mantle plume, but some involvement of depleted mantle material is needed to explain all of the isotope data. The data rule out any significant role for enriched, subcontinental mantle lithosphere. All silicic Damaraland complexes, as well as the Etendeka rhyodacites, classify as A-type granites despite their proven source diversity. This means

  15. Aurora A kinase modulates actin cytoskeleton through phosphorylation of Cofilin: Implication in the mitotic process.

    Science.gov (United States)

    Ritchey, Lisa; Chakrabarti, Ratna

    2014-11-01

    Aurora A kinase regulates early mitotic events through phosphorylation and activation of a variety of proteins. Specifically, Aur-A is involved in centrosomal separation and formation of mitotic spindles in early prophase. The effect of Aur-A on mitotic spindles is mediated by the modulation of microtubule dynamics and association with microtubule binding proteins. In this study we show that Aur-A exerts its effects on spindle organization through the regulation of the actin cytoskeleton. Aurora A phosphorylates Cofilin at multiple sites including S(3) resulting in the inactivation of its actin depolymerizing function. Aur-A interacts with Cofilin in early mitotic phases and regulates its phosphorylation status. Cofilin phosphorylation follows a dynamic pattern during the progression of prophase to metaphase. Inhibition of Aur-A activity induced a delay in the progression of prophase to metaphase. Aur-A inhibitor also disturbed the pattern of Cofilin phosphorylation, which correlated with the mitotic delay. Our results establish a novel function of Aur-A in the regulation of actin cytoskeleton reorganization, through Cofilin phosphorylation during early mitotic stages.

  16. Petrology of the anorogenic, oxidised Jamon and Musa granites, Amazonian Craton: implications for the genesis of Proterozoic A-type granites

    Science.gov (United States)

    Dall'Agnol, Roberto; Rämö, O. Tapani; de Magalhães, Marilia Sacramento; Macambira, Moacir José Buenano

    1999-03-01

    The 1.88 Ga Jamon and Musa granites are magnetite-bearing anorogenic, A-type granites of Paleoproterozoic age. They intrude the Archaean rocks of the Rio Maria Granite-Greenstone Terrain in the eastern part of the Amazonian Craton in northern Brazil. A suite of biotite±amphibole monzogranite to syenogranite, with associated dacite porphyry (DP) and granite porphyry (GP) dykes, dominates in these subalkaline granites that vary from metaluminous to peraluminous and show high FeO/(FeO+MgO) and K 2O/Na 2O. In spite of their broad geochemical similarities, the Jamon and Musa granites show some significant differences in their REE patterns and in the behaviour of Y. The Jamon granites are related by fractional crystallisation of plagioclase, potassium feldspar, quartz, biotite, magnetite±amphibole±apatite±ilmenite. Geochemical modelling and Nd isotopic data indicate that the Archaean granodiorites, trondhjemites and tonalites of the Rio Maria region are not the source of the Jamon Granite and associated dyke magmas. Archaean quartz diorites, differentiated from the mantle at least 1000 m.y. before the emplacement of the granites, have a composition adequate to generate DP and the hornblende-biotite monzogranite magmas by different degrees of partial melting. A larger extent of amphibole fractionation during the evolution of the Musa pluton can explain some of the observed differences between it and the Jamon pluton. The studied granites crystallised at relatively high fO 2 and are anorogenic magnetite-series granites. In this aspect, as well as concerning geochemical characteristics, they display many affinities with the Proterozoic A-type granites of south-western United States. The Jamon and Musa granites differ from the anorthosite-mangerite-charnockite-rapakivi granite suites of north-eastern Canada and from the reduced rapakivi granites of the Fennoscandian Shield in several aspects, probably because of different magmatic sources.

  17. Protein implicated in nonsyndromic mental retardation regulates protein kinase A (PKA) activity

    KAUST Repository

    Al-Tawashi, Azza

    2012-02-28

    Mutation of the coiled-coil and C2 domain-containing 1A (CC2D1A) gene, which encodes a C2 domain and DM14 domain-containing protein, has been linked to severe autosomal recessive nonsyndromic mental retardation. Using a mouse model that produces a truncated form of CC2D1A that lacks the C2 domain and three of the four DM14 domains, we show that CC2D1A is important for neuronal differentiation and brain development. CC2D1A mutant neurons are hypersensitive to stress and have a reduced capacitytoformdendritesandsynapsesinculture. Atthebiochemical level,CC2D1Atransduces signals to the cyclic adenosine 3?,5?-monophosphate (cAMP)-protein kinase A (PKA) pathway during neuronal cell differentiation. PKA activity is compromised, and the translocation of its catalytic subunit to the nucleus is also defective in CC2D1A mutant cells. Consistently, phosphorylation of the PKA target cAMP-responsive element-binding protein, at serine 133, is nearly abolished in CC2D1A mutant cells. The defects in cAMP/PKA signaling were observed in fibroblast, macrophage, and neuronal primary cells derived from the CC2D1A KO mice. CC2D1A associates with the cAMP-PKA complex following forskolin treatment and accumulates in vesicles or on the plasma membrane in wild-type cells, suggesting that CC2D1A may recruit the PKA complex to the membrane to facilitate signal transduction. Together, our data show that CC2D1A is an important regulator of the cAMP/PKA signaling pathway, which may be the underlying cause for impaired mental function in nonsyndromic mental retardation patients with CC2D1A mutation. 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Characterization and origin of the Taishanmiao aluminous A-type granites: implications for Early Cretaceous lithospheric thinning at the southern margin of the North China Craton

    Science.gov (United States)

    Wang, Changming; Chen, Liang; Bagas, Leon; Lu, Yongjun; He, Xinyu; Lai, Xiangru

    2016-07-01

    Late Mesozoic magmatic rocks from the Taishanmiao Batholith were collected for LA-ICP-MS dating, Sr-Nd-Hf isotope systematics, and whole-rock major and trace element geochemistry to help understand the nature of collisional and extensional events along the southern margin of the North China Craton. The batholith consists of three texturally distinguishable phases of a 125 ± 1 Ma medium- to coarse-grained syenogranite, a 121 ± 1 Ma fine- to medium-grained syenogranite, and a 113 ± 1 Ma porphyritic monzogranite. Most of the units in the batholith are syenogranitic in composition with high levels of silica (70-78 wt% SiO2), alkalis (8.0-8.6 wt% Na2O + K2O), Fe* (FeOT/(FeOT + MgO) = 0.76-0.90), and depletion in CaO (0.34-1.37 wt%), MgO (0.12-0.52 wt%), TiO2 (0.09-0.40 wt%), and A/CNK (Al2O3/(Na2O + K2O + CaO)) molar ratios of 1.00-1.11. All samples have high proportions of Ga, Nb, Zr, Ga/Al, and REE, and depletions in Ba, Sr, Eu, and compatible elements, indicating that the batholith consists of A-type granites. The zircon saturation temperature for these units yields a mean value of 890 °C, and zircons with Early Cretaceous magmatic ages have ɛNd( t) values of -14.0 to -12.0, ɛHf( t) values ranging from -18.7 to -2.1, and corresponding Hf model ages of 2339-1282 Ma. These geochemical and isotopic characteristics allowed us to conclude that the primary magma for the Taishanmiao Batholith originated from partial melting of Precambrian crustal rocks in the medium-lower crust. However, the high Nb and Ta contents and low normalized Nb/Ta values for the Taishanmiao granites are due to fractionation in Nb- and Ta-rich amphibole (or biotite). It is further proposed that these aluminous A-type granites were generated in an extensional tectonic setting during the Early Cretaceous, which was induced by lithospheric thinning and asthenospheric upwelling beneath eastern China toward the Paleo-Pacific Plate.

  19. Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase

    Institute of Scientific and Technical Information of China (English)

    Sergiy; Kostenko; Gianina; Dumitriu; Kari; Jenssen; Lgreid; Ugo; Moens

    2011-01-01

    Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.

  20. Implications of compound heterozygous insulin receptor mutations in congenital muscle fibre type disproportion myopathy for the receptor kinase activation

    DEFF Research Database (Denmark)

    Klein, H H; Müller, R; Vestergaard, H;

    1999-01-01

    We studied insulin receptor kinase activation in two brothers with congenital muscle fibre type disproportion myopathy and compound heterozygous mutations of the insulin receptor gene, their parents, and their unaffected brother. In the father who has a heterozygote Arg1174-->Gln mutation, in situ......% of the receptors to become insulin-dependently activated. The mother carries a point mutation at the last base pair in exon 17 which, due to abnormal alternative splicing, could lead to normally transcribed receptor or truncated receptor lacking the kinase region. Kinase activation was normal in the mother...... activation of the receptor kinase in skeletal muscle was reduced about 70%. Selection of only those receptors that bound to anti-phosphotyrosine antibody showed that these receptors had normal kinase activity and that the reduction in overall kinase activity was due to the inability of about 70...

  1. Protein Kinase D family kinases

    OpenAIRE

    Wille, Christoph; Seufferlein, Thomas; Eiseler, Tim

    2014-01-01

    Highly invasive pancreatic tumors are often recognized in late stages due to a lack of clear symptoms and pose major challenges for treatment and disease management. Broad-band Protein Kinase D (PKD) inhibitors have recently been proposed as additional treatment option for this disease. PKDs are implicated in the control of cancer cell motility, angiogenesis, proliferation and metastasis. In particular, PKD2 expression is elevated in pancreatic cancer, whereas PKD1 expression is comparably lo...

  2. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo;

    2013-01-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class...

  3. Role and clinical implications of atypical antipsychotics in anxiety disorders, obsessive-compulsive disorder, trauma-related, and somatic symptom disorders: a systematized review.

    Science.gov (United States)

    Albert, Umberto; Carmassi, Claudia; Cosci, Fiammetta; De Cori, David; Di Nicola, Marco; Ferrari, Silvia; Poloni, Nicola; Tarricone, Ilaria; Fiorillo, Andrea

    2016-09-01

    Atypical antipsychotics (AAs) may play a role in the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), and trauma-related disorders. No reviews on their differential use in these different disorders have been performed recently. The aim of this systematized review was to obtain data on efficacy and comparative effectiveness of AAs as a treatment of anxiety disorders, OCD, and trauma-related disorders to provide guidance for clinicians on when and which AA to use. We searched on PubMed, Psychnet, and Cochrane Libraries from inception to July 2015. Search results were limited to randomized, placebo-controlled trials of adult patients. Evidence of efficacy was considered the presence of positive results in two or more double-blind placebo-controlled studies. Our systematized search identified 1298 papers, of which 191 were subjected to a full-text review and 56 were included. Quetiapine extended-release showed a role in both acute and maintenance treatment of uncomplicated generalized anxiety disorder, whereas more studies are needed before drawing practical recommendations on the use of olanzapine and risperidone; aripiprazole and risperidone are effective in resistant OCD as augmentation treatments. Risperidone and olanzapine add-on may have a role in resistant or chronic post-traumatic stress disorder patients, although only risperidone addition can be recommended on the basis of the criterion of two or more positive placebo-controlled trials. This systematized review supports the evidence that only a few AAs are effective in only a minority of the off-label conditions in which they are currently used and confirms that AAs are not all the same. Their use should be on the basis of a balance between efficacy and side effects, and the characteristics as well as the preference of the patient. PMID:26974213

  4. LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Chakrabarti Ratna

    2011-01-01

    Full Text Available Abstract Background LIM kinase 1 (LIMK1 is an actin and microtubule cytoskeleton modulatory protein that is overexpressed in a number of cancerous tissues and cells and also promotes invasion and metastasis of prostate and breast cancer cells. Membrane type matrix metalloproteinase 1 (MT1-MMP is a critical modulator of extracellular matrix (ECM turnover through pericellular proteolysis and thus plays crucial roles in neoplastic cell invasion and metastasis. MT1-MMP and its substrates pro-MMP-2 and pro-MMP-9 are often overexpressed in a variety of cancers including prostate cancer and the expression levels correlate with the grade of malignancy in prostate cancer cells. The purpose of this study is to determine any functional relation between LIMK1 and MT1-MMP and its implication in cell invasion. Results Our results showed that treatment with the hydroxamate inhibitor of MT1-MMP, MMP-2 and MMP-9 ilomastat inhibited LIMK1-induced invasion of benign prostate epithelial cells. Over expression of LIMK1 resulted in increased collagenolytic activity of MMP-2, and secretion of pro-MMP2 and pro-MMP-9. Cells over expressing LIMK1 also exhibited increased expression of MT1-MMP, transcriptional activation and its localization to the plasma membrane. LIMK1 physically associates with MT1-MMP and is colocalized with it to the Golgi vesicles. We also noted increased expression of both MT1-MMP and LIMK1 in prostate tumor tissues. Conclusion Our results provide new information on regulation of MT1-MMP function by LIMK1 and showed for the first time, involvement of MMPs in LIMK1 induced cell invasion.

  5. Anaplastic lymphoma kinase gene copy number gain in inflammatory breast cancer (IBC: prevalence, clinicopathologic features and prognostic implication.

    Directory of Open Access Journals (Sweden)

    Min Hwan Kim

    Full Text Available Inflammatory breast cancer (IBC is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK copy number change in IBC patients.We retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH assay, and ALK expression status was evaluated by immunohistochemical (IHC staining.Thirty-six IBC patients including those with HER2 (+ breast cancer (16/36, 44.4% and triple-negative breast cancer (13/36, 36.1% were enrolled in this study. ALK copy number gain (CNG was observed in 47.2% (17/36 of patients, including one patient who harbored ALK gene amplification. ALK CNG (+ patients showed significantly worse overall survival compared to ALK CNG (- patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033. Recurrence free survival (RFS after curative mastectomy was also significantly shorter in ALK CNG (+ patients than in ALK CNG (- patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016. Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+ patients (HR 5.63, 95% CI 1.11-28.44, p = 0.037.This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.

  6. Atypical charles bonnet syndrome

    Directory of Open Access Journals (Sweden)

    Priti Arun

    2013-01-01

    Full Text Available Charles Bonnet syndrome (CBS is not uncommon disorder. It may not present with all typical symptoms and intact insight. Here, a case of atypical CBS is reported where antipsychotics were not effective. Patient improved completely after restoration of vision.

  7. Magnetic anisotropy of the Redenção granite, eastern Amazonian craton (Brazil): Implications for the emplacement of A-type plutons

    Science.gov (United States)

    de Oliveira, Davis Carvalho; Neves, Sérgio Pacheco; Trindade, Ricardo I. F.; Dall'Agnol, Roberto; Mariano, Gorki; Correia, Paulo Barros

    2010-10-01

    A magnetic fabric study was performed on the Redenção pluton in an attempt to understand its emplacement history. The Redenção pluton is part of the 1.88 Ga, anorogenic, A-type Jamon suite that intruded 2.97-2.86 Ga-old Archean granitoids of the Rio Maria Granite-Greenstone Terrane in the eastern Amazonian craton (northern Brazil). Previous gravity survey indicates that the pluton is a 6 km-thick, tabular intrusion. It is characterized by a concentric distribution of facies, with rings of seriated and porphyritic granite that cut across the main facies of even-grained monzogranites. The whole set is intruded by leucogranites that occupy the center of the pluton. Petrographic examination, magnetic susceptibilities, coercivity-spectra and thermomagnetic curves indicate that the magnetic fabric is primarily carried by coarse-grained multidomain magnetite. This is reinforced by the coincidence of magnetic susceptibility and remanence anisotropy principal axes. The absence of solid-state deformation features and the low anisotropy degrees indicate that the magnetic fabric is magmatic in origin. The magnetic fabric displays a systematic pattern, with all facies, including the rings of porphyritic granite, being characterized by concentric, gently dipping foliations associated with gently plunging lineations. Only the central leucogranitic facies shows a slightly discordant pattern with steeply dipping fabrics at its northeastern sector. An emplacement model by vertical stacking of successive magma batches is proposed for the construction of the Redenção pluton, which reconciles the tabular shape of the intrusion, the petrographic and geochemical zoning, and the magnetic fabric pattern. Initially, two magma batches were emplaced as sills. First the even-grained monzogranite, then the seriated and porphyritic granites, which formed by mingling of a leucogranitic melt with the host biotite-monzogranitic magma as attested by geochemical data and field evidence. The

  8. DAF-16/FoxO Directly Regulates an Atypical AMP-Activated Protein Kinase Gamma Isoform to Mediate the Effects of Insulin/IGF-1 Signaling on Aging in Caenorhabditis elegans

    OpenAIRE

    Tullet, J. M.; Araiz, C.; Sanders, M J; Au, C.; Benedetto, A.; Papatheodorou, I.; Clark, E.; Schmeisser, K.; Jones, D.; Schuster, E F; Thornton, J M; Gems, D.

    2014-01-01

    The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has α, ...

  9. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    OpenAIRE

    Tullet, Jennifer M. A.; Caroline Araiz; Sanders, Matthew J.; Catherine Au; Alexandre Benedetto; Irene Papatheodorou; Emily Clark; Kathrin Schmeisser; Daniel Jones; Eugene F Schuster; Thornton, Janet M.; David Gems

    2014-01-01

    The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has α, ...

  10. Dengue fever: atypical manifestation

    Directory of Open Access Journals (Sweden)

    Nataraj Gangasiddaiah

    2014-08-01

    Full Text Available Dengue fever is affecting millions of population globally. For the past one decade, we have seen several outbreaks and even causing significant mortality of affected population. We witnessed numerous pattern and multisystem presentation of dengue in this period. The CNS manifestation like encephalitis, polyneuropathy (GB like syndrome and paresthesias were uncommonly reported priorly. Pancreatitis, polyserositis, carditis of varying severity and hepatic failure are the, some of atypical manifestations observed in recent out breaks. So dengue illness can presents with multi system involvement and can account to significant mortality. Here an attempt was done to present varying, uncommon and atypical manifestation of dengue illness. [Int J Res Med Sci 2014; 2(4.000: 1804-1806

  11. Evolutionary relationships of Aurora kinases: Implications for model organism studies and the development of anti-cancer drugs

    Directory of Open Access Journals (Sweden)

    Patrick Denis R

    2004-10-01

    Full Text Available Abstract Background As key regulators of mitotic chromosome segregation, the Aurora family of serine/threonine kinases play an important role in cell division. Abnormalities in Aurora kinases have been strongly linked with cancer, which has lead to the recent development of new classes of anti-cancer drugs that specifically target the ATP-binding domain of these kinases. From an evolutionary perspective, the species distribution of the Aurora kinase family is complex. Mammals uniquely have three Aurora kinases, Aurora-A, Aurora-B, and Aurora-C, while for other metazoans, including the frog, fruitfly and nematode, only Aurora-A and Aurora-B kinases are known. The fungi have a single Aurora-like homolog. Based on the tacit assumption of orthology to human counterparts, model organism studies have been central to the functional characterization of Aurora kinases. However, the ortholog and paralog relationships of these kinases across various species have not been rigorously examined. Here, we present comprehensive evolutionary analyses of the Aurora kinase family. Results Phylogenetic trees suggest that all three vertebrate Auroras evolved from a single urochordate ancestor. Specifically, Aurora-A is an orthologous lineage in cold-blooded vertebrates and mammals, while structurally similar Aurora-B and Aurora-C evolved more recently in mammals from a duplication of an ancestral Aurora-B/C gene found in cold-blooded vertebrates. All so-called Aurora-A and Aurora-B kinases of non-chordates are ancestral to the clade of chordate Auroras and, therefore, are not strictly orthologous to vertebrate counterparts. Comparisons of human Aurora-B and Aurora-C sequences to the resolved 3D structure of human Aurora-A lends further support to the evolutionary scenario that vertebrate Aurora-B and Aurora-C are closely related paralogs. Of the 26 residues lining the ATP-binding active site, only three were variant and all were specific to Aurora-A. Conclusions In

  12. [Atypical presentation of preeclampsia].

    Science.gov (United States)

    Ditisheim, A; Boulvain, M; Irion, O; Pechère-Bertschi, A

    2015-09-01

    Preeclampsia is a pregnancy-related syndrome, which still represents one of the major causes of maternal-fetal mortality and morbidity. Diagnosis can be made difficult due to the complexity of the disorder and its wide spectrum of clinical manifestations. In order to provide an efficient diagnostic tool to the clinician, medical societies regularly rethink the definition criteria. However, there are still clinical presentations of preeclampsia that escape the frame of the definition. The present review will address atypical forms of preeclampsia, such as preeclampsia without proteinuria, normotensive preeclampsia, preeclampsia before 20 weeks of gestation and post-partum preeclampsia.

  13. Dermatofibroma: Atypical presentations

    Directory of Open Access Journals (Sweden)

    Mousumi Roy Bandyopadhyay

    2016-01-01

    Full Text Available Dermatofibroma is a common benign fibrohistiocytic tumor and its diagnosis is easy when it presents classical clinicopathological features. However, a dermatofibroma may show a wide variety of clinicopathological variants and, therefore, the diagnosis may be difficult. The typical dermatofibroma generally occurs as a single or multiple firm reddish-brown nodules. We report here two atypical presentations of dermatofibroma - Atrophic dermatofibroma and keloidal presentation of dermatofibroma. Clinical dermal atrophy is a common phenomenon in dermatofibromas as demonstrated by the dimpling on lateral pressure. However, this feature is exaggerated in the atrophic variant of dermatofibroma. Atrophic dermatofibroma is defined by dermal atrophy of more than 50% of the lesion apart from the usual features of common dermatofibroma. The keloidal variant of dermatofibroma should not be overlooked as a simple keloid. The findings of keloidal change in dermatofibromas may support that trauma is a possible cause of dermatofibroma.

  14. Dermatofibroma: Atypical Presentations.

    Science.gov (United States)

    Bandyopadhyay, Mousumi Roy; Besra, Mrinal; Dutta, Somasree; Sarkar, Somnath

    2016-01-01

    Dermatofibroma is a common benign fibrohistiocytic tumor and its diagnosis is easy when it presents classical clinicopathological features. However, a dermatofibroma may show a wide variety of clinicopathological variants and, therefore, the diagnosis may be difficult. The typical dermatofibroma generally occurs as a single or multiple firm reddish-brown nodules. We report here two atypical presentations of dermatofibroma - Atrophic dermatofibroma and keloidal presentation of dermatofibroma. Clinical dermal atrophy is a common phenomenon in dermatofibromas as demonstrated by the dimpling on lateral pressure. However, this feature is exaggerated in the atrophic variant of dermatofibroma. Atrophic dermatofibroma is defined by dermal atrophy of more than 50% of the lesion apart from the usual features of common dermatofibroma. The keloidal variant of dermatofibroma should not be overlooked as a simple keloid. The findings of keloidal change in dermatofibromas may support that trauma is a possible cause of dermatofibroma. PMID:26955137

  15. Structural evolution of the protein kinase-like superfamily.

    Directory of Open Access Journals (Sweden)

    Eric D Scheeff

    2005-10-01

    Full Text Available The protein kinase family is large and important, but it is only one family in a larger superfamily of homologous kinases that phosphorylate a variety of substrates and play important roles in all three superkingdoms of life. We used a carefully constructed structural alignment of selected kinases as the basis for a study of the structural evolution of the protein kinase-like superfamily. The comparison of structures revealed a "universal core" domain consisting only of regions required for ATP binding and the phosphotransfer reaction. Remarkably, even within the universal core some kinase structures display notable changes, while still retaining essential activity. Hence, the protein kinase-like superfamily has undergone substantial structural and sequence revision over long evolutionary timescales. We constructed a phylogenetic tree for the superfamily using a novel approach that allowed for the combination of sequence and structure information into a unified quantitative analysis. When considered against the backdrop of species distribution and other metrics, our tree provides a compelling scenario for the development of the various kinase families from a shared common ancestor. We propose that most of the so-called "atypical kinases" are not intermittently derived from protein kinases, but rather diverged early in evolution to form a distinct phyletic group. Within the atypical kinases, the aminoglycoside and choline kinase families appear to share the closest relationship. These two families in turn appear to be the most closely related to the protein kinase family. In addition, our analysis suggests that the actin-fragmin kinase, an atypical protein kinase, is more closely related to the phosphoinositide-3 kinase family than to the protein kinase family. The two most divergent families, alpha-kinases and phosphatidylinositol phosphate kinases (PIPKs, appear to have distinct evolutionary histories. While the PIPKs probably have an

  16. Structural Evolution of the Protein Kinase-Like Superfamily.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available The protein kinase family is large and important, but it is only one family in a larger superfamily of homologous kinases that phosphorylate a variety of substrates and play important roles in all three superkingdoms of life. We used a carefully constructed structural alignment of selected kinases as the basis for a study of the structural evolution of the protein kinase-like superfamily. The comparison of structures revealed a "universal core" domain consisting only of regions required for ATP binding and the phosphotransfer reaction. Remarkably, even within the universal core some kinase structures display notable changes, while still retaining essential activity. Hence, the protein kinase-like superfamily has undergone substantial structural and sequence revision over long evolutionary timescales. We constructed a phylogenetic tree for the superfamily using a novel approach that allowed for the combination of sequence and structure information into a unified quantitative analysis. When considered against the backdrop of species distribution and other metrics, our tree provides a compelling scenario for the development of the various kinase families from a shared common ancestor. We propose that most of the so-called "atypical kinases" are not intermittently derived from protein kinases, but rather diverged early in evolution to form a distinct phyletic group. Within the atypical kinases, the aminoglycoside and choline kinase families appear to share the closest relationship. These two families in turn appear to be the most closely related to the protein kinase family. In addition, our analysis suggests that the actin-fragmin kinase, an atypical protein kinase, is more closely related to the phosphoinositide-3 kinase family than to the protein kinase family. The two most divergent families, alpha-kinases and phosphatidylinositol phosphate kinases (PIPKs, appear to have distinct evolutionary histories. While the PIPKs probably have an

  17. Role of protein kinase D signaling in pancreatic cancer.

    Science.gov (United States)

    Guha, Sushovan; Tanasanvimon, Suebpong; Sinnett-Smith, James; Rozengurt, Enrique

    2010-12-15

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with dismal survival rates. Its intransigence to conventional therapy renders PDAC an aggressive disease with early metastatic potential. Thus, novel targets for PDAC therapy are urgently needed. Multiple signal transduction pathways are implicated in progression of PDAC. These pathways stimulate production of intracellular messengers in their target cells to modify their behavior, including the lipid-derived diacylglycerol (DAG). One of the prominent intracellular targets of DAG is the protein kinase C (PKC) family. However, the mechanisms by which PKC-mediated signals are decoded by the cell remain incompletely understood. Protein kinase D1 (PKD or PKD1, initially called atypical PKCμ), is the founding member of a novel protein kinase family that includes two additional protein kinases that share extensive overall homology with PKD, termed PKD2, and PKD3. The PKD family occupies a unique position in the signal transduction pathways initiated by DAG and PKC. PKD lies downstream of PKCs in a novel signal transduction pathway implicated in the regulation of multiple fundamental biological processes. We and others have shown that PKD-mediated signaling pathways promote mitogenesis and angiogenesis in PDAC. Our recent observations demonstrate that PKD also potentiates chemoresistance and invasive potential of PDAC cells. This review will briefly highlight diverse biological roles of PKD family in multiple neoplasias including PDAC. Further, this review will underscore our latest advancement with the development of a potent PKD family inhibitor and its effect both in vitro and in vivo in PDAC. PMID:20621068

  18. Protein Kinases and Transcription Factors Activation in Response to UV-Radiation of Skin: Implications for Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Laurence A. Marchat

    2011-12-01

    Full Text Available Solar ultraviolet (UV radiation is an important environmental factor that leads to immune suppression, inflammation, photoaging, and skin carcinogenesis. Here, we reviewed the specific signal transduction pathways and transcription factors involved in the cellular response to UV-irradiation. Increasing experimental data supporting a role for p38, MAPK, JNK, ERK1/2, and ATM kinases in the response network to UV exposure is discussed. We also reviewed the participation of NF-κB, AP-1, and NRF2 transcription factors in the control of gene expression after UV-irradiation. In addition, we discussed the promising chemotherapeutic intervention of transcription factors signaling by natural compounds. Finally, we focused on the review of data emerging from the use of DNA microarray technology to determine changes in global gene expression in keratinocytes and melanocytes in response to UV treatment. Efforts to obtain a comprehensive portrait of the transcriptional events regulating photodamage of intact human epidermis after UV exposure reveals the existence of novel factors participating in UV-induced cell death. Progress in understanding the multitude of mechanisms induced by UV-irradiation could lead to the potential use of protein kinases and novel proteins as specific targets for the prevention and control of skin cancer.

  19. Atypical vertebral Paget's disease.

    Science.gov (United States)

    Beaudouin, Constance; Dohan, Anthony; Nasrallah, Toufic; Parlier, Caroline; Touraine, Sébastien; Ea, Korng; Kaci, Rachid; Laredo, Jean-Denis

    2014-07-01

    A 40-year-old Mauritanian man consulted for back pain. A computed tomography of the spine showed patchy sclerosis of the fifth and seventh thoracic vertebral bodies with normal neural arch of T5 and sclerosis and hypertrophy of the neural arch of T7, as well as diffuse sclerosis of the T11 vertebral body with a normal neural arch. At MRI, low signal-intensity on T1-weighted images and high signal-intensity on T2-weighted images involved the whole T5 and T7 vertebrae and the vertebral body of T11. Working diagnoses included metastatic disease and lymphoma, and a biopsy of T7 and then T11 was carried out. Both showed pathological findings very suggestive of Paget's disease. Since CT is usually the more specific radiological examination in vertebral Paget's disease, we thought it could be useful to report this atypical CT presentation (patchy sclerosis of the vertebral body without diffuse bone texture changes and isolated involvement of the vertebral body) of vertebral Paget's disease. PMID:24445956

  20. Petrogenesis of Permian A-type granitoids in the Cihai iron ore district, Eastern Tianshan, NW China: Constraints on the timing of iron mineralization and implications for a non-plume tectonic setting

    Science.gov (United States)

    Zheng, Jiahao; Mao, Jingwen; Chai, Fengmei; Yang, Fuquan

    2016-09-01

    The geochronology and geochemistry of granitoids in the Eastern Tianshan, NW China provide important constraints on the timing of iron mineralization, as well as in understanding evolution history of the southern Central Asian Orogenic Belt (CAOB). Here we present results from a detailed study on granitoid rocks from the Cihai iron ore district in the Beishan region, southern part of the Eastern Tianshan. The granitoid rocks are composed of granodiorite, quartz monzonite, granite, and monzonite. Zircon U-Pb analyses yielded the ages of 294.1 ± 2.2 Ma, 286.5 ± 0.7 Ma, 284.3 ± 3.3 Ma, and 265.6 ± 3.0 Ma, respectively, suggesting they were formed in Early-Middle Permian. Among these granitoid rocks, the ages of quartz monzonite and granite are close to the timing of iron mineralization (~ 282 Ma), indicating they may provide a source of iron in the Cihai ore district. Geochemically, the granodiorite, granite, and quartz monzonite samples are characterized by high FeOt/(FeOt + MgO) and Ga/Al ratios (0.84-0.94 and 2.28-3.27, respectively), as well as high zircon saturation temperatures (781-908 °C), similar to those of typical A-type granitoids. Isotopically, they display consistently depleted Hf isotopic compositions (εHf(t) = + 1.18 to + 15.37). Geological, geochemical, and isotopic data suggest that the Cihai A-type granitoids were derived from melting of juvenile lower crust. Some Early Permian A-type granitoids were recently identified in the Tarim and Eastern Tianshan with the ages between 294 and 269 Ma. The A-type granitoids in the Eastern Tianshan formed earlier between 294-284 Ma and exhibit characteristics of A2 type granitoids, whereas the A-type granitoids in the Tarim formed later between 277-269 Ma and show A1 granitoids affinity. We suggest that the Permian Tarim mantle plume does not account for the formation of the A-type granitoids in the Eastern Tianshan area, and the Eastern Tianshan was in a non-plume tectonic setting during Early Permian

  1. Assembly of the transmembrane domain of E. coli PhoQ histidine kinase: implications for signal transduction from molecular simulations.

    Directory of Open Access Journals (Sweden)

    Thomas Lemmin

    Full Text Available The PhoQP two-component system is a signaling complex essential for bacterial virulence and cationic antimicrobial peptide resistance. PhoQ is the histidine kinase chemoreceptor of this tandem machine and assembles in a homodimer conformation spanning the bacterial inner membrane. Currently, a full understanding of the PhoQ signal transduction is hindered by the lack of a complete atomistic structure. In this study, an atomistic model of the key transmembrane (TM domain is assembled by using molecular simulations, guided by experimental cross-linking data. The formation of a polar pocket involving Asn202 in the lumen of the tetrameric TM bundle is crucial for the assembly and solvation of the domain. Moreover, a concerted displacement of the TM helices at the periplasmic side is found to modulate a rotation at the cytoplasmic end, supporting the transduction of the chemical signal through a combination of scissoring and rotational movement of the TM helices.

  2. Identification of EGFR kinase domain mutations among lung cancer patients in China: implication for targeted cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Bao Ming QIN; Xiao CHEN; Jing De ZHU; Duan Qing PEI

    2005-01-01

    Lung cancer is one of the leading causes of death with one of the lowest survival rates. However, a subset of lung cancer patients who are of Asian origin and carry somatic mutations in epidermal growth factor receptor or EGFR have responded remarkable well to two tyrosine kinase inhibitors, gefitinib and erlotinib. While EGFR mutation profiles have been reported from Japan, South Korea, and Taiwan, there is no such report from mainland of China where the largest pool of patients reside. In this report, we identified ten somatic mutations from a total of 41 lung cancer patients in China. Among them, seven mutations were found in 17 adenocarcinomas. In contrast to previous reports, eight of these mutations are deletions in exon 19 and two of these deletions are homozygous. These results suggest that a large portion of Chinese adenocarcinoma patients could benefit from gefitinib or erlotinib. This unique mutation profile provides a rationale to develop the next generation of EGFR inhibitors more suitable for the Chinese population.

  3. The Changes of Protein Kinase C Activity in Peripheral Blood Lymphocytes in the Patients with Obstructive Jaundice and the Implication

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The roles of protein kinase C (PKC) signal pathway in the pathogenesis of obstructive jaundice were studied. PKC from cytosolic and membrane fractions of peripheral blood lymphocytes (PBL) in 51 patients with obstructive jaundice and 16 cases of normal controls was isolated and purified. The activities of PKC were determined by radioactive isotope γ-32P-ATP-catalyzing assay. The results showed that the total PKC activities in PBL in the patients with obstructive jaundice were significantly increased as compared with those in the normal controls (P<0.01). Moreover, the membrane PKC activities and their percentages of the total PKC activities were higher in obstructive jaundice group than in those in the normal controls (P<0.05). The total PKC activities in PBL in the patients with obstructive jaundice were significantly positively correlated with the levels of soluble IL-2 receptor (sIL-2R) (r=0.58, P<0.01) and the degree of jaundice (T-BIL) (r=0.67, P<0.01) in serum. It was concluded that the activities of PKC signal pathway was related with the degree of T-BIL. PKC signal pathway might took part in the activation of T-lymphocytes in the patients with obstructive jaundice and play an important role in the immune regulation and the assessment of pathosis in the patients with obstructive jaundice.

  4. Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation.

    Directory of Open Access Journals (Sweden)

    Douglas W McMillin

    Full Text Available Polo-like kinases (PLKs play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM. We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM and rapid (commitment to cell death <24 hrs in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM

  5. Structural Studies on the Extracellular Domain of Sensor Histidine Kinase YycG from Staphylococcus aureus and Its Functional Implications.

    Science.gov (United States)

    Kim, Truc; Choi, Jongkeun; Lee, Sangho; Yeo, Kwon Joo; Cheong, Hae-Kap; Kim, Kyeong Kyu

    2016-07-31

    Bacterial two-component signal transduction systems are used to adapt to fluctuations in the environment. YycG, a key two-component histidine kinase in Staphylococcus aureus, plays an essential role in cell viability and regulates cell wall metabolism, biofilm formation, virulence, and antibiotic resistance. For these reasons, YycG is considered a compelling target for the development of novel antibiotics. However, to date, the signaling mechanism of YycG and its stimulus are poorly understood mainly because of a lack of structural information on YycG. To address this deficiency, we determined the crystal structure of the extracellular domain of S. aureus YycG (YycGex) at 2.0-Å resolution. The crystal structure indicated two subunits with an extracellular Per-Arnt-Sim (PAS) topology packed into a dimer with interloop interactions. Disulfide scanning using cysteine-substituted mutants revealed that YycGex possessed dimeric interfaces not only in the loop but also in the helix α1. Cross-linking studies using intact YycG demonstrated that it was capable of forming high molecular weight oligomers on the cell membrane. Furthermore, we also observed that two auxiliary proteins of YycG, YycH and YycI, cooperatively interfered with the multimerization of YycG. From these results, we propose that signaling through YycG is regulated by multimerization and binding of YycH and YycI. These structural studies, combined with biochemical analyses, provide a better understanding of the signaling mechanism of YycG, which is necessary for developing novel antibacterial drugs targeting S. aureus. PMID:27389096

  6. Modulation of liver canalicular transport processes by the tyrosine-kinase inhibitor genistein: implications of genistein metabolism in the rat.

    Science.gov (United States)

    Jäger, W; Winter, O; Halper, B; Salamon, A; Sartori, M; Gajdzik, L; Hamilton, G; Theyer, G; Graf, J; Thalhammer, T

    1997-12-01

    Rat liver cells express the multispecific organic anion transporter (cmoat, cmrp, mrp2) and P-glycoprotein (Pgp) in their canalicular membranes, proteins that are homologous to the multidrug-resistance related protein (MRP) and multidrug resistance (MDR) gene products in multidrug resistant tumor cells. We tested whether genistein, a modulator of drug resistance in tumor cells, affects biliary secretion of substrates of canalicular multispecific organic anion transporter (cmoat) (glucuronides of bilirubin and rhodamine, glutathione conjugate of bromsulphthalein) and of P-glycoprotein (Pgp) (rhodamine), respectively. Using the isolated perfused rat liver of control Wistar rats (TR+) and of a mutant strain (TR-) that expresses Pgp but not cmoat, we show that genistein effectively inhibits the secretion of anionic substrates of cmoat in Wistar rats but stimulates secretion of cationic rhodamine in TR- rats. Genistein is subject to glucuronidation and sulfatation and secretion of genistein and its metabolites stimulates bile flow in Wistar rats, but secretion is nearly absent in TR- rats. Because genistein and its metabolites are substrates for cmoat, inhibition of anion secretion by genistein is partially explained by competition for this transporter. Genistein is also a substrate of uridindiphosphate (UDP)-glucuronyltransferase isoenzyme(s). Inhibition of glucuronidation reduces the availability of bilirubin and rhodamine glucuronates for transport via cmoat, but unconjugated cationic rhodamine becomes available for transport via Pgp at an increased cellular concentration. Daidzein, a genistein analogue with no effect on protein tyrosine kinase (PTK) shows Similar effects on secretion of organic anions and cations supporting the conclusion that genistein affects transport in liver mainly through competition with other substrates at the sites of glucuronidation and transport via cmoat.

  7. Chronic Glutathione Depletion Confers Protection against Alcohol-induced Steatosis: Implication for Redox Activation of AMP-activated Protein Kinase Pathway

    Science.gov (United States)

    Chen, Ying; Singh, Surendra; Matsumoto, Akiko; Manna, Soumen K.; Abdelmegeed, Mohamed A.; Golla, Srujana; Murphy, Robert C.; Dong, Hongbin; Song, Byoung-Joon; Gonzalez, Frank J.; Thompson, David C.; Vasiliou, Vasilis

    2016-01-01

    The pathogenesis of alcoholic liver disease (ALD) is not well established. However, oxidative stress and associated decreases in levels of glutathione (GSH) are known to play a central role in ALD. The present study examines the effect of GSH deficiency on alcohol-induced liver steatosis in Gclm knockout (KO) mice that constitutively have ≈15% normal hepatic levels of GSH. Following chronic (6 week) feeding with an ethanol-containing liquid diet, the Gclm KO mice were unexpectedly found to be protected against steatosis despite showing increased oxidative stress (as reflected in elevated levels of CYP2E1 and protein carbonyls). Gclm KO mice also exhibit constitutive activation of liver AMP-activated protein kinase (AMPK) pathway and nuclear factor-erythroid 2–related factor 2 target genes, and show enhanced ethanol clearance, altered hepatic lipid profiles in favor of increased levels of polyunsaturated fatty acids and concordant changes in expression of genes associated with lipogenesis and fatty acid oxidation. In summary, our data implicate a novel mechanism protecting against liver steatosis via an oxidative stress adaptive response that activates the AMPK pathway. We propose redox activation of the AMPK may represent a new therapeutic strategy for preventing ALD. PMID:27403993

  8. Familial benign pemphigus atypical localization

    OpenAIRE

    Reyes, Maria Veronica; Halac, Sabina; Mainardi, Claudio; Kurpis, Maria; Ruiz Lascano, Alejandro

    2016-01-01

    We present an atypical case of familial benign pemphigus (Hailey-Hailey disease), which presented as crusted, annular plaques limited to the back without intertriginous involvement. We could not find in the literature another patient with plaques located solely on the back without a prior history of classical disease.

  9. Atypical moles: diagnosis and management.

    Science.gov (United States)

    Perkins, Allen; Duffy, R Lamar

    2015-06-01

    Atypical moles are benign pigmented lesions. Although they are benign, they exhibit some of the clinical and histologic features of malignant melanoma. They are more common in fair-skinned individuals and in those with high sun exposure. Atypical moles are characterized by size of 6 mm or more at the greatest dimension, color variegation, border irregularity, and pebbled texture. They are associated with an increased risk of melanoma, warranting enhanced surveillance, especially in patients with more than 50 moles and a family history of melanoma. Because an individual lesion is unlikely to display malignant transformation, biopsy of all atypical moles is neither clinically beneficial nor cost-effective. The ABCDE (asymmetry, border irregularity, color unevenness, diameter of 6 mm or more, evolution) mnemonic is a valuable tool for clinicians and patients to identify lesions that could be melanoma. Also, according to the "ugly duckling" concept, benign moles tend to have a similar appearance, whereas an outlier with a different appearance is more likely to be undergoing malignant change. Atypical moles with changes suggestive of malignant melanoma should be biopsied, using an excisional method, if possible.

  10. Recognition and diagnosis of atypical depression.

    Science.gov (United States)

    Thase, Michael E

    2007-01-01

    The term atypical depression dates to the first wave of reports describing differential response to monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). In contrast to more TCA-responsive depressions, patients with so-called atypical symptoms (e.g., hypersomnia, interpersonal sensitivity, leaden paralysis, increased appetite and/or weight, and phobic anxiety) were observed to be more responsive to MAOIs. After several decades of controversy and debate, the phrase "with atypical features" was added as an episode specifier in the DSM-IV in 1994. The 1-year prevalence of the defined atypical depression subtype is approximately 1% to 4%; around 15% to 29% of patients with major depressive disorder have atypical depression. Hardly "atypical" in contemporary contexts, atypical depression also is common in dysthymic bipolar II disorders and is notable for its early age at onset, more chronic course, and high rates of comorbidity with social phobia and panic disorder with agoraphobia. The requirement of preserved mood reactivity is arguably the most controversial of the DSM-IV criteria for atypical depression. When compared with melancholia, the neurobiological profiles of patients with atypical depression are relatively normal. The utility of the atypical depression subtype for differential therapeutics diminished substantially when the TCAs were supplanted as first-line antidepressants by the selective serotonin reuptake inhibitors. Although introduction of safer MAOIs has fostered renewed interest in atypical depression, the validity and importance of the DSM-IV definition of atypical depression for the nosology of affective illness remains an open question. PMID:17640153

  11. Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

    Science.gov (United States)

    Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

    2016-01-01

    The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases. PMID:27187038

  12. Atypical manifestations of early syphilis

    Directory of Open Access Journals (Sweden)

    Koranne R

    1990-01-01

    Full Text Available A study of 36 untreated patients with early syphilis revealed atypical variations namely; long incubation period of 101 days in I patient, more than 3 chancres in 1, undermined margin of the chancre along with tenderness in 1 and moderate to severe tenderness of the ulcers in 2 cases. In 3 patients there was no indurations of the ulcers. Three patients with primary syphilis had unilateral lymphadenitis, and in I case the lymph nodes were not only tender but showed tendency towardsmatingawell. Insecondarysyphilis, 11 out of 16 patients having condylomata lata had no other muco-cutaneous lesions. Concomitant presence of other venereal disease to account for the atypical manifestations was discounted- by appropriate laboratory tests, response to therapeutic agents and follow up.

  13. Atypical fractures, a biased perspective.

    Science.gov (United States)

    Aspenberg, Per

    2016-01-01

    When stress fractures started to show up in the femurs of elderly ladies, it was soon evident that bisphosphonate use lay behind, and the absolute risk increase due to bisphosphonate use was reasonably well estimated already in 2008. Thereafter followed a period of confusion: the term atypical fracture was introduced, with a definition so vague that the true stress fractures tended to disappear in a cloud of ambiguity. This cast doubt on the association with bisphosphonates. The association was then re-established by large epidemiological studies based on radiographic adjudication. Atypical fractures are largely caused by bisphosphonates. With a correct indication, bisphosphonates prevent many more fractures than they cause, at least during the first years of use. With an incorrect indication they are likely to cause more harm than good. PMID:26768286

  14. Geochronology and geochemistry of the Triassic bimodal volcanic rocks and coeval A-type granites of the Olzit area, Middle Mongolia: Implications for the tectonic evolution of Mongol-Okhotsk Ocean

    Science.gov (United States)

    Zhu, Mingshuai; Zhang, Fochin; Miao, Laicheng; Baatar, Munkhtsengel; Anaad, Chimedtseren; Yang, Shunhu; Li, Xingbo

    2016-05-01

    The Olzit volcanism in Middle Mongolia comprises a bimodal suite of basalts and peralkaline rhyolites adjacent to the Main Mongolia Lineament. The basalts are characterized by enrichment in LILE and LREE, and depletion in HFSE with typical Sr-Nd isotopic signatures (εNd(t) = -2.50 to -0.38 and (87Sr/86Sr)i = 0.7058-0.7063), indicating they were likely derived from partial melting of an enriched lithospheric mantle, modified by subducted slab-derived fluids. The rhyolites show a close affinity to A-type granites with enrichment in LILE and LREE, and depletion in Nb, Ta and Ti. They also show a significant negative Eu anomaly, and have εNd(t) values ranging from 0.50 to 1.38 and initial 87Sr/86Sr ratios ranging from 0.7022 to 0.7200, suggesting the rhyolites stem from partial melting of crustal rocks rather than fractional crystallization of the basaltic melt. The rhyolite porphyry yields a SHRIMP zircon U-Pb age of 207 ± 2 Ma (MSWD = 1.42), indicating the bimodal volcanic suite formed in the Late Triassic. The miarolitic per-alkaline granite and biotite-bearing granite, which are associated with the bimodal volcanic rocks, show typical A-type granitic geochemical affinity with εNd(t) = 0.89-0.91 and (87Sr/86Sr)i = 0.7021-0.7043, indicating they are likely generated by partial melting of crustal rocks similar to the rhyolitic end-member of bimodal suite. The miarolitic per-alkaline granite and biotite-bearing granite yielded SHRIMP zircon U-Pb ages of 209 ± 2 Ma (MSWD = 0.91) and 213 ± 3 Ma (MSWD = 1.65) respectively, which are nearly coeval with the age of the bimodal volcanic suites. In view of the new geochemical and chronological data in this study, we suggest the Olzit Late Triassic bimodal volcanic rocks together with the coeval A-type granites represent a back-arc basin extensional environment, which probably related to the roll-back of Mongol-Okhotsk oceanic plate during the southward subduction under the Central Mongolia microcontinent.

  15. Atypical eating disorders: a review

    OpenAIRE

    Garcia, Frederico

    2011-01-01

    Frederico Duarte Garcia1, Héloïse Délavenne2, Pierre Déchelotte11Nutrition and Digestive System Research Group (EA 4311) and Nutrition Unit, Rouen Institute of Medical Research and Innovation, Federative Institute for Peptide Research (IFRMP 23), Rouen University and University Hospital, Rouen, France; 2Department of Addictology of the Rouen University Hospital, Rouen University, Rouen, FranceIntroduction: Atypical eating disorders (AEDs), also known ...

  16. Evolving A-Type Artificial Neural Networks

    CERN Document Server

    Orr, Ewan

    2011-01-01

    We investigate Turing's notion of an A-type artificial neural network. We study a refinement of Turing's original idea, motivated by work of Teuscher, Bull, Preen and Copeland. Our A-types can process binary data by accepting and outputting sequences of binary vectors; hence we can associate a function to an A-type, and we say the A-type {\\em represents} the function. There are two modes of data processing: clamped and sequential. We describe an evolutionary algorithm, involving graph-theoretic manipulations of A-types, which searches for A-types representing a given function. The algorithm uses both mutation and crossover operators. We implemented the algorithm and applied it to three benchmark tasks. We found that the algorithm performed much better than a random search. For two out of the three tasks, the algorithm with crossover performed better than a mutation-only version.

  17. Mineral chemistry and geochemistry of the Late Neoproterozoic Gabal Abu Diab granitoids, Central Eastern Dessert, Egypt: Implications for the origin of rare metal post-orogenic A-type granites

    Science.gov (United States)

    Sami, Mabrouk; Ntaflos, Theodoros; Farahat, Esam S.; Ahmed, Awaad F.; Mohamed, Haroun A.

    2015-04-01

    within A-type granite worldwide. According to Zhang et al., 2012, the garnet crystallized at the expense of biotite from the MnO-rich evolved melt after fractionation of biotite, plagioclase, K-feldspar, zircon, apatite, and ilmenite. The granitoids are alkali feldspar granites showing distinct geochemical features and most likely, belong to the post-orogenic younger Egyptian granitoids. They are peraluminous A-type alkaline rocks but they have lower Fe2O3, MgO, MnO, CaO, TiO2, P2O5, Sr, Ba, V, and higher SiO2, Na2O, K2O, Nb, Ta, U, Zr, Th, Ga/Al and Rb than the typical rocks of this type. The positive correlation between Ba and Sr, and the negative correlation between Rb and K/Rb reveal fractional crystallization of alkali feldspar. The similarity in most geochemical characteristics suggests that Abu Diab granitoids are genetically related to each other and extremely enrichment in incompatible elements such as Nb and Ta, indicating that they crystallized from extremely differentiated magmas. References: Zhang, J., Ma, C. and She, Z., 2012. An Early Cretaceous garnet-bearing metaluminous A-type granite intrusion in the East Qinling Orogen, central China: Petrological, mineralogical and geochemical constraints. Geoscience Frontiers 3 (5), 635-646.

  18. Geochronology- and Geochemistry of Late Carboniferous-Middle Permian I- and A-Type Granites and Gabro-Diorites in the Eastern Jimausi Massif, NE, China: Implications for a Tectonic Transition

    Science.gov (United States)

    Bi, Junhui; Ge, Wenchun

    2016-04-01

    The late Paleozoic magmatism in the Jiamusi Massif of northeast China, located in the eastern segment of the Central Asian Orogenic Belt (CAOB), was dominated by an active continental margin environment due to subduction of the paleo-oceanic plate. Nevertheless, what deep geodynamic processes controlled the late Paleozoic evolution of the Jiamusi Massif are still poorly constrained. In this contribution, we present zircon U-Pb ages and geochemical data of late Carboniferous-middle Permian magmatism in the Jiamusi Massif, aiming to provide constraints on the question. Precise LA-ICP-MS U-Pb zircon ages indicate that the granitoids and gabbro-diorites were emplaced in the late Carboniferous-middle Permian (302-267 Ma). The granites belong to a high-potassium calc-alkaline series, are weakly peraluminous I- and A-type granites, and show high SiO2 and K2O contents; they are depleted in high field strength elements (HFSEs), enriched in light rare earth elements (LREEs) and large ion lithophile elements (LILEs), show weakly to mildly fractionated REE patterns, and on spidergrams show arc-type affinities with strong depletions in Nb, Ta, and Ti. The combination of heterogeneous values of ɛHf(t) for magmatic zircons in all granitoids (ranging from +7.9 to -5.6) and two-stage Hf model ages (TDM2) of 0.8-1.7 Ga suggests that the granites originated from partial melting of a predominantly "old" Meso-Neoproterozoic crustal source. The gabbro-diorites of the Longtouqiao pluton are depleted in Nb, Ta, P, and Ti, and show flat distributions of most LILEs and HFSEs, except for marked large positive anomalies in Ba, K, and Pb. These features reflect limited degrees of crustal contamination associated with subduction-related magma processes. These data, together with previously reported data and the occurrence of arc magmatic rocks along the eastern part of the Jiamusi Massif, suggest that the intrusive rocks formed during westward subduction of the Paleo-Pacific Ocean lithosphere

  19. Gravimetric, radiometric, and magnetic susceptibility study of the Paleoproterozoic Redenção and Bannach plutons, eastern Amazonian Craton, Brazil: Implications for architecture and zoning of A-type granites

    Science.gov (United States)

    de Oliveira, Davis Carvalho; Dall'Agnol, Roberto; Corrêa da Silva, João Batista; Costa de Almeida, José Arimatéia

    2008-02-01

    The 1.88 Ga, anorogenic, A-type Redenção and Bannach granites, representative of the Jamon suite and associated dikes, are intrusive in Archean granitoids of the Rio Maria Granite-Greenstone Terrane in the eastern Amazonian Craton in northern Brazil. Petrographic and geochemical aspects associated with magnetic susceptibility and gamma-ray spectrometry data show that the Redenção and the northern part of Bannach plutons are normally zoned. They were formed by two magmatic pulses: (1) a first magma pulse was fractionated in situ after emplacement at shallow crustal level, generating a series of coarse, even-grained monzogranites with variable modal proportions of biotite and hornblende; and (2) a second, slightly younger magma pulse, located to the center of the plutons, was composed of a more evolved liquid from which even-grained leucogranites derived. Gravity modeling indicates that the Redenção and Bannach plutons are sheeted-like composite intrusions, approximately 6 and 2 km thick, respectively. These plutons follow the general power law for laccolith dimension and are similar in this respect to classical rapakivi granite plutons. Gravity data suggest that the growth of the northern part of the Bannach pluton resulted from the amalgamation of smaller sheeted-like plutons that intruded in sequence from northwest to southeast. The Jamon suite plutons were emplaced in an extensional tectonic setting, and the stress was oriented approximately NNE-SSW to ENE-WSW, as indicated by the occurrence of diabase and granite porphyry dyke swarms, orientated WNW-ESE to NNW-SSE and coeval with the Jamon suite. The 1.88 Ga A-type granite plutons and stocks of Carajás are disposed along a belt that follows the general trend defined by the dikes. The inferred tabular geometry of the studied plutons and the high contrast of viscosity between the granites and their Archean country rocks can be explained by magma transport via dikes.

  20. Sudden discontinuation and reinstitution of olanzapine-associated atypical neuroleptic malignant syndrome in a patient undergoing lung surgery

    OpenAIRE

    Zhao, Zhiyong; Zhang, Hua; Wang, Shaohua; Chen, Xiaofeng

    2015-01-01

    Neuroleptic malignant syndrome (NMS) is a potentially life-threatening idiosyncratic reaction generally associated with neuroleptics. NMS is characterized by hyperthermia, extrapyramidal symptoms, elevated creatinine kinase (CK), altered mental state, leukocytosis, and problems with vegetative functions. Due to its lower affinity for dopaminergic receptors and higher affinity for serotonin receptors, olanzapine-associated atypical NMS were less common than typical neuroleptics. Here we report...

  1. Atypical extragonadal germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mainak Deb

    2012-01-01

    Full Text Available Aim: To review the experience with the diagnosis and management of extragonadal germ cell tumors (GCT with a subset analysis of those with atypical features. Materials and Methods: A retrospective chart review of patients of extragonadal germ cell tumors between 2000 and 2010 was carried out. Results: Fifteen children aged 7 days to 15 years (median, 1.5 years were included. Three had an antenatal diagnosis (one sacrococcygeal, one retrobulbar, one retroperitoneal tumor and were operated in the neonatal period. The locations were distributed between the retrobulbar area (1, anterior neck-thyroid gland (1, mediastinum (4, abdominothoracic extending through the esophageal hiatus (1, retroperitoneal (4 and sacrococcygeal (4. On histological examination, five harbored immature elements while two were malignant; the latter children received postexcision adjuvant chemotherapy. There was no mortality. At a median follow-up of 4.5 years (6 months to 8 years, 14/15 have had an event-free survival. One immature mediastinal teratoma that recurred locally 7.5 years after the initial operation was excised and adjuvant chemotherapy instituted. Conclusions: Extragonadal GCTs in children are uncommon and occasionally present with atypical clinical, radiological and histological features resulting in diagnostic and therapeutic dilemmas.

  2. Atypical Manifestation of Vestibular Schwannoma

    Directory of Open Access Journals (Sweden)

    Webster, Guilherme

    2013-09-01

    Full Text Available Introduction: Vestibular schwannoma (also known as acoustic neuroma is a benign tumor whose cells are derived from Schwann sheaths, which commonly occurs from the vestibular portion of the eighth cranial nerve. Furthermore, vestibular schwannomas account for ∼8% of intracranial tumors in adults and 80 to 90% of tumors of the cerebellopontine angle. Its symptoms are varied, but what stands out most is a unilateral sensorineural hearing loss, with a low index of speech recognition. Objective: Describe an atypical manifestation of vestibular schwannoma. Case Report: The 46-year-old woman had vertigo and binaural hearing loss and fullness, with ear, nose, and throat examination suggestive of cochlear injury. After 6 months, the patient developed worsening of symptoms and onset of right unilateral tinnitus. In further exams the signs of cochlear damage remained, except for the vestibular test (hyporeflexia. Magnetic resonance imaging showed an expansive lesion in the right cerebellopontine angle. Discussion: This report warns about the atypical manifestations of vestibular schwannoma, which must always be remembered in investigating and diagnosing hearing loss.

  3. The small GTPase RhoH is an atypical regulator of haematopoietic cells

    Directory of Open Access Journals (Sweden)

    Kubatzky Katharina F

    2008-09-01

    Full Text Available Abstract Rho GTPases are a distinct subfamily of the superfamily of Ras GTPases. The best-characterised members are RhoA, Rac and Cdc42 that regulate many diverse actions such as actin cytoskeleton reorganisation, adhesion, motility as well as cell proliferation, differentiation and gene transcription. Among the 20 members of that family, only Rac2 and RhoH show an expression restricted to the haematopoietic lineage. RhoH was first discovered in 1995 as a fusion transcript with the transcriptional repressor LAZ3/BCL6. It was therefore initially named translation three four (TTF but later on renamed RhoH due to its close relationship to the Ras/Rho family of GTPases. Since then, RhoH has been implicated in human cancer as the gene is subject to somatic hypermutation and by the detection of RHOH as a translocation partner for LAZ3/BCL6 or other genes in human lymphomas. Underexpression of RhoH is found in hairy cell leukaemia and acute myeloid leukaemia. Some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Therefore other mechanisms of regulating RhoH activity have been described. These include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyl-transferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling. Little is currently known about its signalling, regulation or interaction partners. Recent studies have shown that RhoH negatively influences the proliferation and homing of murine haematopoietic progenitor cells, presumably by acting as an antagonist for Rac1. In leukocytes, RhoH is needed to keep the cells in a resting, non-adhesive state, but the exact mechanism has yet to be elucidated. RhoH has also been

  4. Geochemistry of the Late Neoproterozoic Hadb adh Dayheen ring complex, Central Arabian Shield: Implications for the origin of rare-metal-bearing post-orogenic A-type granites

    Science.gov (United States)

    Moghazi, A. M.; Harbi, H. M.; Ali, K. A.

    2011-11-01

    The Hadb adh Dayheen ring complex (HDRC), Central Arabian Shield, is an alkaline to peralkaline A-type granite complex. It consists of an inner core of monzogranite followed outward by porphyritic alkali feldspar granite (hornblende biotite granite and aegirine riebeckite granite). Field and textural observations indicate that the different granite types were separated from magma reservoir, at different stages, and emplaced at higher levels along pre-existing fractures. The geochemical characteristics indicate that their magma was most plausibly originated by partial melting of juvenile lower crust following collision between East and West Gondwana at the final stage of the Arabian Shield evolution. The alkali feldspar granites have high abundances of albite and fluorite and wide variation of HFSE and REE that indicate interaction with hydrothermal F-rich fluids. Although there are many geochemical, mineralogical and textural evidence of secondary metasomatic alteration superimposed on the granitic rocks, they show textural features such as the arrangement of albite inclusions along growth planes in quartz (snowball texture) and aegirine that indicate early magmatic crystallization of albite. Also, the strong linear positive correlation of Ta vs. Nb and Zr vs. Hf emphasize that the behavior and enrichment of Ta and Nb are largely controlled by magmatic processes. The events that can explain the evolution of these rocks are: (1) during magmatic evolution, F dissolved in the magma and lowered the crystallization temperature causing REE and HFSE to form complexes and thus behave as incompatible elements, (2) prolonged crystallization of the major mineral phases (quartz and feldspar) formed a late-stage magmatic fluid enriched in volatiles (H 2O, F) and trace elements, (3) accessory minerals crystallized from such a phase in the interstices between the major mineral phases, and (4) post-magmatic re-equilibration and formation of secondary albite (Na-metasomatism) has

  5. Impaired inflammatory pain and thermal hyperalgesia in mice expressing neuron-specific dominant negative mitogen activated protein kinase kinase (MEK

    Directory of Open Access Journals (Sweden)

    Kaplan David

    2006-01-01

    Full Text Available Abstract Background Numerous studies have implicated spinal extracellular signal-regulated kinases (ERKs as mediators of nociceptive plasticity. These studies have utilized pharmacological inhibition of MEK to demonstrate a role for ERK signaling in pain, but this approach cannot distinguish between effects of ERK in neuronal and non-neuronal cells. The present studies were undertaken to test the specific role of neuronal ERK in formalin-induced inflammatory pain. Dominant negative MEK (DN MEK mutant mice in which MEK function is suppressed exclusively in neurons were tested in the formalin model of inflammatory pain. Results Formalin-induced second phase spontaneous pain behaviors as well as thermal hyperalgesia measured 1 – 3 hours post-formalin were significantly reduced in the DN MEK mice when compared to their wild type littermate controls. In addition, spinal ERK phosphorylation following formalin injection was significantly reduced in the DN MEK mice. This was not due to a reduction of the number of unmyelinated fibers in the periphery, since these were almost double the number observed in wild type controls. Further examination of the effects of suppression of MEK function on a downstream target of ERK phosphorylation, the A-type potassium channel, showed that the ERK-dependent modulation of the A-type currents is significantly reduced in neurons from DN MEK mice compared to littermate wild type controls. Conclusion Our results demonstrate that the neuronal MEK-ERK pathway is indeed an important intracellular cascade that is associated with formalin-induced inflammatory pain and thermal hyperalgesia.

  6. Typical and atypical AIS. Pathogenesis.

    Science.gov (United States)

    Dudin, M; Pinchuk, D

    2012-01-01

    AIS hypothesis has the right to recognition, if it explains the transition of "healthy" vertebra column into status of "scoliotic" one. AIS is the most investigated disease in the history of orthopedics, but up the present time there is no clear explanation of some its phenomena: vertebra column mono-form deformation along with its poly etiology character, interrelation of its origin and development and child's growth process etc. The key for authors' view at AIS was scoliosis with non-standard (concave side) rotation. On the bases of its' multifunctional instrumental investigation results (Rtg, EMG, EEG, optical topography, hormonal and neuropeptides trials, thermo-vision methods and other) in comparison with typical AIS was worked out the new hypothesis, part of it is suggested for discussion. In the work under observation is the sequence of appearance of typical and atypical scoliosis symptomatology beginning from the preclinical stage. PMID:22744477

  7. Casein kinases

    DEFF Research Database (Denmark)

    Issinger, O G

    1993-01-01

    , no genetic changes are necessarily involved; the observed changes may be entirely due to a signal transduction pathway where CK-2 could be phosphorylated by another kinase(s). CK-2 cDNAs from various organisms have been isolated and characterized. From the deduced amino acid sequence it turns out that CK-2......-specific expression of CK-2 at the mRNA and at the protein level has also been given attention. The fact that the enzyme activity is surprisingly high in brain and low in heart and lung may be indicative of involvement of CK-2 in processes other than proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)...

  8. Petrogenesis, zircon U-Pb age, and geochemistry of the A-type Mogou syenite, western Henan Province: Implications for Mesozoic tectono-magmatic evolution of the Qinling Orogen

    Science.gov (United States)

    He, Xinyu; Wang, Jionghui; Wang, Changming; Carranza, Emmanuel John M.; Chen, Liang; Wu, Bin

    2016-04-01

    The Mogou syenite intruded into the Mesoproterozoic Xiong'er Group is the main lithostratigraphic unit, along the southern margin of the North China Craton (NCC). This paper reports zircon LA-ICP-MS data, whole-rock major and trace element compositions of late Triassic magmatic rocks in the Mogou syenite, in order to constrain the formation age of the Mogou syenite, research the origin and evolution of the magma and analyse the geodynamic setting of the Qinling Orogen (QO) in Late Triassic. These rocks consist of medium- to coarse-grained syenite and fine-grained quartz syenite. Zircon U-Pb dating yields a crystallization age of 226.5±2.7 Ma. The syenites are characterized by high SiO2 (63.49-72.17%), alkali (K2O+Na2O of 11.18-15.38%) and potassium (K2O/Na2O of 2.88-28.11), are peralkaline or metaluminous (molar A/CNK of 0.87-1.02) and belong to shoshonite series. The syenites have ΣREE of 33.01-191.30 ppm, LREE/HREE of 14-20, (La/Yb)N of 11-24, with LREE-rich distribution pattern and obvious differentiation between HREE and LREE. Eu anomalies are positive for the medium- to coarse-grained syenite and weakly negative for the fine-grained quartz syenite. In addition, the syenites are enriched in large-ion lithophile elements (Ba, K, Sr, and Pb) but depleted in high strength field elements (Ti, Ta, Nb, Zr, and Hf), and have high differentiation indices of 91.69-97.06. These geochemical features indicate that the primary magma of the Mogou syenite most likely originated from a mantle source with minor crustal component, and underwent a fractional crystallization process during its emplacement. The late Triassic A-type Moguo syenite along the southern margin of the NCC was generated in the late stage of the syn-collision event of QO, recording a transition period from compression to extension at around 227 Ma.

  9. Petrogenesis, zircon U–Pb age, and geochemistry of the A-type Mogou syenite, western Henan Province: Implications for Mesozoic tectono-magmatic evolution of the Qinling Orogen

    Indian Academy of Sciences (India)

    Xinyu He; Jionghui Wang; Changming Wang; Emmanuel John M Carranza; Liang Chen; Bin Wu

    2016-04-01

    The Mogou syenite intruded into the Mesoproterozoic Xiong’er Group is the main lithostratigraphic unit, along the southern margin of the North China Craton (NCC). This paper reports zircon LAICP-MS data, whole-rock major and trace element compositions of late Triassic magmatic rocks in the Mogou syenite, in order to constrain the formation age of the Mogou syenite, research the origin and evolution of the magma and analyse the geodynamic setting of the Qinling Orogen (QO) in Late Triassic. These rocks consist of medium- to coarse-grained syenite and fine-grained quartz syenite. Zircon U–Pb dating yields a crystallization age of 226.5±2.7 Ma. The syenites are characterized by highSiO_2 (63.49–72.17%), alkali (K_2O+Na_2O of 11.18–15.38%) and potassium (K_2O/Na_2O of 2.88–28.11), are peralkaline or metaluminous (molar A/CNK of 0.87–1.02) and belong to shoshonite series. The syenites have ΣREE of 33.01–191.30 ppm, LREE/HREE of 14–20, (La/Yb)N of 11–24, with LREE-richdistribution pattern and obvious differentiation between HREE and LREE. Eu anomalies are positive for the medium- to coarse-grained syenite and weakly negative for the fine-grained quartz syenite. In addition, the syenites are enriched in large-ion lithophile elements (Ba, K, Sr, and Pb) but depleted inhigh strength field elements (Ti, Ta, Nb, Zr, and Hf), and have high differentiation indices of 91.69–97.06. These geochemical features indicate that the primary magma of the Mogou syenite most likely originated from a mantle source with minor crustal component, and underwent a fractional crystallizationprocess during its emplacement. The late Triassic A-type Moguo syenite along the southern margin of the NCC was generated in the late stage of the syn-collision event of QO, recording a transition periodfrom compression to extension at around 227 Ma.

  10. RhoA, Rho kinase, JAK2, and STAT3 may be the intracellular determinants of longevity implicated in the progeric influence of obesity: Insulin, IGF-1, and leptin may all conspire to promote stem cell exhaustion.

    Science.gov (United States)

    Tapia, Patrick C

    2006-01-01

    The aging process in higher mammals is increasingly being shown to feature a potentially substantial contribution from the longitudinal deterioration of normative stem cell dynamics seen with the passage of time. The precise mechanistic sequence producing this phenomenon is not entirely understood, but recent evidence has strongly implicated intracellular downstream effectors of endocrinologic pathways thought to be engaged by the obese state, specifically the insulin, IGF-1, and leptin signaling pathways. Among the intracellular effectors of these signals, a uniquely potent influence on stem cell dynamics may be attributable to Rho/ROCK, JAK kinase activity and STAT3 activity. In particular, it has already been shown that specific tyrosine kinase activities, such as that seen with Rho kinase, are presently thought to be associated with adverse health outcomes in numerous clinical contexts. Furthermore, the Rho GTPase is thought to be contributing to end-stage renal disease. However, in addition to its contribution to organ system dysfunction, the Rho/ROCK pathway has recently been shown to be activated by insulin and IGF-1, providing a tantalizing connection to nutrition and aging science. The JAK-STAT pathway, in contrast, has long been associated with pro-inflammatory cytokines, but has recently been implicated in leptin signaling as well. Importantly, JAK-STAT signaling has, similarly to Rho/ROCK signaling, been implicated as capable of accelerating stem cell proliferation. The implications of these recent determinations, in light of the recent finding of telomere attrition in humans associated with obesity, are that the intracellular determinants of aging may already be known, and the known common influence of these signaling elements on longitudinal stem cell dynamics is a pronounced induction of proliferation, an elevation that has been linked to the pathologic evolution of longitudinal organ-level dysfunction and the organismal-level physiologic decline

  11. Protein kinase profiling assays: a technology review.

    Science.gov (United States)

    Wang, Yuren; Ma, Haiching

    2015-11-01

    Protein kinases have become one of the most intensively pursued classes of drug targets for many diseases such as cancers and inflammatory diseases. Kinase profiling work seeks to understand general selectivity trends of lead compounds across the kinome, which help with target selection, compound prioritization, and potential implications in toxicity. Under the current drug discovery process, screening of compounds against comprehensive panels of kinases and their mutants has become the standard approach. Many screening assays and technologies which are compatible for high-throughput screening (HTS) against kinases have been extensively pursued and developed.

  12. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan;

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...

  13. ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins.

    Science.gov (United States)

    Fry, D C; Kuby, S A; Mildvan, A S

    1986-02-01

    The MgATP binding site of adenylate kinase, located by a combination of NMR and x-ray diffraction, is near three protein segments, five to seven amino acids in length, that are homologous in sequence to segments found in other nucleotide-binding phosphotransferases, such as myosin and F1-ATPase, ras p21 and transducin GTPases, and cAMP-dependent and src protein kinases, suggesting equivalent mechanistic roles of these segments in all of these proteins. Segment 1 is a glycine-rich flexible loop that, on adenylate kinase, may control access to the ATP-binding site by changing its conformation. Segment 2 is an alpha-helix containing two hydrophobic residues that interact with the adenine-ribose moiety of ATP, and a lysine that may bind to the beta- and gamma-phosphates of ATP. Segment 3 is a hydrophobic strand of parallel beta-pleated sheet, terminated by a carboxylate, that flanks the triphosphate binding site. The various reported mutations of ras p21 that convert it to a transforming agent all appear to involve segment 1, and such substitutions may alter the properties of p21 by hindering a conformational change at this segment. In F1-ATPase, the flexible loop may, by its position, control both the accessibility and the ATP/ADP equilibrium constant on the enzyme.

  14. Phosphorylation of cystic fibrosis transmembrane conductance regulator (CFTR) serine-511 by the combined action of tyrosine kinases and CK2: the implication of tyrosine-512 and phenylalanine-508.

    Science.gov (United States)

    Cesaro, Luca; Marin, Oriano; Venerando, Andrea; Donella-Deana, Arianna; Pinna, Lorenzo A

    2013-12-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) harbors, close to Phe-508, whose deletion is the commonest cause of cystic fibrosis, a conserved potential CK2 phospho-acceptor site (Ser511), which however is not susceptible to phosphorylation by CK2. To shed light on this apparent paradox, a series of systematically substituted peptides encompassing Ser511 were assayed for their ability to be phosphorylated. The main outcomes of our study are the following: (a) Tyr512 plays a prominent role as a negative determinant as its replacement by Ala restores Ser511 phosphorylation by CK2; (b) an even more pronounced phosphorylation of Ser511 is promoted if Tyr512 is replaced by phospho-tyrosine instead of alanine; (c) Tyr512 and, to a lesser extent, Tyr515 are readily phosphorylated by Lyn, a protein tyrosine kinase of the Src family, in a manner which is enhanced by the concomitant Phe508 deletion. Collectively taken, our data, in conjunction with the notion that Tyr515 is phosphorylated in vivo, disclose the possibility that CFTR Ser511 can be phosphorylated by the combined action of tyrosine kinases and CK2 and disclose a new mechanism of hierarchical phosphorylation where the role of the priming kinase is that of removing negative determinant(s).

  15. Atypical presentations of Wolframs syndrome

    Directory of Open Access Journals (Sweden)

    S Saran

    2012-01-01

    Full Text Available Background: Wolfram syndrome is a rare hereditary or sporadic neurodegenerative disorder also known as DIDMOAD. The classically described presentation is of insulin-dependent diabetes, followed by optic atrophy, central diabetes insipidus, and sensory neural deafness. Also included are less well-described presentations of Wolframs syndrome. We here present three cases of atypical presentation of this syndrome. Case 1: A 15-year-old boy with insulin-dependent diabetes was presented for evaluation of depressive symptoms associated with suicidal tendency. Neuropsychiatric manifestations are described with Wolframs syndrome, and wolframin gene, in recessive inheritance, is associated with psychiatric illnesses without other manifestations of Wolframs syndrome. Case 2: A 17-year-old diabetic boy on insulin with good control of blood sugar presented for evaluation of delayed puberty. Central hypogonadism and other anterior pituitary hormone dysfunctions are the less publicized hormone dysfunctions in Wolframs syndrome. Case 3: A 23-year-old female who was on insulin for diabetes for the past 14 years, got admitted for evaluation of sudden loss of vision. This patient had developed a vitreous hemorrhage and, on evaluation, was found to have optic atrophy, sensory neural hearing loss, and diabetes insipidus, and presented differently from the gradual loss of vision described in Wolframs syndrome. Conclusion: Wolframs syndrome being a multisystem degenerative disorder can have myriad other manifestations than the classically described features. Neuropsychiatric manifestations, depression with suicidal risk, central hypogonadism, and secondary adrenal insufficiency are among the less well-described manifestations of this syndrome.

  16. Atypical presentations of neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Douglas Sato

    2011-10-01

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of central nervous system classically characterized by acute, severe episodes of optic neuritis and longitudinally extensive transverse myelitis, usually with a relapsing course. The identification of an autoantibody exclusively detected in NMO patients against aquaporin-4 (AQP-4 has allowed identification of cases beyond the classical phenotype. Brain lesions, once thought as infrequent, can be observed in NMO patients, but lesions have different characteristics from the ones seen in multiple sclerosis. Additionally, some AQP-4 antibody positive patients may present with a variety of symptoms not being restricted to optic neuritis and acute myelitis during the first attack or in a relapse. Examples are not limited to, but may include patients only with brain and/or brainstem lesions, narcolepsy with hypothalamic lesions or patients with intractable hiccups, nausea and vomiting. The prompt identification of NMO patients with atypical presentations may benefit these patients with institution of early treatment to reduce disability and prevent further attacks.

  17. Surgical Options for Atypical Facial Pain Syndromes.

    Science.gov (United States)

    Rahimpour, Shervin; Lad, Shivanand P

    2016-07-01

    Atypical neuropathic facial pain is a syndrome of intractable and unremitting facial pain that is secondary to nociceptive signaling in the trigeminal system. These syndromes are often recalcitrant to pharmacotherapy and other common interventions, including microvascular decompression and percutaneous procedures. Herein, the authors present two other viable approaches (nucleus caudalis dorsal root entry zone lesioning and motor cortex stimulation), their indications, and finally a possible treatment algorithm to consider when assessing patients with atypical facial pain. PMID:27325003

  18. cis-Active Ras G2-like sequence implicated in the heterotropic activation of the deoxyadenosine kinase of Lactobacillus acidophilus R-26.

    Science.gov (United States)

    Guo, S; Ma, N; Ives, D H

    1997-03-14

    Deoxyadenosine kinase (dAK) forms a heterodimer with either deoxyguanosine kinase (dGK) or deoxycytidine kinase (dCK), and is heterotropically activated 3-5 times by dGuo or dCyd. Expressed alone, dAK is inactive and exhibits no response to dGuo or dCyd; activity and heterotropic response are fully restored upon reassociation with dGK or dCK. However, turnover of independently expressed dGK or dCK is nearly maximal, being further activated only 50-100% upon reassociation with dAK. In neither case is the heterotropic activation due to ligand-induced heterodimer formation. A proline/alanine substitution within a dAK segment homologous to loop G2 of Ras proteins yielded a heterodimer with dAK permanently cis-activated 2-fold, with a corresponding reduction in heterotropic activation by dGuo. A chimeric dAK, with 25% of its C terminus substituted by the homologous sequence from dGK, was inactive alone, and its characteristics were unchanged in the reconstituted heterodimer. Superimposing the Pro/Ala substitution on this chimera also reduced heterotropic activation by half. Cross-linking the dimer by 1,5-difluoro-2,4-dinitrobenzene was inhibited by ATP, dATP, dGTP, and dAdo, suggesting the proximity of the active site(s) to the interface. These data suggest that dAK depends on dGK or dCK in a manner resembling the reliance of Ras upon GTPase activating protein.

  19. Clinical Presentation of Atypical Genital Herpes

    Institute of Scientific and Technical Information of China (English)

    李俊杰; 梁沛杨; 罗北京

    2002-01-01

    Objective: To make a clinical analysis on the basis of 36cases of atypical genital herpes (GH) patients. Methods: Thirty-six cases of atypical GH were diagnosedclinically, and their case histories, symptoms and signs wererecorded in detail and followed up. Polymerase chain reaction(PCR) was adopted for testing HSV2-DNA with cotton-tippedswabs. Enzyme-linked immuno sorbent assay (ELISA) forserum anti-HSV2-IgM was done to establish a definfiivediagnosis. Other diagnoses were excluded at the same time bytesting for related pathogens including fungi, Chlamydia,Mycoplasma, Treponema pallidum, gonococci, Trichomonas,etc. Results: The main clinical manifestations of atypical GHwere: (1) small genital ulcers; (2) inflammation of urethralmeatus; (3) nonspecific genital erythema; (4) papuloid noduleson the glands; (5) nonspecific vaginitis. Twenty-three cases(64%) tested by PCR were HSV2-DNA sera-positive, and 36cases (100 %) anti-HSV2-IgM sera-positive by ELISA. Conclusion: atypical HSV is difficult to be diagnosed. Butthe combination of PCR and ELIAS will be helpful to thediagnosis of atypical HSV.

  20. Evolution of acetylcholinesterase and butyrylcholinesterase in the vertebrates: an atypical butyrylcholinesterase from the Medaka Oryzias latipes.

    Directory of Open Access Journals (Sweden)

    Leo Pezzementi

    Full Text Available Acetylcholinesterase (AChE and butyrylcholinesterase (BChE are thought to be the result of a gene duplication event early in vertebrate evolution. To learn more about the evolution of these enzymes, we expressed in vitro, characterized, and modeled a recombinant cholinesterase (ChE from a teleost, the medaka Oryzias latipes. In addition to AChE, O. latipes has a ChE that is different from either vertebrate AChE or BChE, which we are classifying as an atypical BChE, and which may resemble a transitional form between the two. Of the fourteen aromatic amino acids in the catalytic gorge of vertebrate AChE, ten are conserved in the atypical BChE of O. latipes; by contrast, only eight are conserved in vertebrate BChE. Notably, the atypical BChE has one phenylalanine in its acyl pocket, while AChE has two and BChE none. These substitutions could account for the intermediate nature of this atypical BChE. Molecular modeling supports this proposal. The atypical BChE hydrolyzes acetylthiocholine (ATCh and propionylthiocholine (PTCh preferentially but butyrylthiocholine (BTCh to a considerable extent, which is different from the substrate specificity of AChE or BChE. The enzyme shows substrate inhibition with the two smaller substrates but not with the larger substrate BTCh. In comparison, AChE exhibits substrate inhibition, while BChE does not, but may instead show substrate activation. The atypical BChE from O. latipes also shows a mixed pattern of inhibition. It is effectively inhibited by physostigmine, typical of all ChEs. However, although the atypical BChE is efficiently inhibited by the BChE-specific inhibitor ethopropazine, it is not by another BChE inhibitor, iso-OMPA, nor by the AChE-specific inhibitor BW284c51. The atypical BChE is found as a glycophosphatidylinositol-anchored (GPI-anchored amphiphilic dimer (G(2 (a, which is unusual for any BChE. We classify the enzyme as an atypical BChE and discuss its implications for the evolution of ACh

  1. Cutting Edge: Molecular Structure of the IL-1R-Associated Kinase-4 Death Domain and Its Implications for TLR Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lasker, Michael V.; Gajjar, Mark M.; Nair, Satish K. (UIUC)

    2010-07-19

    IL-1R-associated kinase (IRAK) 4 is an essential component of innate immunity. IRAK-4 deficiency in mice and humans results in severe impairment of IL-1 and TLR signaling. We have solved the crystal structure for the death domain of Mus musculus IRAK-4 to 1.7 {angstrom} resolution. This is the first glimpse of the structural details of a mammalian IRAK family member. The crystal structure reveals a six-helical bundle with a prominent loop, which among IRAKs and Pelle, a Drosophila homologue, is unique to IRAK-4. This highly structured loop contained between helices two and three, comprises an 11-aa stretch. Although innate immune domain recognition is thought to be very similar between Drosophila and mammals, this structural component points to a drastic difference. This structure can be used as a framework for future mutation and deletion studies and potential drug design.

  2. Role of protein kinase C β and vascular endothelial growth factor receptor in malignant pleural mesothelioma: Therapeutic implications and the usefulness of Caenorhabditis elegans model organism

    Directory of Open Access Journals (Sweden)

    Sivakumar Loganathan

    2011-01-01

    Full Text Available Purpose: To examine the role of both protein kinase C (PKC-β and vascular endothelial growth factor receptor (VEGFR-2 in malignant pleural mesothelioma (MPM using respective inhibitors, enzastaurin and KRN633. Materials and Methods: MPM cell lines, control cells, and a variety of archived MPM tumor samples were used to determine the protein expression levels of PKC-β, VEGFR-2, VEGF, and p-AKT. Effects of enzastaurin and KRN633 on phosphorylation status of key signaling molecules and viability of the mesothelioma cells were determined. The common soil nematode, Caenorhabditis elegans, was treated with enzastaurin to determine its suitability to screen for highly potent kinase inhibitors. Results: PKC-β1, PKC-β2 and VEGFR-2/KDR were overexpressed in MPM cell lines and MPM tumor tissues. Enzastaurin treatment resulted in significant loss in viability of VEGF induced cell proliferation; however, the effect of KRN633 was much less. Enzastaurin also dramatically decreased the phosphorylation of PKC-β, its downstream target p-AKT, and surprisingly, the upstream VEGFR-2. The combination of the two drugs at best was additive and similar results were obtained with respect to cell viability. Treatment of C. elegans with enzastaurin resulted in clear phenotypic changes and the worms were hypermotile with abnormal pattern and shape of eggs, suggesting altered fecundity. Conclusions: PKC-β1 and VEGFR-2 are both excellent therapeutic targets in MPM. Enzastaurin was better at killing MPM cells than KRN633 and the combination lacked synergy. In addition, we show here that C. elegans can be used to screen for the next generation inhibitors as treatment with enzastaurin resulted in clear phenotypic changes that could be assayed.

  3. cGMP-dependent protein kinase type I is implicated in the regulation of the timing and quality of sleep and wakefulness.

    Directory of Open Access Journals (Sweden)

    Sonja Langmesser

    Full Text Available Many effects of nitric oxide (NO are mediated by the activation of guanylyl cyclases and subsequent production of the second messenger cyclic guanosine-3',5'-monophosphate (cGMP. cGMP activates cGMP-dependent protein kinases (PRKGs, which can therefore be considered downstream effectors of NO signaling. Since NO is thought to be involved in the regulation of both sleep and circadian rhythms, we analyzed these two processes in mice deficient for cGMP-dependent protein kinase type I (PRKG1 in the brain. Prkg1 mutant mice showed a strikingly altered distribution of sleep and wakefulness over the 24 hours of a day as well as reductions in rapid-eye-movement sleep (REMS duration and in non-REM sleep (NREMS consolidation, and their ability to sustain waking episodes was compromised. Furthermore, they displayed a drastic decrease in electroencephalogram (EEG power in the delta frequency range (1-4 Hz under baseline conditions, which could be normalized after sleep deprivation. In line with the re-distribution of sleep and wakefulness, the analysis of wheel-running and drinking activity revealed more rest bouts during the activity phase and a higher percentage of daytime activity in mutant animals. No changes were observed in internal period length and phase-shifting properties of the circadian clock while chi-squared periodogram amplitude was significantly reduced, hinting at a less robust oscillator. These results indicate that PRKG1 might be involved in the stabilization and output strength of the circadian oscillator in mice. Moreover, PRKG1 deficiency results in an aberrant pattern, and consequently a reduced quality, of sleep and wakefulness, possibly due to a decreased wake-promoting output of the circadian system impinging upon sleep.

  4. Atypical RNAs in the coelacanth transcriptome.

    Science.gov (United States)

    Nitsche, Anne; Doose, Gero; Tafer, Hakim; Robinson, Mark; Saha, Nil Ratan; Gerdol, Marco; Canapa, Adriana; Hoffmann, Steve; Amemiya, Chris T; Stadler, Peter F

    2014-09-01

    Circular and apparently trans-spliced RNAs have recently been reported as abundant types of transcripts in mammalian transcriptome data. Both types of non-colinear RNAs are also abundant in RNA-seq of different tissue from both the African and the Indonesian coelacanth. We observe more than 8,000 lincRNAs with normal gene structure and several thousands of circularized and trans-spliced products, showing that such atypical RNAs form a substantial contribution to the transcriptome. Surprisingly, the majority of the circularizing and trans-connecting splice junctions are unique to atypical forms, that is, are not used in normal isoforms.

  5. Genetics Home Reference: atypical hemolytic-uremic syndrome

    Science.gov (United States)

    ... the genes associated with atypical hemolytic-uremic syndrome C3 CD46 CFB CFH CFHR5 CFI THBD Related Information ... Manual Consumer Version: Thrombocytopenia Merck Manual Professional Version: Complement System Orphanet: Atypical hemolytic-uremic syndrome Patient Support ...

  6. The mechanism of protein kinase C regulation

    Institute of Scientific and Technical Information of China (English)

    Julhash U. KAZI

    2011-01-01

    Protein kinase C (PKC) is a family ofserine/threonine protein kinases that plays a central role in transducing extracellular signals into a variety of intracellular responses ranging from cell proliferation to apoptosis.Nine PKC genes have been identified in the human genome,which encode 10 proteins.Each member of this protein kinase family displays distinct biochemical characteristics and is enriched in different cellular and subcellular locations.Activation of PKC has been implicated in the regulation of cell growth and differentiation.This review summarizes works of the past years in the field of PKC biochemistry that covers regulation and activation mechanism of different PKC isoforms.

  7. Atypical fractures on long term bisphosphonates therapy.

    LENUS (Irish Health Repository)

    Hussein, W

    2011-01-01

    Bisphosphonates reduce fractures risk in patients with osteoporosis. A new pattern of fractures is now being noted in patients on prolonged bisphosphonate therapy. We report a case of an atypical femoral fracture with preceding pain and highlight the characteristics of these fractures.

  8. Cohort study of atypical pressure ulcers development.

    Science.gov (United States)

    Jaul, Efraim

    2014-12-01

    Atypical pressure ulcers (APU) are distinguished from common pressure ulcers (PU) with both unusual location and different aetiology. The occurrence and attempts to characterise APU remain unrecognised. The purpose of this cohort study was to analyse the occurrence of atypical location and the circumstances of the causation, and draw attention to the prevention and treatment by a multidisciplinary team. The cohort study spanned three and a half years totalling 174 patients. The unit incorporates two weekly combined staff meetings. One concentrates on wound assessment with treatment decisions made by the physician and nurse, and the other, a multidisciplinary team reviewing all patients and coordinating treatment. The main finding of this study identified APU occurrence rate of 21% within acquired PU over a three and a half year period. Severe spasticity constituted the largest group in this study and the most difficult to cure wounds, located in medial aspects of knees, elbows and palms. Medical devices caused the second largest occurrence of atypical wounds, located in the nape of the neck, penis and nostrils. Bony deformities were the third recognisable atypical wound group located in shoulder blades and upper spine. These three categories are definable and time observable. APU are important to be recognisable, and can be healed as well as being prevented. The prominent role of the multidisciplinary team is primary in identification, prevention and treatment. PMID:23374746

  9. Observing Behavior and Atypically Restricted Stimulus Control

    Science.gov (United States)

    Dube, William V.; Dickson, Chata A.; Balsamo, Lyn M.; O'Donnell, Kristin Lombard; Tomanari, Gerson Y.; Farren, Kevin M.; Wheeler, Emily E.; McIlvane, William J.

    2010-01-01

    Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded…

  10. Atypical visuomotor performance in children with PDD

    NARCIS (Netherlands)

    Schlooz, W.A.J.M.; Hulstijn, W.

    2012-01-01

    Children with autism spectrum disorders (ASD) frequently encounter difficulties in visuomotor tasks, which are possibly caused by atypical visuoperceptual processing. This was tested in children (aged 9–12 years) with pervasive developmental disorder (PDD; including PDD-NOS and Asperger syndrome), a

  11. Atypical pyoderma gangrenosum mimicking an infectious process.

    Science.gov (United States)

    To, Derek; Wong, Aaron; Montessori, Valentina

    2014-01-01

    We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics. PMID:25024856

  12. Atypical Pyoderma Gangrenosum Mimicking an Infectious Process

    Directory of Open Access Journals (Sweden)

    Derek To

    2014-01-01

    Full Text Available We present a patient with atypical pyoderma gangrenosum (APG, which involved the patient’s arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

  13. Disentangling the Emerging Evidence around Atypical Fractures

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Clark, Emma M

    2012-01-01

    Atypical femur fractures are rare but a growing concern, as they are more common in patients who use bisphosphonates. The best radiology-based studies have had access to only short-term exposure data, while the studies using prescription databases with substantial long-term data did not have access...

  14. Infant Perception of Atypical Speech Signals

    Science.gov (United States)

    Vouloumanos, Athena; Gelfand, Hanna M.

    2013-01-01

    The ability to decode atypical and degraded speech signals as intelligible is a hallmark of speech perception. Human adults can perceive sounds as speech even when they are generated by a variety of nonhuman sources including computers and parrots. We examined how infants perceive the speech-like vocalizations of a parrot. Further, we examined how…

  15. Enhanced Uterine Contractility and Stillbirth in Mice Lacking G Protein-Coupled Receptor Kinase 6 (GRK6): Implications for Oxytocin Receptor Desensitization.

    Science.gov (United States)

    Grotegut, Chad A; Mao, Lan; Pierce, Stephanie L; Swamy, Geeta K; Heine, R Phillips; Murtha, Amy P

    2016-04-01

    Oxytocin is a potent uterotonic agent and is used clinically for induction and augmentation of labor, as well as for prevention and treatment of postpartum hemorrhage. Oxytocin increases uterine contractility by activating the oxytocin receptor (OXTR), a member of the G protein-coupled receptor family, which is prone to molecular desensitization. After oxytocin binding, the OXTR is phosphorylated by a member of the G protein-coupled receptor kinase (GRK) family, which allows for recruitment of β-arrestin, receptor internalization, and desensitization. According to previous in vitro analyses, desensitization of calcium signaling by the OXTR is mediated by GRK6. The objective of this study was to determine the role of GRK6 in mediating uterine contractility. Here, we demonstrate that uterine GRK6 levels increase in pregnancy and using a telemetry device to measure changes in uterine contractility in live mice during labor, show that mice lacking GRK6 produce a phenotype of enhanced uterine contractility during both spontaneous and oxytocin-induced labor compared with wild-type or GRK5 knockout mice. In addition, the observed enhanced contractility was associated with high rates of term stillbirth. Lastly, using a heterologous in vitro model, we show that β-arrestin recruitment to the OXTR, which is necessary for homologous OXTR desensitization, is dependent on GRK6. Our findings suggest that GRK6-mediated OXTR desensitization in labor is necessary for normal uterine contractile patterns and optimal fetal outcome. PMID:26886170

  16. Allosteric regulation of protein kinase PKCζ by the N-terminal C1 domain and small compounds to the PIF-pocket

    DEFF Research Database (Denmark)

    Lopez-Garcia, Laura A; Schulze, Jörg O; Fröhner, Wolfgang;

    2011-01-01

    Protein kinases are key mediators of cellular signaling, and therefore, their activities are tightly controlled. AGC kinases are regulated by phosphorylation and by N- and C-terminal regions. Here, we studied the molecular mechanism of inhibition of atypical PKCζ and found that the inhibition by ...

  17. The role of mitogen-activated protein kinases and sterol receptor coactivator-1 in TGF-β-regulated expression of genes implicated in macrophage cholesterol uptake

    Science.gov (United States)

    Salter, Rebecca C.; Foka, Pelagia; Davies, Thomas S.; Gallagher, Hayley; Michael, Daryn R.; Ashlin, Tim G.; Ramji, Dipak P.

    2016-01-01

    The anti-atherogenic cytokine TGF-β inhibits macrophage foam cell formation by suppressing the expression of key genes implicated in the uptake of modified lipoproteins. We have previously shown a critical role for p38 MAPK and JNK in the TGF-β-mediated regulation of apolipoprotein E expression in human monocytes. However, the roles of these two MAPK pathways in the control of expression of key genes involved in the uptake of modified lipoproteins in human macrophages is poorly understood and formed the focus of this study. TGF-β activated both p38 MAPK and JNK, and knockdown of p38 MAPK or c-Jun, a key downstream target of JNK action, demonstrated their requirement in the TGF-β-inhibited expression of several key genes implicated in macrophage lipoprotein uptake. The potential role of c-Jun and specific co-activators in the action of TGF-β was investigated further by studies on the lipoprotein lipase gene. c-Jun did not directly interact with the minimal promoter region containing the TGF-β response elements and a combination of transient transfection and knock down assays revealed an important role for SRC-1. These studies provide novel insights into the mechanisms underlying the TGF-β-mediated inhibition of macrophage gene expression associated with the control of cholesterol homeostasis. PMID:27687241

  18. Atypical face gaze in autism.

    Science.gov (United States)

    Trepagnier, Cheryl; Sebrechts, Marc M; Peterson, Rebecca

    2002-06-01

    An eye-tracking study of face and object recognition was conducted to clarify the character of face gaze in autistic spectrum disorders. Experimental participants were a group of individuals diagnosed with Asperger's disorder or high-functioning autistic disorder according to their medical records and confirmed by the Autism Diagnostic Interview-Revised (ADI-R). Controls were selected on the basis of age, gender, and educational level to be comparable to the experimental group. In order to maintain attentional focus, stereoscopic images were presented in a virtual reality (VR) headset in which the eye-tracking system was installed. Preliminary analyses show impairment in face recognition, in contrast with equivalent and even superior performance in object recognition among participants with autism-related diagnoses, relative to controls. Experimental participants displayed less fixation on the central face than did control-group participants. The findings, within the limitations of the small number of subjects and technical difficulties encountered in utilizing the helmet-mounted display, suggest an impairment in face processing on the part of the individuals in the experimental group. This is consistent with the hypothesis of disruption in the first months of life, a period that may be critical to typical social and cognitive development, and has important implications for selection of appropriate targets of intervention.

  19. Sustained Action of Ceramide on the Insulin Signaling Pathway in Muscle Cells: IMPLICATION OF THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE.

    Science.gov (United States)

    Hage Hassan, Rima; Pacheco de Sousa, Ana Catarina; Mahfouz, Rana; Hainault, Isabelle; Blachnio-Zabielska, Agnieszka; Bourron, Olivier; Koskas, Fabien; Górski, Jan; Ferré, Pascal; Foufelle, Fabienne; Hajduch, Eric

    2016-02-01

    In vivo, ectopic accumulation of fatty acids in muscles leads to alterations in insulin signaling at both the IRS1 and Akt steps. However, in vitro treatments with saturated fatty acids or their derivative ceramide demonstrate an effect only at the Akt step. In this study, we adapted our experimental procedures to mimic the in vivo situation and show that the double-stranded RNA-dependent protein kinase (PKR) is involved in the long-term effects of saturated fatty acids on IRS1. C2C12 or human muscle cells were incubated with palmitate or directly with ceramide for short or long periods, and insulin signaling pathway activity was evaluated. PKR involvement was assessed through pharmacological and genetic studies. Short-term treatments of myotubes with palmitate, a ceramide precursor, or directly with ceramide induce an inhibition of Akt, whereas prolonged periods of treatment show an additive inhibition of insulin signaling through increased IRS1 serine 307 phosphorylation. PKR mRNA, protein, and phosphorylation are increased in insulin-resistant muscles. When PKR activity is reduced (siRNA or a pharmacological inhibitor), serine phosphorylation of IRS1 is reduced, and insulin-induced phosphorylation of Akt is improved. Finally, we show that JNK mediates ceramide-activated PKR inhibitory action on IRS1. Together, in the long term, our results show that ceramide acts at two distinct levels of the insulin signaling pathway (IRS1 and Akt). PKR, which is induced by both inflammation signals and ceramide, could play a major role in the development of insulin resistance in muscle cells. PMID:26698173

  20. Tissue Strain Reorganizes Collagen With a Switchlike Response That Regulates Neuronal Extracellular Signal-Regulated Kinase Phosphorylation In Vitro: Implications for Ligamentous Injury and Mechanotransduction.

    Science.gov (United States)

    Zhang, Sijia; Cao, Xuan; Stablow, Alec M; Shenoy, Vivek B; Winkelstein, Beth A

    2016-02-01

    Excessive loading of ligaments can activate the neural afferents that innervate the collagenous tissue, leading to a host of pathologies including pain. An integrated experimental and modeling approach was used to define the responses of neurons and the surrounding collagen fibers to the ligamentous matrix loading and to begin to understand how macroscopic deformation is translated to neuronal loading and signaling. A neuron-collagen construct (NCC) developed to mimic innervation of collagenous tissue underwent tension to strains simulating nonpainful (8%) or painful ligament loading (16%). Both neuronal phosphorylation of extracellular signal-regulated kinase (ERK), which is related to neuroplasticity (R2 ≥ 0.041; p ≤ 0.0171) and neuronal aspect ratio (AR) (R2 ≥ 0.250; p element based discrete fiber network (DFN) model predicted that at bulk strains above the transition point, heterogeneous fiber strains were both tensile and compressive and increased, with strains in some fibers along the loading direction exceeding the applied bulk strain. The transition point identified for changes in collagen fiber realignment was consistent with the measured strain threshold (11.7% with a 95% confidence interval of 10.2-13.4%) for elevating ERK phosphorylation after loading. As with collagen fiber realignment, the greatest degree of neuronal reorientation toward the loading direction was observed at the NCC distraction corresponding to painful loading. Because activation of neuronal ERK occurred only at strains that produced evident collagen fiber realignment, findings suggest that tissue strain-induced changes in the micromechanical environment, especially altered local collagen fiber kinematics, may be associated with mechanotransduction signaling in neurons. PMID:26549105

  1. Sustained Action of Ceramide on the Insulin Signaling Pathway in Muscle Cells: IMPLICATION OF THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE.

    Science.gov (United States)

    Hage Hassan, Rima; Pacheco de Sousa, Ana Catarina; Mahfouz, Rana; Hainault, Isabelle; Blachnio-Zabielska, Agnieszka; Bourron, Olivier; Koskas, Fabien; Górski, Jan; Ferré, Pascal; Foufelle, Fabienne; Hajduch, Eric

    2016-02-01

    In vivo, ectopic accumulation of fatty acids in muscles leads to alterations in insulin signaling at both the IRS1 and Akt steps. However, in vitro treatments with saturated fatty acids or their derivative ceramide demonstrate an effect only at the Akt step. In this study, we adapted our experimental procedures to mimic the in vivo situation and show that the double-stranded RNA-dependent protein kinase (PKR) is involved in the long-term effects of saturated fatty acids on IRS1. C2C12 or human muscle cells were incubated with palmitate or directly with ceramide for short or long periods, and insulin signaling pathway activity was evaluated. PKR involvement was assessed through pharmacological and genetic studies. Short-term treatments of myotubes with palmitate, a ceramide precursor, or directly with ceramide induce an inhibition of Akt, whereas prolonged periods of treatment show an additive inhibition of insulin signaling through increased IRS1 serine 307 phosphorylation. PKR mRNA, protein, and phosphorylation are increased in insulin-resistant muscles. When PKR activity is reduced (siRNA or a pharmacological inhibitor), serine phosphorylation of IRS1 is reduced, and insulin-induced phosphorylation of Akt is improved. Finally, we show that JNK mediates ceramide-activated PKR inhibitory action on IRS1. Together, in the long term, our results show that ceramide acts at two distinct levels of the insulin signaling pathway (IRS1 and Akt). PKR, which is induced by both inflammation signals and ceramide, could play a major role in the development of insulin resistance in muscle cells.

  2. Novel Library of Selenocompounds as Kinase Modulators

    Directory of Open Access Journals (Sweden)

    Carmen Sanmartín

    2011-07-01

    Full Text Available Although the causes of cancer lie in mutations or epigenic changes at the genetic level, their molecular manifestation is the dysfunction of biochemical pathways at the protein level. The 518 protein kinases encoded by the human genome play a central role in various diseases, a fact that has encouraged extensive investigations on their biological function and three dimensional structures. Selenium (Se is an important nutritional trace element involved in different physiological functions with antioxidative, antitumoral and chemopreventive properties. The mechanisms of action for selenocompounds as anticancer agents are not fully understood, but kinase modulation seems to be a possible pathway. Various organosulfur compounds have shown antitumoral and kinase inhibition effects but, in many cases, the replacement of sulfur by selenium improves the antitumoral effect of compounds. Although Se atom possesses a larger atomic volume and nucleophilic character than sulfur, Se can also formed interactions with aminoacids of the catalytic centers of proteins. So, we propose a novel chemical library that includes organoselenium compounds as kinase modulators. In this study thirteen selenocompounds have been evaluated at a concentration of 3 or 10 µM in a 24 kinase panel using a Caliper LabChip 3000 Drug Discover Platform. Several receptor (EGFR, IGFR1, FGFR1… and non-receptor (Abl kinases have been selected, as well as serine/threonine/lipid kinases (AurA, Akt, CDKs, MAPKs… implicated in main cancer pathways: cell cycle regulation, signal transduction, angiogenesis regulation among them. The obtained results showed that two compounds presented inhibition values higher than 50% in at least four kinases and seven derivatives selectively inhibited one or two kinases. Furthermore, three compounds selectively activated IGF-1R kinase with values ranging from −98% to −211%. In conclusion, we propose that the replacement of sulfur by selenium seems to be

  3. 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1

    DEFF Research Database (Denmark)

    Jensen, Claus Antonio Juel; Buch, M B; Krag, T O;

    1999-01-01

    90-kDa ribosomal S6 kinase-2 (RSK2) belongs to a family of growth factor-activated serine/threonine kinases composed of two kinase domains connected by a regulatory linker region. The N-terminal kinase of RSK2 is involved in substrate phosphorylation. Its activation requires phosphorylation of th...... of Ser(227), Ser(369), and Ser(386). Our study extend recent findings which implicate PDK1 in the activation of protein kinases B and C and p70(S6K), suggesting that PDK1 controls several major growth factor-activated signal transduction pathways.......90-kDa ribosomal S6 kinase-2 (RSK2) belongs to a family of growth factor-activated serine/threonine kinases composed of two kinase domains connected by a regulatory linker region. The N-terminal kinase of RSK2 is involved in substrate phosphorylation. Its activation requires phosphorylation...... of the linker region at Ser(369), catalyzed by extracellular signal-regulated kinase (ERK), and at Ser(386), catalyzed by the C-terminal kinase, after its activation by ERK. In addition, the N-terminal kinase must be phosphorylated at Ser(227) in the activation loop by an as yet unidentified kinase. Here, we...

  4. Contraction stimulates muscle glucose uptake independent of atypical PKC.

    Science.gov (United States)

    Yu, Haiyan; Fujii, Nobuharu L; Toyoda, Taro; An, Ding; Farese, Robert V; Leitges, Michael; Hirshman, Michael F; Mul, Joram D; Goodyear, Laurie J

    2015-11-01

    Exercise increases skeletal muscle glucose uptake, but the underlying mechanisms are only partially understood. The atypical protein kinase C (PKC) isoforms λ and ζ (PKC-λ/ζ) have been shown to be necessary for insulin-, AICAR-, and metformin-stimulated glucose uptake in skeletal muscle, but not for treadmill exercise-stimulated muscle glucose uptake. To investigate if PKC-λ/ζ activity is required for contraction-stimulated muscle glucose uptake, we used mice with tibialis anterior muscle-specific overexpression of an empty vector (WT), wild-type PKC-ζ (PKC-ζ(WT)), or an enzymatically inactive T410A-PKC-ζ mutant (PKC-ζ(T410A)). We also studied skeletal muscle-specific PKC-λ knockout (MλKO) mice. Basal glucose uptake was similar between WT, PKC-ζ(WT), and PKC-ζ(T410A) tibialis anterior muscles. In contrast, in situ contraction-stimulated glucose uptake was increased in PKC-ζ(T410A) tibialis anterior muscles compared to WT or PKC-ζ(WT) tibialis anterior muscles. Furthermore, in vitro contraction-stimulated glucose uptake was greater in soleus muscles of MλKO mice than WT controls. Thus, loss of PKC-λ/ζ activity increases contraction-stimulated muscle glucose uptake. These data clearly demonstrate that PKC-λζ activity is not necessary for contraction-stimulated glucose uptake.

  5. Primary lateral sclerosis mimicking atypical parkinsonism

    DEFF Research Database (Denmark)

    Norlinah, Ibrahim M; Bhatia, Kailash P; Østergaard, Karen;

    2007-01-01

    the atypical parkinsonian syndromes. Here we describe five patients initially referred with a diagnosis of levodopa-unresponsive atypical parkinsonism (n = 4) or primary progressive multiple sclerosis (n = 1), but subsequently found to have features consistent with PLS instead. Onset age varied from......Primary lateral sclerosis (PLS), the upper motor neurone variant of motor neurone disease, is characterized by progressive spinal or bulbar spasticity with minimal motor weakness. Rarely, PLS may present with clinical features resembling parkinsonism resulting in occasional misdiagnosis as one of...... eventually seen in all patients. Anterior horn cell involvement developed in three cases. Early gait disturbances resulting in falls were seen in all patients and none of them responded to dopaminergic medications. Two patients underwent dopamine transporter (DaT) SPECT scanning with normal results. Other...

  6. Primary atypical sacral meningioma- not always benign

    Energy Technology Data Exchange (ETDEWEB)

    Bhadra, A.K.; Casey, A.T.H.; Saifuddin, A.; Briggs, T.W. [Royal National Orthopaedic Hospital, Stanmore, London (United Kingdom)

    2007-06-15

    We present a case of an atypical recurrent meningioma of the sacrum with pulmonary metastasis in a 31-year-old man. He presented with deep-seated buttock pain and urinary hesitancy for 3 months. MRI revealed a lesion occupying the central and left side of the sacral canal at the S1-S2 level. Surgical excision of the lesion via a posterior approach was undertaken, and the patient became symptom-free post-operatively. Histology confirmed atypical meningioma. Eight months later he re-presented with similar symptoms, and MRI confirmed local recurrence. The patient underwent left hemisacrectomy. Six months later he again presented with low back pain and MRI confirmed a second local recurrence. A CT scan of the chest showed multiple lung metastases. The patient died of a severe chest infection 18 months later. (orig.)

  7. Conservation, variability and the modeling of active protein kinases.

    Directory of Open Access Journals (Sweden)

    James D R Knight

    Full Text Available The human proteome is rich with protein kinases, and this richness has made the kinase of crucial importance in initiating and maintaining cell behavior. Elucidating cell signaling networks and manipulating their components to understand and alter behavior require well designed inhibitors. These inhibitors are needed in culture to cause and study network perturbations, and the same compounds can be used as drugs to treat disease. Understanding the structural biology of protein kinases in detail, including their commonalities, differences and modes of substrate interaction, is necessary for designing high quality inhibitors that will be of true use for cell biology and disease therapy. To this end, we here report on a structural analysis of all available active-conformation protein kinases, discussing residue conservation, the novel features of such conservation, unique properties of atypical kinases and variability in the context of substrate binding. We also demonstrate how this information can be used for structure prediction. Our findings will be of use not only in understanding protein kinase function and evolution, but they highlight the flaws inherent in kinase drug design as commonly practiced and dictate an appropriate strategy for the sophisticated design of specific inhibitors for use in the laboratory and disease therapy.

  8. An atypical mycobacterial infection of the shoulder

    Directory of Open Access Journals (Sweden)

    Christopher L Talbot

    2012-01-01

    Full Text Available Mycobacterium malmoense is an acid-fast non-tuberculous organism that most commonly causes pulmonary infection. Extrapulmonary infection has also been reported. With an increased emphasis being placed on the clinical importance of this organism, especially within Europe, we report the first case of septic arthritis of the shoulder caused by this organism. We also highlight the importance of considering atypical mycobacterium infection in the differential diagnosis of shoulder infection and issues surrounding the management of this entity.

  9. Atypical retroperitoneal extension of iliopsoas bursitis

    Energy Technology Data Exchange (ETDEWEB)

    Coulier, B.; Cloots, V. [Department of Diagnostic Imaging, Cliniques St. Luc, Rue St Luc 8, 5004, Bouge, Namur (Belgium)

    2003-05-01

    We report two rare cases of iliopsoas bursitis extending into the retroperitoneal space. The first lesion contained much gas, mimicking a retroperitoneal abscess, and the second was responsible for atypical inguinal pain. The diagnosis was made by contrast-enhanced CT in both cases and arthrography in the first case. Iliopsoas bursitis in these two patients, it is hypothesized, extended into the retroperitoneum, at least in part, by way of intraneural or perineural structures. (orig.)

  10. Atypical anti-glomerular basement membrane disease

    OpenAIRE

    Troxell, Megan L.; Donald C Houghton

    2015-01-01

    Background Anti-glomerular basement membrane (anti-GBM) disease classically presents with aggressive necrotizing and crescentic glomerulonephritis, often with pulmonary hemorrhage. The pathologic hallmark is linear staining of GBMs for deposited immunoglobulin G (IgG), usually accompanied by serum autoantibodies to the collagen IV alpha-3 constituents of GBMs. Methods Renal pathology files were searched for cases with linear anti-GBM to identify cases with atypical or indolent course. Histopa...

  11. Atypical burkitt's lymphoma transforming from follicular lymphoma

    OpenAIRE

    Chung Lap P; Loong Florence; Hwang Yu Y; Chim Chor S

    2011-01-01

    Amongst follicular lymphoma that transforms into a high-grade lymphoma, majority are diffuse large B cell lymphoma. Here we reported a rare atypical Burkitt's lymphoma transformation from an asymptomatic follicular lymphoma. Lymph node biopsy showed a composite lymphoma with infiltration of the inter-follicular areas by high grade small non-cleaved lymphoma cells amongst neoplastic follicles. Moreover, FISH and molecular genetic study confirmed concomitant MYC translocations and t(14;18) in t...

  12. Atypical reactive histiocytosis. A case report.

    Directory of Open Access Journals (Sweden)

    Jorge E. Barleta del Castillo

    2004-08-01

    Full Text Available This paper presents the case of a 50 year old chronic alcoholic and heavy smoker female that was assisted at the provincial university hospital ¨Dr. Gustavo Aldereguía Lima¨ in Cienfuegos city due to a severe adenic syndrome and who was diagnosed as a case of atypical reactive histiocytosis , problem which disappeared with the abstinence of toxic habits, improving her health.

  13. Mnk kinase pathway: Cellular functions and biological outcomes

    Institute of Scientific and Technical Information of China (English)

    Sonali; Joshi; Leonidas; C; Platanias

    2014-01-01

    The mitogen-activated protein kinase(MAPK) interacting protein kinases 1 and 2(Mnk1 and Mnk2) play important roles in controlling signals involved in mRNA translation. In addition to the MAPKs(p38 or Erk), multiple studies suggest that the Mnk kinases can be regulated by other known kinases such as Pak2 and/or other unidentified kinases by phosphorylation of residues distinct from the sites phosphorylated by the MAPKs. Several studies have established multiple Mnk protein targets, including PSF, heterogenous nuclear ribonucleoprotein A1, Sprouty 2 and have lead to the identification of distinct biological functions and substrate specificity for the Mnk kinases. In this review we discuss the pathways regulating the Mnk kinases, their known substrates as well as the functional consequences of engagement of pathways controlled by Mnk kinases. These kinases play an important role in mRNA translation via their regulation of eukaryotic initiation factor 4E(eIF4E) and their functions have important implications in tumor biology as well as the regulation of drug resistance to anti-oncogenic therapies. Other studies have identified a role for the Mnk kinases in cap-independent mRNA translation, suggesting that the Mnk kinases can exert important functional effects independently of the phosphorylation of eIF4 E. The role of Mnk kinases in inflammation and inflammationinduced malignancies is also discussed.

  14. Aggressive papillary adenocarcinoma on atypical localization

    Science.gov (United States)

    Balci, Mecdi Gurhan; Tayfur, Mahir; Deger, Ayse Nur; Cimen, Orhan; Eken, Huseyin

    2016-01-01

    Abstract Introduction: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland tumor that is found on the fingers, toes, and the digits. To date, <100 cases have been reported in the literature. Apart from 1 case reported in the thigh, all of them were on digital or nondigital acral skin. Case presentation: A 67-year-old Caucasian woman was admitted to the hospital due to a mass on the scalp. This lesion was present for almost a year. It was a semimobile cyctic mass that elevated the scalp. There was no change in the skin color. Its dimensions were 1.5 × 1 × 0.6 cm. The laboratory, clinic, and radiologic findings (head x-ray) of the patient were normal. It was evaluated as a benign lesion such as lipoma or epidermal cyst by a surgeon due to a small semimobile mass and no erosion of the skull. It was excised by a local surgery excision. The result of the pathologic examination was aggressive papillary adenocarcinoma. This diagnosis is synonymous with ADPA. Conclusion: In our case, localization was scalp. This localization is the first for this tumor in the literature. In addition, another atypical localization of this tumor (ADPA) is thigh in the literature. This case was presented due to both the rare and atypical localizations. That is why, in our opinion, revision of “digital” term in ADPA is necessary due to seem in atypical localizations like thigh and scalp. PMID:27428196

  15. Surgical follow-up results for apocrine adenosis and atypical apocrine adenosis diagnosed on breast core biopsy.

    Science.gov (United States)

    Hou, Yanjun; Chaudhary, Shweta; Gao, Faye F; Li, Zaibo

    2016-10-01

    Apocrine adenosis (AA) and atypical apocrine adenosis (AAA) are uncommon findings in breast biopsies that may be misinterpreted as carcinoma. The clinical significance and risk implications of AAA diagnosed on core biopsy are not well established. This study aimed to determine the frequency of carcinoma on follow-up excision in patients with a diagnosis of AA or AAA on core biopsy. Forty-one breast core biopsies of AA (n=29) and AAA (n=12) were identified during a study period of 12 years. Of the 41 core biopsies with AA or AAA, 10 biopsies showed coexisting/concurrent atypical hyperplasia or carcinoma. In the absence of coexisting/concurrent atypical hyperplasia or carcinoma in core biopsy, none of the follow-up excision specimens after a diagnosis of AA or AAA showed ductal carcinoma in situ or invasive carcinoma. In conclusion, AA or AAA by itself is an uncommon core biopsy diagnosis that may not require surgical excision.

  16. Surgical follow-up results for apocrine adenosis and atypical apocrine adenosis diagnosed on breast core biopsy.

    Science.gov (United States)

    Hou, Yanjun; Chaudhary, Shweta; Gao, Faye F; Li, Zaibo

    2016-10-01

    Apocrine adenosis (AA) and atypical apocrine adenosis (AAA) are uncommon findings in breast biopsies that may be misinterpreted as carcinoma. The clinical significance and risk implications of AAA diagnosed on core biopsy are not well established. This study aimed to determine the frequency of carcinoma on follow-up excision in patients with a diagnosis of AA or AAA on core biopsy. Forty-one breast core biopsies of AA (n=29) and AAA (n=12) were identified during a study period of 12 years. Of the 41 core biopsies with AA or AAA, 10 biopsies showed coexisting/concurrent atypical hyperplasia or carcinoma. In the absence of coexisting/concurrent atypical hyperplasia or carcinoma in core biopsy, none of the follow-up excision specimens after a diagnosis of AA or AAA showed ductal carcinoma in situ or invasive carcinoma. In conclusion, AA or AAA by itself is an uncommon core biopsy diagnosis that may not require surgical excision. PMID:27649945

  17. Transpupillary thermotherapy for atypical central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Kawamura R

    2012-01-01

    Full Text Available Ryosuke Kawamura1,2, Hidenao Ideta1, Hideyuki Hori1, Kenya Yuki2, Tsuyoshi Uno1, Tatsurou Tanabe1, Kazuo Tsubota2, Tsutomu Kawasaki11Ideta Eye Hospital, Kumamoto, Japan; 2Keio University, School of Medicine, Department of Ophthalmology, Tokyo, JapanBackground: Central serous chorioretinopathy (CSC has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC.Methods: We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50–250 mW, spot size of 500–1200 µm, and exposure time of 13–60 seconds to minimize retinal damage.Results: In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30. Final BCVA

  18. The effects of race and criminal justice involvement on access to atypical antipsychotic medications among persons with schizophrenia.

    Science.gov (United States)

    Van Dorn, Richard A; Swanson, Jeffrey W; Swartz, Marvin S; Elbogen, Eric B

    2005-06-01

    This study examined the impact of race and arrest history on the likelihood of being prescribed, and maintaining an atypical antipsychotic prescription for 90 or more days among patients with schizophrenia in the community. Participants were 224 adults with schizophrenia-spectrum disorders receiving services in public-sector mental health systems in North Carolina. The data used for this report were from a subsample of a larger group of participants being followed in an observational study and consisted of individuals who were prescribed either an atypical or conventional antipsychotic medication for 90 or more days. The purpose of the analyses presented here was to investigate differences in the likelihood of being prescribed an atypical antipsychotic by demographic and other characteristics. Logistic regression analysis indicated that African American patients were significantly less likely to receive atypical antipsychotics than their white counterparts, even when controlling for key clinical and demographic variables. However, white patients with a history of arrest were no more likely than black patients to receive atypical antipsychotics; that is, minority racial status and criminal involvement each functioned to limit patients' access to the novel medications. Implications for equal access to mental health services, in this case, effective psychopharmacologic treatment, are discussed.

  19. A misdiagnosed myasthenia gravis with anti-muscle-specific tyrosine kinase antibodies with possible childhood onset

    Directory of Open Access Journals (Sweden)

    Nikolić Ana V.

    2015-01-01

    Full Text Available Introduction. Childhood onset myasthenia gravis associated with anti-muscle-specific tyrosine kinase antibodies is very rare and atypical in presentation. Case report. As a baby, the pre-sented patient was choking and sleeping with open eyes. She had weak cry and breathing difficulties. In childhood, there were frequent falls and fluctuating swallowing difficulties. At the age of 19 she was misdiagnosed with Miller Fisher syndrome due to the presence of diplopia, ataxia and hyporeflexia with spontaneous recovery. Repetitive nerve stimulation test was normal. Four years later, after several relapses, there was significant decrement on facial muscles. Neostigmine test was negative, provoking muscle fasciculations. Serum anti-muscle-specific tyrosine kinase antibodies were positive. With cyclosporine therapy she achieved the minimal manifestations status. Conclusion. The presented case confirms that childhood onset myasthenia gravis associated with anti-muscle-specific tyrosine kinase antibodies is often with atypical presentation and spontaneous remissions, so it could be easily misdiagnosed.

  20. CK (Creatine Kinase) Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Creatine Kinase Share this page: Was this page helpful? Also known as: CK; Total CK; Creatine Phosphokinase; CPK Formal name: Creatine Kinase Related tests: ...

  1. Characterization of the atypical lymphocytes in African swine fever

    Science.gov (United States)

    Karalyan, Z. A.; Ter-Pogossyan, Z. R.; Abroyan, L. O.; Hakobyan, L. H.; Avetisyan, A. S.; Yu, Karalyan N.; Karalova, E. M.

    2016-01-01

    Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV) infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection. PMID:27536044

  2. Atypical meningioma and extensive calvarium defects in neurofibromatosis type 1

    Energy Technology Data Exchange (ETDEWEB)

    Simsek, Enver [Department of Paediatrics, Duzce Medical Faculty, Abant Izzet Baysal University, Konuralp-Duzce (Turkey); Yavuz, Cevdet [Department of Neurosurgery, Duzce Medical Faculty, Abant Izzet Baysal University, Konuralp-Duzce (Turkey); Ustundag, Nil [Department of Pathology, Abant Izzet Baysal University School of Medicine, Konuralp-Duzce (Turkey)

    2003-08-01

    A 9-year-old girl with neurofibromatosis type 1 (NF1) presented with a massive atypical meningioma and calvarial defect. Skull radiographs and cranial CT showed an extensive lytic bone lesion at the vertex. MRI demonstrated a large mass invading the calvarium and sagittal sinus. The histopathological and immunohistochemical diagnosis of the resected mass was atypical meningioma. To our knowledge, this is the first case of NF1 associated with atypical meningioma and massive calvarial defect in a child. (orig.)

  3. Hematological Side Effects of Atypical Antipsychotic Drugs

    Directory of Open Access Journals (Sweden)

    Serap Erdogan

    2009-10-01

    Full Text Available Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or

  4. Atypical giant chondroblastoma mimicking a chondrosarcoma.

    Science.gov (United States)

    Dhanda, Sunita; Menon, Santosh; Gulia, Ashish

    2015-01-01

    Chondroblastoma is a rare, benign tumor derived from chondroblasts, commonly presenting in the second decade of life. It is usually found in the epiphysis or apophysis of long bones; however, it may rarely affect flat bones like scapula. Occasionally a histologically typical chondroblastoma may exhibit an aggressive behavior that is not normally associated with benign tumors such as a large size, pulmonary metastases, joint and soft-tissue infiltration and local recurrence. We present a case report of a patient with chondroblastoma showing atypical radiological presentation and non-concordance with age. PMID:26458670

  5. Trisomy 18 with unilateral atypical ectrodactyly

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, R.C. [Greenwood Genetic Center, SC (United States)

    1994-01-01

    Becerra et al. recently reported on an infant with multiple congenital anomalies who had trisomy 18. This preterm infant presented with bilateral ectrodactyly of feet, small cleft palate, esophageal atresia with associated tracheoesophageal fistula, congenital heart disease and other anomalies. The authors referenced article by Castle and Bernstein, in which they reported a male with trisomy 18 and cleft foot as well as a review of the literature which showed 2 other infants with trisomy 18 and ectrodactyly of the feet. An additional case of trisomy 18 associated with multiple congenital anomalies, including unilaterial, atypical ectrodactyly of the left foot.

  6. Atypical And Severe Enlargement Of Right Atrium.

    Science.gov (United States)

    Siniscalchi, Carmine; Rossetti, Pietro; Rocci, Anna; Rubino, Pasquale; Basaglia, Manuela; Gaibazzi, Nicola; Quintavalla, Roberto

    2016-01-01

    A 76 year-old woman was admitted to the Emergency Department for recent-onset dyspnea and cough. The electrocardiogram was considered inconclusive. A thoracic X-ray showed global cardiac profile enlargement. Computed tomography, acutely performed in the clinical suspicion of atypical pneumonia/myocarditis or pericardial effusion, showed cardiac enlargement especially of the right chambers. In order to investigate Ebstein's anomaly, pericardial cysts, tumors or other conditions of the right heart a simple trans-thoracic echocardiogram was performed. Four chambers view showed a giant right atrium aneurysm with moderate tricuspid regurgitation without stenosis or typical Ebstein's echocardiographic pattern. PMID:27649002

  7. Atypical Teratoid/Rrhabdoid Tumour of Brain

    Directory of Open Access Journals (Sweden)

    Meena Sidhu,P.Sakhuja,V.Malhotra,R.Gondal S.Kumar

    2003-04-01

    Full Text Available Primitive neuroectodermal tumor (PNET / medulloblastoma (MB are the most commonmalignantcentral nervous tumors of the first decade of life. Atypical teratoid / rhabdoid tumor (ATT / RT isa tumor of infancy and childhood although occasional cases have also been described in adults.ATT/RT has a characteristic histopathological, immunocytochemical and ultrastructural features.ATT /RT is a rare tumor, incidence of which remains to be defined with only hundred publishedcases. The present report docurilents the clinical features, histological and immunohistochemicalfindings of a case ofATT / RT.

  8. Atypical giant chondroblastoma mimicking a chondrosarcoma.

    Science.gov (United States)

    Dhanda, Sunita; Menon, Santosh; Gulia, Ashish

    2015-01-01

    Chondroblastoma is a rare, benign tumor derived from chondroblasts, commonly presenting in the second decade of life. It is usually found in the epiphysis or apophysis of long bones; however, it may rarely affect flat bones like scapula. Occasionally a histologically typical chondroblastoma may exhibit an aggressive behavior that is not normally associated with benign tumors such as a large size, pulmonary metastases, joint and soft-tissue infiltration and local recurrence. We present a case report of a patient with chondroblastoma showing atypical radiological presentation and non-concordance with age.

  9. Atypical Trigeminal Neuralgia Secondary to Meningioma

    OpenAIRE

    Premeshwar Niwant; Mukta Motwani; Sushil Naik

    2015-01-01

    Trigeminal neuralgia is a disorder of the fifth cranial nerve that causes episodes of intense, stabbing, electric shock-like pain that lasts from few seconds to few minutes in the areas of the face where the branches of the nerve are distributed. More than one nerve branch can be affected by the disorder. We report an unusual case of trigeminal neuralgia affecting right side of face presenting atypical features of neuralgia and not responding to the usual course of treatment. The magnetic res...

  10. Atypical presentation of childhood obsessive compulsive disorder

    Directory of Open Access Journals (Sweden)

    Satyakam Mohapatra

    2016-01-01

    Full Text Available Obsessive-compulsive disorder (OCD is one of the most prevalent psychiatric disorders in children and adolescents. The phenomenology of OCD in children and adolescent is strikingly similar to that of adults. But at times, the presentation of OCD may be so atypical or unusual in children and adolescents that may lead to misdiagnosis or delay in diagnosis. We report a case of 10-year-old child who was initially misdiagnosed with schizophrenia, and treated with antipsychotic for 2 months. But once the core symptoms were recognized as obsessions and compulsions and appropriately treated in the line of OCD, the symptoms resolved significantly.

  11. Pontine Infarct Presenting with Atypical Dental Pain: A Case Report.

    Science.gov (United States)

    Goel, Rajat; Kumar, Sanjeev; Panwar, Ajay; Singh, Abhishek B

    2015-01-01

    Orofacial pain' most commonly occurs due to dental causes like caries, gingivitis or periodontitis. Other common causes of 'orofacial pain' are sinusitis, temporomandibular joint(TMJ) dysfunction, otitis externa, tension headache and migraine. In some patients, the etiology of 'orofacial pain' remains undetected despite optimal evaluation. A few patients in the practice of clinical dentistry presents with dental pain without any identifiable dental etiology. Such patients are classified under the category of 'atypical odontalgia'. 'Atypical odontalgia' is reported to be prevalent in 2.1% of the individuals. 'Atypical orofacial pain' and 'atypical odontalgia' can result from the neurological diseases like multiple sclerosis, trigeminal neuralgia and herpes infection. Trigeminal neuralgia has been frequently documented as a cause of 'atypical orofacial pain' and 'atypical odontalgia'. There are a few isolated case reports of acute pontine stroke resulting in 'atypical orofacial pain' and 'atypical odontalgia'. However, pontine stroke as a cause of atypical odontalgia is limited to only a few cases, hence prevalence is not established. This case is one, where a patient presented with acute onset atypical dental pain with no identifiable dental etiology, further diagnosed as an acute pontine infarct on neuroimaging. A 40 years old male presented with acute onset, diffuse teeth pain on right side. Dental examination was normal. Magnetic resonance imaging(MRI) of the brain had an acute infarct in right pons near the trigeminal root entry zone(REZ). Pontine infarct presenting with dental pain as a manifestation of trigeminal neuropathy, has rarely been reported previously. This stresses on the importance of neuroradiology in evaluation of atypical cases of dental pain. PMID:26464604

  12. Atypical Celiac Disease: From Recognizing to Managing

    Directory of Open Access Journals (Sweden)

    B. Admou

    2012-01-01

    Full Text Available The nonclassic clinical presentation of celiac disease (CD becomes increasingly common in physician’s daily practice, which requires an awareness of its many clinical faces with atypical, silent, and latent forms. Besides the common genetic background (HLA DQ2/DQ8 of the disease, other non-HLA genes are now notably reported with a probable association to atypical forms. The availability of high-sensitive and specific serologic tests such as antitissue transglutuminase, antiendomysium, and more recent antideamidated, gliadin peptide antibodies permits to efficiently uncover a large portion of the submerged CD iceberg, including individuals having conditions associated with a high risk of developing CD (type 1 diabetes, autoimmune diseases, Down syndrome, family history of CD, etc., biologic abnormalities (iron deficiency anemia, abnormal transaminase levels, etc., and extraintestinal symptoms (short stature, neuropsychiatric disorders, alopecia, dental enamel hypoplasia, recurrent aphtous stomatitis, etc.. Despite the therapeutic alternatives currently in developing, the strict adherence to a GFD remains the only effective and safe therapy for CD.

  13. Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay.

    Science.gov (United States)

    Floris, Dorothea L; Lai, Meng-Chuan; Auer, Tibor; Lombardo, Michael V; Ecker, Christine; Chakrabarti, Bhismadev; Wheelwright, Sally J; Bullmore, Edward T; Murphy, Declan G M; Baron-Cohen, Simon; Suckling, John

    2016-01-01

    In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC.

  14. [sup 123]I-IMP SPECT studies in schizophrenia and atypical psychosis

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Takuji; Suga, Hidemichi (Aichi Medical University, Nagakute (Japan))

    1993-05-01

    According to the classification of Mitsuda, 23 patients with endogenous psychosis aged 40 years or younger, presenting with hallucination and delusion, were classified as having schizophrenia (n=12) or atypical psychosis (n=11). These patients were studied by single photon emission computed tomography (SPECT) with N-isopropyl-p-I-123-iodoamphetamine (I-123 IMP). Sixteen healthy persons served as controls. Early and delayed SPECT images were obtained 30 min and 4 hr, respectively, after intravenous injection of I-123 IMP. The group of schizophrenic patients had markedly decreased uptake of I-123 in the basal ganglia, as well as the right temporal and left occipital areas on both early and delayed images. In the group of atypical psychosis patients, however, decreased uptake of I-123 was noted in both the right basal ganglia and left occipital area on early images, but none of such findings were seen on delayed images. Regarding the uptake ratio in the frontal area on both early and delayed images, there were significant differences between the two groups. These findings have important implications for the different etiology of both disease types: not only functional disturbance in the frontal area but also irreversible changes may be involved in the occurrence of schizophrenia, and functional disturbance particularly in the right basal ganglia may be involved in the occurrence of atypical psychosis. (N.K.).

  15. Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay.

    Science.gov (United States)

    Floris, Dorothea L; Lai, Meng-Chuan; Auer, Tibor; Lombardo, Michael V; Ecker, Christine; Chakrabarti, Bhismadev; Wheelwright, Sally J; Bullmore, Edward T; Murphy, Declan G M; Baron-Cohen, Simon; Suckling, John

    2016-01-01

    In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC. PMID:26493275

  16. Keloidal Atypical Fibroxanthoma: Case and Review of the Literature

    Science.gov (United States)

    Tongdee, Emily; Touloei, Khasha; Shitabata, Paul K.; Shareef, Shahjahan; Maranda, Eric L.

    2016-01-01

    Keloidal atypical fibroxanthoma (KAF) has recently been categorized as a variant of atypical fibroxanthoma. This paper will emphasize the importance of including KAF in both clinical and histological differential diagnosis of benign and malignant lesions which exhibit keloidal collagen and will also review the current literature on epidemiology, pathogenesis, histology, immunochemistry and treatments. PMID:27462224

  17. Atypical MRI features in soft-tissue arteriovenous malformation: a novel imaging appearance with radiologic-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Anand S. [University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); University of California, San Francisco, Department of Interventional Radiology, San Francisco, CA (United States); Schulman, Joshua M.; Ruben, Beth S. [University of California, San Francisco, Departments of Pathology and Dermatology, San Francisco, CA (United States); Hoffman, William Y. [University of California, San Francisco, Department of Plastic Surgery, Birthmarks and Vascular Anomalies Clinic, San Francisco, CA (United States); Dowd, Christopher F. [University of California, San Francisco, Department of Interventional Neuroradiology, Birthmarks and Vascular Anomalies Clinic, San Francisco, CA (United States); Frieden, Ilona J. [University of California, San Francisco, Department of Dermatology, Birthmarks and Vascular Anomalies Clinic, San Francisco, CA (United States); Hess, Christopher P. [University of California, San Francisco, Department of Neuroradiology, Birthmarks and Vascular Anomalies Clinic, San Francisco, CA (United States)

    2015-09-15

    The absence of a discrete mass, surrounding signal abnormality and solid enhancement are imaging features that have traditionally been used to differentiate soft-tissue arteriovenous malformations from vascular tumors on MRI. We have observed that these findings are not uncommon in arteriovenous malformations, which may lead to misdiagnosis or inappropriate treatment. To estimate the frequency of atypical MRI features in soft-tissue arteriovenous malformations and assess their relationship to lesion size, location, tissue type involved and vascular architecture. Medical records, MRI and histopathology were reviewed in consecutive patients with soft-tissue arteriovenous malformations in a multidisciplinary vascular anomalies clinic. Arteriovenous malformations were divided into those with and without atypical MRI findings (perilesional T2 signal abnormality, enhancement and/or a soft-tissue mass). Lesion location, size, tissue involved and vascular architecture were also compared between groups. Tissue stains were reviewed in available biopsy or resection specimens to assess relationships between MRI findings and histopathology. Thirty patients with treatment-naive arteriovenous malformations were included. Fifteen lesions demonstrated atypical MRI. There was no difference in age, gender, lesion size or involved body part between the groups. However, more than half of the atypical lesions demonstrated multicompartmental involvement, and tiny intralesional flow voids were more common in atypical arteriovenous malformations. Histopathology also differed in atypical cases, showing densely packed endothelial cells with connective tissue architectural distortion and edema. Arteriovenous malformations may exhibit features of a vascular tumor on MRI, particularly when multicompartmental and/or containing tiny internal vessels. These features are important to consider in suspected fast-flow vascular malformations and may have implications with respect to their treatment

  18. [Atypical cerebellar neurocytoma resembling a hemangioblastoma. A case report].

    Science.gov (United States)

    Lista Martínez, Olalla; Rivas López, Luis Alfredo; Pombo Otero, Jorge Francisco; Amaro Cendón, Santiago; Bravo García, Christian; Villa Fernández, Juan Manuel

    2014-01-01

    Through August 2013, 105 cases of intracranial extraventricular neurocytoma (EVN) had been described; 6% were located in cerebellum and 22% were atypical EVN. A rare morphologic form of neurocytoma, atypical EVN has had only 24 cases reported to date. Its prognosis is poorer than the typical central neurocytoma. This case report describes an atypical cerebellar EVN, a form that has not been reported yet, hence the interest of this article. We emphasise its cystic nature and mural nodule, in an infrequent presentation. EVN are low-incidence tumours that we need to take into consideration when making the differential diagnosis of cystic cerebellar lesions with mural nodule. Given that the prognosis of atypical EVNs depends on the atypical nature and on the grade of resection, medical follow up has to be more constant, due to the greater degree of recurrence. PMID:24837842

  19. Thymidine kinases in archaea

    DEFF Research Database (Denmark)

    Clausen, A.R.; Matakos, A.; Sandrini, Michael;

    2006-01-01

    Twenty-six fully sequenced archaeal genomes were searched for genes coding for putative deoxyribonucleoside kinases (dNKs). We identified only 5 human-like thymidine kinase 1 genes (TK1s) and none for non-TK1 kinases. Four TK1s were identified in the Euryarchaea and one was found in the Crenarchaea...... that a functional deoxyribonucleoside salvage pathway is not crucial for the archaeal cell....

  20. Imaging the neurobiological substrate of atypical depression by SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Salmaso, Dario [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Nardo, Davide [University of Rome La Sapienza, Department of Psychology, Rome (Italy); Jonsson, Cathrine; Larsson, Stig A. [Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Jacobsson, Hans [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Gardner, Ann [Karolinska University Hospital Huddinge, Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, Stockholm (Sweden)

    2007-01-15

    Neurobiological abnormalities underlying atypical depression have previously been suggested. The purpose of this study was to explore differences at functional brain imaging between depressed patients with and without atypical features and healthy controls. Twenty-three out-patients with chronic depressive disorder recruited from a service for patients with audiological symptoms were investigated. Eleven fulfilled the DSM-IV criteria for atypical depression (mood reactivity and at least two of the following: weight gain, hypersomnia, leaden paralysis and interpersonal rejection sensitivity). Twenty-three healthy subjects served as controls. Voxel-based analysis was applied to explore differences in {sup 99m}Tc-HMPAO uptake between groups. Patients in the atypical group had a higher prevalence of bilateral hearing impairment and higher depression and somatic distress ratings at the time of SPECT. Significantly higher tracer uptake was found bilaterally in the atypical group as compared with the non-atypicals in the sensorimotor (Brodmann areas, BA1-3) and premotor cortex in the superior frontal gyri (BA6), in the middle frontal cortex (BA8), in the parietal associative cortex (BA5, BA7) and in the inferior parietal lobule (BA40). Significantly lower tracer distribution was found in the right hemisphere in the non-atypicals compared with the controls in BA6, BA8, BA44, BA45 and BA46 in the frontal cortex, in the orbito-frontal cortex (BA11, BA47), in the postcentral parietal cortex (BA2) and in the multimodal association parietal cortex (BA40). The differences found between atypical and non-atypical depressed patients suggest different neurobiological substrates in these patient groups. The putative links with the clinical features of atypical depression are discussed. These findings encourage the use of functional neuroimaging in psychiatric disorders. (orig.)

  1. [Treatment of atypical and neurotic depression].

    Science.gov (United States)

    Leitner, P; Umann, E; Kulawik, H

    1986-10-01

    Hitherto it has not been usual to talk in the German language about the therapy-oriented concept of two forms of the progress of atypical depression (Type A and Type V). The characteristic symptom of Type A is angst, together with phobias, physical complaints, etc. In Type V there are vegetative symptoms, often towards evening (Hypersomnia, difficulty in getting to sleep, increased appetite, increased weight, increased libido), accompanied by hysterical extrovert personality traits, and of intermittent occurrence. These clinical pictures are amenable to psychopharmalogical therapy. In conformity with the assumption of "somatic accommodation" treatment with antidepressives is recommended in the case neurotic depression, too, at least in the initial stages of treatment. PMID:3809300

  2. [Atypical early posttraumatic syndromes (author's transl)].

    Science.gov (United States)

    Muller, G E

    1974-01-01

    In a consecutive series of 1,925 head injuries, 283 patients (14.7%), could not be classified, neither in the group of simple head injuries without cerebral symptoms, nor in the group of typical concussions characterized by immediate amnesia or observed coma. We have prefered the rather neutral term of atypical early posttraumatic syndromes. In this group, apart from neurovegetative manifestations, partial disturbances of consciousness and perception, we have also classified delayed disturbances of consciousness. Special attention has been given to migraineous phenomena and to a syndrome, characteristic for children, described by Mealey. This is an intermediate group important from a medico-legal point of view because certain transient cerebral manifestations risk to be mistaken for psychological reactions. On the other hand symptoms probably of psychic origin were discussed. PMID:4469864

  3. Atypical Radiological Manifestation of Pulmonary Metastatic Calcification

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Hae; Kim, Eun Sun; Kim, Chul Hwan; Ham, Soo Youn; Oh, Yu Whan [Korea University College of Medicine, Seoul (Korea, Republic of)

    2008-04-15

    Metastatic pulmonary calcification is a condition of calcium deposition in the normal pulmonary parenchyma, and this is secondary to abnormal calcium metabolism without any prior soft tissue damage. The predisposing factors for this condition include chronic renal failure, hypercalcemia and increased tissue alkalinity. The most common radiologic manifestation consists of poorly defined nodular opacities in the upper lung zone. These opacities reflect the deposition of calcium salts in the pulmonary interstitium. We present here a case of metastatic pulmonary calcification in a patient who recovered from pneumonia with sepsis and whose high-resolution CT (HRCT) images demonstrated localized parenchymal airspace calcification that was limited to the bilateral lower lobes. These lower lobes had been involved with pneumonic consolidation without calcification, as seen on the previous CT scan. In summary, we report here on an atypical presentation of metastatic pulmonary calcification that showed dense airspace consolidation localized to the bilateral lower lobes in a patient with primary hyperparathyroidism and pneumonia.

  4. Atypical subtrochanteric and diaphyseal femoral fractures

    DEFF Research Database (Denmark)

    Shane, Elizabeth; Burr, David; Abrahamsen, Bo;

    2014-01-01

    Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exp....... Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs. © 2014 American Society for Bone and Mineral Research....... associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may...

  5. Case Report: Atypical Cornelia de Lange Syndrome.

    Science.gov (United States)

    Leanza, Vito; Rubbino, Gabriella; Leanza, Gianluca

    2014-01-01

    Cornelia de Lange Syndrome (CdLS) (also called Bushy Syndrome or Amsterdam dwarfism), is a genetic disorder that can lead to several alterations. This disease affects both physical and neuropsychiatric development. The various abnormalities include facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal alterations. The prevalence of this syndrome is approximately one per 15,000. Ultrasound is not the perfect means to diagnose CdLS, however, many abnormalities can be detected prenatally by scrupulous image observation. We report an atypical CdLS case characterized by increased nuchal translucency in the first trimester, normal karyotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation ending with the interruption of pregnancy. PMID:26834972

  6. A case of atypical progressive supranuclear palsy

    Directory of Open Access Journals (Sweden)

    Spaccavento S

    2013-12-01

    Full Text Available Simona Spaccavento, Marina Del Prete, Angela Craca, Anna Loverre IRCCS Salvatore Maugeri Foundation, Cassano Murge, Bari, Italy Background: Progressive supranuclear palsy (PSP is a neurodegenerative extrapyramidal syndrome. Studies have demonstrated that PSP can present clinically as an atypical dementing syndrome dominated by a progressive apraxia of speech (AOS and aphasia. Aim: We aimed to investigate the clinical presentation of PSP, using a comprehensive multidimensional evaluation, and the disease response to various pharmacological treatments. Methods: A 72-year-old right-handed male, with 17 years education, who first presented with aphasia, AOS, depression, apathy, and postural instability at 69 years; a complete neuropsychological evaluation, tapping the different cognitive domains, was performed. Results: Testing revealed a moderate global cognitive deficit (Mini-Mental State Examination test score =20, low memory test scores (story recall, Rey’s 15-word Immediate and Delayed Recall, and poor phonemic and semantic fluency. The patient’s language was characterized by AOS, with slow speech rate, prolonged intervals between syllables and words, decreased articulatory accuracy, sound distortions, and anomia. Behavioral changes, such as depression, anxiety, apathy, and irritability, were reported. The neurological examination revealed supranuclear vertical gaze palsy, poor face miming, and a mild balance deficit. Magnetic resonance imaging showed only widespread cortical atrophy. Single photon emission computed tomography demonstrated left > right frontotemporal cortical abnormalities. After 6 months, a further neuropsychological assessment showed a progression in cognitive deficits, with additional attention deficits. The patient reported frequent falls, but the neurological deficits remained unchanged. Neuroimaging tests showed the same brain involvement. Conclusion: Our case highlights the heterogeneity of the clinical features in

  7. Protein Kinases and Parkinson’s Disease

    Science.gov (United States)

    Mehdi, Syed Jafar; Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M.; Barger, Steven W.; Sarkar, Sumit; Paule, Merle G.; Ali, Syed F.; Imam, Syed Z.

    2016-01-01

    Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson’s disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules. PMID:27657053

  8. A-type granitoids from the Eastern Pontides, NE Turkey: Records for generation of hybrid A-type rocks in a subduction-related environment

    Science.gov (United States)

    Karsli, Orhan; Caran, Şemsettin; Dokuz, Abdurrahman; Çoban, Hakan; Chen, Bin; Kandemir, Raif

    2012-03-01

    The Eastern Pontides is characterized by the many of intrusive bodies formed throughout the late Mesozoic-early Cenozoic. Most of these are I-type granitoids, but here, we present for the first time an A-type pluton from the region to assess source characteristics and geodynamic implications. The A-type Pirnalli pluton has a SHRIMP zircon U-Pb age of 81.2 ± 1 Ma. It is composed of granite, syenite and quartz monzonite, and its enclaves are monzonitic in composition with elevated Ga/Al ratios and low Mg# (enclaves posses quite similar Sr-Nd isotopic compositions (ISr = 0.70693 to 0.70736, εNd (81 Ma) = - 2.6 to - 2.0, TDM = 0.94 to 1.12 Ga), pointing to a lower crustal parental magma with a minor contribution of lithospheric mantle. We hypothesize that upwelling of asthenosphere triggered melting of chemically enriched upper mantle and basic magma formed. Melting of lower crust was provided by the underplating of this basic magma. Mixing between lower crust- and mantle-derived melts at depths of lower crust appears to be most reasonable petrogenetic process responsible for generation of the pluton. Sr-Nd isotope modeling suggests mixing of 82-90% of the lower crustal-derived melt with ~ 10-18% of the mantle-derived melt. Then the hybrid melt ascended to shallower crustal level and underwent a limited fractionation process to generate a variety of rock types. Our data also suggest that the A-type Pirnalli pluton likely formed at an extensional environment of active continental margin throughout the late Cretaceous. Ongoing extension then led to opening of Black Sea as a back-arc basin further north of the Eastern Pontides.

  9. Atypical antipsychotics in first admission schizophrenia: medication continuation and outcomes.

    Science.gov (United States)

    Mojtabai, Ramin; Lavelle, Janet; Gibson, P Joseph; Bromet, Evelyn J

    2003-01-01

    This study compares the effects of atypical and conventional antipsychotic medications on treatment continuation and outcomes in a first admission sample of patients with schizophrenia treated in usual practice settings. In a sample of 189 participants with a research diagnosis of DSM-IV schizophrenia drawn from the Suffolk County Mental Health Project, we compared the effects of atypical and conventional agents on change of medication, medication gaps, and rehospitalization. For these analyses we used the method of survival analysis for recurrent events, in which the episodes of treatment rather than individual subjects are the units of analysis. In addition, we compared improvement in positive and negative symptoms from intake to 24- or 48-month followups for subjects who stayed on one type of medication or changed to atypicals from conventional antipsychotics. Atypical agents were associated with lower risk of medication change, medication gaps, and rehospitalization. Both conventional and atypical agents were associated with improvement of positive symptoms at followup, but only subjects on atypical agents at followup experienced a significant improvement in negative symptoms. We conclude that in usual practice settings, as in randomized clinical trials, atypical agents are associated with improved treatment continuation and outcomes.

  10. Malignant atypical cell in urine cytology: a diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Kakkar Nandita

    2006-01-01

    Full Text Available Abstract Aims The aim of this study was to find out the characteristic morphology of malignant atypical cells which were missed on routine cytology of urine. Materials and methods In this retrospective study, we examined detailed cytomorphology of 18 cases of atypical urinary cytology which were missed on routine examination and were further proved on histopathology as transitional cell carcinoma (TCC of bladder. The cytological features of these cases were compared with 10 cases of benign urine samples. Results There were 11 cases of high grade TCC and 7 cases of low grade TCC on histopathology of the atypical urine samples. Necrosis in the background and necrosed papillae were mostly seen in malignant atypical cells. The comet cells and cells with India ink nuclei (single cells with deep black structure-less nuclei were only observed in malignant atypical cells. The most consistent features in malignant atypical cells were: i high nuclear and cytoplasmic (N/C ratio ii nuclear pleomorphism iii nuclear margin irregularity iv hyperchromasia and v chromatin abnormalities Conclusion The present study emphasizes that nuclear features such as high N/C ratio, hyperchromasia and chromatin abnormalities are particularly useful for assessing the malignant atypical cells. Other cytological features such as comet cells and cells with India ink nuclei are also helpful for diagnosis but have limited value because they are less frequently seen.

  11. Atypical chemokine receptors in cancer: friends or foes?

    Science.gov (United States)

    Massara, Matteo; Bonavita, Ornella; Mantovani, Alberto; Locati, Massimo; Bonecchi, Raffaella

    2016-06-01

    The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CC-chemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXC-chemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies. PMID:26908826

  12. Functional screen identifies kinases driving prostate cancer visceral and bone metastasis.

    Science.gov (United States)

    Faltermeier, Claire M; Drake, Justin M; Clark, Peter M; Smith, Bryan A; Zong, Yang; Volpe, Carmen; Mathis, Colleen; Morrissey, Colm; Castor, Brandon; Huang, Jiaoti; Witte, Owen N

    2016-01-12

    Mutationally activated kinases play an important role in the progression and metastasis of many cancers. Despite numerous oncogenic alterations implicated in metastatic prostate cancer, mutations of kinases are rare. Several lines of evidence suggest that nonmutated kinases and their pathways are involved in prostate cancer progression, but few kinases have been mechanistically linked to metastasis. Using a mass spectrometry-based phosphoproteomics dataset in concert with gene expression analysis, we selected over 100 kinases potentially implicated in human metastatic prostate cancer for functional evaluation. A primary in vivo screen based on overexpression of candidate kinases in murine prostate cells identified 20 wild-type kinases that promote metastasis. We queried these 20 kinases in a secondary in vivo screen using human prostate cells. Strikingly, all three RAF family members, MERTK, and NTRK2 drove the formation of bone and visceral metastasis confirmed by positron-emission tomography combined with computed tomography imaging and histology. Immunohistochemistry of tissue microarrays indicated that these kinases are highly expressed in human metastatic castration-resistant prostate cancer tissues. Our functional studies reveal the strong capability of select wild-type protein kinases to drive critical steps of the metastatic cascade, and implicate these kinases in possible therapeutic intervention. PMID:26621741

  13. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A;

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  14. Intracranial Tuberculoma Presenting as Atypical Eclampsia: A Case Report

    Science.gov (United States)

    Murugesan, Sharmila; Pradeep, Sunitha; John, Lopamudra; Kolluru, Vasavi

    2016-01-01

    Occurrence of eclampsia before 20 weeks of pregnancy and after 48 hours of delivery in the absence of typical signs of hypertension and or proteinuria is termed as atypical eclampsia. Atypical or non-classic eclampsia will have some symptoms of eclampsia but without the usual proteinuria or hypertension. All patients with atypical onset should undergo neurological evaluation to rule out neurologic causes of seizures. Cerebral tuberculosis is a rare and serious form of disease secondary to haematogenous spread of Mycobacterium tuberculosis. Here we present a case of cerebral tuberculoma with seizures in late pregnancy mimicking eclampsia. PMID:27504359

  15. Protein Kinase D family kinases: roads start to segregate.

    Science.gov (United States)

    Wille, Christoph; Seufferlein, Thomas; Eiseler, Tim

    2014-01-01

    Highly invasive pancreatic tumors are often recognized in late stages due to a lack of clear symptoms and pose major challenges for treatment and disease management. Broad-band Protein Kinase D (PKD) inhibitors have recently been proposed as additional treatment option for this disease. PKDs are implicated in the control of cancer cell motility, angiogenesis, proliferation and metastasis. In particular, PKD2 expression is elevated in pancreatic cancer, whereas PKD1 expression is comparably lower. In our recent study we report that both kinases control PDAC cell invasive properties in an isoform-specific, but opposing manner. PKD1 selectively mediates anti-migratory/anti-invasive features by preferential regulation of the actin-regulatory Cofilin-phosphatase Slingshot1L (SSH1L). PKD2, on the other hand enhances invasion and angiogenesis of PDAC cells in 3D-ECM cultures and chorioallantois tumor models by stimulating expression and secretion of matrix-metalloproteinase 7 and 9 (MMP7/9). MMP9 also enhances PKD2-mediated tumor angiogenesis releasing extracellular matrix-bound VEGF-A. We thus suggest high PKD2 expression and loss of PKD1 may be beneficial for tumor cells to enhance their matrix-invading abilities. In our recent study we demonstrate for the first time PKD1 and 2 isoform-selective effects on pancreatic cancer cell invasion, in-vitro and in-vivo, defining isoform-specific regulation of PKDs as a major future issue. PMID:24847910

  16. [Apropos of atypical melancholia with Sustiva (efavirenz)].

    Science.gov (United States)

    Lang, J P; Halleguen, O; Picard, A; Lang, J M; Danion, J M

    2001-01-01

    The treatment of HIV infection has changed dramatically in recent years as a result of the development of new drugs which allows a variety of multitherapy combinations more adapted to patients' needs and thereby improving compliance. Efavirenz is a non-nucleoside reverse transcriptase inhibitor. In addition to a potent antiretroviral activity, efavirenz is an easy-to-take drug with once-daily dosing and is usually well tolerated. Efavirenz, however, may induce psychic alterations which are variable and atypical in both their clinical presentation and severity. As early as the first days of treatment, efavirenz may provoke surprising phenomena such as nightmares, vivid dreams, hallucinations or illusions, and twilight states. Depersonalization and derealization episodes, personality alterations, stream of thought troubles and unusual thought contents, atypical depression and cognitive disorders have also been observed. These phenomena may occur either early or later on treatment. The prevalence of severe psychic disorders is less than 5%, but they are often responsible for harmful treatment discontinuations. Psychiatric side effects are heterogeneous and probably not related to pre-existing psychologic weakness. We do not have enough data to evaluate these side effects and their etiopathogeny. The drug could act directly on the central nervous system since it crosses the blood-brain barrier, on the serotoninergic and dopaminergic systems. Some authors have compared efavirenz-induced psychic effects to those associated with LSD and found structural similarities between the two molecules. However, the heterogeneity and low prevalence of the psychiatric side effects of efavirenz suggest and individual sensitivity. In order to improve patient care, a better clinical approach, neuropsychological evaluation, and functional brain imagery should be used to progress in the analysis and comprehension of these disorders. We discuss in this paper the case of Mister H. This HIV

  17. Inhibition of protein kinase C intracerebroventricularly attenuates sensitization

    OpenAIRE

    Mrowczynski, Oliver Daniel

    2012-01-01

    Drug relapse, mediated by drug-associated memories, is a major problem associated with addiction. Protein kinase C (PKC) is a family of protein kinase enzymes that has been implicated in learning and memory with regards to addiction. This study used a PKC inhibitor, chelerythrine (10nmol), to investigate the effects of blocking PKC throughout the brain on addiction related memories. Cocaine (15mg/kg) induced locomotor sensitization, used to model the transition from casual to compulsive use, ...

  18. Glycogen synthase kinase 3: more than a namesake

    OpenAIRE

    Rayasam, Geetha Vani; Tulasi, Vamshi Krishna; Sodhi, Reena; Davis, Joseph Alex; Ray, Abhijit

    2009-01-01

    Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by variety of substrates like glycogen synthase, τ protein and β catenin that are phosphorylated leading to their inactivation. GSK3 has been implicated in various diseases such as...

  19. Atypical moral judgment following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Angelica Muresan

    2012-07-01

    Full Text Available Previous research has shown an association between emotions, particularly social emotions, and moral judgments. Some studies suggested an association between blunted emotion and the utilitarian moral judgments observed in patients with prefrontal lesions. In order to investigate how prefrontal brain damage affects moral judgment, we asked a sample of 29 TBI patients (12 females and 17 males and 41 healthy participants (16 females and 25 males to judge 22 hypothetical dilemmas split into three different categories (non-moral, impersonal and personal moral. The TBI group presented a higher proportion of affirmative (utilitarian responses for personal moral dilemmas when compared to controls, suggesting an atypical pattern of utilitarian judgements. We also found a negative association between the performance on recognition of social emotions and the proportion of affirmative responses on personal moral dilemmas. These results suggested that the preference for utilitarian responses in this type of dilemmas is accompanied by difficulties in social emotion recognition. Overall, our findings suggest that deontological moral judgments are associated with normal social emotion processing and that frontal lobe plays an important role in both emotion and moral judgment.

  20. Atypical focal nodular hyperplasia of the liver

    Institute of Scientific and Technical Information of China (English)

    Muhammad Rizwan Khan; Taimur Saleem; Tanveer Ul Haq; Kanwal Aftab

    2011-01-01

    BACKGROUND: Focal nodular hyperplasia, a benign hepatic tumor, is usually asymptomatic. However, rarely the entity can cause symptoms, mandating intervention. METHOD: We present a case of focal nodular hyperplasia of the liver, which caused a considerable diagnostic dilemma due to its atypical presentation. RESULTS: A 29-year-old woman presented with a 15-year history of a progressively increasing mass in the right upper quadrant which was associated with pain and emesis. Examination showed a firm, mobile mass palpable below the right subcostal margin. A computed tomography scan of the abdomen showed an exophytic mass arising from hepatic segments III and IVb. Trucut biopsy of the hepatic mass was equivocal. Angiography showed a vascular tumor that was supplied by a tortuous branch of the proper hepatic artery. Surgical intervention for removal of the mass was undertaken. Intra-operatively, two large discrete tumors were found and completely resected. Histopathological examination showed features consistent with focal nodular hyperplasia. CONCLUSION: This description of an unusual case of focal nodular hyperplasia of the liver highlights the point that the diagnosis of otherwise benign hepatic tumors may be difficult despite extensive work-up in some cases.

  1. Atypical presentation of mucopolysaccharidosis type IVA.

    Science.gov (United States)

    Rush, Eric T

    2016-09-01

    A 14 year old patient with short stature, type I diabetes, and cataracts was referred for evaluation of avascular necrosis of the femoral head. Radiography was suggestive of spondyloepiphyseal dysplasia with decreased bone mineral density for age. Targeted molecular and biochemical testing were normal in this patient. Whole exome sequencing was performed and showed compound heterozygosity for previously reported pathogenic GALNS variants which were diagnostic of mucopolysaccharidosis, type IVA (Morquio A). While this case describes neither a novel condition nor a new mutation, it does illustrate three important points in the diagnosis of patients with atypical forms of MPS IVA. First, that in many instances urine glycosaminoglycan analysis is not sufficient to rule out MPS IVA as a potential diagnosis. Patients in whom biochemical screening is advised should have measurement of leukocyte enzymatic activity. Second, that in patients with radiographic evidence of spondyloepiphyseal dysplasia with additional features or with normal targeted testing, MPS IVA should remain in the differential diagnosis. Third, that whole exome sequencing represents a viable diagnostic platform for evaluation of patients with unknown skeletal or metabolic disease.

  2. Nocturnal manifestations of atypical parkinsonian disorders.

    Science.gov (United States)

    Bhidayasiri, Roongroj; Jitkritsadakul, Onanong; Colosimo, Carlo

    2014-01-01

    Although nocturnal disturbances are increasingly recognized as an integral part of the continuum of daytime manifestations of Parkinson's disease (PD), there is still little evidence in the medical literature to support the occurrence of these complex phenomena in patients with atypical parkinsonian disorders (APDs). Based on the anatomical substrates in APDs, which are considered to be more extensive outside the basal ganglia than in PD, we might expect that patients with APDs encounter the whole range of nocturnal disturbances, including motor, sleep disorders, autonomic dysfunctions, and neuropsychiatric manifestations at a similar, or even greater, frequency than in PD. This article is a review of the current literature on the problems at nighttime of patients with progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. MEDLINE, life science journals and online books were searched by querying appropriate key words. Reports were included if the studies were related to nocturnal manifestations in APDs. Forty articles fulfilled the selection criteria. Differences between these symptoms in APDs and PD are highlighted, given the evidence available about each manifestation. This analysis of nocturnal manifestations of APDs suggests the need for future studies to address these issues to improve the quality of life not only of patients with APDs but the caregivers who encounter the challenges of supporting these patients on a daily basis.

  3. Atypical presentation of mucopolysaccharidosis type IVA.

    Science.gov (United States)

    Rush, Eric T

    2016-09-01

    A 14 year old patient with short stature, type I diabetes, and cataracts was referred for evaluation of avascular necrosis of the femoral head. Radiography was suggestive of spondyloepiphyseal dysplasia with decreased bone mineral density for age. Targeted molecular and biochemical testing were normal in this patient. Whole exome sequencing was performed and showed compound heterozygosity for previously reported pathogenic GALNS variants which were diagnostic of mucopolysaccharidosis, type IVA (Morquio A). While this case describes neither a novel condition nor a new mutation, it does illustrate three important points in the diagnosis of patients with atypical forms of MPS IVA. First, that in many instances urine glycosaminoglycan analysis is not sufficient to rule out MPS IVA as a potential diagnosis. Patients in whom biochemical screening is advised should have measurement of leukocyte enzymatic activity. Second, that in patients with radiographic evidence of spondyloepiphyseal dysplasia with additional features or with normal targeted testing, MPS IVA should remain in the differential diagnosis. Third, that whole exome sequencing represents a viable diagnostic platform for evaluation of patients with unknown skeletal or metabolic disease. PMID:27331011

  4. Orthostatic Hypotension in Patients with Parkinson's Disease and Atypical Parkinsonism

    OpenAIRE

    Seyed-Mohammad Fereshtehnejad; Johan Lökk

    2014-01-01

    Orthostatic hypotension (OH) is one of the commonly occurring nonmotor symptoms in patients with idiopathic Parkinson’s disease (IPD) and atypical parkinsonism (AP). We aimed to review current evidences on epidemiology, diagnosis, treatment, and prognosis of OH in patients with IPD and AP. Major electronic medical databases were assessed including PubMed/MEDLINE and Embase up to February 2013. English-written original or review articles with keywords such as “Parkinson’s disease,” “atypical p...

  5. Atypical fibroxanthoma: An unusual skin neoplasm in xeroderma pigmentosum

    Directory of Open Access Journals (Sweden)

    Ranjana Bandyopadhyay

    2012-01-01

    Full Text Available Xeroderma pigmentosum (XP is a rare autosomal recessive disorder related to defective deoxyribonucleic acid (DNA repair. Various cutaneous manifestations related to ultraviolet (UV damage characterize the clinical course. Primary malignant cutaneous neoplasms like squamous cell carcinoma, basal cell carcinoma and malignant melanoma have been reported. Atypical fibroxanthoma is a rare dermal neoplasm occurring in UV-damaged skin. We report an unusual case of atypical fibroxanthoma in a 20-year-old male with XP.

  6. Atypical Fibroxanthoma: An Unusual Skin Neoplasm in Xeroderma Pigmentosum

    OpenAIRE

    Ranjana Bandyopadhyay; Dipanwita Nag; Sanjay Bandyopadhyay; Swapan Kumar Sinha

    2012-01-01

    Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder related to defective deoxyribonucleic acid (DNA) repair. Various cutaneous manifestations related to ultraviolet (UV) damage characterize the clinical course. Primary malignant cutaneous neoplasms like squamous cell carcinoma, basal cell carcinoma and malignant melanoma have been reported. Atypical fibroxanthoma is a rare dermal neoplasm occurring in UV-damaged skin. We report an unusual case of atypical fibroxanthoma in a 20-y...

  7. Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

    Science.gov (United States)

    Ryan, Aisling M; Bermingham, Niamh; Harrington, Hugh J; Keohane, Catherine

    2006-12-01

    Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

  8. Atypical meningococcal meningitis with rashless presentation:A case report

    Institute of Scientific and Technical Information of China (English)

    Sunita; Singh Manpreet; Kapoor Dheeraj

    2012-01-01

    Meningococcal disease is the major health problem in developing world. The clinical presentation is varied, ranging from transient fever and bacteraemia to fulminant disease with death ensuing within hours of the onset of clinical symptoms. The classical clinical manifestations of meningococcal disease have been well described, but atypical presentations if unrecognized, may lead to a delay in treatment and fatal outcome. We here report a case presented with atypical presentation of meningococcal meningitis without classical rash, which was diagnosed and managed successfully.

  9. Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

    LENUS (Irish Health Repository)

    Ryan, Aisling M

    2012-02-03

    Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

  10. An Atypical Case of Pityriasis Rosea Gigantea after Influenza Vaccination

    Directory of Open Access Journals (Sweden)

    Dimitrios Papakostas

    2014-04-01

    Full Text Available Pityriasis rosea is a common erythematosquamous eruption, typically presenting along the cleavage lines of the skin. A wide spectrum of atypical manifestations may challenge even the most experienced physician. Here we report a rare case of a suberythrodermic pityriasis rosea with gigantic plaques after an influenza vaccination, and we discuss the possible triggers of atypical manifestations of such a common dermatological disease in the setting of an altered immunity.

  11. Structural Bioinformatics and Protein Docking Analysis of the Molecular Chaperone-Kinase Interactions: Towards Allosteric Inhibition of Protein Kinases by Targeting the Hsp90-Cdc37 Chaperone Machinery

    Directory of Open Access Journals (Sweden)

    Gennady Verkhivker

    2013-11-01

    Full Text Available A fundamental role of the Hsp90-Cdc37 chaperone system in mediating maturation of protein kinase clients and supporting kinase functional activity is essential for the integrity and viability of signaling pathways involved in cell cycle control and organism development. Despite significant advances in understanding structure and function of molecular chaperones, the molecular mechanisms and guiding principles of kinase recruitment to the chaperone system are lacking quantitative characterization. Structural and thermodynamic characterization of Hsp90-Cdc37 binding with protein kinase clients by modern experimental techniques is highly challenging, owing to a transient nature of chaperone-mediated interactions. In this work, we used experimentally-guided protein docking to probe the allosteric nature of the Hsp90-Cdc37 binding with the cyclin-dependent kinase 4 (Cdk4 kinase clients. The results of docking simulations suggest that the kinase recognition and recruitment to the chaperone system may be primarily determined by Cdc37 targeting of the N-terminal kinase lobe. The interactions of Hsp90 with the C-terminal kinase lobe may provide additional “molecular brakes” that can lock (or unlock kinase from the system during client loading (release stages. The results of this study support a central role of the Cdc37 chaperone in recognition and recruitment of the kinase clients. Structural analysis may have useful implications in developing strategies for allosteric inhibition of protein kinases by targeting the Hsp90-Cdc37 chaperone machinery.

  12. A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome.

    Science.gov (United States)

    Christianto, Antonius; Katayama, Syouichi; Kameshita, Isamu; Inazu, Tetsuya

    2016-08-01

    Rett syndrome (RTT) is a severe X-linked dominant inheritance disorder with a wide spectrum of clinical manifestations. Mutations in Methyl CpG binding protein 2 (MECP2), Cyclin dependent kinase-like 5 (CDKL5) and Forkhead box G1 (FOXG1) have been associated with classic and/or variant RTT. This study was conducted to identify the responsible gene(s) in atypical RTT patient, and to examine the effect of the mutation on protein function. DNA sequence analysis showed a novel heterozygous mutation in CDKL5 identified as c.530A>G which resulted in an amino acid substitution at position 177, from tyrosine to cysteine. Genotyping analysis indicated that the mutation was not merely a single nucleotide polymorphism (SNP). We also revealed that patient's blood lymphocytes had random X-chromosome inactivation (XCI) pattern. Further examination by bioinformatics analysis demonstrated the mutation caused damage or deleterious in its protein. In addition, we demonstrated in vitro kinase assay of mutant protein showed impairment of its activity. Taken together, the results suggested the mutant CDKL5 was responsible for the disease. PMID:27265524

  13. Atypical femoral fractures and current management

    Directory of Open Access Journals (Sweden)

    Nianye Zheng

    2016-10-01

    Full Text Available With the rapid increase in patients receiving bisphosphonates (BPs for treating osteoporosis, one of the clinical complications associated with its long-term use is atypical femoral fractures (AFFs. Although the absolute risk for AFFs is low and it was a consensus that AFFs were acceptable compared with the amount of osteoporotic fractures BPs have prevented, epidemiological studies have proved that BPs had a strong association with AFFs and possibly more people were going to suffer from this adverse effect with wide prescriptions of this drug. In addition, AFFs seemed to have impaired ability to heal. Thus, to understand the mechanism(s behind AFFs is important and desirable for considering preventive measures. This article reviewed the clinical features of AFFs as well as potential underlining pathological characteristics, such as the decreased turnover rate caused by BPs that led to multiple-level alternations, e.g., changes not only at cellular and tissue levels, but also related to changes in bone micro- and macrostructure and organic/inorganic contents, leading to potentially compromised mechanical properties of cortical bone when exposed to prolonged BP therapy. Severely suppressed bone turnover may also be the underlying mechanism for impaired fracture healing in patients with AFFs. The rising concerns about the risk for AFFs in nonosteoporotic patients receiving high-dose BPs to treat cancers were also discussed. Detailed investigation will help develop potential targeted pharmacological treatments such as parathyroid hormone. In addition, potential innovative internal fixation implants were discussed with regard to dynamic and biological fixation for enhancing AFF repair.

  14. Symptomatic atypical femoral fractures are related to underlying hip geometry.

    Science.gov (United States)

    Taormina, David P; Marcano, Alejandro I; Karia, Raj; Egol, Kenneth A; Tejwani, Nirmal C

    2014-06-01

    The benefits of bisphosphonates are well documented, but prolonged use has been associated with atypical femur fractures. Radiographic markers for fracture predisposition could potentially aid in safer medication use. In this case-control designed study, we compared hip radiographic parameters and the demographic characteristics of chronic bisphosphonate users who sustained an atypical femoral fracture with a group of chronic bisphosphonate users who did not sustain an atypical femur fracture and also a group who sustained an intertrochanteric hip fracture. Radiographic parameters included were neck-shaft angle (NSA), hip-axis length (HAL) and center-edge angle (CE). Multivariate regression was used to evaluate the relationship between radiographic measures and femur fracture. Receiver-operating characteristic analysis determined cut-off points for neck-shaft angle and risk of atypical femur fracture. Ultimately, pre-fracture radiographs of 53 bisphosphonate users who developed atypical fracture were compared with 43 asymptomatic chronic bisphosphonate users and 64 intertrochanteric fracture patients. Duration of bisphosphonate use did not statistically differ between users sustaining atypical fracture and those without fracture (7.9 [±3.5] vs. 7.7 [±3.3] years, p=0.7). Bisphosphonate users who fractured had acute/varus pre-fracture neck-shaft angles (p<0.001), shorter hip-axis length (p<0.01), and narrower center-edge angles (p<0.01). Regression analysis revealed associations between neck-shaft angle (OR=0.89 [95% CI=0.81-0.97; p=0.01), center edge angle (OR=0.89 [95% CI=0.80-0.99]; p=0.03), and BMI (OR=1.15 [95% CI=1.02-1.31; p=0.03) with fracture development. ROC curve analysis (AUC=0.67 [95% CI=0.56-0.79]) determined that a cut-off point for neck-shaft angle <128.3° yielded 69% sensitivity and 63% specificity for development of atypical femoral fracture. Ultimately, an acute/varus angle of the femoral neck, high BMI, and narrow center-edge angle were

  15. Ichthyosiform mycosis fungoides with alopecia and atypical membranous nephropathy

    Directory of Open Access Journals (Sweden)

    Qiang Zhou

    2011-01-01

    Full Text Available We describe here a rare case of variant of mycosis fungoides (MF: ichthyosiform MF with alopecia and atypical membranous nephropathy. The diagnosis was made based on the following findings: generalized ichthyosis-like eruption, alopecia, enlarged superficial lymph nodes, proteinuria, and hematuria, the histological features of the skin biopsy from both ichthyotic and alopecic lesions with immunohistochemical staining, and the renal biopsy examination with immunofluorescence. The histological examination of ichthyotic and alopecic lesions displayed a predominant infiltration of atypical lymphocytes in the upper dermis with the characteristics of epidermotropism and folliculotropism. Immunohistochemical studies demonstrated that most infiltrated atypical lymphocytes were CD3, CD4, and CD45RO positive, whereas negative for CD5, CD7, CD20, CD30, and CD56. A renal biopsy examination revealed atypical membranous nephropathy with deposition of immunoglobulin G (IgG, IgM, IgA, C1q, and C3. In this case atypical membranous nephropathy was involved, which is very uncommon and has never been presented in the literature to date. Although ichthyosiform MF usually features a relatively favorable course, diffuse alopecia and the renal involvement in this case might indicate aggressive disease and poor prognosis.

  16. Acetylation of cyclin-dependent kinase 5 is mediated by GCN5

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Juhyung; Yun, Nuri; Kim, Chiho [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Song, Min-Young; Park, Kang-Sik [Department of Physiology and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701 (Korea, Republic of); Oh, Young J., E-mail: yjoh@yonsei.ac.kr [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of)

    2014-04-25

    Highlights: • Cyclin-dependent kinase 5 (CDK5) is present as an acetylated form. • CDK5 is acetylated by GCN5. • CDK5’s acetylation site is mapped at Lys33. • Its acetylation may affect CDK5’s kinase activity. - Abstract: Cyclin-dependent kinase 5 (CDK5), a member of atypical serine/threonine cyclin-dependent kinase family, plays a crucial role in pathophysiology of neurodegenerative disorders. Its kinase activity and substrate specificity are regulated by several independent pathways including binding with its activator, phosphorylation and S-nitrosylation. In the present study, we report that acetylation of CDK5 comprises an additional posttranslational modification within the cells. Among many candidates, we confirmed that its acetylation is enhanced by GCN5, a member of the GCN5-related N-acetyl-transferase family of histone acetyltransferase. Co-immunoprecipitation assay and fluorescent localization study indicated that GCN5 physically interacts with CDK5 and they are co-localized at the specific nuclear foci. Furthermore, liquid chromatography in conjunction with a mass spectrometry indicated that CDK5 is acetylated at Lys33 residue of ATP binding domain. Considering this lysine site is conserved among a wide range of species and other related cyclin-dependent kinases, therefore, we speculate that acetylation may alter the kinase activity of CDK5 via affecting efficacy of ATP coordination.

  17. Polo-like kinase-1 : activity measurement and RNAi-mediated knockdown

    NARCIS (Netherlands)

    van Vugt, Marcel A T M; Medema, René H

    2005-01-01

    Polo-like kinase-1 (Plk-1) is an important cell cycle regulatory kinase that has been implicated in a multitude of cell cycle events. In this chapter we review those multiple functions of Plk-1 and describe the methods routinely used in our laboratory to purify Plk-1 from cellular lysates and measur

  18. Characterization of the autophagy marker protein Atg8 reveals atypical features of autophagy in Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Rahul Navale

    Full Text Available Conventional autophagy is a lysosome-dependent degradation process that has crucial homeostatic and regulatory functions in eukaryotic organisms. As malaria parasites must dispose a number of self and host cellular contents, we investigated if autophagy in malaria parasites is similar to the conventional autophagy. Genome wide analysis revealed a partial autophagy repertoire in Plasmodium, as homologs for only 15 of the 33 yeast autophagy proteins could be identified, including the autophagy marker Atg8. To gain insights into autophagy in malaria parasites, we investigated Plasmodium falciparum Atg8 (PfAtg8 employing techniques and conditions that are routinely used to study autophagy. Atg8 was similarly expressed and showed punctate localization throughout the parasite in both asexual and sexual stages; it was exclusively found in the pellet fraction as an integral membrane protein, which is in contrast to the yeast or mammalian Atg8 that is distributed among cytosolic and membrane fractions, and suggests for a constitutive autophagy. Starvation, the best known autophagy inducer, decreased PfAtg8 level by almost 3-fold compared to the normally growing parasites. Neither the Atg8-associated puncta nor the Atg8 expression level was significantly altered by treatment of parasites with routinely used autophagy inhibitors (cysteine (E64 and aspartic (pepstatin protease inhibitors, the kinase inhibitor 3-methyladenine, and the lysosomotropic agent chloroquine, indicating an atypical feature of autophagy. Furthermore, prolonged inhibition of the major food vacuole protease activity by E64 and pepstatin did not cause accumulation of the Atg8-associated puncta in the food vacuole, suggesting that autophagy is primarily not meant for degradative function in malaria parasites. Atg8 showed partial colocalization with the apicoplast; doxycycline treatment, which disrupts apicoplast, did not affect Atg8 localization, suggesting a role, but not exclusive, in

  19. Atypical Imaging Findings in Primary Central Nervous System Lymphoma

    Directory of Open Access Journals (Sweden)

    Zahra Afravi

    2010-05-01

    Full Text Available Background/Objective: The incidence of primary CNS lymphomas (PCNSL is increasing. Timely diagnosis of PCNSL can lead to proper therapeutic management. There are some atypical imaging findings that may easily be misdiagnosed as other pathologic processes such as infectious and demyelinative diseases. As a result, histopathologic diagnosis is necessary for all suspected lesions."nPatients and Methods: In this research we studied 120 cases of PCNSL over the past 16 years. Some of them had atypical imaging findings, suggesting many differential diagnoses. Having said that, stereotactic biopsy was performed for all cases and the diagnosis was proved."nResults: We selected some interesting cases with atypical imaging findings of PCNSL, which were unlikely to be diagnosed without histopathologic evaluation. "nConclusion: PCNSL must be kept in mind as a differential diagnosis for other brain lesions. Histopathologic diagnosis is necessary for prompt management.

  20. EPR dosimetry with synthetic A-type carbonated apatite

    International Nuclear Information System (INIS)

    Synthetic A-type carbonated apatite prepared in reproducible conditions were irradiated at room temperature with 60 Co γ rays. The EPR spectrum is associated to axial CO2- and orthorhombic CO3- species. Radicals used as dose marker in biological apatite are long live paramagnetic species. The stability of the post-irradiation signal of A-type apatite was investigated for more than one year. Measurements showed variations in the spectra attributed to unstable CO3- species, which can be eliminated by thermal treatments at 100 deg C for 24 hours. The CO2- spectrum can be identified in samples irradiated up to 0.2 Gy. All results indicate the A-type apatite as an appropriate material for radiotherapy dosimetry. (author)

  1. Atypical pyoderma gangrenosum in a patient with osteomyelofibrosis

    Directory of Open Access Journals (Sweden)

    Živanović Dubravka

    2007-01-01

    Full Text Available Background. Atypical forms of pyoderma gangrenosum generally appear on the upper extremities; most frequently they are associated with myeloproliferative disorders, including osteomyelofibrosis. A response to systemic steroids is more pronounced than in classical form. Sometimes it may be the first sign of an underlying malignancy. Case report. We reported a patient with atypical pyoderma gangrenosum developed during the course of a myeloid malignancy - osteomyelofibrosis. The lesions occurred after a minor trauma. Painful blistering plaques, with an elevated, bluish-gray border were located on the dorsal aspect of hands. No skin malignancy was found. The lesions resolved rapidly to systemic steroids. Conclusion. Considering the unusual clinical presentation which makes the diagnosis difficult, as well as the fact that atypical forms of pyoderma gangrenosum can be the first sign of malignancies, especially myeloproliferative ones, recognizing this entity enables timely guiding future investigations toward their prompt detection.

  2. Atypical femur fractures associated with bisphosphonates: from prodrome to resolution

    Directory of Open Access Journals (Sweden)

    Braulio Sastre-Jala

    2015-10-01

    Full Text Available Atypical fractures related to the prolonged use of bisphosphonates are caused by low energy mechanisms and are characterized by oblique and transverse lines and frequent bilateralism. We present a clinical case of a patient who we believe illustrates, both in clinical and radiological aspects, the new definition of atypical femur fracture related to treatment using bisphosphonates treated conservatively and successfully with discharge and teriparatide 20 mcg/80 mcl s.c./24h. The appearance of painful symptoms in the upper thigh, especially if bilateral, in patients treated with bisphosphonates for long periods of time, makes it necessary to dismiss bone lesions that might otherwise suggest atypical fracture. In those cases where the fracture is incomplete, restoring bone metabolism through the administration of teriparatide 20 mcg/80 mcl s.c./24h could prevent displaced fractures.

  3. Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids

    Energy Technology Data Exchange (ETDEWEB)

    Moravcevic, Katarina; Mendrola, Jeannine M.; Schmitz, Karl R.; Wang, Yu-Hsiu; Slochower, David; Janmey, Paul A.; Lemmon, Mark A. (UPENN-MED)

    2011-09-28

    Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importance of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to coincidence detection, allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.

  4. From Phosphosites to Kinases

    DEFF Research Database (Denmark)

    Munk, Stephanie; Refsgaard, Jan C; Olsen, Jesper V;

    2016-01-01

    Kinases play a pivotal role in propagating the phosphorylation-mediated signaling networks in living cells. With the overwhelming quantities of phosphoproteomics data being generated, the number of identified phosphorylation sites (phosphosites) is ever increasing. Often, proteomics investigations...... sequence motifs, mostly based on large scale in vivo and in vitro experiments. The context of the kinase and the phosphorylated proteins in a biological system is equally important for predicting association between the enzymes and substrates, an aspect that is also being tackled with available...

  5. Phosphatidylinositol kinase from rabbit reticulocytes

    International Nuclear Information System (INIS)

    Phosphatidylinositol (PI) kinase was isolated from the postribosomal supernatant of rabbit reticulocytes. This activity was identified by the formation of a product that comigrated with phosphatidylinositol-4-phosphate (PIP) when purified PI was phosphorylated in the presence of [32P]ATP and Mg2+. Three major peaks of PI kinase activity were resolved by chromatography on DEAE-cellulose. The first peak eluted at 50-100 mM NaCl together with several serine protein kinases, casein kinase (CK) I and protease activated kinase (PAK) I and II. The PI kinase was subsequently separated from the protein kinases by chromatography on phosphocellulose. The second peak eluted at 125-160 mM NaCl and contained another lipid kinase activity that produced a product which comigrated with phosphatidic acid on thin layer chromatography. The third peak, which eluted at 165-200 mM NaCl, partly comigrated with casein kinase (CK) II and an active protein kinase(s) which phosphorylated mixed histone and histone I. CK II and the histone kinase activities were also separated by chromatography on phosphocelluslose. The different forms of PI kinase were characterized and compared with respect to substrate and salt requirements

  6. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine

    Directory of Open Access Journals (Sweden)

    Mishra Biswaranjan

    2007-10-01

    Full Text Available Neuroleptic malignant syndrome (NMS is the most serious of acute neurological side effects produced by antipsychotic medication, characterized by hyperthermia, rigidity, altered consciousness and autonomic dysfunction, the prevalence of which varies from 0.4-1.4%. NMS is usually seen in treatment with high potency typical antipsychotics and very rarely with atypical antipsychotics. However, NMS cases have been reported with risperidone, clozapine, olanzapine and quetiapine. The presentations of NMS have often varied, and we report another atypicality in presentation of NMS due to olanzapine use.

  7. Mitogen activated protein kinases: a role in inflammatory bowel disease?

    DEFF Research Database (Denmark)

    Broom, O J; Widjaya, B; Troelsen, J;

    2009-01-01

    Since their discovery more than 15 years ago, the mitogen activated protein kinases (MAPK) have been implicated in an ever-increasingly diverse array of pathways, including inflammatory signalling cascades. Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease...... and their related signalling proteins in influencing the progression of IBD....

  8. Isoform Specificity of Protein Kinase Cs in Synaptic Plasticity

    Science.gov (United States)

    Sossin, Wayne S.

    2007-01-01

    Protein kinase Cs (PKCs) are implicated in many forms of synaptic plasticity. However, the specific isoform(s) of PKC that underlie(s) these events are often not known. We have used "Aplysia" as a model system in order to investigate the isoform specificity of PKC actions due to the presence of fewer isoforms and a large number of documented…

  9. Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era.

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal

    Full Text Available BACKGROUND: BCR-ABL kinase domain mutations are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CML patients. Recent studies indicate the presence of pre-existing BCR-ABL mutations in a higher percentage of CML patients when CD34+ stem/progenitor cells are investigated using sensitive techniques, and these mutations are associated with imatinib resistance and disease progression. However, such studies were limited to smaller number of patients. METHODS: We investigated BCR-ABL kinase domain mutations in CD34+ cells from 100 chronic-phase CML patients by multiplex allele-specific PCR and sequencing at diagnosis. Mutations were re-investigated upon manifestation of imatinib resistance using allele-specific PCR and direct sequencing of BCR-ABL kinase domain. RESULTS: Pre-existing BCR-ABL mutations were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48, all patients with pre-existing BCR-ABL mutations exhibited imatinib resistance. Of the 68 patients without pre-existing BCR-ABL mutations, 24 developed imatinib resistance; allele-specific PCR and BCR-ABL kinase domain sequencing detected mutations in 22 of these patients. All 32 patients with pre-existing BCR-ABL mutations had the same mutations after manifestation of imatinib-resistance. In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid

  10. Teaching Fluid Mechanics for Undergraduate Students in Applied Industrial Biology: from Theory to Atypical Experiments

    CERN Document Server

    Absi, Rafik; Dufour, Florence; Huet, Denis; Bennacer, Rachid; Absi, Tahar

    2011-01-01

    EBI is a further education establishment which provides education in applied industrial biology at level of MSc engineering degree. Fluid mechanics at EBI was considered by students as difficult who seemed somewhat unmotivated. In order to motivate them, we applied a new play-based pedagogy. Students were asked to draw inspiration from everyday life situations to find applications of fluid mechanics and to do experiments to verify and validate some theoretical results obtained in course. In this paper, we present an innovative teaching/learning pedagogy which includes the concept of learning through play and its implications in fluid mechanics for engineering. Examples of atypical experiments in fluid mechanics made by students are presented. Based on teaching evaluation by students, it is possible to know how students feel the course. The effectiveness of this approach to motivate students is presented through an analysis of students' teaching assessment. Learning through play proved a great success in fluid...

  11. Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase

    DEFF Research Database (Denmark)

    Sayed, M; Kim, S O; Salh, B S;

    2000-01-01

    Protein kinase CK2 has been implicated in the regulation of a wide range of proteins that are important in cell proliferation and differentiation. Here we demonstrate that the stress signaling agents anisomycin, arsenite, and tumor necrosis factor-alpha stimulate the specific enzyme activity of CK2...... to be an allosteric mechanism. Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities....... in the human cervical carcinoma HeLa cells by up to 8-fold, and this could be blocked by the p38 MAP kinase inhibitor SB203580. We show that p38alpha MAP kinase, in a phosphorylation-dependent manner, can directly interact with the alpha and beta subunits of CK2 to activate the holoenzyme through what appears...

  12. Kinase Inhibitors from Marine Sponges

    Directory of Open Access Journals (Sweden)

    Ana Zivanovic

    2011-10-01

    Full Text Available Protein kinases play a critical role in cell regulation and their deregulation is a contributing factor in an increasing list of diseases including cancer. Marine sponges have yielded over 70 novel compounds to date that exhibit significant inhibitory activity towards a range of protein kinases. These compounds, which belong to diverse structural classes, are reviewed herein, and ordered based upon the kinase that they inhibit. Relevant synthetic studies on the marine natural product kinase inhibitors have also been included.

  13. Mammary Analogue Secretory Carcinoma of the Parotid Gland as a Secondary Malignancy in a Childhood Survivor of Atypical Teratoid Rhabdoid Tumor

    OpenAIRE

    Woo, Jennifer; Seethala, Raja R.; Joseph Sirintrapun, S.

    2013-01-01

    We report the first case of mammary analogue secretory carcinoma (MASC) arising as a secondary malignancy in a 14 years old child with a history of atypical teratoid rhabdoid tumor (ATRT). Although MASC and ATRT are both rare malignancies, they do not share the same genetic and molecular profiles. MASC is a salivary malignancy characterized by a t(12;15)(p13;q25) translocation, resulting in an ETV6-NTRK3 fusion product encoding for a tyrosine kinase. ATRT is a highly malignant pediatric tumor...

  14. Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder

    OpenAIRE

    Brett Silverstein; Jules Angst

    2015-01-01

    Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetit...

  15. The Cost-Effectiveness of Atypicals in the UK

    NARCIS (Netherlands)

    Heeg, Bart; Buskens, Erik; Botteman, Marc; Caleo, Sue; Ingham, Mike; Damen, Joep; de Charro, Frank; van Hout, Ben

    2008-01-01

    Background: In 2002, the National Institute for Health and Clinical Excellence (NICE), recommended atypical antipsychotics over conventional ones for first-line schizophrenia treatment, based on their lower risk of extrapyramidal symptoms. Objective: To estimate the incremental cost-effectiveness of

  16. Folie a trois : Atypical presentation as shared transient psychotic episode

    Directory of Open Access Journals (Sweden)

    V K Aravind

    2014-01-01

    Full Text Available Shared psychotic disorder or induced delusional disorder can occur in different clinical settings and profile and is not uncommon. A case of Folie a trois with atypical clinical presentation as shared acute transient episode in a bereavement setting is reported. Suggestibility, close association and intimacy of the affected persons and major stress as psychological trigger act as psychopathological factors.

  17. Atypical pathogens in community acquired pneumonia of Egyptian children

    Institute of Scientific and Technical Information of China (English)

    Deraz TE; El Sahriggy SA; Shaheen MA; Motawea AA; Gomaa HE; Fawzy SH; Mohamed AA

    2009-01-01

    Objective:Diagnosis of atypical pathogens as an aetiology for community-acquired pneumonia (CAP)in chil-dren is a challenge world wide.The aim of this study was to detect the frequency of atypical pathogens as a cause of community-acquired pneumonia (CAP)in Egyptian children.Methods:From 50 children (with age ranged from 2 months to 1 2 years)hospitalized for community-acquired pneumonia;respiratory sputum samples were collected by induction or spontaneously.All samples were subjected to conventional cultures and Polymer-ase Chain Reaction(PCR)technique DNA extraction for identification of Mycoplasma,Chlamydia pneumoniae and Legionella pneumophila.Results:A definite pathogen was identified in 78% of the studied children;30%typical bacteria,8% candida albicans and atypical bacteria in 40% of the pneumonic children.Chlamydia pneumoniae was isolated from 26% of the children while Mycoplasma pneumoniae was isolated from 1 4%, whereas Legionella pneumophilla was not isolated at all.Conclusion:Atypical pathogens are evident as a po-tential aetiology for community-acquired pneumonia in (1 3.3%)of young and (80%)of older Egyptian chil-dren.

  18. ATYPICAL BULLOUS PYODERMA GANGRENOSUM WITH EARLY LESIONS MIMICKING CHICKEN POX

    OpenAIRE

    Ramesh; Kavya Raju; Gopal; Sharath Kumar; Nandini

    2013-01-01

    ABSTRACT : Pyoderma Gangrenosum (PG) rare neutrophilic dermatoses (1/100,00 0), of which Bullous Pyoderma gangrenosum is an atypical form, which is very rare. Bullous PG is usually associated with haematological disorders like myeloproliferative disorders, haematological malignancies specially AML and several other haematological disorders. It presents as a superficial haemorrhagic bulla which ulcerates, ulcers increase in size and heal with scarring. Treatmen...

  19. Treatment of atypical trigeminal neuralgia with microvascular decompression

    Directory of Open Access Journals (Sweden)

    Hai Jian

    2006-01-01

    Full Text Available Aim: To explore the methods for achieving pain relief in patients with atypical trigeminal neuralgia (TN using microvascular decompression (MVD. Study Design and Settings: Retrospective study of 26 patients treated during the years 2000 to 2004. Materials and Methods: Twenty-six patients in whom vascular compression of the trigeminal nerve was identified by high definition magnetic resonance tomographic angiography (MRTA were treated with MVD for atypical TN in our department. Clinical presentations, surgical findings and clinical outcomes were analyzed retrospectively. Results: In this study, single trigeminal division was involved in only 2 patients (8% and two or three divisions in the other 24 patients (92%. Of prime importance is the fact that in 46.2% of the patients, several conflicting vessels were found in association. Location of the conflicts around the circumference of the trigeminal root was supero-medial to the root in 53.5%, supero-lateral in 30.8% and inferior in 15.7%. MVD for atypical TN resulted in complete pain relief in 50% of the patients with complete decompression, partial pain relief in 30.8% and poor pain relief or pain recurrence in 19.2% of the patients without complete decompression postoperatively. Conclusions: Complete decompression of the entire trigeminal root plays an important role in achieving pain relief in patients with atypical TN with MVD.

  20. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

    NARCIS (Netherlands)

    Legendre, C.M.; Licht, C.; Muus, P.; Greenbaum, L.A.; Babu, S.; Bedrosian, C.; Bingham, C.; Cohen, D.J.; Delmas, Y.; Douglas, K.; Eitner, F.; Feldkamp, T.; Fouque, D.; Furman, R.R.; Gaber, O.; Herthelius, M.; Hourmant, M.; Karpman, D.; Lebranchu, Y.; Mariat, C.; Menne, J.; Moulin, B.; Nurnberger, J.; Ogawa, M.; Remuzzi, G.; Richard, T.; Sberro-Soussan, R.; Severino, B.; Sheerin, N.S.; Trivelli, A.; Zimmerhackl, L.B.; Goodship, T.; Loirat, C.

    2013-01-01

    BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We

  1. Atypical radiation response of SCID cells

    Science.gov (United States)

    Chawapun, Nisa

    Murine SCID (severe combined immune deficiency) cells are well known for their defect in DNA double-strand break repair and in variable(diversity)joining [V(D)J] recombination due to a mutation in a catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). As a consequence, scid cells are hypersensitive to ionizing radiation. The present study showed that asynchronous populations of scid cells were about two-fold more sensitive than Balb/c with respect to cell killing and the defect in scid cells was corrected by complementation with human chromosome 8. Analysis of the survival of synchronized populations as a function of the cell cycle revealed that while scid cells were hypersensitive in all cell cycle phases compared to wild-type cells, this hypersensitivity is even more pronounced in G1 phase. The hypersensitivity reduced as the cells progressed into S phase suggested that homologous recombination repair plays a role. The results imply that there are at least two pathways for the repair of DSB DNA, consistent with a model previously proposed by others. The scid cells were also more sensitive to UVC light (254 nm) killing as compared to wild type cells by clonogenic survival. Using a host cell reactivation (HCR) assay to study the nucleotide excision repair (NER) which is the major repair pathway for UV-photoproducts, the results showed that NER in scid cells was not as efficient as CB- 17. This suggests that DNA-PK is involved in NER as well as non-homologous end-joining (NHEJ) DSB repair which is responsible for ionizing radiation sensitivity in scid cells. Repair in scid cells was not totally absent as shown by low dose rate sparing of cell killing after exposure to 137Cs γ-rays at dose rate of 0.6 cGy/h, 1.36 cGy/h, 6 cGy/h as compared to high dose rate at 171 cGy/min, although this phenomenon could be explained partly by proliferation. However, for radiation induced transformation, no significant dose rate effect was seen. A plot of transformation

  2. Trends in Scientific Literature on Atypical Antipsychotics in South Korea: A Bibliometric Study

    OpenAIRE

    López-Muñoz, Francisco; Shen, Winston W.; Pae, Chi-un; Moreno, Raquel; Rubio, Gabriel; Molina, Juan D.; Noriega, Concha; Pérez-Nieto, Miguel A.; Huelves, Lorena; Álamo, Cecilio

    2013-01-01

    Objective We have carried out a bibliometric study on the scientific publications in relation to atypical or second-generation antipsychotic drugs (SGAs) in South Korea. Methods With the EMBASE and MEDLINE databases, we selected those publications made in South Korea whose title included the descriptors atypic* (atypical*) antipsychotic*, second-generation antipsychotic*, clozapine, risperidone, olanzapine, ziprasidone, quetiapine, sertindole, aripiprazole, paliperidone, amisulpride, zotepine...

  3. Association between GRB2/Sos and insulin receptor substrate 1 is not sufficient for activation of extracellular signal-regulated kinases by interleukin-4: implications for Ras activation by insulin.

    Science.gov (United States)

    Pruett, W; Yuan, Y; Rose, E; Batzer, A G; Harada, N; Skolnik, E Y

    1995-03-01

    Insulin receptor substrate 1 (IRS-1) mediates the activation of a variety of signaling pathways by the insulin and insulin-like growth factor 1 receptors by serving as a docking protein for signaling molecules with SH2 domains. We and others have shown that in response to insulin stimulation IRS-1 binds GRB2/Sos and have proposed that this interaction is important in mediating Ras activation by the insulin receptor. Recently, it has been shown that the interleukin (IL)-4 receptor also phosphorylates IRS-1 and an IRS-1-related molecule, 4PS. Unlike insulin, however, IL-4 fails to activate Ras, extracellular signal-regulated kinases (ERKs), or mitogen-activated protein kinases. We have reconstituted the IL-4 receptor into an insulin-responsive L6 myoblast cell line and have shown that IRS-1 is tyrosine phosphorylated to similar degrees in response to insulin and IL-4 stimulation in this cell line. In agreement with previous findings, IL-4 failed to activate the ERKs in this cell line or to stimulate DNA synthesis, whereas the same responses were activated by insulin. Surprisingly, IL-4's failure to activate ERKs was not due to a failure to stimulate the association of tyrosine-phosphorylated IRS-1 with GRB2/Sos; the amounts of GRB2/Sos associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. Moreover, the amounts of phosphatidylinositol 3-kinase activity associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. In contrast to insulin, however, IL-4 failed to induce tyrosine phosphorylation of Shc or association of Shc with GRB2. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Previous studies have indicated that activation of ERks in this cell line is dependent upon Ras since a dominant-negative Ras (Asn-17) blocks ERK activation by insulin. Our findings, taken in the context

  4. Identification of the Early Devonian Shuangfengshan A-type granites in Liuyuan area of Beishan and its implications to tectonic evolution%北山柳园地区双峰山早泥盆世A型花岗岩的确定及其构造演化意义

    Institute of Scientific and Technical Information of China (English)

    李舢; 王涛; 童英; 洪大卫; 欧阳志侠

    2009-01-01

    yielded a ~(206)Pb/~(238)U age of 415 ± 3 Ma(MSWD = 1.5), considered to be the emplacement age of the Shuangfengshan granitic pluton. All these geochemical features indicate that these granites probably resulted from the earlier calc-alkaline granitic magmas which might crystallized from differentiation of granodioritic magmas formed by partial melting of continental crust (oceanic crust and island arc) due to the underplating of the mantle-derived magma. Based on characteristics of outcrops, chronology, geochemistry and geological setting, the authors hold that the Shuangfengshan granitic pluton might be a post-orogenic or late stage orogenic pluton. The Early Devonian Shuangfengshan A-type granite is the oldest A-type granitic pluton ever found in Beishan, which provides important information for the researches on magmatic and tectonic evolution.

  5. Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids

    Science.gov (United States)

    Wang, Kui-Rong; Jia, Yuan-Jing; Zhou, Shui-Hong; Wang, Qin-Ying; Bao, Yang-Yang; Feng, Zhi-Ying; Yao, Hong-Tian; Fan, Jun

    2016-01-01

    Abstract The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No

  6. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  7. Pyruvate Dehydrogenase Kinase 4

    OpenAIRE

    Cadoudal, Thomas; Distel, Emilie; Durant, Sylvie; Fouque, Françoise; Blouin, Jean-Marc; Collinet, Martine; Bortoli, Sylvie; Forest, Claude; Benelli, Chantal

    2008-01-01

    OBJECTIVE—Pyruvate dehydrogenase complex (PDC) serves as the metabolic switch between glucose and fatty acid utilization. PDC activity is inhibited by PDC kinase (PDK). PDC shares the same substrate, i.e., pyruvate, as glyceroneogenesis, a pathway controlling fatty acid release from white adipose tissue (WAT). Thiazolidinediones activate glyceroneogenesis. We studied the regulation by rosiglitazone of PDK2 and PDK4 isoforms and tested the hypothesis that glyceroneogenesis could be controlled ...

  8. Oncoprotein protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Karin, Michael (San Diego, CA); Hibi, Masahiko (San Diego, CA); Lin, Anning (La Jolla, CA); Davis, Roger (Princeton, MA); Derijard, Benoit (Shrewsbury, MA)

    2003-02-04

    An isolated polypeptide (JNK) characterized by having a molecular weight of 46kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.

  9. Cyclin-dependent kinases.

    Science.gov (United States)

    Malumbres, Marcos

    2014-01-01

    Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific members has generated very encouraging results in clinical trials. PMID:25180339

  10. Regulation of Autophagy by Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2011-06-09

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  11. Atypical depression in the structure of organic mental disorders (literature review

    Directory of Open Access Journals (Sweden)

    Leonov S.F.

    2014-09-01

    Full Text Available The review of literature presents current data on cli¬nical picture and diagnostics of atypical depression. Rubric “atypical depression” includes a variety of depressive states characterized by reactively caused changes of mood, sensitivity to interpersonal contacts, inverted vegetative and somatic symptoms such as increased appetite and hypersomnia. The article considers the place of atypical depression in the structure of organic mental disorders. Positions of foreign authors that produce atypical depression as a clinical entity in the structure of Bipolar affective disorder II type are represented, the views of other authors on the structure of atypical depression are considered. The analysis of national concept of non-circular depression is carried out. Questions of atypical affective conditions acquire special significance due to preparation of International Classification of Diseases of the 11th revision, because inclusion in it of Bipolar affective disorder II type, a manifestation of which is considered to be atypical depressions, is under discussion.

  12. Modulation of the MAP kinase signaling cascade by Raf kinase inhibitory protein

    Institute of Scientific and Technical Information of China (English)

    Nicholas TRAKUL; Marsha R. ROSNER

    2005-01-01

    Proteins like Raf kinase inhibitory protein (RKIP) that serve as modulators of signaling pathways, either by promoting or inhibiting the formation of productive signaling complexes through protein-protein interactions, have been demonstrated to play an increasingly important role in a number of cell types and organisms. These proteins have been implicated in development as well as the progression of cancer. RKIP is a particularly interesting regulator, as it is a highly conserved, ubiquitously expressed protein that has been shown to play a role in growth and differentiation in a number of organisms and can regulate multiple signaling pathways. RKIP is also the first MAP kinase signaling modulator to be identified as playing a role in cancer metastasis, and identification of the mechanism by which it regulates Raf-1 activation provides new targets for therapeutic intervention.

  13. Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP–PNP

    Science.gov (United States)

    Zhao, Baoguang; Lehr, Ruth; Smallwood, Angela M.; Ho, Thau F.; Maley, Kathleen; Randall, Tanya; Head, Martha S.; Koretke, Kristin K.; Schnackenberg, Christine G.

    2007-01-01

    Serum and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine protein kinase of the AGC family which participates in the control of epithelial ion transport and is implicated in proliferation and apoptosis. We report here the 1.9 Å crystal structure of the catalytic domain of inactive human SGK1 in complex with AMP–PNP. SGK1 exists as a dimer formed by two intermolecular disulfide bonds between Cys258 in the activation loop and Cys193. Although most of the SGK1 structure closely resembles the common protein kinase fold, the structure around the active site is unique when compared to most protein kinases. The αC helix is not present in this inactive form of SGK1 crystal structure; instead, the segment corresponding to the C helix forms a β-strand that is stabilized by the N-terminal segment of the activation loop through a short antiparallel β-sheet. Since the differences from other kinases occur around the ATP binding site, this structure can provide valuable insight into the design of selective and highly potent ATP-competitive inhibitors of SGK1 kinase. PMID:17965184

  14. Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP-PNP

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Baoguang; Lehr, Ruth; Smallwood, Angela M; Ho, Thau F; Maley, Kathleen; Randall, Tanya; Head, Martha S; Koretke, Kristin K; Schnackenberg, Christine G [GSKPA

    2008-06-30

    Serum and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine protein kinase of the AGC family which participates in the control of epithelial ion transport and is implicated in proliferation and apoptosis. We report here the 1.9 {angstrom} crystal structure of the catalytic domain of inactive human SGK1 in complex with AMP-PNP. SGK1 exists as a dimer formed by two intermolecular disulfide bonds between Cys258 in the activation loop and Cys193. Although most of the SGK1 structure closely resembles the common protein kinase fold, the structure around the active site is unique when compared to most protein kinases. The {alpha}C helix is not present in this inactive form of SGK1 crystal structure; instead, the segment corresponding to the C helix forms a {beta}-strand that is stabilized by the N-terminal segment of the activation loop through a short antiparallel {beta}-sheet. Since the differences from other kinases occur around the ATP binding site, this structure can provide valuable insight into the design of selective and highly potent ATP-competitive inhibitors of SGK1 kinase.

  15. Bacterial Protein-Tyrosine Kinases

    DEFF Research Database (Denmark)

    Shi, Lei; Kobir, Ahasanul; Jers, Carsten;

    2010-01-01

    in exopolysaccharide production, virulence, DNA metabolism, stress response and other key functions of the bacterial cell. BY-kinases act through autophosphorylation (mainly in exopolysaccharide production) and phosphorylation of other proteins, which have in most cases been shown to be activated by tyrosine......Bacteria and Eukarya share essentially the same family of protein-serine/threonine kinases, also known as the Hanks-type kinases. However, when it comes to protein-tyrosine phosphorylation, bacteria seem to have gone their own way. Bacterial protein-tyrosine kinases (BY-kinases) are bacterial...... and highlighted their importance in bacterial physiology. Having no orthologues in Eukarya, BY-kinases are receiving a growing attention from the biomedical field, since they represent a particularly promising target for anti-bacterial drug design....

  16. Map kinases in fungal pathogens.

    Science.gov (United States)

    Xu, J R

    2000-12-01

    MAP kinases in eukaryotic cells are well known for transducing a variety of extracellular signals to regulate cell growth and differentiation. Recently, MAP kinases homologous to the yeast Fus3/Kss1 MAP kinases have been identified in several fungal pathogens and found to be important for appressorium formation, invasive hyphal growth, and fungal pathogenesis. This MAP kinase pathway also controls diverse growth or differentiation processes, including conidiation, conidial germination, and female fertility. MAP kinases homologous to yeast Slt2 and Hog1 have also been characterized in Candida albicans and Magnaporthe grisea. Mutants disrupted of the Slt2 homologues have weak cell walls, altered hyphal growth, and reduced virulence. The Hog1 homologues are dispensable for growth but are essential for regulating responses to hyperosmotic stress in C. albicans and M. grisea. Overall, recent studies have indicated that MAP kinase pathways may play important roles in regulating growth, differentiation, survival, and pathogenesis in fungal pathogens. PMID:11273677

  17. The gene YALI0E20207g from Yarrowia lipolytica encodes an N-acetylglucosamine kinase implicated in the regulated expression of the genes from the N-acetylglucosamine assimilatory pathway.

    Directory of Open Access Journals (Sweden)

    Carmen-Lisset Flores

    Full Text Available The non-conventional yeast Yarrowia lipolytica possesses an ORF, YALI0E20207g, which encodes a protein with an amino acid sequence similar to hexokinases from different organisms. We have cloned that gene and determined several enzymatic properties of its encoded protein showing that it is an N-acetylglucosamine (NAGA kinase. This conclusion was supported by the lack of growth in NAGA of a strain carrying a YALI0E20207g deletion. We named this gene YlNAG5. Expression of YlNAG5 as well as that of the genes encoding the enzymes of the NAGA catabolic pathway-identified by a BLAST search-was induced by this sugar. Deletion of YlNAG5 rendered that expression independent of the presence of NAGA in the medium and reintroduction of the gene restored the inducibility, indicating that YlNag5 participates in the transcriptional regulation of the NAGA assimilatory pathway genes. Expression of YlNAG5 was increased during sporulation and homozygous Ylnag5/Ylnag5 diploid strains sporulated very poorly as compared with a wild type isogenic control strain pointing to a participation of the protein in the process. Overexpression of YlNAG5 allowed growth in glucose of an Ylhxk1glk1 double mutant and produced, in a wild type background, aberrant morphologies in different media. Expression of the gene in a Saccharomyces cerevisiae hxk1 hxk2 glk1 triple mutant restored ability to grow in glucose.

  18. Distinct Mechanisms of Receptor and Nonreceptor Tyrosine Kinase Activation by Reactive Oxygen Species in Vascular Smooth Muscle Cells: Role of Metalloprotease and Protein Kinase C-δ

    OpenAIRE

    Frank, Gerald D.; Mifune, Mizuo; Inagami, Tadashi; Ohba, Motoi; Sasaki, Terukatsu; Higashiyama, Shigeki; Dempsey, Peter J; Eguchi, Satoru

    2003-01-01

    Reactive oxygen species (ROS) are implicated in cardiovascular diseases. ROS, such as H2O2, act as second messengers to activate diverse signaling pathways. Although H2O2 activates several tyrosine kinases, including the epidermal growth factor (EGF) receptor, JAK2, and PYK2, in vascular smooth muscle cells (VSMCs), the intracellular mechanism by which ROS activate these tyrosine kinases remains unclear. Here, we identified two distinct signaling pathways required for receptor and nonreceptor...

  19. Atypical form of cat scratch disease in immunocompetent patient

    Directory of Open Access Journals (Sweden)

    Kojić Miroslav

    2013-01-01

    Full Text Available Introduction. Cat scratch disease (CSD is an acute infectious disease with benign course caused by the bacteria Bartonella henselae. Clinically, it is usually manifested as regional lymphadenopathy and mild infective syndrome. Rare forms of the disease which usually occur in immunocompromised presons are: encephalitis, transverse myelitis, neuroretinitis, granulomatosus conjunctivitis, arthritis, hepatitis etc. Case report. We presented an atypical form of cat scratch disease in a young immunocompetent female person. The disease was manifested with prolonged fever, rash, purulent lymphadenitis and hepatitis. The diagnosis was based on characteristic patohystological finding and exclusion of the other causes of lymphadenopathy. The patient was treated by antibiotics for a few weeks, with surgical incision and drainage of the purulent lymphadenitis. Conclusion. Atypical forms of CSD could be an important differential-diagnostic problem, especially if there is no opportunity for serological confirmation of the disease.

  20. Multiplicity of A-type and related stars

    CERN Document Server

    North, Pierre L

    2013-01-01

    The origin of chemically peculiar stars remains enigmatic, especially regarding their frequency among their "normal" peers. In addition to magnetic fields and rotation, multiplicity may shed light on the question. We mention the main surveys of the three kinds performed so far of intermediate mass stars, either normal or chemically peculiar, magnetic or not: imaging, spectroscopic, and photometric. We also consider the mulitiplicity of red giant stars, since many of them are descendants of A-type stars, through Mermilliod's radial velocity monitoring of open cluster members. We briefly review the orbital properties of binary systems hosting chemically peculiar stars. Some specific objects of special interest are mentioned as deserving further study. Finally, we recall that some binary systems composed of A-type stars are progenitors of Type Ia supernovae, and evoke the potentialities of future surveys like Gaia.

  1. Combined Papillated Bowen Disease and Clear Cell Atypical Fibroxanthoma

    Directory of Open Access Journals (Sweden)

    Dimas Suárez-Vilela

    2010-05-01

    Full Text Available We describe a case of papillated Bowen disease (PBD, associated with a clear cell atypical fibroxanthoma (CCAFXA. The epidermal lesion showed a bowenoid papillomatous growth pattern with histologic features suggestive of infection by human papilloma virus (HPV. In the dermis a neoplasm made up by spindled or polygonal cells with wide clear cytoplasm and moderate nuclear pleomorphism was found. Immunohistochemical characteristics of these two lesions were clearly different. The atypical cells of the intraepidermal proliferation were positive for AE1-AE3 anticytokeratin antibody, EMA, p16, p53 and p63. The dermal tumor was positive for vimentin, CD10, CD68, CD99, alpha-1-antitrypsin and c-kit. Histological features and immunohistochemical profile of the dermal tumor corresponded to a CCAFXA, a very uncommon neoplasm of which only 10 cases have been reported. In situ hybridization for numerous types of HPVs was negative in both lesions.

  2. HOSPITAL OUTBREAK OF POST CAESAREAN WOUND INFECTION WITH ATYPICAL MYCOBACTERIA

    Directory of Open Access Journals (Sweden)

    Battu

    2016-06-01

    Full Text Available Study of 18 cases of post-operative CS wound infection due to Atypical Mycobacterium (M. chelonae were found in a single hospital over a six-month period. Though the contaminating source could not be identified, remedial control measures taken includes changing all the operative equipment, autoclave machine, air conditioners, exhaust fans of OT, linen and mattresses and solutions like betadine, savlon, spirit and also suture material replaced with new ones. Antibiotic protocols are changed and daily cleaning of OT with cetrimide solution and daily fumigation for one month. No further Atypical MB infective episode have occurred in the one and a half year since the study. Awareness of this ubiquitous opportunistic organism that is not easily eradicated from the hospital environment and strong suspicion of chronic post-operative wound infection, careful surveillance, detailed attention to disinfectant methods of medical devices and appropriate control measures are essential to prevent potential outbreaks.

  3. Magnetic field in atypical prominence structures: Bubble, tornado and eruption

    CERN Document Server

    Levens, P J; Ariste, A López; Labrosse, N; Dalmasse, K; Gelly, B

    2016-01-01

    Spectropolarimetric observations of prominences have been obtained with the THEMIS telescope during four years of coordinated campaigns. Our aim is now to understand the conditions of the cool plasma and magnetism in `atypical' prominences, namely when the measured inclination of the magnetic field departs, to some extent, from the predominantly horizontal field found in `typical' prominences. What is the role of the magnetic field in these prominence types? Are plasma dynamics more important in these cases than the magnetic support? We focus our study on three types of `atypical' prominences (tornadoes, bubbles and jet-like prominence eruptions) that have all been observed by THEMIS in the He I D_3 line, from which the Stokes parameters can be derived. The magnetic field strength, inclination and azimuth in each pixel are obtained by using the Principal Component Analysis inversion method on a model of single scattering in the presence of the Hanle effect. The magnetic field in tornadoes is found to be more ...

  4. Acute Zonal Occult Outer Retinopathy with Atypical Findings

    Directory of Open Access Journals (Sweden)

    Dimitrios Karagiannis

    2014-01-01

    Full Text Available Background. To report a case of acute zonal occult outer retinopathy (AZOOR with atypical electrophysiology findings. Case Presentation. A 23-year-old-female presented with visual acuity deterioration in her right eye accompanied by photopsia bilaterally. Corrected distance visual acuity at presentation was 20/50 in the right eye and 20/20 in the left eye. Fundus examination was unremarkable. Visual field (VF testing revealed a large scotoma. Pattern and full-field electroretinograms (PERG and ERG revealed macular involvement associated with generalized retinal dysfunction. Electrooculogram (EOG light rise and the Arden ratio were within normal limits bilaterally. The patient was diagnosed with AZOOR due to clinical findings, visual field defect, and ERG findings. Conclusion. This is a case of AZOOR with characteristic VF defects and clinical symptoms presenting with atypical EOG findings.

  5. Interaction of the Srb10 Kinase with Sip4, a Transcriptional Activator of Gluconeogenic Genes in Saccharomyces cerevisiae

    OpenAIRE

    Vincent, Olivier; Kuchin, Sergei; Hong, Seung-Pyo; Townley, Robert; Vyas, Valmik K; Carlson, Marian

    2001-01-01

    Sip4 is a Zn2Cys6 transcriptional activator that binds to the carbon source-responsive elements of gluconeogenic genes in Saccharomyces cerevisiae. The Snf1 protein kinase interacts with Sip4 and regulates its phosphorylation and activator function in response to glucose limitation; however, evidence suggested that another kinase also regulates Sip4. Here we examine the role of the Srb10 kinase, a component of the RNA polymerase II holoenzyme that has been primarily implicated in transcriptio...

  6. Therapeutic targeting of Janus kinases

    OpenAIRE

    Pesu, Marko; Laurence, Arian; Kishore, Nandini; Zwillich, Sam; Chan, Gary; O’Shea, John J.

    2008-01-01

    Cytokines play pivotal roles in immunity and inflammation, and targeting cytokines and their receptors is an effective means of treating such disorders. Type I and II cytokine receptors associate with Janus family kinases (JAKs) to effect intracellular signaling. These structurally unique protein kinases play essential and specific roles in immune cell development and function. One JAK, JAK3, has particularly selective functions. Mutations of this kinase underlie severe combined immunodeficie...

  7. Visualizing autophosphorylation in histidine kinases

    OpenAIRE

    Casino, Patricia; Miguel-Romero, Laura; Marina, Alberto

    2014-01-01

    Reversible protein phosphorylation is the most widespread regulatory mechanism in signal transduction. Autophosphorylation in a dimeric sensor histidine kinase is the first step in two-component signalling, the predominant signal-transduction device in bacteria. Despite being the most abundant sensor kinases in nature, the molecular bases of the histidine kinase autophosphorylation mechanism are still unknown. Furthermore, it has been demonstrated that autophosphorylation can occur in two dir...

  8. Lipopolysaccharide heterogeneity in the atypical group of novel emerging Brucella species.

    Science.gov (United States)

    Zygmunt, Michel S; Jacques, Isabelle; Bernardet, Nelly; Cloeckaert, Axel

    2012-09-01

    Recently, novel Brucella strains with phenotypic characteristics that were atypical for strains belonging to the genus Brucella have been reported. Phenotypically many of these strains were initially misidentified as Ochrobactrum spp. Two novel species have been described so far for these strains, i.e., B. microti and B. inopinata, and other strains genetically related to B. inopinata may constitute other novel species as well. In this study, we analyzed the lipopolysaccharides (LPS) (smooth LPS [S-LPS] and rough LPS [R-LPS]) of these atypical strains using different methods and a panel of monoclonal antibodies (MAbs) directed against several epitopes of the Brucella O-polysaccharide (O-PS) and R-LPS. Among the most striking results, Brucella sp. strain BO2, isolated from a patient with chronic destructive pneumonia, showed a completely distinct S-LPS profile in silver stain gels that looked more similar to that of enterobacterial S-LPS. This strain also failed to react with MAbs against Brucella O-PS epitopes and showed weak reactivity with anti-R-LPS MAbs. B. inopinata reference strain BO1 displayed an M-dominant S-LPS type with some heterogeneity relative to the classical M-dominant Brucella S-LPS type. Australian wild rodent strains belonging also to the B. inopinata group showed a classical A-dominant S-LPS but lacked the O-PS common (C) epitopes, as previously reported for B. suis biovar 2 strains. Interestingly, some strains also failed to react with anti-R-LPS MAbs, such as the B. microti reference strain and B. inopinata BO1, suggesting modifications in the core-lipid A moieties of these strains. These results have several implications for serological typing and serological diagnosis and underline the need for novel tools for detection and correct identification of such novel emerging Brucella spp.

  9. 不能明确意义的不典型鳞状细胞伴DNA倍体异常在宫预早期病变筛查中的意义%Diagnostic implications of atypical squamous cells of unknown significance with abnormal DNA ploidy for early cervical lesions

    Institute of Scientific and Technical Information of China (English)

    梅金红; 徐姗; 韩永良; 涂轶; 熊一峰; 余燕青

    2013-01-01

    Objective To investigate the clinical significance of atypical squamous cells of unknown significance (ASCUS) with abnormal DNA ploidy in the early diagnosis of cervical lesions.Methods Eight thousand four hundred and forty-eight patients were included in this study and all had DNA quantitative analysis and cervical liquid-based cytology.Among 1041 cases with DNA aneuploidy and/or abnormal cervical liquid-based cytology and additional cervical biopsy,histological review was performed in 247 ASCUS cases with abnormal DNA ploidy.Results (1) Among 8448 cases,7877 were normal or benign,426 were ASCUS,45 were ASC-H,55 were LSIL and 22 were HSIL by TBS diagnosis.The presence of 1-2 abnormal DNA ploidy cells was detected in 15.3% (65/426) of ASCUS,11.1% (5/45) of ASC-H,9.1% (5/55) of LSIL,and 0 (0/22) of HSIL.The presence of ≥ 3 abnormal DNA ploidy cells was detected in 39.0% (166/426) of ASCUS,75.6% (34/45) of ASC-H,76.4% (42/55) of LSIL,and 95.5% (21/22) of HSIL.(2) A total of 67 cases of CIN 2,CIN 3 or cancers were found in 247 patients with ASCUS by colposcopy biopsies,of which 13.9% (5/36) had 1-2 abnormal DNA ploidy cells,45.5% (56/123) had ≥3 abnormal DNA ploidy cells and 6.8% (6/88) had normal DNA polidy.ASCUS with 1-2 abnormal DNA ploidy cells and with ≥ 3 abnormal DNA ploidy cells were compared.The difference was statistically significant (x2 =11.79,P <0.01).But the difference between ASCUS with 1-2 abnormal DNA ploidy cells and normal DNA ploidy had no statistical significance (P > 0.05).Conclusions ASCUS with ≥3 abnormal DNA ploidy cells has higher risk for developing CIN 2,CIN 3 or invasive carcinoma.The application of DNA quantitative analysis and cervical liquid-based cytology test can help in guiding clinical follow-up and treatment options in patients with ASCUS.%目的 通过DNA定量分析与薄层液基细胞学检查,探讨不能明确意义的不典型鳞状细胞(ASCUS)伴DNA倍体异常在宫颈早期

  10. Atypical Papular Purpuric Eruption Induced by Parvovirus B19 Infection

    OpenAIRE

    Şeyma Kayalı; Nilden Tuygun; Halise Akça; Can Demir Karacan

    2016-01-01

    Parvovirus B19 infection’s most common dermatological manifestation is erythema infectiosum as also known the fifth disease. Rare clinical presentations of parvovirus B 19 like papulopurpuric gloves and socks syndrome and acropetechial syndrome has also been described re­cently. This study presents report of a case with atypical feature and distribution of rash due to parvovirus B19 in­fection. We want to emphasize that pediatricians should consider parvovirus B19 infection of any patient who...

  11. Childhood atypical meningioma with perineural spread: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Feng-Yu.; Wong, Alex Mun-Ching; Wong, Ho-Fai; Ng, Shu-Hang [Chang Gung Memorial Hospital, Department of Diagnostic Radiology, Kwei-Shan, Tao-Yuan (Taiwan); Wu, Chieh-Tsai [Chang Gung Memorial Hospital, Department of Neurosurgery, Kwei-Shan, Tao-Yuan (Taiwan); Lin, Kuang-Lin [Chang Gung Memorial Hospital, Division of Pediatric Neurology, Kwei-Shan, Tao-Yuan (Taiwan)

    2005-09-01

    Meningiomas are uncommon in children. When they occur, they are frequently associated with neurofibromatosis type 2. Childhood meningiomas are generally large and commonly associated with cyst formation and an unusual location. Perineural tumor spread, occasionally associated with head and neck malignancies, is very rare in meningiomas. We present the MR findings of an atypical meningioma with perineural spread in a 4.5-year-old girl. (orig.)

  12. Atypical Chronic Myeloid Leukaemia with Trisomy 13: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Guo-yu Hu; Chao-hui Yuan; Kui Tan; Zhen-zhen Chen

    2011-01-01

    ATYPICAL chronic myeloid leukaemia (aCML),which shows both myeloproliferative and myeIodysplastic features,is a type of myeloproliferative/myelodysplastic disease as defined by the World Health Organisation (WHO) classification of the myeloid neoplasms.1 Because of the presence of neutrophilic leukocytosis,aCML may resemble chronic myeIogenous leukemia (CML).However,in contrast with CML,aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.

  13. Epithelioid Schwannomas: An Analysis of 58 Cases Including Atypical Variants.

    Science.gov (United States)

    Hart, Jesse; Gardner, Jerad M; Edgar, Mark; Weiss, Sharon W

    2016-05-01

    The histologic features and outcome of 58 cases of epithelioid schwannoma were studied to determine the significance of atypical histologic features. Cases were retrieved from personal consultation files from 1999 to 2013. Patients (31 male and 26 female patients) ranged in age from 14 to 80 years (median, 38 y). Two patients had schwannomatosis 1. Tumors developed in the dermis/subcutis (n=56) or muscle (n=2) of the upper extremity (34.5%), lower extremity (34.5%), thorax/abdomen/back (18%), and less common anatomic locations including the scalp, neck, lip, and breast. They ranged in size from 0.25 to 4.5 cm (median, 2.0 cm). Typically circumscribed and surrounded by a perineurium, they comprised single or small groups of epithelioid schwann cells with a moderate amphophilic cytoplasm and occasional nuclear pseudoinclusions. Stroma varied from myxoid to hyalinized, often with thick-walled vessels (55 cases). Mitotic rate ranged from 0 to 9 mitoses/10 high-power field (HPF) (2.37 mm) in the most active areas (mean, 2 to 3 mitoses/10 HPFs). Thirteen cases (22%) were "atypical," defined by a high mitotic rate (≥3 mitoses per 10 HPFs) and nuclear size variation (≥3:1). All (56/56) expressed S100 protein; type IV collagen invested groups or individual cells (16/17). Melanoma markers were negative, except for melan A (1 case). Follow-up in 39 patients (median, 78 mo; range, 6 to 174 mo) indicated that 31 (79%) were alive without disease (including 9/13 atypical cases; median, 78 mo), 7 (18%) were alive with unknown status, and 1 patient had died of unrelated causes. One tumor recurred, but none metastasized. Epithelioid schwannomas, even those with atypical features, are benign and do not constitute a histologic continuum with epithelioid malignant peripheral nerve sheath tumors, which typically occur in deep soft tissues and have more anaplastic features. PMID:26752543

  14. Ureterolithiasis: classical and atypical findings on unenhanced helical computed tomography.

    Science.gov (United States)

    Vaswani, Kuldeep K; El-Dieb, Adam; Vitellas, Kenneth M; Bennett, William F; Bova, James G

    2002-03-01

    Evaluation of patients with acute flank pain using helical computed tomography (CT) is a well-accepted, rapid, and safe procedure in the emergency setting. Various primary and secondary signs are described in the literature for evaluation of these patients. Our purpose is to demonstrate both the classical findings associated with ureteral calculi on unenhanced helical CT and atypical findings and potential pitfalls. We also provide readers with a systematic approach to interpreting unenhanced helical CT scans performed for acute flank pain.

  15. Off-label indications for atypical antipsychotics: A systematic review

    OpenAIRE

    Fountoulakis, Konstantinos N; Nimatoudis, Ioannis; Iacovides, Apostolos; Kaprinis, George

    2004-01-01

    Introduction With the introduction of newer atypical antipsychotic agents, a question emerged, concerning their use as complementary pharmacotherapy or even as monotherapy in mental disorders other than psychosis. Material and method MEDLINE was searched with the combination of each one of the key words: risperidone, olanzapine and quetiapine with key words that refered to every DSM-IV diagnosis other than schizophrenia and other psychotic disorders, bipolar disorder and dementia and memory d...

  16. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine

    OpenAIRE

    Mishra Biswaranjan; Mishra Baikunthanath; Sahoo Saddichha; Arora Manu; Khess C.R.J

    2007-01-01

    Neuroleptic malignant syndrome (NMS) is the most serious of acute neurological side effects produced by antipsychotic medication, characterized by hyperthermia, rigidity, altered consciousness and autonomic dysfunction, the prevalence of which varies from 0.4-1.4%. NMS is usually seen in treatment with high potency typical antipsychotics and very rarely with atypical antipsychotics. However, NMS cases have been reported with risperidone, clozapine, olanzapine and quetiapine. The presen...

  17. Atypical Attentional Networks and the Emergence of Autism

    OpenAIRE

    Keehn, Brandon; Müller, Ralph-Axel; Townsend, Jeanne

    2012-01-01

    The sociocommunicative impairments that define autism spectrum disorder (ASD) are not present at birth but emerge gradually over the first two years of life. In typical development, basic attentional processes may provide a critical foundation for sociocommunicative abilities. Therefore early attentional dysfunction in ASD may result in atypical development of social communication. Prior research has demonstrated that persons with ASD exhibit early and lifelong impairments in attention. The p...

  18. Magnetic field in atypical prominence structures: Bubble, tornado and eruption

    OpenAIRE

    Levens, P. J.; Schmieder, B.; Ariste, A. López; Labrosse, N.; Dalmasse, K.; Gelly, B.

    2016-01-01

    Spectropolarimetric observations of prominences have been obtained with the THEMIS telescope during four years of coordinated campaigns. Our aim is now to understand the conditions of the cool plasma and magnetism in `atypical' prominences, namely when the measured inclination of the magnetic field departs, to some extent, from the predominantly horizontal field found in `typical' prominences. What is the role of the magnetic field in these prominence types? Are plasma dynamics more important...

  19. Figurative language processing in atypical populations: The ASD perspective

    OpenAIRE

    Mila eVulchanova; David eSaldaña; Sobh eChahboun; Valentin eVulchanov

    2015-01-01

    This paper is intended to provide a critical overview of experimental and clinical research documenting problems in figurative language processing in atypical populations with a focus on the Autistic Spectrum. Research in the comprehension and processing of figurative language in autism invariably documents problems in this area. The greater paradox is that even at the higher end of the spectrum or in the cases of linguistically talented individuals with Asperger syndrome, where structural la...

  20. Long-term Deformation Measurements of Atypical Roof Timber Structures

    Directory of Open Access Journals (Sweden)

    Jiří Bureš

    2014-06-01

    Full Text Available The paper includes conclusions from evaluation of results obtained from long-termmeasuring of innovative atypical roof timber structures. Based on the results ofmeasurements of vertical and horizontal deformation components it is possible to analyzethe real behavior of structures in given conditions. By assessing deformations in variousstages, including particularly external and internal environment temperatures, relative airhumidity and moisture content of wood, decisive parameters for real structure behaviorcan be established. The data are processed from period 2001 – 2013.

  1. Atypical demyelinating lesions in patients with multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Yetkin, Z. [Dept. of Radiology, Medical Coll. of Wisconsin, Milwaukee, WI (United States); Haughton, V.M. [Dept. of Radiology, Medical Coll. of Wisconsin, Milwaukee, WI (United States)]|[Dept. of Radiology, Medical Coll. of Wisconsin, Froedtert Memorial Lutheran Hospital, Milwaukee, WI (United States)

    1995-05-01

    We describe an atypical MRI appearance of multiple sclerosis (MS). Lesions characterized on T2-weighted images by a well-defined rim of increased signal intensity and a concentric region of higher signal intensity were seen in 6 of 132 patients with MS. On T1-weighted images these lesions were evident as regions of low signal intensity, often with a rim of contrast enhancement or increased signal intensity. These appearances tended to be shown by new, evolving lesions. (orig.)

  2. Phosphatidylinositol 3-kinase in myogenesis.

    Science.gov (United States)

    Kaliman, P; Zorzano, A

    1997-08-01

    Phosphatidylinositol 3-kinase (PI 3-kinase) has been cloned and characterized in a wide range of organisms. PI 3-kinases are activated by a diversity of extracellular stimuli and are involved in multiple cell processes such as cell proliferation, protein trafficking, cell motility, differentiation, regulation of cytoskeletal structure, and apoptosis. It has recently been shown that PI 3-kinase is a crucial second messenger in the signaling of myogenesis. Two structurally unrelated highly specific inhibitors of PI 3-kinase-wortmannin and LY294002-block the morphological and biochemical differentiation program of different skeletal-muscle cell models. Moreover, L6E9 myoblasts overexpressing a dominant-negative mutant of PI 3-kinase p85 regulatory subunit (Δp85) are unable to differentiate. Furthermore, PI 3-kinase is specifically involved in the insulinlike growth factor (IGF)-dependent myogenic pathway. Indeed, the ability of IGF-I, des-1,3-IGF-I, and IGF-II to promote cell fusion and muscle-specific protein expression is impaired after treatment with PI 3-kinase inhibitors or in cells overexpressing Δp85. The identification of additional key downstream elements of the IGF/PI 3-kinase myogenic cascade is crucial to a detailed understanding of the process of muscle differentiation and may generate new tools for skeletal and cardiac muscle regeneration therapies. (Trends Cardiovasc Med 1997;7:198-202). © 1997, Elsevier Science Inc. PMID:21235885

  3. Atypical Findings of Guillain-Barré Syndrome in Children

    Directory of Open Access Journals (Sweden)

    Parvaneh KARIMZADEH

    2012-10-01

    Full Text Available ObjectiveGuillain-Barre syndrome (GBS is an immune-mediated polyneuropathy that occurs mostly after prior infection. The diagnosis of this syndrome is dependent heavily on the history and examination, although cerebrospinal fluid analysis and electrodiagnostic testing usually confirm the diagnosis. This is a retrospective study which was performed to investigate the atypical features of GBS.Materials & MethodsThirty three patients (21/63.6% males and 12/36.4% females with GBS were retrospectively studied and prospectively evaluated at the Child Neurology institute of Mofid Children Hospital of Shahid Beheshti University of Medical Sciences between May 2011 and September 2012.ResultsThe mean age was 5.4 years (range, 1.5-10.5.Twenty one patients (87.9 % had previous history of infections. Eight patients (24.2% admitted with atypical symptoms like upper limb weakness (3%, ptosis (3%, neck stiffness (3%, inability to stand (proximal weakness (9.1%, headache (3% and dysphagia (3%.According to disease process, weakness was ascending in 26 (78.8%, descending in 5 (15.2% and static in 2 (6.1% patients. Cranial nerve involvement was found in 8(24.3% children, most commonly as facial palsy in 3 (9.1%.ConclusionIn this study, 24.3% of our patients presented with atypical symptoms of GBS as upper limb weakness, ptosis, neck stiffness, inability to stand (proximal weakness, headache and dysphagia

  4. Atypical features of nanophthalmic macula- a spectral domain OCT study

    Directory of Open Access Journals (Sweden)

    Rao Aparna

    2012-06-01

    Full Text Available Abstract Background To report atypical features on Spectral domain optical coherence tomography (SD-OCT in a case of non-familial pure adult nanophthalmos. Case presentation A 39 year old male hyperope was found to have biometric and fundus findings typical of nanophthalmos. The additional atypical features included serous pigment epithelial detachment (PED in right eye and a cuff of subretinal fluid with underlying yellow deposits along superotemporal arcade in the left eye. Fundus flourescein angiogram showed hyperfluorescence due to window defect, dye pooling due to serous PED in right eye and leak superior to disc in right eye and superotemporally in left eye. Cirrus-SD OCT horizontal line scan passing through the fovea showed extensive inner limiting membrane corrugations causing distorted foveal contour in both eyes. A large juxtafoveal serous PED and a small extrafoval PED were seen with folds in the retinal pigment epithelium (RPE-choriocapillary layer in the right eye. Conclusion Structural disruptions in the RPE-choriocapillary complex in the form of folds or juxtafoveal serous PED and RPE folds can be atypical features of nanophthalmic macula better discerned on high resolution OCT.

  5. Paranoid personality masking an atypical case of frontotemporal dementia.

    Science.gov (United States)

    Iroka, Nneka; Jehangir, Waqas; Ii, Jay Littlefield; Pattan, Vishwanath; Yousif, Abdalla; Mishra, Arunesh K

    2015-05-01

    Frontotemporal dementia (FTD) is a debilitating disease that is well described in the "Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5)", and typically presents with memory impairment, progressive decline in cortical functioning, and behavioral changes. Age of onset is generally in the late fifties, and usually the first presentation involves a change in behavior and emotional blunting. Treatment of FTD involves management of any neurobehavioral symptoms while trials of atypical antipsychotics are ongoing but suggest some efficacy. We present a case of a patient who first presented with severe paranoid personality traits and frank persecutory delusions. This atypical presentation of our patient first led to her incorrect diagnosis of a psychotic disorder and paranoid personality disorder. As a result of this diagnosis, she was treated unsuccessfully. A subsequent magnetic resonance imaging (MRI) then showed atrophy of frontal and temporal lobes bilaterally (left more prominent than right) which confirmed the diagnosis of FTD. The importance of this case involves the atypical presentation of paranoia and delusions, and our patient's incorrect diagnosis based on her clinical presentation led to a trial of unsuccessful treatment. Only after performing an MRI, which showed atrophy, was the patient appropriately treated and deemed medically stable. This case report illustrates the importance of considering a rare presentation of frontotemporal lobe dementia with patients who are in the typical age range and present with paranoia and delusions.

  6. Evolutionary divergence in the catalytic activity of the CAM-1, ROR1 and ROR2 kinase domains.

    Directory of Open Access Journals (Sweden)

    Travis W Bainbridge

    Full Text Available Receptor tyrosine kinase-like orphan receptors (ROR 1 and 2 are atypical members of the receptor tyrosine kinase (RTK family and have been associated with several human diseases. The vertebrate RORs contain an ATP binding domain that deviates from the consensus amino acid sequence, although the impact of this deviation on catalytic activity is not known and the kinase function of these receptors remains controversial. Recently, ROR2 was shown to signal through a Wnt responsive, β-catenin independent pathway and suppress a canonical Wnt/β-catenin signal. In this work we demonstrate that both ROR1 and ROR2 kinase domains are catalytically deficient while CAM-1, the C. elegans homolog of ROR, has an active tyrosine kinase domain, suggesting a divergence in the signaling processes of the ROR family during evolution. In addition, we show that substitution of the non-consensus residues from ROR1 or ROR2 into CAM-1 and MuSK markedly reduce kinase activity, while restoration of the consensus residues in ROR does not restore robust kinase function. We further demonstrate that the membrane-bound extracellular domain alone of either ROR1 or ROR2 is sufficient for suppression of canonical Wnt3a signaling, and that this domain can also enhance Wnt5a suppression of Wnt3a signaling. Based on these data, we conclude that human ROR1 and ROR2 are RTK-like pseudokinases.

  7. Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Brett Silverstein

    2015-01-01

    Full Text Available Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1 The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2 Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3 Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4 Most probands who report atypical depression meet criteria for “somatic depression,” defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as “reactive” appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression.

  8. Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder.

    Science.gov (United States)

    Silverstein, Brett; Angst, Jules

    2015-01-01

    Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3) Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4) Most probands who report atypical depression meet criteria for "somatic depression," defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as "reactive" appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression. PMID:26258131

  9. IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Miles J.; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R.; van Aalten, Daan M.F.; Downes, C. Peter; Batty, Ian H. (Toronto); (Dundee)

    2012-10-16

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.

  10. Atypical acute urticaria in children and its relationship with urticarial vasculitis

    OpenAIRE

    ARSLAN, Zafer; ÖZMEN, Serap; SÜRMELİ, Sara; ARDA, Nilüfer

    2011-01-01

    In childhood, urticarial lesions are sometimes associated with purpura. This form might be identified as atypical, and may also be related to urticarial vasculitis (UV). The aim of this study was to assess the clinicopathologic characteristics of UV in children with atypical urticaria. Materials and methods: Fifteen children with atypical urticaria were evaluated with medical history, physical examination, and laboratory and skin punch biopsy findings. Results: Infections were detected as...

  11. Solitary Atypical Adenomatous Hyperplasia in a 12-Year-Old Girl.

    Science.gov (United States)

    Jin, Moran; Lee, Yang-Haeng; Kim, Bomi; Yoon, Young Chul; Wi, Jin Hong

    2016-04-01

    Atypical adenomatous hyperplasia is a premalignant lesion reflecting a focal proliferation of atypical cells. These lesions are usually observed as incidental findings in lungs that have been resected due to other conditions, such as lung cancer. We report the youngest case of atypical adenomatous hyperplasia on record in a 12-year-old girl. In this patient, the lesion was found in association with pneumothorax.

  12. Healthcare Costs of Atypical Antipsychotic Use for Patients with Bipolar Disorder in a Medicaid Programme

    OpenAIRE

    Ying Qiu; Fu, Alex Z; Gordon G. Liu; Christensen, Dale B.

    2010-01-01

    Background: A large body of clinical studies have demonstrated the efficacy of atypical antipsychotic use in the treatment of bipolar disorder. Facing increasing budget pressure, third-party payers, such as state Medicaid programmes in the US, are demanding better understanding of the medical costs beyond atypical antipsychotic drug costs alone in treating bipolar disorder. Objective: To examine healthcare costs associated with the atypical antipsychotic treatments for bipolar disorder from a...

  13. Genetic Characterization of Atypical Mansonella (Mansonella) ozzardi Microfilariae in Human Blood Samples from Northeastern Peru

    OpenAIRE

    Marcos, Luis A.; Arrospide, Nancy; Recuenco, Sergio; Cabezas, Cesar; Gary J Weil; Fischer, Peter U.

    2012-01-01

    DNA sequence comparisons are useful for characterizing proposed new parasite species or strains. Microfilariae with an atypical arrangement of nuclei behind the cephalic space have been recently described in human blood samples from the Amazon region of Peru. Three blood specimens containing atypical microfilariae were genetically characterized using three DNA markers (5S ribosomal DNA, 12S ribosomal DNA, and cytochrome oxidase I). All atypical microfilariae were clustered into the Mansonella...

  14. Atypical depression in the structure of organic mental disorders (literature review)

    OpenAIRE

    Leonov S.F.; Shusterman T.Y.; Rokutov S.V.; Shornikov A.V.

    2014-01-01

    The review of literature presents current data on cli¬nical picture and diagnostics of atypical depression. Rubric “atypical depression” includes a variety of depressive states characterized by reactively caused changes of mood, sensitivity to interpersonal contacts, inverted vegetative and somatic symptoms such as increased appetite and hypersomnia. The article considers the place of atypical depression in the structure of organic mental disorders. Positions of foreign authors that produce a...

  15. Atypical depression in the structure of organic mental disorders (literature review).

    OpenAIRE

    Spirina, I. D.; Leonov, S. F.; Shusterman, T. Y.; Rokutov, S. V.; Shornikov, A. V.

    2014-01-01

    The review of literature presents current data on cli­nical picture and diagnostics of atypical depression. Rubric “atypical depression” includes a variety of depressive states characterized by reactively caused changes of mood, sensitivity to interpersonal contacts, inverted vegetative and somatic symptoms such as increased appetite and hypersomnia. The article considers the place of atypical depression in the structure of organic mental disorders. Positions of foreign authors that produce a...

  16. Modeling and Estimation Techniques for Wide-Area Network Traffic with Atypical Components

    OpenAIRE

    Minton, Carl Edward

    2002-01-01

    A critical first step to improving existing and designing future wide-area networks is an understanding of the load placed on these networks. Efforts to model traffic are often confounded by atypical traffic - traffic particular to the observation site not ubiquitously applicable. The causes and characteristics of atypical traffic are explored in this thesis. Atypical traffic is found to interfere with parsimonious analytic traffic models. A detection and modeling tech...

  17. Genome-wide identification and analysis of expression profiles of maize mitogen-activated protein kinase kinase kinase.

    Science.gov (United States)

    Kong, Xiangpei; Lv, Wei; Zhang, Dan; Jiang, Shanshan; Zhang, Shizhong; Li, Dequan

    2013-01-01

    Mitogen-activated protein kinase (MAPK) cascades are highly conserved signal transduction model in animals, yeast and plants. Plant MAPK cascades have been implicated in development and stress responses. Although MAPKKKs have been investigated in several plant species including Arabidopsis and rice, no systematic analysis has been conducted in maize. In this study, we performed a bioinformatics analysis of the entire maize genome and identified 74 MAPKKK genes. Phylogenetic analyses of MAPKKKs from maize, rice and Arabidopsis have classified them into three subgroups, which included Raf, ZIK and MEKK. Evolutionary relationships within subfamilies were also supported by exon-intron organizations and the conserved protein motifs. Further expression analysis of the MAPKKKs in microarray databases revealed that MAPKKKs were involved in important signaling pathways in maize different organs and developmental stages. Our genomics analysis of maize MAPKKK genes provides important information for evolutionary and functional characterization of this family in maize.

  18. Genome-wide identification and analysis of expression profiles of maize mitogen-activated protein kinase kinase kinase.

    Directory of Open Access Journals (Sweden)

    Xiangpei Kong

    Full Text Available Mitogen-activated protein kinase (MAPK cascades are highly conserved signal transduction model in animals, yeast and plants. Plant MAPK cascades have been implicated in development and stress responses. Although MAPKKKs have been investigated in several plant species including Arabidopsis and rice, no systematic analysis has been conducted in maize. In this study, we performed a bioinformatics analysis of the entire maize genome and identified 74 MAPKKK genes. Phylogenetic analyses of MAPKKKs from maize, rice and Arabidopsis have classified them into three subgroups, which included Raf, ZIK and MEKK. Evolutionary relationships within subfamilies were also supported by exon-intron organizations and the conserved protein motifs. Further expression analysis of the MAPKKKs in microarray databases revealed that MAPKKKs were involved in important signaling pathways in maize different organs and developmental stages. Our genomics analysis of maize MAPKKK genes provides important information for evolutionary and functional characterization of this family in maize.

  19. Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2 activity

    DEFF Research Database (Denmark)

    Köpper, Frederik; Bierwirth, Cathrin; Schön, Margarete;

    2013-01-01

    knockdown of the MAP kinase-activated protein kinase 2 (MK2), a kinase currently implicated in p38 stress signaling and G2 arrest. Depletion or inhibition of MK2 also protected cells from DNA damage-induced cell death, and mice deficient for MK2 displayed decreased apoptosis in the skin upon UV irradiation......DNA damage can obstruct replication forks, resulting in replicative stress. By siRNA screening, we identified kinases involved in the accumulation of phosphohistone 2AX (γH2AX) upon UV irradiation-induced replication stress. Surprisingly, the strongest reduction of phosphohistone 2AX followed....... Moreover, MK2 activity was required for damage response, accumulation of ssDNA, and decreased survival when cells were treated with the nucleoside analogue gemcitabine or when the checkpoint kinase Chk1 was antagonized. By using DNA fiber assays, we found that MK2 inhibition or knockdown rescued DNA...

  20. WNK1: analysis of protein kinase structure, downstream targets, and potential roles in hypertension

    Institute of Scientific and Technical Information of China (English)

    Bing-e XU; Byung-Hoon LEE; Xiaoshan MIN; Lisa LENERTZ; Charles J HEISE; Steve STIPPEC; Elizabeth J GOLDSMITH; Melanie H. COBB

    2005-01-01

    The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type Ⅱ, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.

  1. Jadomycin B, an Aurora-B kinase inhibitor discovered through virtual screening

    Institute of Scientific and Technical Information of China (English)

    Da Huafu; Jing Zhang; Jian Tingzheng; Yan Li; Ke Qianyang; Yan Changwang; Shu Yisi

    2008-01-01

    @@ Aurora kinases are clearly implicated in tumorgenesis and have emerged as promising targets for cancer therapy in recent years. In a virtual screening attempt, 22 compounds were identified from nearly 15,000 microbial natural products as potential small-molecule inhibitors of human Aurora-B kinase. When tested in yeast models, 2 compounds (one is Jadomycin B) showed preferential inhibition of ipll-321 (yeast Aurora kinase temperature sensitive mutant) than wild type yeast cell, suggesting these compounds are true Aurora kinase inhibitors. Further in vitro biochemical assay using purified recombinant Aurora-B kinase showed Jadomycin B inhibits Aurora-B activity in a dose-dependent fashion while two Jadomycin congeners, Jadomycin S and T, showed no activity.

  2. Atypical presentation of a cervical breast-cancer metastasis mimicking a dumbbell-shaped neurinoma

    Directory of Open Access Journals (Sweden)

    Christoph Kolja Boese

    2014-01-01

    CONCLUSION: The present case report and the reviewed literature point towards a growing clinical relevance of symptomatic LM in cancer patients and their possible atypical presentations and locations.

  3. Atypical lymphocytes in malaria mimicking dengue infection in Thailand

    Directory of Open Access Journals (Sweden)

    Polrat Wilairatana

    2010-09-01

    Full Text Available Polrat Wilairatana1, Noppadon Tangpukdee1, Sant Muangnoicharoen1, Srivicha Krudsood2, Shigeyuki Kano31Department of Clinical Tropical Medicine, 2Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 3Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, Tokyo, JapanAbstract: Patients with uncomplicated falciparum or vivax malaria usually present with acute febrile illness and thrombocytopenia similar to dengue infection. We retrospectively studied atypical lymphocytes (AL and atypical lymphocytosis (ALO, defined as AL > 5% of total white blood cells in 1310 uncomplicated malaria patients. In 718 falciparum malaria patients, AL and ALO on day 0 were found in 53.2% and 5.7% of the patients, respectively, with median AL on admission of 1% (range 0%–10%, whereas in 592 vivax malaria patients, AL and ALO on day 0 were found in 55.4% and 9.5% of the patients, respectively, with median AL on admission of 1% (range 0%–14%. After antimalarial treatment, AL and ALO declined in both falciparum and vivax malaria. However, AL and ALO remained in falciparum malaria on days 7, 14, and 21, whereas AL and ALO remained in vivax malaria on days 7, 14, 21, and 28. In both falciparum and vivax malaria patients, there was a positive correlation between AL and total lymphocytes, but a negative correlation between AL and highest fever on admission, white blood cells, and neutrophils, eosinophils, and platelets (P < 0.05. In conclusion, AL or ALO may be found in uncomplicated falciparum and vivax malaria mimicking dengue infection. In tropical countries where both dengue and malaria are endemic, presence of AL or ALO in any acute febrile patients with thrombocytopenia (similar to the findings in dengue malaria could not be excluded. Particularly if the patients have risk of malaria infection, confirmative microscopic examination for malaria should be carried out

  4. Macrokinetics of Ethylene Epoxidation over A-type Silver Catalyst

    Institute of Scientific and Technical Information of China (English)

    Liang Rujun; Li Jianwei

    2015-01-01

    By taking the surface chemical reactions as the rate-controlling step, a possible reaction mechanism for ethylene epoxidation to synthesize ethylene oxide over the A-type silver catalyst was developed, while it was assumed that the ep-oxidation reaction would take place between ethylene and the un-dissociated adsorbed oxygen O2a on the solo active sites, while the deep oxidation would occur between ethylene and the dissociated adsorbed oxygen Oa on the adjacent multi-active sites. In order to describe the effect of 1,2-C2H4Cl2 (EDC) inhibitor on the ethylene epoxidation process, the reversible reac-tions between EDC and vinyl chloride (VC) on the active sites of silver catalyst was introduced. According to the assumed mechanism, the hyperbolic macro-kinetic model of ethylene epoxidation over the A-type silver catalyst was established, and the macrokinetic experiments were carried out in an internal-recycle gradientless reactor operating at a pressure of 2.1 MPa and a temperature in the range of 217.8—249.0℃, with the gas composition (molar fraction) consisting of 15.82%—34.65%C2H4, 2.55%—7.80%O2, 0.88%—6.15%CO2, 0.15—2.61μmol/mol of 1,2-C2H4Cl2 and 0.14—1.28μmol/mol of C2H3Cl. By means of the Simplex Optimal Method, the parameters of the macrokinetic models were estimated. Statistical test showed that the macrokinetic models developed for the A-type silver catalyst agree well with the experimental results.

  5. Atypical Papular Purpuric Eruption Induced by Parvovirus B19 Infection

    Directory of Open Access Journals (Sweden)

    Şeyma Kayalı

    2016-03-01

    Full Text Available Parvovirus B19 infection’s most common dermatological manifestation is erythema infectiosum as also known the fifth disease. Rare clinical presentations of parvovirus B 19 like papulopurpuric gloves and socks syndrome and acropetechial syndrome has also been described re­cently. This study presents report of a case with atypical feature and distribution of rash due to parvovirus B19 in­fection. We want to emphasize that pediatricians should consider parvovirus B19 infection of any patient who has leukopenia presenting with petechial/purpuric eruption of an unclear origin.

  6. Dengue Fever Presenting Atypically with Viral Conjunctivitis and Subacute Thyroiditis.

    Science.gov (United States)

    Sheraz, Faizan; Tahir, Hassan; Saqi, Jannavi; Daruwalla, Vistasp

    2016-06-01

    The majority of dengue viral infections are asymptomatic, though symptoms may range from self-limiting febrile illness to life threatening hemorrhagic manifestations. As the burden of disease is dramatically rising in recent years, more patients with atypical presentations and rare complications are increasingly reported. Dengue virus may rarely involve different organ systems including CNS, liver, and heart. However, involvement of eye and thyroid is extremely rare. We present a case of 32-year old patient who presented with conjunctivitis and subacute thyroiditis and was found to have dengue viral infection as the cause of these conditions. PMID:27376214

  7. Atypical presentation of sporotrichosis: report of three cases

    Directory of Open Access Journals (Sweden)

    Melissa Orzechowski Xavier

    2013-01-01

    Full Text Available Sporotrichosis occurs after fungal implantation of Sporothrix spp. in the skin, and is the main subcutaneous mycosis in Latin America. Here we describe three atypical cases of the disease. The first case report an extra-cutaneous occurrence of the disease with joint infection; the second one describes a patient with bilateral lymphocutaneous form of sporotrichosis; and the third shows a zoonotic cutaneous case with the development of an erythema nodosum as a hypersensitivity reaction. These cases show the disease importance on the region and the necessity of fungal culture to the diagnosis confirmation.

  8. Quantitative methods for somatosensory evaluation in atypical odontalgia

    DEFF Research Database (Denmark)

    Porporatti, André Luís; Costa, Yuri Martins; Stuginski-Barbosa, Juliana;

    2015-01-01

    A systematic review was conducted to identify reliable somatosensory evaluation methods for atypical odontalgia (AO) patients. The computerized search included the main databases (MEDLINE, EMBASE, and Cochrane Library). The studies included used the following quantitative sensory testing (QST......) methods: mechanical detection threshold (MDT), mechanical pain threshold (MPT) (pinprick), pressure pain threshold (PPT), dynamic mechanical allodynia with a cotton swab (DMA1) or a brush (DMA2), warm detection threshold (WDT), cold detection threshold (CDT), heat pain threshold (HPT), cold pain detection...... compared with healthy subjects. In clinical settings, the most reliable evaluation method for AO in patients with persistent idiopathic facial pain would be intraindividual assessments using HPT or mechanical allodynia tests....

  9. AMELANOTIC MELANOMA WITH ATYPICAL CLINICAL PRESENTATION AND MULTIPLE METASTASIS

    Directory of Open Access Journals (Sweden)

    Revathy

    2014-11-01

    Full Text Available A 52 year old woman presented with a history of asymptomatic skin lesions over left leg for the past 4 months. On examination she had multiple skin coloured papules and plaques over left leg. Oedema was also seen over left leg. Histopathology and immunohistochemistry proved the diagnosis of malignant melanoma. Radiological investigation showed metastasis to lung, liver and brain. The patient was asymptomatic at the time of admission but she developed rapid metastasis within a very short span of time. This case is reported for the rare atypical presentation of malignant melanoma.

  10. Thrombotic microangiopathy: focus on atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Sperati, C John; Moliterno, Alison R

    2015-06-01

    Thrombotic microangiopathies (TMA) such as atypical hemolytic uremic syndrome (aHUS) have evolved from rare, fulminant childhood afflictions to uncommon diseases with acute and chronic phases involving both children and adults. Breakthroughs in complement and coagulation regulation have allowed redefinition of specific entities despite substantial phenotypic mimicry. Reconciliation of phenotypes and delivery of life saving therapies require a multidisciplinary team of experts. The purpose of this review is to describe advances in the molecular pathophysiology of aHUS and to share the 2014 experience of the multidisciplinary Johns Hopkins TMA Registry in applying diagnostic assays, reporting disease associations, and genetic testing. PMID:26043391

  11. A family of congenital hepatic fibrosis and atypical retinitis pigmentosa

    Directory of Open Access Journals (Sweden)

    Sunil Pawar

    2015-11-01

    Full Text Available Congenital hepatic fibrosis is a rare cause of portal hypertension and esophageal varices in children. We report cases of siblings with biopsy proven congenital hepatic fibrosis and with atypical retinitis pigmentosa. They presented with repeated episodes of jaundice along with progressive decrease of vision in night. They had hepatosplenomegaly and portal hypertension with esophageal varices. One of the siblings had a large regenerating nodule replacing the entire right lobe of the liver and other one developed repeated hematemesis. This constellation of diagnosis belongs to the ciliopathy group of disorders. The spectrum of ciliopathy disorders has been evolving, and it varies from mild to severe manifestations.

  12. MAP Kinase Cascades in Plant Innate Immunity

    Directory of Open Access Journals (Sweden)

    Magnus Wohlfahrt Rasmussen

    2012-07-01

    Full Text Available Plant mitogen-activated protein kinase (MAPK cascades generally transduce extracellular stimuli into cellular responses. These stimuli include the perception of pathogen-associated molecular patterns (PAMPs by host transmembrane pattern recognition receptors (PRRs which trigger MAPK-dependent innate immune responses. In the model Arabidopsis, molecular genetic evidence implicates a number of MAPK cascade components in PAMP signaling, and in responses to immunity-related phytohormones such as ethylene, jasmonate and salicylate. In a few cases, cascade components have been directly linked to the transcription of target genes or to the regulation of phytohormone synthesis. Thus MAPKs are obvious targets for bacterial effector proteins and are likely guardees of resistance (R proteins, which mediate defense signaling in response to the action of effectors, or effector-triggered immunity (ETI. This mini-review discusses recent progress in this field with a focus on the Arabidopsis MAPKs MPK3, 4, 6 and 11 in their apparent pathways.

  13. Regulation of Akt/PKB activity by P21-activated Kinase in Cardiomyocytes

    OpenAIRE

    Mao, Kai; Kobayashi, Satoru; Jaffer, Zahara M.; Huang, Yuan; Volden, Paul; Chernoff, Jonathan; Liang, Qiangrong

    2007-01-01

    Akt/PKB is a critical regulator of cardiac function and morphology, and its activity is governed by dual phosphorylation at active loop (Thr308) by phosphoinositide-dependent protein kinase-1 (PDK1) and at carboxyl-terminal hydrophobic motif (Ser473) by a putative PDK2. P21-activated kinase-1 (Pak1) is a serine/threonine protein kinase implicated in the regulation of cardiac hypertrophy and contractility, and was shown previously to activate Akt through an undefined mechanism. Here we report ...

  14. The Rho kinases I and II regulate different aspects of myosin II activity

    DEFF Research Database (Denmark)

    Yoneda, Atsuko; Multhaupt, Hinke A B; Couchman, John R

    2005-01-01

    The homologous mammalian rho kinases (ROCK I and II) are assumed to be functionally redundant, based largely on kinase construct overexpression. As downstream effectors of Rho GTPases, their major substrates are myosin light chain and myosin phosphatase. Both kinases are implicated in microfilament...... persistent ROCK II and guanine triphosphate-bound RhoA. In contrast, the microfilament cytoskeleton was enhanced by ROCK II down-regulation. Phagocytic uptake of fibronectin-coated beads was strongly down-regulated in ROCK II-depleted cells but not those lacking ROCK I. These effects originated in part from...

  15. Phosphorylation of Human Choline Kinase Beta by Protein Kinase A: Its Impact on Activity and Inhibition

    Science.gov (United States)

    Chang, Ching Ching; Few, Ling Ling; Konrad, Manfred; See Too, Wei Cun

    2016-01-01

    Choline kinase beta (CKβ) is one of the CK isozymes involved in the biosynthesis of phosphatidylcholine. CKβ is important for normal mitochondrial function and muscle development as the lack of the ckβ gene in human and mice results in the development of muscular dystrophy. In contrast, CKα is implicated in tumorigenesis and has been extensively studied as an anticancer target. Phosphorylation of human CKα was found to regulate the enzyme’s activity and its subcellular location. This study provides evidence for CKβ phosphorylation by protein kinase A (PKA). In vitro phosphorylation of CKβ by PKA was first detected by phosphoprotein staining, as well as by in-gel kinase assays. The phosphorylating kinase was identified as PKA by Western blotting. CKβ phosphorylation by MCF-7 cell lysate was inhibited by a PKA-specific inhibitor peptide, and the intracellular phosphorylation of CKβ was shown to be regulated by the level of cyclic adenosine monophosphate (cAMP), a PKA activator. Phosphorylation sites were located on CKβ residues serine-39 and serine-40 as determined by mass spectrometry and site-directed mutagenesis. Phosphorylation increased the catalytic efficiencies for the substrates choline and ATP about 2-fold, without affecting ethanolamine phosphorylation, and the S39D/S40D CKβ phosphorylation mimic behaved kinetically very similar. Remarkably, phosphorylation drastically increased the sensitivity of CKβ to hemicholinium-3 (HC-3) inhibition by about 30-fold. These findings suggest that CKβ, in concert with CKα, and depending on its phosphorylation status, might play a critical role as a druggable target in carcinogenesis. PMID:27149373

  16. Venus kinase receptors: prospects in signaling and biological functions of these invertebrate kinases.

    Science.gov (United States)

    Dissous, Colette; Morel, Marion; Vanderstraete, Mathieu

    2014-01-01

    Venus kinase receptors (VKRs) form a family of invertebrate receptor tyrosine kinases (RTKs) initially discovered in the parasitic platyhelminth Schistosoma mansoni. VKRs are single transmembrane receptors that contain an extracellular venus fly trap structure similar to the ligand-binding domain of G protein-coupled receptors of class C, and an intracellular tyrosine kinase domain close to that of insulin receptors. VKRs are found in a large variety of invertebrates from cnidarians to echinoderms and are highly expressed in larval stages and in gonads, suggesting a role of these proteins in embryonic and larval development as well as in reproduction. VKR gene silencing could demonstrate the function of these receptors in oogenesis as well as in spermatogenesis in S. mansoni. VKRs are activated by amino acids and are highly responsive to arginine. As many other RTKs, they form dimers when activated by ligands and induce intracellular pathways involved in protein synthesis and cellular growth, such as MAPK and PI3K/Akt/S6K pathways. VKRs are not present in vertebrates or in some invertebrate species. Questions remain open about the origin of this little-known RTK family in evolution and its role in emergence and specialization of Metazoa. What is the meaning of maintenance or loss of VKR in some phyla or species in terms of development and physiological functions? The presence of VKRs in invertebrates of economical and medical importance, such as pests, vectors of pathogens, and platyhelminth parasites, and the implication of these RTKs in gametogenesis and reproduction processes are valuable reasons to consider VKRs as interesting targets in new programs for eradication/control of pests and infectious diseases, with the main advantage in the case of parasite targeting that VKR counterparts are absent from the vertebrate host kinase panel.

  17. Toward the rational design of protein kinase casein kinase-2 inhibitors.

    Science.gov (United States)

    Sarno, Stefania; Moro, Stefano; Meggio, Flavio; Zagotto, Giuseppe; Dal Ben, Diego; Ghisellini, Paola; Battistutta, Roberto; Zanotti, Giuseppe; Pinna, Lorenzo A

    2002-01-01

    Casein kinase-2 (CK2) probably is the most pleiotropic member of the protein kinase family, with more than 200 substrates known to date. Unlike the great majority of protein kinases, which are tightly regulated enzymes, CK2 is endowed with high constitutive activity, a feature that is suspected to underlie its oncogenic potential and possible implication in viral infections. This makes CK2 an attractive target for anti-neoplastic and antiviral drugs. Here, we present an overview of our present knowledge about CK2 inhibitors, with special reference to the information drawn from two recently solved crystal structures of CK2alpha in complex with emodin and with 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), this latter being the most specific CK2 inhibitor known to date. A comparison with a series of anthraquinone and xanthenone derivatives highlights the crucial relevance of the hydroxyl group at position 3 for inhibition by emodin, and discloses the possibility of increasing the inhibitory potency by placing an electron withdrawing group at position 5. We also present mutational data corroborating the relevance of two hydrophobic residues unique to CK2, Val66 and Ile174, for the interactions with emodin and TBB, but not with the flavonoid inhibitors quercetin and fisetin. In particular, the CK2alpha mutant V66A displays 27- and 11-fold higher IC(50) values with emodin and TBB, respectively, as compared with the wild-type, while the IC(50) value with quercetin is unchanged. The data presented pave the road toward the rational design of more potent and selective inhibitors of CK2 and the generation of CK2 mutants refractory to inhibition, useful to probe the implication of CK2 in specific cellular functions. PMID:12191608

  18. MAP Kinases in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Yongliang Zhang; Chen Dong

    2005-01-01

    MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses. There are three main families of MAPKs in mammals. Each of them has its own activators, inactivators, substrates and scaffolds, which altogether form a fine signaling network in response to different extracellular or intracellular stimulation. In this review, we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses.

  19. MAP Kinases in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    YongliangZhang; ChenDong

    2005-01-01

    MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses. There are three main families of MAPKs in mammals. Each of them has its own activators, inactivators, substrates and scaffolds, which altogether form a fine signaling network in response to different extracellular or intracellular stimulation. In this review, we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses. Cellular & Molecular Immunology. 2005;2(1):20-27.

  20. Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15

    Directory of Open Access Journals (Sweden)

    Sigman Marian

    2008-01-01

    Full Text Available Abstract Background Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15] that has been called inverted duplication 15 or isodicentric 15 [idic(15], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR that are found clustered in the region. Five recurrent breakpoints have been described in most cases of segmental aneuploidy of chromosome 15q11-q13 and previous studies have shown that most idic(15 chromosomes arise through BP3:BP3 or BP4:BP5 recombination events. Results Here we describe four duplication chromosomes that show evidence of atypical recombination events that involve regions outside the common breakpoints. Additionally, in one patient with a mosaic complex der(15, we examined homologous pairing of chromosome 15q11-q13 alleles by FISH in a region of frontal cortex, which identified mosaicism in this tissue and also demonstrated pairing of the signals from the der(15 and the normal homologues. Conclusion Involvement of atypical BP in the generation of idic(15 chromosomes can lead to considerable structural heterogeneity.

  1. Fungal rhinosinusitis with atypical presentation - a report of two cases

    Institute of Scientific and Technical Information of China (English)

    Rafael da Costa Monsanto; Rodrigo Silva Orem; Fernanda Resende e Silva; Fabio Hiroshi Okuyama; Fabio Tadeu Moura Lorenzetti

    2015-01-01

    Rhinosinusitis affects approximately 20% of the population, and the chronic rhinosinusitis represents over 90% of all cases of rhinosinusitis. The correct diagnosis is important for proper treatment and to predict its evolution. This study presents two cases of atypical frontal sinus disease, which the follow-up revealed a diagnosis of fungal rhinosinusitis. The present study aims to describe the cases of two patients with atypical lesions on the left frontal sinus; the treatment options, surgical approach, results, diagnosis and follow-up are further discussed. A significant increase in the reported cases of fungal rhinosinusitis has been seen in the last two decades, justified by the use of broad-spectrum antibiotics and steroids, as well as the increased number of immunocompromised individuals. This study reports the cases of two patients with a type of fungal rhinosinusitis named "fungal ball", characterized by a tangle of hyphae in the sinuses without tissue invasion. The treatment included surgical removal of the fungal infectious process with aeration of the affected sinus, and the procedure was successfully performed in our patients.

  2. Atypical oculopalatal tremor as the presentation of vertebral artery dolichoectasia

    Science.gov (United States)

    Vanikieti, Kavin; Cheecharoen, Piyaphon; Jindahra, Panitha; Lueangaram, Sirin; Padungkiatsagul, Tanyatuth

    2016-01-01

    Vertebrobasilar dolichoectasia (VBD) is a rare dilative arteriopathy defined as elongation or widening of the intracranial vertebral and/or basilar arteries. The prevalence ranges from 0.06% to 5.8%. The majority of VBDs are asymptomatic. Downbeat nystagmus has been reported as a component of an infrequent ocular movement disorder in VBD. Nevertheless, oculopalatal tremor (OPT), delayed sequelae of a brainstem lesion, has never been demonstrated in VBD cases. Synchronized rhythmic involuntary contractions of the soft palate with an ocular pendular nystagmus, predominantly vertical pendular nystagmus, are the hallmark presentation. Our case demonstrated a 50-year-old female who presented with 3-month history of oscillopsia. Examination showed binocular conjugate torsional jerk nystagmus simultaneous with a contraction of the soft palate, defined as an atypical OPT, resulting from dolichoectatic left vertebral artery compressing on medulla, demonstrated by magnetic resonance imaging. Bilateral conjugate torsional jerk nystagmus simultaneous with palatal tremor, considering as an atypical OPT, should be included as one of the symptomatic presentations of vertebral artery dolichoectasia in spite of its rarity. PMID:27660495

  3. Atypical dermatophilosis of sheep in Kenya : clinical communication

    Directory of Open Access Journals (Sweden)

    J.K. Wabacha

    2007-06-01

    Full Text Available An outbreak of an atypical form of ovine dermatophilosis affecting the lips and muzzle with a very high morbidity in weaners and hoggets in Kenya is reported. Clinical diagnosis of ovine dermatophilosis was made and confirmed by direct microscopic examination as well as isolation and identification of Dermatophilus congolensis from scab material from the affected sheep. The morbidity rate within the flock was 31.8 % (237 / 745 with 98.3 % (233 / 237 of the affected sheep being weaners and hoggets. No fatalities were recorded. The lesions, confined in the lips and the muzzle, were swelling of both the upper and lower lips, circumscribed lumps in the skin of both the upper and lower lips, oedema of the head and the submandibular area and scabs and crusts on the lips and muzzle. Within 1 week following treatment with long acting oxytetracycline (20 % at a rate of 20 mg/kg body weight, intramuscularly and a topical application of oxytetracycline spray, lumps regressed in size and were covered by dark-brown scabs. Removal of the dark-brown scabs revealed erythematous areas covered with purulent material and horny erythematous projections (papillae projecting from the surfaces. Within the 2nd week, the horny erythematous projections formed greyish scabs, which later peeled off leaving alopaecic areas around the lips. The paper highlights atypical dermatophilosis of sheep and we believe that this is the first published report of an outbreak of ovine dermatophilosis in Kenya.

  4. Atypical streptococcal infection of gingiva associated with chronic mouth breathing.

    Science.gov (United States)

    Haytac, M Cenk; Oz, I Attila

    2007-01-01

    Streptococcal infections of oral tissues are mainly seen in young children who experience a variety of upper respiratory tract infections. The disease is characterized by fever, lymphadenopathy, and ulcers on the gingiva, lips, and tonsils. This case report presents an atypical streptococcal infection of the gingiva in an 18-year-old man. The patient was referred to the periodontology department complaining of a 2-month history of gingival enlargement. He had persistent fever (39.5 degrees C) and general malaise for 2 weeks. Intraoral examination revealed extremely inflamed and enlarged gingiva with spontaneous bleeding and suppuration. Based on the otolaryngologic consultation and the hematologic, immunologic, and microbiologic tests, the final diagnosis was an atypical streptococcal gingivitis with chronic adenoid-related mouth breathing and oral hygiene neglect as contributing factors. Treatment consisted of a broad-spectrum antibiotic regimen, supragingival and subgingival debridement, adenoidectomy, and scaling and root planing. A good response to nonsurgical therapy was achieved despite poor patient compliance, and no recurrence of gingival enlargement was observed after 1 year. Streptococcal gingivitis should be included in the differential diagnosis of suppurative gingival enlargements. Furthermore, chronic mouth breathing may initiate and/or contribute to this disease.

  5. Atypical antipsychotics in the treatment of early-onset schizophrenia

    Directory of Open Access Journals (Sweden)

    Hrdlicka M

    2015-04-01

    Full Text Available Michal Hrdlicka, Iva Dudova Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Atypical antipsychotics (AAPs have been successfully used in early-onset schizophrenia (EOS. This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. Keywords: early-onset schizophrenia, atypical antipsychotics, efficacy, onset of action, weight gain

  6. Breast Metastases from Extramammary Malignancies: Typical and Atypical Ultrasound Features

    Energy Technology Data Exchange (ETDEWEB)

    Mun, Sung Hee [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Department of Radiology, Catholic University of Daegu College of Medicine, Daegu 712-702 (Korea, Republic of); Ko, Eun Young; Han, Boo-Kyung; Shin, Jung Hee [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Kim, Suk Jung [Department of Radiology, Inje University College of Medicine, Busan Paik Hospital, Busan 614-735 (Korea, Republic of); Cho, Eun Yoon [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)

    2014-07-01

    Breast metastases from extramammary malignancies are uncommon. The most common sources are lymphomas/leukemias and melanomas. Some of the less common sources include carcinomas of the lung, ovary, and stomach, and infrequently, carcinoid tumors, hypernephromas, carcinomas of the liver, tonsil, pleura, pancreas, cervix, perineum, endometrium and bladder. Breast metastases from extramammary malignancies have both hematogenous and lymphatic routes. According to their routes, there are common radiological features of metastatic diseases of the breast, but the features are not specific for metastases. Typical ultrasound (US) features of hematogenous metastases include single or multiple, round to oval shaped, well-circumscribed hypoechoic masses without spiculations, calcifications, or architectural distortion; these masses are commonly located superficially in subcutaneous tissue or immediately adjacent to the breast parenchyma that is relatively rich in blood supply. Typical US features of lymphatic breast metastases include diffusely and heterogeneously increased echogenicities in subcutaneous fat and glandular tissue and a thick trabecular pattern with secondary skin thickening, lymphedema, and lymph node enlargement. However, lesions show variable US features in some cases, and differentiation of these lesions from primary breast cancer or from benign lesions is difficult. In this review, we demonstrate various US appearances of breast metastases from extramammary malignancies as typical and atypical features, based on the results of US and other imaging studies performed at our institution. Awareness of the typical and atypical imaging features of these lesions may be helpful to diagnose metastatic lesions of the breast.

  7. Breast Metastases from Extramammary Malignancies: Typical and Atypical Ultrasound Features

    International Nuclear Information System (INIS)

    Breast metastases from extramammary malignancies are uncommon. The most common sources are lymphomas/leukemias and melanomas. Some of the less common sources include carcinomas of the lung, ovary, and stomach, and infrequently, carcinoid tumors, hypernephromas, carcinomas of the liver, tonsil, pleura, pancreas, cervix, perineum, endometrium and bladder. Breast metastases from extramammary malignancies have both hematogenous and lymphatic routes. According to their routes, there are common radiological features of metastatic diseases of the breast, but the features are not specific for metastases. Typical ultrasound (US) features of hematogenous metastases include single or multiple, round to oval shaped, well-circumscribed hypoechoic masses without spiculations, calcifications, or architectural distortion; these masses are commonly located superficially in subcutaneous tissue or immediately adjacent to the breast parenchyma that is relatively rich in blood supply. Typical US features of lymphatic breast metastases include diffusely and heterogeneously increased echogenicities in subcutaneous fat and glandular tissue and a thick trabecular pattern with secondary skin thickening, lymphedema, and lymph node enlargement. However, lesions show variable US features in some cases, and differentiation of these lesions from primary breast cancer or from benign lesions is difficult. In this review, we demonstrate various US appearances of breast metastases from extramammary malignancies as typical and atypical features, based on the results of US and other imaging studies performed at our institution. Awareness of the typical and atypical imaging features of these lesions may be helpful to diagnose metastatic lesions of the breast

  8. Differentiation of regions with atypical oligonucleotide composition in bacterial genomes

    Directory of Open Access Journals (Sweden)

    Reva Oleg N

    2005-10-01

    Full Text Available Abstract Background Complete sequencing of bacterial genomes has become a common technique of present day microbiology. Thereafter, data mining in the complete sequence is an essential step. New in silico methods are needed that rapidly identify the major features of genome organization and facilitate the prediction of the functional class of ORFs. We tested the usefulness of local oligonucleotide usage (OU patterns to recognize and differentiate types of atypical oligonucleotide composition in DNA sequences of bacterial genomes. Results A total of 163 bacterial genomes of eubacteria and archaea published in the NCBI database were analyzed. Local OU patterns exhibit substantial intrachromosomal variation in bacteria. Loci with alternative OU patterns were parts of horizontally acquired gene islands or ancient regions such as genes for ribosomal proteins and RNAs. OU statistical parameters, such as local pattern deviation (D, pattern skew (PS and OU variance (OUV enabled the detection and visualization of gene islands of different functional classes. Conclusion A set of approaches has been designed for the statistical analysis of nucleotide sequences of bacterial genomes. These methods are useful for the visualization and differentiation of regions with atypical oligonucleotide composition prior to or accompanying gene annotation.

  9. Atypical Face Perception in Autism: A Point of View?

    Science.gov (United States)

    Morin, Karine; Guy, Jacalyn; Habak, Claudine; Wilson, Hugh R; Pagani, Linda; Mottron, Laurent; Bertone, Armando

    2015-10-01

    Face perception is the most commonly used visual metric of social perception in autism. However, when found to be atypical, the origin of face perception differences in autism is contentious. One hypothesis proposes that a locally oriented visual analysis, characteristic of individuals with autism, ultimately affects performance on face tasks where a global analysis is optimal. The objective of this study was to evaluate this hypothesis by assessing face identity discrimination with synthetic faces presented with and without changes in viewpoint, with the former condition minimizing access to local face attributes used for identity discrimination. Twenty-eight individuals with autism and 30 neurotypical participants performed a face identity discrimination task. Stimuli were synthetic faces extracted from traditional face photographs in both front and 20° side viewpoints, digitized from 37 points to provide a continuous measure of facial geometry. Face identity discrimination thresholds were obtained using a two-alternative, temporal forced choice match-to-sample paradigm. Analyses revealed an interaction between group and condition, with group differences found only for the viewpoint change condition, where performance in the autism group was decreased compared to that of neurotypical participants. The selective decrease in performance for the viewpoint change condition suggests that face identity discrimination in autism is more difficult when access to local cues is minimized, and/or when dependence on integrative analysis is increased. These results lend support to a perceptual contribution of atypical face perception in autism. PMID:25683613

  10. Current status of atypical antipsychotics for the treatment of fibromyalgia.

    Science.gov (United States)

    Rico-Villademoros, F; Calandre, E P; Slim, M

    2014-06-01

    The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms.

  11. Benign occipital lobe seizures: Natural progression and atypical evolution

    Directory of Open Access Journals (Sweden)

    Prithika Chary

    2013-01-01

    Full Text Available Benign occipital seizure syndromes are benign childhood epilepsy syndromes and are mainly of two types, Panayiotopoulos syndrome, an autonomic epilepsy and idiopathic childhood occipital epilepsy of Gastaut (ICOE-G including the idiopathic photosensitive occipital lobe epilepsy. Although both these types are categorized as occipital seizures, they are distinct in presentation and management. They can also be tricky to diagnose as visual symptoms may not always be the presenting feature and it is also not very easy to elicit visual hallucinations during history taking. These seizures have a good response to treatment; however, there could be atypical evolution and refractoriness to treatment especially with ICOE-G. We describe three children who presented with visual and non-visual symptoms and the electroencephalography (EEG in all the three cases showed occipital paroxysms. We have emphasized the clues in the clinical history and EEG leading to the diagnosis of these distinct epilepsy syndromes. We have also discussed the natural course of these epilepsy syndromes with some atypical evolution, which clinicians need to be aware of during treatment of these children.

  12. Dual mechanism of action of the atypical tetracycline chelocardin.

    Science.gov (United States)

    Stepanek, Jennifer J; Lukežič, Tadeja; Teichert, Ines; Petković, Hrvoje; Bandow, Julia E

    2016-06-01

    Classical tetracyclines targeting the protein biosynthesis machinery are commonly applied in human and veterinary medicine. The development and spread of resistance seriously compromise the successful treatment of bacterial infections. The atypical tetracycline chelocardin holds promise as it retains activity against tetracycline-resistant strains. It has been suggested that chelocardin targets the bacterial membrane, thus differing in mode of action from that of classical tetracyclines. We investigated the mechanism of action of chelocardin using global proteome analysis. The proteome profiles after sublethal chelocardin stress were compared to a reference compendium containing antibiotic response profiles of Bacillus subtilis. This approach revealed a concentration-dependent dual mechanism of action. At low concentrations, like classical tetracyclines, chelocardin induces the proteomic signature for peptidyl transferase inhibition demonstrating that protein biosynthesis inhibition is the dominant physiological challenge. At higher concentrations B. subtilis mainly responds to membrane stress indicating that at clinically relevant concentrations the membrane is the main antibiotic target of chelocardin. Studying the effects on the membrane in more detail, we found that chelocardin causes membrane depolarization but does not lead to formation of large pores. We conclude that at growth inhibiting doses chelocardin not only targets protein biosynthesis but also corrupts the integrity of the bacterial membrane. This dual mechanism of action might prove beneficial in slowing the development of new resistance mechanisms against this atypical tetracycline. PMID:26969785

  13. Protein Crystals of Raf Kinase

    Science.gov (United States)

    1995-01-01

    This image shows crystals of the protein raf kinase grown on Earth (photo a) and on USML-2 (photo b). The space-grown crystals are an order of magnitude larger. Principal Investigator: Dan Carter of New Century Pharmaceuticals

  14. Atypical Findings in Massive Bupropion Overdose: A Case Report and Discussion of Psychopharmacologic Issues.

    Science.gov (United States)

    Zhu, Yuanjia; Kolawole, Tiwalola; Jimenez, Xavier F

    2016-09-01

    Bupropion is an atypical antidepressant that is structurally similar to amphetamines. Its primary toxic effects include seizure, sinus tachycardia, hypertension, and agitation; however, at higher amounts of ingestion, paradoxical cardiac effects are seen. We report the case of a 21-year-old woman who ingested 13.5 g of bupropion, a dose higher than any other previously reported. The patient presented with seizure, sinus tachycardia with prolonged QTc and QRS intervals, dilated pupils, and agitation. Four days after overdose, the patient's sinus tachycardia and prolonged QTc and QRS intervals resolved with symptomatic management, but she soon developed sinus bradycardia, hypotension, and mild transaminitis. With continued conservative management and close monitoring, her sinus bradycardia resolved 8 days after the overdose. The transaminitis resolved 12 days after the overdose. Our findings are consistent with previously reported toxic effects associated with common overdose amounts of bupropion. In addition, we have observed transient cardiotoxicity manifesting as sinus bradycardia associated with massive bupropion overdose. These findings are less frequently reported and must be considered when managing patients with massive bupropion overdose. We review the psychopharmacologic implications of this and comment on previous literature. PMID:27648505

  15. Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome.

    Science.gov (United States)

    Soura, Efthymia; Eliades, Philip J; Shannon, Kristen; Stratigos, Alexander J; Tsao, Hensin

    2016-03-01

    Malignant melanoma is considered the most lethal skin cancer if it is not detected and treated during its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (ie, unilateral lineage, multigenerational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. These patients have a high risk of developing multiple primary melanomas and internal organ malignancies, especially pancreatic cancer; therefore, a multidisciplinary approach is necessary in many cases. The value of dermoscopic examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first-degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. This must be performed with care, however, and only by qualified individuals trained in cancer risk analysis.

  16. Multimodal imaging of temporal processing in typical and atypical language development.

    Science.gov (United States)

    Kovelman, Ioulia; Wagley, Neelima; Hay, Jessica S F; Ugolini, Margaret; Bowyer, Susan M; Lajiness-O'Neill, Renee; Brennan, Jonathan

    2015-03-01

    New approaches to understanding language and reading acquisition propose that the human brain's ability to synchronize its neural firing rate to syllable-length linguistic units may be important to children's ability to acquire human language. Yet, little evidence from brain imaging studies has been available to support this proposal. Here, we summarize three recent brain imaging (functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG)) studies from our laboratories with young English-speaking children (aged 6-12 years). In the first study (fNIRS), we used an auditory beat perception task to show that, in children, the left superior temporal gyrus (STG) responds preferentially to rhythmic beats at 1.5 Hz. In the second study (fMRI), we found correlations between children's amplitude rise-time sensitivity, phonological awareness, and brain activation in the left STG. In the third study (MEG), typically developing children outperformed children with autism spectrum disorder in extracting words from rhythmically rich foreign speech and displayed different brain activation during the learning phase. The overall findings suggest that the efficiency with which left temporal regions process slow temporal (rhythmic) information may be important for gains in language and reading proficiency. These findings carry implications for better understanding of the brain's mechanisms that support language and reading acquisition during both typical and atypical development.

  17. Visual Exemplification and Skin Cancer: The Utility of Exemplars in Promoting Skin Self-Exams and Atypical Nevi Identification.

    Science.gov (United States)

    King, Andy J

    2016-07-01

    The present article reports an experiment investigating untested propositions of exemplification theory in the context of messages promoting early melanoma detection. The study tested visual exemplar presentation types, incorporating visual persuasion principles into the study of exemplification theory and strategic message design. Compared to a control condition, representative visual exemplification was more effective at increasing message effectiveness by eliciting a surprise response, which is consistent with predictions of exemplification theory. Furthermore, participant perception of congruency between the images and text interacted with the type of visual exemplification to explain variation in message effectiveness. Different messaging strategies influenced decision making as well, with the presentation of visual exemplars resulting in people judging the atypicality of moles more conservatively. Overall, results suggest that certain visual messaging strategies may result in unintended effects of presenting people information about skin cancer. Implications for practice are discussed. PMID:27337542

  18. Structure and Ubiquitination-Dependent Activation of TANK-Binding Kinase 1

    Directory of Open Access Journals (Sweden)

    Daqi Tu

    2013-03-01

    Full Text Available Upon stimulation by pathogen-associated inflammatory signals, TANK-binding kinase 1 (TBK1 induces type I interferon expression and modulates nuclear factor κB (NF-κB signaling. Here, we describe the 2.4 Å-resolution crystal structure of nearly full-length TBK1 in complex with specific inhibitors. The structure reveals a dimeric assembly created by an extensive network of interactions among the kinase, ubiquitin-like, and scaffold/dimerization domains. An intact TBK1 dimer undergoes K63-linked polyubiquitination on lysines 30 and 401, and these modifications are required for TBK1 activity. The ubiquitination sites and dimer contacts are conserved in the close homolog inhibitor of κB kinase ∊ (IKK∊ but not in IKKβ, a canonical IKK that assembles in an unrelated manner. The multidomain architecture of TBK1 provides a structural platform for integrating ubiquitination with kinase activation and IRF3 phosphorylation. The structure of TBK1 will facilitate studies of the atypical IKKs in normal and disease physiology and further the development of more specific inhibitors that may be useful as anticancer or anti-inflammatory agents.

  19. Elucidating the role of the TRPM7 alpha-kinase: TRPM7 kinase inactivation leads to magnesium deprivation resistance phenotype in mice.

    Science.gov (United States)

    Ryazanova, Lillia V; Hu, Zhixian; Suzuki, Sayuri; Chubanov, Vladimir; Fleig, Andrea; Ryazanov, Alexey G

    2014-12-23

    TRPM7 is an unusual bi-functional protein containing an ion channel covalently linked to a protein kinase domain. TRPM7 is implicated in regulating cellular and systemic magnesium homeostasis. While the biophysical properties of TRPM7 ion channel and its function are relatively well characterized, the function of the TRPM7 enzymatically active kinase domain is not understood yet. To investigate the physiological role of TRPM7 kinase activity, we constructed mice carrying an inactive TRPM7 kinase. We found that these mice were resistant to dietary magnesium deprivation, surviving three times longer than wild type mice; also they displayed decreased chemically induced allergic reaction. Interestingly, mutant mice have lower magnesium bone content compared to wild type mice when fed regular diet; unlike wild type mice, mutant mice placed on magnesium-depleted diet did not alter their bone magnesium content. Furthermore, mouse embryonic fibroblasts isolated from TRPM7 kinase-dead animals exhibited increased resistance to magnesium deprivation and oxidative stress. Finally, electrophysiological data revealed that the activity of the kinase-dead TRPM7 channel was not significantly altered. Together, our results suggest that TRPM7 kinase is a sensor of magnesium status and provides coordination of cellular and systemic responses to magnesium deprivation.

  20. Interleukin-17 induces an atypical M2-like macrophage subpopulation that regulates intestinal inflammation.

    Directory of Open Access Journals (Sweden)

    Kenichiro Nishikawa

    Full Text Available Interleukin 17 (IL-17 is a pleiotropic cytokine that acts on both immune and non-immune cells and is generally implicated in inflammatory and autoimmune diseases. Although IL-17 as well as their source, mainly but not limited to Th17 cells, is also abundant in the inflamed intestine, the role of IL-17 in inflammatory bowel disease remains controversial. In the present study, by using IL-17 knockout (KO mice, we investigated the role of IL-17 in colitis, with special focus on the macrophage subpopulations. Here we show that IL-17KO mice had increased susceptibility to DSS-induced colitis which was associated with decrease in expression of mRNAs implicated in M2 and/or wound healing macrophages, such as IL-10, IL-1 receptor antagonist, arginase 1, cyclooxygenase 2, and indoleamine 2,3-dioxygenase. Lamina propria leukocytes from inflamed colon of IL-17KO mice contained fewer CD11b+Ly6C+MHC Class II+ macrophages, which were derived, at least partly, from blood monocytes, as compared to those of WT mice. FACS-purified CD11b+ cells from WT mice, which were more abundant in Ly6C+MHC Class II+ cells, expressed increased levels of genes associated M2/wound healing macrophages and also M1/proinflammatory macrophages. Depletion of this population by topical administration of clodronate-liposome in the colon of WT mice resulted in the exacerbation of colitis. These results demonstrate that IL-17 confers protection against the development of severe colitis through the induction of an atypical M2-like macrophage subpopulation. Our findings reveal a previously unappreciated mechanism by which IL-17 exerts a protective function in colitis.

  1. Effects of Physical Atypicality on Children's Social Identities and Intergroup Attitudes

    Science.gov (United States)

    Patterson, Meagan M.; Bigler, Rebecca S.

    2007-01-01

    Individuals vary in the degree to which they are representative, or typical, of their social groups. To investigate the effects of atypicality on intergroup attitudes, elementary-school-age children (N = 97) attending a summer school program were assigned to novel color groups that included typical (blue or green) and atypical (light blue or light…

  2. The involvement of limbic structures in typical and atypical absence epilepsy

    NARCIS (Netherlands)

    Onat, F.Y.; Luijtelaar, E.L.J.M. van; Nehlig, A.; Snead, O.C.

    2013-01-01

    Typical and atypical seizures of absence epilepsy are thought to be generated by a rhythmogenic interplay between the cortex and the thalamus. However, the question remains as to which other subcortical and extrathalamic structures are involved in the pathophysiology of typical and atypical absence

  3. Atypical speech and language development : a consensus study on clinical signs in the Netherlands

    NARCIS (Netherlands)

    Visser-Bochane, Margot I; Gerrits, Ellen; van der Schans, Cees P; Reijneveld, Sijmen A; Luinge, Margreet R

    2016-01-01

    BACKGROUND: Atypical speech and language development is one of the most common developmental difficulties in young children. However, which clinical signs characterize atypical speech-language development at what age is not clear. AIM: To achieve a national and valid consensus on clinical signs and

  4. Automated flagging influences the inconsistency and bias of band cell and atypical lymphocyte morphological differentials.

    NARCIS (Netherlands)

    Meer, W. van der; Scott, C.S.; Keijzer, M.H. de

    2004-01-01

    This study evaluated inter- and intra-observer variabilities of band cell and atypical lymphocyte differentials and the influence of instrument flagging information on resulting microscopic differentials. Five stained slides with a range of band cell counts and five with variable numbers of atypical

  5. Traditional and Atypical Presentations of Anxiety in Youth with Autism Spectrum Disorder

    Science.gov (United States)

    Kerns, Connor Morrow; Kendall, Philip C.; Berry, Leandra; Souders, Margaret C.; Franklin, Martin E.; Schultz, Robert T.; Miller, Judith; Herrington, John

    2014-01-01

    We assessed anxiety consistent (i.e., "traditional") and inconsistent (i.e., "atypical") with diagnostic and statistical manual (DSM) definitions in autism spectrum disorder (ASD). Differential relationships between traditional anxiety, atypical anxiety, child characteristics, anxiety predictors and ASD-symptomology were…

  6. The relationship between atypical visual processing and social skills in young children with autism

    NARCIS (Netherlands)

    Hellendoorn, A.; Langstraat, I.; Wijnroks, L.; Buitelaar, J.; Daalen, E. van; Leseman, P.P.

    2014-01-01

    The present study examined whether atypical visual processing is related to the level of social skills in children with autism spectrum disorder (ASD). Thirty-eight young children with ASD (29 boys, 9 girls) were included. Atypical visual processing was assessed by coding the number of lateral glanc

  7. Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates.

    Science.gov (United States)

    García-Pardo, María Pilar; Roger-Sanchez, Concepción; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, María Asunción

    2016-06-15

    Drug addiction shares brain mechanisms and molecular substrates with learning and memory processes, such as the stimulation of glutamate receptors and their downstream signalling pathways. In the present work we provide an up-to-date review of studies that have demonstrated the implication of the main memory-related calcium-dependent protein kinases in opiate and cocaine addiction. The effects of these drugs of abuse in different animal models of drug reward, dependence and addiction are altered by manipulation of the mitogen-activated protein kinase (MAPK) family, particularly extracellular signal regulated kinase (ERK), calcium/calmodulin-dependent kinase II (CaMKII), the protein kinase C (PKC) family (including PKMζ), cAMP-dependent protein kinase A (PKA), cGMP-dependent protein kinase G (PKG), the phosphatidylinositol 3-kinase (PI3K) pathway and its downstream target mammalian target of Rapamycin (mTOR), cyclin-dependent kinase 5 (Cdk5), heat-shock proteins (Hsp) and other enzymes and proteins. Research suggests that drugs of abuse induce dependence and addiction by modifying the signalling pathways that involve these memory-related protein kinases, and supports the idea that drug addiction is an excessive aberrant learning disorder in which the maladaptive memory of drug-associated cues maintains compulsive drug use and contributes to relapse. Moreover, the studies we review offer new pharmacological strategies to treat opiate and cocaine dependence based on the manipulation of these protein kinases. In particular, disruption of reconsolidation of drug-related memories may have a high therapeutic value in the treatment of drug addiction. PMID:27056740

  8. Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates.

    Science.gov (United States)

    García-Pardo, María Pilar; Roger-Sanchez, Concepción; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, María Asunción

    2016-06-15

    Drug addiction shares brain mechanisms and molecular substrates with learning and memory processes, such as the stimulation of glutamate receptors and their downstream signalling pathways. In the present work we provide an up-to-date review of studies that have demonstrated the implication of the main memory-related calcium-dependent protein kinases in opiate and cocaine addiction. The effects of these drugs of abuse in different animal models of drug reward, dependence and addiction are altered by manipulation of the mitogen-activated protein kinase (MAPK) family, particularly extracellular signal regulated kinase (ERK), calcium/calmodulin-dependent kinase II (CaMKII), the protein kinase C (PKC) family (including PKMζ), cAMP-dependent protein kinase A (PKA), cGMP-dependent protein kinase G (PKG), the phosphatidylinositol 3-kinase (PI3K) pathway and its downstream target mammalian target of Rapamycin (mTOR), cyclin-dependent kinase 5 (Cdk5), heat-shock proteins (Hsp) and other enzymes and proteins. Research suggests that drugs of abuse induce dependence and addiction by modifying the signalling pathways that involve these memory-related protein kinases, and supports the idea that drug addiction is an excessive aberrant learning disorder in which the maladaptive memory of drug-associated cues maintains compulsive drug use and contributes to relapse. Moreover, the studies we review offer new pharmacological strategies to treat opiate and cocaine dependence based on the manipulation of these protein kinases. In particular, disruption of reconsolidation of drug-related memories may have a high therapeutic value in the treatment of drug addiction.

  9. Higher protein kinase C ζ in fatty rat liver and its effect on insulin actions in primary hepatocytes.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available We previously showed the impairment of insulin-regulated gene expression in the primary hepatocytes from Zucker fatty (ZF rats, and its association with alterations of hepatic glucose and lipid metabolism. However, the molecular mechanism is unknown. A preliminary experiment shows that the expression level of protein kinase C ζ (PKCζ, a member of atypical PKC family, is higher in the liver and hepatocytes of ZF rats than that of Zucker lean (ZL rats. Herein, we intend to investigate the roles of atypical protein kinase C in the regulation of hepatic gene expression. The insulin-regulated hepatic gene expression was evaluated in ZL primary hepatocytes treated with atypical PKC recombinant adenoviruses. Recombinant adenovirus-mediated overexpression of PKCζ, or the other atypical PKC member PKCι/λ, alters the basal and impairs the insulin-regulated expressions of glucokinase, sterol regulatory element-binding protein 1c, the cytosolic form of phosphoenolpyruvate carboxykinase, the catalytic subunit of glucose 6-phosphatase, and insulin like growth factor-binding protein 1 in ZL primary hepatocytes. PKCζ or PKCι/λ overexpression also reduces the protein level of insulin receptor substrate 1, and the insulin-induced phosphorylation of AKT at Ser473 and Thr308. Additionally, PKCι/λ overexpression impairs the insulin-induced Prckz expression, indicating the crosstalk between PKCζ and PKCι/λ. We conclude that the PKCζ expression is elevated in hepatocytes of insulin resistant ZF rats. Overexpressions of aPKCs in primary hepatocytes impair insulin signal transduction, and in turn, the down-stream insulin-regulated gene expression. These data suggest that elevation of aPKC expression may contribute to the hepatic insulin resistance at gene expression level.

  10. Gender Atypicality and Anxiety Response to Social Interaction Stress in Homosexual and Heterosexual Men.

    Science.gov (United States)

    Jacobson, Roi; Cohen, Hagit; Diamond, Gary M

    2016-04-01

    Gender non-conforming behavior and a homosexual sexual orientation have both been linked to higher levels of anxiety. This study examined the independent and interactive effects of gender atypicality and sexual orientation on levels of state anxiety immediately following a stressful social interaction task among a sample of homosexual and heterosexual Israeli men (n = 36). Gender atypicality was measured via both self-report and observer ratings. State anxiety was measured via both self-report immediately subsequent to the stressful social interaction task and pre- to post task changes in salivary cortisol. Results showed that self-reported gender atypicality and heterosexual sexual orientation predicted higher levels of self-reported social interaction anxiety, but not changes in cortisol. There were no sexual orientation by gender behavior interactions and there were no significant effects for observer rated gender atypicality. These findings suggest that gender atypicality, not homosexuality, place individuals at risk for increased anxiety. PMID:25946903

  11. $\\mathcal{N}=2$ supersymmetric field theories on 3-manifolds with A-type boundaries

    CERN Document Server

    Aprile, Francesco

    2016-01-01

    General half-BPS A-type boundary conditions are formulated for N=2 supersymmetric field theories on compact 3-manifolds with boundary. We observe that under suitable conditions manifolds of the real A-type admitting two complex supersymmetries (related by charge conjugation) possess, besides a contact structure, a natural integrable toric foliation. A boundary, or a general co-dimension-1 defect, can be inserted along any leaf of this preferred foliation to produce manifolds with boundary that have the topology of a solid torus. We show that supersymmetric field theories on such manifolds can be endowed with half-BPS A-type boundary conditions. We specify the natural curved space generalization of the A-type projection of bulk supersymmetries and analyze the resulting A-type boundary conditions in generic 3d non-linear sigma models and YM/CS-matter theories.

  12. Gender Atypicality and Anxiety Response to Social Interaction Stress in Homosexual and Heterosexual Men.

    Science.gov (United States)

    Jacobson, Roi; Cohen, Hagit; Diamond, Gary M

    2016-04-01

    Gender non-conforming behavior and a homosexual sexual orientation have both been linked to higher levels of anxiety. This study examined the independent and interactive effects of gender atypicality and sexual orientation on levels of state anxiety immediately following a stressful social interaction task among a sample of homosexual and heterosexual Israeli men (n = 36). Gender atypicality was measured via both self-report and observer ratings. State anxiety was measured via both self-report immediately subsequent to the stressful social interaction task and pre- to post task changes in salivary cortisol. Results showed that self-reported gender atypicality and heterosexual sexual orientation predicted higher levels of self-reported social interaction anxiety, but not changes in cortisol. There were no sexual orientation by gender behavior interactions and there were no significant effects for observer rated gender atypicality. These findings suggest that gender atypicality, not homosexuality, place individuals at risk for increased anxiety.

  13. Guiding atypical facial growth back to normal. Part 1: Understanding facial growth.

    Science.gov (United States)

    Galella, Steve; Chow, Daniel; Jones, Earl; Enlow, Donald; Masters, Ari

    2011-01-01

    Many practitioners find the complexity of facial growth overwhelming and thus merely observe and accept the clinical features of atypical growth and do not comprehend the long-term consequences. Facial growth and development is a strictly controlled biological process. Normal growth involves ongoing bone remodeling and positional displacement. Atypical growth begins when this biological balance is disturbed With the understanding of these processes, clinicians can adequately assess patients and determine the causes of these atypical facial growth patterns and design effective treatment plans. This is the first of a series of articles which addresses normal facial growth, atypical facial growth, patient assessment, causes of atypical facial growth, and guiding facial growth back to normal.

  14. DETORQUEO, QUIRKY, and ZERZAUST represent novel components involved in organ development mediated by the receptor-like kinase STRUBBELIG in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Lynette Fulton

    2009-01-01

    Full Text Available Intercellular signaling plays an important role in controlling cellular behavior in apical meristems and developing organs in plants. One prominent example in Arabidopsis is the regulation of floral organ shape, ovule integument morphogenesis, the cell division plane, and root hair patterning by the leucine-rich repeat receptor-like kinase STRUBBELIG (SUB. Interestingly, kinase activity of SUB is not essential for its in vivo function, indicating that SUB may be an atypical or inactive receptor-like kinase. Since little is known about signaling by atypical receptor-like kinases, we used forward genetics to identify genes that potentially function in SUB-dependent processes and found recessive mutations in three genes that result in a sub-like phenotype. Plants with a defect in DETORQEO (DOQ, QUIRKY (QKY, and ZERZAUST (ZET show corresponding defects in outer integument development, floral organ shape, and stem twisting. The mutants also show sub-like cellular defects in the floral meristem and in root hair patterning. Thus, SUB, DOQ, QKY, and ZET define the STRUBBELIG-LIKE MUTANT (SLM class of genes. Molecular cloning of QKY identified a putative transmembrane protein carrying four C(2 domains, suggesting that QKY may function in membrane trafficking in a Ca(2+-dependent fashion. Morphological analysis of single and all pair-wise double-mutant combinations indicated that SLM genes have overlapping, but also distinct, functions in plant organogenesis. This notion was supported by a systematic comparison of whole-genome transcript profiles during floral development, which molecularly defined common and distinct sets of affected processes in slm mutants. Further analysis indicated that many SLM-responsive genes have functions in cell wall biology, hormone signaling, and various stress responses. Taken together, our data suggest that DOQ, QKY, and ZET contribute to SUB-dependent organogenesis and shed light on the mechanisms, which are dependent on

  15. The genome of Chelonid herpesvirus 5 harbors atypical genes

    Science.gov (United States)

    Ackermann, Mathias; Koriabine, Maxim; Hartmann-Fritsch, Fabienne; de Jong, Pieter J.; Lewis, Teresa D.; Schetle, Nelli; Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Leong, Jo-Ann C.

    2012-01-01

    The Chelonid fibropapilloma-associated herpesvirus (CFPHV; ChHV5) is believed to be the causative agent of fibropapillomatosis (FP), a neoplastic disease of marine turtles. While clinical signs and pathology of FP are well known, research on ChHV5 has been impeded because no cell culture system for its propagation exists. We have cloned a BAC containing ChHV5 in pTARBAC2.1 and determined its nucleotide sequence. Accordingly, ChHV5 has a type D genome and its predominant gene order is typical for the varicellovirus genus within the alphaherpesvirinae. However, at least four genes that are atypical for an alphaherpesvirus genome were also detected, i.e. two members of the C-type lectin-like domain superfamily (F-lec1, F-lec2), an orthologue to the mouse cytomegalovirus M04 (F-M04) and a viral sialyltransferase (F-sial). Four lines of evidence suggest that these atypical genes are truly part of the ChHV5 genome: (1) the pTARBAC insertion interrupted the UL52 ORF, leaving parts of the gene to either side of the insertion and suggesting that an intact molecule had been cloned. (2) Using FP-associated UL52 (F-UL52) as an anchor and the BAC-derived sequences as a means to generate primers, overlapping PCR was performed with tumor-derived DNA as template, which confirmed the presence of the same stretch of "atypical" DNA in independent FP cases. (3) Pyrosequencing of DNA from independent tumors did not reveal previously undetected viral sequences, suggesting that no apparent loss of viral sequence had happened due to the cloning strategy. (4) The simultaneous presence of previously known ChHV5 sequences and F-sial as well as F-M04 sequences was also confirmed in geographically distinct Australian cases of FP. Finally, transcripts of F-sial and F-M04 but not transcripts of lytic viral genes were detected in tumors from Hawaiian FP-cases. Therefore, we suggest that F-sial and F-M04 may play a role in FP pathogenesis.

  16. Structure-based lead discovery for protein kinase C zeta inhibitor design by exploiting kinase-inhibitor complex crystal structure data and potential therapeutics for preterm labour.

    Science.gov (United States)

    Shao, Qing-Chun; Zhang, Cui-Juan; Li, Jie

    2014-10-14

    The protein kinase C (PKC) is a family of serine/threonine kinases with a broad range of cellular targets. Members of the PKC family participate at the diverse biological events involved in cellular proliferation, differentiation and survival. The PKC isoform zeta (PKCζ) is an atypical member that has recently been found to play an essential role in promoting human uterine contractility and thus been raised as a new target for treating preterm labour and other tocolytic diseases. In this study, an integrative protocol was described to graft hundreds of inhibitor ligands from their complex crystal structures with cognate kinases into the active pocket of PKCζ and, based on the modeled structures, to evaluate the binding strength of these inhibitors to the non-cognate PKCζ receptor by using a consensus scoring strategy. A total of 32 inhibitors with top score were compiled, and eight out of them were tested for inhibitory potency against PKCζ. Consequently, five compounds, i.e. CDK6 inhibitor fisetin, PIM1 inhibitor myricetin, CDK9 inhibitor flavopiridol and PknB inhibitor mitoxantrone as well as the promiscuous kinase inhibitor staurosporine showed high or moderate inhibitory activity on PKCζ, with IC50 values of 58 ± 9, 1.7 ± 0.4, 108 ± 17, 280 ± 47 and 0.019 ± 0.004 μM, respectively, while other three compounds, including two marketed drugs dasatinib and sunitinib as well as the Rho inhibitor fasudil, have not been detected to possess observable activity. Next, based on the modeled structure data we modified three flavonoid kinase inhibitors, i.e. fisetin, myricetin and flavopiridol, to generate a number of more potential molecular entities, two of which were found to have a moderately improved activity as compared to their parent compounds.

  17. Phelan-McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype?

    Directory of Open Access Journals (Sweden)

    Verhoeven WMA

    2012-04-01

    with associated autistic-like features, whereas its psychopathological phenotype comprises an atypical bipolar disorder. The latter may have implications for the treatment regime of the syndrome-related behavioral disturbances.Keywords: 22q13.3 deletion syndrome, 22qter, Phelan-McDermid, SHANK3, autism spectrum, unstable mood disorder, cerebellar vermis

  18. Risk factors for atypical endometrial hyperplasia in infertile women:possible association with polycystic ovarv syndrome

    Institute of Scientific and Technical Information of China (English)

    Lu Qun; Shen Huan; Tian Li; Zhu Sainan; Chen Xi

    2008-01-01

    Objective:Endometrial hyperplasia is considered as a precursor of endometrial carcinoma,in which oncogenic potential is low in hyperplasia without atypia,but high in a-typical hyperplasia.The objective of this study was to identify the risk factors for atypical endo-metrial hyperplasia in infertile women.Methods:Fifty four infertile women with endometrial hy-perplasia,which were selected from a large cohort of 2 098 women who desired for the future childbearing in our center,were diagnosed by hysteroscopy with directed biopsies or dilation and curettage(D&C),including 44 with hyperplasia without atypia,10 with atypical hyperplasia.Clinical characteristics were recorded in terms of age,body mass index(BMI),parity,insulin resistance,polycystic ovary syndrome(PCOS).Statistical comparison was made between women with hyperplasia without atypia and atypical hyperplasia.Logistic regression analysis Was em-ployed to assess the contribution of PCOS,obesity and insulin resistance to atypical hyperplasia.Results:The incidence of endometrial hyperplasia in infertile women Was 2.57%(54/2098),which included 1 0 women(0.48%)were diagnosed as atypical hyperplasia.PCOS in women with atypical hyperplasia(70%,7/10)was significantly higher than those of hyperplasia with-out atypia(27.27%,12/44).Stepwise regression analysis showed that PCOS contributed maximally to atypical endometrial hyperplasia in infertile women.Conclusion:PCOS is an independent risk factor for atypical endometrial hyperplasia in women with infertility.The infertile women with PCOS are at an increased risk for atypical endometrial hyperplasia and endometrial cancer.

  19. Atypical Severe Muscular Dystrophy in a Male: Genetic Implications for Female Relatives

    OpenAIRE

    Soltan, H C; Pyatt, Z.; Hinton, G. G.

    1985-01-01

    Genetic counselling of two younger sisters of a 32-year-old man with a 28-year history of severe progressive muscular dystrophy stimulated efforts to determine his diagnosis and the mode of inheritance. The investigation was complicated by the patient's sudden death during the period of investigation. However, genetic and neurological evaluation, electromyography and nerve conduction studies, serum enzymes and reinterpretation of a muscle biopsy 23 years earlier made it unlikely that inherita...

  20. Atypical myopathy in grazing horses: a first exploratory data analysis.

    Science.gov (United States)

    Votion, Dominique-M; Linden, Annick; Delguste, Catherine; Amory, Hélène; Thiry, Etienne; Engels, Patrick; van Galen, Gaby; Navet, Rachel; Sluse, Francis; Serteyn, Didier; Saegerman, Claude

    2009-04-01

    Over the last decade, atypical myopathy (AM) in grazing horses has emerged in several European countries. An exploratory analysis was conducted to determine horse- and pasture-level indicators or factors associated with AM in Belgium. Belgian cases of AM confirmed by histology (n=57) were compared to their healthy co-grazing horses (n=77) and to pastured horses not involved with AM as controls (n=386). The pastures where confirmed cases were grazing (42 pastures; 38 sites; 44 incidences of AM) were compared with those of the controls (216 pastures; 96 sites; no incidence of AM). Statistically significant (Phorses (young age, inactivity, body condition poor to normal), management practices (permanent pasturing, spreading of manure) and pasture characteristics (humid, sloping pastures, accumulated dead leaves, presence of waterway) may increase the risk of AM. Specific interventions based on these factors might help to reduce the incidence of AM.

  1. Atypical diabetes in children: ketosis-prone type 2 diabetes.

    Science.gov (United States)

    Vaibhav, Atul; Mathai, Mathew; Gorman, Shaun

    2013-01-08

    Ketosis-prone type 2 diabetes mellitus also known as atypical or flatbush diabetes is being increasingly recognised worldwide. These patients are typically obese, middle-aged men with a strong family history of type 2 diabetes. The aetiology and pathophysiological mechanism is still unclear but some initial research suggests that patients with ketosis-prone type 2 diabetes have a unique predisposition to glucose desensitisation. These patients have negative autoantibodies typically associated with type 1 diabetes but have shown to have human leucocyte antigen (HLA) positivity. At initial presentation, there is an impairment of both insulin secretion and action. β Cell function and insulin sensitivity can be markedly improved by initiating aggressive diabetes management to allow for discontinuation of insulin therapy within a few months of treatment. These patients can be maintained on oral hypoglycaemic agents and insulin therapy can be safely discontinued after few months depending on their β cell function.

  2. An atypical presentation of cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Joshi Deepak

    2008-06-01

    Full Text Available Abstract Introduction The presentation of cystic fibrosis is dependant upon which organs are affected. Common presentations include chronic respiratory infections and malabsorption. Patients with atypical disease tend to present late in childhood or as adults. Eye manifestations of cystic fibrosis are less well known. Case presentation A 14-year-old Caucasian boy presented with tiredness and difficulty seeing at night, over a period of 6 months. Good vision was only described in bright conditions. There was no history of jaundice, steatorrhea or diarrhoea. Conclusion This is the first reported case of newly diagnosed cystic fibrosis-related liver disease in a teenage boy, whose presenting symptom was night blindness secondary to vitamin A deficiency.

  3. Atypical measles syndrome: unusual hepatic, pulmonary, and immunologic aspects.

    Science.gov (United States)

    Frey, H M; Krugman, S

    1981-01-01

    The atypical measles syndrome is a relatively new disease that was first recognized 15 years ago. Initially, it occurred in children who were exposed to wild measles virus several years after they were immunized with killed measles vaccine. It was characterized by a two- to three-day prodrome of high fever, cough, headache, and myalgia followed by a rash that resembled Rocky Mountain spotted fever, scarlet fever, or varicella and associated with roentgenographic evidence of pneumonia with or without pleural effusion. This report highlights three unusual manifestations of this syndrome: 1) transient hepatitis, 2) persistence of pulmonary lesions for several years, and 3) occurrence of excessively high measles hemagglutination-inhibition antibody titers. Today, this syndrome occurs predominantly in adolescents and young adults.

  4. Chikungunya fever: Atypical and lethal cases in the Western hemisphere

    Science.gov (United States)

    Torres, Jaime R.; Leopoldo Códova G.; Castro, Julio S.; Rodríguez, Libsen; Saravia, Víctor; Arvelaez, Joanne; Ríos-Fabra, Antonio; Longhi, María A.; Marcano, Melania

    2014-01-01

    A large epidemic of Chikungunya fever currently affects the Caribbean, Central and South America. Despite a high number of reported cases, little is known on the occurrence of severe clinical complications. We describe four Venezuelan patients with a severe and/or lethal course who exhibit unusual manifestations of the disease. Case 1 describes a 75 year-old man with rapid onset of septic shock and multi-organ failure. Cases 2 and 3 describe two patients with rapid aggressive clinical course who developed shock, severe purpuric lesions and a distinct area large of necrosis in the nasal region. Case 4 depicts a splenectomized woman with shock, generalized purpuric lesions, bullous dermatosis and acronecrosis of an upper limb. Chikungunya fever in the Western hemisphere may also associate with atypical and severe manifestations. Some patients experience a life-threatening, aggressive clinical course, with rapid deterioration and death due to multisystem failure. PMID:26793440

  5. Epidermoid cyst of the testis: An atypical sonographic appearance.

    Science.gov (United States)

    Chen, Shu-Ting; Chiou, Hong-Jen; Pan, Chin-Chen; Shen, Shu-Huei; Chou, Yi-Hong; Tiu, Chui-Mei; Wang, Hsin-Kai; Lai, Yi-Chen; Lin, Yung-Hui; Wang, Jane; Chang, Cheng-Yen

    2016-09-01

    Epidermoid cysts are rare. They represent the most common benign tumor of the testis. The sonographic appearances of testicular epidermoid cysts usually include avascular, mostly lamellated, heterogeneous internal echotexture, with hypoechoic and hyperechoic concentric rings, accounting for the typical onion-ring appearance. On MRI, epidermoid cysts show a low-signal-intensity center, with internal concentric rings of alternating high- and low-signal intensity on T2-weighted images, which correlates with the onion-ring appearance. We report a patient with testicular epidermoid cyst with atypical ultrasound and MRI appearances that led to the erroneous initial diagnosis of "burned-out" tumor. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:448-451, 2016. PMID:27028726

  6. Atypical teratoid/rhabdoid tumor: an unusual presentation

    Energy Technology Data Exchange (ETDEWEB)

    Gandhi, Chirag D. [Mount Sinai School of Medicine, Department of Neurosurgery, One Gustave L. Levy Place, Box 1136, Annenberg 8-06, New York, NY (United States); Krieger, Mark D.; McComb, J. Gordon [Children' s Hospital of Los Angeles, Division of Neurosurgery, Los Angeles, CA (United States)

    2004-10-01

    Atypical teratoid/ rhabdoid tumor (AT/RT) of the central nervous system is a rare, highly aggressive malignancy of infancy. Although it is reported infrequently in the literature, it has often been histologically confused with a primitive neuroectodermal tumor (PNET)/medulloblastoma (MB) but has a much worse prognosis. We present an infant with two AT/RT tumors, one suprasellar in location and the other within the vermis without evidence of tumor elsewhere. What makes this case unusual is that there were two separate lesions in different cranial compartments, with no evidence of subarachnoid seeding. In addition, the lesions had different magnetic resonance imaging (MRI) characteristics even though they were histologically the same. (orig.)

  7. Atypical post-finasteride syndrome: A pharmacological riddle

    Directory of Open Access Journals (Sweden)

    Anita K Gupta

    2016-01-01

    Full Text Available Finasteride and dutasteride are commonly used 5-alpha reductase inhibitors. While finasteride is a selective inhibitor of 5-alpha reductase Type II, dutasteride inhibits 5- alpha reductase Type I and II. The United States Food and Drug Administration approved the use of finasteride for benign prostatic hypertrophy (BPH as well as androgenic alopecia (AGA while dutasteride is approved only for BPH. Off-label use of dutasteride is not uncommon in AGA as well. Although the postfinasteride syndrome (PFS is a well-established entity, its symptomatology is quite variable. Here, we describe a case of an atypical PFS in a patient treated with dutasteride and finasteride for AGA. The multisystem involvement and irreversible nature of this case warrant its reporting.

  8. Atypical post-finasteride syndrome: A pharmacological riddle.

    Science.gov (United States)

    Gupta, Anita K; Sharma, Neetu; Shukla, Prashant

    2016-01-01

    Finasteride and dutasteride are commonly used 5-alpha reductase inhibitors. While finasteride is a selective inhibitor of 5-alpha reductase Type II, dutasteride inhibits 5- alpha reductase Type I and II. The United States Food and Drug Administration approved the use of finasteride for benign prostatic hypertrophy (BPH) as well as androgenic alopecia (AGA) while dutasteride is approved only for BPH. Off-label use of dutasteride is not uncommon in AGA as well. Although the postfinasteride syndrome (PFS) is a well-established entity, its symptomatology is quite variable. Here, we describe a case of an atypical PFS in a patient treated with dutasteride and finasteride for AGA. The multisystem involvement and irreversible nature of this case warrant its reporting. PMID:27298504

  9. Gaze Perception Develops Atypically in Children with Autism

    Directory of Open Access Journals (Sweden)

    Simon Webster

    2011-01-01

    Full Text Available The Mindblindness model is the main model of social cognitive development in autism. This model assumes that eye direction detection and eye contact detection develop typically in autism (Baron-Cohen, 1995. The model's assumption of maturational development implies that when these skills are abnormal, they must either be absent or developmentally delayed. In contrast, the atypical modularisation hypothesis predicts that these skills can develop deviantly—successfully but atypically—in children with autism. Two computer-based tasks were used to assess eye direction detection and eye contact detection in children with autism and in typically developing children. These skills were developmentally deviant in children with autism. The findings support a model of social cognition in autism that accounts for developmental processes.

  10. Cholesterol granuloma of the orbit: An atypical presentation

    Directory of Open Access Journals (Sweden)

    Syed A R Rizvi

    2014-01-01

    Full Text Available Cholesterol granuloma is a rare, well-defined lesion of the orbit. In the orbit, diploe of the frontal bone is involved almost exclusively. We report an atypical case of cholesterol granuloma involving superomedial quadrant of orbit. A 42-year-old male presented with progressive, painless, proptosis with infero-temporal displacement of left eye. A large mass was felt beneath the bony orbital margin in the superomedial quadrant of the left orbit. Computerized tomography (CT scan revealed an extraconal superomedial, heterogeneous enhancing mass which was isodense with brain and pushing the globe inferolaterally and anteriorly. Excision biopsy of the tumor revealed the typical features of a cholesterol granuloma without any epithelial elements. Cholesterol granuloma of the orbit is a rare entity, but it can be diagnosed and differentiated from other lesions of the superior orbit by its characteristic clinical, radiological and histopathological features. An appropriate intervention in time carries a good prognosis with almost no recurrence.

  11. Angiolymphoid hyperplasia with eosinophilia: Atypical appeareance in an older patient

    Directory of Open Access Journals (Sweden)

    Karabudak Ozlem

    2008-01-01

    Full Text Available We describe a 76-year-old man presenting with a chronic, non-healing ulcer of six-year duration on his left zygomatic area. The skin biopsy specimen taken from the lesion, showed increased vascular proliferation, edematous endothelial cells in the dermal blood vessels and perivascular eosinophilic/lymphocytic infiltration. The routine and specific blood tests were unremarkable. On the basis of these features, the patient was diagnosed as having angiolymphoid hyperplasia with eosinophilia (ALHE. We present the case because of its rarity in older people, atypical clinical appearance; and stress the consideration of ALHE in the differential diagnosis of chronic non-healing superficial ulcers confined to face and neck.

  12. Crystal structure of EML1 reveals the basis for Hsp90 dependence of oncogenic EML4-ALK by disruption of an atypical β-propeller domain

    Science.gov (United States)

    Richards, Mark W.; Law, Edward W. P.; Rennalls, La’Verne P.; Busacca, Sara; O’Regan, Laura; Fry, Andrew M.; Fennell, Dean A.; Bayliss, Richard

    2014-01-01

    Proteins of the echinoderm microtubule-associated protein (EMAP)-like (EML) family contribute to formation of the mitotic spindle and interphase microtubule network. They contain a unique hydrophobic EML protein (HELP) motif and a variable number of WD40 repeats. Recurrent gene rearrangements in nonsmall cell lung cancer fuse EML4 to anaplastic lymphoma kinase (ALK), causing expression of several fusion oncoprotein variants. We have determined a 2.6-Å crystal structure of the representative ∼70-kDa core of EML1, revealing an intimately associated pair of β-propellers, which we term a TAPE (tandem atypical propeller in EMLs) domain. One propeller is highly atypical, having a discontinuous subdomain unrelated to a WD40 motif in place of one of its blades. This unexpected feature shows how a propeller structure can be assembled from subdomains with distinct folds. The HELP motif is not an independent domain but forms part of the hydrophobic core that joins the two β-propellers. The TAPE domain binds α/β-tubulin via its conserved, concave surface, including part of the atypical blade. Mapping the characteristic breakpoints of each EML4-ALK variant onto our structure indicates that the EML4 TAPE domain is truncated in many variants in a manner likely to make the fusion protein structurally unstable. We found that the heat shock protein 90 (Hsp90) inhibitor ganetespib induced degradation of these variants whereas others lacking a partial TAPE domain were resistant in both overexpression models and patient-derived cell lines. The Hsp90-sensitive EML4-ALK variants are exceptions to the rule that oncogenic fusion proteins involve breakpoints in disordered regions of both partners. PMID:24706829

  13. Reversible acute methotrexate leukoencephalopathy: atypical brain MR imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Ziereisen, France; Damry, Nash; Christophe, Catherine [Queen Fabiola Children' s University Hospital, Department of Radiology, Brussels (Belgium); Dan, Bernard [Queen Fabiola Children' s University Hospital, Department of Neurology, Brussels (Belgium); Azzi, Nadira; Ferster, Alina [Queen Fabiola Children' s University Hospital, Department of Paediatrics, Brussels (Belgium)

    2006-03-15

    Unusual acute symptomatic and reversible early-delayed leukoencephalopathy has been reported to be induced by methotrexate (MTX). We aimed to identify the occurrence of such atypical MTX neurotoxicity in children and document its MR presentation. We retrospectively reviewed the clinical findings and brain MRI obtained in 90 children treated with MTX for acute lymphoblastic leukaemia or non-B malignant non-Hodgkin lymphoma. All 90 patients had normal brain imaging before treatment. In these patients, brain imaging was performed after treatment completion and/or relapse and/or occurrence of neurological symptoms. Of the 90 patients, 15 (16.7%) showed signs of MTX neurotoxicity on brain MRI, 9 (10%) were asymptomatic, and 6 (6.7%) showed signs of acute leukoencephalopathy. On the routine brain MRI performed at the end of treatment, all asymptomatic patients had classical MR findings of reversible MTX neurotoxicity, such as abnormal high-intensity areas localized in the deep periventricular white matter on T2-weighted images. In contrast, the six symptomatic patients had atypical brain MRI characterized by T2 high-intensity areas in the supratentorial cortex and subcortical white matter (n=6), cerebellar cortex and white matter (n=4), deep periventricular white matter (n=2) and thalamus (n=1). MR normalization occurred later than clinical recovery in these six patients. In addition to mostly asymptomatic classical MTX neurotoxicity, MTX may induce severe but reversible unusual leukoencephalopathy. It is important to recognize this clinicoradiological presentation in the differential diagnosis of acute neurological deterioration in children treated with MTX. (orig.)

  14. Skin biopsies in the evaluation of atypical optic neuropathies.

    Science.gov (United States)

    Bielory, L; Kupersmith, M; Warren, F; Bystryn, J; Frohman, L

    1993-01-01

    Patients with atypical clinical presentations of common optic neuropathies such as optic neuritis (ON), anterior ischemic optic neuropathy (AION), or optic neuropathy of unknown etiology (UON) are difficult to distinguish from inflammatory autoimmune optic neuropathy (AON) which is typically associated with a poor visual prognosis, unless treated with high doses of corticosteroids and/or immunosuppressive agents. The authors retrospectively evaluated 34 patients [AON (n = 12); AION (n = 5); ON (n = 9); UON (n = 8)] with visual loss which deteriorated over weeks to months or followed an atypical course, for the presence of immunological markers suggestive of AON. These markers included serological testing for antiphospholipid (APA) and antinuclear (ANA) antibodies, and evaluation of histopathologic and immunofluorescent staining of skin biopsies. All patients underwent a skin biopsy. Four of the 12 patients with AON had urticarial cutaneous lesions which revealed leukocytoclastic and/or lymphohistiocytic vasculitis. Seven of the remaining eight AON patients had skin biopsies of non-lesional skin which revealed immunoreactant deposition. Seven of the 21 skin biopsies obtained from the non-AON patients had findings of vacuolization or mild perivascular infiltration of lymphocytes (n = 5) and immunofluorescent deposits (n = 2). Abnormal skin biopsies (92%;p = 0.0009) and circulating APA (82%; p = 0.013) were common in AON patients while ANA was not statistically increased in AON patients (p = 0.06) when compared to the remaining patients as a whole. AON patients typically demonstrate evidence of systemic autoimmune involvement, as manifested by cutaneous abnormalities such as urticarial vasculitis and/or immunoreactant deposition and circulating APA. These may serve as markers for identifying AON patients who may be treated with immunomodulatory agents. PMID:22822778

  15. Atypical integration of motion signals in Autism Spectrum Conditions.

    Directory of Open Access Journals (Sweden)

    Caroline E Robertson

    Full Text Available Vision in Autism Spectrum Conditions (ASC is characterized by enhanced perception of local elements, but impaired perception of global percepts. Deficits in coherent motion perception seem to support this characterization, but the roots and robustness of such deficits remain unclear. We aimed to investigate the dynamics of the perceptual decision-making network known to support coherent motion perception. In a series of forced-choice coherent motion perception tests, we parametrically varied a single stimulus dimension, viewing duration, to test whether the rate at which evidence is accumulated towards a global decision is atypical in ASC. 40 adult participants (20 ASC performed a classic motion discrimination task, manually indicating the global direction of motion in a random-dot kinematogram across a range of coherence levels (2-75% and stimulus-viewing durations (200-1500 ms. We report a deficit in global motion perception at short viewing durations in ASC. Critically, however, we found that increasing the amount of time over which motion signals could be integrated reduced the magnitude of the deficit, such that at the longest duration there was no difference between the ASC and control groups. Further, the deficit in motion integration at the shortest duration was significantly associated with the severity of autistic symptoms in our clinical population, and was independent from measures of intelligence. These results point to atypical integration of motion signals during the construction of a global percept in ASC. Based on the neural correlates of decision-making in global motion perception our findings suggest the global motion deficit observed in ASC could reflect a slower or more variable response from the primary motion area of the brain or longer accumulation of evidence towards a decision-bound in parietal areas.

  16. Figurative language processing in atypical populations: The ASD perspective

    Directory of Open Access Journals (Sweden)

    Mila eVulchanova

    2015-02-01

    Full Text Available This paper is intended to provide a critical overview of experimental and clinical research documenting problems in figurative language processing in atypical populations with a focus on the Autistic Spectrum. Research in the comprehension and processing of figurative language in autism invariably documents problems in this area. The greater paradox is that even at the higher end of the spectrum or in the cases of linguistically talented individuals with Asperger syndrome, where structural language competence is intact, problems with extended language persist. If we assume that figurative and extended uses of language essentially depend on the perception and processing of more concrete core concepts and phenomena, the commonly observed failure in atypical populations to understand figurative language remains a puzzle.Various accounts have been offered to explain this issue, ranging from linking potential failure directly to overall structural language competence (Brock et al., 2008; Norbury, 2005 to right-hemispheric involvement (Gold and Faust, 2010. We argue that the dissociation between structural language and figurative language competence in autism should be sought in more general cognitive mechanisms and traits in the autistic phenotype (e.g., in terms of weak central coherence, Vulchanova et al., 2012b, as well as failure at on-line semantic integration with increased complexity and diversity of the stimuli (Coulson and van Petten, 2002. This perspective is even more compelling in light of similar problems in a number of conditions, including both acquired (e.g., Aphasia and developmental disorders (Williams Syndrome. This dissociation argues against a simple continuity view of language interpretation.

  17. Atypical teratoid/rhabdoid tumor of the central nervous system in children: an atypical series and review

    Energy Technology Data Exchange (ETDEWEB)

    Fenton, Laura Z. [Department of Radiology, Children' s Hospital, 1056 East 19th Avenue B125, CO 80218, Denver (United States); Foreman, Nicholas K. [Department of Neuro-Oncology, Children' s Hospital, 1056 East 19th Avenue B125, CO 80218, Denver (United States)

    2003-08-01

    Primary atypical teratoid/rhabdoid tumor (AT/RhT) of the central nervous system is a recently described, highly malignant neoplasm in infants and young children. This tumor is an unusual combination of mixed cellular elements, similar but not typical of teratomas, and rhabdoid cells. This tumor is most common in the posterior fossa in children less than 2 years, and is radiologically similar to medulloblastoma. No pathognomonic imaging features are present. The two tumors can be separated on histologic, molecular, and cytogenetic grounds. Separation of these two tumor types is crucial because the prognosis for AT/RhT is grim even with current multimodality treatment. We present four consecutive cases of AT/RhT, three in locations other than the cerebellum, seen at our institution in a 14-month period, indicating that this tumor may be more common than previously thought. (orig.)

  18. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival

    Science.gov (United States)

    Jansen, M.; Mohapatra, G.; Betensky, R.A.; Keohane, C.; Louis, D.N.

    2013-01-01

    Aims Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Postoperative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas. PMID:21988727

  19. Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival.

    LENUS (Irish Health Repository)

    2012-02-01

    Aims: Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods: 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.

  20. Atypical scrapie isolates involve a uniform prion species with a complex molecular signature.

    Directory of Open Access Journals (Sweden)

    Dorothea R Götte

    Full Text Available The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrP(d. To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical scrapie to transgenic mice over-expressing the ovine prion protein (tg338. The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical scrapie isolates and the Nor98, an atypical scrapie isolate from Norway. Together with published data, our results suggest that atypical scrapie is caused by a uniform type of prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent proteinase K-resistant prion protein fragment in atypical scrapie consists of two separate, unglycosylated peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research.

  1. Quinalizarin as a potent, selective and cell-permeable inhibitor of protein kinase CK2.

    Science.gov (United States)

    Cozza, Giorgio; Mazzorana, Marco; Papinutto, Elena; Bain, Jenny; Elliott, Matthew; di Maira, Giovanni; Gianoncelli, Alessandra; Pagano, Mario A; Sarno, Stefania; Ruzzene, Maria; Battistutta, Roberto; Meggio, Flavio; Moro, Stefano; Zagotto, Giuseppe; Pinna, Lorenzo A

    2009-08-01

    Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a moderately potent and poorly selective inhibitor of protein kinase CK2, one of the most pleiotropic serine/threonine protein kinases, implicated in neoplasia and in other global diseases. By virtual screening of the MMS (Molecular Modeling Section) database, we have now identified quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) as an inhibitor of CK2 that is more potent and selective than emodin. CK2 inhibition by quinalizarin is competitive with respect to ATP, with a Ki value of approx. 50 nM. Tested at 1 microM concentration on a panel of 75 protein kinases, quinalizarin drastically inhibits only CK2, with a promiscuity score (11.1), which is the lowest ever reported so far for a CK2 inhibitor. Especially remarkable is the ability of quinalizarin to discriminate between CK2 and a number of kinases, notably DYRK1a (dual-specificity tyrosine-phosphorylated and -regulated kinase), PIM (provirus integration site for Moloney murine leukaemia virus) 1, 2 and 3, HIPK2 (homeodomain-interacting protein kinase-2), MNK1 [MAPK (mitogen-activated protein kinase)-interacting kinase 1], ERK8 (extracellular-signal-regulated kinase 8) and PKD1 (protein kinase D 1), which conversely tend to be inhibited as drastically as CK2 by commercially available CK2 inhibitors. The determination of the crystal structure of a complex between quinalizarin and CK2alpha subunit highlights the relevance of polar interactions in stabilizing the binding, an unusual characteristic for a CK2 inhibitor, and disclose other structural features which may account for the narrow selectivity of this compound. Tested on Jurkat cells, quinalizarin proved able to inhibit endogenous CK2 and to induce apoptosis more efficiently than the commonly used CK2 inhibitors TBB (4,5,6,7-tetrabromo-1H-benzotriazole) and DMAT (2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole). PMID:19432557

  2. Hospitalization and cost after switching from atypical to typical antipsychotics in schizophrenia patients in Thailand

    Science.gov (United States)

    Boonlue, Tuanthon; Subongkot, Suphat; Dilokthornsakul, Piyameth; Kongsakon, Ronnachai; Pattanaprateep, Oraluck; Suanchang, Orabhorn; Chaiyakunapruk, Nathorn

    2016-01-01

    Background Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual atypical antipsychotics therapy. Outcomes were schizophrenia-related hospitalization and total health care cost. Logistic and Poisson regression were used to evaluate the risk of hospitalization, and generalized linear model with gamma distribution was used to determine the health care cost. All analyses were adjusted by employing propensity score and multivariable analyses. All cost estimates were adjusted according to 2013 consumer price index and converted to US$ at an exchange rate of 32.85 Thai bahts/US$. Results A total of 2,354 patients were included. Of them, 166 (7.1%) patients switched to typical antipsychotics. The adjusted odds ratio for schizophrenia-related hospitalization in atypical antipsychotic switching group was 1.87 (95% confidence interval [CI] 1.23–2.83). The adjusted incidence rate ratio was 2.44 (95% CI 1.57–3.79) for schizophrenia-related hospitalizations. The average total health care cost was lower in patients with antipsychotic switching (−$64; 95% CI −$459 to $332). Conclusion Switching from atypical to typical antipsychotics is associated with an increased risk of schizophrenia-related hospitalization

  3. Genetic characterization of atypical Mansonella (Mansonella) ozzardi microfilariae in human blood samples from northeastern Peru.

    Science.gov (United States)

    Marcos, Luis A; Arrospide, Nancy; Recuenco, Sergio; Cabezas, Cesar; Weil, Gary J; Fischer, Peter U

    2012-09-01

    DNA sequence comparisons are useful for characterizing proposed new parasite species or strains. Microfilariae with an atypical arrangement of nuclei behind the cephalic space have been recently described in human blood samples from the Amazon region of Peru. Three blood specimens containing atypical microfilariae were genetically characterized using three DNA markers (5S ribosomal DNA, 12S ribosomal DNA, and cytochrome oxidase I). All atypical microfilariae were clustered into the Mansonella group and indistinguishable from M. ozzardi based on these DNA markers. PMID:22826497

  4. Mapping the residues of protein kinase CK2 alpha subunit responsible for responsiveness to polyanionic inhibitors

    DEFF Research Database (Denmark)

    Vaglio, P; Sarno, S; Marin, O;

    1996-01-01

    The quadruple mutation of the whole basic cluster, K74KKK77 conserved in the catalytic subunits of protein kinase CK2 and implicated in substrate recognition, not only abolishes inhibition by heparin but even induces with some peptide substrates an up to 5-fold stimulation by heparin in the 0...

  5. mTOR independent regulation of macroautophagy by Leucine Rich Repeat Kinase 2 via Beclin-1

    Science.gov (United States)

    Manzoni, Claudia; Mamais, Adamantios; Roosen, Dorien A.; Dihanich, Sybille; Soutar, Marc P. M.; Plun-Favreau, Helene; Bandopadhyay, Rina; Hardy, John; Tooze, Sharon A.; Cookson, Mark R.; Lewis, Patrick A.

    2016-01-01

    Leucine rich repeat kinase 2 is a complex enzyme with both kinase and GTPase activities, closely linked to the pathogenesis of several human disorders including Parkinson’s disease, Crohn’s disease, leprosy and cancer. LRRK2 has been implicated in numerous cellular processes; however its physiological function remains unclear. Recent reports suggest that LRRK2 can act to regulate the cellular catabolic process of macroautophagy, although the precise mechanism whereby this occurs has not been identified. To investigate the signalling events through which LRRK2 acts to influence macroautophagy, the mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) and Beclin-1/phosphatidylinositol 3-kinase (PI3K) pathways were evaluated in astrocytic cell models in the presence and absence of LRRK2 kinase inhibitors. Chemical inhibition of LRRK2 kinase activity resulted in the stimulation of macroautophagy in a non-canonical fashion, independent of mTOR and ULK1, but dependent upon the activation of Beclin 1-containing class III PI3-kinase. PMID:27731364

  6. Cross talk of tyrosine kinases with the DNA damage signaling pathways.

    Science.gov (United States)

    Mahajan, Kiran; Mahajan, Nupam P

    2015-12-15

    Tyrosine kinases respond to extracellular and intracellular cues by activating specific cellular signaling cascades to regulate cell cycle, growth, proliferation, differentiation and survival. Likewise, DNA damage response proteins (DDR) activated by DNA lesions or chromatin alterations recruit the DNA repair and cell cycle checkpoint machinery to restore genome integrity and cellular homeostasis. Several new examples have been uncovered in recent studies which reveal novel epigenetic and non-epigenetic mechanisms by which tyrosine kinases interact with DDR proteins to dictate cell fate, i.e. survival or apoptosis, following DNA damage. These studies reveal the ability of tyrosine kinases to directly regulate the activity of DNA repair and cell cycle check point proteins by tyrosine phosphorylation. In addition, tyrosine kinases epigenetically regulate DNA damage signaling pathways by modifying the core histones as well as chromatin modifiers at critical tyrosine residues. Thus, deregulated tyrosine kinase driven epigenomic alterations have profound implications in cancer, aging and genetic disorders. Consequently, targeting oncogenic tyrosine kinase induced epigenetic alterations has gained significant traction in overcoming cancer cell resistance to various therapies. This review discusses mechanisms by which tyrosine kinases interact with DDR pathways to regulate processes critical for maintaining genome integrity as well as clinical strategies for targeted cancer therapies. PMID:26546517

  7. A multisubstrate deoxyribonucleoside kinase from plants

    DEFF Research Database (Denmark)

    Clausen, Anders R.; Girandon, Lenart; Knecht, Wolfgang;

    2008-01-01

    Deoxyribonucleoside kinases catalyze the rate limiting step during the salvage of deoxyribonucleosides and convert them into the corresponding monophosphate compounds. We have identified and characterized a unique multisubstrate deoxyribonucleoside kinase from plants. The phylogenetic relationship...... in anti-cancer therapy....

  8. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. There are two paralog catalytic subunits, i.e. alpha (A1) and alpha' (A2). The alpha and alpha' subunits are linked to two beta subunits to produce a heterotetrameric structure....... The catalytic alpha subunits are distantly related to the CMGC subfamily of kinases, such as the Cdk kinases. There are some peculiarities associated with protein kinase CK2, which are not found with most other protein kinases: (i) the enzyme is constitutively active, (ii) it can use ATP and GTP and...... specifically target this protein kinase [10]. Since not all the aspects of what has been published on CK2 can be covered in this review, we would like to recommend the following reviews; (i) for general information on CK2 [11-18] and (ii) with a focus on aberrant CK2 [19-22]....

  9. Renal targeting of kinase inhibitors

    NARCIS (Netherlands)

    Dolman, M. E. M.; Fretz, M. M.; Segers, Gj. W.; Lacombe, M.; Prakash, J.; Storm, G.; Hennink, W. E.; Kok, R. J.

    2008-01-01

    Activation of proximal tubular cells by fibrotic and inflammatory mediators is an important hallmark of chronic kidney disease. We have developed a novel strategy to intervene in renal fibrosis, by means of locally delivered kinase inhibitors. Such compounds will display enhanced activity within tub

  10. Inhibitors of protein kinase C

    Institute of Scientific and Technical Information of China (English)

    LIU Shiying; JIANG Yuyang; CAO Jian; LIU Feng; MA Li; ZHAO Yufen

    2005-01-01

    Protein kinase catalyzes the transfer of the γ-phosphoryl group from ATP to the hydroxyl groups of protein side chains, which plays critical roles in signal transduction pathways by transmitting extracellular signals across the plasma membrane and nuclear membrane to the destination sites in the cytoplasm and the nucleus. Protein kinase C (PKC) is a superfamily of phospholipid-dependent Ser/Thr kinase. There are at least 12 isozymes in PKC family. They are distributed in different tissues and play different roles in physiological processes. On account of their concern with a variety of pathophysiologic states, such as cancer, inflammatory conditions, autoimmune disorder, and cardiac diseases, the inhibitors, which can inhibit the activity of PKC and the interaction of cytokine with receptor, and interfere signal transduction pathway, may be candidates of therapeutic drugs. Therefore, intense efforts have been made to develop specific protein kinase inhibitors as biological tools and therapeutic agents. This article reviews the recent development of some of PKC inhibitors based on their interaction with different conserved domains and different inhibition mechanisms.

  11. Comprehension of atypical literary text and scholastic achievement

    Directory of Open Access Journals (Sweden)

    Božin Aurel A.

    2009-01-01

    Full Text Available With the aim of gaining insight into literary text comprehension and the linkage between that comprehension and scholastic achievement during the first years of schooling, a research was conducted on the sample of 152 third and fourth grade pupils from one urban and one rural school. After having read silently a selected atypical excerpt from one literary text, interviewed pupils filled out the questionnaire constructed for the purposes of this research starting from the 11 categories of text comprehension singled out based on the theory of comprehension and interpretation of literary text and the current curriculum. In the first part of the research we applied the Children's orientation scale by Malka Margalit, and school marks were used as a measurement of scholastic achievement. Research results point out that, among other things, inferring on the basis of what has been read poses the greatest difficulty for third and fourth graders, that is, that almost three quarters of them are not capable of determining the meaning of some representative sentences from that text. In the positive sense, it was established that almost three quarters of them perceive beautiful poetic expressions and about 80% of them can at least to a certain extent recognize character descriptions, emotional situations and moods, that is, discover significant facts. Answers to the questions regarding the majority of categories of text comprehension are significantly correlated with scholastic achievement. As expected, the highest correlations between the measures on text comprehension categories are with the marks in native (Serbian language. Partial correlations between the measures on certain categories of text comprehension and measurements of scholastic achievement (excluding the influence of feeling of coherence are not significantly different from bivariate. Based on the obtained data, authors conclude that the utilized system of categories can be a useful tool for

  12. Detection of atypical seismic events on a regional scale

    Science.gov (United States)

    Solano-Hernandez, E. A.; Hjorleifsdottir, V.; Perez-Campos, X.; Iglesias, A.

    2013-12-01

    We propose an event-detection algorithm to locate seismic events on a regional scale. Our goal is to identify non-impulsive or 'atypical' events which are not detected by regional or global networks, due to their low P-wave amplitude. Ekstrom (2006) has developed and implemented a method to detect and locate sources of long-period seismic surface waves on a global scale. Atypical events are generated by, for example, rapid glacial movements (Ekstrom, et al., 2003; Ekstrom, et al., 2006), volcanic events (Schuler and Ekstrom, 2009) and landslides (Ekstrom and Stark, 2013). Furthermore, non-impulsive earthquakes have been located on oceanic transform faults (Abercrombie and Ekstrom, 2001). The current method (Ekstrom, 2006), that is applied on the scale of the globe, routinely detects events with magnitudes around Mw 5 and larger. In this work we wish to lower the detection threshold by using shorter period records registered by regional networks. The difficulty lies in that the shorter period records are strongly influenced by the heterogeneous crust and upper mantle, which need to be accounted for in the modeling process. Our proposed method involves first computing full waveforms, Green's functions or moment tensor responses, between a grid of test locations and existing seismic stations in a 3D medium. We then effectively back propagate observed data through cross correlation with the responses, obtaining a function that localizes in time and space at the source. Our method is a variant of the timereversal method presented by, for example, McMechan (1982), Tromp et al. (2005), Larmat et al. (2006), Gajewski and Tessmer (2005) and Kim et al. (2010). To calibrate the various parameters used by the detection method, we use the aftershocks sequence of the March 20, 2012 Ometepec, Guerrero, Mexico earthquake, recorded by the SSN (Mexican National Network). The lively aftershock sequence provided us with many events of different magnitudes, all occurring approximately

  13. The genome of Chelonid herpesvirus 5 harbors atypical genes

    Science.gov (United States)

    Ackermann, Mathias; Koriabine, Maxim; Hartmann-Fritsch, Fabienne; de Jong, Pieter J.; Lewis, Teresa D.; Schetle, Nelli; Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Leong, Jo-Ann C.

    2012-01-01

    The Chelonid fibropapilloma-associated herpesvirus (CFPHV; ChHV5) is believed to be the causative agent of fibropapillomatosis (FP), a neoplastic disease of marine turtles. While clinical signs and pathology of FP are well known, research on ChHV5 has been impeded because no cell culture system for its propagation exists. We have cloned a BAC containing ChHV5 in pTARBAC2.1 and determined its nucleotide sequence. Accordingly, ChHV5 has a type D genome and its predominant gene order is typical for the varicellovirus genus within thealphaherpesvirinae. However, at least four genes that are atypical for an alphaherpesvirus genome were also detected, i.e. two members of the C-type lectin-like domain superfamily (F-lec1, F-lec2), an orthologue to the mouse cytomegalovirus M04 (F-M04) and a viral sialyltransferase (F-sial). Four lines of evidence suggest that these atypical genes are truly part of the ChHV5 genome: (1) the pTARBAC insertion interrupted the UL52 ORF, leaving parts of the gene to either side of the insertion and suggesting that an intact molecule had been cloned. (2) Using FP-associated UL52 (F-UL52) as an anchor and the BAC-derived sequences as a means to generate primers, overlapping PCR was performed with tumor-derived DNA as template, which confirmed the presence of the same stretch of “atypical” DNA in independent FP cases. (3) Pyrosequencing of DNA from independent tumors did not reveal previously undetected viral sequences, suggesting that no apparent loss of viral sequence had happened due to the cloning strategy. (4) The simultaneous presence of previously known ChHV5 sequences and F-sial as well as F-M04 sequences was also confirmed in geographically distinct Australian cases of FP. Finally, transcripts of F-sial and F-M04 but not transcripts of lytic viral genes were detected in tumors from Hawaiian FP-cases. Therefore, we suggest that F-sial and F-M04 may play a role in FP pathogenesis

  14. Degradation of Activated Protein Kinases by Ubiquitination

    OpenAIRE

    Lu, Zhimin; Hunter, Tony

    2009-01-01

    Protein kinases are important regulators of intracellular signal transduction pathways and play critical roles in diverse cellular functions. Once a protein kinase is activated, its activity is subsequently downregulated through a variety of mechanisms. Accumulating evidence indicates that the activation of protein kinases commonly initiates their downregulation via the ubiquitin/proteasome pathway. Failure to regulate protein kinase activity or expression levels can cause human diseases.

  15. Determinants of homodimerization specificity in histidine kinases

    OpenAIRE

    Ashenberg, Orr; Rozen-Gagnon, Kathryn; Laub, Michael T; Keating, Amy E.

    2011-01-01

    Two-component signal transduction pathways consisting of a histidine kinase and a response regulator are used by prokaryotes to respond to diverse environmental and intracellular stimuli. Most species encode numerous paralogous histidine kinases that exhibit significant structural similarity. Yet in almost all known examples, histidine kinases are thought to function as homodimers. We investigated the molecular basis of dimerization specificity, focusing on the model histidine kinase EnvZ and...

  16. Exploring the role of auditory analysis in atypical compared to typical language development.

    Science.gov (United States)

    Grube, Manon; Cooper, Freya E; Kumar, Sukhbinder; Kelly, Tom; Griffiths, Timothy D

    2014-02-01

    The relationship between auditory processing and language skills has been debated for decades. Previous findings have been inconsistent, both in typically developing and impaired subjects, including those with dyslexia or specific language impairment. Whether correlations between auditory and language skills are consistent between different populations has hardly been addressed at all. The present work presents an exploratory approach of testing for patterns of correlations in a range of measures of auditory processing. In a recent study, we reported findings from a large cohort of eleven-year olds on a range of auditory measures and the data supported a specific role for the processing of short sequences in pitch and time in typical language development. Here we tested whether a group of individuals with dyslexic traits (DT group; n = 28) from the same year group would show the same pattern of correlations between auditory and language skills as the typically developing group (TD group; n = 173). Regarding the raw scores, the DT group showed a significantly poorer performance on the language but not the auditory measures, including measures of pitch, time and rhythm, and timbre (modulation). In terms of correlations, there was a tendency to decrease in correlations between short-sequence processing and language skills, contrasted by a significant increase in correlation for basic, single-sound processing, in particular in the domain of modulation. The data support the notion that the fundamental relationship between auditory and language skills might differ in atypical compared to typical language development, with the implication that merging data or drawing inference between populations might be problematic. Further examination of the relationship between both basic sound feature analysis and music-like sound analysis and language skills in impaired populations might allow the development of appropriate training strategies. These might include types of musical

  17. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    -dependent and kinase-independent functions, both potentially involved in CCRCC progression. These results might have important implications on therapeutic approaches to CCRCC, since the disruption of the interaction between EGFR/SGLT1, mediated by anti-EGFR antibodies and/or SGLT1 inhibitors, might constitute a novel therapeutic target for CCRCC treatment, and new clinical trials should be evaluated on the basis of this therapeutic proposal.

  18. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    -dependent and kinase-independent functions, both potentially involved in CCRCC progression. These results might have important implications on therapeutic approaches to CCRCC, since the disruption of the interaction between EGFR/SGLT1, mediated by anti-EGFR antibodies and/or SGLT1 inhibitors, might constitute a novel therapeutic target for CCRCC treatment, and new clinical trials should be evaluated on the basis of this therapeutic proposal. PMID:27073724

  19. Decreased Diagnostic Accuracy of Multislice Coronary Computed Tomographic Angiography in Women with Atypical Angina Symptoms

    Directory of Open Access Journals (Sweden)

    Wen-Ying Jin

    2016-01-01

    Conclusions: Although MSCT is a reliable diagnostic modality for the exclusion of significant coronary artery stenoses in all patients, gender and atypical symptoms might have some influence on its diagnostic accuracy.

  20. Evaluation of Atypical Lymphocyte Warnings of Sysmex XE-4000 in Outpatient Children

    Institute of Scientific and Technical Information of China (English)

    Xueling GUO; Tingbo ZHANG; Maofan WANG

    2014-01-01

    This study aimed to evaluate the atypical lymphocyte warnings of Sysmex XE-4000 in outpatient children. [Method] Randomly 280 specimens of outpatient children were selected to analyze atypical lymphocytes with Sysmex XE-4000 and artificial smear microscopy simultaneously. [Result] With artificial smear microscopy as the gold standard, the atypical lymphocyte warnings of Sysmex XE-4000 in outpatient children exhibited a sensitivity of 97.4%, specificity of 69.3%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 98.5%. [Conclusion] Sysmex XE-4000 shows a high sensitivity in atypical lymphocyte warnings, which can reduce the number of blood smears, improve the specificity of microscopy, and decline the labor intensity of inspection personnel. However, there are stil certain false positives to be confirmed by artificial microscopy.

  1. Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid-based cervical cytology.

    LENUS (Irish Health Repository)

    Chummun, K

    2012-12-01

    In 2008, the management of women in Ireland with atypical glandular cells changed to immediate referral to colposcopy. The optimal management of these women is unclear. A balance between the detection of occult disease and overtreatment is required.

  2. Research on the significance of TSPOT.TB test in diagnosing the atypical pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    Jin Li; Qi-Huang Chen; Yan-Yu Pan; Wei-Zheng Chen; Wen-Feng Lin; Sai-Li Zeng

    2015-01-01

    Objective:To investigate the sensitivity and specificity of the TSPOT.TB test in diagnosing the atypical pulmonary tuberculosis.Methods:A total of 100 patients with suspected pulmonary tuberculosis were diagnosed by TSPOT.TB test and TST, and the difference between the two detection methods was compared.Results:The positive detection rate in the atypical pulmonary tuberculosis was significantly higher than that in the pulmonary tuberculosis group. The sensitivity (94.21), specificity (94.50), PPV (74.20), NPV (94.17), and LR+ (6.14) in the atypical pulmonary tuberculosis group by TSPOT.TB test were significantly higher than those by TST, while LR-(0.13) was significantly lower than that by TST.Conclusions:When compared with TST, TSPOT. TB test has a higher clinical application value, possesses advantages of rapidness and sensitivity, and plays a vital role in diagnosing atypical pulmonary tuberculosis.

  3. Bronchiectasis Exacerbations: The Role of Atypical Bacteria and Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Eugenios I Metaxas

    2015-01-01

    Full Text Available BACKGROUND: Aside from the known role of common bacteria, there is a paucity of data regarding the possible role of atypical bacteria and viruses in exacerbations of non-cystic fibrosis bronchiectasis.

  4. Patients with atypical hyperplasia of the endometrium should be treated in oncological centers

    DEFF Research Database (Denmark)

    Antonsen, Sofie Leisby; Ulrich, Lian; Høgdall, Claus

    2011-01-01

    OBJECTIVES: To examine the prevalence of undiagnosed endometrial carcinoma (EC) among women with a preoperative diagnosis of atypical endometrial hyperplasia (AEH) in correlation to age, BMI and menopause. METHODS: Data extracted from the Danish Gynecological Cancer Database (DGCD) covering women...

  5. Relations between A-type granites and copper mineralization as exemplified by the Machangqing Cu deposit

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    This paper deals with the relations between the Machangqing rockbody which corresponds to the A-type granites and porphyry copper mineralization in terms of petrochemistry,trace element geochemistry,fluid inclusion geochemistry and isotope geochemistry.The results show that the Machangqing porphyry copper deposit was formed from the fluid predominated by magmatic fluid.This kind of ore-forming fluid was just differentiated from the magma responsible for the A-type granites.Therefore,as viewed from whether they contain water or not,the A-type granites can,at least,be divided into two types:water-bearing and water-free.The water-bearing A-type granites can serve as the host of porphyry copper deposits under certain geological conditions.

  6. Relations between A-type granites and copper mineralization as exemplified by the Machangqing Cu deposit

    Institute of Scientific and Technical Information of China (English)

    毕献武; 胡瑞忠; 叶造军; 邵树勋

    2000-01-01

    This paper deals with the relations between the Machangqing rockbody which corresponds to the A-type granites and porphyry copper mineralization in terms of petrochemistry, trace element geochemistry, fluid inclusion geochemistry and isotope geochemistry. The results show that the Machangqing porphyry copper deposit was formed from the fluid predominated by mag-matic fluid. This kind of ore-forming fluid was just differentiated from the magma responsible for the A-type granites. Therefore, as viewed from whether they contain water or not, the A-type granites can, at least, be divided into two types: water-bearing and water-free. The water-bearing A-type granites can serve as the host of porphyry copper deposits under certain geological conditions.

  7. Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Nielsen, Lars P; Schiotz, Peter Oluf

    2006-01-01

    BACKGROUND: Respiratory viral and atypical bacterial infections are associated with pulmonary exacerbations and hospitalisations in cystic fibrosis patients. We wanted to study the impact of such infections on children attending the outpatient clinic. METHODS: Seventy-five children were followed...

  8. A time frame permissive for Protein Kinase D2 activity to direct angiogenesis in mouse embryonic stem cells

    OpenAIRE

    Müller, Martin; Schröer, Jana; Azoitei, Ninel; Eiseler, Tim; Bergmann, Wendy; Köhntop, Ralf; Lin, Qiong; Costa, Ivan G; Zenke, Martin; Genze, Felicitas; Weidgang, Clair; Seufferlein, Thomas; Liebau, Stefan; Kleger, Alexander

    2015-01-01

    The protein kinase D isoenzymes PKD1/2/3 are prominent downstream targets of PKCs (Protein Kinase Cs) and phospholipase D in various biological systems. Recently, we identified PKD isoforms as novel mediators of tumour cell-endothelial cell communication, tumour cell motility and metastasis. Although PKD isoforms have been implicated in physiological/tumour angiogenesis, a role of PKDs during embryonic development, vasculogenesis and angiogenesis still remains elusive. We investigated the rol...

  9. c-Jun N-terminal Kinase (JNK) signaling as a therapeutic target for Alzheimer’s disease

    OpenAIRE

    Yarza, Ramon; Vela, Silvia; Solas, Maite; Ramirez, Maria J

    2016-01-01

    c-Jun N-terminal kinases (JNKs) are a family of protein kinases that play a central role in stress signaling pathways implicated in gene expression, neuronal plasticity, regeneration, cell death, and regulation of cellular senescence. It has been shown that there is a JNK pathway activation after exposure to different stressing factors, including cytokines, growth factors, oxidative stress, unfolded protein response signals or Aβ peptides. Altogether, JNKs have become a focus of screening str...

  10. Emergence of fatal PRRSV variants: unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark.

    Directory of Open Access Journals (Sweden)

    Kegong Tian

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS is a severe viral disease in pigs, causing great economic losses worldwide each year. The causative agent of the disease, PRRS virus (PRRSV, is a member of the family Arteriviridae. Here we report our investigation of the unparalleled large-scale outbreaks of an originally unknown, but so-called "high fever" disease in China in 2006 with the essence of PRRS, which spread to more than 10 provinces (autonomous cities or regions and affected over 2,000,000 pigs with about 400,000 fatal cases. Different from the typical PRRS, numerous adult sows were also infected by the "high fever" disease. This atypical PRRS pandemic was initially identified as a hog cholera-like disease manifesting neurological symptoms (e.g., shivering, high fever (40-42 degrees C, erythematous blanching rash, etc. Autopsies combined with immunological analyses clearly showed that multiple organs were infected by highly pathogenic PRRSVs with severe pathological changes observed. Whole-genome analysis of the isolated viruses revealed that these PRRSV isolates are grouped into Type II and are highly homologous to HB-1, a Chinese strain of PRRSV (96.5% nucleotide identity. More importantly, we observed a unique molecular hallmark in these viral isolates, namely a discontinuous deletion of 30 amino acids in nonstructural protein 2 (NSP2. Taken together, this is the first comprehensive report documenting the 2006 epidemic of atypical PRRS outbreak in China and identifying the 30 amino-acid deletion in NSP2, a novel determining factor for virulence which may be implicated in the high pathogenicity of PRRSV, and will stimulate further study by using the infectious cDNA clone technique.

  11. Atypical Clinical Behavior of p16-Confirmed HPV-Related Oropharyngeal Squamous Cell Carcinoma Treated With Radical Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang Shaohui [Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Perez-Ordonez, Bayardo [Department of Pathology, University Health Network, Toronto, Ontario (Canada); Liu Feifei [Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Division of Applied Molecular Oncology, Ontario Cancer Institute, University Health Network, Toronto, Ontario (Canada); Waldron, John; Ringash, Jolie [Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Irish, Jonathan [Department of Surgical Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Cummings, Bernard [Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Siu, Lillian L. [Division of Medical Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Kim, John [Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Weinreb, Ilan [Department of Pathology, University Health Network, Toronto, Ontario (Canada); Hope, Andrew [Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Gullane, Patrick; Brown, Dale [Department of Surgical Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Shi, Willa [Division of Applied Molecular Oncology, Ontario Cancer Institute, University Health Network, Toronto, Ontario (Canada); O' Sullivan, Brian, E-mail: Brian.OSullivan@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada)

    2012-01-01

    Purpose: To report atypical clinical behavior observed in human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) treated with radiotherapy. Methods and Materials: A retrospective cohort study was conducted for all newly diagnosed OPC cases treated with radiotherapy on July 1, 2003 to April 30, 2009. HPV positivity was determined by p16 immunostaining in tumors. The incidence of additional malignancies and the pattern of distant metastases (DMs) were compared between the HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Results: HPV status was evaluated in 318 of 613 consecutive OPC cases (52%), showing 236 HPV+ and 82 HPV- patients. Compared with HPV-, HPV+ cases were less likely to have additional malignancies (prior: 11% vs. 20%, p = 0.038; synchronous: 1% vs. 9%, p = 0.001; metachronous: 6% vs. 16%, p = 0.003). Whereas the majority (10 of 12) of HPV- additional head-and-neck (HN) mucosal malignancies were in the oral cavity, there was none (0 of 7) in the HPV+ cohort (p < 0.001). HPV+ synchronous HN second primaries (SPs) were in the supraglottis, post-cricoid, and nasopharynx; metachronous HN SPs were in the glottis, supraglottis, and ethmoid plus glottis/post-cricoid region. All SPs that could be tested were HPV+. There was no difference in DM rate (10% vs. 15%, p = 0.272), but HPV+ DMs were more likely to involve multiple organs (46% vs. 0%, p = 0.005) and unusual sites. Conclusions: This study reports atypical clinical behavior seen in HPV+ OPC, including multicentric lesions in HN mucosa and DM to multiple organs and unusual sites. The frequency of these events is low, but they may have clinical implications. The routine assessment of HPV status for all OPC is warranted.

  12. Functional analysis of related CrRLK1L receptor-like kinases in pollen tube reception.

    Science.gov (United States)

    Kessler, Sharon A; Lindner, Heike; Jones, Daniel S; Grossniklaus, Ueli

    2015-01-01

    The Catharanthus roseus Receptor-Like Kinase 1-like (CrRLK1L) family of 17 receptor-like kinases (RLKs) has been implicated in a variety of signaling pathways in Arabidopsis, ranging from pollen tube (PT) reception and tip growth to hormonal responses. The extracellular domains of these RLKs have malectin-like domains predicted to bind carbohydrate moieties. Domain swap analysis showed that the extracellular domains of the three members analyzed (FER, ANX1, HERK1) are not interchangeable, suggesting distinct upstream components, such as ligands and/or co-factors. In contrast, their intercellular domains are functionally equivalent for PT reception, indicating that they have common downstream targets in their signaling pathways. The kinase domain is necessary for FER function, but kinase activity itself is not, indicating that other kinases may be involved in signal transduction during PT reception. PMID:25490905

  13. MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism.

    Directory of Open Access Journals (Sweden)

    Laura P Bernard

    Full Text Available The Par1 kinases, also known as microtubule affinity-regulating kinases (MARKs, are important for the establishment of cell polarity from worms to mammals. Dysregulation of these kinases has been implicated in autism, Alzheimer's disease and cancer. Despite their important function in health and disease, it has been unclear how the activity of MARK/Par1 is regulated by signals from cell surface receptors. Here we show that MARK/Par1 is activated downstream of NMDA receptors in primary hippocampal neurons. Further, we show that this activation is dependent on protein kinase A (PKA, through the phosphorylation of Ser431 of Par4/LKB1, the major upstream kinase of MARK/Par1. Together, our data reveal a novel mechanism by which MARK/Par1 is activated at the neuronal synapse.

  14. Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

    Institute of Scientific and Technical Information of China (English)

    Soo Ryang Kim; Susumu Imoto; Taisuke Nakajima; Kenji Ando; Keiji Mita; Katsumi Fukuda; Ryo Nishikawa; Yu-ichiro Koma; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

    2009-01-01

    We describe a 15-mm scirrhous hepatocellular carcinoma (HCC) in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase. Contrast-enhanced computed tomography (CT) revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase. Magnetic resonance imaging (MRI) revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hyperintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC. Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically, the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.

  15. Atypical Cutaneous Manifestations in Adult Onset Still’s Disease

    Directory of Open Access Journals (Sweden)

    Champa Nataraja

    2016-01-01

    Full Text Available Adult Onset Still’s Disease (AOSD, an adult variant of systemic onset juvenile idiopathic arthritis, is a rare systemic inflammatory disorder of unknown aetiology. The rarity of this disease is associated with low index of suspicion and delayed diagnosis in patients suffering from it and in the presence of atypical features the diagnosis can be further challenging. This is a case report on a 24-year-old woman, who was a diagnostic dilemma for 2 years due to the nonspecific symptoms of recurrent fever, generalized maculopapular persistent pruritic and tender rash, and polyarthralgia. She was initially diagnosed as leukocytoclastic vasculitis on a skin biopsy and was managed by a dermatologist with various medications including NSAIDs, hydroxychloroquine, dapsone, colchicine, cyclosporine, and high doses of oral steroids with minimal response. Subsequently, she has had multiple admissions with similar symptoms with raised inflammatory markers and negative septic workup. On one occasion, her iron study revealed hyperferritinaemia which led to the suspicion of AOSD. Once the rheumatic fever and infectious, malignant, autoimmune, and lymphoproliferative disorders were excluded, she was diagnosed as probable AOSD and managed successfully with IL-1 (interleukin-1 receptor antagonist, Anakinra, with remarkable and lasting response both clinically and biochemically.

  16. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins

    Directory of Open Access Journals (Sweden)

    Elisa E. Figueroa-Angulo

    2015-11-01

    Full Text Available Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs that interact with an iron responsive element (IRE located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis.

  17. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins.

    Science.gov (United States)

    Figueroa-Angulo, Elisa E; Calla-Choque, Jaeson S; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

    2015-11-26

    Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis.

  18. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Rose M. Ayoob

    2016-01-01

    Full Text Available The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males, mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies.

  19. Atypical Time Course of Object Recognition in Autism Spectrum Disorder

    Science.gov (United States)

    Caplette, Laurent; Wicker, Bruno; Gosselin, Frédéric

    2016-01-01

    In neurotypical observers, it is widely believed that the visual system samples the world in a coarse-to-fine fashion. Past studies on Autism Spectrum Disorder (ASD) have identified atypical responses to fine visual information but did not investigate the time course of the sampling of information at different levels of granularity (i.e. Spatial Frequencies, SF). Here, we examined this question during an object recognition task in ASD and neurotypical observers using a novel experimental paradigm. Our results confirm and characterize with unprecedented precision a coarse-to-fine sampling of SF information in neurotypical observers. In ASD observers, we discovered a different pattern of SF sampling across time: in the first 80 ms, high SFs lead ASD observers to a higher accuracy than neurotypical observers, and these SFs are sampled differently across time in the two subject groups. Our results might be related to the absence of a mandatory precedence of global information, and to top-down processing abnormalities in ASD. PMID:27752088

  20. An Atypical Presentation of Allergic Myocardial İnfarction

    Directory of Open Access Journals (Sweden)

    Veysel Oktay

    2014-09-01

    Full Text Available Acute coronary syndromes secondary to hypersensitivity reactions related with allergic factors are defined as Kounis syndrome. Doxycycline is an antibiotic commonly used in clinical practice. In this report, we described an atypical presentation of Kounis syndrome in a patient who was admitted to the emergency service complaining of chest pain, generalized rash and fever. She was taking doxycycline for 3 days because of urinary tract infection. Non specific ST-T changes were seen on electrocardiography, positive troponin levels were detected and global left ventricular wall motion abnormalities were defined by echocardiography. The patient had no conventional risk factor for acute coronary syndrome. Normal coronary angiography results, improved left ventricular functions and symptoms by antihistaminic and steroid treatments were consistent with Kounis syndrome. All patients admitted with the concurrence of chest pain and allergic symptoms should be asked about exposure to allergens. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 202-4

  1. Atypical Enteropathogenic Escherichia coli Secretes Plasmid Encoded Toxin

    Directory of Open Access Journals (Sweden)

    Rita C. Ruiz

    2014-01-01

    Full Text Available Plasmid encoded toxin (Pet is a serine protease originally described in enteroaggregative Escherichia coli (EAEC prototype strain 042 whose entire characterization was essentially obtained from studies performed with the purified toxin. Here we show that Pet is not exclusive to EAEC. Atypical enteropathogenic Escherichia coli (aEPEC strains, isolated from diarrhea cases, express Pet and its detection in supernatants of infected HEp-2 cells coincides with the appearance of cell damage, which, in turn, were similar to those described with purified Pet. Pet secretion and the cytotoxic effects are time and culture medium dependent. In presence of DMEM supplemented with tryptone cell rounding and detachment were observed after just 5 h of incubation with the bacteria. In the absence of tryptone, the cytotoxic effects were detected only after 24 h of infection. We also show that, in addition to the prototype EAEC, other pet+ EAEC strains, also isolated from diarrhea cases, induce cellular damage in the same degree as the aEPEC. The cytotoxic effects of EAEC and aEPEC strains were significantly reduced in the presence of a serine protease inhibitor or anti-Pet IgG serum. Our results show a common aspect between the aEPEC and EAEC and provide the first evidence pointing to a role of Pet in aEPEC pathogenesis.

  2. ATYPICAL BULLOUS PYODERMA GANGRENOSUM WITH EARLY LESIONS MIMICKING CHICKEN POX

    Directory of Open Access Journals (Sweden)

    Ramesh

    2013-10-01

    Full Text Available ABSTRACT : Pyoderma Gangrenosum (PG rare neutrophilic dermatoses (1/100,00 0, of which Bullous Pyoderma gangrenosum is an atypical form, which is very rare. Bullous PG is usually associated with haematological disorders like myeloproliferative disorders, haematological malignancies specially AML and several other haematological disorders. It presents as a superficial haemorrhagic bulla which ulcerates, ulcers increase in size and heal with scarring. Treatment is mainly to identify and treat the cause. Pyoderma Gangrenosum shows rapid response to oral corticosteroid therapy. 1 , 3 . Clinical presentation: A 32yr old female presented with fever, multiple vesicles on face, upper limb, lower limb and trunk, and these early lesions looked like chicken pox lesions. Lesions increased in size to form haemorrhagic bullas which eroded to form ulcers, ulcers rapidly increased in size with necrotic base and erythematous to violaceous border. Investigation: Haemoglobin: 5.7gm%, Peripheral smear: normocytic and normochromic anaemia. Skin Biopsy: Sub corneal blisters with dermal and perifollicular n eutrophilic infiltrate. A diagnosis of Bullous Pyoderma gangrenosum was made. Patient’s anaemia was treated; oral prednisolone and topical steroids were started. Patient showed marked improvement to treatment.

  3. EVOLUTION OF ROTATIONAL VELOCITIES OF A-TYPE STARS

    International Nuclear Information System (INIS)

    The equatorial velocity of A-type stars undergoes an acceleration in the first third of the main sequence (MS) stage, but the velocity decreases as if the stars were not undergoing any redistribution of angular momentum in the external layers in the last stage of the MS phase. Our calculations show that the acceleration and the decrease of the equatorial velocity can be reproduced by the evolution of the differential rotation zero-age MS model with the angular momentum transport caused by hydrodynamic instabilities during the MS stage. The acceleration results from the fact that the angular momentum stored in the interiors of the stars is transported outward. In the last stage, the core and the radiative envelope are uncoupling, and the rotation of the envelope is a quasi-solid rotation; the uncoupling and the expansion of the envelope indicate that the decrease of the equatorial velocity approximately follows the slope for the change in the equatorial velocity of the model without any redistribution of angular momentum. When the fractional age 0.3 ∼MS ∼< 0.5, the equatorial velocity remains almost constant for stars whose central density increases with age in the early stage of the MS phase, while the velocity decreases with age for stars whose central density decreases with age in the early stage of the MS phase.

  4. Rest mutant zebrafish swim erratically and display atypical spatial preferences.

    Science.gov (United States)

    Moravec, Cara E; Li, Edward; Maaswinkel, Hans; Kritzer, Mary F; Weng, Wei; Sirotkin, Howard I

    2015-05-01

    The Rest/Nrsf transcriptional repressor modulates expression of a large set of neural specific genes. Many of these target genes have well characterized roles in nervous system processes including development, plasticity and synaptogenesis. However, the impact of Rest-mediated transcriptional regulation on behavior has been understudied due in part to the embryonic lethality of the mouse knockout. To investigate the requirement for Rest in behavior, we employed the zebrafish rest mutant to explore a range of behaviors in adults and larva. Adult rest mutants of both sexes showed abnormal behaviors in a novel environment including increased vertical swimming, erratic swimming patterns and a proclivity for the tank walls. Adult males also had diminished reproductive success. At 6 days post fertilization (dpf), rest mutant larva were hypoactive, but displayed normal evoked responses to light and sound stimuli. Overall, these results provide evidence that rest dysfunction produces atypical swimming patterns and preferences in adults, and reduced locomotor activity in larvae. This study provides the first behavioral analysis of rest mutants and reveals specific behaviors that are modulated by Rest.

  5. Transoral robotic surgery for atypical carcinoid tumor of the larynx.

    Science.gov (United States)

    Muderris, Togay; Bercin, Sami; Sevil, Ergun; Acar, Baran; Kiris, Muzaffer

    2013-11-01

    In recent years, transoral robotic surgery has been introduced as an efficient and a reliable method for excision of selected oral cavity, tongue base, and supraglottic tumors in otolaryngology. In this case report, a 39-year-old woman with a history of hoarseness and dysphagia for approximately 6 months is presented. The patient was diagnosed with atypical carcinoid tumor on the laryngeal aspect of the epiglottis, and excision of the tumor was performed through transoral robotic surgery using the robotic da Vinci surgical system, a 0-degree three-dimensional endoscope, 5-mm microinstruments compatible with the da Vinci robot, and a Feyh-Kastenbauer/Weinstein-O'Malley retractor. The mass was removed completely, and no complications occurred. The patient recovered without a need for tracheotomy. Findings of the 1-year clinical follow-up revealed no locoregional recurrence or distant metastasis. This case shows, once again, that transoral robotic surgery could be used safely and effectively regardless of pathologic diagnosis in the supraglottic region tumors. PMID:24220389

  6. Atypical Hemolytic Uremic Syndrome Recurrence after Renal Transplantation

    Science.gov (United States)

    Bouatou, Yassine; Bacchi, Véronique Frémeaux; Villard, Jean; Moll, Solange; Martin, Pierre-Yves; Hadaya, Karine

    2015-01-01

    Abstract Risk for atypical hemolytic uremic syndrome (aHUS) recurrence after renal transplantation is low with an isolated membrane cofactor protein mutation (MCP). We report the case of a 32-year-old woman with a MCP who underwent kidney transplantation with a good evolution at 12 months. At 15 and 35 months, 2 episodes of thrombotic microangiopathy (TMA), after a miscarriage and a preeclampsia, were misinterpreted as triggered by tacrolimus. After each episode however serum creatinine returned to baseline. Five years after transplantation, she had a self-limited rhinosinusitis followed 3 weeks later by an oliguric renal failure. Her complement profile was normal. Graft biopsy showed C3 glomerulonephritis with no “humps” on electron microscopy. No significant renal function improvement followed methylprednisolone pulsing. A second biopsy showed severe acute TMA lesions with C3 glomerular deposits. Despite weekly eculizumab for 1 month, dialysis was resumed. A new workup identified the “at-risk” complement factor H haplotype. Thus, aHUS recurrence should be ruled out in aHUS patients considered at low recurrence risk when a TMA is found in graft biopsy. Prompt eculizumab therapy should be considered to avoid graft loss as aHUS recurrence can first present as a C3 glomerulonephritis. PMID:27500215

  7. Rest Mutant zebrafish swim erratically and display atypical spatial preferences

    Science.gov (United States)

    Moravec, Cara E.; Li, Edward; Maaswinkel, Hans; Kritzer, Mary F.; Weng, Wei; Sirotkin, Howard I.

    2015-01-01

    The Rest/Nrsf transcriptional repressor modulates expression of a large set of neural specific genes. Many of these target genes have well characterized roles in nervous system processes including development, plasticity and synaptogenesis. However, the impact of Rest-mediated transcriptional regulation on behavior has been understudied due in part to the embryonic lethality of the mouse knockout. To investigate the requirement for Rest in behavior, we employed the zebrafish rest mutant to explore a range of behaviors in adults and larva. Adult rest mutants of both sexes showed abnormal behaviors in a novel environment including increased vertical swimming, erratic swimming patterns and a proclivity for the tank walls. Adult males also had diminished reproductive success. At 6 days post fertilization (dpf), rest mutant larva were hypoactive, but displayed normal evoked responses to light and sound stimuli. Overall, these results provide evidence that rest dysfunction produces atypical swimming patterns and preferences in adults, and reduced locomotor activity in larvae. This study provides the first behavioral analysis of rest mutants and reveals specific behaviors that are modulated by Rest. PMID:25712696

  8. MRI features of atypical teratoid/rhabdoid tumors in children

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Biao [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Shanghai Jiaotong University School of Medicine, Department of Radiology, XinHua Hospital (Chongming Branch), Shanghai (China); Feng, Xiao Yuan [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China)

    2013-08-15

    Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, highly malignant tumors of the central nervous system, usually occurring in young children. To investigate the MRI features of AT/RT, with special emphasis on diffusion-weighted imaging (DWI) and MR spectroscopy (MRS). MRI findings of 11 children with AT/RT were reviewed retrospectively, including DWI in 9 AT/RT children and MRS in 6 children. The neoplasms were infratentorial in 4 children and supratentorial in 5 children, both infra- and supratentorial in 1 child and multifocal in 1 child. AT/RT produced heterogeneous signal intensity from peripheral cysts in 7/11 (63%) and hemorrhage in 7/11 (63%). All lesions showed contrast enhancement of varying degrees. Seven (63%) had peritumoral edema. Nine (82%) were hyperintense on DWI with a mean {+-} SD ADC of 0.60 {+-} 0.13 x 10{sup -3} mm{sup 2} s{sup -1}. Six lesions (55%) exhibited elevated levels of choline and decreased NAA, and three had lipid peaks. A childhood intracranial tumor with off-midline location, peripheral cystic components, hemorrhage, low ADC, and lipid peaks on MRS suggests AT/RT to be considered a differential diagnosis. (orig.)

  9. Assesment, treatment and prevention of atypical hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    Azar Nickavar

    2013-01-01

    Full Text Available Hemolytic uremic syndrome (HUS is a heterogeneous group of hemolytic disorders. Different terminologies have been described in HUS, which are as follows: (1 D+ HUS: Presentation with a preceding diarrhea; (2 typical HUS: D+ HUS with a single and self-limited episode; (3 atypical HUS (aHUS: Indicated those with complement dysregulation; (4 recurrent HUS: Recurrent episodes of thrombocytopenia and/or microangiopathic hemolytic anemia (MAHA after improvement of hematologic abnormalities; and (5 familial HUS: Necessary to distinct synchronous outbreaks of D+ HUS in family members and asynchronous disease with an inherited risk factor. aHUS is one of the potential causes of end-stage renal disease (ESRD in children. It has a high recurrence after renal transplantation in some genetic forms. Therefore, recognition of the responsible mechanism and proper prophylactic treatment are recommended to prevent or delay the occurrence of ESRD and prolong the length of survival of the transplanted kidney. A computerized search of MEDLINE and other databases was carried out to find the latest results in pathogenesis, treatment, and prevention of aHUS.

  10. Rotation and surface abundance peculiarities in A-type stars

    CERN Document Server

    Takeda, Yoichi; Kang, Dong-Il; Lee, Byeong-Cheol; Kim, Kang-Min

    2008-01-01

    In an attempt of clarifying the connection between the photospheric abundance anomalies and the stellar rotation as well as of exploring the nature of "normal A" stars, the abundances of seven elements (C, O, Si, Ca, Ti, Fe, and Ba) and the projected rotational velocity for 46 A-type field stars were determined by applying the spectrum-fitting method to the high-dispersion spectral data obtained with BOES at BOAO. We found that the peculiarities (underabundances of C, O, and Ca; an overabundance of Ba) seen in slow rotators efficiently decrease with an increase of rotation, which almost disappear at v_e sin i > 100 km s^-1. This further suggests that stars with sufficiently large rotational velocity may retain the original composition at the surface without being altered. Considering the subsolar tendency (by several tenths dex below) exhibited by the elemental abundances of such rapidly-rotating (supposedly normal) A stars, we suspect that the gas metallicity may have decreased since our Sun was born, contra...

  11. Using atypical symptoms and red flags to identify non-demyelinating disease.

    LENUS (Irish Health Repository)

    Kelly, Siobhan B

    2012-01-01

    Red flags and atypical symptoms have been described as being useful in suggesting alternative diagnoses to multiple sclerosis (MS) and clinically isolated syndrome (CIS); however, their diagnostic utility has not been assessed. The aim of this study was to establish the predictive value of red flags and the typicality\\/atypicality of symptoms at presentation in relation to the final diagnosis of patients referred with suspected MS.

  12. Atypical ultrasound features of parathyroid tumours may bear a relationship to their clinical and biochemical presentation

    OpenAIRE

    Chandramohan, Anuradha; Sathyakumar, Kirthi; John, Reetu Amrita; Manipadam, Marie Therese; Abraham, Deepak; Thomas V Paul; Thomas, Nihal; Paul, M. J.

    2013-01-01

    Objectives To describe atypical ultrasound features of parathyroid lesions and correlate them with clinical presentation and histopathology. Materials and methods Retrospective review of 264 patients with primary hyperparathyroidism who underwent ultrasound imaging prior to parathyroidectomy was performed. Patients with atypical ultrasound findings (n = 26) were identified; imaging findings were correlated with clinical presentation and histopathology. Results Twenty-one (80 %) lesions were a...

  13. CHALLENGE WITH ATYPICAL ANTIPSYCHOTIC DRUGS IN RISPERIDONE INDUCED NEUROLEPTIC MALIGNANT SYNDROME: A CASE REPORT

    OpenAIRE

    Mendhekar, D.N.; Jiloha, R.C.; M M Mehndiratta; War, L.

    2002-01-01

    There are several reports available on neuroleptic malignant syndrome (NMS) associated with risperidone but when a more stringent criterion is applied there are only a few. Report on challenge and rechallenge with various atypical antipsychotic drugs in re-emergence of post NMS psychosis is scanty. Our aim of presenting this is to highlight the differential response of various atypical antipsychotic drugs in the treatment of post NMS psychosis. This paper reports a young male with mild mental...

  14. Atypical depression: useful concept, but it's time to revise the DSM-IV criteria.

    Science.gov (United States)

    Thase, Michael E

    2009-12-01

    Stewart et al (2009) have outlined the evidence in support of the validity of the DSM-IV definition of the 'With Atypical Features' episode specifier. Although recognizing the historical significance and clinical utility of the concept of atypical depression, this article takes issue with the DSM-IV criteria. It is concluded that mood reactivity, the A or obligative criterion, is neither significantly associated with the other symptomatic criteria nor useful to diagnose atypical depression, and thus should be eliminated. Problems with operationalization, specification, and reliability of ratings of the diagnostic criteria further limit validity. Despite these limitations in classification, many of the features associated with atypical depression are linked to an early onset of affective illness, including trait-like interpersonal sensitivity, comorbid social anxiety and agoraphobia, a history of childhood physical or sexual trauma, and indicators of the 'soft' side of the bipolar spectrum. Neurophysiologic studies also suggest that chronic, early-onset atypical depressions differ from both melancholia and normality. Re-analyses of the Columbia group's seminal studies suggest that preferential response to phenelzine vs imipramine--arguably the strongest validator of atypical depression--similarly appears to be limited to patients with chronic, early-onset syndromes. The criteria for atypical depression need to be revised in DSM-V, including sharpening the operational definitions for the specific symptoms. The importance of age of onset and comorbid anxiety warrant further study. Research examining the validity of a subform of atypical depression characterized by trait-like interpersonal sensitivity and a chronic, early-onset course may further enhance the clinical utility of the DSM-V classification. PMID:19741592

  15. Good and bad at numbers: typical and atypical development of number processing and arithmetic

    OpenAIRE

    Iuculano, T.

    2012-01-01

    This thesis elucidates the heterogeneous nature of mathematical skills by examining numerical and arithmetical abilities in typical, atypical and exceptional populations. Moreover, it looks at the benefits of intervention for remediating and improving mathematical skills. First, we establish the nature of the ‘number sense’ and assess its contribution to typical and atypical arithmetical development. We confirmed that representing and manipulating numerosities approximately is fundamentally d...

  16. Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi.

    Science.gov (United States)

    Husain, Ehab A; Mein, Charles; Pozo, Lucia; Blanes, Alfredo; Diaz-Cano, Salvador J

    2011-04-01

    Atypical (dysplastic) melanocytic nevi are clinically heterogeneous malignant melanoma precursors, for which no topographic analysis of cell kinetic, cell cycle regulators and microsatellite profile is available. We selected low-grade atypical melanocytic nevi (92), high-grade atypical melanocytic nevi (41), melanocytic nevi (18 junctional, 25 compound) and malignant melanomas (16 radial growth phase and 27 vertical growth phase). TP53, CDKN2A, CDKN1A, and CDKN1B microsatellite patterns were topographically studied after microdissection; Ki-67, TP53, CDKN2A, CDKN1A, and CDKN1B expressions and DNA fragmentation by in situ end labeling for apoptosis were topographically scored. Results were statistically analyzed. A decreasing junctional-dermal marker expression gradient was observed, directly correlating with atypical melanocytic nevus grading. High-grade atypical melanocytic nevi revealed coexistent TP53-CDKN2A-CDKN1B microsatellite abnormalities, and significantly higher junctional Ki67-TP53 expression (inversely correlated with CDKN1A-CDKN1B expression and in situ end labeling). Malignant melanomas showed coexistent microsatellite abnormalities (CDKN2A-CDKN1B), no topographic gradient, and significantly decreased expression. Melanocytic nevi and low-grade atypical melanocytic nevi revealed sporadic junctional CDKN2A microsatellite abnormalities and no significant topographic kinetic differences. High-grade atypical melanocytic nevi accumulate junctional TP53-CDKN1A-CDKN1B microsatellite abnormalities, being progression TP53-independent and better assessed in the dermis. Melanocytic nevi and low-grade atypical melanocytic nevi show low incidence of microsatellite abnormalities, and kinetic features that make progression unlikely.

  17. Clonal Relationship among Atypical Enteropathogenic Escherichia coli Strains Isolated from Different Animal Species and Humans▿

    OpenAIRE

    Moura, Rodrigo A.; Sircili, Marcelo P.; Leomil, Luciana; Matté, Maria Helena; Trabulsi, Luiz R.; Elias, Waldir P.; Irino, Kinue; Antonio F. Pestana de Castro

    2009-01-01

    Forty-nine typical and atypical enteropathogenic Escherichia coli (EPEC) strains belonging to different serotypes and isolated from humans, pets (cats and dogs), farm animals (bovines, sheep, and rabbits), and wild animals (monkeys) were investigated for virulence markers and clonal similarity by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The virulence markers analyzed revealed that atypical EPEC strains isolated from animals have the potential to cause dia...

  18. Atypical Findings of Guillain-Barré Syndrome in Children

    Directory of Open Access Journals (Sweden)

    Parvaneh KARIMZADEH

    2013-01-01

    Full Text Available How to cite this article: Karimzadeh P, Bakhshandeh Bali MK, Nasehi MM, Taheri Otaghsara SM, Ghofrani M. Atypical Findings of Guillain-Barré Syndrome in Children. Iran J Child Neurol Autumn 2012;6(4:17-22. AbstractObjectiveGuillain-Barre syndrome (GBS is an immune-mediated polyneuropathy that occurs mostly after  prior infection. The diagnosis of this syndrome is dependent heavily on the history and examination, although cerebrospinal fluid analysis and electrodiagnostic testing usually confirm the diagnosis. This is a retrospective study which was performed to investigate the atypical features of GBS.Materials & MethodsThirty three patients (21/63.6% males and 12/36.4% females with GBS were retrospectively studied and prospectively evaluated at the Child Neurology institute of Mofid Children Hospital of Shahid Beheshti University of Medical Sciences between May 2011 and September 2012.ResultsThe mean age was 5.4 years (range, 1.5-10.5.Twenty one patients (87.9 % had previous history of infections. Eight patients (24.2% admitted with atypical symptoms like upper limb weakness (3%, ptosis (3%, neck stiffness (3%, inability to stand (proximal weakness (9.1%, headache (3% and dysphagia (3%.According to disease process, weakness was ascending in 26 (78.8%, descending in 5 (15.2% and static in 2 (6.1% patients. Cranial nerve involvement was found in 8(24.3% children, most commonly as facial palsy in 3 (9.1%.ConclusionIn this study, 24.3% of our patients presented with atypical symptoms of GBS as upper limb weakness, ptosis, neck stiffness, inability to stand (proximal weakness, headache and dysphagia References:Hughes RA, Cornblath DR. Guillain-Barré syndrome. Lancet. 2005 Nov 5;366(9497:1653-66.McGillicuddy DC, Walker O, Shapiro NI, Edlow JA. Guillain-Barré syndrome in the emergency department. Ann Emerg Med. 2006 Apr;47(4:390-3.Cosi V, Versino M. Guillain-Barré syndrome. Neurol Sci. 2006;27(Suppl 1:S47-51.Hughes RA, Cornblath DR. Guillain

  19. The complement of protein kinases of the microsporidium Encephalitozoon cuniculi in relation to those of Saccharomyces cerevisiae and Schizosaccharomyces pombe

    Directory of Open Access Journals (Sweden)

    Vivares Christian P

    2007-09-01

    Full Text Available Abstract Background Microsporidia, parasitic fungi-related eukaryotes infecting many cell types in a wide range of animals (including humans, represent a serious health threat in immunocompromised patients. The 2.9 Mb genome of the microsporidium Encephalitozoon cuniculi is the smallest known of any eukaryote. Eukaryotic protein kinases are a large superfamily of enzymes with crucial roles in most cellular processes, and therefore represent potential drug targets. We report here an exhaustive analysis of the E. cuniculi genomic database aimed at identifying and classifying all protein kinases of this organism with reference to the kinomes of two highly-divergent yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. Results A database search with a multi-level protein kinase family hidden Markov model library led to the identification of 29 conventional protein kinase sequences in the E. cuniculi genome, as well as 3 genes encoding atypical protein kinases. The microsporidian kinome presents striking differences from those of other eukaryotes, and this minimal kinome underscores the importance of conserved protein kinases involved in essential cellular processes. ~30% of its kinases are predicted to regulate cell cycle progression while another ~28% have no identifiable homologues in model eukaryotes and are likely to reflect parasitic adaptations. E. cuniculi lacks MAP kinase cascades and almost all protein kinases that are involved in stress responses, ion homeostasis and nutrient signalling in the model fungi S. cerevisiae and S. pombe, including AMPactivated protein kinase (Snf1, previously thought to be ubiquitous in eukaryotes. A detailed database search and phylogenetic analysis of the kinomes of the two model fungi showed that the degree of homology between their kinomes of ~85% is much higher than that previously reported. Conclusion The E. cuniculi kinome is by far the smallest eukaryotic kinome characterised to date

  20. Atypical Mole (Atypical Nevus)

    Science.gov (United States)

    ... melanoma). Remember the ABCDEs of melanoma lesions: A - Asymmetry: One half of the lesion does not mirror ... York: Mosby, 2003. Last Updated: 22 Dec 2008 Information for other ages: Child Teen Table of Contents: ...

  1. How do we choose between atypical antipsychotics? The advantages of amisulpride.

    Science.gov (United States)

    Mortimer, Ann M

    2004-03-01

    Clinician choice of an atypical antipsychotic may depend on a number of factors such as perceived efficacy, tolerability and cost. It is also important that the choice of treatment takes into consideration the previous response to treatment, experience of side-effects and personal clinical characteristics. The receptor-affinity profiles of the atypical antipsychotics differ; with the exception of amisulpride, a selective D2/D3 antagonist, all the atypical antipsychotics exhibit a greater affinity for the serotonin-2A receptors than dopamine receptors. However, there is no evidence that the variation in receptor affinities is relevant to efficacy. Indeed, the crucial factor may be fast dissociation from low affinity for the D2 receptor. Tolerability also varies between the atypical antipsychotics and the side-effect profile may be related to the receptor-affinity profile of the individual drugs. Extrapyramidal side-effects are generally less of a problem with most atypical drugs than with conventional drugs, but weight gain, loss of glycaemic control, sedation and hyperprolactinaemia remain problematic in some patients. Amisulpride is effective for the treatment of both positive and negative symptoms, and is well tolerated with regard to weight gain, glucose tolerance and sedation. In two clinical trials, the AMIRIS and SOLIANOL studies, amisulpride demonstrated clear advantages over some other atypical antipsychotics with respect to negative symptoms, depressive symptoms and weight gain.

  2. Atypical/Nor98 scrapie in the Basque Country: a case report of eight outbreaks

    Directory of Open Access Journals (Sweden)

    Minguijón Esmeralda

    2010-03-01

    Full Text Available Abstract Background Since 2002, an active surveillance program for transmissible spongiform encephalopathy in small ruminants in European Union countries allowed identification of a considerable number of atypical cases with similarities to the previously identified atypical scrapie cases termed Nor98. Case presentation Here we report molecular and neuropathological features of eight atypical/Nor98 scrapie cases detected between 2002 and 2009. Significant features of the affected sheep included: their relatively high ages (mean age 7.9 years, range between 4.3 and 12.8, their breed (all Latxa and their PRNP genotypes (AFRQ/ALRQ, ALRR/ALRQ, AFRQ/AFRQ, AFRQ/AHQ, ALRQ/ALRH, ALRQ/ALRQ. All the sheep were confirmed as atypical scrapie by immunohistochemistry and immunoblotting. Two cases presented more PrP immunolabelling in cerebral cortex than in cerebellum. Conclusions This work indicates that atypical scrapie constitutes the most common small ruminant transmissible spongiform encephalopathy form in Latxa sheep in the Spanish Basque Country. Moreover, a new genotype (ALRQ/ALRH was found associated to atypical scrapie.

  3. Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors.

    Science.gov (United States)

    Masiá, M; Gutiérrez, F; Padilla, S; Soldán, B; Mirete, C; Shum, C; Hernández, I; Royo, G; Martin-Hidalgo, A

    2007-02-01

    The aim of this study was to characterise community-acquired pneumonia (CAP) caused by atypical pathogens by combining distinctive clinical and epidemiological features and novel biological markers. A population-based prospective study of consecutive patients with CAP included investigation of biomarkers of bacterial infection, e.g., procalcitonin, C-reactive protein and lipopolysaccharide-binding protein (LBP) levels. Clinical, radiological and laboratory data for patients with CAP caused by atypical pathogens were compared by univariate and multivariate analysis with data for patients with typical pathogens and patients from whom no organisms were identified. Two predictive scoring models were developed with the most discriminatory variables from multivariate analysis. Of 493 patients, 94 had CAP caused by atypical pathogens. According to multivariate analysis, patients with atypical pneumonia were more likely to have normal white blood cell counts, have repetitive air-conditioning exposure, be aged <65 years, have elevated aspartate aminotransferase levels, have been exposed to birds, and have lower serum levels of LBP. Two different scoring systems were developed that predicted atypical pathogens with sensitivities of 35.2% and 48.8%, and specificities of 93% and 91%, respectively. The combination of selected patient characteristics and laboratory data identified up to half of the cases of atypical pneumonia with high specificity, which should help clinicians to optimise initial empirical therapy for CAP.

  4. Regulation of mitogen-activated protein kinase pathways by the plasma membrane Na+/H+ exchanger, NHE1

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Darborg, Barbara Vasek; Rentsch, Maria Louise;

    2006-01-01

    The mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK, play a major role in the regulation of pivotal cellular processes such as cell death/survival balance, cell cycle progression, and cell migration. MAPK...... activity is regulated by a three-tiered phosphorelay system, which is in turn regulated by a complex network of signaling events and scaffolding proteins. The ubiquitous plasma membrane Na(+)/H(+) exchanger NHE1 is activated by, and implicated in, the physiological/pathophysiological responses to many of...

  5. DMPD: Bruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15081522 Bruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signall...ruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? PubmedID 15081522 Title Bruton...'s tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? Authors

  6. [Protein kinase C activation induces platelet apoptosis].

    Science.gov (United States)

    Zhao, Li-Li; Chen, Meng-Xing; Zhang, Ming-Yi; Dai, Ke-Sheng

    2013-10-01

    Platelet apoptosis elucidated by either physical or chemical compound or platelet storage occurs wildly, which might play important roles in controlling the numbers and functions of circulated platelets, or in the development of some platelet-related diseases. However, up to now, a little is known about the regulatory mechanisms of platelet apoptosis. Protein kinase C (PKC) is highly expressed in platelets and plays central roles in regulating platelet functions. Although there is evidence indicating that PKC is involved in the regulation of apoptosis of nucleated cells, it is still unclear whether PKC plays a role in platelet apoptosis. The aim of this study was to investigate the role of PKC in platelet apoptosis. The effects of PKC on mitochondrial membrane potential (ΔΨm), phosphatidylserine (PS) exposure, and caspase-3 activation of platelets were analyzed by flow cytometry and Western blot. The results showed that the ΔΨm depolarization in platelets was induced by PKC activator in time-dependent manner, and the caspase-3 activation in platelets was induced by PKC in concentration-dependent manner. However, the platelets incubated with PKC inhibitor did not results in ΔΨm depolarization and PS exposure. It is concluded that the PKC activation induces platelet apoptosis through influencing the mitochondrial functions and activating caspase 3. The finds suggest a novel mechanism for PKC in regulating platelet numbers and functions, which has important pathophysiological implications for thrombosis and hemostasis.

  7. Endocytosis of Receptor Tyrosine Kinases

    Science.gov (United States)

    Goh, Lai Kuan

    2013-01-01

    Endocytosis is the major regulator of signaling from receptor tyrosine kinases (RTKs). The canonical model of RTK endocytosis involves rapid internalization of an RTK activated by ligand binding at the cell surface and subsequent sorting of internalized ligand-RTK complexes to lysosomes for degradation. Activation of the intrinsic tyrosine kinase activity of RTKs results in autophosphorylation, which is mechanistically coupled to the recruitment of adaptor proteins and conjugation of ubiquitin to RTKs. Ubiquitination serves to mediate interactions of RTKs with sorting machineries both at the cell surface and on endosomes. The pathways and kinetics of RTK endocytic trafficking, molecular mechanisms underlying sorting processes, and examples of deviations from the standard trafficking itinerary in the RTK family are discussed in this work. PMID:23637288

  8. RIP Kinases Initiate Programmed Necrosis

    Institute of Scientific and Technical Information of China (English)

    Lorenzo Galluzzi; Oliver Kepp; Guido Kroemer

    2009-01-01

    Some lethal stimuli can induce either apoptosis or necrosis, depending on the cell type and/or experimental setting. Until recently,the molecular bases of this phenomenon were largely unknown. Now, two members of the receptor-interacting serine-threonine kinase (RIP) family, RIP1 and RIP3, have been demonstrated to control the switch between apoptotic and necrotic cell death.Some mechanistic details, however, remain controversial.

  9. Thymidine kinase diversity in bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, A.R.; Munch-Petersen, B.;

    2006-01-01

    Thymidine kinases (TKs) appear to be almost ubiquitous and are found in nearly all prokaryotes, eukaryotes, and several viruses. They are the key enzymes in thymidine salvage and activation of several anti-cancer and antiviral drugs. We show that bacterial TKs can be subdivided into 2 groups. The....... The TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  10. Pantothenate Kinase-Associated Neurodegeneration

    OpenAIRE

    Meitinger, Thomas; Prokisch, Holger; Hartig, Monika B.; Klopstock, Thomas

    2012-01-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a hereditary progressive disorder and the most frequent form of neurodegeneration with brain iron accumulation (NBIA). PKAN patients present with a progressive movement disorder, dysarthria, cognitive impairment and retinitis pigmentosa. In magnetic resonance imaging, PKAN patients exhibit the pathognonomic "eye of the tiger" sign in the globus pallidus which corresponds to iron accumulation and gliosis as shown in neuropathological e...

  11. Regulation and function of TPL-2,an IκB kinase-regulated MAP kinase kinase kinase

    Institute of Scientific and Technical Information of China (English)

    Thorsten Gantke; Srividya Sriskantharajah; Steven C Ley

    2011-01-01

    The IκB kinase(IKK)complex plays a well-documented role in innate and adaptive immunity.This function has been widely attributed to its role as the central activator of the NF-κB family of transcription factors.However,another important consequence of IKK activation is the regulation of TPL-2,a MEK kinase that is required for activation of ERK-1/2 MAP kinases in myeioid cells following Toll-like receptor and TNF receptor stimulation.In unstimulated cells,TPL-2 is stoichiometrically complexed with the NF-κB inhibitory protein NF-κB1 p105,which blocks TPL-2 access to its substrate MEK,and the ubiquitin-binding protein ABIN-2(A20-binding inhibitor of NF-κB 2),both of which are required to maintain TPL-2 protein stability.Following agonist stimulation,the IKK complex phosphorylates p105,triggering its K48-1inked ubiquitination and degradation by the proteasome.This releases TPL-2 from p105-mediated inhibition,facilitating activation of MEK,in addition to modulating NF-κB activation by liberating associated Rel subunits for translocation into the nucleus.IKK-induced proteolysis of 0105,therefore,can directly regulate both NF-κB and ERK MAP kinase activation via NF-κB1 p105.TPL-2 is critical for production of the proinflammatory cytokine TNF during inflammatory responses.Consequently,there has been considerable interest in the pharmaceutical industry to develop selective TPL-2 inhibitors as drugs for the treatment of TNF-dependent inflammatory,diseases,such as rheumatoid arthritis and inflammatory bowel disease.This review summarizes our current understanding of the regulation of TPL-2 signaling function,and also the complex positive and negative roles of TPL-2 in immune and inflammatory responses.

  12. Expression patterns of protein kinase D 3 during mouse development

    Directory of Open Access Journals (Sweden)

    Lutz Sylke

    2008-04-01

    Full Text Available Abstract Background The PKD family of serine/threonine kinases comprises a single member in Drosophila (dPKD, two isoforms in C. elegans (DKF-1 and 2 and three members, PKD1, PKD2 and PKD3 in mammals. PKD1 and PKD2 have been the focus of most studies up to date, which implicate these enzymes in very diverse cellular functions, including Golgi organization and plasma membrane directed transport, immune responses, apoptosis and cell proliferation. Concerning PKD3, a role in the formation of vesicular transport carriers at the trans-Golgi network (TGN and in basal glucose transport has been inferred from in vitro studies. So far, however, the physiological functions of the kinase during development remain unknown. Results We have examined the expression pattern of PKD3 during the development of mouse embryos by immunohistochemistry. Using a PKD3 specific antibody we demonstrate that the kinase is differentially expressed during organogenesis. In the developing heart a strong PKD3 expression is constantly detected from E10 to E16.5. From E12.5 on PKD3 is increasingly expressed in neuronal as well as in the supporting connective tissue and in skeletal muscles. Conclusion The data presented support an important role for PKD3 during development of these tissues.

  13. A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase.

    Directory of Open Access Journals (Sweden)

    Mutsuki Amano

    Full Text Available BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity.

  14. A potential mechanism underlying atypical antipsychotics-induced lipid disturbances.

    Science.gov (United States)

    Cai, H L; Tan, Q Y; Jiang, P; Dang, R L; Xue, Y; Tang, M M; Xu, P; Deng, Y; Li, H D; Yao, J K

    2015-10-20

    Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis. In addition, serum triacylglycerol, total cholesterol, free fatty acids and various hormones including progesterone, corticosterone and insulin were measured simultaneously. Following treatment with clozapine or risperidone, both lipogenesis and cholesterogenesis were enhanced via inhibition of PGRMC1/INSIG-2 and activation of SCAP/SREBP expressions. Such metabolic disturbances, however, were not demonstrated in rats treated with aripiprazole (ARI) or haloperidol (HAL). Moreover, the add-on treatment of MIF was effective in reversing the AAPD-induced lipid disturbances by upregulating the expression of PGRMC1/INSIG-2 and subsequent downregulation of SCAP/SREBP. Taken together, our findings suggest that disturbances in lipid metabolism can occur at an early stage of AAPD treatment before the presence of weight gain. Such metabolic defects can be modified by an add-on treatment of steroid antagonist MIF enhancing the PGRMC1 pathway. Thus, it is likely that PGRMC1/INSIG-2 signaling may be a therapeutic target for AAPD-induced weight gain.

  15. Atypical Endometriosis: a Clinicopathologic Study of 163 Cases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To investigate the clinicopathologic features of atypical endometriosis (AEM), and to discuss the relations between AEMs and tumors.METHODS A retrospective analysis was performed on 163 cases of AEMs. The changes in the glandular epithelium, stroma, and their background and the relationship with coexisting tumors were observed.RESULTS The AEMs account of for 4.4% (163/3,724) of the endometriosis (EM) cases. Of 172 AEM foci of 163 patients, 168 were in the ovary, and the other 4 were in the fallopian tube, cervix and uterine serosa. Of the cases of ovarian EM, 6.8% were AEM. All of the 27 cases (15.7%) of the AEMs associated with a tumor were found in the ovaries, of which 15 were malignant,9 borderline, and 3 benign. Of the ovary AEMs, 14.9% were associated with a borderline or malignant tumor. The AEM epithelia were mainly arranged in the form of surface epithelia, with only a few glands. Present were characteristic features of moderate to marked pleomorphism, epithelial tufting, bud or firework-like structures on microscopy. Epithelial metaplastic changes were observed in 86 cases (50%) of the 172 AEM foci. Epithelium, endometrioid stroma, and fibrotic-collagen formed a three-layer structure in the wall of the AEM cysts. The endometrioid stroma were usually thin compared to the fibro-collagen tissue. The transformation from an AEM to a tumor was found in most of the malignant tumors.CONCLUSION AEM lesions have some features which are similar and also differ from both of the tumor and EM. AEMs have a relative higher potential for tumorigenesis and canceration, especially for ovarian cancer.The process of damage, repair, and scarring in EM foci over a long period may play a role in the development of EM into AEM and eventally into tumor formation.

  16. Atypical sulcal anatomy in young children with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    G. Auzias

    2014-01-01

    Full Text Available Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory

  17. Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Wei; Wernimont, Amy; Tang, Keliang; Taylor, Sonya; Lunin, Vladimir; Schapira, Matthieu; Fentress, Sarah; Hui, Raymond; Sibley, L. David; (Toronto); (WU-MED)

    2009-09-29

    Serine/threonine kinases secreted from rhoptry organelles constitute important virulence factors of Toxoplasma gondii. Rhoptry kinases are highly divergent and their structures and regulatory mechanism are hitherto unknown. Here, we report the X-ray crystal structures of two related pseudokinases named ROP2 and ROP8, which differ primarily in their substrate-binding site. ROP kinases contain a typical bilobate kinase fold and a novel N-terminal extension that both stabilizes the N-lobe and provides a unique means of regulation. Although ROP2 and ROP8 were catalytically inactive, they provided a template for homology modelling of the active kinase ROP18, a major virulence determinant of T. gondii. Autophosphorylation of key residues in the N-terminal extension resulted in ROP18 activation, which in turn phosphorylated ROP2 and ROP8. Mutagenesis and mass spectrometry experiments revealed that ROP18 was maximally activated when this phosphorylated N-terminus relieved autoinhibition resulting from extension of aliphatic side chains into the ATP-binding pocket. This novel means of regulation governs ROP kinases implicated in parasite virulence.

  18. Dancing with the dead: Eph receptors and their kinase-null partners.

    Science.gov (United States)

    Truitt, Luke; Freywald, Andrew

    2011-04-01

    Eph receptor tyrosine kinases and their ligands, ephrins, are membrane proteins coordinating a wide range of biological functions both in developing embryos and in adult multicellular organisms. Numerous studies have implicated Eph receptors in the induction of opposing responses, including cell adhesion or repulsion, support or inhibition of cell proliferation and cell migration, and progression or suppression of multiple malignancies. Similar to other receptor tyrosine kinases, Eph receptors rely on their ability to catalyze tyrosine phosphorylation for signal transduction. Interestingly, however, Eph receptors also actively utilize three kinase-deficient receptor tyrosine kinases, EphB6, EphA10, and Ryk, in their signaling network. The accumulating evidence suggests that the unusual flexibility of the Eph family, allowing it to initiate antagonistic responses, might be partially explained by the influence of the kinase-dead participants and that the exact outcome of an Eph-mediated action is likely to be defined by the balance between the signaling of catalytically potent and catalytically null receptors. We discuss in this minireview the emerging functions of the kinase-dead EphB6, EphA10, and Ryk receptors both in normal biological responses and in malignancy, and analyze currently available information related to the molecular mechanisms of their action in the context of the Eph family. PMID:21455264

  19. MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver

    DEFF Research Database (Denmark)

    Bonnesen, Barbara; Ørskov, Cathrine; Rasmussen, Susanne;

    2005-01-01

    KD) embryos have normal morphology but are anemic due to failure of definitive erythropoiesis. When Mekk1(DeltaKD) fetal liver cells were transferred to lethally irradiated wild-type hosts, mature red blood cells were generated from the mutant cells, suggesting that MEKK1 functions in a non-cell......Mitogen-activated protein kinase/extracellular signal to regulated kinase (MEK) kinase 1 (MEKK1) is a c-Jun N-terminal kinase (JNK) activating kinase known to be implicated in proinflammatory responses and cell motility. Using mice deficient for MEKK1 kinase activity (Mekk1(DeltaKD)) we show a role...... for MEKK1 in definitive mouse erythropoiesis. Although Mekk1(DeltaKD) mice are alive and fertile on a 129 x C57/BL6 background, the frequency of Mekk1(DeltaKD) embryos that develop past embryonic day (E) 14.5 is dramatically reduced when backcrossed into the C57/BL6 background. At E13.5, Mekk1(Delta...

  20. Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A and Quantitative Phosphoproteomics.

    Science.gov (United States)

    Poss, Zachary C; Ebmeier, Christopher C; Odell, Aaron T; Tangpeerachaikul, Anupong; Lee, Thomas; Pelish, Henry E; Shair, Matthew D; Dowell, Robin D; Old, William M; Taatjes, Dylan J

    2016-04-12

    Cortistatin A (CA) is a highly selective inhibitor of the Mediator kinases CDK8 and CDK19. Using CA, we now report a large-scale identification of Mediator kinase substrates in human cells (HCT116). We identified over 16,000 quantified phosphosites including 78 high-confidence Mediator kinase targets within 64 proteins, including DNA-binding transcription factors and proteins associated with chromatin, DNA repair, and RNA polymerase II. Although RNA-seq data correlated with Mediator kinase targets, the effects of CA on gene expression were limited and distinct from CDK8 or CDK19 knockdown. Quantitative proteome analyses, tracking around 7,000 proteins across six time points (0-24 hr), revealed that CA selectively affected pathways implicated in inflammation, growth, and metabolic regulation. Contrary to expectations, increased turnover of Mediator kinase targets was not generally observed. Collectively, these data support Mediator kinases as regulators of chromatin and RNA polymerase II activity and suggest their roles extend beyond transcription to metabolism and DNA repair. PMID:27050516

  1. Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A and Quantitative Phosphoproteomics

    Directory of Open Access Journals (Sweden)

    Zachary C. Poss

    2016-04-01

    Full Text Available Cortistatin A (CA is a highly selective inhibitor of the Mediator kinases CDK8 and CDK19. Using CA, we now report a large-scale identification of Mediator kinase substrates in human cells (HCT116. We identified over 16,000 quantified phosphosites including 78 high-confidence Mediator kinase targets within 64 proteins, including DNA-binding transcription factors and proteins associated with chromatin, DNA repair, and RNA polymerase II. Although RNA-seq data correlated with Mediator kinase targets, the effects of CA on gene expression were limited and distinct from CDK8 or CDK19 knockdown. Quantitative proteome analyses, tracking around 7,000 proteins across six time points (0–24 hr, revealed that CA selectively affected pathways implicated in inflammation, growth, and metabolic regulation. Contrary to expectations, increased turnover of Mediator kinase targets was not generally observed. Collectively, these data support Mediator kinases as regulators of chromatin and RNA polymerase II activity and suggest their roles extend beyond transcription to metabolism and DNA repair.

  2. Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight.

    Science.gov (United States)

    De Moliner, Erika; Moro, Stefano; Sarno, Stefania; Zagotto, Giuseppe; Zanotti, Giuseppe; Pinna, Lorenzo A; Battistutta, Roberto

    2003-01-17

    Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition. PMID:12419810

  3. Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Pan, Cuiping; Olsen, Jesper V; Daub, Henrik;

    2009-01-01

    to identify the direct targets of kinase inhibitors upon affinity purification from cellular extracts. Here we introduce a complementary approach to evaluate the effects of kinase inhibitors on the entire cell signaling network. We used triple labeling SILAC (stable isotope labeling by amino acids in cell......-ABL, which is the cause of chronic myelogenous leukemia, affected nearly 1,000 phosphopeptides. In addition to the proximal effects on ABL and its immediate targets, dasatinib broadly affected the downstream MAPK pathways. Pathway mapping of regulated sites implicated a variety of cellular functions...

  4. Immunochemical characterization of rat brain protein kinase

    International Nuclear Information System (INIS)

    Polyclonal antibodies against rat brain protein kinase C (the Ca2+/phospholipid-dependent enzyme) were raised in goat. These antibodies can neutralize completely the kinase activity in purified enzyme preparation as well as that in the crude homogenate. Immunoblot analysis of the purified and the crude protein kinase C preparations revealed a major immunoreactive band of 80 kDa. The antibodies also recognize the same enzyme from other rat tissues. Neuronal tissues (cerebral cortex, cerebellum, hypothalamus, and retina) and lymphoid organs (thymus and spleen) were found to be enriched in protein kinase C, whereas lung, kidney, liver, heart, and skeletal muscle contained relatively low amounts of this kinase. Limited proteolysis of the purified rat brain protein kinase C with trypsin results in an initial degradation of the kinase into two major fragments of 48 and 38 kDa. Both fragments are recognized by the antibodies. However, further digestion of the 48-kDa fragment to 45 kDa and the 38-kDa fragment to 33 kDa causes a loss of the immunoreactivity. Upon incubation of the cerebellar extract with Ca2+, the 48-kDa fragment was also identified as a major proteolytic product of protein kinase C. Proteolytic degradation of protein kinase C converts the Ca2+/phospholipid-dependent kinase to an independent form without causing a large impairment of the binding of [3H]phorbol 12,13-dibutyrate. The two major proteolytic fragments were separated by ion exchange chromatography and one of them (45-48 kDa) was identified as a protein kinase and the other (33-38 kDa) as a phorbol ester-binding protein. These results demonstrate that rat brain protein kinase C is composed of two functionally distinct units, namely, a protein kinase and a Ca2+-independent/phospholipid-dependent phorbol ester-binding protein

  5. Atypical leg symptoms: does routine measurement of the ankle brachial pressure index (ABPI) in primary care benefit patients?

    OpenAIRE

    Oesterling, Christine; Kalia, Amun; Chetcuti, Thomas; Walker, Steven

    2015-01-01

    Abstract Background : Managing patients with atypical leg symptoms in primary care can be problematic. Determining the ankle brachial pressure index (ABPI) may be readily performed to help diagnose peripheral arterial disease, but is often omitted where signs and symptoms are unclear. Question : Does routine measurement of ABPI in patients with atypical leg symptoms aid management increase satisfaction and safely reduce hospital referral? Methodology : Patients with atypical leg symptoms but ...

  6. Norepinephrine and endothelin activate diacylglycerol kinases in caveolae/rafts of rat mesenteric arteries: agonist-specific role of PI3-kinase.

    Science.gov (United States)

    Clarke, Christopher J; Ohanian, Vasken; Ohanian, Jacqueline

    2007-05-01

    The phosphatidylinositol (PI) signaling pathway mediates norepinephrine (NE)- and endothelin-1 (ET-1)-stimulated vascular smooth muscle contraction through an inositol-trisphosphate-induced rise in intracellular calcium and diacylglycerol (DG) activation of protein kinase C (PKC). Subsequent activation of DG kinases (DGKs) metabolizes DG to phosphatidic acid (PA), potentially regulating PKC activity. Because precise regulation and spatial restriction of the PI pathway is necessary for specificity, we have investigated whether this occurs within caveolae/rafts, specialized plasma membrane microdomains implicated in vascular smooth muscle contraction. We show that components of the PI signaling cascade-phosphatidylinositol 4,5-bisphosphate (PIP(2)), PA, and DGK-theta are present in caveolae/rafts prepared from rat mesenteric small arteries. Stimulation with NE or ET-1 induced [(33)P]PIP(2) hydrolysis solely within caveolae/rafts. NE stimulated an increase in DGK activity in caveolae/rafts alone, whereas ET-1 activated DGK in caveolae/rafts and noncaveolae/rafts; however, [(33)P]PA increased in all fractions with both agonists. Previously, we reported that NE activated DGK-theta in a phosphatidylinositol 3-kinase (PI3-kinase)-dependent manner; here, we describe PI3-kinase-dependent DGK activation and [(33)P]PA production in caveolae/rafts in response to NE but not ET-1. Additionally, PKB, a potential activator of DGK-theta, translocated to caveolae/rafts in response to NE but not ET-1, and PI3-kinase inhibition prevented this. Furthermore, PI3-kinase inhibition reduced the sensitivity of contraction to NE but not ET-1. Our study shows that caveolae/rafts are major sites of vasoconstrictor hormone activation of the PI pathway in intact small arteries and suggest a link between lipid signaling events within caveolae/rafts and contraction. PMID:17208990

  7. Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)

    DEFF Research Database (Denmark)

    Dettori, Rosalia; Sonzogni, Silvina; Meyer, Lucas;

    2009-01-01

    The members of the AGC kinase family frequently exhibit three conserved phosphorylation sites: the activation loop, the hydrophobic motif (HM), and the zipper (Z)/turn-motif (TM) phosphorylation site. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates the activation loop of...... numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites, the...... the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2...

  8. Activation of protein kinase C inhibits synthesis and release of decidual prolactin

    Energy Technology Data Exchange (ETDEWEB)

    Harman, I.; Costello, A.; Ganong, B.; Bell, R.M.; Handwerger, S.

    1986-08-01

    Activation of calcium-activated, phospholipid-dependent protein kinase C by diacylglycerol and phorbol esters has been shown to mediate release of hormones in many systems. To determine whether protein kinase C activation is also involved in the regulation of prolactin release from human decidual, the authors have examined the effects of various acylglycerols and phorbol esters on the synthesis and release of prolactin from cultured human decidual cells. sn-1,2-Dioctanolyglycerol (diC8), which is known to stimulate protein kinase C in other systems, inhibited prolactin release in a dose-dependent manner with maximal inhibition of 53.1% at 100 M. Diolein (100 M), which also stimulates protein kinase C activity in some systems, inhibited prolactin release by 21.3%. Phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-didecanoate, and 4US -phorbol 12,13-dibutyrate, which activate protein kinase C in other systems, also inhibited the release of prolactin, which the protein kinase C inactivate 4 -phorbol-12,13-didecanoate was without effect. The inhibition of prolactin release was secondary to a decrease in prolactin synthesis. Although diC8 and PMA inhibited the synthesis and release of prolactin, these agents had no effect on the synthesis or release of trichloroacetic acid-precipitable (TVS)methionine-labeled decidual proteins and did not cause the release of the cytosolic enzymes lactic dehydrogenase and alkaline phosphatase. DiC8 and PMA stimulates the specific activity of protein kinase C in decidual tissue by 14.6 and 14.0-fold, respectively. The inhibition of the synthesis and release of prolactin by diC8 and phorbol esters strongly implicates protein kinase C in the regulation of the production and release of prolactin from the decidua.

  9. Archival search for historical atypical scrapie in sheep reveals evidence for mixed infections.

    Science.gov (United States)

    Chong, Angela; Kennedy, Iain; Goldmann, Wilfred; Green, Andrew; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-10-01

    Natural scrapie in sheep occurs in classical and atypical forms, which may be distinguished on the basis of the associated neuropathology and properties of the disease-associated prion protein on Western blots. First detected in 1998, atypical scrapie is known to have occurred in UK sheep since the 1980s. However, its aetiology remains unclear and it is often considered as a sporadic, non-contagious disease unlike classical scrapie which is naturally transmissible. Although atypical scrapie tends to occur in sheep of prion protein (PRNP) genotypes that are different from those found predominantly in classical scrapie, there is some overlap so that there are genotypes in which both scrapie forms can occur. In this search for early atypical scrapie cases, we made use of an archive of fixed and frozen sheep samples, from both scrapie-affected and healthy animals (∼1850 individuals), dating back to the 1960s. Using a selection process based primarily on PRNP genotyping, but also on contemporaneous records of unusual clinical signs or pathology, candidate sheep samples were screened by Western blot, immunohistochemistry and strain-typing methods using tg338 mice. We identified, from early time points in the archive, three atypical scrapie cases, including one sheep which died in 1972 and two which showed evidence of mixed infection with classical scrapie. Cases with both forms of scrapie in the same animal as recognizable entities suggest that mixed infections have been around for a long time and may potentially contribute to the variety of scrapie strains.

  10. Effect of Anterior Cervical Discectomy and Fusion on Patients with Atypical Symptoms Related to Cervical Spondylosis.

    Science.gov (United States)

    Muheremu, Aikeremujiang; Sun, Yuqing; Yan, Kai; Yu, Jie; Zheng, Shan; Tian, Wei

    2016-09-01

    Background A considerable number of patients with cervical spondylosis complain about one or multiple atypical symptoms such as vertigo, palpitations, headache, blurred vision, hypomnesia, and/or nausea. It remains unclear whether surgical intervention for cervical spondylosis can also effectively alleviate those symptoms. The current study was performed to see if anterior cervical diskectomy and fusion (ACDF) offers such an extra benefit for patients with cervical spondylosis. Objective To investigate if patients who received ACDF for the treatment of cervical spondylotic myelopathy and/or radiculopathy can also achieve alleviation of certain atypical symptoms associated with cervical spondylosis after the surgery in the long run. Methods Sixty-seven patients who underwent ACDF for the treatment of cervical spondylotic myelopathy and/or radiculopathy were involved in this study. All these patients also complained about various associated atypical symptoms. They were followed up for 26 to 145 months after the surgery. Severity and frequency scores of the atypical symptoms before the surgery and at last follow-up were compared by paired t tests. Results Most patients reported significantly alleviated symptoms at the last follow-up compared with before the surgery. The severity of vertigo, headache, nausea, and palpitations were significantly alleviated at the last follow-up (with p values of p cervical spondylotic myelopathy and/or radiculopathy, but it is not effective in alleviating symptoms such as tinnitus, blurred vision, and hypomnesia. It can be considered for alleviating atypical symptoms when other treatment options prove ineffective. PMID:27168319

  11. Lichen sclerosus: a potpourri of misdiagnosed cases based on atypical clinical presentations

    Directory of Open Access Journals (Sweden)

    Ventolini G

    2015-05-01

    Full Text Available Gary Ventolini, Ravi Patel, Robert Vasquez Texas Tech University Health Sciences Center Permian Basin, Odessa, TX, USA Objective: Lichen sclerosus (LS is a chronic progressive inflammatory autoimmune-induced disease that primarily affects the epidermis and dermis of the external genital-anal region. Intense and recalcitrant pruritus is the hallmark of LS. Physical exam reveals thinning, hyperkeratosis, and parchment-like appearance. However, the classic symptom and signs of LS may not always be present and patients may be asymptomatic for pruritus. Hence, we describe 15 misdiagnosed cases with atypical clinical presentations. We believe that the absence of pruritus contributed to their initial misdiagnosis. The purpose of this paper is to increase awareness of atypical presentations of LS. Methods: Data base review of de-identified clinical case pictures was performed. All patients had histopathology-confirmed diagnoses of LS. The data base file contains 800 cases of vulvovaginal disorders. The Institutional Review Board (IRB considered that searching a de-identified data base of pictures did not require IRB approval. Results: We identified 15 different atypical clinical cases. Patient ages were 18–75 years old. These patients were asymptomatic for pruritus and were misdiagnosed before they presented to the vulvovaginal specialized clinic. Conclusion: Fifteen patients asymptomatic for pruritus with histopathology-confirmed diagnosis of LS were identified. They illustrate atypical clinical presentations that LS may have. Keywords: vulvovaginal, vulvar, atypical, lichen sclerosus, asymptomatic

  12. Exploring atypical verb+noun combinations in learner technical writing

    Directory of Open Access Journals (Sweden)

    María José Luzón Marco

    2011-12-01

    Full Text Available Professional and academic discourse is characterised by a specific phraseology, which usually poses problems for students. This paper investigates atypical verb+noun collocations in a corpus of English technical writing of Spanish students. I focus on the type of verbs that most frequently occurred in these awkward or questionable combinations and attempt to explore the reasons why the learners deviate from NS's norms. The analysis indicates that these learners tend to have problems with a set of sub-technical and high-frequency verbs. Deviant combinations involving these verbs are frequently the result of a deficient knowledge of the phraseology of academic and technical discourse. The unawareness of collocations that are typical of this discourse often leads students to create V+N combinations by relying on the “Open Choice Principle” (Sinclair, 1991 or by using patterns from their mother tongue.El discurso profesional y académico se caracteriza por una fraseología específica, que suele plantear problemas a los estudiantes. Este artículo investiga colocaciones de verbo+nombre atípicas en un corpus de textos técnicos en inglés escritos por estudiantes españoles. El estudio se centra en los verbos que más frecuentemente aparecen en estas combinaciones atípicas y explora las razones por las que los estudiantes se desvían de la norma. El análisis indica que estos estudiantes suelen tener problemas con un grupo de verbos sub-técnicos y verbos de alta frecuencia. Las combinaciones atípicas en las que estos verbos aparecen son frecuentemente el resultado de un conocimiento deficiente de la fraseología del discurso académico y técnico. El desconocimiento de colocaciones que son típicas de este discurso a menudo lleva a los estudiantes a crear combinaciones basándose en el “principio de opción abierta” (Sinclair, 1991 o a usar colocaciones prestadas de su lengua materna.

  13. Diacylglycerol Kinase Inhibition and Vascular Function

    OpenAIRE

    Choi, Hyehun; Allahdadi, Kyan J.; Tostes, Rita C A; Webb, R. Clinton

    2009-01-01

    Diacylglycerol kinases (DGKs), a family of lipid kinases, convert diacylglycerol (DG) to phosphatidic acid (PA). Acting as a second messenger, DG activates protein kinase C (PKC). PA, a signaling lipid, regulates diverse functions involved in physiological responses. Since DGK modulates two lipid second messengers, DG and PA, regulation of DGK could induce related cellular responses. Currently, there are 10 mammalian isoforms of DGK that are categorized into five groups based on their structu...

  14. MAP kinases and histone modification

    Institute of Scientific and Technical Information of China (English)

    Tamaki Suganuma; Jerry L. Workman

    2012-01-01

    Signal transduction pathways alter the gene expression program in response to extracellular or intracellular cues.Mitogen-activated protein kinases (MAPKs) govern numerous cellular processes including cell growth,stress response,apoptosis,and differentiation.In the past decade,MAPKs have been shown to regulate the transcription machinery and associate with chromatin-modifying complexes.Moreover,recent studies demonstrate that several MAPKs bind directly to chromatin at target genes.This review highlights the recent discoveries of MAPK signaling in regard to histone modifications and chromatin regulation.Evidence suggesting that further unknown mechanisms integrate signal transduction with chromatin biology is discussed.

  15. MST kinases in development and disease

    OpenAIRE

    Thompson, Barry J.; Sahai, Erik

    2015-01-01

    The mammalian MST kinase family, which is related to the Hippo kinase in Drosophila melanogaster, includes five related proteins: MST1 (also called STK4), MST2 (also called STK3), MST3 (also called STK24), MST4, and YSK1 (also called STK25 or SOK1). MST kinases are emerging as key signaling molecules that influence cell proliferation, organ size, cell migration, and cell polarity. Here we review the regulation and function of these kinases in normal physiology and pathologies, including cance...

  16. Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1, and c-Jun N-terminal kinase-mediated pathway.

    Science.gov (United States)

    Chikano, Yuri; Domoto, Takahiro; Furuta, Takuya; Sabit, Hemragul; Kitano-Tamura, Ayako; Pyko, Ilya V; Takino, Takahisa; Sai, Yoshimichi; Hayashi, Yutaka; Sato, Hiroshi; Miyamoto, Ken-ichi; Nakada, Mitsutoshi; Minamoto, Toshinari

    2015-02-01

    The failure of current treatment options for glioblastoma stems from their inability to control tumor cell proliferation and invasion. Biologically targeted therapies offer great hope and one promising target is glycogen synthase kinase-3β (GSK3β), implicated in various diseases, including cancer. We previously reported that inhibition of GSK3β compromises the survival and proliferation of glioblastoma cells, induces their apoptosis, and sensitizes them to temozolomide and radiation. Here, we explore whether GSK3β also contributes to the highly invasive nature of glioblastoma. The effects of GSK3β inhibition on migration and invasion of glioblastoma cells were examined by wound-healing and Transwell assays, as well as in a mouse model of glioblastoma. We also investigated changes in cellular microarchitectures, cytoskeletal components, and proteins responsible for cell motility and invasion. Inhibition of GSK3β attenuated the migration and invasion of glioblastoma cells in vitro and that of tumor cells in a mouse model of glioblastoma. These effects were associated with suppression of the molecular axis involving focal adhesion kinase, guanine nucleotide exchange factors/Rac1 and c-Jun N-terminal kinase. Changes in cellular phenotypes responsible for cell motility and invasion were also observed, including decreased formation of lamellipodia and invadopodium-like microstructures and alterations in the subcellular localization, and activity of Rac1 and F-actin. These changes coincided with decreased expression of matrix metalloproteinases. Our results confirm the potential of GSK3β as an attractive therapeutic target against glioblastoma invasion, thus highlighting a second role in this tumor type in addition to its involvement in chemo- and radioresistance. PMID:25504636

  17. Atypical femoral fracture due to chronic use of bisphosphonates: case report☆

    Science.gov (United States)

    Temponi, Eduardo Frois; de Carvalho Junior, Lúcio Honório; Costa, Lincoln Paiva

    2015-01-01

    The causal relationship between chronic use of bisphosphonates and occurrences of atypical femoral fractures has not yet been established. Nonetheless, it is known that their chronic use is more related to fractures with a pattern differing from that of classical osteoporotic fractures. Atypical fractures are still rare events and the benefit from using bisphosphonates remains greater for prevention and treatment of osteoporosis. There are few studies guiding the diagnosis and management of these fractures, thus making it difficult to achieve better results. In this report, we present the case of an elderly patient with an atypical femoral fracture that was managed in accordance with guidance from the American Society for Bone and Mineral Research. PMID:26401508

  18. Atypical p-ANCA in PSC and AIH: a hint toward a "leaky gut"?

    Science.gov (United States)

    Terjung, Birgit; Spengler, Ulrich

    2009-02-01

    Primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are enigmatic chronic inflammatory diseases of the liver, which are frequently associated with chronic inflammatory bowel diseases. Both types of liver disease share various distinct autoantibodies such as atypical perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), and thus are considered autoimmune disorders with atypical features. The discovery that atypical p-ANCA recognize both tubulin beta isoform 5 in human neutrophils and the bacterial cell division protein FtsZ has renewed the discussion on the potential role of microorganisms in the pathogenesis of both diseases. In this paper, we review the evidence for microbial infection in PSC and AIH and discuss new concepts how cross-recognition between microbial antigens in the gut and host components by the immune system along with stimulation of pattern recognition receptors might give rise to chronic hepatic inflammatory disorders with features of autoimmunity.

  19. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients.

    Science.gov (United States)

    Aracki-Trenkić, Aleksandra; Stojanov, Dragan; Trenkić, Milan; Radovanović, Zoran; Ignjatović, Jelena; Ristić, Saša; Trenkić-Bozinović, Marija

    2016-08-01

    Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image. PMID:27483175

  20. Effectiveness of an Inpatient Movement Disorders Program for Patients with Atypical Parkinsonism

    Directory of Open Access Journals (Sweden)

    Anna D. Hohler

    2012-01-01

    Full Text Available This paper investigated the effectiveness of an inpatient movement disorders program for patients with atypical parkinsonism, who typically respond poorly to pharmacologic intervention and are challenging to rehabilitate as outpatients. Ninety-one patients with atypical parkinsonism participated in an inpatient movement disorders program. Patients received physical, occupational, and speech therapy for 3 hours/day, 5 to 7 days/week, and pharmacologic adjustments based on daily observation and data. Differences between admission and discharge scores were analyzed for the functional independence measure (FIM, timed up and go test (TUG, two-minute walk test (TMW, Berg balance scale (BBS and finger tapping test (FT, and all showed significant improvement on discharge (>.001. Clinically significant improvements in total FIM score were evident in 74% of the patients. Results were similar for ten patients whose medications were not adjusted. Patients with atypical parkinsonism benefit from an inpatient interdisciplinary movement disorders program to improve functional status.

  1. [Atypical angiographic appearances of aneurisms of the abdominal aorta (author's transl)].

    Science.gov (United States)

    Chermet, J; Kieffer, E; Taboury, J; Monnier, J P; Chalut, J

    1976-10-01

    On the basis of 72 radio-surgical cases of abdominal aortic aneurism, the authors stress the value of atypical angiographic findings, which are ten in number. The presence of clot within the aneurism itself may explain a disparity between radiological and surgical findings. Failure to recognize these atypical signs is very serious, when the diagnosis of aneurism is not suspected clinically. Antero-posterior and, above all, lateral abdominal aortography is essential in the angiographic study of aneurisms of the abdominal aorta. Careful search for these 10 atypical signs should make it possible to avoid missing latent aneurisms. Lateral abdominal aortography is essential in order to determine the state of the abdominal collaterals of the aorta and, in particular, the superior mesenteric artery. PMID:1003379

  2. Diagnosis of Infectious Mononucleosis by Combined Detection of Atypical Lymphocytes and Transaminase

    Institute of Scientific and Technical Information of China (English)

    HU Lihua; YANG Juhong; CUI Tianpen; XING Hui; CAI Pengcheng

    2006-01-01

    In order to explore the value of combined detection of atypical lymphocytes (ATL) and transaminase (alanine aminotransferase, ALT; asparate aminotransferase, AST) in the diagnosis of infectious mononucleosis (IM), The data of blood routine and liver function were collected from 54 IM patients, 34 acute hepatitis (AH) patients, 44 upper respiratory infection (URI) patients in Union Hospital during March 2002 to March 2005. Same data were also collected from 40 healthy children as normal control. These data were analyzed retrospectively. Both proportion of atypical lymphocytes and enzyme activity of transaminase were elevated simultaneously (ALT>40 IU/L,AST>45 IU/L) in 57.4% (31/54) IM patients. There was significant difference (P<0.01) between IM group and the other groups. Combined detection of atypical lymphocytes and transaminase can be regarded as a diagnostic marker of infectious mononucleosis.

  3. Atypical Antipsychotics and Other Therapeutic Options for Treatment of Resistant Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Allan H. Young

    2010-12-01

    Full Text Available Antidepressant therapies, such as selective serotonin reuptake inhibitors (SSRIs, are current first-line treatments for Major Depressive Disorder. However, over 50% of treated patients show an inadequate response to initial antidepressant therapy. If the therapeutic outcomes from two antidepressant therapies are suboptimal, potentially resulting in Treatment Resistant Depression, subsequent strategies include switching to another antidepressant or augmenting treatment by combining with other agents. When combined with SSRIs, atypical antipsychotics have supplementary action on dopaminergic and noradrenergic systems. Studies on combined treatment with atypical antipsychotics have shown significantly increased remission rates, shortened response times, and favorable side effects. Augmentation of antidepressants with atypical antipsychotics is now an acceptable treatment strategy which leads to increased remission rates and better outcomes for patients.

  4. Atypical scrapie prions from sheep and lack of disease in transgenic mice overexpressing human prion protein.

    Science.gov (United States)

    Wadsworth, Jonathan D F; Joiner, Susan; Linehan, Jacqueline M; Balkema-Buschmann, Anne; Spiropoulos, John; Simmons, Marion M; Griffiths, Peter C; Groschup, Martin H; Hope, James; Brandner, Sebastian; Asante, Emmanuel A; Collinge, John

    2013-11-01

    Public and animal health controls to limit human exposure to animal prions are focused on bovine spongiform encephalopathy (BSE), but other prion strains in ruminants may also have zoonotic potential. One example is atypical/Nor98 scrapie, which evaded statutory diagnostic methods worldwide until the early 2000s. To investigate whether sheep infected with scrapie prions could be another source of infection, we inoculated transgenic mice that overexpressed human prion protein with brain tissue from sheep with natural field cases of classical and atypical scrapie, sheep with experimental BSE, and cattle with BSE. We found that these mice were susceptible to BSE prions, but disease did not develop after prolonged postinoculation periods when mice were inoculated with classical or atypical scrapie prions. These data are consistent with the conclusion that prion disease is less likely to develop in humans after exposure to naturally occurring prions of sheep than after exposure to epizootic BSE prions of ruminants.

  5. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients

    Directory of Open Access Journals (Sweden)

    Aleksandra Aracki-Trenkić

    2016-06-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image.

  6. Flares on A-type stars: Evidence for heating of solar corona by nanoflares?

    CERN Document Server

    Svanda, M

    2016-01-01

    We analyzed the occurrence rates of flares on stars of spectral types K, G, F, and A, observed by Kepler. We found that the histogram of occurrence frequencies of stellar flares is systematically shifted towards a high-energy tail for A-type stars compared to stars of cooler spectral types. We extrapolated the fitted power laws towards flares with smaller energies (nanoflares) and made estimates for total energy flux to stellar atmospheres by flares. We found that for A-type stars the total energy flux density was at least 4-times smaller than for G-stars. We speculate that this deficit in energy supply may explain the lack of hot coronae on A-type stars. Our results indicate an importance of nanoflares for heating and formation of the solar corona.

  7. Flares on A-type Stars: Evidence for Heating of Solar Corona by Nanoflares?

    Science.gov (United States)

    Švanda, Michal; Karlický, Marian

    2016-11-01

    We analyzed the occurrence rates of flares on stars of spectral types K, G, F, and A, observed by Kepler. We found that the histogram of occurrence frequencies of stellar flares is systematically shifted toward a high-energy tail for A-type stars compared to stars of cooler spectral types. We extrapolated the fitted power laws toward flares with smaller energies (nanoflares) and made estimates for total energy flux to stellar atmospheres by flares. We found that, for A-type stars, the total energy flux density was at least four-times smaller than for G stars. We speculate that this deficit in energy supply may explain the lack of hot coronae on A-type stars. Our results indicate the importance of nanoflares for heating and formation of the solar corona.

  8. Total Hip Arthroplasty for Implant Rupture after Surgery for Atypical Subtrochanteric Femoral Fracture

    Directory of Open Access Journals (Sweden)

    Yu Ozaki

    2016-01-01

    Full Text Available Treatment methods for delayed union and nonunion of atypical femoral fracture are still controversial. Moreover, no treatment method has been established for implant rupture caused by delayed union and nonunion. We encountered a 74-year-old female in whom nonunion-induced implant rupture occurred after treatment of atypical subtrochanteric femoral fracture with internal fixation using a long femoral nail. It was unlikely that sufficient fixation could be obtained by repeating osteosynthesis alone. Moreover, the patient was elderly and early weight-bearing activity was essential for early recovery of ADL. Based on these reasons, we selected one-stage surgery with total hip arthroplasty and osteosynthesis with inverted condylar locking plate as salvage procedures. Bone union was achieved at 6 months after surgery. This case illustrated that osteosynthesis-combined one-staged total hip arthroplasty could be considered as one of the options for nonunion-induced implant rupture of atypical femoral subtrochanteric fracture.

  9. Effectiveness of an inpatient movement disorders program for patients with atypical parkinsonism.

    Science.gov (United States)

    Hohler, Anna D; Tsao, Jyeming M; Katz, Douglas I; Dipiero, T Joy; Hehl, Christina L; Leonard, Alissa; Allen, Valerie; Gardner, Maura; Phenix, Heidi; Saint-Hilaire, Marie; Ellis, Terry

    2012-01-01

    This paper investigated the effectiveness of an inpatient movement disorders program for patients with atypical parkinsonism, who typically respond poorly to pharmacologic intervention and are challenging to rehabilitate as outpatients. Ninety-one patients with atypical parkinsonism participated in an inpatient movement disorders program. Patients received physical, occupational, and speech therapy for 3 hours/day, 5 to 7 days/week, and pharmacologic adjustments based on daily observation and data. Differences between admission and discharge scores were analyzed for the functional independence measure (FIM), timed up and go test (TUG), two-minute walk test (TMW), Berg balance scale (BBS) and finger tapping test (FT), and all showed significant improvement on discharge (P > .001). Clinically significant improvements in total FIM score were evident in 74% of the patients. Results were similar for ten patients whose medications were not adjusted. Patients with atypical parkinsonism benefit from an inpatient interdisciplinary movement disorders program to improve functional status. PMID:22135763

  10. Differentiation and accumulation of fluids in A-type granites: Evidence from accessory mineral study

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The Laoshan A-type granite is a highly evolved granite body. The study on accessory minerals indicates that there exist differentiation and accumulation of fluids during the late stage of evolution of the granite. The released fluids are rich in rare-earth elements (REE),high-field- strength elements (HFSE,such as Nb,Ta,Zr,Hf,Th,U,and Y) and volatiles (F,P,CO2,etc.). Owing to the presence of fluid,accessory mineral assemblages have changed during the evolution of A-type granite,and are especially characterized by large amounts of independent REE-Nb-Y-Th minerals present in the late facies. Late-accumulation of fluids may be of the general feature of A-type granites,at least of highly evolved ones.

  11. Sensitive kinase assay linked with phosphoproteomics for identifying direct kinase substrates.

    Science.gov (United States)

    Xue, Liang; Wang, Wen-Horng; Iliuk, Anton; Hu, Lianghai; Galan, Jacob A; Yu, Shuai; Hans, Michael; Geahlen, Robert L; Tao, W Andy

    2012-04-10

    Our understanding of the molecular control of many disease pathologies requires the identification of direct substrates targeted by specific protein kinases. Here we describe an integrated proteomic strategy, termed kinase assay linked with phosphoproteomics, which combines a sensitive kinase reaction with endogenous kinase-dependent phosphoproteomics to identify direct substrates of protein kinases. The unique in vitro kinase reaction is carried out in a highly efficient manner using a pool of peptides derived directly from cellular kinase substrates and then dephosphorylated as substrate candidates. The resulting newly phosphorylated peptides are then isolated and identified by mass spectrometry. A further comparison of these in vitro phosphorylated peptides with phosphopeptides derived from endogenous proteins isolated from cells in which the kinase is either active or inhibited reveals new candidate protein substrates. The kinase assay linked with phosphoproteomics strategy was applied to identify unique substrates of spleen tyrosine kinase (Syk), a protein-tyrosine kinase with duel properties of an oncogene and a tumor suppressor in distinctive cell types. We identified 64 and 23 direct substrates of Syk specific to B cells and breast cancer cells, respectively. Both known and unique substrates, including multiple centrosomal substrates for Syk, were identified, supporting a unique mechanism that Syk negatively affects cell division through its centrosomal kinase activity. PMID:22451900

  12. Bile salts induce expression of the afimbrial LDA adhesin of atypical enteropathogenic Escherichia coli.

    Science.gov (United States)

    Torres, Alfredo G; Tutt, Christopher B; Duval, Lisabeth; Popov, Vsevolod; Nasr, Abdelhakim Ben; Michalski, Jane; Scaletsky, Isabel C A

    2007-04-01

    Atypical enteropathogenic Escherichia coli (aEPEC) strains are frequently implicated in infant diarrhoea in developing countries. Not much is known about the adherence properties of aEPEC; however, it has been shown that these strains can adhere to tissue-cultured cells. A chromosomal region designated the locus for diffuse adherence (LDA) confers aEPEC strain 22 the ability to adhere to culture cells. LDA is an afimbrial adhesin that contains a major subunit, LdaG, whose expression is induced on MacConkey agar at 37 degrees C. We hypothesized that the bile salts found in this culture media induce the expression of LdaG. Strain 22 and the LdaG mutant were grown in Luria-Bertani (LB) media in the presence or absence of bile salts and heat-extracted surface-expressed proteins were separated by SDS-PAGE to determine whether expression of the 25 kDa LdaG protein was induced. Western blot analysis with anti-LdaG confirmed that bile salts enhance LdaG expression at 37 degrees C. Adhesion assays on HeLa cells revealed that adhesion in a diffuse pattern of strain 22 increased in the presence of bile salts. We also confirmed that expression of the localized adherence pattern observed in the ldaG mutant required the presence of a large cryptic plasmid found in strain 22 and that this phenotype was not induced by bile salts. At the transcriptional level, the ldaG-lacZ promoter fusion displayed maximum beta-galactosidase activity when the parent strain was grown in LB supplemented with bile salts. Fluorescence Activated Cell Sorting analysis, immunogold labelling electron microscopy and immunofluorescence using anti-LdaG sera confirmed that LDA is a bile salts-inducible surface-expressed afimbrial adhesin. Finally, LdaG expression was induced in presence of individual bile salts but not by other detergents. We concluded that bile salts increase expression of LDA, conferring a diffuse adherence pattern and having an impact on the adhesion properties of this aEPEC strain.

  13. Benzofuran Small Molecules as Potential Inhibitors of Human Protein Kinases. A Review.

    Science.gov (United States)

    Kwiecień, Halina; Goszczyńska, Agata; Rokosz, Paulina

    2016-01-01

    Kinases are known to regulate the majority of human cellular processes such as communication, division, metabolism, survival and apoptosis therefore they can be promising targets in cancer diseases, viral infection and in other disorders. Small molecules acting as selective human protein kinase inhibitors are very attractive pharmacological targets. This review presents a number of examples of biologically active natural and synthetic benzo[b]furans and their derivatives, such as benzo[b]furan-2- and 3-ones, benzo[b]furan-2- and 3-carboxylic acids, as well as benzo[c]furans as potential inhibitors of various human protein kinases. The pathways of function and implication of the inhibitors in cancer and other diseases are discussed. PMID:26648467

  14. In vitro and in vivo assays of protein kinase CK2 activity.

    Science.gov (United States)

    Prudent, Renaud; Sautel, Céline F; Moucadel, Virginie; Laudet, Béatrice; Filhol, Odile; Cochet, Claude

    2010-01-01

    Protein kinase CK2 (formerly casein kinase 2) is recognized as a central component in the control of the cellular homeostasis; however, much remains unknown regarding its regulation and its implication in cellular transformation and carcinogenesis. Moreover, study of CK2 function and regulation in a cellular context is complicated by the dynamic multisubunit architecture of this protein kinase. Although a number of robust techniques are available to assay CK2 activity in vitro, there is a demand for sensitive and specific assays to evaluate its activity in living cells. We hereby provide a detailed description of several assays for monitoring the CK2 activity and its subunit interaction in living cells. The guidelines presented herein should enable researchers in the field to establish strategies for cellular screenings of CK2 inhibitors. PMID:21050938

  15. Comparison of Peptide Array Substrate Phosphorylation of c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8

    NARCIS (Netherlands)

    Parikh, Kaushal; Diks, Sander H.; Tuynman, Jurriaan H. B.; Verhaar, Auke; Lowenberg, Mark; Hommes, Daan W.; Joore, Jos; Pandey, Akhilesh; Peppelenbosch, Maikel P.

    2009-01-01

    Kinases are pivotal regulators of cellular physiology. The human genome contains more than 500 putative kinases, which exert their action via the phosphorylation of specific substrates. The determinants of this specificity are still only partly understood and as a consequence it is difficult to pred

  16. An Exploration of Eye Movements when Reading Texts with Atypical Spatial Layouts

    Directory of Open Access Journals (Sweden)

    F Hermens

    2012-07-01

    Full Text Available In two experiments we explored eye movements that people make when looking at texts with an atypical spatial layout. In the first experiment, participants repeatedly viewed the same piece of text, containing sections in different languages and printed using different fonts and reading directions, while they answered different questions about what they saw. In agreement with earlier studies showing significant differences in gaze patterns across different tasks, we found that reading was strongly influenced by the questions that participants tried to answer. In the second experiment, we examined gaze patterns for different types of poems while participants performed a single task: To rate their appreciation of the poem. Poems were either in the typical form, with short lines all aligned to the left, or they were in an atypical form (“graphical poem”, with the text dispersed across the page, in different fonts, reading directions, and size. Half of the poems were from an artist known for his graphical poems, the other half were from different authors who posted their poems on a webpage. All these poems were presented in a typical and an atypical form. Participants rated the poems from the web more highly, but took less time to inspect them. Whether the poem was in a typical or an atypical layout did not influence the ratings, even though longer inspection times were found for the atypical forms. Eye movement parameters, such as fixation duration and saccade amplitude, were relatively unaffected by the layout of the poems, although some additional larger amplitude saccades could be observed for the atypical forms.

  17. Atypical Manifestations of Dengue Fever (DF) – Where Do We Stand Today?

    Science.gov (United States)

    Nimmagadda, Satya Sudhish; Mahabala, Chakrapani; Boloor, Archith; Raghuram, Pavan Manibettu; Nayak U., Akshatha

    2014-01-01

    Background and Objectives: Dengue fever (DF) is transmitted by Aedes aegypti mosquitoes. With growing population, rapid urbanization and lack of appropriate sanitary measures, proliferation of mosquitoes and subsequent dengue infections have increased rampantly with an estimated 30-fold increase in incidence over last five decades. With rising disease burden, atypical manifestations have increased as well, which are missed most often due to lack of awareness. Our aim was to look for the atypical manifestations of dengue fever. Materials and Methods: A prospective hospital based observational study was conducted at hospitals of Kasturba Medical College in Mangalore over a period of two years (June–2010 to May–2012). One-hundred fifty ELISA confirmed IgM-dengue sero-positive cases satisfying WHO criteria were examined clinically and laboratory data assessed till they got discharged from hospital after ruling out other causes of fever. Atypical manifestations in dengue fever were noted and analyzed. Results: Most common symptoms noticed were myalgia, headache, rash, arthralgia, pain in abdomen and nausea. More than half of the study group had one or the other atypical manifestation. Liver function test derangement was most often seen. Most common atypical manifestation was hepatitis found in 40.6% patients. Febrile diarrhea, renal failure, Acalculous cholecystitis and conduction abnormalities of heart were among other common manifestations. Three patients died of multi-organ dysfunction, disseminated intravascular coagulation and shock. Platelet count did not correlate well with severity of bleeding. Overall recovery rate was good. Conclusion: Some of the atypical manifestations of dengue fever are no more a rare entity. Clinical vigilance for these manifestations is important for timely detection and management as some of them could be fatal. PMID:24596727

  18. Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin.

    Science.gov (United States)

    Tatara, Ayaka; Shimizu, Saki; Masui, Atsushi; Tamura, Miyuki; Minamimoto, Shoko; Mizuguchi, Yuto; Ochiai, Midori; Mizobe, Yusuke; Ohno, Yukihiro

    2015-11-01

    Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin. PMID:26363311

  19. Does subdivision of the "atypical" urine cytology increase predictive accuracy for urothelial carcinoma?

    Science.gov (United States)

    Bostwick, David G; Hossain, Deloar

    2014-12-01

    Urine cytology is routinely used for early diagnosis and monitoring of patients with hematuria or a history of urothelial carcinoma, but its clinical utility is greatly diminished by a high frequency of "atypical" specimens, reportedly around 20% in the literature. We compared our results with double-stained urine cytology specimens (papanicolaou and acid hematoxylin stains) with published results with only a single or double papanicolaou stain. The acid hematoxylin stain enhanced nuclear chromatin staining, eliminated significant background debris, and improved visibility of diagnostic cells in the presence of obscuring blood. Medical records of all urine cytologies received between 2005 and 2012 in our laboratories were reviewed. The study group consisted of all cases with bladder biopsy follow-up within one year of cytology. Of 43,131 urine cytologies diagnosed in our laboratories, biopsy follow-up results were available within one year in 10,473 cases, including 852 for symptoms and 1,461 for follow-up of bladder cancer. An additional 6,427 cases had cystoscopy results in which no biopsy was obtained. Cases were classified as negative (81.6%), atypical, favor reactive (2.9%), atypical, favor neoplastic (7.3%), suspicious (5.7%), and malignant (2.5%), with subsequent frequencies for urothelial cancer on biopsy of 13.3%, 31.1%, 37.6%, 53.6%, and 74.3%, respectively. No significant difference was found if atypical was subdivided into two categories: favor reactive and favor neoplastic. Subdivision of the atypical category did not improve diagnostic accuracy. Addition of the acid hematoxylin stain decreased the incidence of atypical urine cytologies from about 20% to 10.2%. PMID:24838797

  20. Dominant Rio1 kinase/ATPase catalytic mutant induces trapping of late pre-40S biogenesis factors in 80S-like ribosomes.

    Science.gov (United States)

    Ferreira-Cerca, Sébastien; Kiburu, Irene; Thomson, Emma; LaRonde, Nicole; Hurt, Ed

    2014-07-01

    During eukaryotic ribosome biogenesis, members of the conserved atypical serine/threonine protein kinase family, the RIO kinases (Rio1, Rio2 and Rio3) function in small ribosomal subunit biogenesis. Structural analysis of Rio2 indicated a role as a conformation-sensing ATPase rather than a kinase to regulate its dynamic association with the pre-40S subunit. However, it remained elusive at which step and by which mechanism the other RIO kinase members act. Here, we have determined the crystal structure of the human Rio1-ATP-Mg(2+) complex carrying a phosphoaspartate in the active site indicative of ATPase activity. Structure-based mutations in yeast showed that Rio1's catalytic activity regulates its pre-40S association. Furthermore, we provide evidence that Rio1 associates with a very late pre-40S via its conserved C-terminal domain. Moreover, a rio1 dominant-negative mutant defective in ATP hydrolysis induced trapping of late biogenesis factors in pre-ribosomal particles, which turned out not to be pre-40S but 80S-like ribosomes. Thus, the RIO kinase fold generates a versatile ATPase enzyme, which in the case of Rio1 is activated following the Rio2 step to regulate one of the final 40S maturation events, at which time the 60S subunit is recruited for final quality control check.